Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Preparation of Diosgenin from Dioscorea zingiberensis： A Review / 中国实验方剂学杂志

Direct acid hydrolysis of Dioscorea zingiberensis rhizomes for preparation of diosgenin is wildly used in the traditional industry， which uses a large amount of inorganic acid catalysts， with high wastewater discharge and serious environmental pollution. Therefore， exploring clean and efficient preparation methods and processes has become an inevitable choice to realize the sustainable development of industrial production of diosgenin. Herein， the author reviewed and analyzed the research progress and problems of enzymatic hydrolysis， microbial transformation and modified acid hydrolysis in the preparation of diosgenin from D. zingiberensis rhizomes during the last ten years， and their application prospects are analyzed. Enzymatic hydrolysis has mild reaction conditions， but the yield of diosgenin is low， the economic cost is high， and the purification process of active enzyme is complicated. Microorganism shows specific activity to the substrate and high efficiency for diosgenin production， and microbial transformation is clean and environmentally friendly， but microbial transformation is time-consuming and the metabolic intermediates are complicated. For the modified acid hydrolysis， two-phase acid hydrolysis can reduce the amount of acid catalyst， and sulfonic acid-functionalized ionic liquid displays good recyclable performance by replacing the traditional inorganic acid， however， the wastewater discharge should still be considered. Solid acid catalysts are non-corrosive and easy to be recycled， but the need to use ethanol as the reaction solvent has certain safety hazards， and the catalyst preparation process is cumbersome. In conclusion， exploring clean and efficient conversion methods is an important research trend for preparation of diosgenin from D. zingiberensis rhizomes. For the enzymatic hydrolysis， the key glycoside hydrolases in the bioconversion process should be explored in depth， the conversion pathway of enzymatic saponins and enzyme specificity should be fully elucidated， and efforts should be made to improve the efficiency of enzymatic hydrolysis. For the microbial transformation， we should accelerate its industrial application process based on selecting and breeding efficient transformation strains， and optimizing stable transformation systems and processes， and in-depth investigation of the mechanism of microbial transformation， fully elucidating the specific key hydrolases and its catalytic properties， and striving to improve the efficiency of microbial transformation. For the modified acid hydrolysis， novel acid catalytic system with simple structure， stable performance and good biodegradability should be explored and applied， which can effectively solve the problems of environmental pollution and production safety.

Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease / 中国中药杂志

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Correlation Analysis Between Color and Content Changes of Five Components of Wine-processed Polygonatum kingianum Rhizoma During Processing / 中国实验方剂学杂志

ObjectiveTo study the correlation between the appearance color of the sample powder and the contents of five non-sugar components of wine-processed Polygonatum kingianum rhizoma during processing， and determine the feasibility of color quantitative value for judging the processing end point of the wine-processed products， and to screen steroidal saponins and flavonoids as markers for the control of the wine-processed products during processing. MethodThe changes of apparent color of the sample powder at different time points of the wine-processed products were measured by colorimeter， and the total color value （E*ab），the total color difference value （ΔE*ab） were calculated. The contents of protodioscin， pseudoprotodioscin， dioscin， diosgenin and narcissoside in the wine-processed products （No. S0-S10） after processing for 0， 5， 10， 14， 16， 18， 20， 22， 24， 26， 28 h were determined simultaneously by ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS）. Cluster analysis （HCA）， principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA） and Pearson correlation analysis were used to analyze the chromaticity value of the sample powder and the content of the five components. ResultDuring processing of wine-processed P. kingianum rhizoma， E*ab of the sample powder showed a decreasing trend and the apparent color changed from light yellow to lacquer black. The contents of the five components showed an obvious dynamic change trend with time， and showed different laws. HCA results showed that the processing process of the wine-processed products could be divided into three stages， namely， the early stage （samples S0-S1）， the middle stage （samples S2-S4） and the late stage （samples S5-S10）. PCA results showed that there were significant differences in color and contents of five components between the initial sample and the processing samples， and the difference between samples S8 and S9 was the smallest. PLS-DA results showed that the variable importance in the projection （VIP） values of b*， the contents of pseudoprotodioscin， narcissoside， diosgenin and protodioscin were >1. Pearson correlation analysis showed that the contents of protodioscin， diosgenin and narcissoside had a significant positive correlation with E*ab （P<0.01）， the content of diosgenin had a significant negative correlation with E*ab （P<0.01）， while the content of pseudoprotodioscin had no linear correlation with E*ab. ConclusionIn the process of wine-processed P. kingianum rhizoma， there is a certain linear correlation between color quantitative value and chemical composition， and the processing end point can be determined objectively. It can be considered that protodioscin can be used as a marker for the control of the wine-processed products.

Research on anti-tumor natural product diosgenin / 中国中药杂志

Diosgenin is widely distributed in many plants, such as Polygonatum sibiricum, Paris polyphylla, Dioscorea oppositifolia, Trigonella foenum-graecum, Costus speciosus, Tacca chantrieri, which has good anti-tumor activity and preferable effects on preventing atherosclerosis, protecting the heart, treating diabetes, etc. This review combed through the anti-tumor mechanisms of diosgenin encompassing lung, breast, gallbladder, liver, oral cavity, stomach, bladder, bone marrow, etc. Besides, it was discovered that diosgenin mainly exerts its effect by inhibiting tumor cell migration, suppressing tumor cell proliferation and growth, and inducing cell apoptosis. However, problems like low yield and bioavailability frequently exist in natural diosgenin. This review introduced methods such as structural modification, dosage form optimization and combination medication to improve the yield and anti-tumor activity of diosgenin. Via the summary of this paper, it is expected to provide theoretical basis for the rational exploitation and utilization of diosgenin.

Pathway design and key enzyme analysis of diosgenin biosynthesis / 生物工程学报

As a naturally occurring steroid sapogenin, diosgenin acts as the precursor of hundreds of steroid medicines, and thereby has important medicinal value. Currently, industrial production of diosgenin relies primarily on chemical extraction from plant materials. Clearly, this strategy shows drawbacks of excessive reliance on plant materials and farmland as well as environment pollution. Due to development of metabolic engineering and synthetic biology, bio-production of diosgenin has garnered plenty of attention. Although the biosynthetic pathways of diosgenin have not been completely identified, in this review, we outline the identified biosynthetic pathways and key enzymes. In particular, we suggest heterologous biosynthesis of diosgenin in Saccharomyces cerevisiae. Overall, this review aims to provide valuable insights for future complete biosynthesis of diosgenin.

Protective Effect Of Diosgenin On Streptozotocin Induced Diabetic Nephropathy In Experimental Rats

Diabetes mellitus is a multifactorial metabolic disorder associated with the diabetes related vascular diseases. Oxidative stress along with inflammation is the Key factor leading to diabetic complications. Present study was designed to investigate the protective role of diosgenin, a steroidal saponin, in diabetes induced early kidney injury and oxidative stress markers and histopathological changes in kidney of diabetic rats, induced by single intra-peritoneal injection of streptozotocin (55 mg/kg weight (b.w.). After 72 hrs, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for four weeks. At the end of the experiment, diabetic rats showed a significant increase in the levels of plasma glucose, glycosylated hemoglobin with a significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione, and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in kidney tissues of diabetic rats. Oral administration of diosgenin to diabetic rats considerably shrivelled the plasma glucose and exaggerated the endocrine level supported a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings recommend that diosgenin may have a helpful role against excretory organ harm evoked by aerobic stress within the diabetic state.

UPLC quantitative analysis of Paridis Rhizoma and its comprehensive evaluation of chemical quality / 中草药

Objective: To explore the content of seven active compounds in 10 kinds of medicinal herbs of Paridis Rhizoma, and to carry out chemical composition integration evaluation, which provides a scientific basis for its resource utilization. Methods: A total of 55 batches of medicinal herbs were collected from different areas, and their saponins I, saponins II, saponins VI, saponins VII, diosgenin, saponins H, and saponins were determined by ultra performance liquid chromatography. Then, TOPSIS model was used to normalize the content results and integrate the multi-indicator data to obtain a comprehensive index of content of seven active compounds. Results: The 10 kinds of medicinal herbs of Paridis Rhizoma were ranked from long to low was Paris forrestii (Ci = 0.275 5) > Paris polyphylla (Ci = 0.273 2) > Paris daliensis (Ci = 0.269 8) > Paris polyphylla var. yunnanensis (Ci = 0.244 5) > Paris vietnamensis (Ci = 0.234 5) > Paris polyphylla var. stenophylla (Ci = 0.159 1) > Paris thibetica (Ci = 0.141 6) > Paris polyphylla var. nana (Ci = 0.117 8) > P. vietnamensis (Ci = 0.115 1) > Paris mairei (Ci = 0.114 9), indicating that comprehensive quality of 10 kinds of medicinal herbs of Paridis Rhizoma had a large gap. The overall quality of P. forrestii, P. polyphylla and P. daliensis are better than that of P. polyphylla var. yunnanensis, and the comprehensive evaluation results of P. vietnamensis and P. polyphylla var. yunnanensis are closer that can be used as an alternative species for resource mining. Conclusion: The comprehensive evaluation of chemical quality has certain reference value for the quality evaluation of Paridis Rhizoma

Phytochemical and pharmacological activities of Solanum surattense Burm. f.–A review

Medicinal plants are unique in having the ability to produce diverse chemical compounds with remarkable biologicalactivities. Investigations of medicinal plants resulted in the discovery of a large number of bioactive compoundswith excellent therapeutic properties. Solanum surattense, a perennial wild growing medicinal herb, is widely usedin the traditional medicine. Exhaustive literature availability reveals the presence of phytochemical compounds fromdifferent plant parts like roots, stem, leaves, fruits, and seeds reported to possess a wide range of pharmacologicalactivities like hepatoprotective, cardioprotective, antiasthmatic and mosquito repellents properties. Intensiveinvestigation on phytochemical constituents resulted in isolation of alkaloid and steroidal compounds solasonoine,solamargine, campesterol, and diosgenin. Evaluation of therapeutic activity of isolated compounds proved as potentones with reference to the standard. Current literature on the pharmacological activity of S. surattense confirms thescientific validation of folklore claims and its traditional use to cure various ailments. Present review is undertaken tosummarize all the available information on pharmacological activities, which provide a baseline support for furtherexploration of its unexplored therapeutic effects like immunomodulation, antipiles activity, antianaphylactic activity,and sexual behavior claimed by folklore.

Phytochemical and pharmacological activities of Solanum surattense Burm. f.–A review

Medicinal plants are unique in having the ability to produce diverse chemical compounds with remarkable biologicalactivities. Investigations of medicinal plants resulted in the discovery of a large number of bioactive compoundswith excellent therapeutic properties. Solanum surattense, a perennial wild growing medicinal herb, is widely usedin the traditional medicine. Exhaustive literature availability reveals the presence of phytochemical compounds fromdifferent plant parts like roots, stem, leaves, fruits, and seeds reported to possess a wide range of pharmacologicalactivities like hepatoprotective, cardioprotective, antiasthmatic and mosquito repellents properties. Intensiveinvestigation on phytochemical constituents resulted in isolation of alkaloid and steroidal compounds solasonoine,solamargine, campesterol, and diosgenin. Evaluation of therapeutic activity of isolated compounds proved as potentones with reference to the standard. Current literature on the pharmacological activity of S. surattense confirms thescientific validation of folklore claims and its traditional use to cure various ailments. Present review is undertaken tosummarize all the available information on pharmacological activities, which provide a baseline support for furtherexploration of its unexplored therapeutic effects like immunomodulation, antipiles activity, antianaphylactic activity,and sexual behavior claimed by folklore.

Comparison of Diosgenin Content in Wild Dioscorea zingiberensis from Different Habitats / 中国药房

OBJECTIVE：To establish a method for the content determination of diosgenin in Dioscorea zingiberensis，and to compare the contents of diosgenin in wild D. zingiberensis from different habitats. METHODS：HPLC method was adopted. The determination was performed on Inertsil ODS-3 column with mobile phase consisted of acetonitrile-water （50 ∶ 50，V/V） at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 203 nm，and sample size was 10 μL. Established method was used to determine the contents of diosgenin in wild D. zingiberensis from different habitats （Shaanxi Shangluo，Shaanxi Ankang，Henan Neixiang，Yunnan Xuanwei，Sichuan Deyang，Hubei Shiyan，Hunan Zhangjiajie，Hunan Changde）. The differences of diosgenin content were compared. RESULTS：The linear range of diosgenin were 4.16-165.6 μg/mL （r＝     0.999 9）. RSDs of precision，reproducible and stability tests were all lower than 2％ （n＝5 or n＝6）. The average recovery of diosgenin was 101.18％ （RSD＝1.27％，n＝6）. The content of diosgenin in wild D. zingiberensis from different habitats were in descending order，i.e. Sichuan Deyang （1 405.36 μg/g）＞Shaanxi Shangluo （1 201.79 μg/g）＞Hunan Zhangjiajie （1 035.18 μg/g）＞Shaanxi Ankang （632.64 μg/g）＞Hunan Changde （598.64 μg/g）＞Yunnan Xuanwei （425.34 μg/g）＞Henan Neixiang （350.13         μg/g）＞Hubei Shiyan （338.39 μg/g）. CONCLUSIONS：Established method is simple，accurate and suitable for the content determination of diosgenin in D. zingiberensis. The contents of diosgenin in wild D. zingiberensis from different habitats are different significantly，and the content of diosgenin in the samples from Sichuan Deyang is the highest.

Effect of Diosgenin on Expressions of PPARγ, C/EBPα and Adipokine Secretion in Aplastic Anemia Mice / 中国实验方剂学杂志

Objective: To observe the effect of diosgenin on aplastic anemia (AA) mice and peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), Adiponectin, Leptin, in order to discuss the potential mechanism of bone marrow mesenchymal stem cells in the process of adipemia. Method: BALB/c mice were randomly divided into control group and model group. The model group was established by 60Coy irradiation combined with tail vein infusion with lymphatic suspension cells of DBA/2 mice. After successful evaluation of the model, the mice were randomly divided into 6 groups:model group, low, medium and high-dose diosgenin groups (37.44,74.88,149.76 mg·kg-1·d-1), cyclosporine group (23.5 mg·kg-1·d-1), and tripterygium glycoside group (9.36 mg·kg-1·d-1), and given corresponding drugs by gavage for 14 days. After the intervention, the peripheral blood of mice in each group was detected, and bone marrow smears were collected to evaluate the proliferation of bone marrow. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured by adherent method and induced by adipogenesis. The mRNA and protein expressions of PPARγ, C/EBPα, Adiponectin, Leptin in BMMSCs were detected by quantitative real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result: The white blood cell (WBC), hemoglobin (HGB) and blood platelet (PLT) in peripheral blood of model group were significantly lower than those of normal group (PPγ, C/EBPα, Adiponectin and Leptin in BMMSCs of the model group increased significantly (Pγ, C/EBPα, Adiponectin and Leptin in the middle-dose group diosgenin decreased obviously, which was better than those of Tripterygium glycoside group (P0.05). Conclusion: Diosgenin can promote the recovery of peripheral blood in aplastic anemia mice and improve the hematopoiesis of bone marrow. Diosgenin can reduce the expressions of PPARγ and C/EBPα, the formation of adipocytes and the secretion of Adiponectin and Leptin in adipocytes, and effectively inhibit the process of adipose tissue derived from bone BMMSCs.

Colonization investigation of arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) in roots of Polygonatum kingianum and their correlations with content of main functional components in rhizomes / 中草药

Objective: To investigate the colonization of arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) in the roots of Polygonatum kingianum planted at different areas, and explore the correlations between the colonization rate and the main functional components. Methods: Fresh roots of P. kingianum from five plots in Yunnan Province were taken as research objects. The alkali dissociation method was used to investigate the colonization of AMF and DSE in the roots of P. kingianum. Then the morphological structure was photographed. The content of P. sibiricum polysaccharides, diosgenin, total flavonoids and extractum were separately determined by phonel-sulfate method, colorimetry method of vanillin-acetic acid-perchloric acid, spectrophotometry method with rutin standard and hot dipping method with alcohol. The correlations between the colonization rates of AMF or DSE and four main functional components were analyzed by Pearson correlation coefficient method. Results: The average colonization of AMF and DSE in the five plots were 26.25%-57.54% and 31.67%-45.19%, respectively. The colonization rates of AMF and DSE from HHMZ was higher than the other four others. All of correlations among the colonization rates of AMF, DSE and their typical structure and the four main functional components in the rhizomes were positive correlation, in which the correlations between the content of polysaccharides, diosgenin or total flavonoids and the colonization rates of AMF or DSE were higher, and their correlation coefficient were respectively 0.838/0.887, 0.819/0.703, and 0.785/0.855 (AMF/DSE). Furthermore, the correlations between the content of polysaccharides and the colonization rates of AMF hypha or DSE were significant. In addition, there were high correlations among the colonization rates of AMF, DSE and their typical structures, as well as the content in pairs of four functional components. Conclusion: There were higher colonization rates of AMF and DSE in the fibrous roots of P. kingianum. The correlations between the colonization rates of AMF or DSE and each main functional component were positive. This study provides data support and experimental basis for the implementation of ecological planting of P. kingianum and the use of biological means to increase production and income.rates

Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC20 was calculated using the MTT method. The cells were then pre-treated with IC20 concentrations for 24 and 48 h. Real time PCR was employed to measure expression of liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1C (SREBP-1C), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fibroblast growth factor 21 (FGF21), peroxisome proliferator-activated receptor gamma (PPARγ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXRα (P=0.003, P<0.001), SREBP-1C (P<0.001, P<0.001), ACC (P=0.002, P=0.006), and FAS (P<0.001, P<0.001) were downregulated significantly, while FGF21 (P<0.001, P<0.001), PPARγ (P=0.004, P<0.001), and LDLR (P<0.001, P<0.001) were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat in 24 and 48 h, respectively. Conclusions: Hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes, which is similar to orlistat. Trigonella foenum-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.

Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC

Evaluation Of Immunomodulatory Activity Of Diosgenin In Rats

Background: Theimmune system is intrinsic to health. Modulation of the immune responses to alleviate the diseases by using herbal plants has been of interest for many years. Diosgenin, a naturally occurring steroid saponin mainly present in the seeds of fenugreek (Trigonella foenum graecum)and in the root tubers of wild yams (Dioscorea vil-losa). Activation of specific and nonspecific immunity results in stimulation of immune response. Diosgenin has the positive effects on both specific and nonspecific immunity.Aim: To study the immunomodulatory activity of Diosgen-in in rats. Method: The suspension of Diosgenin wasgiven orally at the dosage level of 50, 100 and 150 mg/kg for 21 days in a rat. The immunomodulatory activity on specific and non-specific immunity was studied by haemagglutina-tion antibody (HA) titer, delayed type hypersensitivity (DTH) response and carbon clearance test. Immunosuppres-sion in a rat was induced by using Cyclophosphamide (100 mg/kg, p.o.). Sheep red blood cells (SRBCs) were used as antigen (0.1ml 20% SRBCs) in haemagglutinating antibody titer and delayed type hypersensitivity response methods. Result: Diosgenin exhibited significant increase in the production of antibody titer in response to SRBC antigen. A significant increase in both primary and secondary HA titer was observed in immunosuppressed group treated with Diosgenin when compared with negative control. A significant increase in the DTH response was observed in immu-nosuppressed animals treated with Diosgenin, pre-sensitized with SRBCs antigen. Diosgenin exhibited significant in-crease in phagocytic index against control group, indicating the stimulation of the reticuloendothelial system. Con-clusion: The study indicates that Diosgenin triggers stimulatory effect on specific and nonspecific immune response. The immunostimulant effect of Diosgenin could be attributed due to its saponin glycoside.

Protective Effect Of Diosgenin Against Carbon Tetrachloride And Cisplatin Induced Hepatotoxicity In Rats

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bili-rubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation.

Synthesis and biological evaluation of new peroxo-bridged diosgenin derivatives / 中草药·英文版

Objective: In order to find lead compound with anti-HBV activity from peroxo-bridged diosgenin derivatives obtained with Eosin Y as the photosensitizer. Method: Eosin Y was used as the photosensitizer to activate the oxygen in the air to synthesize novel diosgenin derivatives with peroxo-bridge. The structures of synthesized compounds were identified by NMR and HR-MS. Their cytotoxicity and antihepatitis B activity were evaluated via MTS assay and ELISA method, respectively. Results: Six diosgenin derivatives were synthesized, three of which contained peroxo-bridge, and their structures were confirmed by spectroscopy. It showed that 5α,8α-peroxo-6-alkenyl-diosgenin (7) could suppress the production of HBsAg on transfected HepG2.2.15 cells at low-toxic concentration and the inhibition rate on HepG2.2.15 cells was 18.28% at 12.50 µg/mL, better than that of 3TC (7.30% at 12.50 µg/mL) and others. Conclusion: Due to its lower cytotoxicity and potential anti-hepatitis B activity, compound 7 could be developed as the promising candidate of anti-hepatitis B drug. It also indicated that the peroxo-bridged derivatives had potential biological values for developing clinical agents.

In vitro study on effects of diosgenin from Dioscorea nipponica on mouse T lymphocytes / 重庆医学

Objective To study the effect of diosgenin(Dio) from Dioscorea nipponica on the proliferation in mouse spleen T lymphocytes and expressions of IL-2 and IFN-γmRNA,in order to investigate the immunity regulatory mechanism of Dio.Methods T lymphocytes stimulated by different concentrations of Dio and concanavalin A(ConA) were co-cultured.CCK-8 was used to detect the Dio effects on T lymphocyte proliferation.The RT-PCR method was adopted to detect the effect of Dio on expression of IL-2 and IFN-γmRNA.Results The Dio concentration in the range of 0.937 5-15.000 0 μg/mL had the inhibiting effect on T lymphocyte proliferation,Dio concentration in the range of 3.750 0-15.000 0μg/mL had the inhibiting effect on IFN-γ and IL-2 expression in T lymphocytes.With the Dio concentration increase,the inhibition effect was enhanced(P＜0.05).7.500 0 μg/mL was the best inhibition concentration.The inhibition effect was decreased when the concentration exceeding 7.500 0 μg/mL.Conclusion Dio has the inhibiting effect on T lymphocyte proliferation and expressions of IL-2 and IFN-γ mRNA.