School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Rd, Hefei 230012, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang Rd, Nanjing 210009, China; Anhui Provincial Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei 230012, China; Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230012, China.
School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Rd, Hefei 230012, China.
Phytomedicine. 2022 Sep;104:154322. doi: 10.1016/j.phymed.2022.154322. Epub 2022 Jul 6.
Traditional Chinese Medicine decoctions (TCMDs) can be used to prepare outstanding pharmaceutical preparations by the patient themselves. Small molecular active ingredients and macromolecular polysaccharides are inevitably co-existed in TCMDs. Different from the pharmacological synergies among small molecules, the macromolecular polysaccharides in TCMDs might contribute to disease treatment in several ways, although it is frequently overlooked.
HYPOTHESIS/PURPOSE: This study proposes that the oral bioavailability of the water-insoluble alkaloids of Coptis chinensis Franch. (Ranunculaceae) (C. chinensis) decoction may be attributed to the co-existing C. chinensis polysaccharides (CCPs) dynamically influencing the small intestine microenvironment and regulating the modulation of the paracellular absorption pathway.
First, the effects of CCPs on the oral bioavailability of the main active ingredient of C. chinensis, berberine, were evaluated in vivo. Next, a series of in situ experimental models of intestinal perfusion and models of isolated jejunal mucosa, Caco-2 cell monolayer membranes, and microfold-like cells were established to assess the correlation among CCPs, intestinal mucosal immunity, and paracellular absorption in the small intestine.
It was observed that CCPs could be endocytosed by the microfold cells on the surface of Peyer's patches, allowing CCPs to activate the lymphocytes, modulate the balance of Th1/Th2, control the secretion of immune effectors IFN-γ and IL-4, and finally regulate the tight junctions in the intestinal epithelial cells. This was a dynamic process with the movement of CCPs in the gastrointestinal tract that altered the flora distribution and functioning of the TLR/NF-κB signal pathway in the small intestine.
The dynamical regulation of CCP on the immune microenvironment of small intestine is responsible for its promotion on the health controlling effects of C. chinensis in traditional dosage forms of decoction.
中药汤剂（TCMDs）可以由患者自己用来制备出色的药物制剂。小分子活性成分和大分子多糖不可避免地共存于 TCMD 中。与小分子之间的药理学协同作用不同，TCMD 中的大分子多糖可能通过多种方式有助于疾病治疗，尽管这经常被忽视。
假设/目的：本研究提出，黄连（毛茛科）汤的水不溶性生物碱的口服生物利用度可能归因于共存的黄连多糖（CCPs）动态影响小肠微环境并调节细胞旁吸收途径的调节。
首先，体内评价 CCPs 对黄连主要活性成分小檗碱口服生物利用度的影响。接下来，建立了一系列肠灌注原位实验模型和分离的空肠黏膜、Caco-2 细胞单层膜和微褶皱样细胞模型，以评估 CCPs、肠黏膜免疫和小肠细胞旁吸收之间的相关性。
观察到 CCPs 可被派尔集合淋巴结表面的微褶皱细胞内吞，使 CCPs 能够激活淋巴细胞，调节 Th1/Th2 平衡，控制免疫效应物 IFN-γ和 IL-4 的分泌，最终调节肠上皮细胞中的紧密连接。这是一个动态过程，CPs 在胃肠道中的运动改变了小肠中 TLR/NF-κB 信号通路的菌群分布和功能。
CCP 对小肠免疫微环境的动态调节是其促进黄连在传统汤剂剂型中健康控制作用的原因。
