期刊：
Evidence-Based Complementary and Alternative Medicine,2020年2020 ISSN：1741-427X
通讯作者：
Peng, Qinghua;Cai, Xiong
作者机构：
[Chen, Xiaojuan; Chen, Xinyi; Peng, Qinghua; Lin, Ye; Song, Houpan] Hunan Univ Chinese Med, Inst Tradit Chinese Med Diagnost, Changsha, Hunan, Peoples R China.;[Chen, Xiaojuan; Chen, Xinyi; Yu, Rong; Lin, Ye; Zeng, Meiyan; Song, Houpan] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Peng, Jun] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha, Hunan, Peoples R China.;[Cai, Xiong] Hunan Univ Chinese Med, Chinese Med, Inst Innovat & Appl Res, Changsha, Hunan, Peoples R China.
通讯机构：
[Peng, Qinghua; Cai, Xiong] H;Hunan Univ Chinese Med, Inst Tradit Chinese Med Diagnost, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Chinese Med, Inst Innovat & Appl Res, Changsha, Hunan, Peoples R China.
摘要：
Background. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) often causes small intestinal ulcers in patients, but few effective drugs are currently available to manage such serious adverse events of NSAIDs. Li-Zhong decoction (LZD), a well-known traditional Chinese medicine (TCM) formula, is commonly prescribed for treatment of gastrointestinal diseases. The present study aimed to investigate the anti-ulcerogenic activity of LZD on indomethacin- (IND-) induced duodenal ulcer in rats. Mechanistic studies of action of LZD were focused on involvement of TLR-2/MyD88 signaling pathway. Methods. Fifty male Sprague-Dawley (SD) rats were randomly and evenly divided into five groups: normal control, ulcer control (IND, 25 mg/kg), IND + esomeprazole (ESO, 4.17 mg/kg), and IND + low and high doses of LZD (3.75 and 7.50 g/kg). Macroscopic and histopathological examinations were performed for evaluation of ulcer index (UI), curative index (CI), and microscopic score (MS). Levels of duodenal inflammatory biomarkers and cytoprotective mediators including interleukin-4 (IL-4), IL-10, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E-2 (PGE(2)) were measured by ELISA. Expression levels of TLR-2 and MyD88 mRNA were assessed by qRT-PCR. The expression and distribution of TLR-2 and MyD88 proteins were analyzed by western blot and immunohistochemistry, respectively. Results. Gross and microscopic examinations of the IND-treated rats revealed severe duodenal hemorrhagic necrosis, inflammatory infiltration, villus destruction, and crypt abscess, while LZD-treated rats manifested these pathological events to a markedly lesser degree. LZD significantly decreased UI and MS, increased CI, preserved the integrity of the villus and crypt, and normalized the tissue architecture of the duodenum of rats. The elevated TNF-alpha levels in the IND-treated rats were markedly diminished in the LZD-treated rats, while lower levels of IL-4, IL-10, and PGE(2) observed in IND-treated rats were significantly increased in LZD-treated rats. Interestingly, improvement of immune function in duodenal mucosa by reduction of mRNA and protein expression levels of TLR-2 and MyD88 was also observed in rats treated with LZD. Consistently, immunohistochemical analyses revealed a lower co-localization of TLR-2 and MyD88 proteins in the duodenal mucosa of LZD-treated rats as compared to the IND-induced rats. Conclusions. Our data demonstrate that LZD protects the duodenal mucosa from IND-caused lesions, which is at least partially attributable to the interaction of its potential cytoprotective and anti-inflammatory mechanisms together with enhancement of the mucosal immunity through TLR-2/MyD88 signaling pathway.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Li-Zhong-Tang (LZT) is a well-known Chinese herbal formulation first described in one of traditional Chinese medicine (TCM) scriptures, Treatise on Febrile Diseases. LZT has been commonly prescribed for the treatment of various gastrointestinal diseases for over 1800 years, and has demonstrated pronounced therapeutic effects on patients with gastric ulcers. AIM OF THE STUDY: The present study aimed to scientifically evaluate protective effects of LZT on indomethacin (IND)-induced gastric injury in rats and to elucidate whether LZT exerts its gastro-protective effects via enhancing mucosal immunity by regulating TLR-2/MyD88 signaling pathway. MATERIAL AND METHODS: Gastric ulcers were induced in male Sprague-Dawley (SD) rats with a single oral dose of 150mg/kg IND. Ulcer index (UI) and curative index (CI) were evaluated. Histopathological examinations were performed and microscopic score (MS) was macroscopically calculated. The volume of gastric juice, free acidity, total acidity, and gastric pH was measured. The gastroprotective and inflammatory biomarkers including levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin E(2) (PGE(2)), and malondialdehyde (MDA) were determined. Expression levels of TLR-2 and MyD88 mRNA were assessed by qRT-PCR. The expression, distribution, and co-localization of TLR-2 and MyD88 protein were determined by Western blot, immunohistochemistry, and immunofluorescence, respectively. RESULTS: Induction of gastric ulcers in rats resulted in very significantly increased UI and elevated volume and acidity of gastric juice, which were markedly attenuated by LZT treatment. Microscopic examinations of the IND-induced gastric ulcers revealed severe gastric hemorrhagic necrosis, submucosal edema, and destruction of epithelial cells, which were significantly attenuated in LZT-treated rats. Moreover, treatment with LZT remarkably increased gastric mucosal levels of PGE(2) and NO, and lowered highly elevated levels of TNF-α and MDA in gastric ulcerative rats. Mechanistically, LZT inhibited mRNA and protein expression of TLR-2 and MyD88 and enhanced immune function in gastric mucosa. Immunohistochemical analyses and immunofluorescent detection further confirmed a markedly decreased co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LZT-treated rats as compared to that of gastric ulcerative rats. CONCLUSIONS: These findings indicate that LZT alleviates serious gastric mucosal ulcerations induced by IND. Protective effects of LZT on gastric ulcers are believed to be associated with the intensification of the anti-oxidative defense system, mitigation of proinflammatory cytokines, stimulation of the production of cytoprotective mediators, and improvement of the mucosal immunity through TLR-2/MyD88 signaling pathway.
作者：
SONG Hou-Pan;ZENG Mei-Yan;CHEN Xiao-Juan;CHEN Xin-Yi;YANG Yi-Jing;...
期刊：
数字中医药(英文),2019年2(3):136-146 ISSN：2096-479X
通讯作者：
Peng Jun
作者机构：
[CAI Xiong] Institute of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[ZENG Mei-Yan] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[YANG Yi-Jing; ZHOU Ya-Sha; TIAN Ye; LIU Xiao-Qing] Hunan Provincial Key Laboratory for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine, Changsha, Hunan 410208, China;[PENG Jun] Department of Ophthalmology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;[SONG Hou-Pan; CHEN Xiao-Juan; CHEN Xin-Yi] Institute of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
通讯机构：
[Peng Jun] D;Department of Ophthalmology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
