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Objective:To study the components with urate anion transporter 1（URAT1） regulation effect and their combination mechanisms of Lagotis brevituba by integrating techniques of HK-2 cell capture，UPLC-Q-TOF-MS and molecular docking，so as to provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba. Method:The HK-2 cells were applied to capture the components of L. brevituba. UPLC-Q-TOF-MS was used to identify those components. The molecular docking technique was adopted to study the interaction mechanism between the compounds and URAT1. Result:Eight components were successfully screened and identified as hyperoside，plantamajoside，kaempferol-3-O-glucoside，lugrandoside，nepitrin，isolugrandoside，homoplantaginin，luteolin，respectively. Those components could combine with URAT1 mainly through hydrogen bond，van der Waals force and hydrophobic action，which were closely related to structure and compound types. Furthermore，the LibDock score of phenylethanoids was higher than that of flavonoids. Conclusion:The integration of target cell capture，UPLC-Q-TOF-MS and molecular docking techniques could be successfully used to identify captured compounds of L. brevituba with URAT1 regulation effects and illustrate their potential combination mechanisms as well as the structure-activity relationships. The findings may provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba.
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OBJECTIVE: To observe the effect of acupuncture at "Shenshu"(BL23)-"Taixi"(KI3)on the levels of serum uric acid (SUA) and expression of renal urate-anion transporter 1 (URAT1) and organic anion transporter 1 (OAT1) proteins in hyperuricemia (HUA) rats, so as to explore its underlying mechanisms in improving HUA. METHODS: A total of 25 male Wistar rats were divided into 4 groups: control (n＝6), HUA model (n＝7), BL23-KI3 (n＝6) and Ganshu (BL18)-Taichong (LR3, BL18-LR3 in short, n＝6). The HUA model was established by gavage of Oteracil Potassium (2 g/kg), once daily for 10 days, then once every other day. For rats of the BL23-KI3 group, BL23 and KI3 were stimulated with filiform needles which were rotated for 10 s at a frequency about 100 r/min, and for rats of the BL18-LR3 group, BL18 and LR3 were stimulated with the same methods to those of the BL23-KI3 group. The treatment of both acupuncture groups was conducted once daily, 6 times a week (except Sundays) for 3 weeks. The contents of SUA and serum creatinine (SCr) were assayed by using an automatic biochemical analyzer. The pathological changes of the right kidney tissue were observed under light microscope after hematoxylin eosin (H.E.) staining, the immunoactivity of URAT1 and OAT1 of the right kidney tissue was determined by immunohistochemistry, and the expression of URAT1 and OAT1 proteins of the left kidney tissue detected by Western blot (WB). RESULTS: After modeling, the content of SUA and the expression of renal URAT1 protein (shown by both immunoactivity and WB) were significantly increased (P0.05). Following acupuncture intervention, the SUA content and URAT1 expression in both BL18-LR3 and BL23-KI3 groups were considerably down-regulated (P<0.05, P<0.01), and the expression of OAT1 protein in the BL23-KI3 group (not the BL18-LR3 group) were obviously up-regulated relevant to the model group (P<0.01). The effects of BL23-KI3 were significant superior to those of BL18-LR3 in down-regulating the expression of URAT1 and up-regulating OAT1 protein (P<0.01, P<0.05). CONCLUSION: Acupuncture of "BL23" and "KI3" can effectively down-regulate SUA level in HUA rats, which may be related to its effects in down-regulating the expression of URAT1 and up-regulating the expression of OAT1 in the kidney tissue.
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Aim To investigate the effect of green tea polyphenols(GTP)on serum level of uric acid in potas-sium oxonate (PO)-induced hyperuricemic mice,and explore the potential mechanism.Methods PO and GTP were intragastricly administered to mice for seven consecutive days.Uric acid level in serum was exam-ined.Meanwhile,activity and expressions of xanthine oxidase(XOD)in liver were tested.In additon,ex-pressions of urate transporters including urate-anion transporter (URAT ) 1 , organic anion transporter (OAT)1 and 3 in kidney were analyzed.Results GTP significantly decreased the serum level of uric acid in PO-induced hyperuricemic mice.At the same time, GTP markedly reduced the activity and expression of XOD in liver of hyperuricemic mice.Finally,GTP markedly reduced the expression of URAT1 ,OAT1 and OAT3 in kidney of hyperuricemic mice.Conclusion GTP has the effect of lowering uric acid in PO-induced hyperuricemic mice through both decreasing the uric acid production and increasing uric acid excretion.