PMID- 29285741 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20200225 IS - 1993-0402 (Electronic) IS - 1672-0415 (Linking) VI - 25 IP - 3 DP - 2019 Mar TI - Effects of Polygonum cuspidatum on AMPK-FOXO3alpha Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage. PG - 182-189 LID - 10.1007/s11655-017-2979-6 [doi] AB - BACKGROUND: To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3alpha (FOXO3alpha), 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(-1)) 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(-1)), and 7.46, 3.73, or 1.87 g*kg(-1)*d(-1) 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, FOXO3alpha, 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 FOXO3alpha in the model group were significantly down-regulated, and protein levels of AMPKalpha1, pAMPKalpha1 and FOXO3alpha 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 AMPKalpha1, pAMPKalpha1 and FOXO3alpha in the high-dose PC group, AMPKalpha1 and pAMPKalpha1 in the mediumdose PC group, and pAMPKalpha1 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 FOXO3alpha in the medium-dose PC group, and protein levels of AMPKalpha1, pAMPKalpha1 and FOXO3alpha 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 FOXO3alpha 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. FAU - Ma, Wei-Guo AU - Ma WG AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Wang, Jie AU - Wang J AD - Department of Endocrinology, Shunyi Branch, Beijing Hospital of Traditional Chinese Medicine, Beijing, 101300, China. FAU - Bu, Xiang-Wei AU - Bu XW AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Zhang, Hong-Hong AU - Zhang HH AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Zhang, Jian-Ping AU - Zhang JP AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Zhang, Xiao-Xu AU - Zhang XX AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - He, Yu-Xi AU - He YX AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Wang, Da-Li AU - Wang DL AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Zhang, Zheng-Ju AU - Zhang ZJ AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Meng, Feng-Xian AU - Meng FX AD - Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. mfx0823@163.com. LA - eng PT - Journal Article DEP - 20171228 PL - China TA - Chin J Integr Med JT - Chinese journal of integrative medicine JID - 101181180 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (FOXO3 protein, rat) RN - 0 (Forkhead Box Protein O3) RN - 0 (Plant Extracts) RN - 268B43MJ25 (Uric Acid) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*physiology MH - Animals MH - Chemokine CCL2/blood MH - Disease Models, Animal MH - *Fallopia japonica MH - Forkhead Box Protein O3/*physiology MH - Hyperuricemia/*complications MH - Kidney Diseases/*drug therapy/etiology MH - Male MH - Plant Extracts/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/*drug effects MH - Uric Acid OTO - NOTNLM OT - AMPK-FOXO3alpha pathway OT - Chinese medicine OT - Polygonum cuspidatum OT - renal damage OT - uric acid EDAT- 2017/12/30 06:00 MHDA- 2019/06/14 06:00 CRDT- 2017/12/30 06:00 PHST- 2017/10/18 00:00 [accepted] PHST- 2017/12/30 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2017/12/30 06:00 [entrez] AID - 10.1007/s11655-017-2979-6 [pii] AID - 10.1007/s11655-017-2979-6 [doi] PST - ppublish SO - Chin J Integr Med. 2019 Mar;25(3):182-189. doi: 10.1007/s11655-017-2979-6. Epub 2017 Dec 28.