Diosgenin

Diosgenin is a naturally occurring steroidal sapogenin that can inhibit the STAT3 signaling pathway and acts as an activator of Pdia3/ERp57, possessing a variety of important pharmacological activities^[1-2]. Diosgenin has been shown in studies to have lipid-lowering, hypoglycemic, antioxidant, anti-inflammatory, and anti-proliferative effects, among others^[3-4].

In vitro, Diosgenin (50μM) treatment of MCF-7 and MDA-MB-231 breast cancer cells for 72 hours, Diosgenin significantly inhibits cell viability, induces apoptosis, and reduces cell invasive ability. Treatment of MCF-7 and MDA-MB-231 cells with Diosgenin (50μM) for 72 hours significantly downregulates the mRNA and protein expression levels of Skp2 and upregulates the protein expression of its downstream targets p57 and FOXO1^[5]. Pretreatment of human periodontal ligament stem cells (hPDLSCs) with Diosgenin (2μM) for 1 hour, followed by culture under lipopolysaccharide (LPS; 1μg/ml) stimulation, Diosgenin significantly inhibits the LPS-induced expression of inflammatory factors TNF-α, IL-1β, and IL-6, and suppresses the activation of the NF-κB pathway (reducing p-IκBα levels and p65 nuclear translocation)^[6].

In vivo, oral administration of Diosgenin (20-80mg/kg/day) to epileptic model rats (starting 7 days before epileptogenesis induction and continuing until the end of the experiment), Diosgenin significantly promotes the differentiation of oligodendrocyte precursor cells (OPCs) into mature myelinating oligodendrocytes in the corpus callosum region and alleviates seizure severity and weight loss^[7]. Intraperitoneal injection of Diosgenin (1, 10, 20mg/kg/day) in Crystalline Silica (50mg/kg) and 500×10⁷CFU Mycobacterium smegmatis-induced pulmonary tuberculosis Sprague-Dawley rats (starting from the first day of crystalline silica induction and continuing for 50 days), Diosgenin significantly inhibits Mycobacterium smegmatis growth (IC₅₀=0.006043μg/mL), reduces lung tissue malondialdehyde (MDA) levels, increases superoxide dismutase (SOD) and catalase (CAT) activity, and improves pathological lung fibrosis damage^[8].

References:
[1] Singh S, Varshney M, Sharma H. Amarogentin, Natural Bitter Terpenoids: Research Update with Pharmacological Potential, Patent and Toxicity Aspects. Curr Top Med Chem. 2025 Aug 21.
[2] Patel K, Kumar V, Verma A, et al. Amarogentin as Topical Anticancer and Anti-Infective Potential: Scope of Lipid Based Vesicular in its Effective Delivery. Recent Pat Antiinfect Drug Discov. 2019;14(1):7-15.
[3] Wölfle U, Haarhaus B, Schempp CM. Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes. Mediators Inflamm. 2015;2015:630128.
[4] Sur S, Pal D, Banerjee K, et al. Amarogentin regulates self renewal pathways to restrict liver carcinogenesis in experimental mouse model. Mol Carcinog. 2016 Jul;55(7):1138-49.
[5] Disasa D, Cheng L, Manzoor M, et al. Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress. Oxid Med Cell Longev. 2020 Aug 1;2020:3184019.
[6] Zhang Y, Zhang Y, Wang J, et al. Amarogentin Inhibits Liver Cancer Cell Angiogenesis after Insufficient Radiofrequency Ablation via Affecting Stemness and the p53-Dependent VEGFA/Dll4/Notch1 Pathway. Biomed Res Int. 2020 Oct 20;2020:5391058.
[7] Li S, Li X, He F, et al. Amarogentin promotes osteoblast differentiation in oestrogen-deficiency-induced osteoporosis rats by modulating the Nrf-2/MAPK/ERK signalling pathway. Arch Med Sci. 2019 Nov 11;19(2):452-457.
[8] Niu HS, Chao PC, Ku PM, et al. Amarogentin ameliorates diabetic disorders in animal models. Naunyn Schmiedebergs Arch Pharmacol. 2016 Nov;389(11):1215-1223.

Diosgenin是一种天然存在的甾体皂苷元，Diosgenin可抑制STAT3信号通路，并作为Pdia3/ERp57的激活剂，具有多种重要的药理活性^[1-2]。Diosgenin在研究中显示出降血脂、降血糖、抗氧化、抗炎和抗增殖等作用^[3-4]。

在体外，Diosgenin（50μM）处理MCF-7和MDA-MB-231乳腺癌细胞72小时，Diosgenin显著抑制细胞活力并诱导细胞凋亡，同时降低细胞侵袭能力。Diosgenin（50μM）处理MCF-7和MDA-MB-231细胞72小时，显著下调Skp2的mRNA和蛋白表达水平，并上调其下游靶标p57和FOXO1的蛋白表达^[5]。在体外，Diosgenin（2μM）预处理人牙周膜干细胞（hPDLSCs）1小时，随后在脂多糖（LPS；1μg/ml）刺激条件下培养，Diosgenin显著抑制LPS诱导的炎症因子TNF-α、IL-1β和IL-6的表达，并抑制NF-κB信号通路的活化（降低p-IκBα水平和p65核转位）^[6]。

在体内，Diosgenin（20-80mg/kg/day）灌胃处理癫痫模型大鼠（从癫痫诱导前7天开始，持续至实验结束），Diosgenin显著促进胼胝体区少突胶质前体细胞（OPCs）分化为成熟的髓鞘形成少突胶质细胞，并改善癫痫发作严重程度和体重减轻^[7]。Diosgenin（1、10、20mg/kg/day）腹腔注射处理Crystalline Silica（50mg/kg）和500 × 10⁷CFU Mycobacterium smegmatis诱导的肺结核Sprague-Dawley大鼠（从Crystalline Silica诱导第1天开始，持续50天），Diosgenin显著抑制Mycobacterium smegmatis生长（IC₅₀=0.006043μg/mL），降低肺组织丙二醛（MDA）水平，并提高超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性，改善肺纤维化病理损伤^[8]。