Amarogentin

Amarogentin is a secoiridoid glycoside natural product extracted from the roots of Swertia and Gentiana plants. Amarogentin possesses a range of biological activities, including immunomodulatory, antidiabetic, and antitumor effects^[1-2]. Amarogentin has demonstrated potential value in research areas such as gastric cancer, colorectal cancer, diabetes, and neuroprotection^[3-4].

In vitro, pretreatment of PC12 cells with Amarogentin (1-10µM) for 24 hours, followed by culture under oxidative stress conditions induced by hydrogen peroxide (0.9mM), Amarogentin significantly inhibited the increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels caused by oxidative stress. Amarogentin upregulated the gene expression of SOD2, CAT, GPx, Nrf2, and Bcl-x1 while enhancing SOD2 enzymatic activity, thereby exerting a neuroprotective effect^[5]. HepG2 and Huh7 cells treated with incomplete radiofrequency ablation (IRFA) were incubated with Amarogentin (120μg/ml) for 24 hours. Amarogentin significantly reduced the proportion of CD133‑positive cells and the secretion of vascular endothelial growth factor A (VEGFA), and inhibited the VEGFA/Dll4/Notch1 signaling pathway via a p53‑dependent mechanism, thereby suppressing angiogenesis^[6].

In vivo, oral administration of Amarogentin (50 or 100mg/kg/day) to ovariectomy-induced estrogen-deficient osteoporotic rats for 5 consecutive weeks, Amarogentin significantly increased whole-body and lumbar spine bone mineral density, improved levels of serum bone formation markers (osteocalcin, C-terminal telopeptide of type I collagen, N-terminal propeptide of type I procollagen, and bone-specific alkaline phosphatase), Amarogentin reduced the expression of inflammatory cytokines (IL-1β, IL-17, and TNF-α), and enhanced osteoblast differentiation by modulating the Nrf-2/MAPK/ERK signaling pathway^[7]. Intravenous administration of Amarogentin (0.5mg/kg/day; for 1 consecutive week) to streptozotocin-induced type 1 diabetic rats, Amarogentin significantly lowered fasting blood glucose, increased skeletal muscle glucose transporter 4 (GLUT4) expression, and inhibited liver phosphoenolpyruvate carboxykinase (PEPCK) activity^[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.

Amarogentin是一种Swertia和Gentiana植物根中提取的裂环烯醚萜苷类天然产物，Amarogentin具有多种生物学活性，包括免疫调节、抗糖尿病和抗肿瘤^[1-2]。Amarogentin在胃癌、结直肠癌、糖尿病以及神经保护的相关研究中显示出潜在的应用价值^[3-4]。

在体外，Amarogentin（1-10μM）预处理PC12细胞24小时，随后在过氧化氢（0.9mM）诱导的氧化应激条件下培养，Amarogentin显著抑制氧化应激诱导的活性氧（ROS）和丙二醛（MDA）水平升高，并上调SOD2、CAT、GPx、Nrf2和Bcl-x1的基因表达，同时增强SOD2酶活性，发挥神经保护作用^[5]。取经不完全射频消融（IRFA）处理的HepG2和Huh7细胞，使用Amarogentin（120μg/ml）孵育24小时，Amarogentin显著降低CD133阳性细胞比例和血管内皮生长因子A（VEGFA）的分泌，并通过p53依赖性途径抑制VEGFA/Dll4/Notch1信号通路，从而抑制血管生成^[6]。

在体内，Amarogentin（50或100mg/kg/day）口服处理双侧卵巢切除诱导的雌激素缺乏性骨质疏松大鼠，连续5周，Amarogentin显著提高全身和腰椎骨密度，改善血清骨形成标志物（骨钙素、I型胶原C端肽、I型前胶原N端前肽和骨特异性碱性磷酸酶）水平，降低炎症因子（IL-1β、IL-17和TNF-α）表达，并通过调节Nrf-2/MAPK/ERK信号通路增强成骨细胞分化^[7]。Amarogentin（0.5mg/kg/day；连续1周）静脉注射处理链脲佐菌素诱导的1型糖尿病大鼠，Amarogentin显著降低空腹血糖，增加骨骼肌葡萄糖转运蛋白4（GLUT4）表达，抑制肝脏磷酸烯醇式丙酮酸羧激酶（PEPCK）活性^[8]。