Written by Angeline A. De Leon, Staff Writer. Chuanhutongfeng mixture, containing resveratrol, significantly reduced the joint pain, swelling and stiffness in participants with chronic gouty arthritis.

gout - joint healthGout is a complex form of inflammatory arthritis caused by excessive levels of uric acid, which crystallize and accumulate in the joints 1. A painful condition causing redness and swelling, gouty arthritis is linked to the activation of pro-inflammatory cytokines (interleukin-1β, IL-1β; tumor necrosis factor-α, TNF-α) 2, and animal research suggests that the upregulated expression of inflammasomes (involved in the activation of pro-inflammatory cytokines) is associated with the development of severe gout 3. MicroRNAs (miRNAs) are non-coding RNA molecules involved in biological processes such as cell growth and apoptosis 4. Deficiencies in the expression of certain miRNAs may contribute to gout through their activation of inflammatory pathways and promotion of circulating levels of pro-inflammatory cytokines 3,5. Overexpression of miR-155, for example, is associated with increased production of IL-1β and TNF-α in patients with acute gouty arthritis 5, and MiR-302b (involved in transcription of IL-1β) has been looked at as a target of therapy for general gouty arthritis 3. Chuanhutongfeng is a mixture of various herbs (primary active component resveratrol) shown to inhibit inflammation in synovial tissue and reduce circulating levels of IL-1β 6. This herbal formula has also been reported to mitigate symptoms of chronic gouty arthritis (CGA) and appears to perform comparably to certain anti-inflammatory drugs 7. In a 2019 study 8, Wang and colleagues investigated the therapeutic actions of a Chuanhutongfeng mixture on CGA by evaluating its potential regulatory effect on miRNAs.

A total of 255 patients with CGA (aged 18 to 70 years) were enrolled in a prospective, randomized, double-blind, parallel controlled study. A group of 195 CGA patients were assigned to one of three groups: a Chuanhutongfeng group instructed to ingest 125 mL of Chuanhutongfeng mixture twice daily for 8 weeks, a positive control group instructed to take 100 mg allopurinol three times daily, or a placebo control group instructed to take 30 mg etoricoxib once daily. At baseline, Week 4, and Week 8, miRNA assays were conducted to quantify differentially expressed miRNAs, and serum levels of chemokine ligand 2 (CCL2) and chemokine ligand 8 (CXCL8, precursor of Il-8) were measured. Real-time quantitative polymerase chain reaction was used to validate differentially expressed miRNAs in plasma samples from a subgroup of 60 CGA patients and 30 age- and gender-matched healthy controls (HC).

Analyses revealed that 48 miRNAs were abnormally expressed in CGA patients, compared to HC: 36 showed significant upregulation (1.5 times greater than HC, p < 0.05) and 12 significant downregulation (1.5 times less than HC, p < 0.05). Relative expressions of miR-486-5, miR-339-5p, and miR-361-5p were also lower in CGA patients vs. HC (p < 0.05) and were, thus, selected as gout-specific miRNAs of interest in the study. Compared to the etoricoxib group, both the Chuanhutongfeng and allopurinol groups showed upregulated expression of miR-486-5, miR-339-5p, and miR-361-5p and lower levels of CCL2 and CXCL8 proteins (p < 0.05 for all). At the end of 8 weeks, the Chuanhutongfeng group exhibited lower levels of uric acid and CCL2 and CXCL8 protein expression, as well as elevated plasma levels of miR-486-5, miR-339-5p, and miR-361-5p, compared to allopurinol (p < 0.05 for all). Cure rate of CGA symptoms was also significantly higher in the Chuanhutongfeng vs. allopurinol group (p < 0.05).

Overall results indicate that CGA is associated with the upregulation of three specific miRNAs and that supplementation with Chuanhutongfeng can directly influence the protein expression of these gout-specific miRNAs. Chuanhutongfeng was also shown to effectively reduce uric acid levels and inflammatory cytokines CCL2 and CXCL8, a complementary finding to the significant symptom improvement seen in CGA patients. It remains for future trials to determine how Chuanhutongfeng mixture compares to pure resveratrol in therapeutic efficacy for CGA. The mechanism associated with Chuanhutongfeng’s upregulation of miRNAs also warrants further study. Study limitations of note include a relatively short follow-up time, a limited sample size, and the lack of correlation between miRNAs expression and inflammatory cytokine levels.

Source: Wang Y, Dong L, Liu P, et al. A randomized controlled trial of chuanhutongfeng mixture for the treatment of chronic gouty arthritis by regulating miRNAs. Evidence-based Complementary and Alternative Medicine. 2019; 5917269. DOI: 10.1155/2019/5917269.

Copyright © 2019 YaoWang et al. This is an open access article distributed under the CreativeCommons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Posted December 9, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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