Potential therapeutic use of Indian medicinal plants for preeclampsia management

Abstract

Preeclampsia (PE), an adverse illness of pregnancy, poses significant risks to maternal and fetal health. Current management strategies focus on symptomatic relief and delivery, often neglecting the underlying pathophysiology. Indian medicinal plants, rich in bioactive compounds, offer a promising alternative by targeting oxidative stress, endothelial dysfunction, and inflammation, which are primary contributors to PE. Hemidesmus indicus exhibits strong anti-inflammatory and antioxidant properties, which may help reduce systemic inflammation and oxidative damage. Allium sativum (garlic) is well known for its ability to enhance nitric oxide (NO) bioavailability, promote vasodilation, and regulate blood pressure. Tribulus terrestris (Gokshura) supports cardiovascular health by stabilizing blood pressure and maintaining endothelial function. Curcuma longa (Turmeric) is known for its anti-inflammatory, antioxidant, and endothelial-protective effects. Withania somnifera (Ashwagandha) has adaptogenic and vasodilatory properties that contribute to improved vascular function and stress response. Rheum officinale (Rhubarb) has anti-inflammatory and vascular-protective effects, which may help improve maternal vascular health and reduce complications associated with PE. By addressing key pathological mechanisms, these medicinal plants offer a promising approach for PE management.

Among these medicinal plants, Asparagus racemosus willd. (AR) (Shatavari) has gained significant attention due to its rich composition of saponins, flavonoids, and antioxidants. These bioactive compounds play a crucial role in enhancing NO production, reducing oxidative stress, and improving endothelial function in PE. While traditional use supports their benefits, rigorous research is needed to confirm efficacy, safety and dosage. Integrating these botanicals into modern therapeutic protocols could offer a holistic and cost-effective strategy for PE management, ultimately improving maternal and fetal health outcomes.

1. Introduction

Preeclampsia is a pregnancy-specific syndrome characterized by the development of hypertension and protein excretion in the urine or impairment of organ function, typically manifesting after 20 weeks of gestation. The underlying pathophysiology of preeclampsia is multifactorial, involving aberrant placental development, endothelial dysfunction, oxidative stress, and inflammatory processes [1]. Current clinical approaches primarily address the symptoms of preeclampsia, such as elevated blood pressure, rather than targeting the underlying pathological mechanisms that drive the disease [2]. These mechanisms include endothelial dysfunction, oxidative stress, inflammation and an imbalance of angiogenic factors, which collectively contribute to the development and progression of preeclampsia [3]. The current treatment options focus on managing hypertension to prevent cerebrovascular, cardiac, and renal complications in the mother [4]. In instances of severe preeclampsia, the prompt delivery of the fetus, irrespective of gestational age, may be deemed necessary to safeguard maternal health; however, this decision carries potential risks for the premature infant [5]. Consequently, innovative therapeutic strategies that address the root causes of preeclampsia are imperative to improve maternal and fetal outcomes and reduce the long-term health consequences associated with this disorder.

Indian medicinal plants, with their rich history of traditional use and diverse array of bioactive compounds, offer a compelling avenue for exploring alternative and complementary therapeutic strategies for preeclampsia [6]. These plants contain a variety of compounds with antioxidant, anti-inflammatory, and vasoactive properties, potentially addressing multiple aspects of the pathophysiology of preeclampsia [7]. Specifically, plants such as Hemidesmus indicus, Allium sativum, Tribulus terrestris, Curcuma longa, Withania somnifera, and Rheum officinale have demonstrated promise in preclinical studies for their ability to mitigate oxidative stress, improve endothelial function, and regulate blood pressure. There have been several studies exploring the role of herbal medicine in managing various pregnancy-related complications such as nausea, vomiting, and general pregnancy sickness [8]. However, our study specifically focuses on preeclampsia, a serious hypertensive disorder unique to pregnancy that significantly contributes to maternal and fetal morbidity and mortality. Unlike general pregnancy ailments, preeclampsia involves complex pathophysiological mechanisms including endothelial dysfunction, oxidative stress, and impaired placental development. This review emphasizes the potential of medicinal plants in modulating these pathways, highlighting their therapeutic promise in the prevention and management of preeclampsia rather than addressing broader pregnancy-related symptoms.

The potential of Indian medicinal plants to address the root causes of preeclampsia is particularly exciting, given the limitations of current treatment options. Hemidesmus indicus, for instance, is known for its potent anti-inflammatory and antioxidant effects, which could help to reduce systemic inflammation and oxidative damage, two key features of preeclampsia [9]. Similarly, Allium sativum, commonly known as garlic, has been shown to enhance nitric oxide bioavailability, promote vasodilation, and regulate blood pressure, all of which are crucial for maintaining healthy vascular function during pregnancy [10]. Tribulus terrestris or Gokshura, supports cardiovascular health by stabilizing blood pressure and maintaining endothelial function, potentially preventing or mitigating the hypertension associated with preeclampsia. Further emphasizing the therapeutic potential of Indian medicinal plants is Curcuma longa or turmeric, which possesses remarkable anti-inflammatory, antioxidant, and endothelial-protective effects. Withania somnifera, also known as Ashwagandha, has adaptogenic and vasodilatory properties that contribute to improved vascular function and stress response, offering a holistic approach to managing preeclampsia. Moreover, Rheum officinale, or rhubarb, demonstrates anti-inflammatory and vascular-protective effects, which may help improve maternal vascular health and reduce complications associated with preeclampsia. These plants, rich in bioactive compounds such as saponins, flavonoids, and antioxidants, are known for their anti-inflammatory, antioxidant, and endothelial-protective properties. Herbs like Asparagus racemosus (Shatavari), Hemidesmus indicus (Anantmul), Allium sativum (garlic), Tribulus terrestris (Gokshura), Curcuma longa (Turmeric), Withania somnifera (Ashwagandha) and Rheum officinale (rhubarb) offer potential therapeutic benefits as shown in Fig. 1 and align with the pathophysiological requirements of PE management. The investigation of the cellular and molecular mechanisms of hypertension in pregnant women can be difficult and costly [11]. Therefore, animal models are often used in the study of preeclampsia [12].

Fig. 1.

Some Indian medicinal plants enhance maternal health during pregnancy.

Among these botanicals, A. racemosus, commonly known as Shatavari, stands out due to its rich composition of saponins, flavonoids, and antioxidants, as illustrated in Fig. 2. These bioactive compounds play a crucial role in enhancing nitric oxide production, reducing oxidative stress, and improving endothelial function, all of which are compromised in preeclampsia [11]. Multiple micronutrient supplements may significantly reduce the risk of preeclampsia. Despite the promising traditional uses of these plants, it is essential to conduct rigorous scientific research to confirm their efficacy, safety, and optimal dosages for use in preeclampsia. Integrating these botanicals into modern therapeutic protocols could offer a holistic and cost-effective approach to managing preeclampsia, particularly in resource-limited settings where access to conventional medical care may be limited. The foremost hypothesis regarding the initiating event in preeclampsia is postulated to be reduced placental perfusion that, in turn, leads to widespread dysfunction of the maternal vascular endothelium. Further research is warranted to evaluate the long-term effects of these plants on both maternal and offspring health, as well as to explore their potential interactions with conventional medications.

Fig. 2.

Phytochemical constituents of Asparagus racemosus.

PE is related to increased oxidative stress, disturbed angiogenesis, and placental apoptosis [12]. Oxidative stress plays a central role in the pathophysiology of preeclampsia [11]. It alters placental remodeling and placental vascular endothelial dysfunction, resulting in an ischemia/reperfusion injury with an increase in xanthine oxidase activity that produces high levels of reactive oxygen species [13]. The use of Indian medicinal plants may help treat this disease. Despite the ongoing research on preeclampsia, its specific cause remains enigmatic. Regardless, scientific evidence supports the assumption that preeclampsia starts in the utero-placental unit, gets amplified by oxidative stress, and culminates in the maternal endothelium. This process leads to hypertension and proteinuria, which are the defining symptoms of the disease [14]. The complexity of PE pathophysiology suggests the need for more research for reliable and more accessible diagnostic and therapeutic strategies.

It is estimated that preeclampsia is responsible for a significant proportion of preterm births each year, resulting in high neonatal morbidity and mortality [7]. The impact of preeclampsia extends beyond the immediate pregnancy, as affected mothers have an increased risk of developing cardiovascular disease, stroke, and other chronic health conditions later in life [15]. Moreover, offspring of preeclamptic pregnancies are at higher risk of neurodevelopmental disorders, metabolic syndrome, and cardiovascular disease in adulthood. Current treatment options for preeclampsia are limited to managing the symptoms, primarily through blood pressure control and the use of anticonvulsants to prevent seizures [16]. Delivery of the baby is often the only definitive treatment, particularly in severe cases, but this can lead to preterm birth and its associated complications if the pregnancy has not reached full term [17]. Targeting placental development defects and the accompanied disturbance in maternal systemic adaptation could improve maternal and fetal outcomes.

Women with preeclampsia have an increased risk of cardiovascular disease later in life, suggesting that preeclampsia may serve as an early marker of future cardiovascular risk [18]. Early-onset preeclampsia, occurring before 34 weeks of gestation, is associated with poorer outcomes than late-onset preeclampsia, which occurs after 34 weeks [19].

The present review aims to comprehensively evaluate the potential of specific Indian medicinal plants as therapeutic interventions for preeclampsia, focusing on their capacity to modulate key pathogenic pathways implicated in the disease etiology [20]. While traditional use supports their benefits, rigorous research is needed to confirm efficacy, safety and dosage. Integrating these botanicals into modern therapeutic protocols could offer a holistic and cost-effective strategy for PE management, ultimately improving maternal and fetal health outcomes.

A comprehensive review of the scientific literature was conducted to explore the potential therapeutic benefits of Indian medicinal plants in the context of preeclampsia. Relevant studies were identified through a systematic search of electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar. Data extracted from the selected articles included study design, sample size, participant characteristics, intervention details (such as the type and dosage of medicinal plants), control measures, outcome variables, and key findings.

1.1. Characteristics of plant phenolic compounds evaluated in preeclampsia

Plant phenolic compounds, widely recognized for their antioxidative, anti-inflammatory, and vasculoprotective properties, play a crucial role in managing preeclampsia, a pregnancy-specific disorder characterized by hypertension, proteinuria, and endothelial dysfunction. Notably, phenolic compounds from Asparagus racemosus (Shatavari), Withania somnifera (Ashwagandha), and Curcuma longa (Turmeric) have shown promising therapeutic potential in animal models of preeclampsia by targeting various aspects of its complex pathophysiology, as summarized in Table 1. Numerous studies have demonstrated their broad spectrum of biological activities, supporting their relevance in the context of pregnancy-related complications [3].

Table 1.

Information on Indian medicinal plants, their phytoconstituents and therapeutic effects.

S.No.	Names	Phytoconstituents	Therapeutic effect	Ref.
1.	Asparagus racemosus (Shatavari)	Saponins: Shatavarins (I-IV), racemosol Flavonoids: Quercetin, rutin, hyperoside Sterols: β-sitosterol, stigmasterol Alkaloids: Asparagamine A Polysaccharides: Immunostimulant polysaccharides Antioxidants: Vitamin C, glutathione	Antioxidant: Reduces oxidative stress by scavenging free radicals. Anti-inflammatory: Inhibits pro-inflammatory cytokines. Endothelial protection: Enhances nitric oxide (NO) production and improves endothelial function.	[21]
2.	Hemidesmus indicus (Anantmul)	Coumarins: Scopoletin, hemidesminine Steroids: β-sitosterol, α-amyrin Phenolic compounds: Vanillin, 2-hydroxy-4-methoxybenzaldehyde Triterpenoids: Lupeol, lupenone Saponins: Hemidesminine	Anti-inflammatory, antioxidant, and immunomodulatory properties. Supports cardiovascular health and reduces oxidative stress	[22]
3.	Allium sativum (garlic)	Sulfur-containing compounds: Allicin, diallyl disulfide, diallyl trisulfide, ajoene Flavonoids: Quercetin, kaempferol Phenolic acids: Gallic acid, caffeic acid Saponins: Proto-eruboside-B Vitamins and minerals: Vitamin C, selenium, zinc	Antioxidant, anti-inflammatory, and antihypertensive properties. Improves endothelial function and reduces oxidative stress.	[23]
4.	Tribulus terrestris (Gokshura)	Saponins: Protodioscin, diosgenin, tribulosin Alkaloids: Harmane, harmine Flavonoids: Quercetin, kaempferol Sterols: β-sitosterol Lignans: Nordihydroguaiaretic acid (NDGA) Tannins: Astringent compounds Vitamins and Minerals: Vitamin C, calcium, magnesium, potassium	Aphrodisiac: Enhances libido, improves sexual performance, and boosts testosterone levels. Adaptogenic: Reduces stress and fatigue, improves energy levels. Cardioprotective: Lowers blood pressure and cholesterol, improves circulation. Anti-inflammatory: Reduces inflammation and pain. Diuretic: Promotes urine flow, supports kidney health. Antioxidant: Protects against oxidative stress and aging. Immunomodulatory: Enhances immune function. Anti-diabetic: Regulates blood sugar levels. Muscle-building: Improves athletic performance and muscle recovery.	[24]
5.	Curcuma longa (Turmeric)	Curcuminoids: Curcumin (diferuloylmethane), demethoxycurcumin, bisdemethoxycurcumin Volatile oils: Turmerone, atlantone, zingiberene Polysaccharides: Ukonan A, B, C, D Phenolic acids: Caffeic acid, ferulic acid Flavonoids: Quercetin, kaempferol	Anti-inflammatory: Reduces inflammation by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and NF-κB signaling, alleviating pain and swelling. Antioxidant: Neutralizes free radicals, enhances endogenous antioxidants, and protects cells from oxidative stress and aging. Vasodilatory: Improves nitric oxide (NO) bioavailability, promotes vasodilation, and helps regulate blood pressure. Cardioprotective: Supports cardiovascular health by reducing cholesterol levels, preventing atherosclerosis, and maintaining endothelial function. Immunomodulatory: Modulates immune responses, balances pro- and anti-inflammatory pathways, and enhances regulatory T-cell function.	[25]
6.	Withania somnifera (Ashwagandha)	Withanolides: Withaferin A, withanolide A, withanolide D Alkaloids: Somniferine, somnine, withanine Steroidal lactones: Withanolides, withanosides Saponins: Sitoindosides Flavonoids: Kaempferol, quercetin Iron and amino acids: Rich in essential nutrients	Adaptogenic: Reduces stress and anxiety, which can be beneficial in high-risk pregnancies. Antioxidant: Scavenges free radicals and reduces oxidative stress. Anti-inflammatory: Inhibits pro-inflammatory cytokines and pathways. Cardioprotective: Improves cardiovascular health and reduces hypertension. Immunomodulatory: Enhances immune function and supports overall maternal health. Neuroprotective: Protects against oxidative damage and supports cognitive function.	[26]
7.	Rheum officinale (rhubarb)	Anthraquinones: Emodin, rhein, aloe-emodin Stilbenes: Resveratrol, piceatannol Flavonoids: Catechin, epicatechin Tannins: Gallotannins, ellagitannins Polysaccharides: Rhubarb polysaccharides	Antioxidant, anti-inflammatory, and vasoprotective properties. Supports cardiovascular health and reduces oxidative stress.	[27]

1.2. Antioxidant properties of medicinal plants

One of the mechanisms underlying the pathogenesis of preeclampsia is oxidative stress, which results from an imbalance between the production of reactive oxygen species and the antioxidant defense system.

Several studies have reported that women with preeclampsia have lower plasma concentrations of antioxidants, such as vitamin C, and increased levels of lipid peroxidation markers, indicating the presence of oxidative stress [14]. Indian medicinal plants are rich in antioxidants that can scavenge free radicals, reduce oxidative stress, and protect the endothelium. Hemidesmus indicus, Allium sativum, Curcuma longa and Withania somnifera, among others, possess potent antioxidant properties that may help mitigate oxidative damage in preeclampsia.

The significance of nitric oxide in the pathophysiology of preeclampsia stems from its critical role as a vasodilator and regulator of vascular function. Reduced bioavailability of NO leads to vasoconstriction, endothelial dysfunction, and hypertension, all of which are hallmarks of preeclampsia. Some Indian medicinal plants, such as Allium sativum and Asparagus racemosus, have been shown to enhance NO production or bioavailability, thereby promoting vasodilation and improving blood flow.

The traditional use of Indian medicinal plants in pregnancy-related disorders suggests their potential efficacy and safety. However, rigorous scientific research is needed to validate these claims and determine the optimal dosages and formulations for therapeutic use. Clinical trials evaluating the efficacy and safety of Indian medicinal plants in preeclampsia are limited.

Future studies should focus on identifying the specific bioactive compounds responsible for the observed effects and elucidating their mechanisms of action. Further research is needed to determine the long-term effects of these medicinal plants on maternal and fetal outcomes and to establish appropriate guidelines for their use in preeclampsia [28].

The pathophysiology of preeclampsia is complex, involving multiple organ systems and molecular pathways [29]. Oxidative stress, endothelial dysfunction, and inflammation are major contributors to the pathogenesis of preeclampsia [30]. Future studies are needed to explore these possibilities, assess long-term safety, and establish optimal dosage regimens. Integrating these botanicals into modern therapeutic protocols could offer a holistic and cost-effective approach to preeclampsia management, especially in resource-limited settings [31]. In patients with preeclampsia, antioxidant nutrients may be utilized to a greater extent to counteract free radical-mediated cell disturbances, resulting in a reduction in serum antioxidant levels [20].

1.2.1. Evaluating plant phenolic compounds in animal models of preeclampsia

Animal models have played a crucial role in elucidating the mechanisms underlying preeclampsia and evaluating potential therapeutic interventions [32]. Supplementation with plant phenolic compounds has shown promising results in animal models of preeclampsia, improving maternal and fetal outcomes [33]. Berries and grapes, rich in anthocyanins, have demonstrated antioxidant and anti-inflammatory effects in pregnant rats with induced preeclampsia [34]. These findings suggest that plant phenolic compounds may offer a potential therapeutic strategy for preeclampsia by targeting multiple pathways involved in its pathogenesis, shown in Table 2.

Table 2.

Overview of pharmacological effects of plant-derived polyphenols and plant extracts in animal models of preeclampsia.

Polyphenols/Plant Extracts	PE rat models	Dose (mg/kg/day)	Type of Extract	Extraction Method	Effects	Ref.
Asparagus racemosus (Shatavari)	l-NAME	200	Aqueous root	Decoction, Filtration	Reduced oxidative stress, improved placental vascular remodeling, and enhanced fetal weight.	[46]
Withania somnifera (Ashwagandha)	l-NAME	100	Hydroalcoholic	Maceration, Solvent evaporation	Decreased pro-inflammatory cytokines (TNF-α, IL-6), improved endothelial function, and NO levels.	[47]
Curcuma longa (turmeric)	RUPP	50–100	Ethanolic	Soxhlet extraction	Lowered oxidative stress, improved placental perfusion, and reduced maternal hypertension.	[48]
Ocimum sanctum (Tulsi)	l-NAME	200	Aqueous leaf	Decoction, Filtration	Reduced oxidative damage, stabilized mitochondrial function, and improved fetal viability.	[49]
Tinospora cordifolia (Giloy)	l-NAME	100	Hydroalcoholic	Maceration, Filtration	Reduced systemic inflammation, enhanced placental integrity, and lowered blood pressure.	[50]
Zingiber officinale (ginger)	Hypertension	200	Ethanolic rhizome	Soxhlet extraction	Reduced blood pressure, improved endothelial function, and decreased lipid peroxidation.	[51]
Moringa oleifera (Drumstick tree)	RUPP	150	Aqueous leaf	Infusion, Filtration	Improved placental blood flow, reduced ROS levels, and lowered maternal hypertension.	[52]
Baicalin	l-NAME	25, 50 and 100	Compound used	Not applicable	Inhibits Caspase-9 and AT1 in rat kidney and liver	[53]
Santalum album (sandalwood)	Hypertension	100	Ethanolic bark	Soxhlet extraction	Vasodilation, improved uteroplacental circulation, and reduced oxidative damage.	[54]
Punica granatum (Pomegranate)	l-NAME	100	Seeds	Cold press	Antioxidant and vasodilatory effects	[55]
Bacopa monnieri (Brahmi)	Stress-induced	100	Ethanolic whole plant	Soxhlet extraction	Reduced oxidative damage, improved placental perfusion, and decreased maternal stress.	[56]

Note: The extract was administered orally via gavage for all models. RUPP stands for (Reduced Uteroplacental Perfusion Pressure), l-NAME (N (G)-Nitro-l-arginine methyl ester).

1.3. Indian medicinal plants in human preeclampsia: evidence from clinical studies

Clinical evidence supporting the use of Indian medicinal plants in the management of human preeclampsia remains limited. Although traditional practices highlight their potential benefits, only a few clinical trials have rigorously evaluated their efficacy, safety, and appropriate dosage. Well-designed studies are essential to establish their role in modern medicine. Integrating these botanicals into current therapeutic protocols could provide a holistic and cost-effective approach to preeclampsia management—especially in low-resource settings where access to conventional treatments is restricted [35]. Future studies need to examine the association between maternal nutritional status in early pregnancy, oxidative stress and telomere attrition in preeclampsia [36].

1.4. Clinical trials and ex vivo studies evaluating plant extracts for preeclampsia

Clinical trials and ex vivo studies have explored the potential of plant extracts to manage preeclampsia. Evaluation of extended-release metformin has been suggested as a potentially effective treatment for women experiencing preterm pre-eclampsia [37]. Glycemic control during pregnancy has been linked to preeclampsia, but more data is needed to control for confounding variables and understand the importance of early versus late pregnancy glycemic control [38]. Further research is warranted to fully understand the potential benefits and risks of using plant extracts in the management of preeclampsia [39]. Vitamin D supplementation has been proposed as a preventive measure against preeclampsia, addressing potential vitamin D deficiencies during pregnancy that may contribute to the condition [40]. Integrating these botanicals into modern therapeutic protocols could offer a holistic and cost-effective approach to preeclampsia management, particularly in low-resource settings where access to conventional treatments may be limited [41]. Additionally, early prediction of preeclampsia can cause considerable anxiety for mothers, and further research is needed to evaluate the effectiveness of interventions in preventing preeclampsia or ameliorating its complications [42,43]. The results of studies on the physiological effects of preeclampsia on the brain, kidney, and liver have provided a better understanding of this condition [44]. Clinical experience shows that early detection and careful monitoring of the pregnancy and timing of delivery benefit both mother and fetus [45]. Future research should focus on identifying reliable biomarkers for early detection and risk stratification, as well as conducting well-designed clinical trials to evaluate the efficacy and safety of Indian medicinal plants in the prevention and treatment of preeclampsia. These trials should incorporate rigorous methodologies, including appropriate controls, standardized preparations, and comprehensive outcome measures, to ensure the validity and reliability of the findings.

1.5. Reducing oxidative stress through plant-based therapeutic interventions

Oxidative stress is a key factor in the pathogenesis of preeclampsia, leading to endothelial dysfunction and placental damage. Plant-based therapeutic interventions, rich in antioxidants, offer a promising strategy to reduce oxidative stress and improve outcomes in preeclampsia [57]. The origin of adverse pregnancy outcomes may occur earlier in gestation than previously thought [58]. Evidence of structural cardiovascular maladaptation in young women with prior preeclampsia suggests potential long-term effects of the condition on cardiovascular health. Many studies suggest that preeclampsia is associated with dyslipidaemia [59]. The hypothesis has been advanced that much of the disease could be explained by alterations in the function of the vascular endothelium [60]. Supplementation with antioxidants, such as vitamin C and vitamin E, has been shown to reduce oxidative stress and improve endothelial function in pregnant women with preeclampsia. Plant-based diets rich in fruits, vegetables, and whole grains provide a wide range of antioxidants that can help neutralize free radicals and protect against oxidative damage. Furthermore, certain plant extracts, such as grape seed extract and green tea extract, have demonstrated potent antioxidant activity and have shown promise in reducing oxidative stress in preeclampsia [20]. The genetic and immunological theories appear to be interlinked [43]. Therefore, the administration of antioxidants may help prevent preeclampsia.

1.6. Plant-based interventions to improve endothelial function

Endothelial dysfunction is a critical component of preeclampsia, contributing to hypertension and impaired placental perfusion. Plant-based interventions offer a potential avenue to improve endothelial function and restore vascular health in preeclampsia. Several mechanisms have been suggested for the oxidative stress found in preeclampsia [61]. Activation of placental NADH oxidase is likely to play an important role in the maternal inflammatory response in pre-eclampsia, possibly through local cytokine release and maternal leucocyte activation [62]. Increasing evidence suggests that preeclampsia is a two-stage disease. The first stage is characterized by abnormal placentation, and the second stage is the maternal response to factors released from the placenta. l-arginine, a precursor to nitric oxide, has been shown to improve endothelial function and reduce blood pressure in pregnant women with preeclampsia. Plant extracts, such as beetroot juice and hawthorn berry extract, have demonstrated vasodilatory effects and have been shown to improve endothelial function in clinical studies. Moreover, lifestyle modifications, such as regular exercise and stress reduction techniques, can complement plant-based interventions in improving endothelial function and vascular health in preeclampsia. The disease of preeclampsia can be described as a failure of the physiological adaptations to pregnancy. The use of Doppler ultrasonography of the uterine arteries can investigate for signs of inadequate placental perfusion. Placental syndromes are characterised by impaired placentation and early placental vascularization, with higher blood pressure before pregnancy being associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth restriction [63].

1.7. Harnessing herbal remedies to modulate the innate immune system

Neutrophil numbers in the maternal systemic circulation and within the decidua steadily increase in pregnancy throughout gestation, yet this increase is further amplified in preeclampsia [64]. However, maternal blood pressure may be a more critical risk factor than the clinical syndrome of preeclampsia itself [63]. The innate immune system plays a critical role in the pathogenesis of preeclampsia, with excessive inflammation contributing to endothelial dysfunction and placental damage. Herbal medicines offer a potential strategy to modulate the innate immune response and reduce inflammation in preeclampsia. The innate immune system, involving Toll-like receptors, has been implicated in the development of preeclampsia [65]. Activation of the innate immune system leads to the release of pro-inflammatory cytokines, such as TNF-α and IL-6, which contribute to endothelial dysfunction and placental injury. Herbal medicines, such as turmeric and ginger, possess potent anti-inflammatory properties and have been shown to suppress the production of pro-inflammatory cytokines. Curcumin, the active compound in turmeric, has demonstrated efficacy in reducing inflammation and improving endothelial function in preclinical studies [66]. Furthermore, herbal formulations, such as those containing astragalus and echinacea, have been shown to modulate the immune response and enhance immune function. Therefore, herbal medicines offer a potential approach to dampen the excessive inflammation associated with preeclampsia and improve maternal and fetal outcomes [67].

1.8. Holistic and cost-effective therapeutic modalities

PE poses a significant global health burden, particularly in low-resource settings where access to conventional medical care may be limited. Integrating Indian medicinal plants into modern therapeutic protocols could offer a holistic and cost-effective approach for preeclampsia management. Women and their families should be educated on possible adverse effects of using unapproved traditional or herbal medicines during pregnancy and on the need to seek timely care before the onset of labor to allow healthcare providers ample opportunity to address labor and birth complications [68]. The most common reasons for intensive care unit admission are hypertensive disorders and massive obstetric hemorrhage [69]. It may be prudent to avoid delivery for mild hypertension, as long as end-organ damage is not present and the pregnancy is less than 37 weeks' gestation. For women with severe preeclampsia at less than 34 weeks' gestation, expectant management with careful maternal and fetal surveillance is indicated. Glucocorticoids should be administered to women with pregnancies less than 34 weeks' gestation. Magnesium sulfate should be administered to prevent seizures. The current management strategies focus on symptomatic relief and delivery, often neglecting the underlying pathophysiology [70]. Indian medicinal plants, rich in bioactive compounds, offer a promising alternative by targeting oxidative stress, endothelial dysfunction, and inflammation-contributors to PE.

1.9. Anti-inflammatory properties

Hemidesmus indicus exhibits strong anti-inflammatory and antioxidant properties, which may help reduce systemic inflammation and oxidative damage. Allium sativum (garlic) is well known for its ability to enhance nitric oxide bioavailability, promote vasodilation, and regulate blood pressure. Tribulus terrestris supports cardiovascular health by stabilizing blood pressure and maintaining endothelial function. Curcuma longa is known for its anti-inflammatory, antioxidant, and endothelial-protective effects. Withania somnifera has adaptogenic and vasodilatory properties that contribute to improved vascular function and stress response. Rheum officinale has anti-inflammatory and vascular-protective effects, which may help improve maternal vascular health and reduce complications associated with PE. A. racemosus has gained significant attention due to its rich composition of saponins, flavonoids, and antioxidants. These bioactive compounds play a crucial role in enhancing NO production, reducing oxidative stress, and improving endothelial function in PE. While traditional use supports their benefits, rigorous research is needed to confirm efficacy, safety and dosage. Poor maternal health and nutrition predispose women to pregnancy difficulties like PE and gestational diabetes [36]. Proper supplements and care can help them.

1.10. Indian medicinal plants for placental and vascular health improvement

The placenta, acting as the interface between maternal and fetal circulations, assumes a pivotal role in pregnancy, orchestrating endocrine, metabolic, and nutritional activities that are indispensable for fetal development and survival [71]. Abnormal placentation, characterized by poor trophoblast invasion and incomplete vascular formation of spiral arteries, is implicated in placental dysfunction during the initial stages of preeclampsia [72]. Several studies have concluded that pregnancy-induced hypertension severely limits the blood flow to the placenta and thus contributes to reduced fetal growth [73]. These studies have demonstrated that impaired uteroplacental perfusion during pregnancy is closely associated with hypertension and fetal growth restriction [74]. A recent study indicated that impaired trophoblast invasion and subsequent shallow placentation are considered key factors in the pathogenesis of preeclampsia, leading to inadequate placental perfusion and placental ischemia/hypoxia. Herbal medicines may play a role in promoting appropriate trophoblast invasion and vascular remodeling, thereby enhancing placental function and averting the pathogenesis of preeclampsia [20]. In mice, the mature placenta consists of three principal layers: an outer layer of trophoblast giant cells, a middle spongiotrophoblast layer and the innermost labyrinth [75]. The syncytiotrophoblast, the transporting epithelium and the primary endocrine cell of the human placenta, plays a critical role in determining fetal growth and development, mediated by a multitude of functions including nutrient transport to the fetus and orchestrating the maternal physiological adaptation to pregnancy. Thus, nutrient-sensing in the trophoblast is unique in that it not only directly regulates trophoblast metabolism and growth but may also influence the development and long-term health of the fetus [76]. Syncytiotrophoblast is formed by the fusion of underlying cytotrophoblasts. The outer layer of the placenta facilitates the exchange of nutrients, wastes, and gases between the maternal and fetal circulations [77]. The differentiation of trophoblasts toward syncytium triggers an endocytosis strategy, macropinocytosis, to uptake large extracellular molecules. Moreover, the syncytial layer lines the placental villi. The maternal side of this syncytial layer is in direct contact with maternal blood, making it particularly vulnerable to oxidative stress.

It has been demonstrated that placenta-specific protein PLAC1 is important in preeclampsia and that decreased placental PLAC1 expression is linked to the condition [78]. Additionally, it has been demonstrated that tissue factor pathway inhibitor 2 overexpression reduces trophoblast proliferation and invasion in preeclampsia [79]. This shows how critical placental function is for both maternal and fetal health and emphasizes the necessity of encouraging healthy placental development and function in order to prevent problems like preeclampsia [80].

1.11. Bioactive compounds and mechanisms of action

The effectiveness of Indian medicinal plants is based on the synergistic action of their bioactive components, which address the key pathophysiological pathways involved in preeclampsia [81]. For example, Hemidesmus indicus has anti-inflammatory and antioxidant properties that help to lower systemic inflammation and oxidative damage [11]. The bioactive compounds in Allium sativum, such as allicin, improve the bioavailability of nitric oxide, which results in vasodilation and blood pressure control [6]. Blood pressure is stabilized and endothelial function is preserved by Tribulus terrestris, which supports cardiovascular health. Curcuma longa's curcumin has anti-inflammatory, antioxidant, and endothelial-protective properties that may reverse the endothelial dysfunction that is characteristic of preeclampsia. Withania somnifera serves as an adaptogen, aiding in stress response modulation and enhancing vascular function. The anti-inflammatory and vascular-protective effects of Rheum officinale may help to lower preeclampsia-related complications and enhance maternal vascular health. A. racemosus is notable for its capacity to boost NO production, lessen oxidative stress, and enhance endothelial function by virtue of its saponins, flavonoids, and antioxidants.

1.12. Animal models and clinical evidence

The complex nature of preeclampsia, which affects only humans, presents difficulties in fully recreating its characteristics in animal models. Still, experimental investigations employing animal models have offered insightful information on the condition's underlying mechanisms. It has been difficult to conduct mechanistic studies on pregnant women; thus, the majority of experimental data on the underlying mechanisms of preeclampsia has come from animal models. Many excellent reviews have gone into great detail on the general pathophysiology and clinical aspects of preeclampsia, and readers are encouraged to consult some of them. Rodent models, particularly rats and mice, are frequently employed in preeclampsia research due to their relative ease of genetic manipulation, short gestation periods, and well-characterized physiological responses. These models enable researchers to investigate particular elements of the disease, such as hypertension, proteinuria, and placental ischemia. The results from animal studies have shown the protective effects of various medicinal plants on preeclampsia-like symptoms. These studies frequently involve the administration of plant extracts or isolated bioactive compounds to pregnant animals subjected to experimental preeclampsia induction methods, such as reduced uterine perfusion pressure or administration of pro-inflammatory agents.

The ability of these herbal treatments to lower blood pressure, enhance endothelial function, and lessen oxidative stress in animal models has been documented. Although clinical trials in humans are still limited, the available data point to the potential advantages of employing Indian medicinal plants as adjuncts to conventional preeclampsia treatment. To confirm efficacy, safety, and ideal dosage, more thorough research is required, particularly well-designed randomized controlled trials. Incorporating these botanicals into contemporary therapeutic regimens could offer a comprehensive and affordable approach to preeclampsia management.

1.13. Clinical and ex vivo evidence

Clinical trials and ex vivo studies supported the potential of plants like A. racemosus and Curcuma longa in reducing oxidative stress and enhancing endothelial function in pregnant women. Improved maternal outcomes, such as reduced blood pressure and oxidative markers, were consistently reported.

2. Discussion

PE is still a major cause of maternal and fetal morbidity and mortality; thus, new therapeutic approaches are urgently needed. Based on their capacity to target critical pathological pathways like oxidative stress, endothelial dysfunction, and inflammation, Indian medicinal plants offer a promising alternative for the treatment of preeclampsia [11]. These botanicals, which include Withania somnifera, Tribulus terrestris, Allium sativum, Hemidesmus indicus, Curcuma longa and Rheum officinale, have a variety of bioactive components that work synergistically to restore vascular function and promote overall maternal health. Despite encouraging preclinical data, more clinical research is required to determine their efficacy, safety profiles, and optimal dosages. Combining these medicinal plants with conventional treatment approaches may offer a comprehensive and customized strategy for managing PE, which would improve outcomes for both mothers and their offspring.

Current management strategies for preeclampsia are largely focused on controlling symptoms and timing delivery, but these approaches often do not address the underlying causes of the condition [7]. The symptoms of preeclampsia may be lessened and pregnancy outcomes may be improved by multiple micronutrient supplements. Preeclampsia is linked to increased oxidative stress, disturbed angiogenesis, and placental apoptosis. Indian medicinal plants can target these underlying processes and provide a more all-encompassing strategy for treating the condition. These plants are rich in bioactive compounds that have antioxidant and anti-inflammatory properties, which can help to reduce oxidative stress, systemic inflammation, and endothelial dysfunction—all key factors in the development of preeclampsia [13].

These medicinal plants have the potential to be used as complementary treatments for preeclampsia because they target the underlying pathological mechanisms. By reducing oxidative stress, enhancing vascular function, and controlling blood pressure, these botanicals offer a synergistic strategy to support overall maternal health and enhance pregnancy outcomes [2,15]. To fully realize the therapeutic potential of Indian medicinal plants in the management of preeclampsia and to incorporate them into contemporary healthcare practices, more research is required to confirm their safety and effectiveness. Given the high morbidity and mortality associated with severe cases of preeclampsia, any therapeutic strategy that allowed avoiding maternal complications and prolonging pregnancy would have a clear benefit for the health of the mother [7]. In addition to the generally recognized risk factors, changes in paternity between pregnancies, decreased exposure to paternal semen, interpregnancy weight change, history of migraine headaches, and a variety of biomarkers and clinical readings are topics of continuous investigation with less reliable evidence [10]. The most reliable risk factors for preeclampsia, based on the patient's medical history, are prior preeclampsia, certain chronic medical conditions, and multifetal pregnancy.

The pathophysiology of preeclampsia involves complex interactions between the placenta, maternal vasculature, and immune system [12]. The initiating event in preeclampsia is thought to be poor placental perfusion, which results in widespread maternal vascular endothelium dysfunction. Endothelial dysfunction, in turn, causes hypertension, proteinuria, and other systemic symptoms seen in preeclampsia. Oxidative stress is considered to play a pivotal role in the pathology of preeclampsia which leads to enhanced placental superoxide generation [14]. It has been demonstrated that the imbalance between pro-oxidant and antioxidant mechanisms is the main factor. The excessive generation of free radicals and reactive oxygen species overwhelms the antioxidant defenses, leading to oxidative damage to cellular components, including lipids, proteins, and DNA.

Preeclampsia is a major contributor to maternal deaths, premature births, and long-term health complications for both mother and child [16]. Although the exact cause of preeclampsia is not fully understood, it is widely accepted that abnormal placental development and function play a critical role. Defective placentation results in inadequate blood supply to the fetus, leading to placental ischemia and the release of factors that trigger systemic endothelial dysfunction and inflammation in the mother. The increased levels of sFlt-1 in preeclampsia have been linked to mitochondrial dysfunction, which disrupts normal endothelial and placental cell function.

Indian medicinal plants have a long history of traditional use in various healthcare systems, including Ayurveda and Unani. The bioactive components found in these plants possess diverse pharmacological properties, making them attractive candidates for the development of novel therapeutic interventions. Hemidesmus indicus has strong anti-inflammatory and antioxidant properties, making it useful for reducing oxidative damage and systemic inflammation [13]. Allium sativum can improve nitric oxide bioavailability, regulate blood pressure, and promote vasodilation [28]. Tribulus terrestris can help maintain endothelial function and stabilize blood pressure, both of which promote cardiovascular health. Curcuma longa has significant anti-inflammatory, antioxidant, and endothelial-protective properties. Withania somnifera has adaptogenic and vasodilatory effects that improve vascular function and stress response, and Rheum officinale can improve maternal vascular health and lower the risk of preeclampsia-related complications thanks to its anti-inflammatory and vascular-protective properties [9].

Asparagus racemosus has become well-known due to its high concentration of antioxidants, flavonoids, and saponins. These bioactive substances are essential for boosting nitric oxide production, lowering oxidative stress, and enhancing endothelial function in preeclampsia. Preeclampsia affects 3–5 % of all pregnancies and is the result of an angiogenic imbalance, which remains one of the main causes of maternal mortality and a public health issue [46]. Reduced plasma concentrations of vitamin C are consistently reported in women with preeclampsia. Elevated lipid peroxidation markers combined with decreased antioxidant capacity clearly indicate oxidative stress [14]. Future research should focus on investigating the relationship between oxidative stress, maternal nutritional status in early pregnancy, and telomere attrition in preeclampsia [36]. Although current treatments like diuretics, beta blockers, labetalol, methyldopa, and slow-release nifedipine are helpful, they should not be used with angiotensin-converting enzyme inhibitors [4] and angiotensin II receptor blockers due to their potential to harm the fetus [41]. Early detection of symptoms, timely presentation to healthcare facilities, and subsequent treatment with antihypertensive medications, magnesium sulfate, and delivery of the fetus and placenta have all been shown to improve outcomes in pregnancies complicated by preeclampsia and eclampsia.

Vitamin D supplementation may reduce the likelihood of recurrent preeclampsia in pregnant women who have previously experienced the condition [40]. Asparagus racemosus exhibited antagonistic activity against oxytocin-induced uterine contractions, reduced the frequency of uterine contractions, and decreased the expulsion time of pups, which could be attributable to its antioxytocic effects. It shows promising results in the treatment of preeclampsia by enhancing NO production, reducing oxidative stress, and improving endothelial function [82]. Further research is required to fully understand the underlying mechanisms and determine optimal dosage and safety profiles. Additional research is required to assess the long-term safety and effectiveness of these treatments in preeclampsia management.

Integrating medicinal plants such as Asparagus racemosus, Hemidesmus indicus, Allium sativum (garlic), Tribulus terrestris, Curcuma longa, Withania somnifera and Rheum officinale into preeclampsia treatment offers a comprehensive strategy that addresses multiple aspects of the condition's pathophysiology. This approach has the potential to enhance maternal and fetal outcomes by reducing oxidative stress, improving endothelial function, and controlling blood pressure [83]. Indian medicinal plants contain a variety of bioactive substances with diverse pharmacological effects that may have therapeutic benefits for preeclampsia. It is crucial to conduct more research to determine the safety and efficacy of medicinal plants in treating preeclampsia, despite encouraging results. It is crucial to consider cultural relevance, patient preferences, and potential interactions with conventional treatments when incorporating Indian medicinal plants into preeclampsia care. Indian medicinal plants have a lot of potential to improve preeclampsia management and offer a more comprehensive approach to care, but more research is required to fully realize this potential.

3. Conclusion

Indian medicinal plants offer a promising complementary approach to the management of preeclampsia by targeting key pathological mechanisms such as oxidative stress, endothelial dysfunction, and inflammation. While traditional use supports their benefits, rigorous research is needed to confirm efficacy, safety, and dosage. By addressing key pathological mechanisms, these medicinal plants offer a promising approach for PE management. Integrating these botanicals into contemporary therapeutic regimens may provide a comprehensive and economically viable strategy for managing preeclampsia, particularly in resource-constrained environments, warranting thorough investigation and clinical validation.

Author contributions

The concept and design of the review were developed by M.I.A. S.W. conducted the literature search and data compilation. Y.A. H.Q. and S.A.F. were responsible for the critical evaluation and interpretation of the reviewed studies. S.A. contributed to the structuring and refinement of the manuscript. All the authors revised and approved the final draft.

Sources of funding

None

Declaration of generative AI in scientific writing

Not used.

Conflict of interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sheema Wazib reports financial support was provided by Hamdard Institute of Medical Sciences and Research. Reports a relationship with that includes:. Has patent pending to. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.