Hypouricemic effect of allopurinol are improved by Pallidifloside D based on the uric acid metabolism enzymes PRPS, HGPRT and PRPPAT.

Allopurinol is a commonly used medication to treat hyperuricemia and its complications. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to enhanced hypouricemic effect of allopurinol based on uric acid metabolism enzyme XOD. In this study, we evaluated whether Pallidifloside D (5mg/kg) enhanced hypouricemic effect of allopurinol (5mg/kg) related to others uric acid metabolism enzymes such as PRPS, HGPRT and PRPPAT. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly up-regulated HGPRT mRNA expression and down-regulated the mRNA expression of PRPS and PRPPAT in PC12 cells (all P<0.01). These results strongly suggest that hypouricemic effect of allopurinol are improved by Pallidifloside D via numerous mechanisms and our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Pallidifloside D from Smilax riparia enhanced allopurinol effects in hyperuricemia mice.

Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be effective in hyperuricemic control. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Pallidifloside D could enhance allopurinol's effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum, urine creatinine and BUN supported these observations. Our results showed that the synergistic effects of allopurinol combined with Pallidifloside D were linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia, a traditional Chinese herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Smilax riparia are called "Niu-Wei-Cai" in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Smilax riparia could enhance allopurinol׳s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. MATERIALS AND METHODS: We examined the effects of allopurinol (5mg/kg) administration alone or in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. RESULTS: Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum and urine creatinine and BUN supported these observations. The attenuation of hyperuricemia-induced renal dysfunction was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. CONCLUSION: The anti-hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Pallidifloside D, a saponin glycoside constituent from Smilax riparia, resist to hyperuricemia based on URAT1 and GLUT9 in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating hyperuricemia and gout symptoms. This study was designed to isolate a saponin glycoside named pallidifloside D from the total saponins of Smilax riparia and to examine its effect in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. MATERIALS AND METHODS: We examined the effects of pallidifloside D treated with 5, 10 and 20mg/kg on serum uric acid levels (SUA), Serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse. A colorimetric method was used to evaluate the effects of pallidifloside D on the XOD activities, and Western Blotting analysis were carried out to observe protein levels of mURAT1, mGLUT9 and mOTA1 in hyperuricemic mice after treatment with pallidifloside D. RESULTS: The levels of serum uric acid levels (SUA) were suppressed significantly with dose-dependence by pallidifloside D treated with 5, 10 and 20mg/kg (p<0.05, p<0.01 and p<0.01 respectively). Pallidifloside D could down-regulate the expression levels of renal mURAT1 protein in hyperuricemic mice in a dose-dependent manner (p<0.05, p<0.01, and p<0.001 respectively), and the protein levels of mGLUT9 could be down-regulated with dose-dependence (p<0.05 and p<0.01 respectively) by pallidifloside D at the dose of 10 and 20mg/kg. CONCLUSION: These results suggest that pallidifloside D possesses a potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 and GLUT9, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction.

Effects of Smilaxchinoside A and Smilaxchinoside C, two steroidal glycosides from Smilax riparia, on hyperuricemia in a mouse model.

The roots and rhizomes of Smilax riparia, called 'Niu-Wei-Cai' in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia-induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia.

Riparoside B and timosaponin J, two steroidal glycosides from Smilax riparia, resist to hyperuricemia based on URAT1 in hyperuricemic mice.

The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the active constituents and uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we isolated two steroidal glycosides named riparoside B and timosaponin J from the total saponins of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction. Riparoside B and timosaponin J may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia.

Design, synthesis, biological activity and molecular dynamics studies of specific protein tyrosine phosphatase 1B inhibitors over SHP-2.

Over expressing in PTPN1 (encoding Protein tyrosine phosphatase 1B, PTP1B), a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of diabetes and obesity. The relationship between PTP1B and human diseases exhibits PTP1B as the target to treat these diseases. In this article, small weight molecules of the imidazolidine series were screened from databases and optimized on silicon as the inhibitors of PTP1B based on the steric conformation and electronic configuration of thiazolidinedione (TZD) compounds. The top three candidates were tested using an in vitro biological assay after synthesis. Finally, we report a novel inhibitor, Compound 13, that specifically inhibits PTP1B over the closely related phosphatase Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) at 80 µΜ. Its IC50 values are reported in this paper as well. This compound was further verified by computer analysis for its ability to combine the catalytic domains of PTP1B and SHP-2 by molecular dynamics (MD) simulations.

Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method.

The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.

[Relationship of TCM syndrome type of gastric mucosal epithelial growth factor, vascular endothelial growth factor and proliferative cell nuclear antigen in patients with chronic atrophic gastritis].

OBJECTIVE: To study the relationship of TCM syndrome type of gastric mucosal epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) in patients with chronic atrophic gastritis (CAG) for exploring the essence of TCM type and providing a theoretical basis of clinical treatment. METHODS: TCM syndrome type of 200 patients with diagnosis of CAG confirmed by fibro-gastroscope and pathological examination were differentially classified, and the expressions of EGF, VEGF and PCNA in different types were determined using immunohistochemistry. RESULTS: Patients were differentiated as Pi-Wei deficiency type (Type I ) in 72; Gan-Wei disharmony type (Type II ) in 43; Pi-deficiency with qi stagnation type (Type III) in 32; Wei-yin deficiency type (Type IV) in 24; Pi-Wei damp-heat type (Type V) in 14; and Wei-collateral stasis obstruction type (Type VI) in 5. The difference of PCNA expression level between Type II with Type I , III and IV was significant (P < 0.05). No significant difference in expression levels of EGF and VEGF was found among the 6 types (P > 0.05). CONCLUSION: Type I and II were the dominant TCM syndrome types in CAG patients; the high expression of PCNA might be a diagnostic evidence for Gan-Wei disharmony syndrome.

[Clinical study on treatment of chronic aplastic anemia assisted by TCM for reinforcing shen and activating blood circulation to dredge channels].

OBJECTIVE: To observe the clinical efficacy of TCM for reinforcing Shen and activating blood circulation to dredge Channels in auxiliary treating chronic aplastic anemia (CAA), and to explore its mechanism. METHODS: Seventy-nine patients with CAA were randomly divided into the treated group treated with TCM plus western medicine and the control group treated with western medicine alone. The clinical efficacy was observed and levels of plasma sFas and sFasL before and after treatment were determined by ELISA. RESULTS: The basic cure rate and total effective rate in the treated group were 37.50% and 87.50%; while in the control group were 20. 51% and 61.54% respectively. Comparison between the two groups showed significant difference (P < 0.01). The sFas level was markedly lower in both groups before treatment, but after treatment, it got elevated in the treated group significantly (P < 0.05), as compared with that in the control group, the difference was significant (P < 0.01). CONCLUSION: TCM is effective in treating CAA with less toxic and side-effect, the mechanism might be the inhibition on over apoptosis of hematopoietic cells in CAA patients through regulating immune function of organism.