期刊：
Journal of Ethnopharmacology,2024年318(Pt B):116990 ISSN：0378-8741
通讯作者：
Li, H;Liu, WH
作者机构：
[Li, Hua; Chen, Cong; Zhou, Xiao-qing; Qiu, Shi-wei; Liu, Wang-hua; Li, Jin-xia; Zhou, Chang; Zheng, Cai-xing] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Li, Hua; Liu, Wang-hua; Zhou, Chang] Key Lab TCM Diagnost Hunan Provine, Changsha 410208, Hunan, Peoples R China.;[Zhou, Chang] Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Liu, Wang-hua] Key Lab TCM Heart & Lung Syndrome Differentiat & M, Changsha 410208, Hunan, Peoples R China.;[Liu, Wang-hua] Hunan Engn Technol Res Ctr Med & Funct Food, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Li, H ; Liu, WH ] H;Hunan Univ Tradit Chinese Med, 300 Bachelor Rd,Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, 300 Bachelor Rd,Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.
关键词：
Ischemic stroke;Microglial;Pyroptosis;Inflammation;Glial-vascular unit
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. AIM OF THE STUDY: This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). MATERIALS AND METHODS: Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36g/kg/day), JDHXD-M group (10.71g/kg/day), JDHXD-H group (21.42g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. RESULTS: In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). CONCLUSIONS: Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.
作者机构：
[Qiu, Jingyue; Xiong, Meng; Zhong, Meiqi; Yu, Chang; Ren, Baoping; Song, Houpan] Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan Province, China;[Yu, Chang] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address: yuc@stu.hnucm.edu.cn;[Qiu, Jingyue] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address: QiuJY@stu.hnucm.edu.cn;[Xiong, Meng] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address: xiongmeng@stu.hnucm.edu.cn;[Ren, Baoping] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address: rbp@stu.hnucm.edu.cn
通讯机构：
[Yu, Chang; Qiu, Jingyue; Zhong, Meiqi; Xiong, Meng; Song, Houpan; Zeng, Meiyan; Ren, Baoping] C;[Zhou, Sainan; Li, Yuejun] D;College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address:;Department of Gastroenterology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China. Electronic address:;Department of Oncology, The Third Affiliated Hospital of Hunan University of Chinese Medicine, Zhuzhou, Hunan Province, China. Electronic address:
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Lizhong Pill (LZP) and its herbal constituents are frequently utilized in Asian (China, Saudi Arabia, India, Japan, etc.) and some European (Russia, Sweden, UK, etc.) nations to treat various gastrointestinal ailments. AIM OF THE STUDY: This study aimed to investigate the protective impact and potential mechanism of LZP against indomethacin (IND)-induced gastric mucosal injury in rats. MATERIAL AND METHODS: Using a biochemical kit, we investigated the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in rat serum, as well as pepsin in rat stomach tissue, using an IND-induced rat model of gastric mucosal injury. Various imaging tools, including HE staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to examine the gastric mucosa's surface morphology and ultrastructure. Furthermore, molecular docking was employed to predict the binding capacity of the primary bioactive components of LZP to the critical molecular protein targets in the IL-17 and TNF signaling pathways. At the same time, immunofluorescence was used to determine the protein expressions of CASP3, VCAM1, MAPK15, MMP3, IL-17RA, and TNFR1. RESULTS: The present study demonstrates that LZP (3.75 and 7.50g/kg) significantly reduces the gastric mucosal injury index induced by IND. This effect is evidenced by the improved morphology, surface, and structure of the gastric mucosa, as determined by HE, SEM, and TEM findings. Additionally, 3.75 and 7.50g/kg LZP intervention significantly increased SOD and CAT contents and inhibited pepsin and GST activities. Molecular docking analysis revealed that the small molecular components of LZP can bind spontaneously to crucial proteins involved in the IL-17 and TNF signaling pathways, including MAPK15, MMP3, VCAM1, and CASP3. The immunofluorescence findings proved that LZP (3.75 and 7.50g/kg) can inhibit the protein expressions of MAPK15, MMP3, VCAM1, CASP3, IL-17RA, and TNFR1. CONCLUSIONS: Our investigation findings demonstrate that LZP can potentially ameliorate IND-induced damage to the gastric mucosa by inhibiting IL-17 and TNF signaling pathways. These results offer encouraging support for using alternative medicine to manage drug-induced gastric mucosal injury.
