Hydroxy-γ-sanshool

Hydroxy-γ-sanshool is a natural alkaloid extracted from Zanthoxylum plants and belongs to the class of unsaturated fatty acid amide compounds^[1]. Hydroxy-γ-sanshool has multiple physiological activities such as neuroactivation, analgesia, anti-inflammatory, and antioxidant^{[2, 3]}. Hydroxy-γ-sanshool can activate TRPV1 channels in human sensory neurons and trigger calcium ion influx^[4].

In vitro, treatment of human colon adenocarcinoma HCT-116 cells with Hydroxy-γ-sanshool (0-130µM) for 24-48h inhibited cell growth, induced cell morphological distortion, induced cell cycle arrest in the G1 phase, caused programmed cell death, reduced the mRNA and protein levels of Cyclin D1, CDK4, and PCNA, and increased the mRNA and protein levels of P21, P53, Fas, and Caspase 8^[5].

In vivo, oral administration of Hydroxy-γ-sanshool (2.5mg/kg) to mice induced by dextran sulfate sodium (DSS)-induced oxidative stress increased the hepatic antioxidant capacity (T-AOC) and the levels of colonic GSH-Px and SOD^[6].

References:
[1] Lu I C, Hu P Y, Lin C H, et al. Alkamides in Zanthoxylum Species: Phytochemical Profiles and Local Anesthetic Activities[J]. International Journal of Molecular Sciences, 2024, 25(22): 12228.
[2] Yan H, Zhou F, Liu Y, et al. Zanthoxylum bungeanum Maxim: A Review of Its Phytochemistry, Pharmacology, and Pharmacokinetics[J]. Natural Product Communications, 2023, 18(10): 1934578X231209153.
[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] Luo J, Ke J, Hou X, et al. Composition, structure and flavor mechanism of numbing substances in Chinese prickly ash in the genus Zanthoxylum: A review[J]. Food Chemistry, 2022, 373: 131454.
[5] Zhaojun C, Lulin T, Xin F, et al. Hydroxy-γ-sanshool from Zanthoxylum bungeanum (prickly ash) induces apoptosis of human colorectal cancer cell by activating P53 and Caspase 8[J]. Frontiers in Nutrition, 2022, 9: 914638.
[6] Chen Z, Tan L, Li L, et al. Sanshools from Zanthoxylum genus and their antioxidant properties in vitro and in vivo[J]. Frontiers in Sustainable Food Systems, 2024, 8: 1256568.

Hydroxy-γ-sanshool是一种从花椒属植物中提取的天然生物碱，属于不饱和脂肪酸酰胺类化合物^[1]。Hydroxy-γ-sanshool具有神经激活、镇痛、抗炎、抗氧化等多种生理活性^{[2, 3]}。Hydroxy-γ-sanshool能够激活人感觉神经元TRPV1通道，触发钙离子内流^[4]。

在体外，Hydroxy-γ-sanshool（0-130µM）处理人结肠腺癌HCT-116细胞24-48h，抑制了细胞生长，诱导了细胞形态扭曲，诱导了细胞周期停滞在G1期，引起程序性细胞死亡，降低了Cyclin D1、CDK4、PCNA的mRNA和蛋白质水平，增加了P21、P53、Fas和Caspase 8的mRNA和蛋白质水平^[5]。

在体内，Hydroxy-γ-sanshool（2.5mg/kg）通过口服治疗葡聚糖硫酸钠（DSS）诱导的氧化应激模型小鼠，提高了肝抗氧化剂能力（T-AOC）和结肠GSH-Px和SOD的水平^[6]。