Panax quinquefolium saponins protect against cisplatin evoked intestinal injury via ROS-mediated multiple mechanisms |
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| Affiliation: | 1. College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China;2. National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China;3. College of Life Science, Dalian Minzu University, Dalian 116600 China;1. Basic Medical School, Binzhou Medical University, Yantai, P. R. China;2. School of Pharmacy, Binzhou Medical University, Yantai, P. R. China;3. Department of Biomedical Engineering, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA;1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;2. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming China;3. Department of PIVAS, Yanbian University Hospital, Yanji, China;4. Department of Phathology, Yanbian University Hospital, Yanji, China;1. College of Pharmaceutical Sciences & College of Chinese Medicine, Southwest University, Chongqing 400715, China;2. Department of Hematology, Sichuan Provincial People''s Hospital, Chengdu 610212, Sichuan, China;3. Department of Oncology and Hematology, Chongqing Ninth People''s Hospital, Jialing Village 69, Beibei District, Chongqing 400700, China;1. Department of Pediatric Surgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan;2. Department of Pediatric Surgery, Osaka City General Hospital, 2-13-22, Miyakojima-Hondori, Miyakojima-ku, Osaka 534-0021, Japan |
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| Abstract: | BackgroundCisplatin is one of the most common chemotherapeutic drugs. Cisplatin-induced toxicity gives rise to gastrointestinal cell damage, subsequent diarrhea and vomiting, leading to the discontinuation of its clinical application in long-term cancer chemotherapy. Panax quinquefolium L., also known as American ginseng, has many pharmacological activities such as improving immunity, anti-tumor, anti-radiation and blood sugar lowering.PurposePreviously, our laboratory reported that American ginseng berry extract could alleviate chemotherapeutic agents-induced renal damage caused by cisplatin. Hence, this study further explored the protective effect of P. quinquefolium saponins (PQS) on cisplatin-induced intestinal injury in mice and the possible molecular mechanisms.MethodsBiochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze intestinal injury based on various molecular mechanisms.ResultsWe demonstrated the destruction of the intestinal barrier caused by cisplatin exposure by detecting the activity of diamine oxidase (DAO) and the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Meanwhile, cisplatin exposure changed SOD and MDA levels in the small intestine, causing oxidative damage to the intestinal mucosa. The inflammation associated-intestinal damage was further explored by the measurement of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and analysis of nuclear factor-kappa B (NF-κB) inflammatory pathway protein expression. Moreover, apoptotic cells labeled with TUNEL staining-positive cells and activated caspase family proteins suggest that cisplatin induces intestinal apoptosis. Interestingly, PQS pretreatment significantly reversed these situations.ConclusionThese evidences clearly suggest that PQS can alleviate cisplatin-induced intestinal damage by inhibiting oxidative stress, reducing the occurrence of inflammation and apoptosis, and improving intestinal barrier function. |
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