Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control

Abstract

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

Graphical Abstract

Highlights

• • S. aizoon L. is frequently prescribed in both China and other countries as a traditional folk herbal remedy for various diseases

• • This review contributes to updating the herbalogical textual research, traditional use, botany, phytochemistry, pharmacology, toxicity, and nutritional value and quality control of S. aizoon L.

• • In earlier literature, there was no systematic review of S. aizoon L

1 Introduction

Sedum aizoon L. (Chinese name:景天三七) is a perennial herbaceous plant that is widely distributed in China, Russia, Mongolia, Japan, North Korea, and Mexico. It is a member of the Sedum genus in the Sedum family (Crassulaceae) (Guo and Lin, 2007). Its name is also consistent with the plant name recorded in “The Plant List” (http://www.theplantlist.org), which is now incorporated into the requirement for traditional medicine in the provinces of Jiangsu and Fujian (Jia et al., 2014). It is one of the renowned “Taibai seven medicine (太白七药)” in the Qinling Mountains, which has the effects of dispersing blood stasis, stopping bleeding, tranquilizing the mind, detoxifying, and analgesia, and is used in the treatment of various kinds of bleeding, palpitations, and insomnia. Growing in the natural environment, S. aizoon is a unique pest-free plant that does not require pesticides during its whole phenological cycle and has been designated as AA grade green food by the China Green Food Development Center. Its fresh stems and leaves are consumed as vegetables (Xue, 2015).

Despite the fact that the phytochemistry and ethnopharmacology of S. aizoon have been previously reviewed, a comprehensive study linking its bioactive metabolites with its pharmacological properties is lacking. Therefore, this paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

2 Materials and methods

Information about S. aizoon was gathered from scientific literature sources, including PubMed, Baidu Scholar, Google Scholar, Web of Science, SciFinder, CNKI, Wanfang, the Plant List (www.theplantlist.org), and books. The history, nutritional value, traditional uses, botany, phytochemistry, pharmacology, toxicology, and quality control or a combination between them was used as keywords to search for data up to July 2023. Approximately, 767 research studies of S. aizoon were gathered from various databases. With the removal of duplicate literatures, 300 literatures were selected according to research purpose, relevance, and article type. The articles which contained information apart from that mentioned above or written in languages rather than English were also excluded. ChemBioDraw Ultra version 14.0 was used to draw chemical structures.

3 History and traditional uses

3.1 History

S. aizoon was first recorded in “Jiu Huang Ben cao” (救荒本草) (Ming Dynasty), which is the earliest book with agronomy and botany as its monograph on the history of China. Later, it was also included in many other famous works on Chinese herbal medicine, including “Wild Vegetables Bo lu” (野菜博录) (Ming Dynasty), “Plants Ming Shi Tu Kao” (植物名实图考), and “Discussion on varieties of Chinese medicinal materials” (中药材品种论述).

The medicinal parts of S. aizoon were roots and grass in S. aizoon, and S. kamshaticum. S. aizoon has more than 60 synonyms and is distributed in more than 20 provinces or autonomous regions. In addition, the herb and the syrup were included in the Pharmacopoeia of the People’s Republic of China (Part I) (1977 edition) (Chinese Pharmacopoeia Committee, 2005).

3.2 Traditional uses

In folk medicine, the flat and sweet whole herb and the roots of S. aizoon are widely used for dispersing blood stasis and stopping blood bleeding. For instance, daily administration of 60–90 g of S. aizoon decoction can treat bleeding symptoms, including hemoptysis, bleeding gums, epistaxis, gingival bleeding, and internal bleeding. The fresh juice was effectively used for the treatment of leukemia, aplastic anemia, thrombocytopenic purpura, hemoptysis, and different forms of bleeding (i.e., gingival, digestive tract, and hematuria) (Chinese herbal medicine research group, 1971). In addition, ancient medical classics, such as Li Shizhen’s “Compendium of Materia Medica” (本草纲目), Chen Shiduo’s “New Compilation of Materia Medica” (本草新编), and Zhang Xichun’s “Intergrating Chinese And Western Medicine” (医学衷中参西录), explicitly stated that S. aizoon had good hemostasis and analgesic function, which was known as “the god medicine for hemostasis” (止血神药). It is also used as a heart and mind tranquillizing agent with an excellent effect on hysteria palpitation, restlessness, hypertension, and rheumatic heart disease (Chen, 2003). Likewise, the detoxifying and clearing heat effects have also been reported.

Of note, S. aizoon has a long history as both an edible and medicinal herb. For example, vegetables with S. aizoon’s stems and leaves as metabolites have good nutritional value. “Jiu Huang Ben Cao” (救荒本草) in the Ming Dynasty stated that the regular consumption of the fresh, tender stems and leaves of S. aizoon can promote blood circulation and calm the heart.

4 Nutritional value

The tender stems and leaves contain moisture (87 g), protein (2.1 g), fat (0.7 g), carbohydrate (8.0 g), crude fiber (1.5 g), ash (1.2 g), energy (196.65 KJ), Ca (315 mg), P (39 mg), Fe (3.2 mg), carotene (2.54 mg), vitamin B1 (0.05 mg), vitamin B2 (0.07 mg), vitamin PP (90 mg), and vitamin C (90 mg) (Yi, 2000; Liu et al., 2012). Owing to its unique aroma and taste, S. aizoon is used for the preparation of cookies, jellies, and tea (Wang, 2013).

5 Botany

5.1 Geographical repartition

S. aizoon belongs to the genus Sedum of the Crassulaceae family. There are approximately 600 species widely distributed in the temperate and subtropical regions of the northern hemisphere with Mexico being the largest center of origin and diversity of Sedum species.

5.2 Morphology

S. aizoon is an annual or perennial, succulent herb, growing in clusters and has a strong ability to bifurcate. S. aizoon has coarse, woody rhizomes that resemble ginseng in form. The stems are erect, cylindrical, and glabrous, which can reach heights of 15–50 cm. At each node, the stems carry just one leaf, which is nearly opposite on both sides. The leaves are 2.5–5 cm long, 5–12 mm wide, obovate or long oval in shape, and broad and thick with more juice. Additionally, they feature a cuneate base, a serrated border toward the apex, a moderately rounded top, and few sessile leaves. The loose, terminal verticillaster contains ten stamens that are around the same length as the petals, five distinct pistils that are slightly longer than the stamens, five orange–yellow petals with lancolate, sharp tips, and five sepals with blunt ends. Follicles are either reddish or brown in color and are grouped in a star pattern. Seeds are obovate, smooth, have wings along the edge, and have a wider apical. Flowers usually bloom in summer. The photos of S. aizoon are pictured and shown in Figure 1.

FIGURE 1.

Morphological characteristics of S. aizoon: (A) leaves, (B) roots, (C) dry drug, (D) buds, and (E) whole plant.

6 Phytochemistry

Up to now, more than 234 metabolites, including flavonoids (1–48), phenolic acids (49–78), triterpenes and phytosterols (79–90), alkaloids (91–98), volatile constituents (99–216), and others (217–234), have been preliminarily isolated or identified from S. aizoon. Among these, flavonoids are the main metabolites of S. aizoon. The main metabolites and their structure are given in Table 1 and Figures 2–5.

TABLE 1.

Main active metabolites identified in S. aizoon.

Metabolite	Plant part	Molecular formula	Reference
Flavonoid
Trifolin	Leaves and stems	C21H20O11	Xu et al. (2019)
Rutin		C27H30O16
Isoquercitrin		C21H20O12
Isorhamnetin		C16H12O7
Astragalin		C21H20O11
Genistein		C15H10O5
Lonicerin		C27H30O15
Scutellarein		C15H10O6
Catechin		C15H14O6
Rhamnetin-3-O-β-D-glucopyranoside	Rhizome	C22H22O12	Li et al. (2020a)
Isorhamnetin-3-O-β-D-xylopyranoside		C21H20O11
Isorhamnetin-3-O-α-L-arabinopyranoside		C21H20O11
Rhamnazin-3-O-β-D-glucopyranoside	Aerial parts	C23H26O12	Xiong et al. (2019)
Quercetin	Aerial parts, rhizome, and leaves and stems	C15H10O7
Myricetin	Aerial parts and leaves and stems	C15H10O8
Luteoloside	N/A	C21H20O11
Quercitrin	Aerial parts and leaves and stems	C21H20O11	Wolbi and Olszewska (1996), Li et al. (2007)
Myricitrin	Aerial parts	C21H20O12
Quercetin-3-o-(2′-galloyl) rhamnoside	N/A	C28H30O9	Wolbi and Olszewska (1996)
Quercetin-3-O-α-L-arabinopyranoside	Leaves and stems and rhizome	C20H18O11	Han et al. (2017)
Myricetin-3-O-α-L-arabinopyranoside	Aerial parts	C20H18O12
Kaempferol-7-O-glucoside	Leaves and stems	C21H20O11
Kaempferol-3-O-β-D-glucopyranoside		C21H20O11
Herbacetin-3-O-α-L-arabinopyranoside		C20H18O10
Myricetin-3-β-D-glucopyranoside	Aerial parts and leaves and stems	C21H20O13	Li et al. (2008)
Myricetin-3-β-D-(6″-o-galloyl)-glucopyranoside	Whole grass	C28H24O17
Myricetin-3-o-β-D-(6″-o-galloyl)-galactopyranoside		C28H24O17
Myricetin-3′-o-β-D-glucopyranoside	Leaves and stems	C21H20O13	Jia et al. (2014)
Kaempferol	Leaves and stems and rhizome	C15H10O6	Lin et al. (2014), Xiong et al. (2019)
Kaempferol-3-O-α-L-rhamnoside	Leaves and stems	C21H20O10	Zhang et al. (2010)
Herbacetin-8-O-α-D-lyxoside		C20H18O11
Herbacetin-8-O-β-D-xylopyranoside		C20H18O11
Luteolin		C15H10O6
Herbacetin-8-O-β-D-glucopyranoside	Aerial parts	C25H23O7D3	Xu et al. (2015)
Herbacetin-3-O-β-D-glucopyranosyl-8-O-α-L-arabinopyranoside		C74H105O32
Herbacetin-3-O-α-L-rhamnopyranosyl-8-O-α-D-lyxopyranoside		C26H28O14
Herbacetin-3-O-α-L-arabinopyranosyl-8-O-β-D-xylopyranoside		C25H26O14
Gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranoside		C73H106O34
3′-Methoxyl-gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranosie		C27H30O17
6″-O-(E)-feruloyl isorhamnetin	Whole plant	C32H30O15	(Li J. X. et al., 2011)
6″-O-(E)-feruloyl quercetin		C31H28O15
3,4′,5,7-Tetrahydroxyflavone-7-O-α-D-xylopyranoside	Whole grass	C20H18O10	Han et al. (2021)
Sedacin A	Whole plant	C28H32O7	Li J. X. et al. (2011)
Sedacin B		C29H34O7
1,3,8,10,10b-Pentahydroxy-5a-(4-hydroxy-3-methoxyphenyl)-9-(4-hydroxybenzoyl)-5a,10b-dihydro-11H-benzofuro[2,3-b]chromen-11-one	Roots	C29H21O12	Li et al. (2017)
1,3,8,10,10b-Pentahydroxy-9-(4-hydroxybenzoyl)-5a-(4-hydroxyphenyl)-5a,10b-dihydro-11H-benzofurochromen-11-one		C28H19O11
5a-(3,4-Dihydroxyphenyl)-1,3,8,10,10b-pentahydroxy-9-(4-hydroxybenzoyl)-5a,10b-dihydro-11H-benzofurochromen-11-one		C28H19O12
1,8,10,10b-Tetrahydroxy-5a-(4-hydroxy-3-methoxyphenyl)-9-(4-hydroxybenzoyl)-3-methoxy-5a,10b-dihydro-11H-benzofuro[2,3-b]chromen-11-one		C30H23O12
Phenolic acids
Sedumol	Whole grass	C12H16O8	Han et al. (2021)
Vanillic acid	Aerial parts	C8H8O4	Lin (2014)
Protocatechuic acid	Aerial parts and leaves and stems	C7H6O4
Caffeic acid	N/A	C9H8O4
P-hydroxybenzoic acid	Aerial parts and leaves and stems	C7H6O3	Lin et al. (2014)
Pyrogallol	Aerial parts	C6H6O3
5,7-Dihydroxychromone	N/A	C9H6O4
Glucosyringic acid	Leaves and stems	C15H20O10	Jia et al. (2014)
P-hydroxybenzoyl arbutin		C19H20O9
Pyroside		C14H18O8
Arbutin	Roots and leaves and stems	C12H16O7
4-Methoxy-3,5-dihydroxybenzoic acid	Whole grass	C8H8O5	Han et al. (2021)
4-Hydroxybenzeneethanol		C8H10O2
4-Hydroxybenzaldehyde		C7H6O2
cis-4-Coumaric acid	Aerial parts	C9H8O3	Xiong et al. (2019)
2-O-(trans-caffeoyl) malic acid		C13H12O8
2-O-(trans-caffeoyl)-malic acid 1-methyl-ester		C14H14O8
2-O-(trans-caffeoyl)-malic acid 1,4-dimethyl ester		C15H16O8
Isolariciresinol-9-O-β-D-glucopyranoside		C26H34O11
Iriflophenone-2-O-β-D-glucopyranoside		C19H20O10
Ethyl gallate	Aerial parts and leaves and stems	C9H10O5
Gallic acid	Aerial parts, whole plant, and leaves and stems	C7H6O5	Zhang et al. (2010)
Methyl gallate	Aerial parts and leaves and stems	C8H8O5
Echinochlorin A	Rhizome	C26H40O8	Li et al. (2020a)
1-O-sinapoyl glucopyranoside	Aerial parts	C17H22O10	Xu et al. (2015)
Chrysophanol-8-O-β-D-glucoside	Whole grass	C21H20O9	Li et al. (2008)
Hydroquinone	Roots and whole grass	C6H6O2
Vanilloloside	Leaves and stems	C14H20O8	Han et al. (2017)
Woodorien		C13H9N3O2
Iriflophene	Aerial parts and rhizome	C13H10O5	Xiong et al. (2019), Li et al. (2020a)
Triterpenes
Ginsenoside Re	Roots	C48H82O18	Gong (2020)
α-Amyrin	N/A	C30H50O
Ursolic acid	Roots	C30H48O3	Li et al. (2008)
Glutin-5-en-3-one	Leaves and stems	C30H48O
Isomoliol-3β-acetate		C32H52O2
Taraxerone	Rhizome	C30H48O	Li et al. (2020a)
Isomotiol		C30H50O
Oleanolic acid	Roots	C30H48O3	Lin (2014)
Phytosterols
β-Sitosteryl linoleate	Rhizome	C47H80O2	Li et al. (2020a)
Daucosterol	Rhizome and whole grass	C35H60O6
β-Sitosterol	Rhizome, leaves and stems, and roots	C29H50O	Zhang et al. (2010)
Stigmasterol	N/A	C29H48O	Cao (2011)
Alkaloids
Sedinine	N/A	C17H25NO2	Kim et al. (1996)
Despun methylisopelletierine		C9H17NO
Sedamine	Roots	C14H21NO	Li et al. (2008)
Aizoonoside A	Aerial parts	C18H19NO8	Xu et al. (2015)
Thymine	Aerial parts	C5H6N2O2	Lin et al. (2014)
Senecionine	Roots	C18H25NO5	Wu et al. (2008)
Seneciphylline		C18H23NO5
Integerrimine		C18H25NO5
Volatile oils
2,6-Di(tbutyl)-4-hydroxy-4-methyl-2,5-cyclohexadien-1-one	Whole plant	C15H24O2	Qian et al. (2018)
β-Ionone		C13H20O
Epiglobulol		C15H26O
α-Guaiene		C15H24
Isophytol		C20H40O
Squalene		C30H50
Tritriacontane		C33H68
Hexadecane		C16H34
Pristane		C19H40
Octadecane		C18H38
Tricosane		C23H48
Tetracosane		C24H50
Pentacosane		C25H52
Hexacosane		C26H54
Heptacosane		C27H56
Octacosane		C28H58
Nonacosane		C29H60
Hentriacontane		C31H64
Cetyl palmitate		C32H64O2
4, 8, 12, 16-Tetramethyl heptadecan-4-olide		C21H40O2
Cyclohexyl benzoate		C13H16O2
Methyl palmitoleate		C17H32O2
Methyl palmitate		C17H34O2
Ethyl palmitate		C18H36O2
Methyl linolelaidate		C19H34O2
Methyl oleate		C19H36O2
Methyl stearate		C19H38O2
Ethyl linoleate		C20H36O2
Ethyl oleate		C20H38O2
1-Hexacosanol		C26H52O
Hexahydrofarnesyl acetone	Whole plant and fresh herbs	C18H36O	Guo et al. (2006), Qian et al. (2018)
2-Undecanone	Fresh herbs	C11H22O	Guo et al. (2006)
2-Tridecanone		C13H26O
Nerolidol		C15H26O
(−)-Spathulenol		C15H24O
Cedrol		C15H26O
Globulol		C15H26O
1-Nonene		C9H18
(十)-Aromadendrene		C15H24
Calamenene		C15H22
Caryophyllene epoxide		C15H24
Bornyl acetate		C12H20O2
Geraniol acetate		C12H20O2
15-ene-heptadecanal		C17H48O
Hexadecanoic acid		C16H32O2
Phytol	Leaves, stems, fruits, and fresh herbs	C20H40O
4-hepten-2-one	Aerial parts	C7H12O	Chen et al. (2014)
Elsholtzia ketone		C10H14O2
3-Methyl-2-butanol		C5H12O
2,3-Butanediol		C4H10O2
1-Octanol		C8H18O
4-Terpineol		C10H18O
3-Hexen-1-ol		C6H12O
Pentylfuran		C9H14O
β-Phellandrene		C10H16
4-Carene		C10H16
β-Terpinene		C10H16
Isoterpinolene		C10H16
α-Thujene		C10H16
β-Farnesene		C15H24
π-Muurolene		C15H24
Heptanal		C7H14O
Benzaldehyde		C7H6O
Hexanal		C6H12O
Furfural		C5H4O2
Octanal		C8H16O
Benzeneacetaldehyde		C8H8O
Nonanal		C9H18O
Decanal		C10H20O
1-Octadecanol	Roots and leaves	C18H38O	Chen and Qiang (2017)
(Z) 9-Octadecenoic acid, methyl ester	Roots and stems	C19H36O2
2,2′-Methylenebis(6-tert-butyl-4-methylphenol	Leaves, stems, and fruits	C23H32O2
Dimethyl phthalate		C10H10O4
Methyl tetradecanoate		C15H30O2
Heptadecanoic acid methyl ester		C18H36O2
Pentatriacontane	Leaves, stems, and roots	C35H72
Heptadecane	Leaves, and whole plant	C17H36
3-Ethyl-2,4-dimethyl-pentane	Leaves	C9H20
2,6-Dimethyl-octane		C10H22
6,10,14-Trimethyl2 pentadecanone		C18H36O
1-Pentadecanol		C15H32O
Oxacycloheptadec-8-en-2-one		C16H28O2
Tridecanoic acid, methyl ester		C14H28O2
2,6,11-Trimethylodlodecane		C15H32
3-Methyl-undecane		C12H26
Octadecane	Fruits	C18H38
2,6,10,14-Tetramethyl-hexadecane		C20H42
Icosane	Stems	C20H42
Nonadecane		C19H40
3,8-Dimethyl-decane		C12H26
4-Methyl-pentadecane		C16H34
1-Octadecene		C18H36
2-Methyl-tridecane		C14H30
Tetratetracontane		C44H90
Tetradecane		C14H30
Pentadecane	Leaves and stems	C15H32
2,4,4-Trimethylhexane		C9H20
2,4-Dimethylhexane		C8H18
4,6-Dimethyl-dodecane		C14H30
Heneicosanoic acid-methyl ester		C22H44O2
Tricosanoic acid, methyl ester		C24H48O2
2,4-bis(1,1-Dimethylethyl)-phenol		C14H22O
Hexadecyl-oxirane		C18H36O
3,3- Dimethylhexane		C8H18
3, 3-Dimethyl-heptane	Roots	C9H20
Tetratriacontane		C34H70
1-Heptadecanol		C17H36O
Octacosanoic acid, methyl ester		C29H58O2
Octadecanal		C18H36O
2-Hexadecyl-1,1′-bi-cyclopentyl		C26H50
P-Cymene	Aerial parts	C10H14
Pentadecanoic acid, methyl ester	Roots, leaves, stems, and fruits	C16H32O2
Dibutyl phthalate		C16H22O4
(Z,Z,Z)-9, 12, 15-octadecatrienoic acid, methyl ester		C19H32O2
Eicosanoic acid, methyl ester		C21H42O2
Docosanoic acid, methyl ester		C23H46O2
Tetracosanoic acid, methyl ester		C25H50O2
Hexacosanoic acid, methyl ester		C27H54O2
Others
Glucose	Whole grass	C6H12O6	Zheng (1975)
Fructose		C6H12O6
Sedoheptulose		C7H14O7
Sucrose		C12H22O11
(3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol 9-O-β-D-glucopyranoside	Aerial parts	C28H35O4D	Xu et al. (2015)
(3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol 3-O-β-D-glucopyranoside		C28H35O4D
Picein	Leaves and stems	C14H18O7	Jia et al. (2014)
Koaburaside		C14H20O9
Hexacosoic acid	Whole grass	C26H52O2	Li et al. (2008)
Salidroside		C14H20O7
Malic acid	N/A	C4H6O5	Xuan (2014)
N-triacontanoic acid	Roots and stem	C33H66O2	Li et al. (2020a)
1-Hexadecanol		C16H34O
Dioctadecylsulfide		C36H74S
1-Naphthalen-2-yl-ethanone	Whole grass	C12H10O	Lin et al. (2011)
Lotaustralin	Aerial parts	C11H19NO6	Xiong et al. (2019)
Butanedioic acid		C4H6O4
9(Z)-octadecenamide		C18H35NO

N/A: not applicable or not explicitly stated.

FIGURE 2.

Structures of flavonoids from S. aizoon (1–48).

FIGURE 5.

Structures of alkaloids (91–98) from S. aizoon.

6.1 Flavonoids

So far, 48 flavonoid metabolites (1–48) with definite structure have been isolated and identified from S. aizoon, which are grouped into flavonols (1–36), isoflavones (37–39), flavones (40–43), flavanonols (44–47), and flavan-3-ol (48). Among flavonols, rhamnazin-3-O-β-D-glucopyranoside (4), myricitrin (10), myricetin-3-O-α-L-arabinopyranoside (14) (Xiong et al., 2019), herbacetin-8-O-β-D-glucopyranoside (26), herbacetin-3-O-β-D-glucopyranosyl-8-O-α-L-arabinopyranoside (27), herbacetin-3-O-α-L-rhamnopyranosyl-8-O-α-D-lyxopyranoside (28), herbacetin-3-O-α-L-arabinopyranosyl-8-O-β-D-xylopyran-oside (29), gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranoside (31), and 3′-methoxyl-gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranosie (35) (Xu et al., 2015) were obtained mainly from the aerial part of S. aizoon. Later, Xu et al. (2019) successfully identified four flavonols [i.e., trifolin (1), rutin (2), astragalin (32), and isoquercitrin (5)], two flavones [i.e., lonicerin (43) and scutellarein (46)], and one isoflavone [i.e., genistein (39)] in the leaves and stems of S. aizoon. Two new prenylated isoflavones, sedacin A (37) sedacin B (38), and two flavonols, sedacin C (6″-O-(E)-feruloyl quercetin) (33) and sedacin D (6″-O-(E)-feruloyl isorhamnetin) (34), were isolated from the whole plant of S. aizoon (Li W. L. et al., 2011). Among them, sedacin A and sedacin B had the function of scavenging DPPH and ABTS+ free radicals (Li J. X. et al., 2011). Rhamnetin-3-O-β-D-glucopyranoside (3), quercetin-3-O-α-L-arabinopyranoside (8), isorhamnetin-3-O-β-D-xylopyranoside (22), and isorhamnetin-3-O-α-L-arabinopyranoside (23) have also been detected in rhizomes (Li et al., 2020a). Four flavanonols (44–47) with rare dimeric structures, with the character of an iriflophene unit and a flavonoid unit connecting via a furan ring, were isolated from the roots and identified using NMR, IR, UV, HRESIM, DEPT, HSQC, HMBC, and CD methods. In addition, studies were conducted to assess the activity of these four substances, and they revealed that 5a-(3,4-dihydroxyphenyl)-1,3,8,10,10b-pentahydroxy-9-(4-hydroxybenzoyl)-5a,10b-dihydro-11H-benzofurochromen-11-one (46) and 1,8,10,10b-tetrahydroxy-5a-(4-hydroxy-3-methoxyphenyl)-9-(4-hydroxybenzoyl)-3-methoxy-5a,10b-dihydro-11H-benzofuro[2,3-b]chromen-11-one (47) had good anti-proliferative activities in vitro against the tumor cell lines BXPC-3, A549, and MCF-7 (Li et al., 2017). The structures of flavonoids from S. aizoon are displayed in Figure 2.

6.2 Phenolic acids

Phenolic acids are the most important chemical derivatives of plant secondary metabolites. Currently, 31 phenolics (49–78) have been found from S. aizoon, including phenolic acids (49–58, 60), lignans (61), phenylpropanoids (59, 62–63), and other phenolics (64–78). Two phenolic acids, namely, sedumol (49) and 4-methoxy-3,5-dihydroxybenzoic acid (56) (Han et al., 2021), were obtained from the 95% ethanol extract of S. aizoon ^’s whole grass. Other phenolic acids, including vanillic acid (50) (Lin, 2014), protocatechuic acid (51), cis-4-coumaric acid (52), p-hydroxybenzoic acid (54) (Xiong et al., 2019), and caffeic acid (53) (Lin et al., 2014), were isolated from the aerial part of S. aizoon. Isolariciresinol-9-O-β-D-glucopyranoside (61) is classified as cyclolignans, which was obtained from the 70% ethanol extract via silica gel column chromatography (300–400 mesh). 2-O-(trans-caffeoyl)-malic acid 1,4-dimethyl ester (59) (Xiong et al., 2019), echinochlorin A (62) (Li et al., 2020a), 1-O-sinapoyl glucopyranoside (63) (Xu et al., 2015), and chrysophanol-8-O-β-D-glucoside (64) (Li et al., 2008) have been identified in S. aizoon. The structures of phenolic acids from S. aizoon are displayed in Figure 3.

FIGURE 3.

Structures of phenolic acids from S. aizoon (49–78).

6.3 Triterpenes and phytosterol

6.3.1 Triterpenes

A type of terpenoids known as triterpenoids has a parent nucleus that contains 30 carbon atoms. Triterpenoids exist in plants in free form or as glycosides or esters and have various biochemical activities. Up to now, eight triterpenes (79–86) were separated from S. aizoon, including one tetracyclic triterpenes (79) and seven pentacyclic triterpenes (80–86). The only tetracyclic triterpene, ginsenoside Re (79), is a dammarane-type triterpene. Seven pentacyclic triterpenes are divided into four groups: ursane type (80), oleanane type (81–83), friedelane type (84), and fernane type (85–86). In the studies of Li et al. (2008, 2020a), glutin-5-en-3-one (84), isomoliol-3β-acetate (86), taraxerone (82), and isomotiol (85) were isolated from S. aizoon for the first time. The structures of triterpenoids from S. aizoon are displayed in Figure 4.

FIGURE 4.

Structures of triterpenoids (79–86) and phytosterol (87–90) from S. aizoon.

6.3.2 Phytosterols

Up to now, a total of four phytosterols (87–90) have been identified in S. aizoon. These include β-sitosteryl linoleate (87) (Li et al., 2020a), daucosterol (89) (Guo et al., 2010; Lin et al., 2011), β-sitosterol (88), and stigmasterol (90) (Cao, 2011). The structures of phytosterol from S. aizoon are displayed in Figure 4.

6.4 Alkaloids

Eight alkaloids (91–98) have been isolated and identified from S. aizoon. In 1996, Kim et al. (1996) examined the alkaloids in Sedum species and discovered the presence of three alkaloids, namely, sedinine (91), sedamine (92), and despun methylisopelletierine (93) in S. aizoon. Thymine (95) was obtained from the ethyl acetate fraction of aqueous extracts of Sedum aizoon L. In the study of Gao et al. (2006), three pyrrolizidine alkaloids (PAs), namely, senecionine (96), seneciphylline (97), and integerrimine (98) were identified in the extracts of S. aizoon’s root, which had strong hepatotoxicity. The structures of alkaloids from S. aizoon are displayed in Figure 5.

7 Pharmacological activities

According to pharmacological studies, S. aizoon has a wide range of pharmacological activities, including antioxidant, anti-fatigue, and anti-inflammatory activities, improving cardiovascular disease, and other activities. The related biological activities and main effects are listed in Table 2.

TABLE 2.

Biological activities of the S. aizoon extracts and bioactive metabolites.

Tested substance	Model	Key result	Reference
Ethanol extract	In vitro, total antioxidant capacity, superoxide anion, OH radical scavenging assay, and blood antioxidant	Obvious antioxidant activity	Ma et al. (2019), Qi et al. (2022)
	Stomach bleeding model in mice, clean grade healthy ICR Mice	Reduced gastric mucosal injury and shortened the bleeding time and clotting time in mice	Zhong et al. (2014)
	In vitro, aeromonas, Rhizopus nigricans, Botrytis cinerea, Penicillium italicum, Pseudomonas fragi, and Shewanella putrefaciens isolated from sea food	Exhibited antibacterial activity, caused membrane damage, disruption of mycelial morphology, the bacterial surface, and internal ultrastructure, resulted in the leakage of sugars and proteins, retarded the microbial growth, and delayed meat spoilage	Xu et al. (2019), Luo et al. (2020), Wang et al. (2020), Wang et al. (2022a), Wang et al. (2022b), Wang et al. (2023c), Ge et al. (2023)
	Human liver cancer cell line	The inhibitory rate of liver cancer cells was as high as 52.04% with 200 μg/mL ethanol extract	Wang et al. (2013)
	ICR mice weigh 18∼20 g	Reduced the weight gain of mice and TC and TG levels increased HDL-C levels	Wang et al. (2013)
	Type 1 diabetes mellitus mice	Significantly restored body weight gain, improved food utilization, decreased the coefficients for both the liver and kidney, the levels of TC and TG, and the MDA content, increased the levels of HO-1 and NQO1 in the livers of mice, activated the Nrf2 pathway, thereby regulating the expression of downstream proteins, and regulated glucose metabolism in T1DM mice	Qi et al. (2022)
	In vitro, MDRPA, Staphylococcus aureus, Staphylococcus epidermidis, Micrococcaceae, Escherichia coli, Salmonella paratyphi B, bacillary dysentery, Proteus mirabilis, Clostridium perfringens, Bacillus subtilis, Bacillus anthracis, Candida parapsilosis, Candida tropicalis, and Candida albicans	The MIC50 for pseudomonas aeruginosa was 0.125 g/mL, which exerted definite bacteriostatic effects on bacteria and weak effect on fungus	Zhang et al. (2011), Zhang et al. (2012)
Sap	In vivo, the liver in Cyprinus carpio Linnaeus	Increased SOD, POD activities, and MDA content	Zhang and Wang (2012)
	College students who have completed exhaustive exercise	Prolonged the time of extreme exercise in mice, decreased BUN and MDA levels and LDH, increased SOD, muscle glycogen content, and liver glycogen content, play an anti-fatigue role, increased the amount of blood return and the content of hemoglobin in the blood, reduced the blood flow at the end of the limb and the concentration of cortisol and serum creatine kinase in the blood, improved the ability of metabolic regulation and response speed, accelerated fatigue recovery, and prevented and relieved fatigue	Ding, 2019; Ren (2020)
	In vivo, rats with gastrointestinal tract hemorrhage induced by aspirin	Turned positive rat fecal occult blood into negative, increased PC, GPⅡb/Ⅲa, P selectin, PLT, IL8, ET-1, and platelet number and aggregation, decreased PAF, significantly shortened TT and APTT, and significantly increased FIB	Liu et al. (2011), Liu et al. (2015), Bai et al. (2016)
	Senile stroke patients	Promoted blood circulation, removed blood stasis, and reduced blood pressure	Chen (2000)
Ethyl acetate extracts	LPS-stimulated RAW 264.7 cells	Inhibited LPS-induced NO, TNF-α, and IL-6 production	Lin et al. (2015a)
	α-Glucosidase activity assay	Inhibit α-glucosidase activity	Cao (2011)
N-Butanol extracts	α-Glucosidase activity assay	Inhibit α-glucosidase activity	Cao (2011)
Methanol extracts	α-Glucosidase activity assay	Inhibit α-glucosidase activity	Cao (2011)
	In vivo , male ICR mouse croton oil-induced ear edema, rat CGN-induced paw edema, TPA-induced ear edema assay of sub-chronic inflammation, mouse acetic acid-induced writhing, and LPS-stimulated RAW 264.7 cells	Inhibited PGE2 production by the downregulation of COX-2 expression and COX-2 induction and inhibited acute as well as sub-chronic inflammation dose-dependently	Kim et al. (2004)
	In vivo, H/R model in neonatal rat cardiomyocytes	Decreased the LDH, apoptosis, and caspase-3 activity, activated P13K/Akt, increased eNOS phosphorylation, NO, and the Bcl-2/Bax ratio, reduced H/R-induced cardiomyocyte damage, and protected cardiomyocytes	Qiang (2013)
S. aizoon tablet	244 cases with peptic ulcer bleeding	Increased the PC and shortened bleeding time	Xu (2012)
Aqueous extracting—ethanol precipitating extract	Stomach bleeding model in mice	Exerted the strongest protective effects on gastric mucosa	Zhong et al. (2014)
Petroleum ether	Stomach bleeding model in mice	Reduced gastric mucosal injury and shortened the bleeding time and clotting time in mice	Chen et al. (2012)
Ethyl acetate of water extraction	Clean grade healthy ICR mice	Good hemostatic effect	Chen et al. (2012)
Aqueous extracts	Stomach bleeding model in mice	Reduced gastric mucosal injury and shortened the bleeding time and clotting time in mice	Chen et al. (2012)
	In vitro, MDRPA, Staphylococcus aureus, and Pseudomonas aeruginosa	Have certain bacteriostasis, and the MIC50 for pseudomonas aeruginosa was 0.5 g/mL	Tan et al. (2001)
	In vivo, male Kunming mice	Increased the amount of sleeping mice and decreased the autonomic activities in mice	Guo et al. (2009)
	Esophageal carcinoma cells	Destroyed the structure of phospholipid and resulted in the damage of the ultrastructure of esophageal carcinoma cells	Fu et al. (2008)
	In vivo, patients with cardiovascular and cerebrovascular diseases	Protected blood vessels, removed blood stasis, and prevented blood clots	Xuan (2015)
Herbacetin-3-O-α-L-rhamnopyranosyl-8-O-α-D-lyxopyranoside	Escherichia coli; Staphylococcus aureus	Showed certain growth inhibition, and it showed more potency against Gram-positive than against Gram-negative bacteria	Xu et al. (2015)
	Rosenbach and Bacillus subtilis
Myricetin-3-O-β-D-glucopyranoside	Escherichia coli, Staphylococcus aureus Rosenbach, and Bacillus subtilis	Showed more potency against Gram-positive than against Gram-negative bacteria	Xu et al. (2015)
Gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranoside	Escherichia coli, Staphylococcus aureus Rosenbach, and Bacillus subtilis	Showed more potency against Gram-positive than against Gram-negative bacteria	Xu et al. (2015)
Ethyl acetate from alcohol extract	In vivo, male Kunming mice	Obviously decreased the autonomic activities in mice, prolonged the sleeping time, and increased the amount of sleeping mice	Guo et al. (2010)
N-butanol extracted from alcohol extract	In vivo, the male Kunming mice	Obviously decreased the autonomic activities in mice, prolonged the sleeping time, and increased the amount of sleeping mice	Guo et al. (2010)
Yangxincao Anshen Granule	In vivo, Kunming mice	Significantly decreased spontaneous activity, prolonged sleep time, and increased rates of sleeping in mice on the high (12 g/kg/d) and medium dosages (6 g/kg/d)	Zhang et al. (2015b)
S. aizoon (30 g) and Semen Ziziphus Spinosa (15 g)	In vivo, Kunming mice	Extented the sleep time significantly and increased the sleep rate	Zhang et al. (2015a)
S. aizoon (22.5 g) and Semen Ziziphus Spinosa (22.5 g)	In vivo, Kunming mice	Extended the sleep time and increased the sleep rate	Zhang et al. (2015a)
Myricetin-3-O-β-D-glucopyranoside	In vitro, human hepatoma cell line (HepG2), human breast cancer (MCF-7), and human lung carcinoma (A549) tumor cell lines	Had anti-proliferative activities on cell proliferation with IC50 values of 46.30, 75.27, and 49.76 μmol/L, respectively	Xu et al. (2015)
5a-(3,4-Dihydroxyphenyl)-1,3,8,10,10b-pentahydroxy-9-(4-hydroxybenzoyl)-5a,10b-dihydro-11H-benzofuro chromen-11-one, an iriflophene unit, and a quercetin unit connecting via a furan ring	In vitro , in situ pancreatic adenocarcinoma cell (BXPC-3), A549, and human breast cancer (MCF-7) tumor cell lines	Exhibited moderate cytotoxic activities against BXPC-3, A549, and MCF-7 tumor cell lines with IC50 ranging from 24.84 to 37.22 μmol/L	Li et al. (2017)
1,8,10,10b-Tetrahydroxy-5a-(4-hydroxy-3-methoxyphenyl)-9-(4-hydroxybenzoyl)-3-methoxy-5a,10b-dihydro-11H-benzofuro [2,3-b]chromen-11-one, an iriflophene unit and a rhamnazin unit connecting via a furan ring	In vitro, anti-proliferative activities against BXPC-3, A549, and MCF-7 tumor cell lines	Exhibited moderate cytotoxic activities against BXPC-3, A549, and MCF-7 tumor cell lines with IC50 ranging from 24.84 to 37.22 μmol/L	Li et al. (2017)
EtOAc fraction of aqueous extract	In vitro, LPS-stimulated RAW 264.7 macrophages	Inhibited the release of NO from inflammatory cells	Lin (2014)
3′,4′,5,7-Tetrahydroxy	In vitro, LPS-stimulated RAW 264.7 macrophages	Inhibited the release of TNF-α	Lin (2014)
Galuteolin	In vitro, LPS-stimulated RAW 264.7 macrophages	Inhibited the release of NO and TNF-α	Lin (2014)
Protocatechuic acid	In vitro, LPS-stimulated RAW 264.7 macrophages	Inhibited the release of TNF-α, IL-6, NO, and IL-1β	Huang, 2014; Lin (2014)
Caffeic acid	In vitro, LPS-stimulated RAW 264.7 macrophages	Inhibited the release of TNF-α, IL-6, NO, and IL-1β	Huang, 2014; Lin (2014)
6% S. aizoon	Renal hypertensive male rat model	Lowered SBP and MAP, thereby lowering blood pressure	Han et al. (2022)
10% S. aizoon	Renal hypertensive male rat model	Decreased SBP, MAP, blood pressure, serum creatine kinase CK activity, left ventricular stroke index LVWI (LW/BW) and HWI (HW/BW), and the expression of AT1 protein, increased the expression of AT2 and catalase protein, reversed myocardial remodeling, and protected the heart	Han et al. (2022)
Yangxincao capsules	Hyperlipidemia rat model	Significantly decreased the levels of serum TC, TG, and LDL-C, decreased the level of apoB, and increased the levels of HDL-C and its subcomponents HDL2-C, HDL3-C, and the ratio of HDL-C/TC; significantly increased the activities of LCAT and LPL and the level of apoA in the serum	Liu et al. (2005)
Leaching solution	Rabbit and frog	Stimulated the action of the heart and reduced the toxicity of amphetamine	Zheng (1975)
Polysaccharide	Mice	Significantly improved thymus index and spleen index, T- and B-lymphocyte transformation and proliferation, and NK cell activity; increased the percentage values of CD3+, CD4+, CD19+, and CD4+/CD8+ in the peripheral blood	Huang (2019)

N/A, not applicable or not explicitly stated.

7.1 Antioxidant activity

S. aizoon has excellent antioxidant activity, as demonstrated by several pharmacological studies in vitro and in vivo. An in-depth in vivo study showed that the juice from the stems and leaves of S. aizoon increased the peroxidase (POD) and superoxide dismutase (SOD) of the liver in Cyprinus carpio Linnaeus as well as reduced the content of malondialdehyde (MDA), thus preventing the peroxidation damage of the liver cell membrane (Zhang and Wang, 2012). Experimental tests in vivo showed that ethanol extracts of S. aizoon were able to enhance antioxidant enzymes in T1DM mice and successfully alter the Nrf2/Keap1/ARE signaling pathway (Qi et al., 2022). Additionally, 95% ethanol extract of S. aizoon increased the activity of SOD, CAT, and GSH-Px and reduced the contents of MDA and ROS on the rat adrenal pheochromocytoma cell line (PC12) induced by H₂O₂, showing a protective effect on the cell (Zhao, 2015).

7.2 Anti-fatigue effects

As national fitness activities expand, more individuals participate in sports, and the negative consequences of exercise fatigue on the body become more obvious. The effective recuperation of the body and the rapid removal of exercise exhaustion are becoming increasingly vital to society. The animal experiments (mice) demonstrated that the extracts of S. aizoon (3.6 and 0.9 mL/kg, 30 days) prolonged the time of extreme exercise in mice, reduced the contents of blood urea nitrogen (BUN), lactic acid (LAC), MDA, and lactate dehydrogenase (LDH) in the serum of mice, improved the activity of SOD and GSH-Px, and increased the contents of liver and muscle glycogen of mice (Ding, 2019). In a human clinical trial, it has been found that the administration of the sap (0.225 mL/kg.d, 0.9 mL/kg.d, and 3.6 mL/kg.d, 28 days) of the aerial part from S. aizoon [5 mL/(60 kg.d), 14 days] reduced the response time of male college students to the stimulus signal, improved fatigue resistance, and accelerated fatigue recovery by decreasing the content of blood perfusion index, cortisol, and creatine kinase in the serum and increasing hemoglobin and the load of final exercise (Ren, 2020). The above studies showed that S. aizoon improved exercise endurance, affected their metabolic activity, and produced anti-fatigue effect. S. aizoon’s probable anti-fatigue effects of action are shown in Figure 6.

FIGURE 6.

Schematic diagram of anti-fatigue effects of S. aizoon.

7.3 Hemostatic activity

S. aizoon has an effect comparable to that of Notoginseng Radix in terms of reducing bleeding without causing stasis and nourishing blood. A series of experiments in vivo and in vitro revealed that extracts and preparations of S. aizoon exhibited good hemostatic activities. Previous studies showed that alcohol and aqueous extracts (6, 12 g/kg b.w) of S. aizoon could significantly shorten the bleeding time and clotting time of mice (Chen et al., 2012). The juice of the whole herb from S. aizoon could increase the levels of GP Ⅱb/Ⅲa, P selectin, and ET-1 and the number of platelets and enhance the platelet aggregation and release function of the rats with aspirin-induced gastric hemorrhage, thus achieving hemostasis. Since S. aizoon could increase the level of IL-8, it was used in patients with bleeding accompanied by inflammation (Huang, 2014).

S. aizoon combined with other drugs can also be used for the treatment of bleeding diseases. Patients with bleeding peptic ulcers was treated upon treatments with herbs S. aizoon in conjunction with omeprazole (Xu, 2012). After intravenous injection in rabbits and intraperitoneal injection in mice of S. aizoon syrup, the blood coagulation time and bleeding time were decreased (Chinese Academy of Medical Sciences, 1972). The probable hemostatic mechanism is shown in Figure 7.

FIGURE 7.

S. aizoon’s probable hemostatic activity.

7.4 Antimicrobial activity

The crude extracts from S. aizoon have antimicrobial activity. According to transcriptome and RNA sequencing analyses, the ethanol extracts extracted from S. aizoon had significant antimicrobial activities against B. cinerea (Wang K. et al., 2022), Aeromonas (Xu et al., 2019), postharvest citrus blue mold (Luo et al., 2020), Shewanella putrefaciens (Wang et al., 2020), and Pseudomonas fragi (Wang H. X. et al., 2022). Studies revealed that alcohol extracts had a good inhibitory ability against 20 strains of multidrug-resistant Pseudomonas aeruginosa (MIC50 value = 0.125 g/mL) (Zhang et al., 2012; Wang H. et al., 2023), Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus (MIC value = 0.125 g/mL). However, the inhibitory impact on three types of fungus, including Candida tropicalis, Candida parapsilosis, and Candida albicans, was very poor, with MIC values above 0.5 g/mL (Zhang et al., 2011).

Furthermore, monomer metabolites isolated from S. aizoon also have antimicrobial activity. Xu et al. (2015) revealed that herbacetin-3-O-α-L-rhamnopyranosyl-8-O-α-D-lyxopyranoside (28), myricetin-3-O-β-D-glucopyranoside (12), and gossypetin-3-O-β-D-glucopyranosyl-8-O-β-D-xylopyranoside (31) exhibited more potency against Gram-positive than against Gram-negative bacteria. S. aizoon’s probable antimicrobial actions are shown in Figure 8.

FIGURE 8.

S. aizoon’s probable antimicrobial action.

7.5 Sedative and hypnotic effects

Traditional Chinese medicine and its preparations are commonly used to treat sleeplessness, agitation, and other symptoms. They offer the benefits of safety and dependability, as well as fewer toxicity and side effects, as compared to Western medication with sedative and hypnotic properties. Using the mouse model, Guo et al. (2009) showed that the water and alcohol extracts have tranquilizing mind and the calming effects. Later, they also found that the ethyl acetate and butanol extracts could effectively lower the autonomic activity in mice, lengthen sleeping duration in mice, and increase the number of sleeping mice (Guo et al., 2010).

Additionally, the S. aizoon’s prescription or in combination with other drugs also possess sedative and hypnotic properties, which are often used to treat sleeplessness, restlessness, and other disorders. For instance, Yangxincao Anshen Granules made with S. aizoon (12, 6 g/kg/d) significantly reduced the spontaneous movements of mice, and the granules, in conjunction with pentobarbital, extended the duration of their sleep, providing good sedative and hypnotic effects without negative side effects (Zhang R. Z. et al., 2015). Similar results have been recorded for the combination between S. aizoon and Semen ziziphus spinosa (Zhang L. et al., 2015).

7.6 Anti-cancer activity

S. aizoon’s active metabolites and crude extracts with anti-cancer potential have piqued the interests of researchers in recent years. The ethanol extracts isolated from S. aizoon (50, 100, and 200 μg/mL) could lower the survival rate of human liver cancer cells HepG2 and inhibit human hepatocarcinoma proliferation by 11.15%, 41.96%, and 52.04%, respectively. With the increase in concentration, the inhibition rate of liver cancer cells increased, showing a certain dose–effect relationship (Wang et al., 2013). The aqueous extracts of S. aizoon [equivalent to adding 15.9 mg raw drug, containing 31.7 μg gallic acid (60)] could destroy the phospholipid-dominated structures and block nucleic acid synthesis and metabolism, which caused the death of cancer cells, and the killing effect was improved when the drug treatment period was extended (Fu et al., 2008).

Among the active metabolites tested, myricetin-3-O-D-glucopyranoside (12) obtained from the aerial portion of S. aizoon exhibited an effect on cell proliferation against HepG2, MCF-7, and A549 tumor cells, with IC50 values of 46.30, 75.27, and 49.76 mol/L, respectively (Xu et al., 2015). Li et al. (2017) found that 5a-(3,4-dihydroxyphenyl)-1,3,8,10,10b-pentahydroxy-9-(4-hydroxybenzoyl)-5a,10b-dihydro-11H-benzofuro chromen-11-one, an iriflophene unit, and a quercetin unit connecting via a furan ring (44) and 1,8,10,10b-tetrahydroxy-5a-(4-hydroxy-3-methoxyphenyl)-9-(4-hydroxybenzoyl)-3-methoxy-5a,10b-dihydro-11H-benzofuro[2,3-b]chromen-11-one, an iriflophene unit, and a rhamnazin unit connecting via a furan ring (47) isolated from the roots of S. aizoon exhibited cytotoxic activities against BXPC-3, A549, and MCF-7 tumor cell lines, with IC50 ranging from 24.84 to 37.22 μmol/L. S. aizoon’s probable anti-cancer actions are shown in Figure 9.

FIGURE 9.

S. aizoon’s probable anti-cancer action.

7.7 Anti-inflammatory effect

In Northeast Asia, S. aizoon has been used as a traditional medicine to treat inflammatory illnesses. Several extracts (PE, EtOAc, and H₂O) of S. aizoon were administered to LPS-stimulated RAW 264.7 cells to investigate anti-inflammatory activities. The phenolic and flavonoid-rich EtOAc extracts reduced NO, TNF-α, and IL-6 production induced by LPS (Lin et al., 2015a). In a study by Kim et al. (2004), methanol extracts of S. kamtschaticum Fischer showed a significant inhibitory effect in the inflammation models of mouse ear edema (50–400 mg/kg for 3 days) and rat paw edema (400–800 mg/kg for 3 days) induced by croton oil and multiple phorbol ester. The cyclooxygenase-2 expression was downregulated. Possible mechanisms of action are given in Figure 10.

FIGURE 10.

S. aizoon’s probable anti-inflammatory mechanism of action.

7.8 Cardioprotective effects

S. aizoon lowered blood pressure, serum CK activity, and AT1 protein expression, reversed myocardial remodeling, and increased AT2 and catalase protein expression (Han et al., 2022). Chen (2000) showed that fresh S. aizoon grass could help stroke victims regain consciousness. It is thought that this herb has evident effects in improving blood circulation, reducing blood stasis, and decreasing blood pressure. Using the method of network pharmacology and molecular docking, studies found that S. aizoon had the effect of treating atherosclerosis and coronary heart disease (Zhu et al., 2022, 2023).

Interestingly, the extract of S. aizoon increased cardiac activity and decreased amphetamine toxicity (Zheng, 1975). According to the study of Wang et al. (2013), S. aizoon had the ability to regulating blood lipid levels and could dramatically lower the mice’s liver index and fat coefficient. Additionally, when hyperlipidemia rats were treated with Yangxincao capsules (derived from whole grass extract), the serum levels of TC, TG, and LDL-C were decreased, while HDL-c and its subcomponents (HDL-c, HDL-3-C, and HDL-C/TC) were increased, implying that the mechanism of lipid regulation of S. aizoon was related to the enhancement of the activities of LPL, LCAT, and HDL2-C (Wu et al., 2006).

7.9 Other activities

In T1MD mice, it has been shown that S. aizoon extract has the ability to enhance glucolipid metabolism and organ coefficient and decrease liver tissue damage (Qi et al., 2022). In addition, polysaccharides from S. aizoon have an immune-stimulating effect by increasing the thymus index, spleen index, T- and B-lymphocyte transformation proliferation, and NK cell activity of mice, as well as enhancing the percentage values of CD3⁺, CD4⁺, and CD19⁺ and the percentage values of CD4+/CD8+ in the peripheral blood. Such effect was associated with the increased secretion of IL-2 and IFN-γ(Huang, 2019).

8 Acute toxicity

A previous study showed that excessive consumption may cause small hepatic vein occlusion disease with upper quadrant abdominal pain, hepatomegaly, liver dysfunction, and ascites as the main symptoms (Wu et al., 2008; Shao et al., 2015).

9 Quality control

The quality of traditional Chinese medicine is the basis for ensuring the stability of its efficacy and the safety of its application, and its standardization and modernization are the important prerequisites for promoting Chinese medicine toward internationalization. In order to better identify the plant, Scholars (Han, 2008) have controlled the quality of S. aizoon from four aspects: morphology, microscopy, TLC, and RAPD. It is required that the water content shall not exceed 10.53%, the ash content shall not exceed 14.70%, and the leaching content shall not be less than 32.57% (Wei et al., 2020). The linear ranges of quercitroside, quercetin, and kaempferol were 0.0029 ∼ 0.183, 0.0016 ∼ 0.1020, and 0.0045 ∼ 0.260 μg/μL, respectively (He and Du, 2016), and those of luteolin and isorhamnetin were 1.12 ∼ 112.00 and 0.98 ∼ 97.60 μg/mL (Lin et al., 2013), respectively. However, these methods may not be sufficient to evaluate the quality of S. aizoon.

Traditional Chinese medicine (TCM) fingerprints can comprehensively and quantitatively reflect the chemical information contained in TCM and is an effective means of quality control of TCM. Lin et al. (2015b) used 11 standards to analyze the phytochemical profiles of the active extracts by HPLC fingerprints. Yang et al. (2023) established the HPLC-ECD fingerprint spectra of S. aizoon from different origins and identified 12 metabolites.

10 Conclusion and future perspectives

This review provides comprehensive and detailed information about the history, traditional uses, botany, phytochemistry, pharmacological activities, and acute toxicity of S. aizoon. So far, more than 200 metabolites have been identified with a variety of pharmacological activities. These modern pharmacological studies supported most traditional uses of S. aizoon as folk medicine. However, gaps still exist in the systematic study of S. aizoon.

First, S. aizoon has many nicknames, which results in being mixed with other herbs. Therefore, molecular biological studies are required to screen out the reference genes for better identification of S. aizoon.

Second, the pharmacological potential of S. aizoon has not yet been fully discovered, which may be further investigated by a combination of in vitro and in vivo bioactivity assays, metabolomics, network pharmacology, and in silico bioactivity prediction methods. In addition, the therapeutic potential of S. aizoon and its bioactive metabolites, safety, efficacy, and potential mechanism of action require further preclinical and clinical studies to validate for future clinical applications.

Third, S. aizoon is widely popular in herbal healthcare as a commonly used medicinal and edible substance and is especially used in immunomodulation and blood lipid regulation. Nevertheless, the use of S. aizoon in combination with other herbs in healthcare products should be strengthened, and studies on improving memory and promoting digestion may be conducted.

Fourth, the spectrum–efficacy relationship of S. aizoon in immunomodulation and anti-inflammatory therapy should be further investigated in order to better uncover its active metabolites.

Funding Statement

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This research was carried out with the support of the Natural Science Foundation of Hubei Provincial Department of Education, grant number B2020104, the Innovation and Entrepreneurship Training Program for college students of Hubei University of Medicine, grant number X202110929016, and Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), grant number WDCM2023025.

Author contributions

B-LW: conceptualization, funding acquisition, methodology, and writing–original draft. Z-KG: writing–review and editing, formal analysis and validation. J-RQ: writing–review and editing, formal analysis and validation. S-QL: data curation, investigation, visualization, and writing–original draft. X-CH: funding acquisition and writing–review and editing. Y-HZ: writing–review and editing and visualization.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Glossary

ABTS	2, 2′-Azinobis-(3-ethylbenzothiazoline-6-sulfonate)
AGG	Abrus agglutinin
APTT	Activated partial thromboplastin time
BXPC-3	Human pancreatic adenocarcinoma cells
CAT	catalase
CNKI	China National Knowledge Infrastructure
CT	Coagulation time
DPPH	2, 2-Diphenyl-1-picrylhydrazyl
EtOAc	Ethyl acetate
FBG	Fasting blood glucose
GP Ⅱb/Ⅲa	Platelet membrane glycoprotein
HepG2	Human hepatoma cell line
H/R	Hypoxia/reoxygenation
HSQC	Heteronuclear singular quantum correlation
IL-1β	Interleukin 1β
IR	Infrared spectroscopy
LDH	Lactate dehydrogenase
LPS	Lipopolysaccharide
MAPK	Mitogen-activated protein kinase
MDA	Malondialdehyde
MTD	Maximum tolerance dose
NMR	Nuclear magnetic resonance
PC12	Adrenal pheochromocytoma cell line
Pseud. aeruginosa	Pseudomonas aeruginosa
RAPD	Random amplified polymorphic DNA
ROS	Reactive oxygen species
SOD	Superoxide dismutase
STz	Streptozotocin
TCM	Traditional Chinese medicine
TG	Triglyceride
TNF-α	Tumor necrosis factor-α
T-SOD	Total superoxide dismutase
UV	Ultraviolet and visible spectrum
Ac	Acetate
Ara	Arabinopyranoside
A549	Human lung carcinoma
BUN	Blood urea nitrogen
CD	Circular dichroic
CGN	λ-Carrageenan
DEGS	Differentially expressed genes
E.coli	Escherichia coli
ET-1	Endothelin 1
Glu	Glucopyranoside
GSH-Px	Glutathione peroxidase
HMBC	1H-detected heteronuclear multiple-bond correlation
HRESIMS	High-resolution electrospray ionization mass spectroscopy
IC50	50% inhibitory concentration
IL-6	Interleukin 6
LAC	Lactic acid
LD50	Semi-lethal dosage
MAP	Mean arterial pressure
MCF-7	Human breast cancer
MDRPA	Multidrug-resistant pseudomonas aeruginosa
MTT	3-(4,5-Dimethylthiazol-2yl) −2,5-diphenyltetrazolium bromide
OGTT	Oral glucose tolerance test
POD	Peroxidase
PT	Prothrombin time
Rha	Rhamnopyranosyl
SBP	Systolic blood pressure
Staphy.Auren	Staphylococcus aureus
TC	Total cholesterol
T1DM	Type 1 diabetes mellitus
TLC	Thin-layer chromatography
TPA	12-O-tetradecanoylphorbol 13-acetate
TT	Thrombin time
Xyl	Xylopyranoside