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.

Effect of Modified Guipitang Combined with Xingnao Kaiqiao Acupuncture in Treatment of Heart and Spleen Insufficiency Syndrome of Non-dementia Vascular Cognitive Impairment / 中国实验方剂学杂志

Objective: To explore the curative effect and partial mechanism of modified Guipitang combined with Xingnao Kaiqiao acupuncture in the treatment of non-dementia vascular cognitive impairment (VCIND). Method: Totally 122 patients with VCIND admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TCM) from May 2017 to October 2018 were randomly divided into modified decoction group (39 cases), acupuncture group (42 cases) and combination group (41 cases). All of the three groups were orally given routine anticoagulants and lipid-lowering drugs. The decoction group was orally given modified Guipitang 150 mL/times, 2 times/day, in addition to the routine treatment, the acupuncture group was treated with Xingnao Kaiqiao acupuncture method in addition to the routine treatment, involving Shuigou, Neiguan (bilateral), Sanyinjiao (bilateral), Sishencong, Xuanzhong (bilateral) and Taixi (bilateral) acupoints, 2 times/day, for six days a week, the combined group was treated with Xingnao Kaiqiao acupuncture in addition to modified Guipitang. All of the three groups were treated for 8 weeks. The Montreal cognitive assessment scale (MoCA scale, Beijing version) and activity of daily life (ADL) scale, TCM symptoms and clinical efficacy were scored before treatment, 4 weeks after treatment and 8 weeks after treatment in three groups. Serum levels of calcitonin gene-related peptide (CGRP) and cone-like protein-1 (VILIP-1) were measured by enzyme-linked immunosorbent assay at different time points. Result: Compared with decoction group and acupuncture group, MoCA score, ADL score and TCM syndrome score of the combined group were decreased, the total effective rate was increased significantly after 4 and 8 weeks of treatment, the serum CGRP content was increased, and the VILIP-1 content was decreased. Conclusion: Modified Guipitang combined with Xingnao Kaiqiao acupuncture has a definite curative effect on VCIND with heart and spleen insufficiency syndrome. Its mechanism may be related to the expansion of blood vessels, the alleviation of blood supply of brain and the reduction of neuron injury.