A comprehensive quality evaluation method of Corydalis yanhusuo by HPLC fingerprints, chemometrics, and correlation analysis.

A novel quality evaluation method of Corydalis yanhusuo was established by researching the high-performance liquid chromatography behavior of alkaloids under different buffer solutions and exploring the correlation between alkaloids in C. yanhusuo. The retention times of tetrahydropalmatine and corydaline were significantly influenced by pH, while the peak shape was affected by buffer types and ionic strength. The resolution of compounds in fingerprint was satisfactory under acetonitrile-0.2% phosphoric acid buffer (adjusted pH to 5.0 with triethylamine). Twelve common peaks were found by comparing 20 batches of C. yanhusuo fingerprints, and three tertiary alkaloids and four quaternary alkaloids were identified. The fingerprints were analyzed by similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. All samples were divided into three groups, and the contents of dehydrocorydaline and coptisine from Zhejiang province were relatively higher than other origins. There were six components performing more contributions to the quality of C. yanhusuo. The correlations between alkaloids were conducted by Pearson correlation analysis and mathematical model analysis. The content correlation between palmatine and berberine was y = 0.28x2  + 0.03x + 0.03, and the dehydrocorydaline and coptisine was y = -7.54/(1 + (x/0.14)0.5 ) + 2.61. The established mathematical model of alkaloids provided a guiding significance for the quality control of C. yanhusuo.

Wuling San protects kidney dysfunction by inhibiting renal TLR4/MyD88 signaling and NLRP3 inflammasome activation in high fructose-induced hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuling San, a famous prescription in Chinese medicine, is composed of Polyporus, Poria, Alismatis rhizoma, Cinnamomi cortex and Atractylodis macrocephalae rhizoma, and promotes kidney function and diuresis. The main purpose of this study was to investigate its renal protective effect in high fructose-induced hyperuricemic mice. MATERIALS AND METHODS: ICR mice were fed with 30% fructose in drinking water for 6 weeks to induce hyperuricemia and renal dysfunction. Then mice were orally administrated for other 6 weeks with Wuling San (987, 1316, 1755 and 2340mg/kg), allopurinol (5mg/kg) and water daily, respectively. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Hematoxylin and eosin staining was used to assess renal histological changes. Renal interleukin (IL)-1ß concentrations were measured using ELISA kit. Renal protein levels of organic ion transporters, as well as toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling and pyrin domain containing 3 (NLRP3) inflammasome were determined by Western blot assay. RESULTS: Wuling San significantly decreased serum uric acid, creatinine and BUN levels, increased fractional excretion of uric acid (FEUA) in fructose-fed mice. It restored fructose-induced dysregulation of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2) and organic anion transporter 1 (OAT1), as well as organic cation transporter 1 (OCT1) and OCT2 in mice. Wuling San obviously alleviated infiltration of inflammation cells in kidney glomerulus of fructose-fed mice. Moreover, Wuling San suppressed the activation of TLR4/ MyD88 signaling to inhibit nuclear factor κB (NF-κB) signaling and mitogen-activated protein kinases (MAPKs) activation in fructose-fed mice. Additionally, Wuling San decreased NLRP3 inflammasome activation and IL-1ß secretion in the kidney of fructose-fed mice. CONCLUSION: Wuling San exerts renal protective effect by modulating renal organic ion transporters in fructose-induced hyperuricemic mice. The molecular mechanism of its action may be associated with the suppression of TLR4/MyD88 signaling and NLRP3 inflammasome activation to reduce IL-1ß production in high fructose-induced hyperuricemic mice.

Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ramulus Mori, the branch of Morus alba, is widely used in traditional Chinese medicine prescriptions to treat gout and hyperuricemia. AIM OF THIS STUDY: To evaluate the uricosuric and nephroprotective effects of ethanol extract of Ramulus Mori (ERM) and explore its possible mechanisms in hyperuricemic mice. MATERIALS AND METHODS: HPLC analysis was employed to determine the main constituents. Hyperuricemia was induced by potassium oxonate (250 mg/kg) in male mice. ERM (10, 20 and 40 mg/kg) was orally administered to hyperuricemic and normal mice for 7 days. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Simultaneously, renal mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1/2, mOCTN1/2) were analyzed by RT-PCR and Western blotting methods. RESULTS: ERM mainly contained mulberroside A, oxyresveratrol, 4-hydroxycinnamic acid, resveratrol, 7-hydroxycumarin and morin. ERM significantly reduced serum urate levels and increased 24h-urine urate excretion and fractional excretion of uric acid in hyperuricemic mice. It effectively restored oxonate-induced expression alteration of renal mURAT1, mGLUT9 and mOAT1, resulting in urate excretion enhancement. Moreover, ERM decreased serum creatinine and BUN levels and increased creatinine clearance, and up-regulated expression of mOCT1/2 and mOCTN1/2, contributing to kidney function improvement in this model. CONCLUSION: These results suggest that ERM exerts the uricosuric and nephroprotective actions by the regulation of these renal organic ion transporters in hyperuricemic mice, and provide scientific support for the empirical use of Ramulus Mori.

Mulberroside a possesses potent uricosuric and nephroprotective effects in hyperuricemic mice.

Mulberroside A is a major stilbene glycoside of MORUS ALBA L. (Moraceae), which is effectively used for the treatment of hyperuricemia and gout in traditional Chinese medicine. We examined whether mulberroside A had effects on renal urate underexcretion and dysfunction in oxonate-induced hyperuricemic mice and investigated the potential uricosuric and nephroprotective mechanisms involved. Mulberroside A at 10, 20, and 40 mg/kg decreased serum uric acid levels and increased urinary urate excretion and fractional excretion of uric acid in hyperuricemic mice. Simultaneously, it reduced serum levels of creatinine and urea nitrogen (10-40 mg/kg), urinary N-acetyl- ß-D-glucosaminidase activity (10-40 mg/kg), ß2-microglobulin (10-40 mg/kg) and albumin (20-40 mg/kg), and increased creatinine clearance (10-40 mg/kg) in hyperuricemic mice. Furthermore, mulberroside A downregulated mRNA and protein levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1), and upregulated mRNA and protein levels of renal organic anion transporter 1 (mOAT1) and organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1, and mOCTN2) in hyperuricemic mice. This is the first study demonstrating that mulberroside A exhibits uricosuric and nephroprotective effects mediated in part by cooperative attenuation of the expression alterations of renal organic ion transporters in hyperuricemic mice. These data suggest that mulberroside A may be a new drug candidate for the treatment of hyperuricemia with renal dysfunction.

[Study on the preparation of effervescent tablets of EGb and its quality].

OBJECTIVE: To prepare effervescent tablets of EGb and establish quality preparation. METHOD: Taking pH, disintegration time and rigidity as index, the formulation and technique of EGb effervescent tablets were optimized by orthogonal experiment, the products were prepared and its stability were tested. RESULT: The optimum procedure condition was adding 12.5% citric acid, 20% sodium bicarbonate encapsulated by PEG6000, the products were tested by stability, the preparation was stable. CONCLUSION: It is valuable to be further studied as a new preparation of EGb.