Traditional Uses, Phytochemistry, and Multi‐Target Pharmacological Activities of Senna alexandrina

ABSTRACT

Senna alexandrina has been widely used in traditional medicine for gastrointestinal, dermatological, metabolic, and musculoskeletal disorders. Despite extensive ethnobotanical knowledge, a comprehensive integration of its chemical constituents with pharmacological evidence remains limited. This review aimed to synthesize the traditional uses, pharmacological activities, and chemical constituents of S. alexandrina, highlighting the alignment between ethnobotanical applications and experimental evidence. Literature on ethnomedicinal usage, in vitro and in vivo pharmacological studies, and chemical characterization of S. alexandrina was systematically reviewed. A total of 219 chemical structures were compiled, along with the reported bioactivities and traditional applications. Extracts of leaves, pods, and aerial parts exhibit dose‐dependent laxative, anticancer, anti‐inflammatory, hepatoprotective, antioxidant, antimicrobial, antiviral, and metabolic regulatory activities. Anthraquinones, flavonoids, polysaccharides, and other secondary metabolites underpin these effects. The integration of 219 chemical structures, pharmacological data and traditional uses is rare and provides a unique resource for future mechanistic studies and drug discovery. The alignment between traditional usage and experimental pharmacology is promising, though the available evidence remains largely preclinical and extract based. Future research should isolate and characterize specific bioactive compounds to enable precise dosing, elucidate mechanisms, and advance clinical translation.

Senna alexandrina is a medicinally important plant with documented use across Traditional Chinese, Islamic, Ayurvedic, and Unani medicine systems. Phytochemical investigations have yielded 219 characterized compounds, predominantly anthraquinones, flavonoids, and polysaccharides, distributed across leaves, pods, and aerial parts. Pharmacological activities include laxative, anticancer, anti‐inflammatory, antioxidant, antimicrobial, antiviral, and hepatoprotective effects, with a strong alignment between traditional therapeutic claims and pharmacological evidence.

Abbreviations

ABTS

2,2’‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid)

ACAE

Acarbose equivalents

ALP

Alkaline phosphatase

ALT

Alanine aminotransferase

ASC

Adipose‐derived stem cell

AST

Aspartate aminotransferase

BCL2

B‐cell lymphoma 2

BSA

Bovine serum albumin

CC₅₀

Half‐maximal cytotoxic concentration

CCl₄

Carbon tetrachloride

CUPRAC

Cupric ion reducing antioxidant capacity

DPPH

2,2‐diphenyl‐1‐picrylhydrazyl

EAC

Ehrlich ascites carcinoma

EC₅₀

Half‐maximal effective concentration

FRAP

Ferric reducing antioxidant power

GALAE

Galanthamine equivalents

GSH

Reduced glutathione

HCEC

Human corneal epithelial cells

HCT‐116

Human colorectal carcinoma

HDL

High‐density lipoprotein

HEK‐293

Human embryonic kidney 293

HeLa

Human cervical cancer cell line

Hep2

Human epidermoid larynx carcinoma cell line

HepG2

Human hepatoma cancer cell line

HIV‐1

Human immunodeficiency virus type 1

IC₅₀

Half‐maximal inhibitory concentration

IGF1

Insulin‐like growth factor 1

IL‐1β

Interleukin‐1 beta

IL‐6

Interleukin‐6

KAE

Kojic acid equivalents

LDL

Low‐density lipoprotein

LS 180

Human colon adenocarcinoma cell line

MAO‐B

Monoamine oxidase B

MCF‐7

Michigan cancer foundation‐7

MIC

Minimum inhibitory concentration

MIR

Maximum inhibition rate of NO production under the nontoxic tested concentration

MQI

Maximum folds of QR inducing activity under the tested concentration

MTT

3‐(4,5‐Dimethylthiazolyl)‐2,5‐diphenyltetrazolium bromide

NF‐κB

Nuclear factor kappa B

NO

Nitric oxide

NRF2

Nuclear factor erythroid 2‐related factor 2

PBD

Phosphomolybdenum

PI

Propidium iodide

QR

Quinone reductase

ROS

Reactive oxygen species

SEM

Scanning electron microscope

SOD

Superoxide dismutase

STZ

Streptozotocin

TC

Total cholesterol

TFC

Total flavonoid content

TG

Triglycerides

TNF‐α

Tumor necrosis factor alpha

TPC

Total phenolic content

VEGF

Vascular endothelial growth factor

VLDL

Very‐low‐density lipoprotein

γ‐GT

Gamma‐glutamyl transferase

1. Introduction

Senna Mill. is a widely distributed genus of perennial herbs belonging to the family Fabaceae. The genus comprises approximately 282 accepted species that are distributed globally, with a predominance in tropical and subtropical regions [1]. Among these species, Senna alexandrina is one of the most prominent and extensively utilized medicinal plants. It is known by several taxonomic synonyms, including Cassia angustifolia Vahl, Cassia acutifolia Delile, Cassia alexandrina (Mill.) Spreng., Cassia lanceolata Forssk., Cassia senna L., and Senna acutifolia Batka. Commonly referred to as Indian senna, S. alexandrina is widely distributed from the Sahara and Sahel to the Indian subcontinent [1, 2]. The vernacular names of this species vary according to geographical regions and include Alexandria senna, Cassia senna, Egyptian senna, Indian senna, Khartoum senna, Markandika, Senna makkai, Sona, Sonamukhi, Swarnapatri, Tirunelveli senna, and Senna [3].

Morphologically, the leaves of S. alexandrina are eglandular and measure approximately 5–15 cm in length. The stipules are 3–5 mm long and exhibit a subulate, linear, or narrowly triangular shape. The leaves typically bear 4–8 pairs of leaflets, which are lanceolate to elliptic in form and show appressed puberulous or pubescent surfaces. The inflorescences are arranged in racemes ranging from 5 to 30 cm in length [1]. Anatomical characteristics of the leaflets provide important diagnostic features for species identification within the genus Senna. The lamina mesophyll displays an isobilateral arrangement, and in S. alexandrina, the trichomes are thicker than the epidermal cells. Additionally, the midrib contains two to three layers of collenchyma cells located beneath the epidermis [4].

The floral morphology of S. alexandrina includes greenish sepals and yellow to yellowish‐orange petals measuring 0.7–1.7 cm in length. Each flower bears 10 stamens, comprising two large, five medium‐sized, and three small anthers. The fruit is an oblong pod that is nearly straight or slightly curved, flattened, dehiscent, and transversely septate [1]. Each pod typically contains 5–8 obovate, compressed seeds that darken from green to dark brown or black as the pod matures. The seeds are small, silky, and highly durable, retaining viability for several years and facilitating long‐term propagation [5].

The medicinal use of senna dates back to the ninth century, when Arab physicians introduced senna leaves and pods as therapeutic agents. Owing to its potent purgative properties, senna is commonly administered orally in the form of tablets, encapsulated powders, or herbal teas. Senna leaves and pods are globally valued as essential raw materials for pharmaceutical and herbal preparations. Notably, dried senna leaves constitute a key component of herbal teas in Europe. S. alexandrina is predominantly cultivated in Asian countries, a factor that has significantly influenced the ethnopharmacological research and traditional medicinal applications of the plant [3].

Despite its long‐standing medicinal use and commercial importance, existing reviews on S. alexandrina have largely emphasized its laxative effects or addressed isolated pharmacological activities, with limited integration of ethnobotanical knowledge, phytochemical diversity, and experimentally supported bioactivities. Accordingly, this review aims to comprehensively compile traditional uses across medical systems, critically evaluate pharmacological evidence from in vitro and in vivo studies, systematically present the 219 chemical structures reported from S. alexandrina, an approach rarely undertaken in ethnopharmacological literature, and align the pharmacological findings with traditional therapeutic claims, thereby providing an integrated framework to support mechanistic insight, identify research gaps, and guide future drug discovery and clinical investigations [6].

To make this distinction explicit, it is useful to compare the present work with existing reviews of this species. Several prior reviews have concentrated on a single dimension of the plant. Lal et al. [7] reviewed it chiefly from a horticultural and agronomic standpoint, while Jahan et al. [8] focused on its traditional use within the Unani system of medicine, and Ikram et al. [9] emphasized its dietary and health‐promoting properties. More comprehensive treatments have also appeared: Thaker et al. [3] reviewed the ethnopharmacology and phytochemistry of the plant, documenting approximately 22 chemical structures. The present review differs from all of the earlier studies in both scale and integration. By comparison, the present review documents 219 fully characterized compounds, a nearly tenfold increase over the most compound‐rich prior review and is the first to align this inventory with a structured, indication‐by‐indication comparison of traditional uses and pharmacological evidence (Table 7).

TABLE 7.

Traditional uses and pharmacological evidence of S. alexandrina.

Disease category	Reported ailment or condition	Potential therapeutic indications	Putative pharmacological mechanisms	Pharmacological evidence
Gastrointestinal / Digestive	Constipation; colon cleansing; [2, 9, 10]	Laxative; bowel‐cleansing	Anthraquinone glycosides (sennosides) stimulate colonic peristalsis and reduce water/electrolyte absorption	Direct experimental support: Dose‐dependent laxative activity confirmed in vivo (rats); sennosides fraction strongest; poor systemic absorption but colonic conversion to active metabolites mediates effect (Section 5.3)
	Digestive disorders; digestive diseases; jaundice; [2, 11]	Digestive and hepatobiliary support	Choleretic and laxative effects mediated by anthraquinones enhancing bile secretion and intestinal transit	Indirect mechanistic support: Significant antidiabetic and metabolic support observed in vivo in diabetic and hyperlipidemic rodent models; antioxidant and hepatoprotective effects observed (Section 5.3)
	Severe constipation; back pain; [2]	Enhanced purgation; pain relief	Potentiation of laxative activity and lipid‐mediated anti‐inflammatory effects	Direct experimental support: Confirmed laxative effect and anti‐inflammatory activity in vivo in rodent models; olive oil may potentiate activity (Section 5.3)
Dermatological / Skin & Hair	Scabies; itching; pustules; freckles; vitiligo; [2]	Relief of skin diseases	Antimicrobial, anti‐inflammatory, keratolytic effects of phenolics and anthraquinones	Indirect mechanistic support: Antimicrobial activity against bacteria and fungi observed in vitro; anti‐inflammatory and wound‐healing effects observed in vitro and in vivo (Sections 5.2, 5.6.2)
	Malignant wounds; skin diseases; [2]	Wound cleansing and healing	Synergistic antimicrobial, anti‐inflammatory, and wound‐healing effects	Direct experimental support: Wound closure, collagen organization, and antimicrobial effects confirmed in vivo in a burn‐wound model; synergistic activity with other herbs (Sections 5.2, 5.6.1)
	Alopecia furfuracea; alopecia areata; hair loss; [2]	Hair and scalp care	Antimicrobial action against scalp pathogens and improved local microcirculation	Indirect mechanistic support: Moderate antimicrobial and antioxidant activity observed in vitro supports scalp and hair health (Sections 5.2, 5.6.1)
Musculoskeletal / Pain	Neuralgia; sciatica; gout; joint pain; [2]	Relief of joint and nerve pain	Anti‐inflammatory activity and elimination of bodily impurities	Indirect mechanistic support: Anti‐inflammatory and antioxidant effects confirmed in vitro and in vivo; reduced markers of inflammation and oxidative stress (Section 5.2)
	Back pain; [2]	Pain relief	Anti‐inflammatory and potentiated laxative effects	Indirect mechanistic support: Anti‐inflammatory activity demonstrated in vivo; potentiation by lipid fraction observed (Sections 5.2, 5.3)
Neurological / Neuropsychiatric	Obsessive‐compulsive disorder; melancholia; [2]	Relief of mental conditions	Neuroprotective and neuromodulatory effects via antioxidant and anti‐inflammatory pathways	Indirect mechanistic support: MAO‐B inhibition observed in vitro, consistent with a possible mood‐related effect (Section 5.7); direct neuroprotective or neuropsychiatric testing has not been conducted.
	Epilepsy; chronic headache; migraine; [2]	Relief of nervous system disorders	Central anti‐inflammatory and neuroprotective effects	Traditional use: No pharmacological studies identified.
Respiratory	Cough; dyspnea; [2]	Relief of respiratory symptoms	Expectorant, bronchodilatory, and anti‐inflammatory effects	Indirect mechanistic support: Anti‐inflammatory and immunomodulatory activity observed in vitro; may support respiratory symptom relief (Section 5.2)
Reproductive / Obstetric	Difficult labor; post‐partum haemorrhage; [14]	Support during childbirth	Uterotonic activity via stimulation of uterine smooth muscle contraction	Traditional use: No pharmacological studies identified.
Cardiovascular / General tonic	Heart weakness; [2]	General heart support	Antioxidant‐mediated cardioprotective effects	Indirect mechanistic support: Antioxidant and cardioprotective activity demonstrated in vitro; may support cardiovascular health (Section 5.5)
Metabolic / Endocrine	Diabetes; [13]	Blood sugar control	Antihyperglycemic effects via antioxidant activity and modulation of carbohydrate‐metabolizing enzymes	Direct experimental support: Antidiabetic, antihyperglycemic, and antioxidant effects confirmed in vivo in multiple rodent models; α‐glucosidase inhibition observed in vitro (Section 5.3)
Oncological	Cancer; [12]	Digestive and general health support	Antioxidant, cytotoxic, and antiproliferative effects of anthraquinones and flavonoids	Direct experimental support: Dose‐dependent cytotoxic and antiproliferative activity observed in vitro and in vivo; immunomodulatory and antioxidant effects contribute to antitumor activity (Section 5.1)

2. Materials and Methods

The data for this review paper were primarily sourced from CAS SciFinder database (https://scifinder‐n.cas.org/). The initial search was conducted on December 13, 2024 and was subsequently updated on November 17, 2025 to capture recently relevant published literature. The literature search was conducted by searching keyword “Senna alexandrina”, which initially retrieved 1463 records. A stepwise filtering process was implemented to select relevant literature. First, the references results were filtered by language (English), which resulted in 912 results. Next, the results were further restricted by document type to include only journal articles and review papers, excluding patents, clinical trials, conferences, dissertations, letters and reports. Subsequently, a Concept filter was applied using the species name (Senna alexandrina) to restrict the dataset strictly to studies involving the targeted plant. The results were then filtered by Chemical Abstracts (CA) Sections to focus on biomedical and phytochemical relevance, specifically selecting ‘Plant Biochemistry’, ‘Pharmaceuticals’, ‘Pharmaceutical Analysis’, and ‘Pharmacology’. A total of 320 papers retrieved were checked manually for publication in peer‐reviewed journals, complete analytical and experimental data; and verifiable DOI (Digital Object Identifier) links, which finally led to evaluation of 80 articles used for the content of this review. The literature search encompasses publications from 1985 to 2025, providing a comprehensive overview of research on this species from the foundational report to the most recent data. Duplicate phytochemical structures identified across multiple literature sources were removed to establish the final list of compounds. The complete study selection process is summarized in the PRISMA flow diagram (Figure 1).

FIGURE 1.

PRISMA flow diagram.

3. Ethnopharmacology

Senna has been extensively utilized for therapeutic purposes across several ancient medical systems, including Traditional Chinese Medicine (TCM), Islamic Traditional Medicine (ITM), Ayurveda, and Unani medicine. Historically, senna has been employed in the management of a wide range of ailments, such as skin disorders, jaundice, gastrointestinal disturbances, and respiratory conditions. Among the species within the genus, S. alexandrina is the most widely recognized and frequently used in traditional medical practices. Ethnomedical studies indicate that S. alexandrina occupies a prominent position in both TCM and ITM, where it has been extensively documented and prescribed [2].

S. alexandrina was initially identified growing wild in the Makkah region of Hijaz, where it became widely incorporated into traditional medicine, particularly as a purgative agent [9, 10]. The plant is abundant in this region and has historical significance in Islamic medicine, having been reportedly used as a herbal remedy by Prophet Muhammad (S.A.W.) [9]. In Makkah, S. alexandrina remains one of the most commonly utilized medicinal plants. Traditionally, a decoction prepared from its leaves or the entire plant is administered orally to alleviate digestive disorders, relieve constipation, and cleanse the colon. Its inclusion in the narratives of the Prophet's life highlights the substantial influence of prophetic medicine on local therapeutic practices, suggesting that religious beliefs play an important role in shaping traditional medical systems in the region [11]. More broadly, senna is regarded as a whole‐body remedy and is widely used in herbal markets throughout Pakistan and Arab countries as a digestive cleanser and general tonic [9].

The medicinal application of senna dates back more than 2000 years. Pedanius Dioscorides (40–90 AD), a Greek physician and pharmacologist, described senna in De Materia Medica as possessing diuretic, warming, and drying properties. He recommended its use for the treatment of amenorrhea, internal inflammation, kidney disorders, and snakebites. Additionally, Dioscorides suggested vaginal bathing or fumigation with senna decoctions to facilitate uterine dilation. In TCM, S. alexandrina leaves have been traditionally used as a laxative and for the management of bowel disorders. In ITM, the plant is known as Sannā Makki and is characterized by its warming and drying effects on the body. ITM practitioners have documented the use of S. alexandrina leaves in treating conditions related to the skin, hair, respiratory system, joints, and neurological disorders [2].

Topical and internal applications of senna have been extensively described in traditional literature. Senna leaves boiled in vinegar are commonly applied as a poultice for skin conditions such as scabies, itching, pustules, freckles, and vitiligo. According to Aʿqili, a topical preparation containing senna, vinegar, common fumitory (Fumaria officinalis L.), and henna (Lawsonia inermis L.) is traditionally applied during bathing to treat these conditions and promote wound healing, including malignant ulcers. Decoctions of senna leaves have also been used to manage alopecia furfuracea, alopecia areata, and general hair loss. Internally, senna has been administered to treat cough and dyspnea, particularly when combined with licorice (Glycyrrhiza glabra L.), and has additionally been recommended as a cardiac tonic. Traditional physicians also prescribed senna for neuropsychiatric conditions such as obsessive–compulsive disorder and melancholia, as well as for epilepsy, chronic headache, and migraine. Owing to its strong laxative action, senna was believed to expel accumulated bodily impurities, especially those associated with the humoral concept of “phlegm,” thereby contributing to the management of neuralgia, sciatica, gout, and joint pain. Oral administration of a senna leaf decoction prepared with olive oil was particularly valued for its purgative effects and its reported ability to relieve back pain [2].

Despite its broad therapeutic applications, prolonged or excessive use of S. alexandrina has been associated with adverse effects, including melanosis coli, diarrhea, and perineal blistering [10]. To minimize these side effects, several ITM practitioners recommended the use of senna in decoction form rather than as raw leaves. Furthermore, traditional guidelines advise thorough purification of the plant material and its co‐administration with sweet violet (Viola odorata L.), black myrobalan (Terminalia chebula Retz.), and anise (Pimpinella anisum L.) to mitigate potential toxicity [2].

Globally, S. alexandrina continues to play an important role in ethnomedicine. In Iraq, the leaves are traditionally used as a purgative [2], while in clinical settings senna is commonly administered to empty the bowels prior to diagnostic procedures such as colonoscopy [9]. In Morocco, decoctions and powdered preparations of S. alexandrina leaves are used for treating digestive disorders and cancer [12]. The plant is also among the most frequently used traditional remedies in villages surrounding Makkah for managing reproductive and gastrointestinal ailments [11]. In Gunung Sari, Indonesia, senna leaf decoction is employed as a traditional antidiabetic remedy [13], whereas in Niger, Africa, it is used to facilitate labor and control postpartum hemorrhage [14].

The wide‐ranging therapeutic effects of S. alexandrina are attributed to its rich phytochemical composition. This Ayurvedic herb contains essential bioactive compounds, including antioxidants, phytochemicals, minerals, and vitamins that contribute to disease prevention and immune system enhancement. Notably, its vitamin C content supports the formation of lymphocytes and phagocytes, which are critical components of the immune response [9]. Additionally, the abundance of anthraquinones, flavonoids, and alkaloids in S. alexandrina underlies its diverse biological activities, such as antioxidant, antimicrobial, antidiabetic, anti‐inflammatory, anti‐atherosclerotic, antiulcer, hypolipidemic, and hepatoprotective effects [2].

Taken together, these traditional uses cover a range of gastrointestinal, dermatological, musculoskeletal, neurological, respiratory, obstetric, cardiovascular, metabolic, and oncological conditions reported across Asia, Africa, and the Middle East, and are classified by disease category in Figure 2 [2, 9, 10, 11, 12, 13, 14].

FIGURE 2.

Ethnopharmacology Uses of S. alexandrina (multiple illustrations from NIAID NIH BIOART Source (bioart.niaid.nih.gov)).

4. Phytochemical Constituents

Phytochemical investigations of S. alexandrina have revealed a chemically diverse profile comprising anthraquinones and related anthracene derivatives, flavonoids, terpenoids, phenolic compounds, long‐chain aliphatic constituents, and miscellaneous volatile compounds, which are summarized in Table 1 and Figures 3, 4, 5, 6, 7, 8, 9, 10, 11.

TABLE 1.

Reported Phytochemical Constituents of S. alexandrina.

Anthraquinones and related anthracene derivatives (Figure 3)
Chrysophanol (1), leaf, aerial parts, [15, 16, 17] Aloe‐emodin (2), leaf, pod/fruit, aerial parts, [15, 16, 17, 18, 19, 20, 21] Emodin (3), fruit/pod, leaf, aerial parts, [16, 19, 21] Rhein (4), leaf, pod, [15, 17, 18, 19, 21, 22, 23, 24] Rhein‐8‐glucoside (5), fruit/pod, leaf, [18, 19] Aloe‐emodin‐8‐O‐glucoside (6), fruit, leaf, [19, 25] Emodin 8‐O‐sophoroside (7), leaf, [25] 1‐Hydroxy‐6,8‐dimethoxy‐3‐methylanthraquinone (8), seed, [26] 1,5,7‐Trihydroxy‐8‐methoxy‐3‐methyl‐anthraquinone (9), seed, [27] Emodin‐1‐O‐beta‐D‐glucopyranoside (10), leaf, [24] 1‐Hydroxy‐3,6,7,8‐tetramethoxy‐2‐isopropyl anthraquinone (11), seed, [27] 3‐isopentenyloxyemodin (12), leaf, fruit, [28] 3‐Geranyloxyemodine (13), leaf, fruit, [28] Tinnevellin (14), aerial parts, leaf, pod, [1, 18]	Torachrysone (15), aerial parts, [1] Tinnevellin 8‐O‐glucoside (16), leaf, pod, [18, 22] Aloin A (17), leaf, fruit/pod, [21] Aloin B (18), leaf, fruit/pod, [21] Sennidin A (19), leaf, pod/fruit, [18, 19, 22, 29] Sennidin B (20), leaf, pod/fruit, [18, 19, 22, 29] Sennoside A (21), leaf, pod/fruit, aerial parts, flower, stem, root, [1, 15, 16, 19, 22, 29, 30, 31, 32, 33, 34, 35] Sennoside C (22), pod/fruit, leaf, [19, 22] Sennoside B (23), pod/fruit, leaf, aerial part, flower, stem, root, [1, 16, 19, 21, 22, 23, 29, 30, 31, 32, 35, 36, 37] Sennoside D (24), pod/fruit, leaf, [19, 22, 24] Sennoside A1 (25), pod/fruit, leaf, [19, 22, 30] Sennoside D1 (26), pod/fruit, leaf, [19, 22] Aloe‐emodin dianthrone 8,8’‐di‐O‐glucoside (27), leaf, [25, 34] Sennoside E (28), leaf, [24]
Flavonoids and derivatives (Figure 4)
Scutellarein (29), leaf, [38] Quercitrin (30), leaf, [39] Kaempferol‐3‐glucoside (31), leaf, pod, [18, 39] Hyperoside (32), leaf, aerial parts, [1, 39] Isoquercitrin (33), leaf, aerial parts, [1, 39] Rutin (34), leaf, aerial parts, [1, 38, 39] Quercetin 3‐O‐gentiobioside (35), leaf, [25] Isorhamnetin 3‐O‐gentiobioside (36), leaf, [25] Kaempferol 3‐O‐gentiobioside (37), leaf, [25] Vicenin‐2 (38), pod, leaf, [22, 40] Quercetin (39), leaf, [39, 41] Isorhamnetin (40), leaf, aerial parts, [1, 39] Quercimeritrin (41), leaf, [38] Kaempferol (42), leaf, pod, [18, 22, 24, 39] Myricetin (43), leaf, [39] 3,7‐Dihydroxy‐4’,8‐dimethoxyflavone (44), flower, leaf, [42] Rhamnetin (45), aerial parts, [1]	5,7,4’‐Trihydroxy‐6,8,3’,6’‐tetramethoxy‐2,3‐dihydroflavonol (46), seed, [26] 14‐Hydroxyartonin E (47), flower, leaf, [42] Catechin (48), leaf, [39, 41] Epicatechin (49), leaf, flower, [39, 42] Kaempferol‐3‐O‐[(6″′‐O‐trans‐sinnapoyl)‐β‐D‐glucopyranosyl (1→6)]‐β‐D‐glucopyranoside (50), leaf, [40] Procyanidin A2 (51), leaf, [39] Hesperidin (52), leaf, [39] (‐)‐(2S)‐6‐Methoxy‐[2″,3″:7,8]‐furanoflavanone (53), flower, leaf, [42] (2S)‐7,8,Bis‐3’,4’‐(2,2‐dimethyl‐chromano)‐5‐hydroxyflavanone (54), flower, leaf, [42] Cyanidin‐3‐glucoside (55), leaf, [39] Petunidin‐3‐glucoside (56), leaf, [39] Malvidin‐3‐galactoside (57), leaf, [39] Delphindin 3,5‐diglucoside (58), leaf, [39]
Monoterpenoids (Figure 5)
Methyl acetate (59), leaf, [43] Bornyl acetate (60), leaf, [43] Menthol (61), leaf, [43] Neomenthol (62), leaf, [43] α‐Terpineol (63), leaf, [43] Menthone (64), leaf, [43] Linalool (65), leaf, [43] Isogeraniol (66), leaf, [43] Terpinen‐4‐ol (67), leaf, [43] Borneol (68), leaf, [43] Isomenthone (69), leaf, [43] 1,8‐Cineol (70), leaf, [43] Pulegone (71), leaf, [43] Piperitone (72), leaf, [43] Camphor (73), leaf, [43] α‐Thujone (74), leaf, [43] β‐Cyclocitral (75), leaf, [43] Fenchone (76), leaf, [43] α‐Terpinene (77), leaf, [43] γ‐Terpinene (78), leaf, [43]	α‐Phellandrene (79), leaf, [43] α‐Pinene (80), leaf, aerial parts, [43] Camphene (81), leaf, [43] Terpinolene (82), leaf, aerial parts, [43] β‐Phellandrene (83), leaf, [43] Sabinene (84), leaf, [43] Limonene (85), leaf, [43] 3‐Carene (86), leaf, [43] β‐Pinene (87), leaf, aerial parts, [43] Myrcene (88), leaf, [43] Carvone (89), leaf, [43] Thymol (90), leaf, [43] Carvacrol (91), leaf, [43] 2,6,6‐Trimethylcyclohexa‐1,3‐diene‐1‐carbaldehyde (92), leaf, [43] p‐Cymene (93), leaf, [43] (E)‐Anethole (94), leaf, aerial parts, [43] Estragole (95), leaf, aerial parts, [43] p‐Cymenene (96), leaf, [43]
Sesquiterpenoids (Figure 6)
(E)‐β‐Farnesene (97), leaf, [43] (E)‐Nerolidol (98), leaf, [43] Ar‐curcumene (99), leaf, [43] δ‐Cadinene (100), leaf, [43] α‐Humulene (101), leaf, [43]	β‐Caryophyllene (102), leaf, aerial parts, [43] Junipene (103), leaf, [43] Longicyclene (104), leaf, [43] Caryophyllene oxide (105), leaf, aerial parts, [43]
Diterpenoids (Figure 7)
(2E)‐3,7,11,15‐Tetramethyl‐2‐hexadecene (106), leaf, [44] Phytol (107), leaf, [43, 44, 45] 2,6,10‐Trimethyl, 14‐ethylene‐14‐pentadecene (108), leaf, [44]	6,10,14‐trimethylpentadecane‐2‐one (109), leaf, [43] Geranyllinalool (110), leaf, [44] Phytol acetate (111), leaf, [43]
Triterpenoids (Figure 8)
Squalene (112), leaf, [44] Oleanolic acid (113), seed, [46] β‐sitosterol (114), leaf, [24, 44] Stigmasterol (115), leaf, [24, 44]	3‐O‐{β‐D‐glucuronopyranosyl‐(1→4)‐[β‐D‐galactopyranosyl‐(1→2)]‐β‐D‐xylopyranosyl‐ (1→3)–β‐D‐glucopyranosyl}‐2, 16α‐dihydroxy‐4, 20‐hydroxy methyl olean‐12‐ene‐28‐oic acid (116), seed, [46]
Phenolic compounds (Figure 9)
Caffeic acid (117), leaf, [39, 41] Ferulic acid (118), leaf, [39, 41] 4‐Hydroxy benzoic acid (119), leaf, [39] Gallic acid (120), leaf, [39, 41] Vanillic acid (121), leaf, [39] Syringic acid (122), leaf, [39] Phenol, 2,4‐bis (1,1‐dimethylethyl)‐ (123), leaf, [44] Phenol, (1,1‐dimethylethyl)‐4‐methoxy‐ (124), leaf, [44] 4‐Vinyl‐2‐methoxyphenol (125), leaf, [43] Eugenol (126), leaf, [43] Ellagic acid (127), leaf, [39] 2‐Acetyl‐3‐methyl‐8‐methoxy‐1,4‐naphthoquinone‐6‐O‐β‐D‐glucopyranoside (128), leaf, [47] p‐Coumaric acid (129), leaf, [39, 41] trans‐Cinnamic acid (130), leaf, [39]	Vidalenolone (131), flower, leaf, [42] Methyl salicylate (132), leaf, [43] 3,5‐Dicaffeoylquinic acid (133), leaf, [39] Chlorogenic acid (134), leaf, [39] Neochlorogenic acid (135), leaf, [39] 6‐Hydroxy musizin (136), leaf, pod, [18] Torachrysone‐8‐O‐glucoside (137), leaf, [25] Cassiaphenone B‐2‐glucoside (138), leaf, pod, [18, 22] Cassiaphenone A‐2‐glucoside (139), pod, [22] Phloridzin (140), leaf, [39] Phloretin (141), leaf, [39] Syringaresinol 4‐O‐glucoside (142), leaf, [25] γ‐tocopherol (143), leaf, [44] Vitamin E (144), leaf, [44, 48]
Long‐chain aliphatic compounds and their derivatives (Figure 10)
Hexanoic acid (145), leaf, [43] Heptanoic acid (146), leaf, [43] Octanoic acid (147), leaf, [43] Nonanoic acid (148), leaf, [43] Decanoic acid (149), leaf, [43] Dodecanoic acid (150), leaf, [43] Tridecanoic acid (151), leaf, [43] Tetradecanoic acid (152), leaf, [43, 44] Pentadecanoic acid (153), leaf, [43, 44] Hexadecanoic acid (154), leaf, aerial parts, [43, 45] Heptadecanoic acid (155), leaf, [43] Octadecanoic acid (156), leaf, [43, 44] 9‐Octadecenoic acid (157), leaf, [43] 9,12‐Octadecadienoic Acid (Z, Z)‐ (158), leaf, [44, 45] Linolenic acid (159), leaf, [43, 44, 45] n‐Hexanol (160), leaf, [43] Octanol (161), leaf, aerial parts, [43] n‐Nonanol (162), leaf, [43] 1‐Heptacosanol (163), leaf, [44] 3‐Heptadecanol (164), leaf, [44] Pentanal (165), leaf, [43]	6‐Methyl‐hepta‐3,5‐dien‐2‐one (174), leaf, [43] Octa‐3,5‐dien‐2‐one (175), leaf, [43] 6‐Methyl‐5‐hepten‐2‐one (176), leaf, [43] 2,3‐Octandione (177), leaf, [43] Geranylacetone (178), leaf, [43] Pseudoionone (179), leaf, [43] Hexadecanoic acid, methyl ester (180), leaf, [44] Methyl stearate (181), leaf, [44] Methyl 9‐octadecenoate (182), leaf, [43] 9,12‐Octadecadienoic acid (Z, Z)‐, methyl ester (183), leaf, [44] 9,12,15‐Octadecatrienoic acid, methyl ester, (Z, Z, Z)‐ (184), leaf, [43, 44] Hexadecanoic acid, 2‐hydroxy‐1 (hydroxymethyl) ethyl ester (185), leaf, [44] 9‐Octadecenamide (186), leaf, [44] n‐Decane (187), leaf, [43] n‐Undecane (188), leaf, [43] Tridecane (189), leaf, [43] Pentadecane (190), leaf, [43] n‐Heptadecane (191), leaf, [43] n‐Octadecane (192), leaf, [43]
n‐Hexanal (166), leaf, [43] n‐Heptanal (167), leaf, [43] Octanal (168), leaf, [43] Nonanal (169), leaf, [43] 4‐Heptenal (170), leaf, [43] (2E)‐Hexenal (171), leaf, [43] 2‐Heptanone (172), leaf, [43] 2‐Octanone (173), leaf, [43]	Eicosane (193), leaf, [43] Heneicosane (194), leaf, [43] Docosane (195), leaf, [43] Tricosane (196), leaf, [43] Tetracosane (197), leaf, [43] Pentacosane (198), leaf, [43, 44] Hexacosane (199), leaf, [43] Heptacosane (200), leaf, [43] Tetracontane (201), leaf, [44]
Others (Figure 11)
2‐Ethylhexanol (202), leaf, [43] 1‐Octen‐3‐ol (203), leaf, [43] Benzaldehyde (204), leaf, [43] 3‐Methylbutanal (205), leaf, [43] 1‐Phenylpropan‐1‐one (206), leaf, [43] 3‐Methyl‐3‐buten‐2‐one (207), leaf, [43] 2,2,6‐Trimethylcyclohexanone (208), leaf, [43] Phenylmethyl acetate (209), leaf, [43] Benzoic acid, 4‐ethoxy‐, ethyl ester (210), leaf, [44]	Isoamyl formate (211), leaf, [45] 1‐Butanol, 3‐methyl‐, acetate (212), leaf, [44] 2‐Methylfuran (213), leaf, [43] 2‐Ethylfuran (214), leaf, [43] 2‐Pentylfuran (215), leaf, [43] Benzene, 1,2,4‐trimethoxy‐5‐(1‐ propenyl)‐, (Z)‐ (216), leaf, [44] 5,6‐Epoxy‐5,6‐dihydro‐β‐ionone (217), leaf, [43] β‐Ionone (218), leaf, [43] β‐Damascenone (219), leaf, [43]

FIGURE 3.

Anthraquinones and related anthracene derivatives reported from S. alexandrina.

FIGURE 4.

Flavonoids and derivatives reported from S. alexandrina.

FIGURE 5.

Monoterpenoids reported from S. alexandrina.

FIGURE 6.

Sesquiterpenoids reported from S. alexandrina.

FIGURE 7.

Diterpenoids reported from S. alexandrina.

FIGURE 8.

Triterpenoids reported from S. alexandrina.

FIGURE 9.

Phenolic compounds reported from S. alexandrina.

FIGURE 10.

Long‐chain aliphatic compounds and their derivatives reported from S. alexandrina.

FIGURE 11.

Other compounds reported from S. alexandrina.

Anthraquinones constitute the most characteristic and pharmacologically significant class in S. alexandrina. Major aglycones, including chrysophanol (1), aloe‐emodin (2), emodin (3), and rhein (4), have been widely reported from leaves, pods, fruits, and aerial parts [15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. Several glycosylated derivatives such as rhein‐8‐glucoside (5), aloe‐emodin‐8‐O‐glucoside (6), emodin 8‐O‐sophoroside (7), and emodin‐1‐O‐β‐D‐glucopyranoside (10), indicate extensive anthraquinone glycosylation within the species [18, 19, 25]. Dianthrones, including sennidin A (19) and sennidin B (20), and their corresponding glycosides, particularly sennosides A (21) and B (23), together with sennosides C–E (22, 24 & 28), are broadly distributed across different plant organs and account for the well‐established laxative activity of S. alexandrina [1, 15, 16, 18, 19, 21, 22, 23, 29, 30, 31, 32, 33, 34, 35, 36, 37]. Additional anthraquinones such as tinnevellin (14), torachrysone (15), and aloin derivatives (17 & 18) further contribute to the chemical diversity of this group [1, 18, 21, 22].

Flavonoids represent another major group, predominantly isolated from leaves and aerial parts. These include quercetin (39), kaempferol (42), myricetin (43), and isorhamnetin (40), along with their glycosides such as rutin (34), hyperoside (32), isoquercitrin (33), quercitrin (30), and kaempferol‐3‐glucoside (31) [1, 18, 22, 24, 38, 39, 41]. More complex glycosides, including quercetin and kaempferol gentiobiosides (35‐37), as well as catechins, procyanidins, and anthocyanins (48‐58), further enhance the antioxidant and anti‐inflammatory potential of the species [25, 39, 40, 41, 42].

The volatile fraction of S. alexandrina leaves is rich in monoterpenoids and sesquiterpenoids, including menthol (61), linalool (65), α‐terpineol (63), thymol (90), carvacrol (91), α‐pinene (80), β‐pinene (87), limonene (85), β‐caryophyllene (102), and caryophyllene oxide (105), which are commonly associated with antimicrobial, anti‐inflammatory, and spasmolytic activities [43]. Diterpenoids such as phytol (107) and geranyllinalool (110), and triterpenoids including squalene (112), oleanolic acid (113), β‐sitosterol (114), and stigmasterol (115), have also been reported and are linked to hepatoprotective, antioxidant, and lipid‐modulating effects [24, 43, 44, 45, 46].

Phenolic compounds are represented by a wide range of phenolic acids, including caffeic (117), ferulic (118), gallic (120), ellagic (127), chlorogenic (134), and p‐coumaric acids (129), as well as phenolic and naphthoquinone glycosides such as torachrysone‐8‐O‐glucoside (137) and cassiaphenone derivatives (138 & 139) [18, 22, 25, 39, 41]. In addition, long‐chain fatty acids, hydrocarbons, alcohols, aldehydes, ketones, and esters (145‐201), together with antioxidant tocopherols, including γ‐tocopherol (143) and vitamin E (144), have been identified in the leaves [43, 44, 45, 48].

Overall, the phytochemical profile of S. alexandrina is dominated by anthraquinone glycosides, particularly sennosides, that underpin its primary laxative use, while flavonoids, phenolics, and terpenoids collectively contribute to its antioxidant, anti‐inflammatory, antimicrobial, hepatoprotective, and metabolic activities [39, 49].

5. Biological Activities of S. alexandrina

S. alexandrina is a pharmacologically diverse botanical agent whose therapeutic applications extend far beyond its traditional use as a purgative. Modern research highlights its notable anticancer and antiproliferative properties, particularly in leaf ethanol and methanol extracts, which demonstrate dose‐dependent cytotoxicity against various cell lines, including Michigan cancer foundation‐7 (MCF‐7) and human colorectal carcinoma (HCT‐116), via reactive oxygen species (ROS) generation and antiangiogenic mechanisms. In the domain of metabolic health, the plant exhibits significant antidiabetic and antiobesity activities; specifically, aqueous extracts have been shown to normalize blood glucose and lipid profiles, while hexane fractions provide α‐glucosidase inhibition that can outperform standard pharmaceuticals like acarbose.

Furthermore, the species serves as a robust hepatoprotective and anti‐inflammatory agent, with methanol extracts normalizing critical liver enzymes (Alanine aminotransferase ALT, Aspartate aminotransferase AST, Alkaline phosphatase ALP) and downregulating pro‐inflammatory markers such as Tumor necrosis factor alpha (TNF‐α) and Interleukin‐6 (IL‐6). Its antimicrobial spectrum is equally broad, encompassing potent antibacterial action against S. aureus, antifungal efficacy in seed extracts, and specialized antiviral activity against Human Immunodeficiency Virus Type 1 (HIV‐1) integrase. These diverse bioactivities are fundamentally solvent‐dependent, meaning the therapeutic outcome, whether it be anthelmintic, antioxidant, or laxative, is determined by the specific extraction methodology employed.

The primary therapeutic activities of S. alexandrina are presented in Figure 12, while the detailed discussion is presented in Sections 5.1–5.7. The evidence supporting these activities varies considerably in robustness, ranging from independently replicated studies with appropriate controls to single preliminary reports. Throughout this section, greater emphasis has been placed on the quality and robustness of the available evidence rather than summarizing reported activities. Findings supported by established methodological criteria are distinguished from those that remain preliminary and require further investigation.

FIGURE 12.

Primary therapeutic activities of S. alexandrina (multiple illustrations from NIAID NIH BIOART Source (bioart.niaid.nih.gov)).

5.1. Anticancer and Antiproliferative Activities

The anticancer potential of S. alexandrina has been extensively investigated using both in vitro and in vivo experimental models, with a predominant focus on leaf‐derived extracts. Overall, the findings consistently demonstrate that methanolic and ethanolic extracts exhibit marked cytotoxic and antiproliferative effects, whereas aqueous extracts show little to no activity (Table 2).

TABLE 2.

Anticancer activities of S. alexandrina.

Plant part & extract	Experimental model	Key findings
Leaves; ethanol extracts; [38, 45, 48, 50, 51, 52]	In vitro (MCF‐7, HeLa, HCT‐116, Hep2, HepG2; murine neuroblastoma cells); In vivo (EAC‐ and prostate cancer–bearing rats)	Consistent dose‐dependent cytotoxic and antiproliferative effects in vitro (IC50 ≈ 13–40 µg/mL; LC50 0.275 mg/mL against neuroblastoma cells), selective over normal HEK‐293 cells; significant antitumor, antiangiogenic, antioxidant, hepatoprotective, hypolipidemic, and hematological normalization effects, in some cases comparable to methotrexate
Leaves; methanol extracts; [1, 38, 53]	In vitro (MCF‐7, HeLa, Hep2, HepG2, lung cancer cells)	Marked cytotoxic and antiproliferative activity (IC50 ≈ 4‐30 µg/mL), associated with ROS generation and relatively low toxicity toward normal cells
Leaves; ethanol‐precipitated polysaccharide fraction; [54]	In vivo (Sarcoma‐180 tumor–bearing mice)	Significant antitumor activity (∼52% tumor inhibition at 5 mg/kg), likely mediated via immunostimulatory mechanisms
Aerial parts; methanol extracts; [1]	In vitro (HepG2 cells)	Marked cytotoxicity at higher concentrations (50‐100 µg/mL), with minimal activity at lower doses
Leaves; acetone and ethyl acetate extracts; [38]	In vitro (MCF‐7, HeLa cells)	Moderate cytotoxic effects compared to polar organic extracts
Leaves; aqueous extracts; [38, 45, 55]	In vitro (Breast, lung, liver cancer cells; HepG2 cells)	No significant cytotoxicity or pathway modulation (IC50 > 1000‐2000 µg/mL); absence of NF‐κB and NRF2 regulation

In vitro 3‐(4,5‐Dimethylthiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays revealed that methanolic leaf extracts show cytotoxicity against human breast (MCF‐7), cervical (HeLa), and laryngeal (Hep2) cancer cell lines, with half‐maximal inhibitory concentration (IC₅₀) values ranging from 4.0 to 7.28 µg/mL. These same extracts showed comparatively lower toxicity toward normal human corneal epithelial cells (HCEC), indicating selective anticancer activity [38]. Similarly, ethanolic leaf extracts showed strong tumoricidal effects against murine neuroblastoma cells, yielding an LC₅₀ value of 0.275 mg/mL [50]. Comparable antiproliferative activity was observed against colorectal (HCT‐116), cervical (HeLa), liver (HepG2), and lung cancer cell lines, with IC₅₀ values generally falling within the range of approximately 13‐40 µg/mL, depending on extract concentration and cancer type [1, 45, 51, 52, 53]. Benchmarked against the National Cancer Institute's cytotoxicity threshold for crude plant extracts of IC₅₀ < 30 µg/mL [56], the methanolic leaf extracts (IC₅₀ 4.0–7.28 µg/mL) meet this criterion comfortably, while the ethanolic extract results (IC₅₀ 13–40 µg/mL) fall partly within and partly outside the accepted screening range. The neuroblastoma finding (LC₅₀ 0.275 mg/mL) exceeds this threshold and should therefore be regarded as weak activity by these criteria.

Several investigations further confirmed the dose‐dependent nature of the cytotoxic response, particularly for ethanolic and methanolic extracts, which significantly reduced cancer cell viability at concentrations ≥50–100 µg/mL [1, 45, 52]. Mechanistic insights from selected studies suggest that these effects may involve oxidative stress–mediated pathways, as evidenced by a substantial increase in reactive oxygen species (ROS) levels in lung cancer cells treated with methanolic extracts [53]. Importantly, multiple studies reported negligible cytotoxic effects on non‐malignant cell lines such as human embryonic kidney 293 (HEK‐293), reinforcing the selective action of S. alexandrina extracts toward cancer cells [38, 51]. However, it should be noted that these studies report reduced toxicity against the normal‐cell controls qualitatively rather than as calculated selectivity indices; a formal Selectivity Index of > 2 [57] would provide a more rigorous demonstration of selective anticancer activity, and this represents a specific methodological gap that future work on S. alexandrina should address.

In contrast, aqueous extracts consistently failed to demonstrate significant anticancer activity. Water‐based leaf extracts showed no cytotoxicity against breast, lung, or liver cancer cells, with IC₅₀ values exceeding 2000 µg/mL, and were ineffective in modulating molecular targets such as Nuclear Factor Kappa B (NF‐κB) and Nuclear Factor Erythroid 2‐related Factor 2 (NRF2) in HepG2 cells [45, 55]. These findings highlight the critical role of extraction solvent polarity in recovering bioactive anticancer constituents.

Additionally, polysaccharide fractions isolated from leaves demonstrated notable antitumor activity in Sarcoma‐180–bearing mice, achieving a tumor inhibition rate of 51.9%, likely mediated through immunostimulatory mechanisms rather than direct cytotoxicity [54]. In prostate cancer–induced rat models, ethanolic extracts improved hematological parameters, antioxidant enzyme status, lipid profiles, renal and hepatic biomarkers, and reduced oxidative stress, collectively indicating chemoprotective and anticancer effects [48].

Cross‐study comparison is limited by differences in plant parts, extraction solvents, cancer models, and reported endpoints (IC₅₀, LC₅₀, tumor inhibition rate). Despite these differences, methanolic and ethanolic leaf extracts generally show anticancer activity across studies, whereas aqueous extracts have not shown similar activity.

5.2. Anti‐inflammatory and Hepatoprotective Properties

Anti‐inflammatory activity has been consistently reported for leaf‐derived extracts in both in vitro and in vivo systems. Ethyl acetate extracts of the leaves exhibited notable inhibition of lipoxygenase activity, an effect that was mechanistically linked to the presence of aloe‐emodin (2), which acted as a competitive lipoxygenase inhibitor with an IC₅₀ of 29.49 µM [20]. The magnitude of enzyme inhibition by aloe‐emodin was comparable to that of the reference compound vanillin, supporting a direct contribution of this anthraquinone to the observed anti‐inflammatory effect. Similarly, crude extracts demonstrated appreciable activity in protein denaturation models; both 96% ethanolic and aqueous leaf extracts showed strong inhibition of bovine serum albumin (BSA) denaturation (>92%) at identical concentrations (0.5 mg/mL), suggesting comparable efficacy in this simplified in vitro assay [45].

Ethanolic extracts further demonstrated dual modulation of oxidative stress and inflammatory mediators. A 75% ethanol extract moderately induced NADP(H):quinone oxidoreductase activity and inhibited nitric oxide production in murine hepatoma cells, indicating antioxidant‐linked anti‐inflammatory potential [58]. Moreover, methanolic extracts preconditioned on adipose‐derived stem cell (ASC) enhanced cell viability, provided strong cytoprotection against heat‐induced injury in vitro (10–40 µg/mL), and when applied in vivo to burn wounds in rats, accelerated wound closure, normalized epidermal thickness, organized collagen fibers, and promoted development of skin appendages. These effects were accompanied by upregulation of proliferation, migration, angiogenesis, antioxidant defense, and anti‐apoptotic genes (Insulin‐like growth factor 1 IGF1, Vascular endothelial growth factor VEGF, B‐cell lymphoma 2 BCL2, etc.) and downregulation of pro‐inflammatory markers (IL‐6, TNF‐α, NF‐κB1), demonstrating combined anti‐inflammatory and tissue‐regenerative activity [59].

In vivo, a leaf decoction significantly reduced circulating TNF‐α levels in mice, reinforcing the systemic anti‐inflammatory effect of aqueous preparations [24]. In line with this, dietary supplementation with leaf powder attenuated inflammation, oxidative stress, and fibrosis in carbon tetrachloride (CCl₄)‐induced hepatic injury, as evidenced by reductions in pro‐inflammatory markers, nitric oxide levels, and histopathological damage [60].

Beyond inflammation, several studies highlighted hepatoprotective and hepatopreventive activities, which appear closely intertwined with the plant's anti‐inflammatory and antioxidant actions. Methanolic leaf extracts markedly ameliorated CCl₄‐induced hepatotoxicity in rats by normalizing liver enzymes, lipid profiles, oxidative stress parameters, and histological architecture [61]. Comparable protective trends were observed with powdered leaf preparations and aqueous decoctions, indicating that both polar extracts and whole‐plant preparations can exert hepatoprotective effects, albeit through potentially overlapping mechanisms involving antioxidant defense and suppression of inflammatory signaling [24, 60, 61].

However, not all findings uniformly support anti‐inflammatory activity. One study reported pro‐inflammatory effects following administration of ethanolic leaf extract in mice, characterized by elevated Interleukin‐1 beta (IL‐1β) and IL‐6 levels, reduced IgA, increased oxidative stress, and compromised intestinal barrier integrity [62]. This apparent contradiction may reflect differences in dosage, administration route, extract concentration, or target tissue, underscoring the importance of experimental context when interpreting biological activity [63].

Overall, while the majority of investigations support the anti‐inflammatory and hepatoprotective potential of S. alexandrina, direct quantitative comparison across studies remains limited due to heterogeneity in extraction methods, assay systems, doses, and biological models. Enzyme‐based assays, cell‐based systems, and animal studies collectively indicate beneficial effects, but variability in endpoints and units of measurement constrains strict comparability. Nonetheless, converging evidence suggests that methanolic and hydroethanolic leaf extracts of S. alexandrina consistently exhibit strong anti‐inflammatory and hepatoprotective properties, mediated via reduction of oxidative stress, nitric oxide (NO), and inflammatory cytokines, as well as normalization of liver enzymes and antioxidant systems (Table 3).

TABLE 3.

Anti‐inflammatory and hepatoprotective properties of S. alexandrina.

Plant part & extract	Experimental model	Key findings
Leaves; methanol, ethanol & aqueous extracts; [24, 45, 58, 61]	In vitro (Hepa 1c1c7 cells, BSA denaturation); In vivo (mice, rats)	Notable anti‐inflammatory effects: inhibition of NO production (MIR a 79.7%), QR b induction (MQI c 1.54 fold); hepatoprotective effects: normalized ALT, AST, ALP, γ‐GT d , lipid profile, and antioxidant enzymes; prevented pathological hepatic lesions
Leaves; methanol extract; [59]	In vitro (Adipose‐derived stem cells); In vivo (Burn wounds in rats)	Enhanced ASC viability (25–40 µg/mL), strong cytoprotection against heat‐induced injury; promoted early wound closure, normalized epidermal thickness, organized collagen fibers, proper skin appendages; upregulated genes for proliferation, migration, angiogenesis, antioxidant defense, anti‐apoptosis (IGF1, VEGF, BCL2, etc.); downregulated pro‐inflammatory markers (IL‐6, TNF‐α, NF‐κB1)
Leaves; ethyl acetate extract & isolated compound aloe‐emodin (2); [20]	In vitro (Lipoxygenase assay)	Moderate anti‐inflammatory activity: lipoxygenase inhibition (54–60% at 40 mg/mL / 0.2 mM); aloe‐emodin acts as a competitive inhibitor (IC50 = 29.49 µM)
Leaves; powder (dietary supplementation); [60]	In vivo (CCl4‐induced liver injury in mice)	Hepatoprotective and anti‐inflammatory: reduced oxidative stress, lipid peroxidation, fibrosis, NO levels, hepatic cell infiltration, and liver enzyme levels
Leaves; aqueous extract; [24, 45]	In vivo (Mice, TNF‐α measurement); In vitro (BSA denaturation)	Significant anti‐inflammatory activity: ↓ TNF‐α (105.1 ± 28.0 pg/mL), inhibition of protein denaturation (>93%); minimal impact on adiponectin
Leaves; ethanol extract; [62]	In vivo (Mice, intestinal inflammation)	Pro‐inflammatory effect: ↑ IL‐1β, IL‐6, oxidative stress; impaired intestinal barrier and tight‐junction protein expression

^aMIR: Maximum inhibition rate of NO production under the nontoxic tested concentration.

^bQR: Quinone reductase.

^cMQI: Maximum folds of QR inducing activity under the tested concentration.

^dγ‐GT: Gamma‐glutamyl transferase.

Ethyl acetate extracts and isolated compounds (e.g., aloe‐emodin (2)) show moderate, mechanistically supported activity, while methanolic extracts preconditioned on stem cells demonstrate combined anti‐inflammatory and wound‐healing effects, highlighting both in vitro and in vivo relevance, while aqueous decoctions retain anti‐inflammatory potential but are less hepatoprotective than organic extracts. Powdered leaves and polysaccharide fractions show hepatoprotective and immunomodulatory effects, highlighting additional in vivo relevance. High‐dose ethanol extracts in gut models may induce pro‐inflammatory responses, emphasizing dose‐ and context‐dependent effects.

5.3. Metabolic and Gastrointestinal Activities

In addition to its anti‐inflammatory properties, S. alexandrina has been investigated in vivo and in vitro for a range of metabolic activities, including enzyme inhibition relevant to carbohydrate and lipid digestion, antidiabetic, antiobesity, antihyperlipidemic, and laxative effects (Table 4).

TABLE 4.

Metabolic, antidiabetic, antiobesity, and laxative activities of S. alexandrina.

Plant part & extract	Experimental model	Key findings
Leaves; powder (dietary supplementation); [64]	In vivo (High‐fat diet–fed rats)	Marked anti‐obesity and metabolic effects: reduced body and liver weight, adipose deposition, plasma glucose, cholesterol, triglycerides; improved antioxidant enzymes (SOD a , GSH b ), downregulated inflammatory and lipogenic genes; prevented hepatic steatosis, fibrosis, and inflammation. Effects comparable to atorvastatin.
Leaves, aqueous extract; [65]	In vivo (Poloxamer‐407–induced hyperlipidaemic rats)	Strong antihyperlipidemic effect (400 mg/kg dosage): decreased TC c , TG d , LDL e , VLDL f , non‐HDL g cholesterol, atherogenic indices; comparable to atorvastatin, with no observed toxicity.
Leaves; 80% aqueous ethanol extract; [66]	In vivo (Nicotinamide‐STZ h –induced type 2 diabetic mice)	Antihyperglycemic effect at low doses (10–50 mg/kg) via an apparently insulin‐independent mechanism, possibly improved peripheral glucose utilization or delayed intestinal glucose absorption; reduced fasting and post‐prandial glucose levels.
Leaves; aqueous extract; [67]	In vivo (STZ‐induced type 1 diabetic mice)	Neuroprotective antidiabetic effect: prevented diabetic neuropathy and cognitive deficits; preserved myelin, synaptic proteins, and neuronal integrity.
Leaves; methanol–water (80:20) extract and hexane, chloroform, and ethyl acetate fractions; [37]	In vitro (α‐Glucosidase inhibition assay)	Strong enzyme inhibition: hexane fraction (94%) and main extract (58%) at 484 µg/mL, exceeding acarbose (50% at 750 µM); weak activity in chloroform and ethyl acetate fractions.
Leaves; methanol extract; [39]	In vitro (Enzyme inhibition assays)	Moderate inhibition of α‐glucosidase and α‐amylase, expressed as ACAE i equivalents; activity dependent on assay expression rather than IC50 values.
Herbal tea (leaf infusion); [41]	In vitro (Digestive enzyme inhibition assays)	Minimal α‐amylase (1.23%) and α‐glucosidase (<10%) inhibition; moderate lipase inhibition (<65%), suggesting mild supportive metabolic effects.
Plant part not specified; methanol extract; [68]	In vitro (α‐Amylase inhibition assay)	No inhibitory activity (0% inhibition at 2 mg/mL), indicating lack of consistency across extracts and assays.
Leaves; hot‐water infusion; [32]	In vivo (Rat laxative bioassay)	Clear dose‐dependent laxative activity; >50% wet feces at 500 mg/kg, confirming traditional purgative use.
Pods (no extraction); [36]	In vivo (Rat laxative model)	Strong laxative effect with increased soft feces, reversal of water absorption, and elevated colonic prostaglandins; peak effect at 6–8 h.
Leaves; 50% ethanol extract; semi‐purified sennosides fraction; isolated compound sennoside A (21); [33]	In vivo (Rat diarrhea and toxicity models)	Sennosides fraction showed strongest laxative activity; crude extract caused dose‐dependent diarrhea and organ toxicity at high doses; sennoside A highly potent but associated with colonic damage at higher doses.
Commercially purchased sennoside A (21), sennoside B (23), sennidin A (19), and sennidin B (20); [29]	In vivo (Caco‐2 intestinal transport model)	Poor systemic absorption; active efflux into lumen; supports a laxative effect mediated by colonic conversion to rhein anthrone rather than parent compounds (19‐21 & 23).
Isolated compounds from leaves; sennoside A (21) and Glycoside I (aloe‐emodin dianthrone diglucoside) (27); [34]	In vivo (Mouse laxative assay)	No laxative effect alone; enhanced sennoside A (21) activity (∼1.3‐fold), indicating synergistic rather than intrinsic activity.

^aSOD: Superoxide dismutase.

^bGSH: Reduced glutathione.

^cTC: Total cholesterol.

^dTG: Triglycerides.

^eLDL: Low‐density lipoprotein.

^fVLDL: Very‐low‐density lipoprotein.

^gHDL: High‐density lipoprotein.

^hSTZ: Streptozotocin.

ⁱACAE: Acarbose equivalents.

Enzyme inhibition studies provide initial mechanistic evidence supporting the metabolic effects of S. alexandrina. Methanolic leaf extracts showed measurable inhibitory activity against α‐glucosidase and α‐amylase, expressed as acarbose equivalents, although the magnitude of inhibition was moderate [39]. Fractionation of methanol‐water extracts further revealed that nonpolar fractions, particularly the hexane fraction, exhibited strong α‐glucosidase inhibition (94%), outperforming acarbose under the tested conditions, whereas more polar chloroform and ethyl acetate fractions were weakly active [37]. In contrast, other investigations reported negligible or absent α‐amylase inhibition by methanolic extracts even at higher concentrations [68], indicating variability likely attributable to differences in extraction protocols, enzyme sources, assay conditions, and reporting units. Aqueous preparations, including decoctions and infusions, generally exhibited weak to moderate inhibition of digestive enzymes, with limited α‐amylase and α‐glucosidase inhibition and modest pancreatic lipase inhibition [41]. These findings suggest that while enzyme inhibition may contribute to metabolic effects, it alone does not fully explain the in vivo efficacy observed in animal models.

More consistent and biologically relevant evidence for antidiabetic activity has been demonstrated in vivo. Distilled water extracts prevented neurological complications in type 1 diabetic mice, preserving cognitive function and neuronal integrity, thereby extending the antidiabetic effect to diabetes‐associated neuropathy [67]. Leaf extracts prepared with 80% aqueous ethanol also exhibited strong antihyperglycemic effects in type 2 diabetic mouse models, despite not restoring insulin levels, suggesting insulin‐independent mechanisms such as improved peripheral glucose utilization or delayed intestinal glucose absorption [66].

Antiobesity and lipid‐modulating effects have been reported primarily through long‐term dietary intervention studies [69, 70]. Leaf powder supplementation in high‐fat diet–fed rats led to significant reductions in body weight, adipose tissue accumulation, plasma glucose, lipid levels, oxidative stress markers, and hepatic inflammation. These effects were accompanied by modulation of fat‐metabolizing and inflammatory gene expression and were reported to be comparable to atorvastatin treatment [64]. In line with these findings, aqueous leaf extracts improved hyperlipidemia and atherogenic indices in chemically induced hyperlipidemic rats, again showing efficacy comparable to atorvastatin without evident toxicity [65]. Collectively, these studies suggest that whole‐leaf preparations exert systemic metabolic benefits that extend beyond simple enzyme inhibition.

The laxative activity of S. alexandrina remains its most well‐established and mechanistically elucidated pharmacological effect. Multiple in vivo studies consistently demonstrated dose‐dependent induction of soft or watery stools following administration of leaf or pod preparations, hot water infusions, crude extracts, or sennoside‐enriched fractions [32, 33, 36]. Mechanistic investigations using Caco‐2 intestinal cell monolayers showed that sennosides and related dianthrones exhibit poor absorption in the upper gastrointestinal tract and are actively effluxed back into the intestinal lumen, supporting the concept that these compounds function as prodrugs [29]. Their conversion by colonic microbiota into the active metabolites underlie the laxative effect [71]. Comparative studies further indicated that purified sennoside fractions exert stronger laxative activity with lower systemic toxicity than crude extracts, which at high doses were associated with hepatic and renal alterations [33]. The hepatic effects associated with anthraquinone exposure have been attributed to metabolic activation by cytochrome P450 enzymes, sulfotransferases and glucuronosyltransferases, generating reactive metabolites that deplete glutathione and bind hepatic proteins [72]. Synergistic interactions among dianthrones were also reported, as glycoside I (27) enhanced the laxative potency of sennoside A (21) despite being inactive on its own [34].

In vitro enzyme inhibition assays have yielded variable and, in some cases, contradictory results. In contrast, in vivo evidence for antidiabetic, antiobesity, antihyperlipidemic, and laxative activities is more consistent, although differences in extract composition and dosing limit direct comparisons across studies. Aqueous, hydroethanolic, and powdered leaf preparations account for most of the reported metabolic effects, whereas the laxative activity is primarily attributed to isolated sennosides and related anthraquinones.

5.4. Safety Profile: Genotoxicity, Cytotoxicity, and Anthraquinone‐Related Concerns

The safety profile of S. alexandrina has been investigated through multiple genotoxicity, cytotoxicity, and antimutagenicity assays, employing diverse biological models, plant parts, extract types, and endpoints. Overall, the available evidence indicates a predominantly low genotoxic and cytotoxic risk, although some context‐dependent and assay‐specific effects have been reported.

Several studies support the absence or minimal expression of genotoxicity. In vivo assessment in mice showed that oral administration of isolated constituents, including sennoside B (23) and rhein (4), as well as a 50% methanolic leaf extract, did not induce significant chromosomal aberrations in bone marrow cells, despite weak genotoxic signals observed for the isolated compounds at tested doses [23]. Similarly, human peripheral blood leukocytes exposed to aqueous and methanolic leaf extracts (125‐500 µg/mL) showed no detectable DNA damage when evaluated using the alkaline comet assay, supporting the non‐genotoxic nature of these extracts in a human cell‐based model [73]. Consistently, ethanol–water (60:40) extracts of leaves and pods did not induce micronuclei formation in cultured human lymphocytes and were non‐cytotoxic at concentrations up to 5000 µg/mL, further reinforcing their apparent genomic safety under these conditions [21].

Additional complexity is highlighted by studies reporting dual genotoxic and antimutagenic properties. An aqueous leaf extract induced plasmid DNA strand breaks in vitro in a concentration‐dependent manner at low microgram levels; however, the same extract was neither cytotoxic nor mutagenic in Escherichia coli–based assays and significantly reduced hydrogen peroxide–induced mutagenesis and toxicity in oxidative stress–sensitive bacterial strains [74]. This dual behavior points toward an antioxidant‐driven protective effect, despite the extract's ability to interact directly with DNA under certain experimental conditions.

Cytotoxicity assessments across studies generally indicate low acute toxicity. These findings align with results from mammalian cell‐based assays reporting no cytotoxic effects for leaf and pod extracts across broad concentration ranges [21, 74].

Collectively, the evidence points to a favorable safety margin for S. alexandrina extracts, particularly in mammalian in vivo and human cell‐based systems, though direct comparison across studies is limited by heterogeneity in experimental models, endpoints, extract composition, and dose. The genotoxic signals that have been detected occur mainly in simplified or DNA repair–deficient systems, suggesting that risk is context‐, dose‐, and model‐dependent rather than an intrinsic property of the plant. At pharmacologically relevant doses, S. alexandrina therefore appears to carry low genotoxic and cytotoxic potential, with some extracts additionally showing antimutagenic and antioxidant protective effects.

The studies reviewed above focus on genotoxic and cytotoxic endpoints under typical experimental conditions. The broader toxicological literature has additionally raised specific concerns about the anthraquinone class in the context of chronic use. Long‐term use of anthraquinone‐containing laxatives is well established as the primary cause of melanosis coli, a benign brown pigmentation of the colonic mucosa that resolves on discontinuation of the laxative [75]. This is consistent with the melanosis coli signal already noted in Section 3 as an adverse effect of prolonged S. alexandrina use. Concerns regarding colorectal cancer risk have also been examined; a recent systematic review and meta‐analysis of observational studies did not find a statistically significant association between anthraquinone laxative use and colorectal cancer, though the authors noted that the underlying evidence base remains limited [76]. Notably, these safety concerns are strongly linked to the isolated free anthraquinones (emodin, aloe‐emodin) and to chronic high‐dose exposure, rather than to the whole traditional preparation used short‐term, which is consistent with the low genotoxicity of whole extracts already reported in this review. This distinction, between short‐term whole‐preparation use and chronic exposure to isolated anthraquinones, is an important one for interpreting the safety profile of S. alexandrina in traditional practice.

5.5. Antioxidant Potential

The antioxidant activity of S. alexandrina has been extensively investigated across multiple plant parts, extraction solvents, and in vitro assay systems, with leaves consistently demonstrating the highest activity. Overall, polar organic extracts, particularly methanolic, ethanolic, and aqueous‐ethanolic preparations, exhibit the strongest free radical scavenging and reducing capacities, whereas aqueous extracts and infusions show moderate to weak activity.

Comparative studies consistently indicate that leaf methanol and ethanol extracts display superior 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity, often with IC₅₀ values in the low µg/mL range [38, 61]. These extracts also demonstrate broad‐spectrum antioxidant effects across 2,2’‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric ion reducing antioxidant capacity (CUPRAC), phosphomolybdenum (PBD), and metal chelation assays [39, 73]. The high activity of these extracts correlates strongly with total phenolic content (TPC) and total flavonoid content (TFC), highlighting a phenolic‐driven antioxidant mechanism [38, 39, 48, 53, 61]. Ethanolic extracts further exhibit hydroxyl, superoxide, and nitric oxide radical scavenging, alongside significant levels of vitamins, tannins, and carotenoids [48]. Mechanistically, the antioxidant activity is putatively attributed to the phenolic acids and flavonoids catalogued in Section 4, which include known radical scavengers such as quercetin (39), rutin (34), gallic acid (120), and ferulic acid (118). These compounds are established donors of hydrogen atoms and single electrons to reactive oxygen species and are also capable of chelating transition metal ions that catalyze oxidative damage.

Aqueous‐ethanolic (70%) leaf and flower fractions extracted via microwave‐assisted, Soxhlet, sonication, marination, or reflux techniques show activity that depends on both plant part and extraction method. Microwave extraction consistently yielded the strongest DPPH scavenging activity, with flower fractions slightly outperforming leaves [42]. These results emphasize that extraction methodology and plant organ selection are important determinants of antioxidant yield.

Aqueous preparations, including herbal tea infusions, exhibit moderate antioxidant effects. Herbal tea infusions show modest radical scavenging activity and phenolic content [41, 77], while water‐extracted polymeric fractions retain substantial DPPH scavenging and ferric reducing power at higher concentrations [78]. Water extracts additionally demonstrate effective metal chelating, nitric oxide scavenging, and reducing power activities, in some cases surpassing standard antioxidants such as vitamin C [55]. These observations indicate that high‐molecular‐weight constituents in aqueous extracts may contribute meaningfully to antioxidant effects.

Methanolic extracts of other plant parts, including pods, stems, and roots, exhibit antioxidant activity in descending order: leaves > pods > stems > roots, which parallels their respective TPC and TFC values [53]. Methanolic extracts of unspecified plant parts also show moderate DPPH scavenging activity, consistent with the solvent‐driven extraction of phenolic antioxidants [68].

High‐concentration ethanolic and aqueous leaf extracts consistently demonstrate strong DPPH scavenging in simplified assays [16, 45, 52], and standardized aqueous‐ethanolic and methanol extracts support this potency across ABTS and FRAP assays [39, 73], though direct quantitative comparison across studies is limited by variability in assay conditions, extract concentrations, units of measurement, and extraction protocols. S. alexandrina, particularly its leaves, is therefore best characterized as a rich source of natural antioxidants, with polar organic extracts consistently outperforming aqueous and infusion preparations. This activity tracks closely with phenolic and flavonoid content, which serve as reliable predictors of antioxidant potential regardless of the specific extraction method or plant part used.

5.6. Antimicrobial and Anthelmintic Activities

5.6.1. Antibacterial Activity

The antimicrobial potential of S. alexandrina has been extensively evaluated in vitro against a broad range of bacteria, using diverse plant parts, extraction solvents, and susceptibility assays. The sole in vivo evidence, which demonstrated improved survival in Caenorhabditis elegans following infection is presented alongside the corresponding in vitro findings in Table 5. Overall, leaf‐derived extracts, particularly those obtained using polar organic solvents, consistently demonstrated the strongest antimicrobial effects, while aqueous preparations generally exhibited weaker or variable activity (Table 5).

TABLE 5.

Antibacterial activities of S. alexandrina.

Plant part & extract	Bacteria species	Key findings
Leaves; methanol extract; [35, 38, 53, 79]	S. aureus, E. coli, P. aeruginosa, K. pneumoniae, Bacillus spp., S. typhi, E. cloacae; C. elegans infection model	Broad‐spectrum, strongest antibacterial activity; large inhibition zones, low MICs; induces ROS, membrane disruption, reduces bacterial viability; improves survival of infected C. elegans; leaf extract generally most active among plant parts
Leaves; methanol & 50% aqueous‐ethanol extracts; [80, 81]	Streptococcus sobrinus, Porphyromonas gingivalis	Modest anti‐caries activity (MIC 2.0 mg/mL); moderate inhibition of P. gingivalis (MIC 1 mg/mL)
Leaves; ethanol extract; [45, 51, 82]	S. aureus, E. coli	Moderate‐strong activity; concentration‐dependent inhibition; sub‐mg/mL to low mg/mL MICs; ultrastructural damage to bacterial cells
Leaves; acetone extract; [38]	B. cereus, S. saprophyticus, P. acne, S. enterica	Moderate activity; strongest against B. cereus and S. saprophyticus; MIC 312.5 µg/mL for best strains
Leaves; ethyl acetate extract; [38]	S. aureus, E. coli, S. marcescens, P. aeruginosa	Moderate activity; generally weaker than methanol and ethanol extracts
Leaves; refluxed/macerated & aqueous‐methanolic extract (80:20); [79]	S. aureus, E. coli, P. aeruginosa, K. pneumoniae, E. cloacae, E. faecalis	Low antibacterial activity; MIC 1.6‐12.8 mg/mL; no inhibition at 1 mg/disc
Leaves; aqueous extract; [38]	S. aureus, E. coli, X. citri, X. campestris	Weak activity; smaller inhibition zones; moderate activity at high concentrations; generally, less potent than organic solvent extracts

Among the different solvents tested, methanolic leaf extracts emerged as the most notable and broad‐spectrum antimicrobial preparations. Multiple studies using disc diffusion, agar well diffusion, and minimum inhibitory concentration (MIC)‐based assays reported consistent inhibitory effects of methanolic leaf extracts against both gram‐positive and gram‐negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus spp., Salmonella typhi, and Enterobacter cloacae [35, 38, 53, 79]. In comparative evaluations of different plant parts, methanol extracts of leaves showed superior antibacterial activity relative to pods, stems, and roots, correlating with higher phenolic content and enhanced membrane‐disruptive effects [35, 53]. Mechanistic studies further demonstrated that methanolic extracts induce reactive oxygen species (ROS) generation, compromise bacterial membrane integrity, and reduce cell viability, supporting a multi‐target antibacterial mode of action [35].

In addition to antibacterial effects, methanolic leaf extracts also exhibited notable antifungal activity, particularly against Candida albicans, with inhibition zones and MIC values comparable or superior to those of ethanol and ethyl acetate extracts [38]. However, when tested against oral pathogens such as Streptococcus sobrinus, methanol and 50% hydroethanolic leaf extracts showed only modest anticaries activity, with relatively high MIC values (2.0 mg/mL), indicating limited potency against this specific organism [80]. These findings highlight that antimicrobial efficacy is pathogen‐dependent, even for otherwise active extracts.

Ethanolic leaf extracts, including high‐strength (96%) ethanol preparations, consistently demonstrated moderate to strong antibacterial activity, particularly against S. aureus and E. coli, with MIC values in the sub‐mg/mL to low mg/mL range [45, 51, 82]. Concentration‐dependent inhibition and ultrastructural damage to bacterial cells were confirmed using scanning electron microscopy (SEM), reinforcing the biological relevance of these findings [51]. Ethanolic extracts also showed antifungal and anthelmintic activities in broader antimicrobial screenings reported elsewhere, although their antibacterial potency was generally slightly lower than that of methanolic extracts.

Acetone and ethyl acetate leaf extracts displayed moderate antibacterial and antifungal activities across several studies. Acetone extracts were particularly effective against Bacillus cereus and Staphylococcus saprophyticus, with relatively low MIC values, while ethyl acetate extracts showed consistent inhibition of S. aureus, E. coli, and Serratia marcescens [38]. Nonetheless, these extracts were typically less potent and less broad‐spectrum than methanolic counterparts.

Aqueous extracts, whether prepared as decoctions, infusions, or cold‐water extracts, generally exhibited the weakest antimicrobial effects. A study reported minimal to moderate inhibition zones against plant‐pathogenic bacteria such as Xanthomonas citri and Xanthomonas campestris, as well as reduced activity against human pathogens compared with organic solvent extracts [38]. These discrepancies likely reflect differences in extraction protocols, extract concentration, and target organisms.

In addition to activity against common Gram‐positive and Gram‐negative pathogens, leaf methanolic and 50% ethanolic extracts also exhibited moderate inhibitory effects against the oral pathogen Porphyromonas gingivalis (MIC = 1 mg/mL), extending the antimicrobial spectrum of S. alexandrina to periodontal‐associated bacteria [81].

Despite the overall consistency in identifying methanolic and ethanolic leaf extracts as the most active antimicrobial preparations quantitative comparison across studies is limited by variability in assay methods, extract concentrations, bacterial strains tested. The qualitative pattern nonetheless holds: leaf extracts outperform other plant parts, polar organic solvents recover the most active constituents, and methanol‐based preparations show the highest antibacterial and antifungal efficacy, with mechanistic studies pointing to membrane disruption and oxidative stress induction as contributing factors. Aqueous extracts retain only limited activity, while synergistic combinations may offer a promising avenue for future pharmacological development, putatively through the combined action of anthraquinones, which disrupt bacterial membrane integrity, and phenolic constituents, which are known to inhibit bacterial enzymes and interfere with quorum sensing.

5.6.2. Antifungal Activity

The antifungal potential of S. alexandrina has been investigated using different plant parts, extraction solvents, and in vitro bioassay systems. Overall, the findings indicate that S. alexandrina exhibits measurable antifungal activity against a range of phytopathogenic and human‐pathogenic fungi, with efficacy influenced by plant part, solvent polarity, extract complexity, and target organism (Table 6). However, substantial methodological variability across studies limits direct quantitative comparison.

TABLE 6.

Antifungal activities of S. alexandrina.

Plant part & extract	Fungal species	Key findings
Seeds; methanol extract and isolated triterpenoid saponin (116); [46]	Colletotrichium dematium, Alternaria alternata, Curvularia lunata, Fusarium roseum, Aspergillus flavus	Strong antifungal activity; crude methanolic extract showed highest inhibition (up to 72.5%) and was more active than isolated saponin; butanol fraction and compound 116 showed moderate‐strong inhibition
Leaves; ethanol extract; [83]	Candida auris, Candida parapsilosis, Candida albicans	Strong activity with low MICs (0.78–1.56 mg/mL), particularly against C. auris and C. parapsilosis
Aerial parts; aqueous extract; [84]	Aspergillus flavus	Dose‐dependent inhibition; strong growth suppression at 600–800 µg/mL; MIC = 600 µg/mL
Plant part not stated; methanol extract; [85]	Aspergillus fumigatus	Weak antifungal activity (inhibition zone 5.56 ± 0.11 mm)

Seed‐derived extracts have provided early evidence of antifungal activity. In a detailed bioassay‐guided study, methanolic seed extracts were fractionated using n‐hexane, chloroform, n‐butanol, and water, leading to the isolation of a triterpenoid saponin, (1→3)‐β‐D‐glucopyranosyl‐2,16α‐dihydroxy‐4,20‐hydroxymethyl olean‐12‐ene‐28‐oic acid (116) [46]. At 1000 µg/mL, this compound exhibited its highest inhibition (69.5%) against Colletotrichum dematium, while lower activity was observed against Aspergillus flavus (37%). Acid hydrolysis of the compound yielded a related aglycone with reduced activity. Notably, the crude methanolic seed extract showed slightly higher antifungal efficacy than the isolated compound, achieving 71.5% inhibition against C. dematium and 55.5% against A. flavus. The crude extract also demonstrated broad‐spectrum activity against Alternaria alternata, Curvularia lunata, and Fusarium roseum suggesting synergistic interactions among multiple phytoconstituents [46]. These results highlight the importance of extract complexity in antifungal efficacy.

Leaf‐derived extracts generally display consistent antifungal effects. Ethanolic leaf extracts demonstrated comparatively stronger antifungal activity against clinically relevant Candida species. An ethanol extract showed MIC values of 0.78125 mg/mL against Candida auris and Candida parapsilosis, and 1.5625 mg/mL against C. albicans, indicating higher potency than most aqueous and methanolic preparations reported elsewhere [83]. This enhanced activity may reflect improved solubility of specific antifungal compounds in ethanol or differences in assay sensitivity.

Antifungal activity has also been reported for extracts derived from aerial and unspecified part materials. An aqueous extract of aerial parts exhibited strong, dose‐dependent inhibition of Aspergillus flavus, with fungal growth diameters decreasing markedly as extract concentration increased from 200 to 800 µg/mL. A minimum inhibitory concentration of 600 µg/mL was established after 48 h, indicating substantial antifungal efficacy at higher concentrations [84]. In another study, a crude extract of unspecified plant part, the methanolic extracts showed measurable inhibition against Aspergillus fumigatus, producing a zone of inhibition of 5.56 ± 0.11 mm, although extract concentration and extraction parameters were not reported [85].

Antifungal results across studies are only partially comparable, given variation in plant parts, extraction solvents, assay methods, and fungal strains tested. Even so, three qualitative trends hold consistently: crude extracts tend to outperform isolated compounds, likely reflecting synergistic effects; polar solvents, particularly methanol and ethanol, yield more active extracts than non‐polar or aqueous systems; and leaf and seed extracts are the most promising sources of antifungal constituents. Taken together, S. alexandrina shows moderate to strong antifungal activity, though standardized methodologies are needed to support more reliable cross‐study comparison. The molecular basis of the antifungal activity has not been directly investigated in these studies but is putatively attributed to the triterpenoid saponin (116) isolated from the seeds and to the anthraquinone constituents present throughout the plant; saponins classically disrupt fungal membranes through interaction with membrane sterols, and anthraquinones are established inhibitors of fungal respiration through interference with the electron transport chain.

5.6.3. Antiviral, Antiprotozoal, and Antimalarial Activities

The antiviral, antiprotozoal and antimalarial potential of S. alexandrina has been explored in vitro in a limited number of studies using different plant parts, extraction solvents, and biological targets. Overall, these investigations suggest that S. alexandrina exhibits selective and generally moderate activity against certain viruses and protozoa, with efficacy strongly influenced by solvent polarity, extract concentration, and the biological system employed.

Antiviral activity has been reported primarily for leaf and fruit extracts. In an early screening against hepatitis C virus (HCV), the aqueous fruit extract demonstrated modest inhibitory activity against HCV protease, achieving 24.4% ± 1.5% inhibition at 100 µg/mL, whereas the corresponding methanolic extract showed no detectable activity at the same concentration [86]. This finding indicates that water‐soluble constituents in the fruits may contribute to anti‐HCV effects, although the relatively low level of inhibition suggests limited potency.

More pronounced antiviral effects were observed against HIV‐1, particularly with ethanolic leaf extracts. An ethanol extract of the leaves inhibited HIV‐1 integrase with an IC₅₀ value of 4.9 ± 1.4 µg/mL, whereas the aqueous extract was ineffective (IC₅₀> 100 µM), highlighting the importance of organic solvents for extracting active antiviral constituents [87]. However, when evaluated in a cell‐based MT‐4 assay measuring HIV‐1–induced cytopathic effects, the ethanol extract did not achieve complete viral inhibition (IC₁₀₀), and cytotoxicity was observed at 100 µg/mL, indicating a narrow therapeutic window in this system [87]. In a separate and more mechanistic study, an ethanolic leaf extract significantly reduced HIV‐1 infectivity and viral particle release, with half‐maximal effective concentration (EC₅₀) and half‐maximal cytotoxic concentration (CC₅₀) values of 29 µg/mL and 88 µg/mL, respectively [88]. This study further demonstrated that the extract interferes with HIV‐1 maturation by disrupting the processing of the Gag (Pr55) polyprotein, thereby impairing proper core formation and reducing viral infectivity [88]. Taken together, these findings suggest that leaf ethanol extracts possess moderate but mechanistically supported anti‐HIV activity, although variability in assay endpoints and cytotoxicity limits direct quantitative comparison between studies.

In addition to antiviral investigations, several studies examined the antiprotozoal and antimalarial activities of S. alexandrina. A water extract prepared from commercial pod material exhibited weak to moderate growth inhibition against a panel of protozoan parasites. At 10 µg/mL, the extract inhibited Trypanosoma brucei rhodesiense (17.2%), Leishmania donovani (34.4%), and Plasmodium falciparum (14.0%), but showed no activity against Trypanosoma cruzi at either tested concentration [89]. The generally low inhibition percentages indicate limited antiparasitic potency, although some degree of selectivity toward specific protozoa was evident.

Further antiprotozoan evaluation focused on Acanthamoeba triangularis, an opportunistic free‐living amoeba. A 70% aqueous ethanol extract of the leaves demonstrated inhibitory activity against trophozoites, with MIC values of 1024 µg/mL at 24 h and 2048 µg/mL at 48–72 h; however, the extract was largely ineffective against cyst forms, with MICs exceeding 2048 µg/mL at all time points [90]. These high MIC values suggest relatively weak activity, particularly against the more resistant cyst stage, limiting the practical relevance of this extract for anti‐amoebic applications.

Comparisons across these studies are limited by differences in viral or protozoal targets, assay formats, and extract concentrations. Despite these differences, ethanolic leaf extracts consistently exhibit greater activity than aqueous preparations, particularly against HIV‐1, while aqueous extracts of fruits or pods show weaker and more selective activity. Overall, the reported antiviral and antiprotozoal activities of S. alexandrina range from limited to moderate and appear to be highly dependent on the experimental conditions. Further studies using standardized bioassays are therefore warranted.

5.6.4. Anthelmintic Activity

S. alexandrina leaf extracts exhibit notable in vitro anthelmintic activity against both tapeworms and earthworms, with efficacy depending on solvent, concentration, and combination with other Senna species. Ethanol‐based extracts, particularly 90% ethanol, consistently induced dose‐dependent paralysis and mortality of Hymenolepis diminuta and Raillietina tetragona, with higher concentrations acting faster [31, 91, 92].

Synergistic effects were observed when S. alexandrina extracts were combined with other Senna species. For example, combinations of S. alexandrina and S. alata accelerated paralysis and mortality of H. diminuta compared to individual extracts, indicating potential enhancement of anthelmintic efficacy through combined preparations [92].

Overall, the available evidence demonstrates that leaf ethanol and methanol extracts of S. alexandrina are effective anthelmintic agents, with activity modulated by concentration, extract type, and synergistic combinations. These findings are consistent across studies, highlighting reproducible, concentration‐dependent effects. The anthelmintic mechanism has not been directly investigated in these studies, but is putatively attributed to the anthraquinone constituents, which are known to interfere with parasite mitochondrial function and neuromuscular transmission, consistent with the paralysis observed prior to worm mortality.

5.7. Other Activities

In vitro, decoctions of S. alexandrina leaves inhibited intestinal P‐glycoprotein in human colon adenocarcinoma cell line (LS 180) cells by 16%–46% at 0.125–5.0 mg/mL, indicating potential modulation of drug transport [15]. Methanol and water extracts showed modest anti‐sickling activity, with slightly stronger effects for water (71.16%–64.69%) than methanol (72.45–67.22%) across 125–500 µg/mL [73]. Ethanol extracts weakly inhibited human monoamine oxidase B (MAO‐B) (IC₅₀ ≈ 0.7 mg/mL), suggesting limited neuroprotective potential [93], while methanol extracts inhibited acetylcholinesterase and tyrosinase (2.41 ± 0.07 mg galanthamine equivalents GALAE/g and 15.12 ± 0.59 mg kojic acid equivalents KAE/g, respectively) [39].

6. Traditional Applications and Pharmacological Relevance of S. alexandrina

S. alexandrina has a long history of use in traditional medicine for the management of gastrointestinal, dermatological, metabolic, musculoskeletal, neurological, and systemic conditions. The leaves and pods are most commonly administered orally as decoctions or powders for purgative, bowel‐cleansing, and digestive tonic purposes, while topical preparations are employed to treat skin disorders, wounds, and hair‐related conditions. Additional traditional indications include relief of joint and nerve pain, management of respiratory symptoms, support during childbirth, and use as a general tonic.

Contemporary pharmacological investigations largely support these ethnomedical applications. Leaf‐ and pod‐derived extracts exhibit pronounced laxative, anti‐inflammatory, hepatoprotective, metabolic, antioxidant, antimicrobial, antiviral, and anthelmintic activities, as well as notable anticancer potential. These effects are primarily attributed to anthraquinone glycosides (particularly sennosides), phenolic compounds, polysaccharides, and related bioactive constituents, which provide a mechanistic basis for the reported activities, although the evidence supporting therapeutic efficacy varies considerably across indications.

Traditional gastrointestinal uses are supported by experimental evidence. Dose‐dependent laxative activity has been consistently demonstrated in animal models and is mediated by sennosides that stimulate colonic peristalsis and reduce water and electrolyte absorption (Section 5.3). Regular consumption of leaf decoctions is further supported by hepatobiliary benefits through choleretic effects and by metabolic relevance demonstrated via antihyperglycemic, antidiabetic, and α‐glucosidase inhibitory activities in multiple rodent models (Section 5.3).

Dermatological applications, including the use of leaf poultices boiled in vinegar for scabies, itching, and pigmentary disorders, are consistent with antimicrobial, keratolytic, anti‐inflammatory, and antioxidant activities of S. alexandrina extracts, although these have not been tested against the specific conditions concerned (Sections 5.2 and 5.6.2). Enhanced wound healing and tissue regeneration observed in a burn‐wound model provide direct support for traditional use in malignant wounds, while the reported antimicrobial and antioxidant activities are only indirectly relevant to scalp disorders, which have not been investigated experimentally (Sections 5.2 and 5.6.1). These anti‐inflammatory and antioxidative properties may also be relevant to musculoskeletal applications for neuralgia, sciatica, and joint pain by mitigating oxidative stress and inflammatory mediators (Section 5.2). Notably, traditional formulations combining Senna with olive oil appear to potentiate both laxative and anti‐inflammatory effects, likely through lipid‐mediated enhancement of bioactivity (Sections 5.2 and 5.3).

In neurological and neuropsychiatric contexts, in vitro inhibition of monoamine oxidase B (Section 5.7) is consistent with a possible mood‐related effect relevant to traditional use for melancholia and obsessive‐compulsive disorder, although neuroprotective activity has not been directly examined. The traditional applications for epilepsy, chronic headache, and migraine have not been investigated pharmacologically. Respiratory applications, often involving combination with licorice (G. glabra), may relate to anti‐inflammatory and immunomodulatory actions (Section 5.2). In contrast, the traditional obstetric use of S. alexandrina during labor and for the control of post‐partum haemorrhage has not been investigated pharmacologically in the available literature. Antioxidant activity may be relevant to its traditional role as a general cardiac tonic, although this has not been evaluated in a cardiac model (Section 5.5). Finally, the traditional application of S. alexandrina in oncological contexts is supported by consistent in vitro and in vivo evidence demonstrating dose‐dependent cytotoxic and antiproliferative activities against multiple cancer cell lines, largely driven by anthraquinones and flavonoids (Section 5.1).

The primary therapeutic activities of S. alexandrina are illustrated in Figure 12, while a comprehensive synthesis of traditional applications and corresponding pharmacological evidence is presented in Table 7. To reflect differences in the strength of the underlying evidence, each entry is classified as direct experimental support, where the activity was tested in a model of the traditional indication itself; indirect mechanistic support, where a relevant mechanism has been shown but not for that specific indication; or traditional use, not experimentally confirmed, where no supporting pharmacological data were identified.

7. Current Limitations and Strategic Directions for Future Research

The current pharmacological landscape of S. alexandrina identifies it as a rich reservoir of bioactive secondary metabolites with promising applications in oncology, metabolic regulation, and viral defense. However, as documented in the literature, most reported biological activities have been demonstrated using crude or semi‐purified extracts, predominantly methanolic, ethanolic, and aqueous preparations. To facilitate the transition from botanical characterization to clinical application, future research should prioritize the isolation and structural elucidation of individual bioactive constituents. The hexane fraction of leaf extracts, which inhibits α‐glucosidase more effectively than acarbose (94%) [37], and the ethanolic extracts with potent inhibition of HIV‐1 integrase [87, 88], represent the two clearest priorities for further investigation, since the specific compounds responsible for these effects remain largely unidentified. This “extract‐level bottleneck” represents a significant hurdle, as compound‐level identification is necessary to establish precise dosing, and clarify the biological effects of individual constituents. Bioassay‐guided fractionation will therefore be essential to identify lead compounds and establish their specific pharmacological activities. This knowledge gap also extends to pharmacokinetics. Except for the sennosides, whose limited intestinal absorption and colonic bioactivation contribute to their laxative effect [29], there is currently little information on the absorption, metabolism, and excretion of constituents associated with the non‐laxative activities discussed in this review. Therefore, further pharmacokinetic studies should be considered a priority to better understand the bioavailability, metabolic fate, and potential therapeutic relevance of these compounds.

Furthermore, future studies must address the persistent issue of methodological heterogeneity. The current body of research is characterized by inconsistent extraction methodologies, varying concentrations, and diverse reporting units (e.g., IC₅₀ vs. percent inhibition), which constrains the ability to perform quantitative cross‐study comparisons or synthesize “gold standard” data for regulatory approval. Establishing standardized experimental protocols, along with quality‐controlled plant material given that phytochemical yield can vary with growing conditions, harvest time, and extraction method, is a critical prerequisite for pharmaceutical development.

Another critical area for future investigation is the elucidation of the molecular mechanisms underlying the observed therapeutic effects. Current evidence highlights the ability of S. alexandrina extracts to downregulate key pro‐inflammatory mediators, including TNF‐α, IL‐6, and NF‐κB1 [24, 45, 58, 61]; however, the precise signaling pathways involved, such as specific apoptotic cascades or the NRF2 antioxidant pathway, remain only partially characterized. Additionally, research must resolve the “inflammatory paradox” identified in recent literature, where specific ethanol extracts have demonstrated pro‐inflammatory responses and compromised intestinal integrity in certain models, while other preparations exhibit potent anti‐inflammatory benefits [24, 45, 60, 61, 62]. Investigating the specific phytochemical triggers and context‐dependent factors (e.g., tissue type or dosage thresholds) that cause this shift from therapeutic to irritant is essential for ensuring patient safety.

Further exploration of synergistic effects suggested by traditional polyherbal formulations, as summarized in Table 7, is warranted. Traditional preparations incorporating olive oil or vinegar imply that lipid‐mediated transport and pH‐dependent extraction may substantially influence the bioavailability and pharmacological efficacy of anthraquinones and phenolic compounds. Investigating these practices using modern pharmacokinetic and formulation approaches may support the development of more effective oral and topical delivery systems.

Finally, there is a pressing need for comprehensive safety evaluation and well‐designed clinical trials. Although S. alexandrina is generally considered safe at low doses, high concentrations of sennosides have been associated with colonic damage and systemic organ toxicity in animal models [21, 23, 74]. Future studies must clearly define the therapeutic window for non‐laxative applications, including its potential use in neuroprotection for epilepsy or as an adjuvant in cancer therapy. The transition from in vitro and animal models to rigorously controlled human clinical trials is the final and most critical gap; such trials are essential to establish the efficacy of the plant in treating complex human conditions as suggested by its extensive ethnobotanical history.

8. Conclusion

S. alexandrina is a medicinal plant of longstanding ethnopharmacological importance, traditionally used for gastrointestinal, dermatological, metabolic, musculoskeletal, and neurological conditions. This review integrates ethnobotanical knowledge with contemporary pharmacological evidence, highlighting substantial concordance between traditional uses and experimentally supported biological activities. Beyond its well‐established laxative effects, S. alexandrina exhibits promising anticancer, anti‐inflammatory, hepatoprotective, metabolic regulatory, antioxidant, antimicrobial, antiviral, and anthelmintic properties.

The current pharmacological evidence is largely derived from crude or semi‐purified extracts, most commonly methanolic, ethanolic, and aqueous preparations rather than isolated compounds. While these extracts consistently demonstrate notable bioactivities in vitro and in vivo, the specific molecules responsible for many effects remain poorly characterized. Anthraquinone glycosides such as sennosides are well recognized for laxative activity, but other effects, including anticancer, antiviral, enzyme‐inhibitory, and neuroprotective activities, likely involve distinct or synergistic phytochemicals, such as phenolics, flavonoids, and polysaccharides. The absence of compound‐level resolution limits mechanistic understanding, dose standardization, and translational application.

The novelty of this review lies in the integration of 219 chemical structures with their reported pharmacological activities and traditional uses in a single resource, representing the most extensive compilation of chemical constituents reported for this species to date. However, the robustness of the available evidence is not uniform. The laxative activity of sennosides is supported by converging in vitro, animal, and mechanistic evidence, whereas the anticancer, anti‐inflammatory, antimicrobial, and other non‐laxative activities are based predominantly on extract‐level in vitro and animal studies, with limited compound‐level investigation and clinical follow‐up. Future research should therefore be directed according to the strength of the existing evidence. Priority should be given to the isolation and characterization of compounds responsible for the most promising extract‐level activities, particularly the α‐glucosidase inhibition observed in the hexane fraction and the HIV‐1 integrase inhibition reported for the ethanolic extract. In the longer term, well‐designed clinical studies are needed to determine the efficacy and safety of these activities in humans. At present, clinical translation remains limited, and most non‐laxative indications require further evaluation in controlled human studies.

Author Contribution

The authors confirm contribution to the paper as follows. Y. M. C.: study conception and design. D. A. R. and K.‐L. H.: Data collection. D. A. R., K.‐L. H., and Y.‐M. C.: Analysis, interpretation of results, and draft manuscript.

Funding

The authors would like to express their gratitude to the Ministry of Higher Education (MOHE), Malaysia, for funding this research through (Grant No. IF070‐2020). This work was also supported in part by the Science and Technology Research Partnership for Sustainable Development (SATREPS) Programme, Japan Agency for Medical Research and Development (AMED) and Japan International Cooperation Agency (JICA).

Consent for Publication

All authors reviewed the results and approved the final version of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest financial or otherwise.

Biographies

Diana Afrina Rella is a researcher and Master's student in the Department of Chemistry at the University of Malaya, Malaysia. She earned her Bachelor's degree in Chemistry with Management from Universiti Teknologi MARA (UiTM) in 2024. Her research focuses on the identification of bioactive compounds derived from medicinal plants, aiming to integrate ethnobotanical knowledge with contemporary chemical research.

Khai‐Lin Hew is a researcher and PhD student in the Department of Chemistry, University of Malaya, Malaysia. She obtained her Bachelor's degree in Chemistry from University of Malaya in 2024. Her research focuses on the discovery of bioactive compounds from medicinal plants, integrating traditional knowledge with modern drug discovery strategies.

Yeun‐Mun Choo is an Associate Professor in the Department of Chemistry at the University of Malaya, Malaysia. She received her Ph.D. and B.Sc. (Hons., Class I) in Chemistry from the University of Malaya and completed her postdoctoral fellowship at the University of Mississippi, USA. Her research focuses on the discovery and characterization of bioactive compounds from Malaysia's ethnomedicinal flora, integrating phytochemical and computational approaches to identify potential therapeutic agents for infectious diseases, cancer, and neuroinflammation.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.