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A virtual screening combined with experimental verification identified the potential mechanism of fuzitang decoction in the treatment of Gouty Arthritis.
Virtual screening in combination with experimental verification identified the potential mechanism of fuzitang decoction, a prescription of traditional Chinese medicine, in the treatment of Gouty Arthritis, according to a new study.1
A team of investigators from China explored the underlying mechanisms of fuzitang decoction, identifying a novel anti-inflammatory compound, deoxyandrographolide, that may provide clinical evidence to support use in Gouty Arthritis.
“Fuzitang decoction is a classical Traditional Chinese Medicine formula and has been widely used to treat joint pain diseases for thousands of years,” wrote the investigative team, led by Yuhe Lei and Ziliang Qian, from the Shenzhen Hospital of Guangzhou University of Chinese Medicine. “Previous studies have also confirmed that fuzitang decoction is positive and effective in the treatment of Gouty Arthritis. However, the underlying mechanism of its anti-Gouty Arthritis effects is elusive.”
The quality of life of patients with Gouty arthritis is often severely impacted by the disease, due to the potential for the presence of several comorbidities, including kidney disease, hypertension, obesity, diabetes, and cardiovascular diseases. Gout treatment has focused on eliminating flares and preventing tophus. However, the inflammatory reaction of monosodium urate in the joint is a key pathogenesis of flares, making anti-inflammatory therapy crucial for treatment.
First-line therapies for Gouty Arthritis can include colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, but anti-inflammation for the disease can remain challenging.2 Many patients with Gouty Arthritis experience incomplete responses or contradictions, as well as gastrointestinal and cardiovascular adverse reactions, when receiving treatment with anti-inflammatory drugs. Lei and colleagues suggested exploring better, more optimized treatments to control these limitations.1
Recent clinical literature has reported fuzitang decoction had a good clinical effect in the treatment of Gouty Arthritis.3 Significant reduction of joint pain and swelling of Gouty Arthritis, as well as white blood cell counts and serum uric acid, have been linked to its treatment. Adverse reactions were additionally significantly lower compared with those of the anti-inflammatory treatment group, according to the data.
However, fuzitang decoction also contains a toxic ingredient, aconitine, which can cause some side effects and impact clinical use.1 Extreme caution is necessary for its usage, making specific anti-inflammatory components and mechanisms unclear for the treatment of Gouty Arthritis. For their analysis, Lei and colleagues explored the main bioactive ingredients of fuzitang decoction for Gouty Arthritis, to clarify the molecular mechanisms.
In the study, the active components of fuzitang decoction and corresponding targets were obtained from the Traditional Chinese Medicine System Pharmacology and TargetNet database. Related targets corresponding to the active ingredients were collected to create a network.
Investigators performed pathway enrichment analyses of protein-protein interaction, herbal-component target, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes to examine potential targets and signaling pathways. Moreover, molecular docking simulations were used to identify the interactions between drugs and targets, while in vitro experiments helped to validate the potential targets and signaling pathways.
Upon analysis, investigators identified 49 important targets and 41 active ingredients for herb-ingredient-target-disease network construction. The complex network suggested that most components of fuzitang decoction adjusted multiple targets. Results indicated that 5 key ingredients of fuzitang decoction (kaempferol, luteolin, catechin, perlolyrine, and deoxyandrographolide) had strong binding effects on the target proteins.
After performing protein-protein interaction network analysis, multiple potential targets to treat Gouty Arthritis were developed, including PPARG, CYP3A4, PTGS2, VEGFA, and CYP1A1. Further experimental validation indicated that deoxyandrographolide significantly reduced the expression of IL-1β, COX2, NLRP3, and IL-6 in inflammatory monocyte cells.
“The expression of IL-1β, COX2, NLRP3, and IL-6 were decreased in the deoxyandrographolide-treatment group, indicating that deoxyandrographolide could reduce the inflammatory reaction in Gouty Arthritis model in vitro,” investigators wrote.1 “These results further provided a theoretical basis for explaining fuzitang decoction used in treating Gouty Arthritis.”