Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, PR China; Key Laboratory of Xinjiang Phytomedicine Resources and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, PR China.
Key Laboratory of Xinjiang Phytomedicine Resources and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, PR China.
J Ethnopharmacol. 2023 Mar 1;303:115990. doi: 10.1016/j.jep.2022.115990. Epub 2022 Dec 9.
As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear.
This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy.
The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses.
Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro.
TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.
作为一种用于祛风止痛的彝族药物，三叶崖爬藤 var. yunnanensis（S. Y. Hu）H. S. Lo（TSY）被广泛用于治疗喉咙痛、胃痛、骨伤和肿瘤；然而，其物质基础和作用机制尚不清楚。
本研究旨在采用多靶点策略研究 TSY 的潜在活性化合物及相关抗胃癌药理机制。
通过文献回顾和数据库搜索收集 TSY 的主要化学成分。进一步筛选这些成分的 ADMET 特性，并使用网络药理学（admetSAR）和基于亚结构-药物-靶标网络推断（SDTNBI）方法进行计算机预测。通过体内和体外生化分析鉴定 TSY 提取物的镇痛、镇静和抗胃癌作用的药理机制。
在此，鉴定出 28 种化学成分，选择 7 种活性化合物，预测 TSY 提取物的 75 个靶标。一个化合物-靶标-疾病网络拓扑方法表明，预测的靶标与消化系统和神经系统高度相关。网络药理学结果表明，TSY 的抗胃癌活性与其镇痛和镇静靶标以及 MAPK 高度相关。体内实验证实，TSY 提取物不仅减少了小鼠模型中的自发活动次数，而且对戊巴比妥钠诱导的睡眠具有协同作用，减少了醋酸诱导的扭体反应小鼠的数量，并提高了热板疼痛的小鼠痛阈。因此，TSY 提取物具有良好的镇痛和镇静作用。TSY 提取物通过调节凋亡蛋白（BAX、BCL-2 和 BCL-XL）抑制 HGC-27 细胞增殖并诱导细胞凋亡。
TSY 具有镇痛、镇静和抗胃癌的综合作用。
