Cao JingWen, Chen MiaoYu, Xu Ran, Guo MengYao
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Microbiol. 2022 Jul 22;13:961885. doi: 10.3389/fmicb.2022.961885. eCollection 2022.
Inflammatory bowel disease (IBD), a disease that seriously harms human and animal health, has attracted many researchers' attention because of its complexity and difficulty in treatment. Most research has involved rats and dogs, and very little was cats. We should know that gut microbiota varies significantly from animal to animal. Traditional Chinese Medicine and its monomer component have many advantages compared with antibiotics used in pet clinics. Numerous studies have shown berberine (berberine hydrochloride) therapeutic value for IBD. However, the specific mechanism remains to consider.
We assessed gut pathology and analyzed fecal bacterial composition using Histological staining and 16S rRNA sequence. Dioctyl sodium sulfosuccinate (DSS) administration destroyed intestinal mucosal structure and changed the diversity of intestinal flora relative to control. RT-PCR and western blot confirmed specific molecular mechanisms that trigger acute inflammation and intestinal mucosal barrier function disruption after DSS treatment. And autophagy inhibition is typical pathogenesis of IBD. Interestingly, berberine ameliorates inflammation during the development of the intestinal by modulating the toll-like receptors 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and activating autophagy. Berberine significantly reduces tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β expression in cats' serum. Enhancing the antioxidant effect of IBD cats is one of the protective mechanisms of berberine. We demonstrated that berberine repairs intestinal barrier function by activating the mammalian target of rapamycin (mTOR) complex (MTORC), which inhibits autophagy.
Berberine can restore intestinal microbiota homeostasis and regulate the TLR4/NF-κB pathway, thereby controlling inflammatory responses. We propose a novel mechanism of berberine therapy for IBD, namely, berberine therapy can simultaneously activate MTORC and autophagy to restore intestinal mucosal barrier function in cats, which should be further studied to shed light on berberine to IBD.
炎症性肠病（IBD）是一种严重危害人类和动物健康的疾病，因其复杂性和治疗难度而受到众多研究者的关注。大多数研究涉及大鼠和狗，涉及猫的研究很少。我们应该知道，不同动物的肠道微生物群差异很大。与宠物诊所使用的抗生素相比，中药及其单体成分具有许多优势。大量研究表明黄连素（盐酸黄连素）对IBD具有治疗价值。然而，具体机制仍有待探讨。
我们使用组织学染色和16S rRNA序列评估肠道病理学并分析粪便细菌组成。相对于对照组，给予磺基琥珀酸二辛酯钠（DSS）破坏了肠道黏膜结构并改变了肠道菌群的多样性。RT-PCR和蛋白质印迹法证实了DSS处理后引发急性炎症和肠道黏膜屏障功能破坏的特定分子机制。自噬抑制是IBD的典型发病机制。有趣的是，黄连素通过调节Toll样受体4（TLR4）/活化B细胞核因子κB（NF-κB）信号通路并激活自噬来减轻肠道炎症。黄连素显著降低猫血清中肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-6和IL-1β的表达。增强IBD猫的抗氧化作用是黄连素的保护机制之一。我们证明黄连素通过激活抑制自噬的哺乳动物雷帕霉素靶蛋白（mTOR）复合物（MTORC）来修复肠道屏障功能。
黄连素可以恢复肠道微生物群稳态并调节TLR4/NF-κB通路，从而控制炎症反应。我们提出了一种黄连素治疗IBD的新机制，即黄连素治疗可以同时激活MTORC和自噬以恢复猫的肠道黏膜屏障功能，这应该进一步研究以阐明黄连素对IBD的作用。
