PMID: 

J Sci Food Agric. 2015 Dec ;95(15):3177-82. Epub 2015 Jan 22. PMID: 25530163

Abstract Title: 

Diosgenin reorganises hyperglycaemia and distorted tissue lipid profile in high-fat diet-streptozotocin-induced diabetic rats.

Abstract: 

BACKGROUND: Diabetes is often connected with significant morbidity, mortality and also has a pivotal role in the development of cardiovascular diseases. Diet intervention, particularly naturaceutical antioxidants have anti-diabetic potential and avert oxidative damage linked with diabetic pathogenesis. The present study investigated the effects of diosgenin, a saponin from fenugreek, on the changes in lipid profile in plasma, liver, heart and brain in high-fat diet-streptozotocin (HFD-STZ)-induced diabetic rats. Diosgenin was administered to HFD-STZ induced diabetic rats by orally at 60 mg kg(-1) body weight for 30 days to assess its effects on body weight gain, glucose, insulin, insulin resistance and cholesterol, triglycerides, free fatty acids and phospholipids in plasma, liver, heart and brain.RESULTS: The levels of body weight, glucose, insulin, insulin resistance, cholesterol, triglycerides, free fatty acids, phospholipids, VLDL-C and LDL-C were increased significantly (P

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PMID: 

J Physiol Sci. 2014 Nov ;64(6):393-400. Epub 2014 Aug 24. PMID: 25150984

Abstract Title: 

Anti-arrhythmic effect of diosgenin in reperfusion-induced myocardial injury in a rat model: activation of nitric oxide system and mitochondrial KATP channel.

Abstract: 

This study was designed to investigate the anti-arrhythmic effect of diosgenin preconditioning in myocardial reperfusion injury in rat, focusing on the involvement of the nitric oxide (NO) system and mitochondrial ATP-dependent potassium (mitoKATP) channels in this scenario. After isolation of the hearts of male Wister rats, the study was conducted in an isolated buffer-perfused heart model. Global ischemia (for 30 min) was induced by interruption of the aortic supply, which was followed by 90-min reperfusion. Throughout the experiment, the electrocardiograms of hearts were monitored using three golden surface electrodes connected to a data acquisition system. Arrhythmias were assessed based on the Lambeth convention and were categorized as number, duration and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular complexes (PVC), and arrhythmic score. Additionally, lactate dehydrogenase (LDH) levels in coronary effluent were estimated colorimetrically. Diosgenin pre-administration for 20 min before ischemia reduced the LDH release into the coronary effluent, as compared with control hearts (P 

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PMID: 

PLoS One. 2014 ;9(9):e106039. Epub 2014 Sep 12. PMID: 25216353

Abstract Title: 

Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity againstα-amylase and α-glucosidase.

Abstract: 

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG).α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

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PMID: 

Int J Clin Exp Med. 2015 ;8(2):2476-9. Epub 2015 Feb 15. PMID: 25932192

Abstract Title: 

Role of SB203580 in the regulation of human esophageal cancer cells under the effection of Diosgenin.

Abstract: 

In order to investigate the mechanism of human esophageal Eca109 cells induced by Diosgenin (Dio), the p38 specific inhibitor SB203580 was used to inhibit the expression of p38 and Western blot was employed to detect the effect of SB203580 in Eca109 cells. MTT experiments were executed to detect the proliferation of the cells. Western blot was also applied to find the expression of phosphorylated p38 (p-p38). It is found that SB203580 can inhibit the expression of p38 in human esophageal cell Eca109. After treated with 50μg/mL of Dio and 10 μg/mL of SB203580, the proliferation of cells showed significantly increase and the apoptosis of cells showed significantly decrease compared with the proliferation in the cells treated with Dio only. Moreover, p-p38 protein level was significantly decreased after treated by the two drugs. It is concluded that Dio may regulate esophageal Eca109 cells through p-p38 pathway.

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PMID: 

Lab Anim Res. 2016 Jun ;32(2):105-15. Epub 2016 Jun 24. PMID: 27382379

Abstract Title: 

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection.

Abstract: 

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreasedphosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75(NTR) expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of braindamage through stimulation of NGF biosynthesis.

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PMID: 

Steroids. 2016 09 ;113:103-12. Epub 2016 Jul 16. PMID: 27425638

Abstract Title: 

Diosgenin attenuates the brain injury induced by transient focal cerebral ischemia-reperfusion in rats.

Abstract: 

The aim of the present study is to explore the potential cerebroprotection of diosgenin against the transient focal cerebral ischemia-reperfusion (I/R) injury and its possible underlying mechanisms. The diosgenin at two dose levels, namely 100 and 200mgkg(-1), was intragastrically administrated once daily for 7-day period prior to the surgery. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) using the intraluminal thread for 90min. After 24h reperfusion, several diagnostic indicators were evaluated and all animals were sacrificed to harvest their brains and blood for subsequent biochemical analyses. The results indicated that diosgenin treatment significantly inhibited the death rate and improved the impaired neurological functions along with neurological deficit scores and cerebral infarct size as compared with the rats exposed to I/R insult without agents administration. The increase in the number of apoptotic cells determined by TUNEL in the hippocampus CA1 and cortex was also apparently attenuated in the diosgenin treatment group, which was closely correlated with suppression of Caspase-3 activity and Bax/Bcl-2 ratio. In addition the elevated concentrations of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in blood serum of the I/R treated rats were reduced almost to their normal level. Further results obtained from the Western blotting analysis revealed that the protein expression of IκBα in the injured brain was up-regulated, while the p65 subunit of NF-κB was down-regulatedin nucleus after the treatment. Collectively, this neuroprotection of diosgenin against I/R injury may be attained through its anti-apoptosis, anti-inflammation and intervening the NF-κB signal pathway properties. Due to the satisfactory findings, diosgenin might be a powerful therapeutic agent tocombat the similar disease in future clinic.

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PMID: 

J Diabetes Res. 2017 ;2017:7309816. Epub 2017 Sep 5. PMID: 29038789

Abstract Title: 

Diosgenin, a Novel Aldose Reductase Inhibitor, Attenuates the Galactosemic Cataract in Rats.

Abstract: 

OBJECTIVE: To seek efficient aldose reductase inhibitors (ARIs) with excellent in vitro and in vivo biological activities against rat galactosemic cataract.METHODS: The method was firstly optimized to screen strong ARIs from nonoriented synthetic compounds and natural extracts. Then, diosgenin was assessed on osmotic expansion of primarily cultured lens epithelial cells (LECs) induced by galactose (50 mM). Diosgenin was administered to galactosemic rats by oral (100 and 200 mg/kg) or direct drinking (0.1%) to evaluate its anticataract effects.RESULTS: Diosgenin was found as the strongest ARI with ICof 4.59 × 10 mol/L. Diosgenin (10 M) evidently inhibited the formation of tiny vacuoles and upregulation of AR mRNA in LECs. In vivo, diosgenin delayed lens opacification, inhibited the increase of ratio of lens weight to body weight, and decreased AR activity, galactitol level, and AR mRNA expression, especially in the diosgenin drinking (0.1%) group.CONCLUSIONS: Diosgenin was an efficient ARI, which not only significantly decreased the LECs' osmotic expansion in vitro but also markedly delayed progression of rat galactosemic cataract in vivo. Thus, diosgenin rich food can be recommended to diabetic subjects as dietary management to postpone the occurrence of sugar cataract, and diosgenin deserves further investigation for chronic diabetic complications.

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PMID: 

Oncol Lett. 2019 Oct ;18(4):4278-4287. Epub 2019 Aug 23. PMID: 31579425

Abstract Title: 

Diosgenin inhibits the epithelial-mesenchymal transition initiation in osteosarcoma cells via the p38MAPK signaling pathway.

Abstract: 

Diosgenin is an important basic raw material for the production of steroid hormone drugs. It can be isolated and purified from a variety of traditional Chinese medicines or plants. Modern molecular biological studies have shown that diosgenin inhibits various tumor cells migration and invasion ability to varying degreesand. The aim of the present study was to observe the inhibitory effects of diosgenin on the invasive and metastatic capabilities of osteosarcoma cells and to determine the association between the effects of diosgenin on the epithelial-mesenchymal transition (EMT). Wound healing and Transwell assays were used to observe the inhibitory effects of diosgenin on the invasion and migration of two osteosarcoma cell lines. Immunofluorescence was used to observe changes in transforming growth factorβ1 (TGF-β1) protein expression levels in the osteosarcoma cells following drug administration. EMT-associated proteins, including TGFβ1, E-cadherin and vimentin were detected by western blotting, which demonstrated that the drug may inhibit the initiation of EMT in osteosarcoma cells. Western blot analysis of the expression of all the proteins in the mitogen-activated protein kinase (MAPK) pathway demonstrated that the drug inhibited the MAPK signaling pathway. The primary mechanism of action of diosgenin was the inhibition of the phosphorylated p38 (pP38) protein. Through a combination ofinhibitors of the p38MAPK signaling pathway and detection of the downstream EMT marker protein E-cadherin by quantitative PCR, pP38 was confirmed to be a target of diosgenin in the inhibition of EMT in the osteosarcoma cells via the MAPK molecular signaling pathway. Diosgenin may exhibit utility asan auxiliary drug for the clinical reduction of metastasis in patients with osteosarcoma.

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PMID: 

Food Funct. 2019 Nov 1 ;10(11):7022-7036. Epub 2019 Nov 5. PMID: 31687707

Abstract Title: 

Effects of diosgenin and its derivatives on atherosclerosis.

Abstract: 

Atherosclerosis is one of the leading causes of death in patients with cardiovascular diseases worldwide. Although some progress has been made in the treatment of cardiovascular diseases, the morbidity and mortality of cardiovascular diseases still continue to rise. At present, it is an important topic for researchers to develop safe and effective drugs from natural products to prevent and treat cardiovascular diseases. Diosgenin (DSG) is a plant sterol saponin mainly found in natural medicinal plants such as fenugreek seeds and wild yam tubers. More and more studies have reported that DSG has significant pharmacological activities such as anticancer, cardiovascular protection, hypolipidemic, anti-inflammatory, and neuroprotection. Furthermore, diosgenin is also an important basic raw material for the preparation of steroids and contraceptives in the pharmaceutical industry. Numerous preclinical studies have shown that DSG has great potential in the treatment of various cardiovascular diseases in vivo and in vitro, especially in atherosclerosis. This review mainly discusses the effects of DSG on endothelial dysfunction, lipid profile, and macrophage foam cell formation, VSMC viability, thrombosis and inflammation during the formation of atherosclerosis. Also, the mechanism of DSG on atherosclerosis was elaborated in detail. It is noteworthy that newly synthesized DSG derivatives and DSG delivery systems have good antithrombotic activity and pharmacokinetic characteristics.

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PMID: 

J Biochem Mol Toxicol. 2019 Nov 15:e22422. Epub 2019 Nov 15. PMID: 31729780

Abstract Title: 

Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis.

Abstract: 

M1 macrophages serve one edge as proinflammatory and M2 macrophages serve the other edge as an anti-inflammatory macrophage. It appears that a related"switch"in macrophage morphology may also happen in the course of atherosclerosis, which has not yet been elucidated. An atherogenic diet (AD) was given to rats, and induction of macrophage differentiation and the nuclear localization of nuclear factor-kappa B (NFκB) were investigated by Western blot and immunofluorescence. Chemokines were analyzed using an antibody array with 32 target proteins. M2 macrophage transformation was confirmed in diosgenin-treated aorta by immunofluorescence and was validated in vitro using THP-1 cells. MAC387 (macrophage marker) and NFκBp65 (inflammatory hub) were upregulated in oxidatively-modified low-density lipoprotein (OxyLDL) and AD-induced condition. Macrophage differentiation, which induced the formation of inflammatory mediators, was not significantly suppressed by the inhibition of NFκB using dexamethasone. M1macrophage polarization was identified in OxyLDL-induced monocytes, which are proinflammatory in nature, whereas M2 macrophage polarization was noticed in diosgenin-treated monocytes, which exhibit anti-inflammatory properties. M1-and M2-specific chemokines were analyzed using chemokine antibody array. Furthermore, the expression of proinflammatory macrophage (M1) was noticed in AD-induced aorta and anti-inflammatory macrophage (M2) was observed in diosgenin-treated aorta. This is the first report where, unifying the mechanism of diosgenin as aan nti-atherosclerotic and the expression of M1 and M2 specific chemokines is shown by downregulating NFκB and not by preventing the differentiation of monocyte into a macrophage, but by allowing macrophage to differentiate into M2, which aids in preventing the atherosclerotic progression.

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