作者机构：
[戴宗顺; 宋厚盼; 胡胜涛; 刘乐平; 林也; 张逢; 蔡雄; 张二兵] Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China;[黄宇明] Hunan Zhengqing Pharmaceutical Group Co. Ltd., Huaihua, 418000, China;[刘良] State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, Macau;[陆晓珊; 唐琳] Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China
通讯机构：
[Cai, X.] I;[Liu, L.] S;Institute of Innovation and Applied Research in Chinese Medicine, China;State Key Laboratory of Quality Research in Chinese Medicine, Macau
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.
作者机构：
[Cai, Xiong; Shehla, Nuzhat; Wang, Wei; Peng, Cai-Yun; Liu, Le-Ping; Liao, Duan-Fang; Cao, Liang; Peng, CY; Jian, Yu-Qing; Li, Bin; Sheng, Wen-Bing; Gong, Li-min] Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab,Acad Attaur, Changsha 410208, Peoples R China.;[Cao, Liang] Hunan Acad Agr Sci, Inst Agr Environm & Agroecol, Changsha 410125, Peoples R China.;[Choudhary, M. Iqbal; Shehla, Nuzhat] Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.;[Man, Rong-Yong] First Peoples Hosp Huaihua, Clin Expt Res Ctr, Huihua 418000, Peoples R China.
通讯机构：
[Peng, CY; Wang, W] H;Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab,Acad Attaur, Changsha 410208, Peoples R China.
摘要：
In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 muM.
作者机构：
[丁长松; 黄辛迪; 梁力伟] School of Informatics, Hunan University of Chinese Medicine, Changsha, 410208, China;[梁昊] Institute of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, 410208, China;[蔡雄] Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构：
[Ding, C.-S.] S;School of Informatics, China
作者机构：
[Cai, Xiong; Shehla, Nuzhat; Peng, Caiyun; Sheng, Wenbing; Wang, Wei; Liao, Duan-Fang; Liu, Leping; Cao, Liang; Jian, Yuqing; Li, Bin] Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Academician Atta ur Rahman Belt & Rd Tradit Med R, Innovat Mat Med Res Inst,Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Choudhary, M. Iqbal; Shehla, Nuzhat; Rahman, Atta-ur] Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.;[Cao, Liang] Hunan Acad Agr Sci, Inst Agr Environm & Agroecol, Changsha 410125, Hunan, Peoples R China.;[Man, Rongyong] First Peoples Hosp Huaihua, Clin Expt Res Ctr, Huaihua 418000, Peoples R China.
通讯机构：
[Li, B; Wang, W] H;Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Academician Atta ur Rahman Belt & Rd Tradit Med R, Innovat Mat Med Res Inst,Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
In the present work, we take advantage of the characteristic NMR signal (delta(C-10) = 96.0-99.9) for guiding the isolation of schinortriterpenoids (SNTs) from n-butanol fraction of stems of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the identification of three unreported 3,4:9,10-disecocycloartane triterpenoids xuetongdilactones A-C and three undescribed SNTs xuetongdilactones D-F, along with two known SNTs, namely, wuweizidilactone B and micrandilactone B. The structures of the unreported compounds were established based on 1D, and 2D NMR, HRESIMS, and ECD spectroscopic data analysis. The absolute stereochemistry of xuetongdilactone A was determined by X-ray diffraction analysis along with ECD calculation. The antioxidant and cytotoxic activities were evaluated for all the isolated compounds.
期刊：
Journal of International Medical Research,2020年48(9) ISSN：0300-0605
通讯作者：
Wang, Yuhong
作者机构：
[Cai, Xiong; Ling, Chengli; Lei, Chang; Wang, Yuhong; Zou, Manshu; Xiang, Yun; Huang, Dan] Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Training Base Prov Minist Joint State Key Lab Chi, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Xie, Yu] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha, Hunan, Peoples R China.;[Li, Xuran] Hunan Univ Chinese Med, Sch Pharm, Changsha, Hunan, Peoples R China.
通讯机构：
[Wang, Yuhong] H;Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Training Base Prov Minist Joint State Key Lab Chi, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
Cerebral ischemia;reperfusion;neuropharmacology;apigenin;flavonoids;PC12 cell model;oxidative stress;mitochondria;middle cerebral artery occlusion rat model
摘要：
Objective The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, both in vitro and in vivo. Methods We first treated PC12 cells with cobalt chloride (CoCl2) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores. Results The half-inhibitory concentration of CoCl2 was 1.2 mM. Pretreatment with 10 µg ⋅ mL−1 apigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl2-induced injury in vitro. In addition, apigenin treatment in vivo significantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation. Conclusions Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injury in vitro and in vivo.
期刊：
Journal of Separation Science,2020年43(7):1382-1392 ISSN：1615-9306
通讯作者：
Yan, Jianye;Xia, Xinhua
作者机构：
[Cai, Xiong; Zhang, Ye; Yan, Jianye; Tan, Shihan; Huang, Dan; Lei, Yating] Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, 300 Xueshi Rd, Changsha 410004, Peoples R China.;[Wang, Yuanqing] Cent South Univ Forestry & Technol, Sch Life Sci & Technol, Changsha, Peoples R China.;[Sun, Zhicheng] Cent South Univ, Dept Spine Surg, Xiangya Hosp, Changsha, Peoples R China.;[Xia, Xinhua; Lin, Meiyu; Luo, Kun; Yan, Jianye] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410004, Peoples R China.
通讯机构：
[Yan, Jianye; Xia, Xinhua] H;Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, 300 Xueshi Rd, Changsha 410004, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410004, Peoples R China.
关键词：
chromatographic fingerprints;quality control;quantitative analysis;traditional Chinese medicine
摘要：
The present study aimed to develop a strategy involving quantitative analysis of multicomponents by single marker in combination with high-performance liquid chromatography fingerprint qualitative analysis for performing the quality control of Aurantii Fructus. The content of 12 components (eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, meranzin, poncirin, naringenin, nobiletin, tangeretin, and auraptene) in samples was determined using reliable relative correction factors that were obtained using naringin as an internal reference standard. The new method demonstrated good applicability, and no significant differences were observed between the external standard method and the new method as determined by calculating standard method difference. Qualitative evaluation of samples was conducted using similarity analysis, hierarchical cluster analysis, and quality fluctuation analysis. Chromatographic fingerprint data were divided into three groups by similarity and hierarchical cluster analyses, and seven components may have a more significant impact on the quality of Aurantii Fructus in quality fluctuation analysis. Overall, the study suggests that the qualitative and quantitative analyses of multicomponents using quantitative analysis of multicomponents by single marker combined with chromatographic fingerprinting can be considered good quality criteria for performing quality control and providing technical support for the further pharmacological and pharmaceutical research of Aurantii Fructus.
