Study on alleviate effect of Wuzhi capsule (Schisandra sphenanthera Rehder & E.H. Wilson extract) against mycophenolate mofetil-induced intestinal injury

• Published in: Journal of ethnopharmacology Vol. 288; p. 114987
• Main Authors: Zhang, Zhe, Deng, Yiyun, Feng, Lijuan, Su, Yong, Xu, Dujuan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 24.04.2022
• Subjects: Animals; Animals, Outbred Strains; Anti-inflammation; Anti-Inflammatory Agents - pharmacology; Antioxidant; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Drugs, Chinese Herbal - pharmacology; Immunosuppressive Agents - toxicity; Inflammation - chemically induced; Inflammation - drug therapy; Intestinal Diseases - chemically induced; Intestinal Diseases - drug therapy; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestines - drug effects; Intestines - pathology; Male; Mice; Mycophenolate mofetil; Mycophenolic Acid - toxicity; Oxidative Stress - drug effects; Tight junction; Wuzhi capsule; Tight junction; Mycophenolate mofetil; Wuzhi capsule; Antioxidant; Anti-inflammation; Apoptosis
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2022.114987

Schisandra sphenanthera Rehder & E.H. Wilson (S. sphenanthera) is a botanical medicine included in the 2020 edition of the ChP that has a variety of medicinal activities, including hepatoprotective, anticancer, antioxidant and anti-inflammatory properties. Wuzhi capsule (WZ) is a proprietary Chinese medicine made from an ethanolic extract of S. sphenanthera that is commonly used to treat drug-induced liver injury. However, there are no research reports exploring the effects of WZ on the prevention of mycophenolate mofetil (MMF)-induced intestinal injury and its underlying mechanisms. This experiment aimed to evaluate the ameliorative effect of WZ on MMF-induced intestinal injury in mice and its underlying mechanisms. A mouse model of MMF-induced intestinal injury was established and treated with WZ during the 21-day experimental period. The pathological characteristics of the mouse ileum were observed. Tight junction (TJ) protein changes were observed after immunofluorescence staining and transmission electron microscopy, and ROS levels were measured by using DHE fluorescent dye and the TUNEL assay for apoptosis. The expression of p65, p-p65, IκBα, p-IκBα, the TJ proteins occludin and ZO-1 and the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 and caspase-3 were analysed by Western blot. Levels of DAO, ET, TNF-α, IL-1β, IL-6, IFN-γ, MDA and SOD were analysed by using kits. MMF activated the NF-κB signaling pathway to cause intestinal inflammation, increased intestinal permeability, changed the expression of TJ protein in the intestinal epithelium, and increased oxidative stress and apoptosis levels. WZ significantly downregulated the expression of p-p65 and p-IκBα to relieve the inflammatory response, reduced intestinal permeability, maintained intestinal TJ protein expression, and reduced intestinal oxidative stress and apoptosis. Our research suggested that MMF can cause intestinal injury; by contrast, WZ may exert anti-inflammatory, antioxidant and apoptosis-reducing effects to alleviate MMF-induced intestinal injury. [Display omitted] •WZ reduces MMF-induced increase in intestinal permeability.•WZ restores expression of tight junction proteins in intestinal epithelial cells.•WZ reduces MMF-induced apoptosis in intestinal epithelial cells.•WZ reduces MMF-induced oxidative stress and inflammation.