Lipoamide

Lipoamide is a neutral amide derivative with coenzyme activity. Lipoamide stimulates mitochondrial biogenesis by activating the eNOS-cGMP-PKG signaling pathway and prevents abnormal protein aggregation and promotes nuclear function recovery by regulating stress granule dynamics. Lipoamide can be used for research on obesity, type 2 diabetes, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)^[1-4].

In vitro, human retinal pigment epithelial (ARPE-19) cells were pretreated with Lipoamide (40μM) for 48h, followed by acrolein (75μM) stimulation for 24h. Lipoamide significantly inhibited the decrease in cell viability, mitochondrial dysfunction, and oxidative stress damage, while enhancing the intracellular antioxidant defense system^[5]. ARPE-19 cells were treated with Lipoamide (5–80μM) for 48h. Lipoamide significantly increased mitochondrial DNA copy number, viable mitochondria mass, and the expression of electron transport chain complexes, while activating the Nrf2 pathway and inducing the expression and activity of phase II antioxidant enzymes (NQO-1, GST, GCL, catalase, and Cu/Zn SOD)^[6].

In vivo, nude mice transplanted with Nfkd SW10 cells were subcutaneously injected with Lipoamide (8mg/kg/day) for one week. Lipoamide significantly inhibited the growth of Nfkd xenograft tumors^[7]. db/db mice (type 2 diabetes model) were administered Lipoamide (50mg/kg/day) by gavage for 8 weeks. Lipoamide significantly restored renal function, improved mitochondrial dysfunction, and ameliorated tubulointerstitial fibrotic lesions^[8].

References:
[1] Arnér ES, Nordberg J, Holmgren A. Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. Biochem Biophys Res Commun. 1996 Aug 5;225(1):268-74.
[2] Hou Y, Li X, Peng S, et al. Lipoamide Ameliorates Oxidative Stress via Induction of Nrf2/ARE Signaling Pathway in PC12 Cells. J Agric Food Chem. 2019 Jul 24;67(29):8227-8234.
[3] Shen W, Hao J, Feng Z, et al. Lipoamide or lipoic acid stimulates mitochondrial biogenesis in 3T3-L1 adipocytes via the endothelial NO synthase-cGMP-protein kinase G signalling pathway. Br J Pharmacol. 2011 Mar;162(5):1213-24.
[4] Sumegi B, Butwell NB, Malloy CR, et al. Lipoamide influences substrate selection in post-ischaemic perfused rat hearts. Biochem J. 1994 Jan 1;297 ( Pt 1)(Pt 1):109-13.
[5] Li X, Liu Z, Luo C, et al. Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction. Free Radic Biol Med. 2008 Apr 1;44(7):1465-74.
[6] Zhao L, Liu Z, Jia H, et al. Lipoamide Acts as an Indirect Antioxidant by Simultaneously Stimulating Mitochondrial Biogenesis and Phase II Antioxidant Enzyme Systems in ARPE-19 Cells. PLoS One. 2015 Jun 1;10(6):e0128502.
[7] Zhang Y, Zhou R, Qu Y, et al. Lipoamide Inhibits NF1 Deficiency-induced Epithelial-Mesenchymal Transition in Murine Schwann Cells. Arch Med Res. 2017 Aug;48(6):498-505.
[8] Zhang HF, Liu HM, Xiang JY, et al. Alpha lipoamide inhibits diabetic kidney fibrosis via improving mitochondrial function and regulating RXRα expression and activation. Acta Pharmacol Sin. 2023 May;44(5):1051-1065.

Lipoamide是一种辅酶活性的中性酰胺衍生物。Lipoamide可通过激活eNOS-cGMP-PKG信号通路刺激线粒体生物发生，同时通过调节应激颗粒动态以防止蛋白质异常聚集并促进核功能恢复。Lipoamide可用于肥胖症、2型糖尿病以及肌萎缩侧索硬化症（ALS）等神经退行性疾病的相关研究^[1-4]。

在体外，Lipoamide（40μM）预处理人类视网膜色素上皮（ARPE-19）细胞48小时，随后以丙烯醛（75μM）刺激24小时。Lipoamide显著抑制细胞活力下降、线粒体功能障碍及氧化应激损伤，同时增强细胞内抗氧化防御系统^[5]。Lipoamide（5–80μM）处理人类视网膜色素上皮（ARPE-19）细胞48小时。Lipoamide显著增加线粒体DNA拷贝数、 viable mitochondria质量及电子传递链复合物的表达，同时激活Nrf2通路并诱导II相抗氧化酶系统（NQO-1、GST、GCL、过氧化氢酶及Cu/Zn SOD）的表达与活性^[6]。

在体内，Lipoamide（8mg/kg/day）皮下注射于接种了Nf^kd SW10细胞的裸鼠，连续1周。Lipoamide显著抑制了Nf^kd异种移植肿瘤的生长^[7]。Lipoamide（50mg/kg/day）灌胃于db/db小鼠（2型糖尿病模型），持续给药8周。Lipoamide显著恢复了肾功能，改善了线粒体功能障碍及肾小管间质纤维化病变^[8]。