1.Study on the Optimization of the Extraction Technology of Shengmaiyin Polysaccharide and Its Regulation Effects on Intest- inal Function of Spleen Deficiency Model Rats
Yu YOU ; Lin LUO ; Zhejie CHEN ; Meisi LIN ; Heying XU ; Bo XIONG ; Chaomei FU ; Tian XIE
China Pharmacy 2019;30(4):493-498
OBJECTIVE: To optimize the extraction technology of Shengmaiyin polysaccharide, and to investigate the regulation effects of Shengmaiyin and its polysaccharide on intestinal function of spleen deficiency model rats. METHODS: The contents of polysaccharide were determined by phenol-sulfuric acid method, and the extraction rate of polysaccharide was calculated. Using extraction rate of Shengmaiyin polysaccharide as investigation index, singel factor and orthogonal tests were used to optimize material-liquid ratio, extraction time, extraction temperature and extraction times of Shengmaiyin polysaccharide. Validation test was also conducted. Totally 80 male SD rats were randomly divided into blank group, model group, Shengmaiyin low-dose, medium-dose and high-dose groups (350, 700, 1 400 g/L, by crude drug), Shengmaiyin polysaccharide low-dose, medium-dose and high-dose groups (24.5, 49, 98 g/L, by crude drug), with 10 rats in each group. Except for blank group, other groups were given Rheum palmatum water decoction 10 mL/kg to induce spleen deficiency model, once a day, for consecutive 15 d. Since the 16th day, blank group and model group were given isovolumic water intragastrically, while other groups were given corresponding drugs, once a day, for consecutive 10 d. The general status of rats and body weights were recorded in each group. The serum contents of D-xylose, gastrin (GAS) and vasoactive intestinal peptide (VIP) were detected by phloroglucinol method or ELISA. RESULTS: The optimal extraction technology of Shengmaiyin polysaccharide was material-liquid ratio 1 ∶ 10(g/mL), extraction time 45 min, extraction temperature 80 ℃, extracting for 1 time. Results of validation test showed that extraction rates of the polysaccharide in 3 times were 7.43%, 7.64%, 7.80% (RSD=1.01%, n=3). After modeling, except for blank group, other groups suffered from loose stools, thin body and reduced food intake, and the body weight and serum level of D-xylose were decreased significantly compared with blank group (P<0.01). After last medication, above symptoms of administration groups were improved to different extents. Except for model group, body weight and serum contents of D-xylose in other groups were increased significantly than those before modeling or before medication (P<0.05 or P<0.01). Compared with blank group, body weight and serum content of GAS were decreased significantly in model group, while serum content of VIP was increased significantly (P<0.01). Compared with model group, body weight of Shengmaiyin medium-dose group and Shengmaiyin polysaccharide low-dose and high-dose groups, serum contents of D-xylose and GAS in Shengmaiyin medium-dose and high-dose groups and Shengmaiyin polysaccharide low-dose and medium-dose groups were increased significantly, while serum contents of VIP in Shengmaiyin groups and Shengmaiyin polysaccharide low-dose and medium-dose groups were all decreased significantly (P<0.05 or P<0.01). CONCLUSIONS: The optimized extraction technology of Shengmaiyin polysaccharide is stable and feasible. Shengmaiyin and its polysaccharide contribute to the recovery of intestinal function of spleen deficiency model rat, the effects of which may be associated with the secretion regulation of GAS and VIP.
2.A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis.
Zhejie CHEN ; Wei HAO ; Caifang GAO ; Yangyang ZHOU ; Chen ZHANG ; Jinming ZHANG ; Ruibing WANG ; Yitao WANG ; Shengpeng WANG
Acta Pharmaceutica Sinica B 2022;12(8):3367-3382
With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.