Search

Diosgenin, a natural steroid saponin, holds promise as a multitarget therapeutic for various diseases, including neurodegenerative conditions. Its efficacy in slowing Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke progression has been demonstrated. However, the role of diosgenin in anti‐epilepsy and its potential connection to the modulation of the intestinal microbiota remain poorly understood. In this study, exogenous diosgenin significantly mitigated pentylenetetrazole (PTZ)‐induced seizures, learning and memory deficits, and hippocampal neuronal injury. 16S ribosomal RNA (16S rRNA) sequencing revealed a reversal in the decrease of Bacteroides and Parabacteroides genera in the PTZ‐induced mouse epileptic model following diosgenin treatment. Fecal microbiota transplantation (FMT) experiments illustrated the involvement of diosgenin in modulating gut microbiota and providing neuroprotection against epilepsy. Our results further indicated the repression of enteric glial cells (EGCs) activation and the TLR4‐MyD88 pathway, coupled with reduced production of inflammatory cytokines in the colonic lumen, and improved intestinal barrier function in epilepsy mice treated with diosgenin or FMT. This study suggests that diosgenin plays a role in modifying gut microbiota, contributing to the alleviation of intestinal inflammation and neuroinflammation, ultimately inhibiting epilepsy progression in a PTZ‐induced mouse model. Diosgenin emerges as a potential therapeutic option for managing epilepsy and its associated comorbidities. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non‐alcoholic fatty liver disease, focusing particularly on ferroptosis‐related pathways and its reliance on nuclear factor erythroid 2‐related factor 2. Materials and Methods: Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis‐related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Results: Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low‐density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin‐1β and tumour necrosis factor‐α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high‐fat diet‐induced non‐alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2‐related factor 2 and its downstream ferroptosis‐related genes to inhibit ferroptosis in the livers of rats with non‐alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis‐related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2‐related factor 2. Conclusions: This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2‐related factor 2 regulation, offering novel insights into the treatment of non‐alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Context: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. Objective: to investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. Materials and methods: Fourty male sprague-Dawley rats were randomized into four groups. the MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. at the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. Results: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDa (0.82-fold) and NO (0.83-fold) levels while increasing the activity of sOD (1.56-fold), cat (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. additionally, DG decreased IL-2 (0.55-fold), tNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), iKKβ (0.93-fold), p-iKKβ (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), McP-1 (0.88-fold) and e-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). Discussion and conclusions: the results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials. [ABSTRACT FROM AUTHOR]

Diosgenin is a phytosteroid sapogenin with reported antitumoral activity. Despite the evidence indicating a lower incidence of prostate cancer (PCa) associated with a higher consumption of phytosteroids and the beneficial role of these compounds, only a few studies have investigated the effects of diosgenin in PCa, and its mechanisms of action remain to be disclosed. The present study investigated the effect of diosgenin in modulating PCa cell fate and glycolytic metabolism and explored its potential interplay with G protein-coupled oestrogen receptor (GPER). Non-neoplastic (PNT1A) and neoplastic (LNCaP, DU145, and PC3) human prostate cell lines were stimulated with diosgenin in the presence or absence of the GPER agonist G1 and upon GPER knockdown. Diosgenin decreased the cell viability, as indicated by the MTT assay results, which also demonstrated that castrate-resistant PCa cells were the most sensitive to treatment (PC3 > DU145 > LNCaP > PNT1A; IC50 values of 14.02, 23.21, 56.12, and 66.10 µM, respectively). Apoptosis was enhanced in diosgenin-treated cells, based on the increased caspase-3-like activity, underpinned by the altered expression of apoptosis regulators evaluated by Western blot analysis, which indicated the activation of the extrinsic pathway. Exposure to diosgenin also altered glucose metabolism. Overall, the effects of diosgenin were potentiated in the presence of G1. Moreover, diosgenin treatment augmented GPER expression, and the knockdown of the GPER gene suppressed the proapoptotic effects of diosgenin in PC3 cells. Our results support the antitumorigenic role of diosgenin and its interest in PCa therapy, alone or in combination with G1, mainly targeting the more aggressive stages of the disease. [ABSTRACT FROM AUTHOR]

Diosgenin (DSG) is a phytosterol saponin mainly found in Dioscorea zingiberensis C.H. Wright. It has shown promising results in treating various diseases such as cancer, diabetes, arthritis, asthma, and cardiovascular diseases. Diosgenin is also an important medicinal chemical for synthesizing various steroid medicines. The production of diosgenin by acid hydrolysis generates a large amount of wastewater, leading to severe environmental pollution. However, producing diosgenin through microbial fermentation can effectively reduce environmental pollution. Numerous studies have demonstrated that various microorganisms can produce diosgenin via solid-state fermentation. Nevertheless, due to the complexity, high maintenance costs, uneven heat production, and other characteristics of solid-state fermentation, it is not commonly used in the industrial production of diosgenin. In contrast, liquid fermentation offers advantages such as simple operation, easy maintenance, and stable fermentation, making it more suitable for the industrial production of diosgenin. However, few studies have focused on producing diosgenin using liquid fermentation. In this study, endophytic Bacillus licheniformis SYt1 was used to produce diosgenin via liquid fermentation, with Dioscorea tuber powder as a substrate. Soxhlet extraction and silica gel column chromatography were employed to identify the diosgenin from the liquid fermentation products. Suitable fermentation conditions were screened and identified. The environmental variables that significantly affect the diosgenin yield were determined by the Plackett–Burman design (P-BD) with eight factors. The three factors (peptone, yeast extract powder and inorganic salt) with the greatest influence on the diosgenin yield were selected and further optimized using a response surface methodology (RSM). The final culture conditions were determined to be 35.79 g/L of peptone, 14.56 g/L of yeast extract powder, and 1.44 g/L of inorganic salt. The yield of diosgenin under these conditions was 132.57 mg/L, which was 1.8 times greater than the yield under pre-optimization conditions. This effective, clean, and promising liquid fermentation method possesses the potential to replace the traditional acid hydrolysis method for the industrial production of diosgenin. [ABSTRACT FROM AUTHOR]

Plant steroids such as ecdysterone (ECDY) or diosgenin (DIO) have been associated with anabolic and performance-enhancing effects for years. However, the molecular mechanisms have not yet been extensively studied in skeletal muscle cells. Consequently, the anabolic activity and associated molecular mechanisms of ECDY and DIO alone and in combination were investigated in C2C12 myotubes. Dose-dependent effects of both compounds on myotube diameter, mRNA expression of IGF-1 and PI3KR1 as well as expression of myosin heavy chain (MHC) proteins were analyzed in differentiated C2C12 cells. In addition, the binding affinities to androgen and estrogen receptors were analyzed. Treatment with ECDY and DIO significantly induced hypertrophy of C2C12 myotubes. Partially additive effects were observed. This is supported by the mRNA expression of IGF-1 and PI3KR1 as well as in the expression of MHC. However, no clear statement can be made regarding which combination has the strongest additive effects. Besides the results suggest that, in contrast to ECDY, DIO has antiandrogenic effects and bind on AR. Consequently, it indicate that two different mechanisms of action are activated in ECDY and DIO combinations. However, this must be confirmed in further cell cultures studies and human interventions concerning anti-doping regulations. • ECDY and DIO combinations significantly induced hypertrophy of C2C12 myotubes. • mTOR signaling is involved in combination mediated hypertrophy. • DIO induced hypertrophy is not mediated by the estrogen receptor but through androgen receptor. • ECDY and DIO are mediated by different receptors. • DIO has antiandrogenic activity and ECDY has antiestrogenic activity in yeast cell. [ABSTRACT FROM AUTHOR]

Diosgenin, a hydrolyzed product of phytosteroid saponin, has widely been studied for its medicinal properties. In an effort to find bioactive molecules, 25 novel thiazole‐fused diosgenin molecules have been synthesized by an efficient reaction protocol. The chemistry involves the Oppenauer oxidation followed by double bond isomerization in a one‐pot reaction, epoxidation, and the reaction of urea derivatives with the epoxyketone to synthesize the target compounds. These novel chimeric compounds were tested for their potential antimicrobial and cytotoxic properties. Antimicrobial studies against a panel of Gram‐positive and Gram‐negative led to the discovery of some of these molecules as narrow‐spectrum antimicrobial agents against Bacillus subtilis bacteria. In preliminary cytotoxicity studies, 2‐fluorophenyl derivative (10) inhibited the growth of several cell lines of the NCI‐60 cell line panels including >93 % inhibition of UO‐31 cell line. Furthermore, the hit antibacterial compounds are non‐toxic to human cancer cell lines, and the cytotoxic compound is not active against the bacterial strains, showing the selective therapeutic potential of the chimeric compounds. [ABSTRACT FROM AUTHOR]

Background: Podocyte injury is crucial in diabetic kidney disease (DKD) progression, and the mechanism remains unclear. The previous studies indicated Diosgenin played a key role in inhibiting podocyte injury progression. However, more research is needed to explore Diosgenin in inhibiting-molecular mechanisms in the process of podocyte injury. Methods: The content of Diosgenin in HeShenwan was detected by High-Performance Liquid Chromatography-mass spectrometry (HPLC-MS) method. The podocyte injury model was constructed by high glucose (HG)-induced mpc5 cells. The Cell Counting Kit-8 (CCK-8) assay was utilized to evaluate the activity of mpc5 cells. Pyroptosis in mpc5 cells was assessed using flow cytometry. Molecular docking studies of Diosgenin and Nrf2 were carried out using VINA 1.1.2 software. The levels of Superoxide dismutase (SOD), Malondialdehyde (MDA), Reactive oxygen species (ROS), Interleukin 1β (IL-1β), Interleukin 18 (IL-18), Lactate dehydrogenase (LDH) and High mobility group protein B1 (HMGB1) were assessed using related kits. The levels of Nod-like receptor protein 3 (NLRP3), Nuclear factor erythroid-2-related factor 2 (Nrf2), Cysteinyl aspartate specific proteinase 1 (Caspase-1), Gasdermin (GSDMD), and Apoptosis-associated speck-like protein contain a CARD (ASC) were detected. Results: The Diosgenin content was the highest in HeShenwan. The addition of Diosgenin enhanced HG-induced mpc5 cell activity and reduced oxidative stress and pyroptosis. Molecular docking results showed that Diosgenin bound to the Nrf2 through hydrogen bonds and hydrophobic interactions, regulating the Nrf2 expression. Overexpression of Nrf2 reduced the levels of NLRP3, reducing oxidative stress and inhibiting pyroptosis in mpc5 cells. Knockdown of Nrf2 reduced HG-induced mpc5 cell activity and increased pyroptosis and oxidative stress. Diosgenin inhibited pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway. Conclusion: Diosgenin inhibited HG-induced pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

A convenient protocol for the synthesis of A-ring lactones derived from cholesterol was developed. A lactone reduction–lactol separation–reoxidation sequence, applied to the inseparable mixture of diastereomeric lactones, allows the production of multigram amounts of each lactone in pure form. The same sequence applied to A-ring lactones derived from diosgenin produced similar results. A detailed NMR characterization of all the obtained lactones is also provided. X-ray diffraction corroborated the structure of the obtained compounds. [ABSTRACT FROM AUTHOR]

In this study, we compared the physiological effects of diets containing Dioscorea esculenta (Togedokoro), which is rich in diosgenin, Taro, and Jerusalem artichoke (Kikuimo) on lipid and blood glucose metabolism in KK-Ay mice, a hyperglycemic animal model. Diosgenin is known to have anti-obesity, blood glucose and lipid lowering effects. In addition, we also examined the effect of feeding KK-Ay mice diosgenin. Mice fed a diet of Togedokoro showed significantly increased total lipids and total bile acids in the feces, and significantly decreased serum total cholesterol levels. However, the significant effect on blood glucose levels observed in mice fed the Kikuimo diet was not observed in mice fed the Togedokoro diet. We speculate that this disparity may depend, in part, on the water-soluble dietary fiber content in each diet. In the diosgenin feeding experiment, diosgenin intake did not have a significant effect on glucose and lipid metabolism, but a significant increase in total lipids and total bile acids was observed in the feces. The results suggest that Togedokoro has a physiological effect on lipid metabolism, especially cholesterol metabolism, partly due to its diosgenin content. However, unlike the Kikuimo diet, the Togedokoro diet had no apparent effect on blood glucose metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly linked disorders due to their association with the aging population. Several studies have reported the beneficial effects of diosgenin and pterostilbene in treating neurodegenerative diseases. This study aimed to investigate the neuroprotective mechanisms of diosgenin and pterostilbene through molecular docking and dynamics studies and assess their pharmacokinetic parameters. Methods: To understand the link between diabetes and AD, molecular docking of the natural ligands diosgenin and pterostilbene against the specific targets of AD, including β-secretase, glycogen synthetase kinase beta (GSK-3β), gamma-secretase, tumor necrosis factor-alpha (TNF-ɑ), and interleukin-6 (IL-6) was done to find out their binding affinities to explain the molecular mechanisms involved in their neuroprotection. Further molecular dynamics studies and binding energy calculations for the ligands with GSK-3β and β-secretase were carried out to confirm their docking activities. Additionally, pharmacokinetic analysis of these two phytoconstituents was performed by the SWISSADME server. Results: Molecular docking and dynamics studies revealed the good docking activity of diosgenin and pterostilbene with the selected targets. Further, the two phytoconstituents revealed suitable pharmacokinetic parameters along with blood-brain barrier permeability, confirming their druggable nature. Conclusion: This research identified multiple neuroprotective pathways of diosgenin and pterostilbene that might be significant for treating diabetes-associated Alzheimer’s disease.

Ning Cui,1 Feng Ding2 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Feng Ding, Email dingfengkt@163.comBackground: Tumor-Node-Metastasis (TNM) stage of gastric cancer (GC) is one of the main factors affecting clinical outcome. The aim of this study was to explore the targets related to TNM stage of GC, and screening natural bioactive drug.Methods: RNA sequencing data of the TCGA-STAD cohort were downloaded from UCSC database. Genes associated with TNM staging were identified by weighted gene co-expression network analysis (WGCNA). Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (Xgboost), random forest (RF) and cytohubba plug-in of cytoscope were applied to screen hub genes. Natural bioactive ingredients were available from the HERB database. Molecular docking was used to evaluate the binding activity of active ingredients to the hub protein. CCK-8, flow cytometry, transwell and Western blot assays were used to analyze the effects of diosgenin on GC cells.Results: 898 TNM-related genes were screened out through WGCNA. Three genes associated with GC progression/prognosis were identified, including nuclear receptor subfamily 3 group C member 2 (NR3C2), solute carrier family 1 member 5 (SLC1A5) and FAT atypical cadherin 1 (FAT1) based on the machine learning algorithms and hub co-expression network analysis. Diosgenin had good binding activity with SLC1A5. SLC1A5 was highly expressed in GC and was closely associated with tumor stage, overall survival and immune infiltration of GC patients. Diosgenin could inhibit cell viability and invasive ability, promote apoptosis and induce cell cycle arrest in G0/G1 phase. In addition, diosgenin promoted cleaved caspase 3 expression and inhibited Ki67, cyclin D1, p-S6K1, and SLC1A5 expression levels, while the mTORC1 activator (MHY1485) reversed this phenomenon.Conclusion: For the first time, this work reports diosgenin may inhibit the activation of mTORC1 signaling through targeting SLC1A5, thereby inhibiting the malignant behaviors of GC cells.Keywords: gastric cancer, weighted gene co-expression network analysis, diosgenin, molecular docking, diosgenin

This study explores the bioconversion of diosgenin by Yarrowia lipolytica P01a, focusing on enhancing the antioxidant, antifungal, and herbicidal activities of the resulting extracts. The bioconversion process, involving glycosylation and hydroxylation, produced significant amounts of protodioscin and soyasaponin I. The extracts showed superior antioxidant activity, with up to 97.02% inhibition of ABTS· radicals and 33.30% inhibition of DPPH· radicals at 1000 mg L−1 of diosgenin. Antifungal assays revealed strong inhibitory effects against Botrytis cinerea, Alternaria sp., and Aspergillus niger, with maximum inhibition rates of 67.34%, 35.63%, and 65.53%, respectively. Additionally, the herbicidal activity of the bioconverted extracts was comparable to commercial herbicides, achieving 100% inhibition of seed germination in both monocotyledonous and dicotyledonous plants. These findings suggest that the Y. lipolytica P01a-mediated bioconversion of diosgenin could provide a sustainable and eco-friendly alternative for developing natural biofungicides and bioherbicides. [ABSTRACT FROM AUTHOR]

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR. [ABSTRACT FROM AUTHOR]

Background Diosgenin, extracted from Dioscorea esculenta, has been reported to decrease prostaglandin E2 (PGE2) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo (p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake (p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women. [ABSTRACT FROM AUTHOR]

Tribulus terrestris L. is an herbaceous plant belonging to the Zygophyllaceae family that is rich in diosgenin. It has anti-diabetes, anti-obesity, anti-Alzheimer, anti-inflammation, anti-leukemia, and anti-cancer activities and is a precursor of steroidal drugs. Various parts of medicinal plants have different potentials to synthesize natural compounds, so it is necessary to know which part contains higher amounts of natural compounds. Therefore, this research examined various organs of T. terrestris for their phytochemical composition and antioxidant and antibacterial properties. The highest levels of total phenolic and flavonoid content [per g of plant dry weight (DW)] were found in the leaves with 3.18 mg of gallic acid and 4.69 mg of rutin. The analysis of antioxidant activity revealed that the leaves and fruits had the highest and lowest activities (81.46 and 21.73 µmol Fe/g DW, respectively). The high-performance liquid chromatography-photodiode array (HPLC-PDA) analysis showed vanillic acid, rutin, rosmarinic acid, and chlorogenic acid as the main phenolic acids. Based on the results, diosgenin amounts varied from 1.65 to 7.78 mg/g DW, and the highest and lowest values were observed in fruits and stems, respectively. The leaf extracts exhibited outstanding antimicrobial activity against E. coli, S. aureus, and C. albicans. Overall, the leaves outperformed other organs, considering total phenol content, total flavonoid content, antioxidant activity, and antimicrobial activity. Although the fruits had higher diosgenin content, there was no significant difference between the leaves and fruits regarding this trait. Therefore, the leaves and fruits could be used as raw materials in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and oxidative stress play a crucial role in the pathogenesis of Alzheimer's disease (AD). The neuroprotective effects of the diosgenin derivative ML5 were investigated in vitro and in vivo, and the underlying mechanisms were explored. The results showed that ML5 ameliorated the study and cognitive deficits in beta-amyloid (Aβ1-42)-induced mouse model and protected neurons in the hippocampal region. In addition, ML5 attenuated H2O2-induced damage to SH-SY5Y cells and increased mitochondrial membrane potential and ATP levels. Western blot and immunofluorescence results showed that ML5 activated nuclear factor-erythroid-2-related factor 2 (NRF2) signaling pathway and increased the expression of NRF2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1). Our findings suggest that ML5 may be used as a therapeutic drug for AD treatment via targeting the NRF2 pathway, thereby exerting antioxidant and neuroprotective effects. [ABSTRACT FROM AUTHOR]

Background: Fenugreeks (Trigonella L. spp.), belonging to the legume family (Fabaceae), are well-known multipurpose crops that their materials are currently received much attention in the pharmaceutical and food industries for the production of healthy and functional foods all over the world. Iran is one of the main diversity origins of this valuable plant. Therefore, the aim of the present study was to explore vitamins, minerals, and fatty acids profile, proximate composition, content of diosgenin, trigonelline, phenolic acids, total carotenoids, saponins, phenols, flavonoids, and tannins, mucilage and bitterness value, and antioxidant activity of the seed of thirty populations belonging to the ten different Iranian Trigonella species. Results: We accordingly identified notable differences in the nutrient and bioactive compounds of each population. The highest content (mg/100 g DW) of ascorbic acid (18.67 ± 0.85‒22.48 ± 0.60) and α–tocopherol (31.61 ± 0.15‒38.78 ± 0.67) were found in the populations of T. filipes and T. coerulescens, respectively. Maximum content of catechin was found in the populations of T. teheranica (52.67 ± 0.05‒63.50 ± 0.72 mg/l). Linoleic acid (> 39.11% ± 0.61%) and linolenic acid (> 48.78 ± 0.39%) were the main polyunsaturated fatty acids, with the majority in the populations of T. stellata (54.81 ± 1.39‒63.46 ± 1.21%). The populations of T. stellata were also rich in trigonelline (4.95 ± 0.03‒7.66 ± 0.16 mg/g DW) and diosgenin (9.06 ± 0.06‒11.03 ± 0.17 mg/g DW). Conclusions: The obtained data provides baseline information to expand the inventory of wild and cultivated Iranian Trigonella species for further exploitation of rich chemotypes in the new foods and specific applications. [ABSTRACT FROM AUTHOR]

Health is the most important and primary thing in human life. Industry and human lifestyle development have both positive and negative impacts. One of the adverse consequences to be aware of is the proliferation of a variety of degenerative diseases. Sidaguri leaves (Sida rhombifolia L.) grow naturally on roadsides, grasslands, forests, fields, areas exposed to bright sunlight, and slightly sheltered places. It is a plant that is widespread in tropical areas ranging from lowlands to 1,450 m above sea level throughout the world. The plant's chemical content includes alkaloids, hypoparin, flavonoids, triterpenoids, sterols, sugars, vaccissinol, vaccissinone, betaine, and phenylalanineSidaguri leaves (Sida rhombifolia L.) are medicinal plants from the Malvaceae family. Almost all parts of this plant can be used for medicinal purposes, particularly in alternative medicine. This study aimed to determine the total saponin content in a 70% ethanol extract of Sida rhombifolia L. Sidaguri leaves, extracted using the maceration method and a 70% ethanol solvent. Using vanillin, H2SO4, and diosgenin as standards, we used UV-Vis spectrophotometry to find out how much total saponin was present. We measured antioxidant activity using the DPPH free radical scavenging test. The test showed that the 70% Sidaguri ethanol extract had a total saponin content of 196.28 ± 1.60 mg DE/g. It also had an IC50 value of 208.63 ± 7.73 mg/mL against DPPH in the antioxidant activity test. This shows the potential of Sidaguri leaf extract as a natural antioxidant. [ABSTRACT FROM AUTHOR]

A common approach to cancer therapy is the combination of a natural product with chemotherapy to overcome sustained cell proliferation and chemotherapy resistance obstacles. Diosgenin (DG) is a phytosteroidal saponin that is naturally present in a vast number of plants and has been shown to exert anti-cancer activities against several tumor cells. Herein, we assessed the chemo-modulatory effects of DG on volasertib (Vola) as a polo-like kinase 1 (PLK1) inhibitor and doxorubicin (DOX) in hepatocellular carcinoma (HCC) cell lines. DOX and Vola were applied to two human HCC cell lines (HepG2 and Huh-7) alone or in combination with DG. The cell viability was determined, and gene expressions of PLK1, PCNA, P53, caspase-3, and PARP1 were evaluated by RT-qPCR. Moreover, apoptosis induction was determined by measuring active caspase-3 level using ELISA method. DG enhanced the anticancer effects of Vola and DOX. Moreover, DG enhanced Vola- and DOX-induced cell death by downregulating the expressions of PLK1 and PCNA, elevating the expressions of P53 and active caspase-3. DG showed promising chemo-modulatory effects to Vola and DOX against HCC that may be attributed partly to the downregulation of PLK1 and PCNA, upregulation of tumor suppressor protein P53, and apoptosis induction. Thus, DG combination with chemotherapy may be a promising treatment approach for HCC. [ABSTRACT FROM AUTHOR]

Abstract Background Diosgenin is an important steroidal precursor renowned for its diverse medicinal uses. It is predominantly sourced from Dioscorea species, particularly Dioscorea zingiberensis. Dioscorea zingiberensis has an ability to accumulate 2–16% diosgenin in its rhizomes. In this study, a diverse population of 180 D. zingiberensis accessions was used to evaluate the genomic regions associated with diosgenin biosynthesis by the genome wide association study approach (GWAS). Results The whole population was characterized for diosgenin contents from tubers by gas chromatography mass spectrometry. The individuals were genotyped by the genotyping-by-sequencing approach and 10,000 high-quality SNP markers were extracted for the GWAS. The highest significant marker-trait-association was observed as an SNP transversion (G to T) on chromosome 10, with 64% phenotypic variance explained. The SNP was located in the promoter region of CYP94D144 which is a member of P450 gene family involved in the independent biosynthesis of diosgenin from cholesterol. The transcription factor (TF) binding site enrichment analysis of the promoter region of CYP94D144 revealed NAC TF as a potential regulator. The results were further validated through expression profiling by qRT-PCR, and the comparison of high and low diosgenin producing hybrids obtained from a bi-parental population. Conclusions This study not only enhanced the understanding of the genetic basis of diosgenin biosynthesis but also serves as a valuable reference for future genomic investigations on CYP94D144, with the aim of augmenting diosgenin production in yam tubers.

Ling Tang,1 Yu-Jia Wang,2 Yuan-Yuan Wang,2 Shu-Tong Li,3 Liang Kong,3 Xue-Tao Li,3 Ling-Ling Ma,1 Xiu-Xiu Liu1 1Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of ChinaCorrespondence: Ling-Ling Ma; Xiu-Xiu Liu, Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China, Email 826269013@qq.com; 1225949002@qq.comPurpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.Keywords: ovarian cancer, functional liposomes, paclitaxel, diosgenin, ROS-response, HA

Abstract Diosgenin as a potential phytoconstituent and steroidal saponin manifested significant anticancer agents against various cancers. To enhance its solubility and bioavailability in cancer treatment, we loaded diosgenin (PubChem CID: 99474) in poly(lactic-co-glycolide) (PLGA) nanoparticle coated with folic acid-chitosan (Da-PFC-NPs). The diosgenin nano-formulation was characterized and its antioxidant and anticancer properties were surveyed respectively. The obtained results illustrated that the Da-PFC-NPs were spherical and stable with a size of 218 nm and a polydispersity index of 0.41. The Da-PFC-NPs indicated potential free radical scavenging using ABTS and DPPH assay. Meanwhile, it demonstrated selective toxicity against the TUBO breast cancer cell with IC50 values of 104.45 μg/ml and did not show toxicity on normal cells (I929 cell line). The invivo funding exhibited that Da-PFC-NPs notably altered the liver enzymes (AST, ALT, ALP) and immunoglobulins (IgA, IgG, IgM). Besides that, different doses of Da-PFC-NPs (50 and 100 mg/kg) remarkedly enhance the expression of caspase 3 and decrease HER2 genes. In light of this experiment, we can conclude that Da-PFC-NPs have promise as novel carrier for improving the delivery of diosgenin in cancer therapy.

Background: Diosgenin is an important steroidal precursor renowned for its diverse medicinal uses. It is predominantly sourced from Dioscorea species, particularly Dioscorea zingiberensis. Dioscorea zingiberensis has an ability to accumulate 2–16% diosgenin in its rhizomes. In this study, a diverse population of 180 D. zingiberensis accessions was used to evaluate the genomic regions associated with diosgenin biosynthesis by the genome wide association study approach (GWAS). Results: The whole population was characterized for diosgenin contents from tubers by gas chromatography mass spectrometry. The individuals were genotyped by the genotyping-by-sequencing approach and 10,000 high-quality SNP markers were extracted for the GWAS. The highest significant marker-trait-association was observed as an SNP transversion (G to T) on chromosome 10, with 64% phenotypic variance explained. The SNP was located in the promoter region of CYP94D144 which is a member of P450 gene family involved in the independent biosynthesis of diosgenin from cholesterol. The transcription factor (TF) binding site enrichment analysis of the promoter region of CYP94D144 revealed NAC TF as a potential regulator. The results were further validated through expression profiling by qRT-PCR, and the comparison of high and low diosgenin producing hybrids obtained from a bi-parental population. Conclusions: This study not only enhanced the understanding of the genetic basis of diosgenin biosynthesis but also serves as a valuable reference for future genomic investigations on CYP94D144, with the aim of augmenting diosgenin production in yam tubers. [ABSTRACT FROM AUTHOR]

The successful isolation and characterization of diosgenin from the roots of C. forskohlii was accomplished by a combination of multiple analytical methods, including HPTLC, HPLC, UV, FT-IR, NMR, and mass spectroscopy. The primary goal of this research was to quantify the anticancer capabilities of the human ovarian SKOV-3 cancer cell line. The acquired compound is persisted to the preparative TLC using ethyl acetate and methanol (70:30 v/v) as eluents. Maximum absorbance was reported in the UV-Vis spectrum at 232 nm. The presence of the functional group was subsequently established by a variety of peaks in the FT-IR spectra, including 3450.06, 2947.74, 1236.38, 1054.99, and 894.11 cm-1. Structural elucidation of diosgenin had been performed through spectrum analysis for instance 13C and ¹H profoundly nuclear magnetic resources. The molecular formula C27H42O3 coincides with the parent molecular ion [M+] peak at m/z 414.63 g/mol, which is apparent in the mass spectra. The presently proceeding study's findings tend to show diosgenin has an astonishing cytotoxic action (IC50:75.47 µg/ml) on human ovarian cancer cells. [ABSTRACT FROM AUTHOR]

In recent decades, high consumption of antibiotics has led to substantial discharge into the water bodies, which may harm the non-target organisms in the aquatic environment by inducing oxidative stress. Increased oxidative stress leads to DNA damage, and disrupts cellular homeostasis and other cellular activities. Plant compounds can be potential therapeutics for various diseases, including antibacterial, anti-inflammation, and antioxidant activity. Nano-based drug formulations have also shown promising antibacterial and antioxidant activity. In this study, diosgenin-conjugated zinc oxide nanoparticles (ZnONPs) are synthesized to evaluate their antibacterial and antioxidant activity. Diosgenin-ZnONPs exhibited an average size of 21–25 nm. Diosgenin-ZnONPs also showed antibacterial efficacy similar to streptomycin against Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Citrobacter freundii. In vitro antioxidant investigations, diosgenin-ZnONPs showed effective free radicals scavenging activity. Furthermore, in vivo toxicity study, diosgenin-ZnONPs did not exhibit any toxicity in zebrafish embryos and larvae at 1.25–10 µg/ml concentrations. Antioxidant studies on zebrafish larvae indicated that diosgenin-ZnONPs significantly reduced streptomycin-induced oxidative stress by increasing antioxidant enzyme levels in zebrafish larvae. In Real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) studies, there was a significant upregulation of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In summary, our findings indicate that diosgenin-ZnONPs can act as an effective antibacterial and antioxidant agent. [ABSTRACT FROM AUTHOR]

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. [ABSTRACT FROM AUTHOR]

Diosgenin, an essential dietary steroidal sapogenin, possess multiple pharmacological activities. This study aimed to assess the effects of diosgenin on periodontitis and elucidate the mechanisms. Lipopolysaccharide (LPS)‐stimulated human periodontal ligament stem cells (hPDLCs) and a Porphyromonas gingivalis (P.g) plus ligation‐induced animal model were used for in vitro and in vivo studies, respectively. Inflammatory responses, nuclear factor κ‐B (NF‐κB) signaling and osteogenesis‐related markers were measured both in LPS‐stimulated hPDLSCs and in gingival tissue of periodontitis rats. Treatment with diosgenin significantly inhibited the production of tumor necrosis factor α (TNF‐α), interleukin (IL)‐1β, and interleukin (IL)‐6 and the activation of NF‐κB pathway in LPS‐stimulated hPDLSCs. Further, treatment with diosgenin enhanced the expression of osteoblast‐related genes and increased the osteogenic differentiation capacity. Further, activation NF‐κB pathway largely abolished the protective effects of diosgenin. Consistent with the in vitro studies, in vivo studies showed that administering diosgenin to periodontitis rats significantly lowered the levels of the TNF‐α, IL‐1β, and IL‐6 and the inflammatory transcription factor NF‐κB in gingival tissue. In addition, osteoblast‐related genes were promoted. Diosgenin attenuates periodontitis by adjusting NF‐κB signaling to inhibit inflammatory effects and promoting osteogenesis, suggesting diosgenin might be developed as a therapeutic strategy for treating periodontitis in the future. [ABSTRACT FROM AUTHOR]

Medicinal plants are rich sources for treating various diseases due their bioactive secondary metabolites. Fenugreek (Trigonella foenum-graecum) is one of the medicinal plants traditionally used in human nutrition and medicine which contains an active substance, called diosgenin, with anticancer properties. Biosynthesis of this important anticancer compound in fenugreek can be enhanced using eliciting agents which involves in manipulation of metabolite and biochemical pathways stimulating defense responses. Methyl jasmonate elicitor was used to increase diosgenin biosynthesis in fenugreek plants. However, the molecular mechanism and gene expression profiles underlying diosgening accumulation remain unexplored. In the current study we performed an extensive analysis of publicly available RNA-sequencing datasets to elucidate the biosynthesis and expression profile of fenugreek plants treated with methyl jasmonate. For this purpose, seven read datasets of methyl jasmonate treated plants were obtained that were covering several post-treatment time points (6–120 h). Transcriptomics analysis revealed upregulation of several key genes involved in diosgenein biosynthetic pathway including Squalene synthase (SQS) as the first committed step in diosgenin biosynthesis as well as Squalene Epoxidase (SEP) and Cycloartenol Synthase (CAS) upon methyl jasmonate application. Bioinformatics analysis, including gene ontology enrichment and pathway analysis, further supported the involvement of these genes in diosgenin biosynthesis. The bioinformatics analysis led to a comprehensive validation, with expression profiling across three different fenugreek populations treated with the same methyl jasmonate application. Initially, key genes like SQS, SEP, and CAS showed upregulation, followed by later upregulation of Δ24, suggesting dynamic pathway regulation. Real-time PCR confirmed consistent upregulation of SQS and SEP, peaking at 72 h. Additionally, candidate genes Δ24 and SMT1 highlighted roles in directing metabolic flux towards diosgenin biosynthesis. This integrated approach validates the bioinformatics findings and elucidates fenugreek's molecular response to methyl jasmonate elicitation, offering insights for enhancing diosgenin yield. The assembled transcripts and gene expression profiles are deposited in the Zenodo open repository at https://doi.org/10.5281/zenodo.8155183. [ABSTRACT FROM AUTHOR]

Key message: Both bacterial and fungal endophytes exhibited one or more plant growth-promoting (PGP) traits. Among these strains, the Paenibacillus peoriae SYbr421 strain demonstrated the greatest activity in the direct biotransformation of tuber powder from D. nipponica into diosgenin. Endophytes play crucial roles in shaping active metabolites within plants, significantly influencing both the quality and yield of host plants. Dioscorea nipponica Makino accumulates abundant steroidal saponins, which can be hydrolyzed to produce diosgenin. However, our understanding of the associated endophytes and their contributions to plant growth and diosgenin production is limited. The present study aimed to assess the PGP ability and potential of diosgenin biotransformation by endophytes isolates associated with D. nipponica for the efficient improvement of plant growth and development of a clean and effective approach for producing the valuable drug diosgenin. Eighteen bacterial endophytes were classified into six genera through sequencing and phylogenetic analysis of the 16S rDNA gene. Similarly, 12 fungal endophytes were categorized into 5 genera based on sequencing and phylogenetic analysis of the ITS rDNA gene. Pure culture experiments revealed that 30 isolated endophytic strains exhibited one or more PGP traits, such as nitrogen fixation, phosphate solubilization, siderophore synthesis, and IAA production. One strain of endophytic bacteria, P. peoriae SYbr421, effectively directly biotransformed the saponin components in D. nipponica. Moreover, a high yield of diosgenin (3.50%) was obtained at an inoculum size of 4% after 6 days of fermentation. Thus, SYbr421 could be used for a cleaner and more eco-friendly diosgenin production process. In addition, based on the assessment of growth-promoting isolates and seed germination results, the strains SYbr421, SYfr1321, and SYfl221 were selected for greenhouse experiments. The results revealed that the inoculation of these promising isolates significantly increased the plant height and fresh weight of the leaves and roots compared to the control plants. These findings underscore the importance of preparing PGP bioinoculants from selected isolates as an additional option for sustainable diosgenin production. [ABSTRACT FROM AUTHOR]

Rationale: Emerging evidence indicates that persistent alcohol consumption escalates psychosocial trauma achieved by social defeat stress (SDS)-induced neurobiological changes and behavioral outcomes. Treatment with compounds with neuroprotective functions is believed to reverse ethanol (EtOH)-aggravated SDS-induced behavioral impairments. Objectives: We investigated the outcomes of diosgenin treatment, a phytosteroidal sapogenin in mice co-exposed to repeated SDS and EtOH administration. Methods: During a period of 14 days, SDS male mice were repeatedly administered EtOH (20%, 10 mL/kg) orally from days 8–14 (n = 9). Within days 1–14, SDS mice fed with EtOH were simultaneously treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) by oral gavage. Locomotor, cognitive-, depressive-, and anxiety-like behaviors were assessed. Adrenal weight, serum glucose, and corticosterone levels were assayed. Brain markers of oxido-inflammatory, neurochemical levels, monoamine oxidase-B, and acetylcholinesterase activities were measured in the striatum, prefrontal cortex, and hippocampus. Results: The anxiety-like behavior, depression, low stress resilience, social, and spatial/non-spatial memory decline exhibited by SDS mice exposed to repeated EtOH administration were alleviated by diosgenin (25 and 50 mg/kg) and fluoxetine, illustrated by increased dopamine and serotonin concentrations and reduced monoamine oxidase-B and acetylcholinesterase activities in the prefrontal cortex, hippocampus, and striatum. Diosgenin attenuated SDS + EtOH interaction induced corticosterone release and adrenal hypertrophy, accompanied by reduced TNF-α, IL-6, malondialdehyde, and nitrite levels in the striatum, prefrontal cortex, and hippocampus. Diosgenin increased glutathione, superoxide dismutase, and catalase levels in SDS + EtOH-exposed mice. Conclusions: Our data suggest that diosgenin reverses SDS + EtOH interaction-induced behavioral changes via normalization of hypothalamic–pituitary–adrenal axis, neurochemical neurotransmissions, and inhibition of oxidative and inflammatory mediators in mice brains. [ABSTRACT FROM AUTHOR]

This article discusses a study on the anti-angiogenic properties of diosgenin saponin from fenugreek using zebrafish embryos as a model organism. The study found that diosgenin inhibits angiogenesis in zebrafish embryos by suppressing VEGF-A expression and may also be linked to the inhibition of the NF-¿B pathway. The results suggest that natural substances like diosgenin have potential therapeutic effects against diseases characterized by pathological angiogenesis, such as cancer. However, the study has limitations, including a limited dose range, a brief treatment period, and reliance on a single model organism. Further research is needed to understand the underlying mechanisms and their clinical relevance. [Extracted from the article]

Inflammatory bowel disease (IBD) is a growing global health problem. IBD is commonly prevalent in Europe and America and the incidence rate in Asia is on the rise due to altered dietary structure. Diosgenin is a natural steroidal saponin derived from Dioscorea plants. Diosgenin is the main active ingredient of some Chinese medicines which are mainly used to treat coronary heart disease, angina and hyperlipidemia. Recently, growing evidence has exhibited a crucial role of diosgenin and dioscin in alleviating IBD in multiple ways. However, the precise mechanism of diosgenin against IBD needs further exploration.In this study, network pharmacological and systematic bioinformatic analyses were performed to investigate the diosgenin's targets against IBD. 71 targets such as SRC, TNF and STAT3 were identified as overlapped genes between diosgenin and IBD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis exhibited their involvement in the tyrosine kinase signaling pathway and its membrane receptors. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance and its downstream Ras-MAPK pathway and PI3K-Akt pathway might become the mechanism of diosgenin against IBD. In addition, molecular docking analysis showed that diosgenin has the massive potential of direct binding to tyrosine kinase and its receptors such as SRC, EGFR, FGFR1 and VEGFR. The results above collectively provided evidence that diosgenin is a promising nutraceutical food against IBD.

Introduction: In Alzheimer's disease (AD), neural circuit disconnection primarily causes memory dysfunction, which leads to the hypothesis that repairing neural networks may be an appropriate treatment strategy for AD. We previously found that diosgenin stimulated neurite regeneration and synapse formation in AD model mice, and diosgenin-rich Yam extract enhanced cognitive function in healthy people and normal mice. In this study, we investigated the efficacy and safety of Yam extract in patients with mild cognitive impairment (MCI) and mild AD. Methods: Patients were administered either diosgenin-rich Yam extract or placebo, respectively, for 24 weeks. The primary outcome was cognitive function, which was evaluated using the Mini Mental State Examination Japanese version (MMSE-J), Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog), and verbal fluency test; the secondary outcomes were plasma biomarker levels [neurofilament light chain (NfL); axonal marker, glial fibrillary acidic protein levels; reactive astrocyte marker, and the Aβ42/40 ratio; marker of brain Aβ]. Results: Diosgenin-rich Yam extract improved the ADAS-Cog Praxis domain score and plasma NfL (12 to 24 weeks) in all patients. The number of patients with improved/maintained ADAS-Cog total, Praxis or Memory scores was high in the Yam extract group, but not in placebo group. Divided by severity of pathology, diosgenin-rich Yam extract also improved the total and Memory domain in ADAS-Cog, and plasma NfL levels in patients with MCI. In the Yam extract group, improvement of MMSE-J was related to plasma Aβ42/40 increase, and improvement of plasma NfL was related to better MMSE-J. Conclusion: Treatment with diosgenin-rich Yam extract for 24 weeks resulted in modest cognitive improvement and a decrease in plasma NfL levels, which may suggest axonal protection in the brain.

Post-traumatic stress disorder (PTSD) is a mental disorder linked to neurochemical, hypothalamic-pituitary-adrenal (HPA)-axis dysregulations, inflammatory and pro-oxidant challenges in response to traumatic events. It is one of the leading causes of neurocognitive declines, hence prompting the need for a pharmacological intervention. However, the impact of diosgenin, a naturally occurring steroidal saponin with adaptogenic-like action, on PTSD-induced neuropsychiatric disturbances and its underlying mechanisms are unknown. In this study, we investigated the outcome of diosgenin treatment in a multimodal traumatic, single prolonged stress (SPS)-induced PTSD in mice. Following the SPS-induced 7 days of PTSD, mice (n = 9) were thereafter treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally from days 8–20 (14 days). Locomotory, cognitive-, depressive- and anxiety-like behaviors were investigated. We assayed for changes in adrenal weight, serum glucose and corticosterone concentrations. Neurochemical, inflammatory, oxido-nitrergic dysfunctions and monoamine oxidase-B and acetylcholinesterase activities, were measured in the striatum, prefrontal-cortex and hippocampus. The results revealed that the SPS challenge inhibited locomotor, spatial/non-spatial memory functions, increased anxiety and depressive-like features, which were reversed by diosgenin. Diosgenin reduced SPS-induced increased monoamine oxidase-B, acetylcholinesterase activities, TNF-α, IL-6, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. Antioxidants such as glutathione, superoxide-dismutase, and catalase levels in SPS-mice brains were increased by diosgenin. Moreover, diosgenin attenuated SPS-induced hyper-HPA-axis mediation of PTSD by decreasing serum corticosterone, glucose levels and adrenal gland hypertrophy. Herewith, we suggest that diosgenin convenes adaptogenic-like protection against mice exposed to PTSD by enhancing antioxidant machinery, neurochemical modulations, and inhibition of oxido-nitrergic, inflammatory, and HPA-axis dysfunctions.

Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.

Introduction. Results of original research carried out by means of high performance thin layer chromatography (HPTLC) of various plant samples (air-dry raw material) of Dioscoreaceae, Ranunculaceae, Fabaceae, Melanthiaceae, Scrophulariaceae families are presented in this article.Aim. To carry out preliminary qualitative analysis by HPTLC method of steroidal sapogenins composition in hydrolyzed extracts, obtained from vegetative samples of above-ground and underground organs of some Dioscoreaceae, Ranunculaceae, Fabaceae, Melanthiaceae, Scrophulariaceae families.Materials and methods. Extraction from pre-dehydrated raw materials was carried out with 50 % aqueous isopropanol (c.p.) in an ultrasonic bath, followed by acidic hydrolysis of O-glycoside bonds, evaporation and redissolution of dry residue in 99 % methanol (c.p.); purification from suspended solids by filtering through filters with 20 µm perforation diameter. HPTLC was performed on apparatus complex CAMAG (Switzerland) using HPTLC Aluminium sheets Silica gel 60 F254 plates 20 × 20 cm, which were cut to the size 20 × 10 cm.Results and discussion. After scanning densitometry at 254 nm, we found that the separation of isopropanol extracts, followed by redissolution in strong methanol in this solvent system allows a fairly acceptable separation and identification of the compounds studied. Comparison of the tracks of plant extracts was performed with standard samples of steroid sapogenins, whose methanol solutions were applied to one stain-strobe of track 1, provided that they had different Rf indices and coloration after derivatization.Conclusion. Diosgenin was identified in plant extracts of rhizomes and roots of Dioscorea nipponica and Dioscorea caucasica and in seeds of Trigonella foenum-graecum preliminarily. Sarsasapogenin was verified in extracts of fruits of Sophora japonica, tigogenin in extracts of seeds of Trigonella foenum-graecum, herb of Pulsatilla patens and herb of Veronica officinalis. Yamogenin was detected in extracts of seeds of Trigonella foenum-graecum and herb of Veronica officinalis. This work is exploratory in nature, assessing the presence of certain saponins by their sapogenins in selected extracts. We will optimize the HPLC separation procedure and choose other detection methods to unambiguously assess the co-presence of the studied sapogenins with approximately the same staining shades after derivatization and matching retention indices: there are pairs of steroidal sapogenins that have the same retention, we decided to group them in mixtures so that there would be separation within the group and subsequent comparison with the original extracts would make it possible to identify those or other sapogenins in such extracts.

Tribulus terrestris L. is an annual herb, known worldwide as a noxious weed or as medicinal plant. Phytochemicals from Tribulus terrestris are well known in area of fitness suplements for muscle gain, in medicine, where those phytochemicals are used to treat cancer, obesity, diabetes, dyslipidemia, hypercholesterolemia, inflammatory diases and especially fertility in both women and man. Animal studies showed an increase in ovulation, an improvement in spermatogenesis and increase in the number of sperm, lowering serum glucose, triglycerides and cholesterol in diabetic mice.

Diosgenin (DSG) is a phytosterol saponin mainly found in Dioscorea zingiberensis C.H. Wright. It has shown promising results in treating various diseases such as cancer, diabetes, arthritis, asthma, and cardiovascular diseases. Diosgenin is also an important medicinal chemical for synthesizing various steroid medicines. The production of diosgenin by acid hydrolysis generates a large amount of wastewater, leading to severe environmental pollution. However, producing diosgenin through microbial fermentation can effectively reduce environmental pollution. Numerous studies have demonstrated that various microorganisms can produce diosgenin via solid-state fermentation. Nevertheless, due to the complexity, high maintenance costs, uneven heat production, and other characteristics of solid-state fermentation, it is not commonly used in the industrial production of diosgenin. In contrast, liquid fermentation offers advantages such as simple operation, easy maintenance, and stable fermentation, making it more suitable for the industrial production of diosgenin. However, few studies have focused on producing diosgenin using liquid fermentation. In this study, endophytic Bacillus licheniformis SYt1 was used to produce diosgenin via liquid fermentation, with Dioscorea tuber powder as a substrate. Soxhlet extraction and silica gel column chromatography were employed to identify the diosgenin from the liquid fermentation products. Suitable fermentation conditions were screened and identified. The environmental variables that significantly affect the diosgenin yield were determined by the Plackett–Burman design (P-BD) with eight factors. The three factors (peptone, yeast extract powder and inorganic salt) with the greatest influence on the diosgenin yield were selected and further optimized using a response surface methodology (RSM). The final culture conditions were determined to be 35.79 g/L of peptone, 14.56 g/L of yeast extract powder, and 1.44 g/L of inorganic salt. The yield of diosgenin under these conditions was 132.57 mg/L, which was 1.8 times greater than the yield under pre-optimization conditions. This effective, clean, and promising liquid fermentation method possesses the potential to replace the traditional acid hydrolysis method for the industrial production of diosgenin.

Background Information: Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)‐spirost‐5‐en‐3β‐ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored. Results: This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)‐spirost‐5‐en‐3β‐yl β‐D‐glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside (3), and diosgenin 2‐amino‐2‐deoxy‐β‐D‐glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected. Conclusions: Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non‐tumour cells. Significance: This study evidences the pro‐apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines. [ABSTRACT FROM AUTHOR]

Diosgenin, a natural steroidal sapogenin, has recently attracted a high amount of attention, as an effective anticancer agent in ovarian cancer. However, diosgenin mediated anticancer impacts are still not completely understood. Thus, the present study evaluated the effect of diosgenin on the proliferation, apoptosis, and metastasis of ovarian cancer cells. OVCAR‐3 and SKOV‐3 cells were treated with diosgenin, cellular viability was assessed by MTT assay and apoptosis was measured by ELISA and evaluated the protein expression levels of apoptotic markers through western blotting. Cell migration was examined by measuring the mRNA levels of genes involved in the cell invasion. The protein expression levels of main components of PI3K signaling were evaluated via western blotting. Diosgenin led to significant inhibition of cellular proliferation in a dose‐dependent manner. It also induced apoptosis through upregulating pro‐apoptotic markers and downregulating antiapoptotic mediators. In addition, OVCAR‐3 cells exposure to diosgenin decreased cell migration and invasion. More importantly, diosgenin downregulated the expression levels of main proteins in PI3K signaling including PI3K, Akt, mTOR, and GSK3. Diosgenin inhibited the proliferation and migration of OVCAR‐3 ovarian cancer cells and induced apoptosis, which may be mediated by targeting PI3K signaling. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obstruct pharmacokinetics and low bioavailability of diosgenin (DG) and emodin (ED) are major limitations for their therapeutic success in several inflammatory diseases. Nanoencapsulation of both drugs will promisingly overcome these limitations. Herein, polylactic-co-glycolic acid (PLGA) was used for nanoformulation of diosgenin- and emodin-loaded PLGA nanoparticle (DGn and EDn) via modified solvent-emulsion-diffusion-evaporation method. Functional stability of prepared nanoparticles and in vitro physiological characterization including mean particle sizes distribution, polydispersity index, surface zeta potential, and morphological examinations were performed. Moreover, drug loading and encapsulation efficiency were also evaluated by measuring drug concentration through spectroscopy and HPLC method. Both drug nanoformulations demonstrated functional drug stability, 200–270 nm sizes with homogeneous particle distribution, negative surface zeta potential stability, and uniform spherical morphology. Moreover, nanoparticles showed in vitro controlled drug release pattern over 24 h with 40–70% of drug depletion. Pharmacokinetics analysis was performed on sixteen rats equally distributed in four groups (DG, ED, DGn, and EDn). Pure drugs and nanoformulations were orally (10 mg/kg) administrated to animal model, and pharmacokinetic profiles of both drugs were evaluated. PLGA nanoparticles were significantly able to alter the pharmacokinetics of DG, while little improvement was observed for ED. Consequently, changes in pharmacokinetics of both drugs are attributed to size and surface characteristics of nanoparticles. DGn and EDn subsidize increased mean plasma residence time and maximize area under curve with decreased drug clearance rate. Resulting in vitro characteristics and in vivo pharmacokinetics data reveal the efficacy of DGn and EDn to be suitable nano-drug delivery modalities with improved bioavailability and pharmacological strength. [ABSTRACT FROM AUTHOR]