Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.

Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.

[Proteomic study of Jingfang Mixture on urticaria based on label-free quantitative proteomics technology].

This study aims to explore the effect of Jingfang Mixture on the protein expression of urticaria in mice and explain the mechanism of Jingfang Mixture in the treatment of urticaria. Twenty-seven male Kunming mice were randomly divided into a normal group, a model group and a Jingfang Mixture group according to body weight. Except for the normal group, mice in the model group and the Jingfang Mixture group were injected with the mixture of ovalbumin and Al(OH)_3 gel for the first immunization, and the second immunization was performed on the 10 th day to induce the urticaria model. Mice in the Jingfang Mixture group started to be administered on the 6 th day after the initial immunization, and was administered continuously for 21 days. The normal group and the model group were replaced with the same amount of purified water. Twenty-four hours after the last administration, an appropriate amount of skin was taken, and label-free quantitative proteomics technology was used to detect the differences in protein expression in skin tissue. The signaling pathways involved in the differential proteins was further analyzed. The results of proteomics indicated that seventy-six proteins were involved in the intervention of Jingfang Mixture on mice with urticaria, and the differential proteins were mainly enriched in biological process(BP), molecular function(MF), and cellular component(CC). Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the signaling pathways regulated by Jingfang Mixture mainly involved carbon metabolism, metabolic pathways, glucagon signaling pathway, glycolysis/gluconeogenesis, pentose phosphate pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, purine metabolism, adherens junction, calcium signaling pathway, leukocyte transendothelial migration, and inflammatory mediator regulation of transient receptor potential(TRP) channels, which were involved in skin tissue energy metabolism and immune regulation. The findings of this study showed that the protective effect of Jingfang Mixture on mice with urticaria was closely related to the regulation of immune disorders, and the regulatory effect on immune system may be achieved through the regulation of energy metabolism by Jingfang Mixture.