Diosgenin: An Updated Pharmacological Review and Therapeutic Perspectives

Abstract

Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin's pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin's nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin's safety profile.

Figure 1

The biosynthetic pathways of diosgenin. Dioscorea zingiberensis, for diosgenin biosynthesis uses two P450 genes, DzinCYP94D144 and DzinCYP90G6, the orthologs of PpCYP94D108 and PpCYP90G4, which, from cholesterol, catalyze the formation of diosgenin.

Figure 2

Diagram with cellular targets and molecular mechanisms involved in anticancer effect of diosgenin. Abbreviations and symbols: ↑: increased; ↓: decreased; MMPs: matrix metalloproteinases; abbreviated mRNA: messenger RNA; TIMP: metallopeptidase inhibitor 1; AKT: serine/threonine kinase 1; PI3K: phosphatidylinositol-3-kinase; ERK: extracellular signal-regulated kinase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; VEGF: vascular endothelial growth factor; DNA: deoxyribonucleic acid; TNFR1: tumor necrosis factor receptor 1; TNFα: tumor necrosis factor; PGE2: prostaglandin E₂; COX: cyclooxygenase; LOX: 5-lipoxygenase; LTB4: leukotriene B4; PARP-1: poly(ADP-ribose) polymerase 1; ERα: estrogen receptor alpha; Src: proto-oncogene tyrosine-protein kinase; Cyt C: cytochrome C.

Figure 3

Schematic diagram showing the beneficial effect in atherosclerosis, thus preventing cardiovascular and neurodegenerative diseases. Abbreviations: Cox-2: cyclooxygenase-2; TNF-α: tumor necrosis factor-alpha; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells.

Figure 4

Summarized scheme showing the most representative biological activities of the diosgenin. Abbreviations and symbols: ↑: increase; ↓: decrease; T4: thyroxine; LDL: low-density lipoprotein; OPG: osteoprotegerin; RANKL: receptor activator of nuclear factor kappa beta; IL: interleukin; TNF-α: tumor necrosis factor-alpha.