HNGF6A is a synthetic polypeptide belonging to the Humanin analogue class[1-2]. HNGF6A improves glucose metabolism and inhibits the production of reactive oxygen species (ROS). HNGF6A is used in research related to diabetes, atherosclerosis, and osteoarthritis[3].
In vitro, meniscus cells were pretreated with HNGF6A (5–100ng/ml) for 48 hours and were then stimulated with TBHP (50µM) or IL-1β (10ng/ml). HNGF6A significantly restored the expression of extracellular matrix synthesis-related genes (COL1A1, COL3A1, ACAN) and inhibited the expression of degradation-related genes (MMP1, MMP3, ADAMTS5), while maintaining mitochondrial redox homeostasis, reducing ROS levels, and decreasing cell apoptosis[4]. Murine osteoblastic cell line MC3T3-E1 cells were pretreated with HNGF6A (5–50ng/mL) for 3 days and were then exposed to H₂O₂ (400µM) for 4 hours. HNGF6A significantly inhibited apoptosis, downregulated the expression of pro-apoptotic proteins (Caspase-3, Cyto C, Bax), and upregulated the expression of the anti-apoptotic protein (Bcl-2). HNGF6A also promoted the expression of osteoblast phenotype-related proteins (ALP, BMP-2, OCN, RUNX2), enhanced alkaline phosphatase (ALP) activity, and increased mineralization nodule formation[5].
In vivo, three-month-old Sprague-Dawley rats were treated with HNGF6A (0.07mg/kg/h) via continuous intravenous infusion for 2 hours. HNGF6A significantly increased the glucose infusion rate during a hyperglycemic clamp and caused a sustained increase in plasma insulin levels. C57BL/6N mice received a single intravenous injection of HNGF6A (2mg/kg) 10 minutes before a glucose tolerance test, which showed a trend toward increased first-phase insulin secretion[6]. Apolipoprotein E (ApoE)-deficient mice fed a high-cholesterol diet were treated with HNGF6A (0.4mg/kg/day) via daily intraperitoneal injection for 16 weeks. HNGF6A significantly improved acetylcholine-induced endothelium-dependent vasodilation, reduced atherosclerotic plaque size in the proximal aorta, decreased nitrotyrosine immunoreactivity and apoptosis within the plaques, and preserved endothelial nitric oxide synthase expression[7].
References:
[1] Ding Y, Feng Y, Zhu W, et al. [Gly14]-Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin-like Oxidized Low-density Lipoprotein Receptor-1-Dependent Manner. Lipids. 2019 Nov;54(11-12):697-705.
[2] Chin YP, Keni J, Wan J, et al. Pharmacokinetics and tissue distribution of humanin and its analogues in male rodents. Endocrinology. 2013 Oct;154(10):3739-44.
[3] Peña Agudelo JA, Pidre ML, et al. Mitochondrial Peptide Humanin Facilitates Chemoresistance in Glioblastoma Cells. Cancers (Basel). 2023 Aug 11;15(16):4061.
[4] Liu R, Du X, Chen Y, et al. HNGF6A ameliorates oxidative stress-mediated mitochondrial dysfunction in degenerative meniscus. Bone Joint Res. 2025 Apr 7;14(4):318-330.
[5] Zhu X, Zhao Z, Zeng C, et al. HNGF6A Inhibits Oxidative Stress-Induced MC3T3-E1 Cell Apoptosis and Osteoblast Phenotype Inhibition by Targeting Circ_0001843/miR-214 Pathway. Calcif Tissue Int. 2020 May;106(5):518-532.
[6] Kuliawat R, Klein L, Gong Z, et al. Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the β cell. FASEB J. 2013 Dec;27(12):4890-8.
[7] Oh YK, Bachar AR, Zacharias DG, et al. Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. Atherosclerosis. 2011 Nov;219(1):65-73.
HNGF6A是一种人工合成的多肽，属于人类素（Humanin）类似物[1-2]。HNGF6A可改善糖代谢和抑制抑制活性氧的产生。HNGF6A用于糖尿病、动脉粥样硬化和骨关节炎的相关研究[3]。
在体外，HNGF6A（5–100ng/ml）预处理半月板细胞48小时，随后以TBHP（50μM）或IL-1β（10ng/ml）刺激。HNGF6A显著恢复细胞外基质合成相关基因（COL1A1，COL3A1，ACAN）的表达并抑制降解相关基因（MMP1，MMP3，ADAMTS5）的表达，同时维持线粒体氧化还原稳态、降低ROS水平、减少细胞凋亡[4]。HNGF6A（5–50ng/mL）预处理小鼠成骨细胞系MC3T3-E1细胞3天，随后以H₂O₂（400μM）刺激4小时。HNGF6A显著抑制细胞凋亡并下调促凋亡蛋白（Caspase-3，Cyto C，Bax）的表达、上调抗凋亡蛋白（Bcl-2）的表达，同时促进成骨细胞表型相关蛋白（ALP，BMP-2，OCN，RUNX2）的表达、增强碱性磷酸酶（ALP）活性及细胞矿化结节形成[5]。
在体内，HNGF6A（0.07mg/kg/h）通过持续2小时的静脉输注，用于处理3月龄的Sprague-Dawley大鼠。HNGF6A显著提高了高血糖钳夹实验期间的葡萄糖输注率，并持续增加了血浆胰岛素水平。HNGF6A（2mg/kg）在葡萄糖耐量试验前10分钟单次静脉注射，用于处理C57BL/6N小鼠，其第一时相胰岛素分泌有增加趋势[6]。HNGF6A（0.4mg/kg/day）通过每日腹腔注射，持续16周，用于处理喂食高胆固醇饮食的载脂蛋白E（ApoE）缺陷小鼠。HNGF6A显著改善了乙酰胆碱诱导的内皮依赖性血管舒张功能、减少了主动脉近端动脉粥样硬化斑块的大小，同时降低了斑块中的硝基酪氨酸免疫反应性和细胞凋亡、并维持了内皮型一氧化氮合酶的表达[7]。