Study Shows Promise of Guizhi-Shaoyao-Zhimu Decoction Helping Gout

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A new study demonstrated the guizhu-shaoyao-zhimu decoction improves clinical symptoms and laboratory indicators of gout.¹

Gout (also called gouty arthritis) is a common inflammatory arthritis worldwide, which leads to economic burdens and productivity setbacks, as well as a risk factor for chronic kidney disease, hypertension, cardiocerebrovascular disease, and diabetes. In 2017, the global prevalence of gout was 0.52%, and that percentage grows every year.

In China, the guizhi-shaoyao-zhimu decoction—an herb formula—has been used to treat rheumatic and joint diseases for thousands of years, specifically for arthromyodynia.² It is a formula of TCM, containing 9 herbs: Fuzi, Fangfeng, Baizhu, Shengjiang, Mahuang, Zhimu, Shaoyao, Guizhi, and Gancao.¹

The formula has been tested in clinical trials, which found the substance can help clinical symptoms and laboratory signs of gout. Despite previous studies examining the decoction, no study evaluated the efficacy, safety, and underlying mechanisms of the formula.

Thus, a new meta-analysis, led by Pengda Qu, MD, from Yunnan University of Chinese Medicine in Kunming, China, sought to determine the efficacy, safety, and underlying mechanisms of guizhi-shaoyao-zhimu decoction. The investigators retrieved randomized controlled trials of guizhi-shaoyao-zhimu decoction, as well as related ingredients of herbs and targets of herbs and gout from several databases.

“Collectively, [guizhu-shaoyao-zhimu decoction] could be used as an important alternative therapy for [gout],” the investigators wrote. “Its therapeutic effects may be exerted by multiple related ingredients, targets, mechanisms, and signaling pathways.”

The team used 20 studies, published between 1998 – 2022, with 1633 patients. Participants in the experimental group (n = 823) received the guizhu-shaoyao-zhimu decoction alone or with another conventional treatment (n = 810), such as toricoxib, febuxostat, allopurinol, or benzbromarone. Meanwhile, participants in the control group received only conventional treatment. The investigators looked for effective rate, blood uric acid, c-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-a, visual analogue scale, and adverse events.

Qu and colleagues found the guizhu-shaoyao-zhimu decoction can reduce levels of the following, greater than with conventional therapy:

• Blood uric acid (word mover’s disease (WMD) = -1.55; 95% CI, -2.45 to – 0.66; P <.001)
• C-reactive proteins (WMD = −0.43; 95% CI, −0.70 to −0.17; P <.001)
• Erythrocyte sedimentation rate (WMD = −0.51, 95% CI, −0.79 to −0.23; P <.001)
• Interleukin 6 (WMD = −0.49; 95% CI, −0.71 to −0.28; P <.001)
• Interleukin 8 (WMD = −1.12; 95% CI, −1.33 to −0.90; P <.001),
• Tumor necrosis factor-a (WMD = −0.64; 95% CI, −0.86 to −0.41; P <.001)
• Visual analogue scale (WMD = −1.25; 95% CI, −2.29 to −0.21; P = .02)

Thus, the formula showed promise in helping patients with gout. Furthermore, a pharmacology analysis revealed the core related ingredients in guishi-shaoyao-zhimu was quercetin, kaempferol, sitosterol, luteolin, and catechin. Meanwhile, the core intersection targets had AKT1, TNF-a, TP53, and IL6. Then, the critical signaling pathways had IL-17, HIF-1, TNF, and PI3K-Akt. Out of these molecular docking results, 8 results had binding energy values >- 5.0 kcal/mol.

The guizhu-shaoyao-zhimu decoction had adverse events reported in 6 studies, which had 254 patients in the treatment group and 251 in the control group. Adverse events included palpitation, rash, dizziness, diarrhea, abdominal pain, nausea, and vomiting. Symptoms were mild, tolerable, and could be quickly relieved. Patients on guizhu-shaoyao-zhimu decoction treatment had less adverse events than patients on conventional treatment (relative risk [RR], -0.77; 95% CI, -1.44 to -0.10; P = .02).

“The evidence from this study suggests that [guizhu-shaoyao-zhimu decoction] could be a satisfactory complementary and alternative therapy for the treatment of [gout], especially in improving the clinical efficiency and [visual analogue scale] score and reducing the level of [blood uric acid] and inflammatory biomarkers, including [c-reactive protein],[erythrocyte], IL-6, IL-8, and TNF-α,” the investigators wrote. “However, given the quality of the included studies, further research is needed to improve the scientific credibility of the literature.”

References

1. ^{Qu, Pengda MDa; Wang, Haiyang MDa; Wang, Wei MMb; Hu, Qian MMb; Du, Shiyu MMa; Peng, Zhaorong MMa; Tang, Xiaohu MDa,c,*. Clinical efficacy evaluation and potential mechanism prediction on Guizhi-Shaoyao-Zhimu decoction in the treatment of gouty arthritis based on meta-analysis, network pharmacology analysis, and molecular docking. Medicine 102(47):p e35973, November 24, 2023. | DOI: 10.1097/MD.0000000000035973}
2. ^{Zhang Q, Li R, Liu J, et al. Efficacy and tolerability of Guizhi-Shaoyao-Zhimu decoction in gout patients: a systematic review and Meta-analysis. Pharm Biol. 2020;58(1):1023-1034. doi:10.1080/13880209.2020.1823426}