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Abstract

The present study is aimed to explore the therapeutic attributes of diosgenin against atherosclerosis and associated health disorder. Side effects associated with synthetic drugs for the treatment and management of diseases worldwide have necessitated scientists to investigate and evaluate the therapeutic potential of phytochemicals and their pharmacological activities. Plants including Smilax China, Dioscorea alata, and the Trigonella foenum graecum are rich sources of diosgenin. In addition to being a crucial component in the creation of several steroidal medications, this bioactive phytochemical has shown great promise in the treatment of a wide range of diseases, including cancer, hypercholesterolemia, inflammation, and multiple infections. Diosgenin can reduce hyperlipidemia by lowering the amount of low-density lipoproteins, interfering with the absorption of cholesterol and increasing its excretion. Diosgenin inhibits the expression of NPCIL1 receptor, LXR-alpha, HMG CoA and SRB1, increases expression of ABC G5/G8 transporters to prevent dietary cholesterol accumulation in the body. Diosgenin exhibits antithrombotic activity by inhibiting platelet activation, and modulating anti coagulation by significantly decreasing factor Viii activity. Diosgenin inhibits the oxidation of LDLs, hence preventing atherosclerosis. It also possesses antithrombotic activity by inhibiting pancreatic lipase activity. Diosgenin provides anti-inflammatory benefits to the human body. It inhibits inflammatory markers including Interlukin-1 beta (IL-1β), Tumor necrosis factor – alpha (TNF-α), Nitric Oxide and cytokines. Moreover, it promotes the synthesis of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. By modifying the IKKβ pathway, it reduces endothelial damage linked to insulin resistance. This review discusses the recent advancements to explore diosgenin potential in reducing atherosclerotic cardiovascular diseases, diabetes, cancer, inflammation, clinical application, pharmacokinetics underlying mechanism with existing scientific evidences.

Keywords

bioactive compound chronic diseases diosgenin inflammation therapeutic potential

Introduction

Atherosclerosis is the most common and well-known arterial disorder, which is characterised by the thickening or hardening of arteries caused by the accumulation of fatty acids, lipids (cholesterols), cellular waste products and other substances, collectively called a plaque. This condition causes arteries to narrow, blocking blood flow and oxygen supply which eventually causes chronic complications¹ that affect blood vessels of heart, brain, arms and legs as well as pelvis and in some cases, kidneys. Despite the slow progression of atherosclerosis, clinically significant anomalies have been observed at higher rate especially in older adults. Atherosclerotic cardiovascular diseases (ASCVD) have become a leading cause of morbidity and mortality worldwide.² In 2015, atherosclerosis accounted for 31% of all fatalities worldwide. In 2019, 17.9 million deaths worldwide were ascribed to cardiovascular diseases (CVDs), which accounted for 32% of all global deaths. The number of deaths attributed to ASCVD is even expected to surpass 23.6 million by 2030.³

Classical trigger markers of atherosclerosis include hyperlipidemia, diabetes, hypertension, obesity, age, smoking and some genetic factors/family history. In addition, stress, sleep deprivation, poor dietary habits; intake of high fat diets and sedentary lifestyles are also some of the risk factors that are linked to atherosclerosis.⁴ Due to the potential resistance and toxic effects of certain synthetic medication, public interest has been shifted towards the use of novel and alternative options for the disease management. Natural bioactive and phytochemicals of herbs and spices are being studied and researched for modulating effects on atherosclerotic cardiovascular diseases.⁵ In this context, utilization of steroidal products has gained prime importance being therapeutically active compounds. Numerous studies have discovered the remedial properties of sapogenin and steroidal saponins. The plant based bioactive are generally non-toxic and cost effective. One such bioactive compound is diosgenin, a naturally occurring plant steroidal sapogenin, richly present in Fenugreek seeds (Trigonella foenum-graecum), China root (Smilax China) and wild yams (Dioscorea Villosa L.).⁶

Sources of Diosgenin

Diosgenin is mainly present in almost 137 members of Dioscorea genus including Dioscorea deltoidea, Dioscorea nipponica, Dioscorea villosa, Dioscorea composite, Dioscorea zingiberensis etc.⁷ Diosgenin has also been extracted from various other botanicals such as Rhizoma polgonati, and Paris polyphylla but the most studied and explored one is Trigonella foenum-graecum. Diosgenin mainly produced by hydrolysis process but the microbial production is also gaining importance due to its low cost, being highly specific and environmentally friendly.⁸

Biochemical and Biomedical Attributes of Diosgenin

Diosgenin is 27 carbon containing spiroketal steroid, appearing as white needle like crystal with molecular formula as C₂₇H₄₂O₃ (Figure 1). Diosgenin is stable for various physical conditions like chemical, temperature, thermal and light. It is highly hydrophobic ie water insoluble with a solubility in aqueous medium as 0.7 ng/mL. However, it is highly soluble in non-polar solvents including ethyl acetate, propanol, chloroform, dichloroethane, propyl acetate etc.⁹

Figure 1.

Diosgenin (3β-hydroxy-5-spirostene) is a “spirostan, with molecular formula; C₂₇H₄₂O₃, substituted by hydroxy group at beta 3 position, a double bond at 5-6 position and an R configuration at position 25.

In most of the plants, diosgenin is biosynthesized by cholesterol via isoprenoid pathway. Poor water solubility, instability for various physiological conditions and low pharmacokinetic limits the utilization of diosgenin as potential drug in clinical investigations. However, its vast pharmaceutical properties have forced the researchers to discover novel ways of diosgenin effective delivery as well as identification of its derivatives alongside their biological properties. One of the potent derivative of diosgenin ie, dioscin has shown therapeutic potential against CVDs, hepatic anomalies, pulmonary fibrosis and numerous types of cancers in vivo as well as in vitro.¹⁰ Moreover, amino acid based derivatives of diosgenin have also been extensively studied for their effective biological properties. As far as the bioavailability of diosgenin is concerned, the creation of conjugate complexes or nano-formulations is being investigated to improve the pharmacokinetics and bioavailability of diosgenin. Currently researchers are focusing on the development of effective carrier systems including development of nanoparticles to explore the diosgenin's mechanism of action, how its therapeutic effects can be enhanced besides, minimizing the adversities.⁸

After its discovery in 1963 by Fuji and Matsukawa, diosgenin has been explored for its biomedical properties. Diosgenin extracted from the seeds of fenugreek is said to exhibit diabetic modulating properties and is being used in various anti-diabetic formulation, playing pivotal role in restoration of beta cells, downregulation of hepatic gluconeogenesis and upregulation of glucokinase.⁶ In the medicinal field, diosgenin has gained prominence due to its therapeutic potential against lethal disorders such as asthma, neural anomalies, obesity, cancer, CVDs etc Researchers have explored it in the treatment of malignancies, inflammation, hyperlipidemia and infectious disorders due to its vast pharmacological properties.¹¹ Diosgenin has been used in industries as a precursor of variety of steroidal drugs and corticosteroids, therefore has an important medicinal value.¹²

Atherosclerosis and its Effects

Atherosclerosis is an outcome of series of events (Figure 2) starting with an injury to endothelial cells because of certain factors including hypertension, hyperglycemia, smoking, hyperlipidemia and reactive oxygen species. Damaged endothelial cells result in increased permeability of vessel and this allows LDL particles to enter tunica intima. The monocytes which in normal state flow freely also enter tunica intima. Monocytes are capable of producing free radicals which oxidize LDL particles. The process goes on and leads to the accumulation of highly oxidized LDL particles. Macrophages and smooth muscle cells start to engulf these fat LDL particles and form foam cells (fat accumulation). These foam cells rupture due to excessive accumulation of LDL and releases its contents and new macrophages engulf these particles and the process goes on. The accumulation of foam cells, LDL particles, dead cells lead to plaque formation. The plaque hardens over time with the accumulation of calcium salts resulting in denser dead cells leading to atherosclerosis. Damaged endothelial cells over the clot get compromised and result in clot thrombus formation.¹ With the passage of time, thrombus gets detached from vessels and now called an embolus. This embolus travels to blood stream and may affect blood vessels of heart (myocardial infarction), brain (strokes), legs (deep vein thrombosis).

Figure 2.

Schematic flowchart depicting the events that result in the development of thrombus formation and Stroke Thrombus formation leading to stroke involves endothelial damage, platelet activation via receptors like platelet glycoprotein GPIb/IX/V and GPIIb/IIIa, and the coagulation cascade mediated by various clotting factors.

Advance Techniques to Understand the Prognosis of Atherosclerosis

The advancement in technology has further facilitated to study the creation and development of plaque. Intraplaque Hemorrhage (IPH) is an important imaging biomarker that indicates the atherosclerosis progression. Recently radiation free and highly sensitive Magnetic Particle Imaging (MPI) has been devised to identify the atherosclerosis plaques with IPH. This invitro study found a haemoglobin degradation product, haemosiderin, as a potential source of MPI signals. On contrary to this the 7T T1-weighted MRI could not detect the small sized IPH.¹³ Cardiac fibrosis is another health complication accompanied with the expansion of the cardiac interstitium due to net accumulation of Extracellular Matrix (ECM) proteins, resulting into most of cardiac pathologic condition. Discovery of targeted proteomic technologies help to quantify low abundance circulating proteins to understand cardiac fibrosis mechanisms. A study analyzed the plasma serum proteome using proximity extension assays to determine regulation of 92 proteins previously associated with cardiovascular disease. Results were assessed using volcano plots of statistical significance versus magnitude of change and Bayesian additive regression tree (BART) models to determine importance. It was found that 17 proteins were associated with higher ECV. Using BART, Insulin-like growth factor-binding protein 1, Plasminogen activator inhibitor 1 and N-terminal pro-B-type natriuretic peptide were associated with higher Extra Cellular Volume (ECV) after accounting for other proteins and traditional cardiovascular risk factors.¹⁴ A traditional Chinese medicine Dan-Shen-Yin (DSY) is used in the treatment of cardiovascular disease. Hong et al (2023) found mechanism of action of the DSY by following the network pharmacological techniques and revealed that PI3K/AKT pathway was the principal signaling pathway of DSY against EndMT (Endothelial-to-Mesenchymal Transition) in atherosclerosis. DSY showed a stringent impact to modify the expression of signature EndMT genes and decrease the expression of PI3K/AKT pathway signals. Moreover, DSY strongly downregulated LASP 1 (LIM and SH3 domain protein 1), an upstream of the PI3K/AKT pathway. DSY potentially exerted anti-EndMT activity through the LASP1/PI3K/AKT pathway, providing a possible new therapeutic intervention for atherosclerosis.¹⁵ Eating habits and planning also play a vital role in the development of CVDs. Time-restricted eating is a dietary strategy that emphasizes on when one eats. Recently it was found that Time Restricted Feeding (TRF) could be a promising strategy for the prevention of CVD risk in mice. The study found that TRF showed a promising effect on reducing the size of atherosclerotic lesion, prevented the elevation of macrophage content in atherosclerotic lesions during circadian disturbance, increased the relative abundance of anti-inflammatory monocytes, prevented activation of T cells, and lowered plasma total cholesterol levels and markers of hepatic cholesterol synthesis.¹⁶ Coronary artery disease (CAD) and Type 2 diabetes (T2D) both have known genetic determinants, but the mechanisms through which their associated genetic variants lead to disease onset remained poorly understood. Smith et al (2023) used large-scale metabolomics data in a two-sample reverse Mendelian randomization (MR) framework to estimate the effects of genetic liability to T2D and CAD on 249 circulating metabolites in the UK Biobank. They followed Inverse Variance Weighted (IVM) models to estimate the effects of genetic liability to Type 2 Diabetes (T2D) to decrease Low density Lipoprotein (LDL) cholesterol and High-Density Lipoprotein (HDL) cholesterol while increasing all triglyceride groups and branched chain amino acids.¹⁷

Immunotherapy is also considered to be an effective measure to control atherosclerosis. Atherosclerosis, being considered as a long immune mediated inflammatory response, can be reduced by inducing a protective immune response through auto-antigens or exogenous antigens. The studies have demonstrated that atherosclerotic is associated with the presence of immune cells and immune factors in the body.¹⁸ Similarly, under pro-inflammatory conditions, endothelial cells adopt a mesenchymal phenotype by a process called endothelial-to-mesenchymal transition (EndMT) which plays an important role in the pathogenesis of atherosclerosis. A network pharmacology-based system was followed to determine the therapeutic impact of Dan-Shen-Yin (DSY) and it was found that it exerted anti-EndMT activity through the LASP1/PI3K/AKT pathway, providing a new therapeutic approach for atherosclerosis.¹⁵ Likewise, an in vitro method was estabilished to induce EndoMT with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and angiotensin II (Ang II) followed by a protocol to study the reversibility of EndoMT and showed that the combination of L-NAME and a combination of Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and angiotensin II (Ang II) may stimulate EndoMT in Human umbilical vascular endothelial cells (HUVECs). This method may serve as a model to screen and identify potential pharmacological molecules to target and regulate the EndoMT process, with applications in drug discovery for human diseases.¹⁹ Activin receptor-like kinase 1 (ALK1) plays an important role in the production of EMT and tissue fibrosis. Martínez-Salgado et al, (2022) suggested regulatory role of ALK1 in vascular rarefaction and emergence of myofibroblasts.²⁰ Similarly, polydatin, a natural potent stilbenoid polyphenol and a resveratrol derivative, can inhibit EndMT, thereby reducing the pulmonary endothelial dysfunction and pulmonary vascular remodeling.²¹ The results of the study provide new ideas for the further treatment of PAH injury. Cai et al, (2023) conducted a study on 882 patients with atherosclerosis in single and multiple arteries, determined a relationship between Acetaldehyde dehydrogenase 2 (ALDH2) rs671 and methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphisms. The proportion of ALDH2 rs671 A allele and MTHFR rs1801133T allele in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The study concluded that these genotypes could be independent factor for atherosclerosis in multiple arteries.²² Ursolic acid (UA) is a natural triterpene carboxylic acid, mediates the inhibitory effect of cholesterol esterase (CEase) and pancreatic lipase PL that might provide an additional insight into understanding the role of UA in the hypolipidemic effect.²³ In another study it was shown that the phlorizin could potentially possess cholesterol-lowering activity by increasing the excretion of sterols and mediating the endogenous cholesterol metabolic management.²⁴ Similarly, Endothelial function is impaired in a lot of tissues in people with diabetes. Previously, the role of aquaporin 4 (AQP₄)-AS1 in retinal neurovascular dysfunction induced by diabetes was elucidated.²⁵ In vivo analysis determined that silencing of AQP4-AS1 reduced the vascular dysfunction and retinal neurodegeneration as evident by retinal capillary degeneration, decreased reactive gliosis, and reduced retinal ganglion cell loss. AQP4-AS1 had a promising effect on endothelial cell and RGC function. While it regulated retinal neurovascular dysfunction through affecting AQP4 levels.

Diosgenin has been largely discussed and investigated for its huge potential in pharmacological studies, as well as the intriguing rudimentary modes of action, validating and expanding the comprehensive knowledge gained through its conventional use. In the last two decades, several mechanistic and preclinical studies have been conducted to better understand the true advantages and importance of diosgenin against manifold illnesses. Overall, the findings of multiple investigations suggest that diosgenin could be used as a novel multi-target-based therapeutic or chemopreventive drug for a variety of chronic diseases. Recently, the role of diosgenin in cardiac and diabetic diseases has been reviewed, but a holistic review of various biological activities based on preclinical and clinical studies is still missing in the literature to the best of our literature review. The fundamental objective of this review is to summarize the in-depth pharmacological activity discussing the preclinical, clinical evidences and techniques to overcome health disorders specifically atherosclerosis and safety issues of diosgenin, and the upcoming strategies to overcome present limitations. In this context, this review investigates the pharmacological impact of diosgenin as an antithrombotic agent. To give effect to the aim, the review addresses the following objectives: (a) to explore bioactive potential of diosgenin in treating and managing atherosclerosis, cancer, diabetes, and inflammation, (b) to establish mechanism of actions of diosgenin in preventing and ameliorating the abovementioned chronic diseases and (c) finally, to discuss the limitations and issues related to its bioavailability and the possible solutions, safety and toxicity concerns and its clinical and preclinical studies to establish its pharmacological significance.

Results and Discussions

Therapeutic Attributes of Diosgenin

This review investigates the most recent findings to explore the potential therapeutic applications of diosgenin bioactivity on reducing atherosclerotic markers such as hyperlipidemia, hyperglycemia, thrombosis, associated cancers, reactive oxygen species and chronic inflammation. Mechanism of actions behind the therapeutic potential of diosgenin has been summarized in Table 1.

Table 1.

Mechanism of Action Behind the Therapeutic Potential of Diosgenin.

Activity	Mechanism of Action	Reference
Antihyperlipidemic activity	↓intestinal cholesterol absorption↓NPCILI* and LXR-α* expression↑ABC G5/G9* expression↑Cholesterol excretion	¹⁰
	↑ expression of SRB1* receptor	¹⁷
	↓HMG-CoA* activity	¹⁵
	↓ pancreatic lipase activity	²⁰
Antithrombotic/Anticoagulant activity	↓Platelet activation↓ Clotting factor VIII *	¹¹
Anticancer Activity	↑p53Arrest G1 cell cycle↑STAT3 expression	²⁶ ²⁷
	↓ Matrix Metalloproteinase Enzyme	²⁴
	↓ Guanine Nucleotide Exchange Factor (VAV2)↓ Nuclear Factor Kappa B	⁶
Anti-inflammatory	↓ IL-1β, TNF-α↑Prostaglandin E2* (PGE2)	²⁸ ²⁹
	↓ Cyclooxygenase enzyme (COX-2*)	³⁰
	↑ Adenosine monophosphate-activated protein kinase (AMPK*)	³¹ ³²
	↑ AMPK*↓ HMG-CoA reductase	⁶
Anti-oxidant Activity	↑ Superoxide Dismutase and Glutathione Peroxidase	³³
	↓Hypoxia	³⁴
	↓ lactate dehydrogenase↓ creatine phosphokinase	³⁵
	↑phosphodiesterase-5 activity	³⁶
Anti-diabetic Activity	Modulates IKKβ* pathway	³⁷
	↓ α-amylase↓ α-glucosidase	³⁸
	↓High Glucose-Induced Renal Tubular Fibrosis↓Myeloperoxidase	³⁹ ⁴⁰

Notes: NPCILI: Niemann-Pick C1-Like 1; LXR-α: Liver X receptor alpha; ABC G5/G9: ATP Binding Cassette; SRB1: scavenger receptor class b type 1; HMG-CoA: β-Hydroxy β-methylglutaryl-Coenzyme A; Clotting factor VIII: antihemophilic factor; p53: Tumor protein p53; STAT3: signal transducer and activator of transcription 3; IL-1β: cytokine interleukin-1β; TNF-α: Tumor necrosis factor alpha; PGE2: Prostaglandin E2; COX-2: Cyclooxygenase enzyme; AMPK: Adenosine monophosphate-activated protein kinase; IKKβ: Inhibitor of nuclear factor kappa-B kinase subunit beta.

Antihyperlipidemic Activity

Hyperlipidemia is one of the classical trigger markers of atherosclerosis. Elevated blood lipids or triglycerides in blood induce hyperlipidemia. Epidemiological data reinforce the causal role of cholesterol, triglycerides and low-density lipoproteins in mediating atherosclerosis.⁴¹ In place of statins as the first line of defense against hyperlipidemia, diosgenin has been under research as a potential regulator of lipid metabolism disorders.⁴² In humans, lipid metabolism and homeostasis are regulated by various elusive mechanisms and involve various transcription factors. Numerous studies and clinical trials suggested that diosgenin can reduce hyperlipidemia by lowering the amount of low density lipoproteins, interfering with the absorption of cholesterol and increasing its excretion.¹²

NPC1L1 “(Niemann-Pick C1-Like 1)” is a cholesterol importer protein that regulates intestinal absorption of cholesterol and some fat-soluble vitamins. It has been considered that diosgenin blocks NPCIL1 receptor and prevents cholesterol endocytosis in intestinal lining, thus interferes its absorption.⁴³ The ABC “(ATP-binding cassette) transporters”, G5 and G8 are responsible for preventing dietary cholesterol accumulation. Diosgenin increases their expression and contributes to cholesterol excretion. Li et al investigated the molecular mechanisms of diosgenin action on cholesterol metabolism in rat model. Rats were fed with high fat diets for approximately four weeks, followed by intragastric doses of diosgenin, once a day for 8 weeks. mRNA and protein expression levels of NPC1L1, ABC G5/G8 and LXR-alpha were measured. The study concluded that diosgenin reduced intestinal absorption by lowering NPCILI and LXR-alpha expression and increased cholesterol excretion by increasing ABC G5/G9 expression.¹⁰

In addition, diosgenin also modulates cholesterol transport by upregulating the expression of Caveolin-1 protein that controls intracellular cholesterol levels.⁴⁴ Diosgenin also reduces reverse transport of cholesterol by inhibiting SRB1 (scavenger receptor class b, type 1) receptor present on HDL. Yu et al investigated the expression of SRB1 receptor, CES-1 (carboxyl esterase 1; shows cholesteryl ester hydrolase activity) etc pathways for cholesterol elimination. The study was done in a rat model fed with high fat diets. The results revealed that in rats, diosgenin helped in reducing the weight and lipid levels in their blood and increased expression of receptors which inhibited cholesterol absorption and increased cholesterol excretion.²⁶

Another underlying mechanism is that diosgenin inhibits endogenous synthesis of fats by inhibiting hepatic lipogenic enzyme called HMG CoA (3 methyl, 3 glutaryl coenzyme A) which is highly expressed in liver.²⁷ A study analyzed the activity of diosgenin on expression of HMG CoA in diabetic rats. Diosgenin administration for 45 days significantly reduced blood glucose, lipids and cholesterol levels and HMG CoA activity.³⁰

Furthermore, diosgenin also inhibits pancreatic lipase activity and reduces lipids absorption.⁴⁵ Navarro Del Hierro et al studied the impact of fenugreek and quinoa derived diosgenin on pancreatic lipase activity in vitro digestion models concluded that these extracts inhibit pancreatic lipase activity.³⁷ A diagram of mechanisms of cholesterol homeostasis and its modulation by diosgenin bioactivity is represented in Figure 3.

Figure 3.

Depicts the mechanisms of cholesterol homeostasis and its modulation by diosgenin bioactive. Diosgenin regulates lipid metabolism through multiple routes and various targets. These mechanisms are highly complexed and lacks animal trials/evidence. Therefore, this bioactive can be manipulated in different formulations to manage hyperlipidemic disorders.

Antithrombotic/Anticoagulant Activity

Antithrombotic activity refers to the inhibition of platelet function.³⁸ Endothelial cells are responsible for maintaining vascular function by regulating platelet function and coagulation. Endothelial cells are capable of releasing Factor Viii, a blood clotting protein. Any injury or damage to endothelial cells leads to high levels of Factor Viii proteins which leads to aberrant aggregation or platelet activation resulting in thrombus formation.⁴⁶ Diosgenin exhibits antithrombotic activity by inhibiting platelet activation, and modulating anti coagulation by significantly decreasing factor Viii activity.¹¹ However, the studies are limited and required more in vivo trials to further understanding the properties of diosgenin an antithrombotic therapy.

Anti-Cancer Activity

Diosgenin has demonstrated efficacy as a therapeutic agent against numerous organ tumors by suppressing proinflammatory signaling pathways and initiating apoptosis.⁴⁷ A schematic representation of the potential molecular mechanisms for the anticancer activity of diosgenin has been illustrated in Figure 4. Anticancer effect of diosgenin bioactivity depends on concentration and type of the cell. Diosgenin prevents proliferation in different types of cancers like, prostate cancer (cells: PC-3 and DU-145),⁴⁸ breast cancer (MCF-7),³⁹ intestinal carcinoma (the HCT-116 and HT-29 cells),⁴⁰ hepatic carcinoma (the HepG2 and HCC cells),⁴⁹ lung cancer (A549 cells)⁵⁰ etc The anticancer mechanism is associated with cell signaling modulation of growth, proliferation, and differentiation that take part in critical phases of tumorigenesis.⁶

Figure 4.

Schematic representation of the potential molecular mechanisms for the anticancer activity of diosgenin. Diosgenin inhibits transcriptional factors STAT3, NF-κB, and sterol-regulatory element binding protein (SREBP) regulated genes involved in tumor cell proliferation, phenotypic switching, invasion, migration, and angiogenesis, partly by modulating the PI3K-Akt-mTOR and MAPK pathways. Besides, telomerase is also a target of diosgenin which is important for most cancer cells to grow and proliferate.

Diosgenin activates p53, a tumor suppressor gene, arrests the G1 cycle which results in decreased potential to grow and multiply, modulates the activity of Caspase-3 which executes apoptosis after the activation of Signal Transducer and Activator Of Transcription 3 (STAT3), a protein coding gene.^51,52 Figure 5 depicts the anti-cancer activity of diosgenin by activation of p53 system and STAT3 signaling pathway which leads to planned cell death.

Figure 5.

Depicts the anti-cancer activity of diosgenin by activation of p53 system and STAT3 signaling pathway which leads to planned cell death; apoptosis.

While diosgenin also activates another pathway that causes a decrease in the matrix metalloproteinase enzyme (MMP). This results in decreased cancer cell invasion. The activation of MMP induces a series of events summarized in Figure 6. It causes the collagen to degrade because of its activity on collagen bonds. This results in the migration of smooth muscle cells into the vessel blockage, leading into occlusion and the subsequent development of atherosclerosis. Diosgenin decreases MMP activation thereby preventing the risk of atherosclerosis.⁴⁷ Diosgenin also exhibits anti-metastatic effects. It does so by suppressing the activity of guanine nucleotide exchange factor (VAV2). Moreover, it also decreases the angiogenesis process which is essential for the spread of cancer through the cells of body.⁶ It also abolishes the production of “Nuclear Factor Kappa B” that is induced by “Tumor Necrosis Factor alpha”.⁴⁶

Figure 6.

Representation of MMP (matrix metalloproteinase) role in metastasis. MMPs (MMP-2 and MMP-9) participate in progression of atherosclerosis by contributing to extracellular matrix degradation, macrophage recruitment, inflammation and plaque formation. Integrins (α4β1 and αLβ2), and TLRs (TLR2 and TLR4) are key receptors involved in mediating cell adhesion, inflammation, and migration within atherosclerotic plaques.

Cytotoxicity Against Cancer Cells

Many researchers have designed diosgenin and diosgenin based derivatives and their dose specific studies have been conducted to evaluate their toxicity level against cancer cells. Ma et al (2021) synthesized 28 diosgenin amino acid ester derivative products (3a-3 g and 7a-7 g). They conducted the cytotoxicity research on six different human cancer cell lines including MNK45, T24, K562, HepG2, A549, and MCF-7. The majority of the compounds demonstrated the ability to cause cytotoxicity in these tumor cells. Compound 7 n, out of 28 derivatives, exerted a significant cytotoxic effect on K562 cells (IC50: 4.41 μM) in comparison to diosgenin (IC50: 30.04 μM). Compound 7 also caused the apoptosis of K562 cells by means of pathways associated to the mitochondria.⁵³

The cytotoxic effect of diosgenin rich extract obtained from the rhizome of Paris polyphylla was also investigated against the Hep-2 cell lines, MDA-MB-231 and MCF-7 human breast cancer cells, and cervical cancer cells (HeLa). The diosgenin-rich extract demonstrated the profound effectiveness against MCF-7 cells and inhibited the growth of all malignant cells. A diosgenin-rich extract has increased the expression of the gene Bax and decreased the expression of the gene pre-mRNA transcripts for Bcl-2 and BIRC5.⁵⁴

Yin et al developed 32 novel derivatives of diosgenin and assessed their cytotoxic effect against A549, MCF-7, and HepG2 human cancer cells. In comparison to diosgenin, they discovered that compounds 8, 18, 26, and 30 had more potential to reduce the cancer cell growth. Compound 8 exhibited minimum and maximum cytotoxic activity on L02 cells (IC50: 18.6 μM), and HepG2 cells (IC50: 1.9 μM) respectively. Furthermore, compound 8 also instigated G0/G1 cell cycle arrest and programmed cell death in HepG2 cells. Additionally, docking investigation indicated that the compound 8's target, p38α-MAPK, fit well on its active site.⁵⁵

Anti-diabetic Activity

Diosgenin also demonstrates protective effect on endothelial dysfunction that is often associated with diabetes and resistance to insulin. By regulating the IKKβ pathway, it not only guards against CVDs but also inhibits endothelial dysfunction linked to insulin resistance.⁵⁶ Diosgenin elevates adipocyte differentiation and possesses inhibitory effect on inflammation in adipose tissue. It also exhibits a significant level of α-amylase and α-glucosidase inhibitory effect which reinforces its impact on reduction of high blood glucose levels. Previously it was found that the prolonged diosgenin administration to diabetic rats can lower blood sugar levels, restores vascular responsiveness through endothelium-dependent and independent pathways, and at least partially do so by reducing inflammation, lipid peroxidation, and apoptosis.²⁸

It also shows anti-diabetic effect on enzyme systems. It was reported that diosgenin administration to diabetic rats increased glucose-6-phosphatase and fructose-1,6-bisphosphatase activity in the liver and decreased the glucokinase activity. Additionally, supplementation with diosgenin reduced blood glucose levels in diabetic rats as compared to the group of rats fed a regular diet, along with other favorable changes in a number of parameters related to diabetes. This outcome is consistent with other studies that suggested diosgenin had hypoglycemic effects.²⁹ In this regard, diosgenin modified other significant diabetic enzymes.^32,57

Diabetes exerts a significant impact on renal function, and numerous studies have explored this fact. Because of its anti-inflammatory properties, diosgenin, for instance, was shown to play a protective function against high glucose-induced renal tubular fibrosis, presumably through the epithelial-to-mesenchymal transition (EMT) pathway.⁵⁸ Diosgenin efficacy as an antioxidant agent was further demonstrated by its effects on oxidative indicators including myeloperoxidase and lipid peroxidation as well as the renal antioxidant system. In light of the fact that diosgenin had a protective effect on the kidney in diabetic rats, it is possible to consider it as a therapy option for diabetes with renal problems.³¹

Effect of Diosgenin on Osteoporosis and Post Menopause Symptoms

Osteoporosis is an age-related bone disorder that results into bone fragility and susceptibility to fracture due to deterioration of bone tissue and low bone mass.⁵⁹ It is a widely characterized condition that primarily affects older people in poor countries and affects both men and women. However, the prevalence of osteoporosis is lower in the men as compared to the women.⁶⁰ Diosgenin has been investigated for its ability to promote the bone formation and prevent the resorption of existing bone. Wnt (Wingless-related integration site) and BMPs (Bone Morphogenic Proteins) pathways are the two recognized signaling pathways that regulate the osteogenic differentiation of mesenchymal stem cells or pre-osteoblasts. Many studies^33,34 have evaluated lncRNA and mRNA profiles using microarray technique and confirmed the anti-osteoporotic effects of diosgenin on alveolar bone. Diosgenin is considered to exert this effect by activating the Wnt and BMPs pathways. This finding was further supported by Zhang et al who demonstrated that the anti-bone loss action of diosgenin on alveolar bone was achieved by the regulation of molecular expression in the Wnt, P13K (Phosphatidylinositol 3-kinase), RANK/RANKL (receptor activator of nuclear factor kappa beta) or osteoclastogenic cytokine pathways.³⁵

Menopause is a physiological condition that involves a complete termination of menstruation because of reduced estrogen. Many psychological changes like dementia, anxiety, depression, irritability, and sleep disturbances are experienced by women passing through menopause. Moreover, postmenopausal diseases like obesity, hyperlipidemia, blood pressure variations, and cardiovascular disease (CVD) are common in women. This hormonal deficiency also results in the production of ROS-mediated inflammatory cytokine in postmenopausal women leading towards changes in renal architecture.

A study determined that sapogenins (diosgenins), present in seed extract of Trigonella foenum-graecum L³⁶ reduced the activity of pro-inflammatory cytokine. Similarly, TFG plays effective role in providing the defense against morphological alterations in the kidneys of diabetic rats. This action is achieved by enhancing the antioxidant activity thereby protecting the accumulation of oxidized DNA.⁶¹

Other Symptomatic and Bioactive Attributes of Diosgenin

Anti-inflammatory Attributes

Atherosclerosis is an inflammatory disease of chronic origin depending on the health of vascular system of the body.⁶² Inflammation damages the vessels and result in Atherogenesis which causes the development of atherosclerotic plaques. Diosgenin provides anti-inflammatory benefits to the human body. It has shown to inhibit inflammatory markers including Interlukin-1 beta (IL-1β), Tumor necrosis factor – alpha (TNF-α), Nitric Oxide and cytokines. IL-1β that stimulates Prostaglandin E2 (PGE2) synthesis which is a proinflammatory mediator, while nitric oxide formed due to endothelial nitric oxide synthase, deteriorates the intima of coronary arteries due to disturbance in the vascular tone regulation process of the arteries.^63,64 However, further studies and trials are needed to understand the properties regarding inflammation. Some studies provide evidence regarding decreased inflammation on treatment with diosgenin. Due to its capability to mediate nitric oxide and other inflammatory mediators.⁶⁵

Diosgenin acts as an inhibitor of Cyclooxygenase enzyme (COX-2) and reduce cellular inflammation.³⁸ Moreover, diosgenin also activates Adenosine Monophosphate-activated Protein Kinase (AMPK) which helps in reducing Atherosclerosis. AMPK is a sensor for metabolism and regulates metabolic processes.⁶⁶ AMPK regulates autophagy which is essential for maintenance of heart functioning and promotion of cholesterol regulation. Autophagy is regulated via a downstream pathway.^66,67 Treatment of Diosgenin have shown to inhibit markers associated with inflammation.⁶⁵ It has a protective effect on endothelial cells by increasing AMPK activity.⁶⁸ AMPK inhibits HMG-CoA reductase (HMGR) which then inhibits fatty acids and sterol synthesis leading to the regulation of lipid metabolism by decreasing deposition of LDL in arteries.⁶ Diosgenin suppresses inflammation present in the lesions and also modulates responses of immune system. It also regulates adipokines expression in adipose tissue and protect the heart against inflammatory episodes.⁶⁹

Anti-oxidant Activity

Oxidation of low density lipoproteins (LDLs) results in endothelial cell injury which then causes a cascade of reactions, involving pro-inflammatory molecules.⁷⁰ Diosgenin has potent antioxidant capabilities. It has free radical scavenging properties that helps in keeping reactive oxygen species at bay. Diosgenin inhibit the oxidation of LDLs, hence preventing Atherosclerosis. Moreover, it boosts the synthesis of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase.⁷¹ The other important effect of Diosgenin is the ability to prevent hypoxia related injury to cardiac cells. By using ATP-sensitive channels and adjusting cell survival, it can be repaired.⁷² Diosgenin acts as a natural antioxidant to protects brain from age-related disorders.⁶⁹

Chemotherapeutic drugs such as Doxorubicin results in oxidative stress which leads to cardiotoxicity. Here, Diosgenin also works to prevent oxidative damage.⁷³ A study on mice revealed that Doxorubicin causes increased levels of lactate dehydrogenase enzymes and creatine phosphokinase. This leads to development of cardiotoxicity. Not only this, but it also reduced the levels of antioxidant enzymes like superoxide dismutase and glutathione enzymes. When Supplemented with Diosgenin, these effects got minimized and the serum levels of markers decreased. It decreased the inflammatory markers such as the expression of nuclear factor kappa B (NF-Kb). It also caused increase in phosphodiesterase-5 activity, which helped in improving myocardial fibrosis also..^74,75

Clinical Studies

The clinical studies to evaluate diosgenin and it derivatives as a therapeutic drug are limited. However, some of the clinical trials have determined that diosgenin and its analogs exhibit anti-proliferation, antioxidant, anti-inflammatory, plasma cholesterol-lowering, and anti-thrombotic effects, suggesting that these drugs may be potential candidates for the treatment of atherosclerosis. Dioscin is the main active component of three drugs Dioscorea saponin tablets, Dunyeguanxinning tablets, and Di’ao Xinxuekang capsules manufactured in China were employed to treat cardiovascular disease. Among these, Di’ao Xinxuekang capsules have been used for more than 30 years to treat the coronary heart disease.⁷⁶ Recently, a randomized, multi-center, double-blind, parallel-group study of 733 patients with chronic stable angina pectoris was performed by Yu et al revealing that the number of patients with angina were significantly reduced when they were treated with Di’ao Xinxuekang capsules and after 20 weeks of treatment, the frequency of angina pectoris episodes and nitroglycerin usage per week were decreased.⁷⁷ The efficacy of Dioscorea saponin tablets was evaluated in another study and found that the total effective rate of Dioscorea saponin tablets with regard to angina pectoris symptoms was 90%, and the electrocardiogram improvement efficiency was 65%.⁷⁸ According to these studies, dioscin has a therapeutic or adjuvant therapeutic effect against heart disease.

Diosgenin has been examined in a number of clinical studies for its efficacy to treat different health related disorders. Tohda et al⁷⁹ studied the effects of a diosgenin-rich yam extract on cognitive enhancement in healthy volunteers. A 28 healthy volunteers (aged 20-81) were randomly assigned to receive a 12-week yam extract or placebo in a double-blind, placebo-controlled research. The study had a 6-week washout period. The negative effects were assessed for the Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) exam. Diosgenin-rich yam extract was shown to have no adverse effects and to considerably improve synaptic fluency and cognitive performance over the course of 12 weeks.

In another study, one hundred women undergoing IVF/ICSI, intracytoplasmic sperm injection, were received a multinutrient supplementation named PROfertil^® consisting of selenium, folic acid, catechins, vitamin E, glycyrrhizin, diosgenin, damiana, and omega-3-fatty acids showed beneficial effects in terms of embryo quality.⁸⁰ It determined the curative effects of Dioscorea villosa (wild yam containing steroidal saponins, including diosgenin) extract given to healthy 23 women suffering from menopausal symptoms in a placebo-controlled, randomized, double-blind and cross-over study. No significant adverse effects were observed in both the treatments. Additionally, there were no changes found in weight, systolic or diastolic blood pressure, total serum cholesterol, triglyceride, high-density lipoprotein cholesterol, glucose, estradiol, or serum.

Pharmacokinetics and Bioavailability Studies of Diosgenin

The low water solubility, pharmacokinetics, quick biotransformation under physiological circumstances, and poor bioavailability of diosgenin greatly limit its therapeutic utilization, despite its pharmacological effects in the treatment of numerous disorders.⁸¹ A previous study examined pharmacological effect of cyclodextrin bound diosgenin on a rat model and it was observed that the oral administration in the skin at six hours reached at highest level (Okawara et al). AUC (a measure of total systemic exposure to the drug) was 4121.9 ± 1354.7 ng h/mL, and the absolute oral bioavailability was 4.45 ± 1.46%. Other studies revealed that the plasma concentration of diosgenin reached Cmax (the time it takes for a drug to reach the maximum concentration after administration of a drug that needs to be absorbed) 132.5 ± 48.2 ng/mL after 5.01 ± 0.5 h of oral administration.^82,83 Some other studies elucidated the plasma concentration of diosgenin reached C_max (The time it takes for a drug to reach the maximum concentration after administration of a drug that needs to be absorbed) 132.5 ± 48.2 ng/mL after 5.01 ± 0.5 h of oral administration with an AUC (a measure of total systemic exposure to the drug) of 4121.9 ± 1354.7 ng . h/mL and an absolute oral bioavailability of 4.45 ± 1.46%.^27,30 Similarly, it was demonstrated that rat model treated with diosgenin resulted in a C_max of 42.1 ± 30.6 ng/mL at 11.3 ± 3.9 h along with an AUC_0–60 h of 1309.3 ± 849.8 ng h/mL and t_1/2 (The half-life is the time it takes for the plasma concentration of a drug or the amount of drug in the body to be reduced by 50%.) of 10.4 ± 4.2 h. It was proposed that when diosgenin was given to rats, dogs, and monkeys in one dosage, the majority of the drug was evacuated by feces and the remaining portion was quickly removed by bile. Rats’ liver, adrenal glands, and stomach walls were the tissues where diosgenin was most commonly found. When dogs were given numerous concentrations (100 as/kg/day for 4 weeks), diosgenin at concentrations as high as 15 μg/mL was found to remain unchanged. Rats and dogs’ bile contained many DG metabolites, however the patterns of metabolites varied between the two examined species. Its main biliary metabolite in the F ring was monohydroxylated diosgenin. Less than 1 mg/mL of diosgenin was found in human serum after 4 weeks of oral dosing at a dose of 3 g/day.⁸⁴ Even while albite diosgenin has significant physiological activity, its hydrophobic properties cause it to be poorly soluble in digestive juices and have a low bioavailability, which makes it nearly impossible for the blood to absorb. Diosgenin cannot fulfill its pharmacological function as a result, which severely restricts the therapeutic use of diosgenin formulations. Different adultrants generated by diosgenin, however, can improve the synergistic action of their components and exert pharmacological activity.⁸⁵ To increase the solubility and dissolution of diosgenin, it is thus required to alter its chemical makeup, create various structural derivatives, and change its structure. This strategy could intensify diosgenin's pharmacological effects.

Strategies to Ameliorate the Pharmacological Efficiency of Diosgenin

Due to strong hydrophobicity and lipophilic impact of diosgenin, several strategies based on diosgenin derivatives synthesis have been devised to increase its pharmacological efficiency. These include diosgenin meta-carbamate, diosgenin amino acid derivatives, diosgenin F ring-opening derivatives, and diosgenin glycosylated derivatives have been synthesized many researchers and observed their impact on ameliorating different diseases. Diosgeninogen carbamate derivatives were produced in a number of studies that clarified their anti-oxidant and anti-inflammatory properties. The compound (22R,25R)-3β-(N-benzylcarboxylate)-5-en-20α-spirostan was found to be the most useful among all the produced carbamate derivatives due to its anti-inflammatory and anti-AD capabilities.⁸⁶

Amino acid molecule when introduced into the molecular structure of insoluble drugs, can improve the solubility of drugs in water and enhance the active transport process in the intestine, thus promoting drug absorption, solving the phenomenon of low oral bioavailability and improving its utilization value.⁸⁷

Toxicity Profile of Diosgenin

Diosgenin's toxicity has been recorded by only a few studies⁸⁸ conducted a dose dependent study that involved different doses of steroidal saponins, from Dioscorea zingiberensis, given to mice. The primary metabolite and constituent of these saponins was diosgenin. According to the study, mice receiving doses up to 562.5 mg/kg showed no negative effects. Nevertheless, at concentrations of 1125 g /kg and above, these saponins demonstrated lethal effects. It's interesting to note that the standard dose for steroidal saponins is 510 mg/kg/day, which suggests that neither the steroidal saponins nor diosgenin pose a serious risk at this level.

It was recently shown that derivatives of diosgenin possessed antithrombotic properties. These compounds could be protective and comparable to aspirin, with a decreased risk of bleeding and less harm to the stomach mucosa.⁸⁹ Additionally, studies have revealed that diosgenin has a little inhibitory impact on cytochrome P450 enzymes (CYPs), indicating that diosgenin is safe to use in combination with any other medication and has no toxicity.²² Most of the investigations determined that diosgenin and its derivatives are nontoxic and have underlined their utility in the medicaments of chronic disorders including cancer.

A Comparison on use of Isolated Diosgenin and Whole Fenugreek Seeds

Consuming pure diosgenin or whole fenugreek seeds as part of the diet have its own set of advantages and disadvantages. Pure diosgenin can be isolated and used specifically for its potential benefits.³⁸ Isolating diosgenin allows for consistent dosing and standardization in research studies and pharmaceutical applications making it easier to ensure reproducibility. Pure diosgenin supplements provide a concentrated source of the compound, potentially allowing individuals to achieve therapeutic effects with smaller amounts compared to consuming whole fenugreek seeds.²²

However, fenugreek seeds contain a variety of other compounds besides diosgenin, including dietary fiber, minerals, vitamins, and other bioactive compounds.⁵¹ These components work synergistically to provide overall health benefits that isolated diosgenin lack. Isolating diosgenin may not provide the same broad spectrum of health benefits as consuming whole fenugreek seeds. These seeds are a source of variety of bioactive compounds that contribute to its various potential effects, such as supporting digestion, managing blood sugar levels, and promoting lactation in breastfeeding mothers.⁹⁰

This review encompasses the most recent advances regarding therapeutic effects of natural antioxidant compound diosgenin, performing different biological activities such as antiatherosclerosis, anticancer, antidiabetic, antiosteoporosis and post-menopausal symptoms and helps in the management of these diseases and envisages the futuristic stratetigies to ameliorate the issues regarding its bioavailability and toxicity. On the other hand, the review lacks in silico studies to explore new diosgenin-specific targets, critical for further validating its use in the treatment and elimination of diseases.

Conclusion

Diosgenin is a saponin that is abundant in fenugreek and is also present in many other plant species. It possesses several bioactive properties that include antihyperlipidemic, antihyperglycemic, antioxidant, anti-inflammatory, and antiproliferative activities. Diosgenin can be a potential alternative to some conventional drugs which have adverse reactions. Since it is a plant-based remedy, it is believed to be less toxic and can be a good strategy to replace conventional drugs as more cost-effective option. However, its poor bioavailability due to its steroidal structure and less evidence on its potential targets often limits its disease ameliorating applications. The present evidence is limited to rat models; therefore, more researches and trials are needed to prove its effect on humans in order to utilize its maximum potential. Moreover, in addition to the promising therapeutic activities of diosgenin, several challenges are needed to be addressed for the successful translation of diosgenin into clinical applications. As research on diosgenin bioactive advances, its potential for personalized medicine and targeted therapy has become increasingly relevant and therefore can be studied further. In addition, issues such as bioavailability, optimization of formulations, and safety profile assessment for appropriate dosage require further research and investigation. Moreover, the development of effective delivery systems and standardized extraction methods are crucial in understanding its therapeutic potential.

Materials and Methods

We analyzed the latest and most appropriate studies on diosgenin's pharmacological attributes to conduct this study. Using the following MeSH keywords, we did search for scientific papers which were published in the electronic journals including the PubMed/MEDLINE, Scopus, SciFinder, and The Web of Science. “Diosgenin/ therapeutic use,” “Diosgenin/pharmacology,” “Diosgenin/analogs & derivatives,” “Humans,” “Chronic Disease/prevention & control,” “Cardiovascular Diseases/drug therapy,” “Inflammation/drug therapy,” “Saponins/therapeutic use,” “Saponins/toxicity,” “steroids,” including the “Signal Transduction/drug effects.” There were researches focusing on molecular processes and targets, the signaling pathways, and advised dosages of clinical trials. Excluded were homeopathic formulations and experimental pharmacological investigations with additional tested drugs, and the duplicates. A table and pictures were used to summarize the most important facts. The Plant List^91,92 has been used to validate plant taxonomy, while the PubChem database⁹³ has been used to validate chemical formulas.

Summary

Since ages plants have been utilized as potential therapeutics and the phytotherapy to address health disorders. Humans have been relying on plant-based materials to meet their nutrition needs as well as for the treatment of a wide range of diseases. Plants have served as the foundation of traditional medicine systems. Therefore, much of the research has been focused on isolating and identifying the active components in plant-based extracts and investigating for their therapeutic attributes. One of the such components is diosgenin and its derivatives that have attracted the considerable attention of scientists owing to their pharmacological properties. This review encapsulates the recent advances, both in vitro and in vivo, on exploring the therapeutic attributes of diosgenin, its mode of action, bioavailability, toxicity profile and clinical trials to explore its efficacy for the human use. This is accomplished by searching for scientific papers which were published in the electronic journals including the PubMed/MEDLINE, Scopus, SciFinder, and The Web of Science. Several studies have described the pharmacological effects of diosgenin against a variety of diseases such as atherosclerosis, cancer, diabetes, osteoporosis and cardiovascular diseases. This natural bioactive compound owes these pharmacological effects by downregulating, blocking or upregulating the expressional markers and initiating the specific signaling pathways. This review will further facilitate to explore new horizons for further research on diosgenin and its derivatives focusing on treatment of these diseases. Recently the pharmacokinetic efficacy of diosgenin has been increased by designing its derivatives including diosgenin meta-carbamate, diosgenin amino acid derivatives, diosgenin F ring-opening derivatives, and diosgenin glycosylated derivatives, cyclodextrin bound diosgenin and plasma concentration of diosgenin. Moreover, the clinical application of diosgenin has found no changes in weight, systolic or diastolic blood pressure, total serum cholesterol, triglyceride, high-density lipoprotein cholesterol, glucose, estradiol, or serum that determines its putative potential against diseases.

Footnotes

Data Availability

Data is available in public repositories that issue datasets (provided in references).

Declaration of Conflicting Interests

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

Ethical Approval

Ethical approval is not applicable for this review article

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Rizwan ur-Rehman

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Diosgenin: A Potential Therapeutic Phytocompound for the Management of Atherosclerosis and Other Physiological Disorders

Abstract

Keywords

Introduction

Sources of Diosgenin

Biochemical and Biomedical Attributes of Diosgenin

Atherosclerosis and its Effects

Advance Techniques to Understand the Prognosis of Atherosclerosis

Results and Discussions

Therapeutic Attributes of Diosgenin

Antihyperlipidemic Activity

Antithrombotic/Anticoagulant Activity

Anti-Cancer Activity

Cytotoxicity Against Cancer Cells

Anti-diabetic Activity

Effect of Diosgenin on Osteoporosis and Post Menopause Symptoms

Other Symptomatic and Bioactive Attributes of Diosgenin

Anti-inflammatory Attributes

Anti-oxidant Activity

Clinical Studies

Pharmacokinetics and Bioavailability Studies of Diosgenin

Strategies to Ameliorate the Pharmacological Efficiency of Diosgenin

Toxicity Profile of Diosgenin

A Comparison on use of Isolated Diosgenin and Whole Fenugreek Seeds

Conclusion

Materials and Methods

Summary

Footnotes

Data Availability

Declaration of Conflicting Interests

Ethical Approval

Funding

ORCID iD

References