Construction of various lipid carriers to study the transdermal penetration mechanism of sinomenine hydrochloride.

OBJECTIVE: To investigate the transdermal mechanisms and compare the differences in transdermal delivery of Sinomenine hydrochloride (SN) between solid lipid nanoparticles (SLN), liposomes (LS), and nanoemulsions (NE). METHODS: SN-SLN, SN-LS and SN-NE were prepared by ultrasound, ethanol injection and spontaneous emulsification, respectively. FTIR, DSC, in vitro skin penetration, activation energy (Ea) analysis were used to explore the mechanism of drug penetration across the skin. RESULTS: The particle size and encapsulation efficiency were 126.60 nm, 43.23 ± 0.48%(w/w) for SN-SLN, 224.90 nm, 78.31 ± 0.75%(w/w) for SN-LS, and 83.22 nm, 89.01 ± 2.16%(w/w) for SN-LS. FTIR and DSC showed the preparations had various levels of impacts on the stratum corneum's lipid structure which was in the order of SLN > NE > LS. Ea values of SN-SLN, SN-LS, and SN-NE crossing the skin were 2.504, 1.161, and 2.510 kcal/mol, respectively. CONCLUSION: SLN had a greater degree of alteration on the skin cuticle, which allows SN to permeate skin more effectively.

The intestinal mucosal barrier - A key player in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a recurrent chronic autoimmune disease, which is not only difficult to treat, but also has a great adverse impact on the physical and mental health of patients. The intestinal mucosa barrier has some relationship with RA and it consists of mechanical barrier, chemical barrier, immune barrier, and microflora barrier. It is a dynamic system that contributes to the stability of the intestinal environment by regulating the absorption of relevant substances from the lumen into the circulation, while limiting the passage of harmful substances. This article summarizes the connection between the intestinal mucosa barrier and RA, and proposes the role of relevant Chinese medicines on RA from the point of improving barriers, to provide new perspectives on the pathogenesis and therapeutic strategies of RA.

Chinese herb couple against diabetes: integrating network pharmacology and mechanism study.

Cassia twig is a dry twig of Cinnamomum cassia Presl, a Lauraceae plant. Astragalus L is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. Chinese herb couple refers to the matching of two herbs in pairs, mostly with synergistic effects or toxicity reduction. This Chinese herb couple (Cassia twig-Astragalus) come from the classic famous book "Zhang Xichun's book on Chinese herb couple", which is widely used to treat diabetes. Moreover, both Cassia twig and Astragalus belong to the homology of medicine and food. However, its mechanism is still unclear. The study identified the effective components of Cassia twig-Astragalus by UPLC-Q-TOF-MS/MS and investigated the mechanism of Cassia twig-Astragalus in treating diabetes by virtue of network pharmacology, molecular docking and experimental verification. Firstly, based on UPLC-Q-TOF-MS/MS and network pharmacology, a total of 10 active ingredients of Astragalus and 6 active ingredients of Cassia twig were screened, and a total of 13 key targets were obtained. There were 64 targets at the intersection of Cassia twig-Astragalus with diabetes, mainly including IL-17, TNF, NF-κß, AGE-RAGE signaling pathway, etc. It mainly involves the response of cells to insulin stimulation, the response to insulin and the positive regulation of cell adhesion. Secondly, molecular docking results showed that quercetin has good binding activities with AKT1 and TNF. Calycosin has good binding activities with AKT1, TNF and CAV1. Formononetin has good binding activities with TNF and IL-6. Isorhamnetin has good binding activities with AKT1, TNF and IL-6. Finally, the animal experiments showed that Cassia twig-Astragalus could improve the body weight, blood glucose and glucose tolerance in diabetic rats. After the intervention with Cassia twig-Astragalus, the inflammatory factors (IL-10, TNF-α, IL-6) were significantly improved in diabetic rats, which also effectively reduced TG and TC.Communicated by Ramaswamy H. Sarma.

Pharmacodynamic and pharmacokinetic study of Shaoyao Gancao decoction for repairing intestinal barrier damage in ulcerative colitis.

OBJECTIVE: To study the therapeutic effect and mechanism of Shaoyao Gancao Decoction (SGD) on ulcerative colitis (UC) mice based on the perspective of intestinal barrier, and this study provides a new consultation for the clinical application of SGD. METHODS: The chemical composition of SGD was characterized by HPLC. The UC mouse model was constructed by 3 % dextran sodium sulfate (DSS), which were randomly divided into the model group (DSS), the positive drug group (5-ASA), the Shaoyao group (SYD), Gancao group (GCD), and the Shaoyao Gancao Decoction group (SGD) at low, medium, and high dosages, respectively. The effects of each drug treatment group on UC were evaluated by the rate of body weight loss, disease activity index (DAI), colon length, spleen index, histopathological evaluations, and the levels of serum inflammatory factors (IL-1ß, IL-6, IL-10, IL-21, and TNF-α). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining, ELISA was used to detect the content of LPS in serum, and Western blot was used to detect the changes in the expression of tight junction proteins ZO-1, occludin, and the pathway proteins TLR4 and NF-κBp65 in the colonic tissues, to explore the protective effect of SGD on the intestinal barrier of UC mice. The vivo absorption process of the main active ingredients in the SG, SY and GC groups was determined by LC-MS. RESULTS: The contents of albiflorin, paeoniflorin, liquiritin apioside, liquiritin and glycyrrhetinic acid were 6.1227 mg/g, 20.8993 mg/g, 4.0054 mg/g, 3.6140 mg/g and 8.2515 mg/g, respectively. Compared with DSS group, SGD reduced weight loss(P<0.01) and DAI scores(P<0.05), prevented colon shortening(P<0.01), and ameliorated histopathological damage of the colon in UC mice(P<0.01). SGD also protected the intestinal barrier to alleviate UC by significantly reducing serum LPS and inflammatory factor levels, altering the number of goblet cells, promoting tight junction proteins (ZO-1 and occludin) and decreasing the expression of TLR4 and NF-κB in colonic tissues. Pharmacokinetic results showed that there was no significant difference in Cmax, AUC0-t (µg/L.h) and Tmax of albiflorin and paeoniflorin between the SY and SG groups, the Tmax was within 1 h; the AUC0-t (µg/L.h) of liquiritin and glycyrrhizic acid were about 1.6 and 1.9 times higher in the SG group compared to the GC group, respectively. The Cmax, Tmax and AUC0-t (µg/L.h) of glycyrrhizinic acid were significantly reduced to 0.73, 0.68 and 0.68 times of that of the GC group. CONCLUSION: SGD may have a therapeutic effect on DSS-induced UC mice by repairing the damaged intestinal barrier through the TLR4/NF-κB pathway. The combination of Shaoyao and Gancao increased the absorption of liquiritin and glycyrrhizic acid in vivo. The combination of Shaoyao and Gancao could promote the absorption of Gancao, and that the pairing of the two herbs could have a synergistic effect.