Hydroxy-α-sanshool is a transient receptor potential base 1 (TRPA1) and TRP vanilloid 1 (TRPV1) agonist with EC50 values of 69 and 1.1µM, respectively, commonly used in hyperlipidemia studies[1].
In HaCaT cells, Hydroxy-α-sanshool (10-40μM; 24h) effectively inhibited intracellular ROS production induced by C. acnes.10μM of Hydroxy-α-sanshool significantly reduced ROS levels in THP-1 cells[2]. Hydroxy-α-sanshool showed a significant protective effect on H2O2-stimulated PC12 cells without significant cytotoxicity against normal PC12 cells. Hydroxy-α-sanshool also reduced H2O2-induced apoptosis of PC12 cells by decreasing intracellular ROS and increasing mitochondrial membrane potential (MMP)[3].
Hydroxy-α-sanshool (0.5, 1.25, 2.5, 5mg/kg; po) reduces blood glucose in the T2DM mouse model by regulating glycogen metabolism through a mechanism involving the regulation of the PI3K/Akt/GSK3β/GS signaling pathway[4]. In the insulin resistance model, the Hydroxy-α-sanshool (8mg/kg) intervention lowered serum total cholesterol and LDL cholesterol and significantly reduced triacylglycerol[5].
References:
[1]. Riera C E, Menozzi‐Smarrito C, Affolter M, et al. Compounds from Sichuan and Melegueta peppers activate, covalently and non‐covalently, TRPA1 and TRPV1 channels[J]. British journal of pharmacology, 2009, 157(8): 1398-1409.
[2]. Zhou X, Su Y, Wang H, et al. Hydroxy-α-sanshool has anti-inflammatory and antioxidant effects and affects the NF-κB/STAT3 pathway via TRPV1 in acne[J]. Journal of Functional Foods, 2023, 110: 105823.
[3]. Li R L, Zhang Q, Liu J, et al. Hydroxy‐α‐sanshool Possesses Protective Potentials on H2O2‐Stimulated PC12 Cells by Suppression of Oxidative Stress‐Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway[J]. Oxidative Medicine and Cellular Longevity, 2020, 2020(1): 3481758.
[4]. Zhang Q, Li R L, Wang L Y, et al. Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3β/GS signaling[J]. Frontiers in Pharmacology, 2022, 13: 1089558.
[5]. Xu F, Zhu Y, Lu M, et al. Effects of hydroxy-alpha-sanshool on intestinal metabolism in insulin-resistant mice[J]. Foods, 2022, 11(14): 2040.
Hydroxy-α-sanshool是一种TRPA1和TRPV1激动剂，其EC50值分别为69和1.1µM，常用于高脂血症的研究[1]。
在HaCaT细胞中，Hydroxy-α-sanshool（10-40μM；24h）可有效抑制痤疮丙酸杆菌诱导的细胞内ROS生成，10μM的Hydroxy-α-sanshool能明显降低THP-1细胞中的ROS水平[2]。Hydroxy-α-sanshool 对H2O2刺激的PC12细胞有明显的保护作用，对正常PC12细胞无明显的细胞毒性。Hydroxy-α-sanshool能够通过降低细胞内ROS和提高线粒体膜电位（MMP）来减少H2O2诱导的PC12细胞凋亡[3]。
Hydroxy-α-sanshool（0.5，1.25，2.5，5mg/kg； po）通过调节PI3K/Akt/GSK3β/GS信号通路的机制，调节糖原代谢，降低2型糖尿病小鼠模型中的血糖[4]。在胰岛素抵抗模型中，Hydroxy-α-sanshool（8mg/kg）干预可降低血清总胆固醇和LDL胆固醇，并显著降低三酰甘油[5]。