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      The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

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          Abstract

          Ulcerative colitis (UC) is an idiopathic inflammatory disease mainly affects the large bowel and the rectum. The pathogenesis of this disease has not been fully elucidated, while the disruption of the intestinal barrier function triggered by various stimulating factors related to the host genetics, immunity, gut microbiota, and environment has been considered to be major mechanisms that affect the development of UC. Given the limited effective therapies, the treatment of this disease is not ideal and its incidence and prevalence are increasing. Therefore, developing new therapies with high efficiency and efficacy is important for treating UC. Many recent studies disclosed that numerous herbal decoctions and natural compounds derived from traditional herbal medicine showed promising therapeutic activities in animal models of colitis and have gained increasing attention from scientists in the study of UC. Some of these decoctions and compounds can effectively alleviate colonic inflammation and relieve clinical symptoms in animal models of colitis via regulating intestinal barrier function. While no study is available to review the underlying mechanisms of these potential therapies in regulating the integrity and function of the intestinal barrier. This review aims to summarize the effects of various herbal decoctions or bioactive compounds on the severity of colonic inflammation via various mechanisms, mainly including regulating the production of tight junction proteins, mucins, the composition of gut microbiota and microbial-associated metabolites, the infiltration of inflammatory cells and mediators, and the oxidative stress in the gut. On this basis, we discussed the related regulators and the affected signaling pathways of the mentioned traditional medicine in modulating the disruption or restoration of the intestinal barrier, such as NF-κB/MAPK, PI3K, and HIF-1α signaling pathways. In addition, the possible limitations of current studies and a prospect for future investigation and development of new UC therapies are provided based on our knowledge and current understanding. This review may improve our understanding of the current progression in studies of traditional medicine-derived therapies in protecting the intestinal barrier function and their roles in alleviating animal models of UC. It may be beneficial to the work of researchers in both basic and translational studies of UC.

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          A simple practice guide for dose conversion between animals and human

          Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
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            Ulcerative colitis

            Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
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              Oxidative Stress: Harms and Benefits for Human Health

              Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                09 October 2023
                2023
                : 14
                : 1228969
                Affiliations
                [1] 1 Department of Immunology , School of Medicine , Nantong University , Nantong, Jiangsu, China
                [2] 2 Basic Medical Research Center , School of Medicine , Nantong University , Nantong, China
                Author notes

                Edited by: Lixin Zhu, The Sixth Affiliated Hospital of Sun Yat-sen University, China

                Reviewed by: Xiao Zhu, Guangdong Medical University, China

                Atsushi Kitani, National Institute of Allergy and Infectious Diseases (NIH), United States

                *Correspondence: Liming Mao, lmmao@ 123456ntu.edu.cn
                Article
                1228969
                10.3389/fphar.2023.1228969
                10590899
                37876728
                a47f577e-784d-45d8-ac01-6e6cbe1d2fde
                Copyright © 2023 Xu, Yao, Liu, Zhang and Mao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 May 2023
                : 26 September 2023
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                This study was partially supported by the National Natural Science Foundation of China (32070919 and 32270919), the Natural Science Foundation of Jiangsu Province (BK20201442), Jiangsu Specially-Appointed Professor, and Start-up funds for young scientists of Nantong University (03083051).
                Categories
                Pharmacology
                Review
                Custom metadata
                Ethnopharmacology

                Pharmacology & Pharmaceutical medicine
                ulcerative colitis,traditional medicine,intestinal barrier function,mechanism,natural compound,decoction

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