ABSTRACT
Objective::To explore the protective mechanism of Shenteng Sanhuang decoction and Gegen Qinlian Tang on diabetic nephropathy (DN). Method::Rat DN models were duplicated with unilateral nephrectomy combined with streptozotocin (STZ). The rats were randomly divided into blank group, model group, irbesartan group and traditional Chinese medicine group. After 8 weeks of administration of corresponding drugs, the body weight, blood sugar, blood urea nitrogen (BUN), 24-hour urine volume (24 h U-vol), 24-hour urinary protein (24 h U-pro), serum creatinine (SCr), kidney weight/body weight (KW/BW) mass index of rats in each group were measured. The kidney tissues of rats in each group were homogenized, and supernatant was taken. Expressions of Smad ubiquitination regulatory factor 2 (Smurf2), matrix metalloprotein-9 (MMP-9), TGF-β1 and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were detected by Western blot or special test kit. Result::Compared with the blank group, the biochemical indicators, body weight, KW/BW, blood sugar, BUN, 24 h U-vol, 24 h U-pro, SCr and MDA were significantly higher or increased(P<0.05), while SOD and CAT were significantly decreased in the model group(P<0.05). Western blot showed that the expression of Smurf2 and TGF-β1 was high, while the expression of MMP-9 was low(P<0.05). Compared with the model group, the biochemical indicators of irbesartan group and traditional Chinese medicine group improved significantly(P<0.05), KW/BW were reduced, and blood sugar, BUN, 24 h U-vol, 24 h U-pro, SCr and MDA were significantly decreased (P<0.05), SOD and CAT was obviously increased (P<0.05), expressions of Smurf2 and TGF-β1 were decreased significantly(P<0.05), and expression of MMP-9 was increased significantly(P<0.05). Conclusion::Shenteng Sanhuang decoction and Gegen Qinlian Tang can effectively improve many biochemical indexes of rat DN models, and improve renal function. Its mechanism is closely related to reducing the expressions of Smurf2 and TGF-β1, and enhancing the expression of MMP-9.
ABSTRACT
Objective:To investigate the tissue distribution of major bioactive components from Gegen qinlian Tang(GQT) in rats,and to reveal the mechanism for the efficacy of GQT by the tissue targeting of its bioactive ingredients in vivo. Method:After oral administration of GQT in rats,tissues were collected at different time points,including small and large intestine,liver,heart,spleen,lung,and kidney.Samples were prepared for determination of 14 bioactive components of GQT in tissue homogenate by HPLC-MS/MS.The chromatography separation was performed on an Agilent ZORBAX SB-C18 column(2.1 mm×100 mm,3.5 μm) with acetonitrile-0.1% formic acid in water for gradient elution.Electrospray ionization(ESI) was applied and operated in the positive ion mode.Meanwhile,naringin was used as the internal standard for determining. Result:HPLC-MS/MS for simultaneous determination of 14 components from GQT in tissue homogenate was developed and validated by specificity,calibration curves,recovery test,matrix effect,precision,accuracy,and stability.In the small intestine,the the area under the curve(AUC0-10 h) of major isoflavonoids(puerarin,3'-hydroxypuerarin,and daidzein) were 22 174.9,15 893.1,3 882.5 h·mg·L-1,major flavonoids(baicalein,wogonin,wogonoside,and baicalin) were 15 423.6,15 408.4,7 017.3,3 697.7 h·mg·L-1,and major alkaloid(berberine) was 2 544.0 h·mg·L-1,respectively.The distribution of these ingredients in the small intestine was significantly higher than that in other tissues. Conclusion:The effective ingredients of GQT are mainly distributed in the intestinal tissues,which speculates that the anti-inflammatory and antidiarrheal activities of GQT may be related to its targeting in the intestine.
ABSTRACT
Objective: To investigate the effect of modified Gegen Qinlian Tang on learning and memory ability and interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), nuclear factor-κB(NF-κB) protein expression in hippocampus of type 2 diabetic (T2DM) rats. Method: A total of 62 rats were randomly divided into normal group (n=12),and the remaining 50 rats were established by feeding high sugar and high fat diet and injecting with low dosage of streptozocin(STZ) to T2DM. The successful modeling rats were selected and randomly divided into model group, Saxagliptin and modified Gegen Qinlian Tang group. The normal group and the model group received 10 mL·kg-1·d-1 nomal saline by intragastric administration. 0.005 g·kg-1·d-1 Saxagliptin crude drug and 0.435 g·kg-1·d-1 modified Gegen Qinlian Tang crude drug were given in Saxagliptin group and modified Gegen Qinlian Tang group, and all the treatment lasted for 8 weeks. Learning and memory ability of rats was observed by using Morris water maze. Histopathological changes of hippocampus was observed by hematoxylin-eosin staining.Western blot was used to test the NF-κB p65 in the cytoplasmic and nucleus in rat hippocampus. Enzyme-linked immunosorbent assay(ELISA) was used to test the levels of IL-1β and TNF-α. Result: Compared with normal group, the mean incubation period of model group was significantly prolonged on the 4th day(PPκB p65 in the nucleus was significantly increased (Pβ, TNF-α in the hippocampus were significantly increased (PPPPPβ, TNF-α and NF-κB p65 in hippocampus were significantly improved. Conclusion: Modified Gegen Qinlian Tang could obviously improve the learning and memory ability of the T2DM rat model which was induced by the high-sugar, high-lipid diet and low-dose STZ, and the mechanism may be achieved by suppressing the inflammation of the rat' s hippocampus.
ABSTRACT
The biopharmaceutical properties (solubility, permeability, etc.) of active pharmaceutical ingredients are playing an important role in understanding of disposition of drugs in the body, screening of drugs and evaluation of drug delivery system. The active ingredients of Chinese materia medica (CMM) are various and complex, the research on biopharmaceutics provides a train of thought and practical method for the prediction and research on the process of active ingredients from CMM in vivo. The multi-components system is one of the main differences between CMM and chemical medicine, and the study on biopharmaceutics of active ingredients in CMM under multi-components system has become a hot topic. The progress on biopharmaceutics of active ingredients in CMM under multi-components system was reviewed in this article, which may provide the reference for data integration, theoretical induction and system construction in this field, and provide new train of thought for the research on CMM theories and the development of CMM in the perspective of biopharmaceutics.