Exploring the mechanism of action of Jinqiancao in treating gout based on network pharmacology and molecular docking
Gout is a metabolic disease characterized by elevated blood uric acid levels caused by disorders in uric acid excretion and/or purine metabolism. Gout often causes joint pain, deformity and kidney damage, and is often associated with hypertension, diabetes, cardiovascular and other diseases. Due to the change of diet structure, the incidence of gout is increasing year by year, and the incidence rate is positively related to age. The incidence rate of gout above 80 years old is as high as 12%. Western medicine often uses drugs that inhibit uric acid production (such as allopurinol), drugs that promote uric acid excretion (such as sinuola, tranilast, etc.), anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs, colchicine), and corticosteroids to treat gout, with the aim of correcting hyperuricemia and preventing gout. However, due to significant adverse reactions and the need for long-term medication, the patient’s compliance is poor, which limits its application.

Traditional Chinese medicine has the characteristics of multi-target, good efficacy, and high safety in treating gout. It has advantages that cannot be replaced by Western medicine in reducing uric acid levels and anti-inflammatory effects. Gout belongs to the category of “Bi syndrome” in traditional Chinese medicine, also known as “Baihu Li Jie” or “wet disease”. Jinqiancao has the effects of promoting dampness, reducing jaundice, diuresis, and promoting diuresis. It is used for conditions such as damp heat jaundice, stone reflux, heat reflux, and painful urination. The compound of Jinqiancao can significantly improve the symptoms of gout patients and has achieved good therapeutic effects in clinical practice. Modern pharmacological studies have shown that goldenrod can reduce serum uric acid levels in mice with hyperuricemia. The total flavonoids of goldenrod can reduce serum creatinine, urea nitrogen levels, and mouse kidney index, weaken the activity of xanthine oxidase and adenosine deaminase, lower serum TNF – α, COX-2, MCP-1 levels, improve kidney disease, and restore atrophy of thymus and spleen immune organs. At present, there is a lack of systematic understanding of the active ingredients and mechanisms of action of Jinqiancao in treating gout. Therefore, this study uses network pharmacology to explore the potential pharmacological components, targets, and signaling pathways of Lonicera japonica in treating gout as a whole, providing reference for further research and clinical application of Lonicera japonica.

From the “Active Ingredient Predictive Target” network, it can be inferred that quercetin, luteolin, kaempferol, naringenin, isorhamnetin, acacetin, quercetin, glycyrrhizin, quercetin, and naringenin may be the main active ingredients in the treatment of gout in Chinese herbal medicine. Research has shown that flavonoids may be active ingredients in the anti gout activity of Scutellaria baicalensis. Quercetin can reduce the activity of xanthine oxidase (XO) and decrease the expression of glucose transporter 9 in the liver and intestine, resulting in a decrease in serum uric acid (UA), urea nitrogen, and creatinine levels in hyperuricemia mice; Shannai phenol can significantly inhibit XO activity, and its mechanism may be that Shannai phenol inserts into the XO active center site, competitively inhibits substrate entry, and thereby reduces XO catalyzed xanthine to produce uric acid; Isorhamnetin can directly inhibit XO activity in the liver, thereby suppressing the production of UA; Osmanthus extract can alleviate ankle swelling in acute gouty arthritis model rats by downregulating the levels of IL-1 β, IL-17, TNF – α, and IL-6. PPI network analysis shows that goldenrod can control inflammation and improve gout symptoms by reducing the expression and levels of inflammatory and chemokines such as IL6, IL1B, CXCL8, CCL2 induced by urate deposition. The main active ingredients in goldenrod play a therapeutic role in gout by inhibiting uric acid production, promoting uric acid excretion, and improving inflammation.

The enrichment analysis of KEGG pathway showed that the pathway of Lysimachia christinae to treat gout mainly involved TNF signaling pathway, AGE-RAGE signaling pathway in diabetes complications, fluid shear stress and atherosclerosis, hepatitis B, Kaposi sarcoma associated herpesvirus infection, human cytomegalovirus infection, hepatitis C, IL-17 signaling pathway, etc. IL-17 is a pro-inflammatory cytokine mainly secreted by helper T cells and innate immune cells, playing an important role in inflammatory and autoimmune diseases. Intraarticular injection of monosodium urate crystals can stimulate the production of Th17 cells and the inflammatory cell chemokine IL-17 associated with Th17. IL-17 neutralizing antibodies can significantly reduce leukocyte infiltration and myeloperoxidase activity, decrease the expression of IL-1 α, IL-1 β, IL-16, and IL-17, thereby alleviating inflammatory responses. The IL-17 receptor activates downstream signaling pathways such as NF – κ B and JNK, thereby inhibiting the release of other inflammatory mediators and exerting significant anti-inflammatory effects to alleviate gout symptoms. TNF is mainly produced by macrophages, monocytes, natural killer cells, and other cells. It can induce leukocyte endothelial activation, cytokine and chemical factor amplification, and promote the release of proteolytic enzymes and oxygen free radicals, thereby promoting the occurrence and development of inflammation. Research has found that serum TNF – α levels are elevated in gout patients, and blocking TNF significantly reduces pro-inflammatory cytokines and chemokines such as IL-1, IL-6, IL-8, or GMCSF. TNF, as a pro-inflammatory cytokine, induces the pathological process of gouty arthritis by inducing IL-1 activation, enhancing IL-6 mediated inflammatory response, and activating the NF – κ B inflammatory signaling pathway. TNF – α antagonists play an important role in the treatment of gout; In the TNF signaling pathway, TNF – α can upregulate NF – κ B and other factors, leading to an increase in various effector factors and achieving effects such as leukocyte recruitment and inflammatory cascade amplification to control the inflammatory response. Urate crystals, as an endogenous danger signal related molecule, are recognized by cell membrane surfaces and Toll like receptors, activating NF – κ B and inducing the release of inflammatory factors (TNF – α, IL-6, IL-1 β, IFN – α, IFN – β, etc.), promoting gouty inflammation attacks. Research has shown that inhibiting the mRNA and protein expression of TLR2, TLR4, and NF – κ B can reduce the synthesis and release of inflammatory factors such as TNF – α, IL-1 β, and IL-6 in serum.

This study used network pharmacology methods to predict the active ingredients, targets, and molecular mechanisms of Lonicera japonica in treating gout. The results showed that Lonicera japonica exerts its therapeutic effect on gout through multiple components, targets, and pathways. But further biological experiments are needed to validate the active ingredients and core targets, in order to clarify the mechanism of Jinqiancao in treating gout.