Abstract
Introduction
It is estimated by World Health Organization that around 80% of Africans are currently using traditional medicines to manage their prevailing ailments. 1 Since ancient times in Egypt till today, medicinal plants have been used as remedies by people to cure their diseases. 2
Sesbania sesban L. Merr., Fabaceae family, commonly known as Egyptian riverhemp, is a perennial legume tree (up to 8 m tall) and with pinnately compound leaves. 3 It has several synonyms; Sesbania aegyptiaca Pers., Aeschynomene aegyptiaca (Pers.) Steud., Sesbania pubescens sensu auct., Aeschynomene sesban L., Sesbania confaloniana Chiov., Sesbania punctata DC. and Emerus sesban (L.) Kuntze. 4 S. sesban grows in the wild, as well as being cultivated in tropical Africa and Asia. 3
The plant is widely cultivated due to its ability to fix nitrogen and to shade wind. 5 S. sesban L. Merr. is also used in Egypt, mixed with sorghum, in the feed of growing lambs 6 and also to increase milk production in animals. 7
Traditionally, S. sesban L. Merr. leaves were used as a poultice for inflammatory conditions such as boils, abscesses, and rheumatic swellings. 3 The juice of the fresh leaves was used as an anthelmintic and purgative, 8 as well as for treating scorpion stings. Its leaves have a clinical application in Eczema treatment with excellent results (73.3%) demonstrated by a paste of plant leaves. 3
Several review articles have been published on S. sesban L. Merr. 9–11 However, all of these discussed the biological activities and the ethnomedical uses and scarcely reported the phytochemistry of the plant. Therefore, the aim of this review is to present a comprehensive account of the isolated constituents from S. sesban L. Merr. leaves, along with the correlation between these constituents and the reported biological activities.
Methodology
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) 12 guided the development of the protocol for conducting this investigation (Figure 1). At first, duplicate articles were excluded. After reading the titles and abstracts, the inclusion and exclusion criteria were determined. After reading each article thoroughly, the inclusion and exclusion criteria were once again applied. Finally, we reached the papers that were chosen for the present study.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of included studies.
This systematic review was conducted through searches using SciFinder, Google, Google Scholar, and CrossRef using the following keywords: “Sesbania sesban”, “Sesbania aegyptiaca”, “Egyptian riverhemp”, “phytochemistry”, “phytochemical constituents”, “isolation”, “steroids”, “triterpenoids”, “saponins”, “coumarins”, “lipoidal contents”, “pharmacological properties”, “biological activities”, “therapeutic uses”, and “review”. Articles from the database's launch through to September 2022 were investigated. Only English was utilized for keywords.
The following criteria were taken into account when including articles: original and review journal articles were allowed, but only articles in English were permitted. All articles which described the phytochemical constituents, as well as the pharmacological activities, were incorporated. Studies were accepted for inclusion regardless of how they were specifically constructed.
Articles that lacked the search terms in the title and abstract; articles with no full text available; and papers showing preliminary phytochemical screening results were excluded.
The findings of the laboratory tests were briefly discussed to present possible mechanisms of action for the compounds under study. Finally, further studies are recommended for isolating bioactive metabolites from the crude active extracts or fractions and also for potential clinical implications.
Results and Discussion
This review summarizes all the active constituents and biological activities reported for S. sesban L. Merr. leaves.
Phytochemistry
Phytochemical investigations of S. sesban L. Merr. leaves resulted in the isolation of several classes of compounds such as steroids, triterpenoids, saponins, flavonoids, coumarins, and miscellaneous constituents, (Tables 1–4, Figures 2–5).
Steroids and Steroidal Saponins Reported in Sesbania sesban L. Merr. Leaves.
Triterpenoids and Triterpenoid Saponins Reported in Sesbania sesban L. Merr. Leaves.
Flavonoids Reported in Sesbania sesban L. Merr. Leaves.
Coumarins Reported in Sesbania sesban L. Merr. Leaves.
Several steroids were isolated from S. sesban L. Merr. leaves, such as β-Sitosterol (

Chemical structures of reported steroids in Sesbania sesban L. Merr. Leaves.
Triterpenoids such as Lupeol (

Chemical structures of reported triterpenoids and saponins in Sesbania sesban L. Merr. Leaves.
S. sesban L. Merr. leaves also contain a considerable amount of saponins of both steroidal and triterpenoidal types such as Stigmasta-5,24(28)-diene-3β,O-β-D-galactopyranoside (
A large number of flavonoids were also isolated from S. sesban L. Merr. leaves, such as 3-hydroxy-4′,7-dimethoxyflavone (

Chemical structures of reported flavonoids and coumarins in Sesbania sesban L. Merr. Leaves.
Moreover, 3 coumarins were reported in S. sesban L. Merr. leaves which were named Herniarin (
S. sesban L. Merr. leaves were proved to be rich in fatty acids such as Palmitic acid (
Miscellaneous compounds include Galactomannan (

Chemical structures of reported fatty constituents and miscellaneous structures in Sesbania sesban L. Merr. Leaves.
Biological Activities
Antioxidant Activity
The ethanolic extract of S. sesban L. Merr. leaves demonstrated a dose-dependent antioxidant activity using DPPH and nitric oxide scavenging assays with ascorbic acid as a standard.
29
No previous report on the antioxidant metabolites in S. sesban L. Merr. leaves could be traced. By exploring the isolated compounds reported in this article, the antioxidant activity of S. sesban L. Merr. leaves could be correlated to the presence of flavonoids, known for their antioxidant potential.
30
The antioxidant activity of Quercetin-3-O-β-D-glucoside (
Antiviral Activity
A recent patent explained the antiviral activity following the clinical administration of an effective herbal mixture containing S. sesban L. Merr. in the treatment of patients infected with hepatitis viruses (HCV and HBV). A 6 months of treatment resulted in serum negative for HCV-RNA and HBV-DNA in 37.5% and 50% of the patients, respectively. 37 The antiviral activity of S. sesban L. Merr. leaves could be attributed to their triterpene and saponin contents. Olean-type triterpenes were reported as HCV entry inhibitors through binding to E2 protein present in the HCV envelope and thus, block it from binding to the CD81 receptor and consequently, preventing the recognition of the virus by the host cell. 38 Moreover, Oleanolic and Ursolic acids were reported as noncompetitive inhibitors of HCV through suppressing HCV NS5B RdRp (IC50 = 0.8 and 3.1 μg/mL, respectively). 39 Saponins were also reported to diminish HCV replication by potentiating IFN- alpha and suppressing the signaling of (SOCS2) protein level. 40
Antimicrobial Activity
The methanol extract of S. sesban L. Merr. was tested, at a concentration of 250 μg/mL, for its antibacterial activity using the agar well diffusion method. S. sesban L. Merr. inhibited Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Erwinia amylovora, Pseudomonas aeruginosa and Bacillus subtilis (inhibition zone diameters = 13, 16, 12.75, 17.25, 7.5 and 9.25 mm, respectively). However, it was not active against Salmonella typhi, Proteus vulgaris, Klebsiella pneumoniae and Shigella dysenteriae. 41
The antifungal activity was assessed as well using a poison plate method, at a concentration of 500 μg/mL. The sesban methanolic extract exhibited antifungal effects against Curvularia lunata, Verticillium glaucum, Fusarium oxysporum, Colletotrichum gloeosporioides and Aspergillus fumigatus (with inhibition zone diameters = 18.75, 14.75, 23.25, 11 and 10.5 mm, respectively). 41
The presence of constituents such as flavonoids, phenols, tannins, and saponins can be linked with the antimicrobial properties of the different extracts. 42 These findings illustrate the reason why S. sesban L. Merr. has been traditionally used in the treatment of diarrhea, skin infections and typhoid. 42 The reported activity of S. sesban L. Merr. extract against Aspergillus fumigatus could also explain its usage in the management of several opportunistic infections. 41
Anthelmintic Activity
The hydroethanolic and aqueous leaf extracts of S. sesban L. Merr. (at a concentration of 5 and 10 mg/mL) were evaluated for their anthelmintic activity in vitro, against Moneizia expansa and Paramphistomes by a petri-dish method, (Table 5), with fenbendazole as the control. 43
Summary of the Anthelmintic Activity of Sesbania sesban L. Merr. Leaves, Time (hr.) at Different Concentrations.
The methanolic extract was also evaluated in rats for its anthelmintic effect in vitro and in vivo against two intestinal parasites Hymenolepis diminuta (in rats), a cestode, and Syphacia obvelata (in mice), a nematode, with Praziquantel and Albendazole as reference drugs (Table 5). 43 The bio-guided fractionation of the methanolic extract showed that the ethyl acetate fraction was the most bio-active fraction, which showed mortality at 3.56 ± 0.12 h and 9.21 ± 0.02 h against H. diminuta and S obvelata, respectively. 44
Condensed tannins and saponin, as well as flavonoids, were reported as the main plant constituents responsible for the anthelmintic effect. 45 Betulinic and Ursolic acids (at conc. of 1.00 mg/mL) exhibited in vitro anthelmintic activity (paralysis and mortality) against the mouse pinworm, S obvelata (1.20 ± 0.04 and 2.30 ± 0.03 h, respectively). Betulinic acid when administered for 5 days in vivo at a dose of 10.00 mg/kg, exhibited 68.8% and 84.1% reduction in egg counts and worm counts of the infected mice, respectively. 46 Betulinic and Ursolic acids were reported as well for their activity against H diminuta. 47 These findings could explain the traditional use of S. sesban L. Merr. as an anthelmintic herb, 8 which is due to its triterpenoids, saponins and tannins.
Molluscicidal Activity
The methanolic extract of S. sesban L. Merr. leaf exhibited a molluscicidal activity against Bulinus truncates snail infected with Schistosoma haematobium, 48 while the aqueous extract demonstrated a molluscicidal activity against Biomphalaria alexandrina snail infected with Schistosoma mansoni. 49 The two extracts significantly lowered the infection rates of the snails (% inhibition at LC25 = 14 ppm and 44.9 ppm, respectively).
Furthermore, the extracts significantly decreased the snail survival rates; egg productivity; eggs hatchability and snails’ infectivity. The mechanism of inhibition of Bulinus truncatus was by glucose level elevation in the hemolymph of affected snails, in addition to lowering of the glycogen level, and activities of hexokinase, pyruvate kinase and lactate dehydrogenase in soft tissues.
48
The mechanism of inhibition of Biomphalaria alexandrina was reported to be due to elevating the activities of AST, ALT, ACP and AKP, and also decreasing the activity of ACP in treated tissues compared to the control. Both studies showed that the extracts of S. sesban L. Merr. interfere with the snails, both biologically and physiologically.
49
The crude coumarin fraction containing Herniarin (
The molluscicidal activity of S. sesban L. Merr. saponins was also studied against Biomphalaria glabrata.
22
The results showed that three compounds; 3-O-[α-L-rhamnopyranosyl-(1→3)-3-D-glucuronopyranosyl]-oleanolic acid (
Antifertility or Spermicidal Activity
The spermicidal effect of Oleanolic acid 3-O-β-D-glucuronopyranoside (
Anti-Inflammatory Properties
The anti-inflammatory properties of crude S. sesban L. Merr. saponins have been discussed in several in vivo animal studies, such as carrageenan and histamine-induced edema in rat paws, cotton pellet granuloma, vascular permeability induced by acetic acid, and delayed-type hypersensitivity induced by oxazolone. Additionally, heat-induced hemolysis and in vitro protein denaturation inhibition assays were used to study the mechanism of action of the inflammation. At a dose of 500 mg/kg body weight orally, the crude saponin extract demonstrated considerable activity in both in vivo and in vitro studies when compared to control drugs. These activities might be connected to the presence of triterpenoid and steroid compounds reported by HPTLC and GC/MS in this fraction and represented by Oleanolic acid (
Another study evaluated the topical anti-inflammatory activity of a gel formulation containing crude saponins extracted from S. sesban L. Merr. (at concentrations of 1% and 2% w/w) on Wistar albino rats using the carrageenan-induced edema in rat paw method, with 1% w/w Diclofenac sodium gel as a reference drug. The 2% w/w crude saponins gel formulation demonstrated a remarkable anti-inflammatory activity compared to the control group and to the reference drug. 44
Antidiabetic and Antihyperlipidemic Activities
Diabetes was induced by a single streptozotocin intraperitoneal injection in healthy adult male albino wistar rats, and normal and diabetic rats orally administered with S. sesban L. Merr. aqueous extract at doses of 250 and 500 mg/kg (b.w.); Glibenclamide was used as a reference drug (0.25 mg/kg b.w.). Blood glucose levels and body weights were estimated after 1, 10, 20, and 30 days of the consumption of the extract. The fasting blood glucose level, serum insulin level, glycosylated hemoglobin, triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL) were evaluated. The S. sesban L. Merr. aqueous extract at both doses of 250 and 500 mg/kg caused a reduction in the blood glucose level. After 30 days of treatment, the results showed a prominent elevation in serum insulin, liver glycogen, body weight, and HDL levels and inhibitions in the levels of blood glucose, TC, glycosylated hemoglobin and serum TG in comparison to Glibenclamide.
52
There is no report on the antidiabetic constituents of S. sesban L. Merr. leaves. However, the plant was reported to be rich in saponins,
19
known for their antidiabetic activity.53,54 Oleanolic acid 3-O-β-D-glucuronopyranoside (
Anticancer Activity
There are only two anticancer studies discussing the activity of S. sesban L. Merr. leaves on antileukemic activity. One article described the cytotoxicity of the methanol extract and 3-hydroxy-4′,7-dimethoxyflavone (
It is worth mentioning that there are no reports concerning the cytotoxicity against other types of cancers. Thus, further investigations of the anticancer properties of the extracts and the isolated compounds against different tumor cell lines are to be encouraged.
Antianxiety Activity
Melatonin is a hormone that controls the sleep-wake cycle. Recently some researchers in Thailand evaluated the melatonin content of the methanolic extract S. sesban L. Merr. leaves using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). They reported that the leaves contain 7.3 ± 2.8 ng/g and 8.7 ± 1.3 ng/g dry weight Melatonin determined by ELISA and HPLC, respectively. 28
Mosquito Repellant Activity
The plant water extract was used to wash animal bodies as a protection against mosquito bites. Also, the leaf decoction was used as a cattle drench to expel tsetse fly. 56
Reviewing the previous literature, compounds responsible for the activity of S. sesban L. Merr. extracts were determined in some pharmacological studies, but not in others. Some of the pharmacological effects were given by a crude fraction, and not a single constituent. For example, the anti-inflammatory properties of the crude saponin fraction isolated from S. sesban 16 L. Merr. leaves, and the anthelmintic activity of the ethyl acetate fraction against H diminuta and S obvelata. 44 These types of studies need further phytochemical bio-guided investigations with the aim of isolating the active metabolites.
Also, the reported antioxidant and antimicrobial studies were too preliminary and the relevance of data generated with these procedures should be carefully considered.29,30
Generally, the above review highlights the chemical classes of phytoconstituents isolated from S. sesban L. Merr. leaves, together with the reported pharmacological activities which infer the biological importance of this plant. Moreover, further preclinical and clinical research is required to confirm both the efficacy and safety of both plant extracts and metabolites before introducing them to the pharmaceutical industry.
Conclusions and Perspective
S. sesban L. Merr. is a traditionally used plant with diverse constituents. The presented study inspected the different bioactive compounds identified from the leaves of this plant. Triterpenoid saponins contributed to the majority of pharmacological activities such as antiviral, anthelmintic, molluscicidal, antifertility, anti-inflammatory, antidiabetic, antihyperlipidemic and anticancer properties. However, this extensive literature review indicated that other traditional uses have not been investigated enough, such as antimicrobial activity. Consequently, it is necessary to execute future research on sesban leaves through bioassay-guided isolation, structure-activity relationship, mechanisms of action and in vivo studies to investigate and confirm their reported therapeutic activities. Additionally, this review may be able to help investigate the pharmacological and phytochemical properties of S. sesban L. Merr. leaves.
Footnotes
Acknowledgments
Authors are grateful to the Egyptian Ministry of Higher Education Missions Sector. Support from the National Center for Natural Products Research (NCNPR), University of Mississippi to access SciFinder database is gratefully acknowledged.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
