Potential Of Diosgenin Research Articles

Evaluating in-vitro antioxidant and in-silico anti-inflammatory potential of Diosgenin

Chronic diseases are inextricably tied up with oxidative stress and inflammatory responses. Oxidative stress triggers an antioxidant imbalance that elicits a multitude of inflammatory reactions, inevitably culminating in death-causing diseases by integrating free radicals. Rising research approaches intensely focus on identifying natural antioxidants with efficient anti-inflammatory potency. Diosgenin is a potent bioactive therapeutic candidate spotted in Fenugreek and Yams and has varied pharmacological properties. Concerning the therapeutic importance of this compound, the current study intends to explore its antioxidant and anti-inflammatory potential. The antioxidant ability of diosgenin was tested by using free radical scavenging assays such as 1,1-diphenyl-2- picrylhydrazyl radical (DPPH), 2, 2’-Azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) (ABTS●+), Hydroxyl radical and Superoxide anion. Furthermore, the screening of Diosgenin’s anti-inflammatory potential was done by ligand interactions via Autodock software to explore its binding affinity with inflammatory receptors (NF-κB and TNF-α). On comparing this with standard ascorbic acid, Diosgenin has nearly equivalent IC50 values. The IC50 values of Diosgenin and Ascorbic acid were found to be 48.24 μg/mL and 47.93 μg/mL (DPPH), 41.18 μg/mL and 40.19 μg/mL (ABTS●+), 50.14 μg/mL and 48.99 μg/mL (Hydroxyl radical), 44.33 μg/mL and 50.02 μg/mL (Superoxide anion). Additionally, Diosgenin has good binding scores (-7.7, -9.8 kcal/mol) with target inflammatory receptors (NF-κB and TNF-α). In-vitro and in-silico modeling proves that diosgenin has effectively high antioxidant and antiinflammatory potency. Hereby, diosgenin seems to be a promising antioxidant against inflammatory diseases.

The nephroprotective potential of diosgenin against ischemia-reperfusion acute renal damage via suppression of oxidative stress and downregulating inflammatory mediators

ABSTRACT Renal ischemia/reperfusion injury (I/R) is caused by short impairment of the blood supply to the kidney. Acute renal damage (ARD) is still a major problem in today’s clinical practice. Diosgenin (DG), a steroidal sapogenin mainly present infenugreek, yams, Costus species in high amounts. DG as a leading phytoconstituents is beneficial in several disease conditions due to its multifunction including antioxidant, hypolipidemic, anti-inflammatory, hypoglycemic, anticancer and anti-proliferative effects. The purpose of this study was to investigate the nephroprotective potential of DG on ischemia-reperfusion induced kidney damage in rats. Thirty male Wistar rats were divided into five groups. DG was given orally at doses of 20, 40 and 80 mg/kg for 10 days. On day 11th ARD was induced by unilateral ischemia for 45 min followed by 24-hour reperfusion. The levels of creatinine, blood urea nitrogen, total proteins, pro-inflammatory cytokines were decreased in DG + I/R rats compared to NC rats, along with a significant amelioration of oxidative stress. Histopathological analysis exhibited less histological damage in DG + I/R rats as compared with NC rats. Pretreatment of rats with DG (40 and 80 mg/kg) was able to improve these damages significantly, though DG (20 mg/kg) was insignificantly effective. In conclusion, DG proved nephroprotective potential against kidney damage induced by I/R injury via mitigation of inflammation, oxidative stress, and histopathologic injuries.

Evaluation of antigenotoxic effects of diosgenin in mice exposed to cyclophosphamide

Diosgenin is a steroidal saponin found in a variety of plants including fenugreek and roots of wild yam and is widely used in traditional medicine systems. Diosgenin is shown to have anti-invasive, anti-proliferative and proapoptotic activities on wide range of cancer cells and a well known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. The present investigation explores the genotoxic and antigenotoxic properties of diosgenin in experimental mice exposed to cyclophosphamide. CP increases the formation of micronucleated PCEs in the bone marrow of mice significantly and lowers the total WBC. In mice pre-treated with diosgenin, the formation of mnPCEs is lowered in a dose dependent manner and the immune parameters are restored. Diosgenin also reduces the lipid per oxidation levels indicated by MDA assessment and restores the antioxidant GSH in the liver tissues of the mice, counteracting the effects of CP. In our study, Diosgenin did not exhibit inherent genotoxic properties nor had a synergistic effect with CP. These results indicate the potential of diosgenin as an antigenotoxic agent with a possibility to be used as an adjuvant, to counteract the side-effects of chemotherapeutic drugs. 
 Keywords: Antigenotoxicity; Cyclophosphamide; Diosgenin; Micronucleated PCEs; WBC; Lipid peroxidation; Reduced glutathione

Abstract 4105: Diosgenin and temozolamide: A potential combinatorial chemotherapy to overcome temozolamide resistance in glioblastoma multiforme

Abstract Introduction: Glioblastoma multiforme (GBM) accounts for the most aggressive form of tumor showing poor prognosis. Prevailing treatment modality includes chemotherapy with temozolomide (TMZ) concomitant with surgical resection and/or irradiation. However, it has been observed that a number of patients are developing resistance to TMZ owing to its high dosage regimen. The aim of this study is to examine the effects of diosgenin (DSG), a natural steroidal saponin obtained from fenugreek, in combination with TMZ in human GBM cells and TMZ resistant GBM cells. Methodology: The potential of combinatorial chemotherapy for overcoming TMZ resistance was evaluated through development of TMZ resistant GBM clones. These clones were generated by treatment of GBM cells with sub-lethal dose of TMZ over several cycles. Cellular effects were studied by viability assay, flow cytometry and wound healing assay on both single and combined drug treated GBM cells and TMZ resistant cells, respectively. The morphological study and cellular uptake in combined or individual drug treated cells was assessed by microscopy and immunofluorescence staining. The time dependant effect of drugs on invasive and migratory potential of GBM cells and TMZ resistant cells was analysed through zymography for matrix metalloproteinases (MMPs) activity and western blot for apoptotic proteins, epithelial and mesenchymal (EMT) markers, MMPs and VEGF expression. Further, the drug induced apoptosis was also assessed through chromatin condensation and DNA laddering assay. Results: Our investigation shows that co-administration of DSG and TMZ resulted in a substantial increase in GBM cell apoptosis and marked inhibition of cell growth in vitro. Anti-angiogenic and anti-invasive potential of DSG and TMZ were assessed through in vitro studies. At molecular level, DSG and TMZ synergistically lower XIAP expression and cleavage of intracellular death substrates such as PARP thereby shifting the balance from survival to apoptosis as indicated by the rise in the sub-G1 cell population. This combination also alters EMT markers, downregulates the expression of Bcl-xL, Bcl-2, Mcl1, MMPs and VEGF and induces expression of Bax, AIF, cytochrome C. Conclusion: The results suggested that DSG in combination with TMZ reduced the dose of TMZ, when administered singly, and also inhibited the migration and invasion of GBM and TMZ resistant cells. It induced apoptosis and altered the expression of EMT markers. These findings reveal a new therapeutic potential for overcoming TMZ resistance in GBM therapy. This novel modality may be a promising tool for GBM treatment. Citation Format: Y Rajesh, Angana Biswas, Subhayan Das, Mahitosh Mandal. Diosgenin and temozolamide: A potential combinatorial chemotherapy to overcome temozolamide resistance in glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4105. doi:10.1158/1538-7445.AM2017-4105