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Abstract

Saponins are natural compounds that predominate in numerous plant species and are characterized by foaming in aqueous solutions. Chemically, they are composed of a hydrophobic structure of triterpene or steroidal nature that is linked to hydrophilic sugar chains; this combination gives them the ability to interact uniquely with cell membranes and even modulate physiological processes, which provides them with versatile properties with applications as therapeutic agents for various diseases of public health importance. Given the need for safer and less invasive therapeutic approaches, the study of bioactive compounds of plant origin has gained relevance. In this context, saponins emerge as potential biopharmaceuticals, thanks to their multiple mechanisms of action and relatively low toxicity compared to synthetic drugs. This review aims to deepen the knowledge of plant-derived saponins, explore their therapeutic applications validated by in vitro and in vivo pharmacological studies, and identify the main challenges in their development as pharmaceuticals.

Keywords

Biological activity saponins steroids therapeutic agents triterpenes

Introduction

Saponins constitute a class of secondary metabolites of the plant kingdom, where they play the essential role of defense agents against herbivores, pathogens, and abiotic stress. Moreover, they exhibit antifungal, antibacterial, and antiviral activity, contributing to plant survival, and modulate the rhizosphere microbiome by participating in symbiotic relationships in some legumes, which has sparked interest in phytoremediation and genetic engineering for the development of more resilient crops.^1,2

Saponins have shown broad biological activities with therapeutic potential in medicine, ranging from anti-inflammatory, antitumor, antiviral, hypocholesterolemic, and immunostimulant activities. They may even participate as adjuvants in vaccines, facilitating the immunological response of the antigen without generating serious adverse effects.³ On the other hand, they are widely used as active ingredients in cosmetic products due to their cleansing, antimicrobial, and antioxidant properties.⁴ Another sector that makes vast use of saponins is the food industry, employing them as nutraceutical components and supplements; however, since they also possess hemolytic capacity, they are applied with moderation under the regulations of international organizations.^5,6

From the point of view of scientific research, saponins are models for studying membrane-compound interactions due to their affinity for cholesterol and their ability to alter cell permeability.⁷ Likewise, the structure of saponins allows a versatile range of chemical modifications, favoring the development of derivatives for pharmacological, nutraceutical, and biotechnological purposes.⁸ In addition, obtaining them through plant tissue culture, metabolic engineering, and bacterial biotransformation is a potential area for optimizing yields and reducing environmental impact compared to conventional extraction, which promotes industrial economy and sustainability.^9,10 It should be noted that the potential of saponins is not yet fully exploited, so it is undoubtedly necessary to continue examining the different areas, plant sources, and process optimization.

Saponins and Their Classification

Saponins are molecules composed of two units: a water-soluble part called glycone (one or more sugar molecules), which is linked by a glycosidic bond to the liposoluble part commonly known as aglycone or sapogenin, which can be steroidal, triterpene or steroidal glycoalkaloids in nature.^3,11–13 This duality gives them an amphiphilic character (a combination of sugar chains and sapogenin).

According to the structure of the main sapogenin ring, saponins are classified as triterpene and steroidal.^9,14,15 Triterpene saponins are distributed in dicotyledonous angiosperms; their representative skeletons are of the pentacyclic oleane, ursane and lupane type, and tetracyclic damarane^16–19; while steroidal ones can be tetracyclic cholestane, hexacyclic spirostane, pentacyclic furostane and lactone-containing cardenolide,^14,20–23 and are mainly reported in monocotyledonous angiosperm species. Depending on the carbohydrate, saponins can be classified according to the number of sugar residues connected. They are called mono, di, or tridesmosidic (if they have one, two, or three sugar residues). In steroidal saponins, the sugar molecules are usually connected to carbons 3 and 26, while in triterpenic saponins, the sugars are linked to carbons 3 and 28.^24,25

Because of the above, there are numerous possibilities of combinations in the aglycone (Figure 1) with sugars, such as glucose, galactose, 6-deoxyhexoses (rhamnose), arabinose, xylose, glucuronic acid, and glucosamine.^26,27 Sapogenin and sugar combinations give rise to a considerable variety of saponins. This vast group of compounds is abundant in numerous species; it is even common to find more than one type of saponin in the same species.^24,28 More than 200 steroidal saponins are known, reported mainly in cotyledonous species, while triterpene saponins are reported in dicotyledons.^29–33

Figure 1.

Composition of saponins (oleananes, lupanes, ursanes, dammarans), the steroidal saponins (furostanes, cardenolides, cholestanes, spirostans), and the steroidal glycoalkaloids (solanidanes and spirosolane).

Functions of Saponins in Plants

Plants cannot move, fluidity to move or any ability that allows them to take refuge when they are exposed to environmental situations, attack by herbivores, or any cause that compromises their survival,^34,35 they have developed, through secondary metabolism, the ability to biosynthesize compounds that allow them to defend themselves from all situations that pose a risk to them,^16,36 in the face of each type of attack, the plant has developed a defense mechanism.^37,38 Pathogens and herbivores can enter plants through stomata or by penetrating the cell wall. In response, neighboring cells activate defense mechanisms that depend on the plant's ability to recognize the pathogen through specific molecular patterns. This recognition is mediated by transmembrane domain proteins that trigger kinase cascades and induce both constitutive and induced defense responses.^39–42

The constitutive system, active throughout the entire cell cycle, protects the plant from pathogens without requiring additional energy expenditure.^43–45 This mechanism includes physical barriers—such as cell walls, cuticles, bark, trichomes, and spines—and chemical barriers composed of compounds that deter predators, including saponins, cyanogenic glycosides, and cyclic hydroxamic acids.^42,46,47

The induced system, in turn, produces chemical compounds derived from secondary metabolism.^38,48 This system is activated in cells located in areas affected by pathogens or abiotic stress, such as water, light, or nutrient deficiency or excess. Depending on the stimulus perceived, it triggers the biosynthesis of chemical compounds that contribute to plant defense.^40,49 Among the metabolites synthesized in response to pathogen attack, saponins are particularly notable, accumulating in seeds, stems, fruits, and roots.^3,32,33

The literature reports that saponins can permeate cells due to their liposoluble nature through aglycone, managing to anchor themselves to the cell membrane; at the same time, their sugar diffuses into the cell, causing an increase in osmotic pressure to the point of lysing the cell of the pathogen.^50–52 With this mechanism, saponins protect plants from predators. However, research into plant defense mechanisms using saponins is still underway.

More than 200 steroidal saponins are reported in cotyledons’ species, while triterpene saponins are reported in dicotyledons. Their function has been associated with defense against pathogens and herbivores, and they can be found in seeds, fruits, leaves, stems, and roots.^3,53

Properties of Saponins

The word saponin comes from the Latin “sapo” and means soap; this name was coined due to its ability to generate foam when it meets water.^5,54 The foam formed is a consequence of the reduction of the force of attraction between the molecules; the saponin substance is located at the interface of the fluid as occurs with water and oil or air and water.^2,55 This property is called “surfactant,” that is, they disperse one liquid in another, avoiding the immiscible character, which in turn gives them the moisturizing capacity.^8,56,57 Also, their amphiphilic property allows them to form micelles, which facilitate cleaning when used as soaps.^58,59

They are therefore considered natural surfactants with applications in the formation of emulsions and foams, and they are the replacement for synthetic surfactants since they are obtained from natural renewable sources.^8,55,60,61 Some even comply with regulatory specifications such as the United States Food and Drug Administration (FDA), which has granted them the “Generally Recognized as Safe” (GRAS) recognition, and the Codex Alimentarius has approved their use as a food additive.^5,62,63

Another important property of saponins is hemolytic (destruction of red blood cells in a short period). Although it has been studied for years, the most accepted theory reports that the cell membrane is penetrated by saponin (Figure 2) because the aglycone is similar to the cholesterol in the membrane and eliminates it leaving pores permeable to the cytosol,^64,65 this action causes an increase in the fluidity of the membrane and its permanent permeability to large molecules, which consequently allows hemolytic action.^54,66,67 Other authors argue that hemolytic activity is related to specific receptors.^65,68,69 Regardless of the theory, saponins exhibit this effect even if evaluated at the extract level.

Figure 2.

Cell membrane structure. a) ordinary cell membrane, b) cell membrane after interacting with saponins.

Key Findings

This review highlights the medical applications of saponins. Google Scholar, PubMed, Scie Finder, and Elsevier databases were consulted to do so. The search words were “saponins,” “triterpene saponins,” “steroidal saponins,” “anti-inflammatory saponins,” “cytotoxic saponins,” and “antimicrobial saponins.” Articles, reviews, and mini reviews were selected and organized in a database, and those lacking clear information were excluded.

Potential Therapeutic of Saponins

Saponins exhibit a broad spectrum of therapeutic properties, positioning them as promising candidates for drug development. Numerous studies have highlighted their potential in anticancer, antimicrobial, antiviral, anti-inflammatory, and hepatoprotective therapies, among others.^30,31,70

Antiproliferative Activity of Cancer Cells

Cancer remains one of the leading causes of death globally, and chemotherapy is a primary treatment for its prevention and control. Natural products, known for their remarkable chemical diversity, continue to be extensively studied for their anticancer potential. Among these, saponins isolated from various plant species have shown significant cytotoxic effects.⁷¹ For instance, soyasaponins key bioactive compounds in Glycine max (soybean), have demonstrated promising anticancer properties. An extract containing the majority of soybean saponins I (62%) and III (29%), was found to inhibit the growth of Hep-G2 cancer cells.^72,73 Another study revealed that soyasaponin I (1), III (2) and soyasapogenol B (3) may be a colon cancer (Caco-2 cell line) suppressive component and determinate that the suppression of cell growth and disruption of cell membrane integrity is intensified with increases in lipophilicity of these.⁷⁴ Similarly, ginsenoside-Rb2 (4), a glycosylated steroidal triterpene extracted from Panax ginseng and P. notoginseng, has been shown to inhibit angiogenesis associated with lung tumors, potentially contributing to reduced tumor metastasis^75,76 and ginsenoside Rg1 (5), other ginseng saponin plays a vital role in LPS- induced apoptosis via regulating the TLR4/NF-κB/ NLRP3 axis.⁷⁷ Saikosaponin D (6) is the main toxic component of Bupleuri radix, exhibits antitumor activity through various mechanisms, including the inhibition of proliferation, invasion, metastasis and angiogenesis, as well as the induction of cell apoptosis, autophagy and differentiation.⁷⁸ Also has been demonstrated that Saikosaponin D (6) enhances the sensitivity of chemoresistant BC cells to doxorubicin by disrupting cellular redox homeostasis through inactivation of the STAT1/NQO1/PGC-1α signaling pathway.⁷⁹ Furthermore, α-hederin (7), a pentacyclic triterpene saponin from Nigella sativa, has been demonstrated to induce apoptosis in the SKOV-3 ovarian cancer cell line through the intrinsic mitochondrial pathway.⁸⁰ The triterpene-type oleanane saponins, tubeimosides I, II, and III (8, 9, 10) isolated from the Bolbostemma paniculatum (Maxim) Franquet, show antitumor, and antitumor-promoting effects with tubeimoside III (10) emerging as the most potent among them.⁸¹ Additionally, tubeimoside II (9) has been reported to exert a remarkable inhibitory effect on cell viability in hepatocellular carcinoma by inducing methuosis.⁸² On the other hand, the triterpenoid saponins, avicin D (11) and G (12) from Acacia victoriae induce cell cycle (G1) arrest of the human MDA-MB-453 breast cancer cell line and apoptosis of the Jurkat (T-cell leukemia) and the MDA-MB-435 breast cancer cell line.⁸³ Other saponin of anticancer interest is timosaponin AIII (13), isolated from Anemarrhena asphodeloides which showed cytotoxicity against five different cancer cell lines (A549, HepG2, Hep3B, Bcap37, MCF7)⁸⁴ (Table 1). These findings highlight the potential of plant-derived saponins as valuable components in developing novel anticancer therapies (Figure 3), (Table 1).

Figure 3.

Saponins with therapeutic potential (Antiproliferative activity of cancer cells).

Table 1.

Saponins with Antiproliferative Activity of Cancer Cells.

Saponin source	Saponin name	Experiment	Cell line	Reference
Glycine max	Soyasaponins I, (1) and III (2)	MTT viability assay	Hep-G2 cells	⁷³
Glycine max	Soyasaponins I (1), III (2) and soyasapogenol B (3)	Caco-2 colon cancer cell proliferation	Caco-2 cell cultures	⁷⁴
Panax ginseng and P. notoginseng	Ginsenoside-Rb2 (4)	Syngeneic mice	B16-BL6 melanoma cells	⁷⁵
Panax ginseng	Ginsenoside Rg1 (5)	Male C57BL/6J mice and neonatal rat cardiomyocytes (NRCMs)	LPS- induced apoptosis	⁷⁷
Bupleuri radix, dried root of Bupleurum chinense and B. scorzonerifolium	Saikosaponin D (6)	Antitumour assays	Cell apoptosis	⁷⁸
Radix Bupleuri	Saikosaponin D (6)	Cell viability, clone formation, three-dimensional tumor spheroid growth, and apoptosis analysis	Disrupting cellular redox homeostasis	⁷⁸
Nigella sativa	α-hederin (7)	SKOV-3 Cell Line	Cell apoptosis	⁸⁰
Bolbostemma paniculatum	Tubeimosides I (8), II (9), III (10)	BALB/c mice	DMBA and TPA	⁸¹
Chengdu Biopurify Phytochemicals Ltd	Tubeimoside II (9)	HCC cell lines	Cell viability in hepatocellular carcinoma	⁸²
Acacia victoriae	Avicin D (11) and G (12)	Annexin V-FITC Binding and PI3 K Assays	Breast cancer cell lines	⁸³
Anemarrhena asphodeloides	Timosaponin AIII (13)	in vivo and in vitro metabolism	Cancer cell lines	⁸⁴

Anti-Inflammatory Activity

Inflammation is a complex biological response to harmful stimuli such as pathogens, damaged cells, or irritants.⁸⁵ However, when inflammation becomes uncontrolled, it can lead to significant tissue and organ damage. Therefore, it is valuable to discover anti-inflammatory agents from natural sources.⁸⁶

Among these natural compounds, soyasaponin A1 (14) and A2 (15) decrease inflammation by inhibiting the ROS-mediated activation of the PI3 K/Akt/NF-kB pathway.⁸⁷ Similarly, tubeimoside I (7), II (8), and III (9), also saponins, exhibit notable anti-inflammatory properties.⁸¹ Avicins, such as Avicin G (11) suppress the activation of nuclear factor NF-κB pathway by inhibiting both its nuclear localization and ability to bind DNA, reducing both oxidative and nitrosative cellular stress and thus suppressing the development of malignancies and inflammation-related diseases.⁸⁸ Consistent with these findings, ginsenoside Rg1 (5) has been reported to attenuate LPS-induced inflammation and may exert its role by blocking the TLR4/NF-kB/NLRP3 pathway.⁷⁷ In line with this, escin (16), a saponin used clinically to treat inflammation and edema following trauma or surgery, has demonstrated potent topical anti-inflammatory effects in animal models. These effects are associated with the suppression of TNF-α and IL-1β levels and involve the upregulation of glucocorticoid receptor (GR) expression, along with inhibition of GR-related signaling pathways such as NF-κB and AP-1.⁸⁹ Additionally, saikosaponin B2 (17), oleanane-type triterpenoids from the Bupleurum genus, have shown significant anti-inflammatory activity. inhibits the IKKβ/IκBα/NF-κB signaling pathway in LPS-induced macrophages, resulting in decreased production of pro-inflammatory mediators including NO, PGE2, and cytokines.⁹⁰ Both in vivo and in vitro studies have demonstrated that saikosaponin D (SSD) (6) effectively suppresses the production of pro-inflammatory factors such as IL-1β, IL-6, and TNF-α. Its anti-inflammatory action may be attributed to the prompt inhibition of these key cytokines. Additionally, one report has shown that SSD contributes to the autophagic death of tumor cells by promoting autophagosome formation.⁹¹ In topical inflammation models, fruticesaponins A (18), B (19), and C (20) (lupane-type saponins from Bupleurum fruticescens) reduced ear edema induced by TPA, arachidonic acid (AA), and ethyl phenylpropionate (EPP), with fruticesaponin B (19) being the most effective. Orally, fruticesaponin B (18) (100 mg/kg) also significantly inhibited carrageenan-induced paw edema by 33%.⁹² Finally, loniceroside C (21) a triterpenoid saponin isolated of Lonicera japonica exhibits in vivo anti-inflammatory activity against croton oil-induced ear edema in mice, producing 15%–31% inhibition at doses ranging from 50 to 200 mg/kg⁹³ (Table 2), (Figure 4).

Figure 4.

Saponins with therapeutic potential (Anti-inflammatory activity).

Table 2.

Saponins with Anti-Inflammatory Activity.

Saponin source	Saponin name	in vitro/in vivo study	Experiment	Reference
Glycine max	Soyasaponin A1 (14), A2 (15)	in vitro	Lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2)	⁸⁷
Bolbostemma paniculatum	Tubeimosides I (7), II (8), and III (9)	in vivo	BALB/c mice	⁸¹
Acacia victoriae	Avicin G (11)	in vitro	Jurkat cells (human T cell leukemia)	⁸⁸
Beijing Bellancom Chemistry Company	Ginsenoside Rg1 (5)	in vivo and in vitro	Cell Apoptosis	⁷⁷
Aesculus hippocastanum	Escin (16)	in vivo	Carrageenan-induced paw edema and histamine-induced capillary permeability in rats	⁸⁹
Bupleurum falcatum	Saikosaponin B2 (17)	in vitro	LPS-induced RAW	⁹⁰
Bupleurum falcatum	Saikosaponin D (6)	in vivo	Mouse OA model	⁹¹
Bupleurum fruticescens	Fruticesaponin A (18), B (19), C (20)	in vivo	Carrageenan-induced paw edema	⁹²
Lonicera japonica	Loniceroside C (21)	in vivo	Mouse ear edema	⁹³

Antimicrobial Activity

Infectious diseases have profoundly influenced the course of human history. Infection is defined as the multiplication of microbes in the tissues of the host. These microorganisms include bacteria, viruses, fungi, and protozoa. Antimicrobial activity refers to the ability of a substance or drug to inhibit or kill the growth and reproduction of such microorganisms.^94,95

Among these, fungal infections are common in immunosuppressed patients, and overcoming these diseases is often a prolonged process due to the limited availability of antifungal drugs. Consequently, there is an urgent and essential need to develop antifungal agents that are non-toxic, biocompatible, and environmentally friendly.⁹⁶ Monodesmosidic triterpenoid saponins, phytolaccoside B (22), and E (23) isolated from Phytolacca tetramera showed antifungal activities against a panel of human pathogenic opportunistic fungi. Phytolaccoside B (22) demonstrated activity against Trichophyton mentagrophytes, Candida albicans, C. tropicalis, Saccharomyces cerevisiae, Cryptococcus neoformans, Aspergillus fumigatus, A. flavus, A. niger, Microsporum canis, M. gypseum, T. rubrum, Epidermophyton floccosum, with MICs around 50–125 μg/ml. In contrast, phytolaccoside E (23) showed activity against M. canis, M. gypseum, T. rubrum, E. floccosum and T. mentagrophytes, with MICs around 125–250 μg/ml. These findings suggest that monodesmosidic triterpenoid saponins containing phytolaccagenin as the aglycone exhibit antifungal properties.⁹⁷ Similarly, dioscin (24), a steroidal saponin isolated from the root bark of Dioscorea nipponica (wild yam), exhibited notable antifungal activity. It was effective against C. albicans, C. parapsilosis, Trichosporon beigelii, and Malassezia furfur, with minimum inhibitory concentrations (MICs) ranging from 11.3 ± 4.6 to 22.5 ± 9.2 μg/ml.⁹⁸ C-27 steroidal saponins, primarily recognized as precursors in the synthesis of steroidal hormones, have also demonstrated anti-fungal activity. Compounds such as agamenoside G (25), degalactotigonin (26), cantalasaponin I (27), deltonin (28), and dioscin (24) showed efficacy against C. albicans, C. glabrata, C. krusei, C. neoformans, and A. fumigatus, with reported minimum inhibitory concentrations (MICs) ranging from 2.5 to 20 μg/ml.⁹⁹

On another point, viruses are among the leading pathogenic agents responsible for numerous serious diseases in humans, animals, and plants. In the search for new antivirals, some saponins have been of great interest. In vivo studies have shown that oral administration of ginsenoside Rb2 (4) and 20(R)-ginsenoside Rg3 (29) (an epimer of 20(S)-ginsenoside Rg3) at a dose of 75 mg/kg effectively inhibited rotavirus (RV) replication in the intestines of mice.^46,100 Furthermore, saikosaponins SSA (30), SSB2 (31), SSC (32), and SSD (6) have been reported to potently inhibit HCV infection at non-cytotoxic concentrations by targeting the early stages of the viral life cycle. Among them, SSB2 (30) was identified as particularly effective, capable of neutralizing HCV particles, blocking viral attachment, and preventing entry/fusion mechanisms associated with its interaction with the HCV E2 protein. In addition, SSB2 (30) effectively inhibited HCV infection in primary human hepatocytes.¹⁰¹

Antibiotic resistance has become a serious concern due to antibiotic overuse, making the development of new antimicrobial agents essential.²¹ Several studies have identified various saponins of plant origin with remarkable antibacterial efficacy. Fruticoside I (33), isolated from the leaves of Cordyline fruticosa, has demonstrated inhibitory activity against Enterococcus faecalis, with a reported minimum inhibitory concentration (MIC) of 128 μg/mL.¹⁰² Flabelliferin B (34), obtained from Borassus flabellifer L. fruit, exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus.¹⁰³ In addition, chonglouoside SL-6 (35), a saponin derived from Paris polyphylla var. yunnanensis, has shown potent activity against Propionibacterium acnes (MIC: 3.9 μg/mL).¹⁰⁴ Furthermore, quinoa saponins (36) extracted from Chenopodium quinoa husks have exhibited antimicrobial effects against several oral and intestinal pathogens, including Porphyromonas gingivalis (MIC: 62.5 μg/mL), Clostridium perfringens (MIC: 31.3 μg/mL), and Fusobacterium nucleatum (MIC: 31.3 μg/mL).¹⁰⁵ Aridanin (37) and lotoidoside E (38), isolated from Paullinia pinnata, have also demonstrated potent antibacterial activity, with MIC values ranging from 1.56 to 6.25 μg/mL for S. aureus, and 0.78 to 3.13 μg/mL for both E. coli and Pseudomonas smartii.¹⁰⁶ These findings reinforce the potential of saponins as a valuable source of novel antimicrobial agents (Table 3) (Figure 5).

Figure 5.

Saponins with therapeutic potential (Antimicrobial activity).

Table 3.

Saponins with Antimicrobial Activity.

Saponin source	Saponin name	Biological activity	Test assays	Reference
Phytolacca tetramera	Phytolaccoside B (22), Phytolaccoside E (23)	Antifungal	Agar dilution method	⁹⁷
Dioscorea nipponica	Dioscin (24)	Antifungal	Micro-dilution method	⁹⁸
Agave americana, Polianthes tuberosa, Polygonatum zanlanscianense, Dioscorea parviflora	Dioscin (24) Agamenoside G (25), Degalactotigonin (26), Cantalasaponin I (27), Deltonin (28)	Antifungal	Micro-dilution method	⁹⁹
Panax ginseng P. quinquefolius	Ginsenoside Rb2 (4) 20(R)-Ginsenoside Rg3 (29)	Antiviral	Mice assays	^46,100
Bupleurum kaoi	Saikosaponins SSA (30), SSB2 (31), SSC (32), and SSD (6)	Antiviral	HCV culture	¹⁰¹
Cordyline fruticosa	Fruticoside I (33)	Antimicrobial	Micro-dilution method	¹⁰²
Borassus flabellifer	Flabelliferin B (34)	Antibacterial	Clinical trial	¹⁰³
Paris polyphylla var. yunnanensis	ChonglouosideSL-6 (35)	Antimicrobial	Micro-dilution method	¹⁰⁴
Chenopodium quinoa	Quinoa saponins (36)	Antimicrobial	Micro-dilution method	¹⁰⁵
Paullinia pinnata	Aridanin (37), lotoidoside E (38)	Antimicrobial	Micro-dilution method	¹⁰⁶

Other Therapeutic Potentials and Uses of Saponins

Beyond the therapeutic properties previously described, several studies have also highlighted the potential of saponins in other biomedical applications. For instance, triterpenoid saponins, including escin (16) and escin IIa (39), as well as protopanaxadiol-type saponins such as ginsenoside Rb1 (40) and Rb2 (4), have demonstrated anti-obesity effects in both in vivo and in vitro models.¹⁰⁷ Obesity significantly contributes to lifestyle-related diseases such as coronary heart disease, dyslipidemia, glucose intolerance, diabetes, hyperglycemia, and hypertension. Consequently, specific saponins with anti-obesity activity, such as ginsenosides Rg1 (5), Rb1 (40), and Rb2 (4), also exhibit therapeutic potential for these associated conditions Ginsenoside Rh2 (41).^108–111 Furthermore, majonoside R2 (MR2) (42), an oleanane-type saponin of particular interest, has demonstrated hepatoprotective effects by inhibiting TNF-α production in activated macrophages and directly blocking TNF-α is able to induce apoptotic pathways.¹¹² Additionally, majonoside (42) has been reported to attenuate opioid-induced antinociception by acting at both spinal and supraspinal levels.¹¹³ Steroidal glycoalkaloid saponins, such as solanine (40), have been shown to exert an anti-allergic effect against nightshades and cereals.¹¹⁴ In addition to their anti-inflammatory and antimicrobial effects and specific anticancer activity, α-tomatine (41) also possesses the ability to reduce cholesterol levels.¹¹⁵ (Table 4), (Figure 6).

Figure 6.

Saponins with therapeutic potential (Other Therapeutic Potentials of Saponins).

Table 4.

Saponins with Other Therapeutic Potentials.

Saponin source	Saponin name	Biological activity	Test assays	Reference
Aesculus turbinata	Escin (16), Escin IIa (39), Ginsenoside Rb1 (40) and Rb2 (4)	Anti-obesity	Lipase activity, mice	¹⁰⁷
Panax ginseng	Ginsenoside Rb1 (40), Ginsenoside Rg1 (5)	Anti-obesity	Mouse insulinoma cell line	¹⁰⁹
Panax ginseng	Ginsenoside Rh2 (41)	Antihyperglycemic	mice	¹¹⁰
Panax vietnamensis	Majonoside R2 (42)	Hepatoprotective	mice	¹¹²
Panax vietnamensis	Majonoside R2 (42)	Antinociceptive	mice	¹¹³

On the other hand, food technology takes advantage of its antimicrobial properties, while the cosmetic and pharmaceutical industry exploits its emulsifying and foaming properties with moisturizing and cleaning capacity.^1,5 These novel applications position saponins as molecules that replace synthetic surfactants; even the FDA suggests their use as an additive in foods and beverages, likewise the FAO, through the Codex Alimentarius, establishes the consumption limits of plant extracts rich in saponins.^60,115–117

Perspectives

Saponins constitute a group of compounds with extremely versatile therapeutic applications; however, their clinical implementation faces significant challenges, including their low bioavailability, hemolytic activity at high doses, and limited standardization of plant extracts. Given these limitations, the development of innovative technologies such as encapsulation, semisynthetic synthesis, and clinical studies is essential to realize their pharmacological potential.

Furthermore, saponin's structural complexity and composition variability among different plant species complicate their standardization and large-scale synthesis. In this context, a multidisciplinary approach integrating phytochemistry, pharmacology, molecular biology, and nanotechnology is necessary to deepen our understanding of their composition, mechanisms of action, toxicity, and biopharmaceutical behavior.

Furthermore, using sustainable technologies, such as plant tissue cultures using plant biotechnology and metabolic engineering tools, represents a viable strategy for the controlled and sustainable scaling of these metabolites. Added to this effort are omics techniques—such as metabolomics and transcriptomics—that provide valuable information on the biosynthetic pathways involved and allow for the selection of species or genotypes with optimized saponin production profiles.

Recently, saponins have shown a propensity to form nanoemulsions, improving their stability and reducing toxicity at high concentrations. Some reports even indicate that they are potential substitutes for synthetic surfactants such as Tween 80. This application is crucial in the food industry, allowing for extended shelf life and the incorporation of bioactive lipid compounds. Furthermore, due to their immunoadjuvant capacity, saponins are being encapsulated and used in some vaccines, enhancing immunity while avoiding the toxic effects of free saponins. Additionally, saponins are integrated into formulations as biostimulants, improving the dispersion and wetting of agricultural products. This, in turn, promotes the absorption of active ingredients by plants by reducing surface tension.

Finally, controlled clinical trials with purified saponins are essential to overcome the obstacle posed by their hemolytic activity and move toward regulatory approval. Most available studies have been limited to in vitro research or animal models, restricting their direct clinical applicability.

In conclusion, these key aspects constitute strong arguments for continuing and intensifying the study of saponins from diverse perspectives to consolidate their use as effective and safe therapeutic agents.

Conclusion

Saponins are consolidating their position as secondary metabolites of immense strategic value, thanks to their proven biological and amphipathic multifunctionality. This versatility establishes them as a fundamental pillar for both the development of innovative therapeutic solutions and the transition to a sustainable bioeconomy. The therapeutic relevance of saponins in human health is undeniable, given their broad spectrum of biological activities, which make them promising candidates for the design of treatments for complex diseases, including cancer, infections, and metabolic disorders. To fully realize this potential, nanotechnology is indispensable. Optimizing nanoformulations overcomes the challenges of bioavailability and toxicity, enabling controlled, targeted release of active compounds.

Additionally, saponins extend their usefulness to the sustainable industry. Their capacity as natural surfactants confers a significant environmental advantage, facilitating the replacement of synthetic and aggressive components in sectors such as food, agriculture (as biostimulants), and detergents. In short, the successful and safe integration of saponins into the market requires ongoing interdisciplinary research. This effort must focus on the systematic study of their vast structural diversity and the clinical validation of nanoformulations. Because saponins are obtained sustainably and utilize plant byproducts, they represent not only a fertile field for scientific advancement but also a strategic opportunity to develop safer therapies and more environmentally friendly industrial processes.

Footnotes

Acknowledgments

We thank the Director of the National Polytechnic Institute (IPN, Mexico), the Rector General of the Metropolitan Autonomous University (UAM, Mexico), and the Rector of the Autonomous University of the State of Mexico (UAEMex, Mexico) for their support in developing applied research, technological development, and social impact activities.

ORCID iDs

Mariana Sánchez-Ramos

Francisco Cruz-Sosa

Authors’ Contributions

Mariana Sánchez-Ramos, Araceli Guerrero-Alonso: Conceptualization; Francisco Cruz-Sosa, Juan Orozco-Villafuerte: Funding acquisition; Mariana Sánchez-Ramos, Araceli Guerrero-Alonso: Writing-original draft: Leticia Buendía-González, Carmen Hernández-Jaimes: Data curation; Mariana Sánchez-Ramos^, Francisco Cruz-Sosa: Writing-review & editing, Angélica Román-Guerrero: Supervision; Mariana Sánchez-Ramos, Francisco Cruz-Sosa: Revision.

Funding

The authors declared having received financial support for the preparation of this review article: This work was funded through the research project “Development of new vaccine adjuvants from medicinal plant saponins, towards sovereignty in the coverage of the national vaccination scheme. Area: Public Health. within the framework of Consortia of the Call for inter-institutional collaboration projects in the State of Mexico IPN-UAM-UAEMex. Grant award numbers SIP-CC-002-2024, PE012, 7157/2024ECON

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The authors declare that molecular structures 1, 3–6 were drawn using the online tool ChemDraw, while the cell membrane in was created using the authors’ own Canva software.

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Therapeutic Value of Plant Saponins,Challenges and Opportunities: A Review

Abstract

Keywords

Introduction

Saponins and Their Classification

Functions of Saponins in Plants

Properties of Saponins

Key Findings

Potential Therapeutic of Saponins

Antiproliferative Activity of Cancer Cells

Anti-Inflammatory Activity

Antimicrobial Activity

Other Therapeutic Potentials and Uses of Saponins

Perspectives

Conclusion

Footnotes

Acknowledgments

ORCID iDs

Authors’ Contributions

Funding

Declaration of Conflicting Interests

References