Exploring the Mechanism through which Phyllanthus emblica L. Extract Exerts Protective Effects against Acute Gouty Arthritis: A Network Pharmacology Study and Experimental Validation

Increased uric acid levels and inflammatory reactions are the main factors considered responsible for the development of gouty arthritis. Phyllanthus emblica L. (PEL) has several promising pharmacological properties, including anti-inflammation and antioxidation. However, only a few studies have investigated its use for treating acute gouty arthritis (AGA), and the mechanism of action of PEL has not yet been clarified. The aim of this study was to verify the protective effects of PEL against gout and explore its underlying mechanism through network pharmacology and animal experiments. The main active components of the extract from PEL including mucic acid, mucic acid lactone, gallic acid, ethyl hexyl phthalate, and glucose were identified by UPLC-ESI-qTOF-MS. Network pharmacological analysis results revealed 13 active compounds in PEL and 85 related targets for the treatment of gout. The core mechanism of action of PEL is mainly associated with inflammation-related pathways, including the HIF-1, PI3K-Akt, TNF, and NOD-like receptor signaling pathways. Previous studies revealed that the NOD-like receptor signaling pathway, especially the NLRP3 inflammasome, plays an important role in the pathogenesis of AGA; therefore, we mainly investigated the effect of PEL on the NLRP3/ASC/caspase-1 pathway in gout rats. In the animal experiments, PEL was shown to have a satisfactory antigout effect, as it effectively reduced uric acid (UA) and xanthine oxidase (XOD) levels. In terms of inhibiting AGA-associated inflammatory reactions, our results showed that PEL significantly decreased the expression of NLRP3 and caspase-1 in ankle synoviocytes as well as the levels of downstream inflammatory factors, such as TNF-α, IL-10, and IL-1β in serum. Moreover, the results of our study show that PEL reduced MMP13 expression in the ankle synovium. Overall, the results of this study indicate that PEL exerted a therapeutic effect against AGA. Reducing uric acid levels, inhibiting inflammation, and decreasing the expression of MMP13 may be responsible for the therapeutic effect of PEL, which suggests that PEL can be further developed as a drug for the treatment of gout.