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Acta Pharmaceutica Sinica ; (12): 1069-1076, 2017.
Article in Chinese | WPRIM | ID: wpr-779696


It is investigated that the hepatotoxicity of Polygonum multiflorum (PM)was attenuated by its processed products of nine times steaming and nine times sunning(RPM)based on immunological stress-mediated animal model by using metabolomics method. Sprague-Dawley(SD)rats were intragastrically administered with(5.4 g crude drug per kg body weight)of 50% alcohol extracts of PM and its processed products of nine times steaming and nine times sunning respectively or co-treated with non-toxic dose of lipopolysaccharide(LPS, 2.8 mg·kg-1)via tail vein injection. The plasma alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were assayed and the isolated livers were evaluated for histopathological changes. Global metabolomics profiling, multivariate analysis and data base searching were performed to discover common differential metabolites for idiosyncratic liver injury. The results showed that co-treatment with non-toxic dose of LPS and PM could result in significant liver injury, indicated by the elevation of plasma ALT and AST activities, as well as obvious liver histologic damage; whereas RPM failed to induce detectable liver injury. Furthermore, 10 potential metabolomics biomarkers that differentially expressed in LPS/PM group compared with LPS/RPM without liver injury were identified by untargeted metabolomics, mainly involved ten pathways: sphingolipid metabolism, linoleic acid metabolism, taurine and hypotaurine metabolism, steroid hormone biosynthesis, galactose metabolism, steroid biosynthesis, metabolism of xenobiotics by cytochrome P450, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis. This work illustrated the idiosyncratic hepatotoxicity of heshouwu and provided a metabolomic insight into diosyncratic liver injury of PM and RPM.

Acta Pharmaceutica Sinica ; (12): 1041-1047, 2017.
Article in Chinese | WPRIM | ID: wpr-779692


This study was designed to investigate the correlation between idiosyncratic liver injury and content of cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(cis-SG)in radix Polygoni multiflori Preparata(RPMP). In order to compare the effect of hepatotoxicity of different cis-SG contents in RPMP, rats were administered with 50% alcohol extracts of RPMP(7.56 g·kg-1, via intragastric administration)alone or co-treated with lipopolysaccharide(LPS, 2.8 mg·kg-1, via tail vein injection). The results showed that no significant alterations of plasma ALT and AST activities were observed in the normal rats. In the LPS treated rats, the group without light treatment and the group with 0.10% cis-SG after light treatment did not exhibit obvious injury in liver. The group with 0.35% cis-SG after light treatment and the group with 0.70% cis-SG after light treatment showed significant increases in ALT, AST, TNF-α, IL-6, NF-κB p65 and apoptosis rate(P < 0.05), causing pathological changes in the liver tissue. Through the content analysis of drug in patients with liver injury, we found that the content of cis-SG(> 0.40%)was generally higher than that of pieces collected from different origins(< 0.10%). The comparative analysis of experiments and clinical data showed that there was a relationship between the content of cis-SG and idiosyncratic liver injury. In order to reduce the risk of clinical medication, the content of cis-SG of 0.10% should be a limit of quality control in the production processing of Polygonum multiflorum.

Article in Chinese | WPRIM | ID: wpr-852740


Objective: To study the effect of Lianhua Qingwen Capsule (LQC) on the growth and metabolism of Pseudomonas aeruginosa and to establish a new method to evaluate the consistency of LQC. Methods: The power-time curves and corresponding thermodynamic parameters such as appearance time (T), total heat output (Q), maximum power output (P), and growth rate constant (k) of P. aeruginosa were determined by microcalorimetry. The regression analysis was carried out with T, P, Q, and k as parameters, and the optimal parameters were selected according to the correlation coefficient to calculate the antibacterial effective rate. The effects of 11 batches of LQC and specially treated LQC samples on growth and metabolism of P. aeruginosa were determined by an index antibacterial effective rate to evaluate the antibacterial activity of LQC. Results: LQC had obvious inhibitory effect on P. aeruginosa in the range of 10.00 to 47.68 mg/mL, and the bacteriostatic efficacy and dosage of LQC had good correlation. By regression analysis, it was found that T was the best parameter in the four thermodynamic parameters, r = 0.990. The change of this parameter could directly evaluate the effect of LQC on the growth and metabolism of P. aeruginosa, with good stability. The appearance time was selected as a parameter to calculate its antibacterial effective rate (E). The results showed that there was no significant difference in E of different batches of LQC samples. And the E value was significantly changed when the sample was placed in a humid/high temperature environment. Conclusion: The microcalorimetric method can be used to evaluate the antibacterial activity and the quality consistency of LQC capsule, which has the high precision and good accuracy. The study has provided a new method to evaluate the quality consistency of TCM.

Article in Chinese | WPRIM | ID: wpr-350128


To explore the active substance of antiplatelet aggregation of Polygoni Multiflori Radix by using chemical fingerprints and antiplatelet aggregation bioactivity test for spectrum-effect correlation analysis. The Polygoni Multiflori Radix was tested by antiplatelet aggregation in vitro, and the results showed that 50% aqueous ethanol extract of Polygoni Multiflori Radix had more potent antiplatelet aggregation effect than 10% or 90% aqueous ethanol extract, and ultrasonic extraction was superior to refluxing extraction in the aspect of antiplatelet aggregation. The antiplatelet aggregation bioactivity of the different Polygoni Multiflori Radix extracts was evaluated and the results showed that the inhibition rate was 32.03%-74.56%. Spectrum-effect correlation analysis indicated that trans-stilbene glucoside, cis-stilbene glucoside and catechinic acid had higher correlation coefficient and they were 0.963 (P<0.01), 0.902 (P<0.01) and 0.656 (P<0.05) respectively; furthermore, all of the above three compounds demonstrated significant antiplatelet aggregation bioactivities. Considering their content difference in Polygoni Multiflori Radix, we calculated the relative active contributions, and the results suggested that trans-stilbene glucoside was the main active substance of Polygoni Multiflori Radix in the aspect of antiplatelet aggregation in vitro.