Integrated pharmacology reveals the mechanism of action of Bu-Shen-Tong-Du prescription against collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Bu-Shen-Tong-Du prescription (BSP) has traditionally been used in to treat RA but its underlying mechanisms remain unclear. In this study, we explored the potential mechanisms of BSP in collagen-induced arthritis (CIA) rats, a classic animal model of RA. We employed an integrated pharmacology approach in combination with network pharmacology, 1H-nuclear magnetic resonance (NMR) metabolomics, and biochemical analyses to determine the mechanisms of BSP for treating RA. We found that BSP can regulate immunity and inflammation by decreasing the spleen index; inhibiting hyperplasia of the white pulp; reducing the levels of IL-1ß, IL-6, IL-17A, and IFN-γ; and increasing the levels of IL-10 in the serum. Network pharmacology was utilized to predict related signal transduction pathways of BSP in RA treatment. 1H NMR metabolomics of the serum confirmed that BSP regulated energy metabolism and amino acid metabolism. Finally, we validated the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway using immunohistochemical methods, which demonstrated that BSP controlled RA-induced inflammation by inhibiting the TLR4/NF-κB signaling pathway. These results confirm the therapeutic effect of BSP in a CIA rat model, which is exerted via the inhibition of the inflammation and the improvement of the immune function, balancing energy metabolism and amino acid metabolism, and inhibiting the TLR4/NF-κB signaling pathway. This study provides an experimental basis for using BSP as a combinatorial drug to inhibit inflammation and regulate immunity in the treatment of RA.

Vasorelaxant effect of taurine is diminished by tetraethylammonium in rat isolated arteries.

Although the vasorelaxant effects of taurine have been studied in rabbit ear artery, rat isolated aorta and mesenteric artery, its pharmacological properties in other vascular beds and underlying mechanism(s) are still not well clarified. The present study was designed to observe the effects of taurine on the contractions induced by depolarization and phenylephrine in rat isolated aortic, renal and mesenteric arterial rings, and to get an insight into its mechanism(s). Arterial rings were suspended in organ baths and tension was recorded isometrically. Taurine 20-80 mM produced concentration-dependent relaxations of rat isolated aortic rings precontracted by 30 mM potassium chloride and 1 microM phenylephrine; the maximal relaxation was 17.17+/-3.18% and 22.23+/-1.83% respectively. The relaxation was not affected by 0.1 mM NG-nitro-L-arginine methylester ester (a nitric oxide synthetase inhibitor), 10 microM indomethacin (a cyclooxygenase inhibitor), 1 mM 4-aminopyridine (a K(V) blocker), 10 muM glibenclamide (a K(ATP) blocker), 1 mM barium chloride (BaCl(2), a K(IR) blocker), and 100 nM iberiotoxin (a BK(Ca) blocker), but was nearly abolished by 10 mM tetraethylammonium (TEA, a non-selective potassium channel blocker). Preincubation with taurine 20-60 mM did not affect the basal tone but inhibited the contraction induced by phenylephrine, and the inhibitory effect was attenuated by TEA in isolated renal and mesenteric arterial rings. Present experiments show that taurine relaxes contracted rat aorta and inhibits the phenylephrine-induced contraction of renal and mesenteric arteries, and suggest that a mechanism related to potassium channel opening may be involved in the action of taurine.