Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage / 中国结合医学杂志

BACKGROUND@#To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism.@*METHODS@#A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg), and 7.46, 3.73, or 1.87 g•kg•d PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum.@*RESULTS@#Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05).@*CONCLUSION@#PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.

Metabolism study of phillygenin in human liver microsomes by UPLC-Q-TOF-MS / 中国药学杂志

OBJECTIVE: To establish a UPLC-Q-TOF-MS method to characterize the metabolites of phillygenin in human liver microsomal incubation system for the first time. METHODS: The chromatography separation was performed on a C18 reversed phase LC column (Phenomenex Kinetex C18, 2.1 mm×100 mm, 2.6 μm). The mobile phase consisted of water-formic acid (100:0.1, V/V) and acetonitrile and a gradient elution program was adopted at the flow rate of 400 μL·min-1. The mass spectral analysis was performed in a positive electrospray ionization mode, and the turbo spray temperature was 550℃. The full MS experiment was run with a scan range from m/z100 to m/z 1 000. RESULTS: The possible fragmentation pathways of phillygein were speculated in a positive electrospray ionization mode, and eight metabolites was identified in human liver microsomal incubation system. CONCLUSION: The UPLC-Q-TOF-MS method is very convenient and efficient for detecting phillygein in human liver mirosomes. The developed method is suitable for the metabolism research of phillygein in human liver microsomes, which providing valuable reference for pharmacokinetic study of phillygenin.

Research of bleeding volume and method in blood-letting acupuncture therapy based on data mining / 中国针灸

Through computer-based technology and data mining method, with treatment in cases of bloodletting acupuncture therapy in collected literature as sample data, the association rule in data mining was applied. According to self-built database platform, the data was input, arranged and summarized, and eventually required data was acquired to perform the data mining of bleeding volume and method in blood-letting acupuncture therapy, which summarized its application rules and clinical values to provide better guide for clinical practice. There were 9 kinds of blood-letting tools in the literature, in which the frequency of three-edge needle was the highest, accounting for 84.4% (1239/1468). The bleeding volume was classified into six levels, in which less volume (less than 0.1 mL) had the highest frequency (401 times). According to the results of the data mining, blood-letting acupuncture therapy was widely applied in clinical practice of acupuncture, in which use of three-edge needle and less volume (less than 0.1 mL) of blood were the most common, however, there was no central tendency in general.

Exploration on the application characteristics of bloodletting therapy for the diseases relevant with soft tissue infection by data mining technology / 中国针灸

<p><b>OBJECTIVE</b>Using the data mining technology to analyze the application law of bloodletting therapy for the diseases relevant with soft tissue infection and explore the effect specificity of bloodletting therapy.</p><p><b>METHODS</b>The variety of diseases treated with bloodletting therapy was taken as the sample data by collecting the reports from the periodical literatures. The network database of bloodletting literature was set up. The association rule of data mining technology was adopted to extract the information on the diseases relevant with soft tissue infection in the periodical literatures. The frequency item of the superiority disease category was calculated. And the deep mining was done in terms of the needle device, point selection and the bleeding amount separately. The application law of bloodletting therapy was summarized in the treatment of the diseases relevant with soft tissue infection.</p><p><b>RESULTS</b>Fourteen kinds of relevant diseases of soft tissue infection treated with bloodletting therapy were included in the contemporary periodical literatures, of which, the reported case number and the reporting frequency were the highest for hordeolum and breast abscess. The three-edged needle was used the most frequently in the manipulation. The acupoints selected were the local Ashi points, combined with the symptomatic acupoints. The bleeding amount was not normalized by the ideas of different physicians.</p><p><b>CONCLUSION</b>The bloodletting therapy achieves the better curative effect on some diseases relevant with soft tissue infection and this therapy deserves to be further promoted in clinical practice.</p>