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Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy.
Yang, Tongao; Lang, Wuying; Zhao, Yun; Yang, Yahan; Liu, Hongli; Li, Sufen; Li, Xianglong; Zhang, Shuangqi; Zhang, Haihua.
Afiliação
  • Yang T; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Lang W; College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, China.
  • Zhao Y; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Yang Y; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Liu H; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Li S; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Li X; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
  • Zhang S; College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, China.
  • Zhang H; Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Hebei Normal University of Science and Technology, Qinhuangdao, China.
Clin Exp Pharmacol Physiol ; 50(11): 855-866, 2023 11.
Article em En | MEDLINE | ID: mdl-37582493
One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1ß. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Enterite / Inflamassomos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Clin Exp Pharmacol Physiol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Enterite / Inflamassomos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Clin Exp Pharmacol Physiol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China País de publicação: Austrália