Guangzhou General Pharmaceutical Research Institute, Guangzhou, Guangdong 510240, PR China; Integrated Chinese and Western Medicine, Post-doctoral Research Station, Jinan University, Guangzhou, PR China; Shenzhen Institute of Geriatrics, Shenzhen 518020, PR China.
Basic Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Bioorg Med Chem. 2020 Oct 15;28(20):115697. doi: 10.1016/j.bmc.2020.115697. Epub 2020 Aug 6.
Structural modification of active natural compoundswhichwereoriginated fromTraditional Chinese Medicine (TCM) have showedgreat advantagesin thedevelopmentof new drugs. In TCM, "Huangqin-Huanglian" is a classic "medicine couple"thathas been used to treat intestinal diseases for thousands ofyears, while baicalinand berberine are the major active compoundsof Huangqin and Huanglianrespectively. Based onthis"medicine couple",wedesignedand synthesizeda newbaicalin and berberine hybrid compound (BBH).Its molecular structure wasconfirmedby spectroscopy.The antibacterial activity of BBH was detected in vitro.Results indicatedthat the new hybrid compound exhibited the best antibacterial activity forproteobacteria as compared with its original synthetic materials (baicalin andberberine). In vivo, the effect of BBHon ulcerative colitiswas alsoinvestigated.BBH treatment significantly ameliorated the disease symptoms andpreventedthe colon damage of ulcerative colitis. Furthermore, BBH showed asignificant anti-inflammatory effect through regulating activities of SOD, MPOandexpressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in colontissue. Data also suggested that BBH was more superior than baicalin and berberine inameliorating colonic damage. This indicated that the new hybrid compound BBHshowed enhanced efficacy in treating ulcerative colitis.
结构修饰的活性天然化合物起源于传统中药（TCM）已经显示出巨大的优势在新药的开发。在中医中，“黄芩黄连”是一个经典的“药对”，已经被用于治疗肠道疾病数千年，而黄芩苷和小檗碱是黄芩和黄连的主要活性化合物。基于这个“药对”，我们设计并合成了一种新的黄芩苷和小檗碱的混合化合物（BBH）。它的分子结构通过光谱学来确认。BBH 的体外抗菌活性被检测到。结果表明，与原始合成材料（黄芩苷和小檗碱）相比，新的混合化合物对变形菌表现出最好的抗菌活性。在体内，也研究了 BBH 对溃疡性结肠炎的作用。BBH 治疗显著改善了疾病症状，防止了溃疡性结肠炎的结肠损伤。此外，BBH 通过调节 SOD、MPO 的活性和结肠组织中促炎细胞因子（TNF-α、IL-1β和 IL-6）的表达来发挥显著的抗炎作用。数据还表明，BBH 在改善结肠损伤方面比黄芩苷和小檗碱更有优势。这表明新的混合化合物 BBH 在治疗溃疡性结肠炎方面具有增强的疗效。
