Anti-Inflammatory and Hypouricemic Effect of Bioactive Compounds: Molecular Evidence and Potential Application in the Management of Gout

Abstract

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular hyperuricemia. Besides gout, hyperuricemia leads to an increased inflammatory state of the body with consequent increased risk of comorbidities such as cardiovascular diseases. Increasing evidence shows that bioactive compounds have a significant role in fighting inflammatory and immune chronic conditions. In gout and hyperuricemia, these molecules can exert their effects at two levels. They can either decrease serum uric acid concentrations or fight inflammation associated with monosodium urate crystals deposits and hyperuricemia. In this view, they might be considered valuable support to the pharmacological therapy and prevention of the disease. This review aims to provide an overview of the beneficial role of bioactive compounds in hyperuricemia, gout development, and inflammatory pathways of the disease.

Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy

“…However, large interspecies difference in the expression of metabolic enzymes and drug elimination pathways, which influence both drug pharmacokinetics and pharmacology, requires careful selection of the animal model. Several animal models of arthritis, either experimentally induced or spontaneous, have been developed that significantly contributed to understanding disease pathogenesis and permitted evaluation of new potential anti-arthritic agents, despite no single animal model being able to fully replicate all the clinical features of human arthritis [ 7 , 41 , 42 , 43 , 44 , 45 ]. Both spontaneous and induced animal models of arthritis are available.…”

“…Therefore, induced models of arthritis are preferable for the assessment of anti-arthritic agents. These models involve mechanically induced joint destabilization or chemical treatment, usually by intra-articular injection of the chemical agent, causing an inflammatory reaction that mimics arthritis development [ 7 , 41 , 42 , 44 , 45 ]. The knee is the joint most often employed in animal models of arthritis [ 41 , 42 ].…”

“…Monoiodoacetate (MIA) is often used to induce knee osteoarthritis upon intra-articular injection, mimicking human joint pathology and osteoarthritic pain [ 41 , 42 ]. On the other hand, injection of MSU crystals (suspended in saline or in mineral oil) is the commonly employed method to trigger acute gout inflammation and gouty arthritis [ 7 , 44 ]. Immunization with immunogenic adjuvants, such as complete Freund’s adjuvant (CFA) and cartilage antigens (e.g., CII) by intradermal or subcutaneous injection, induces immune-mediated chronic polyarthritis of systemic nature that resembles RA [ 41 , 43 , 45 , 46 ].…”

“…Several natural triterpenoids with anti-inflammatory and anti-arthritic activities described in recent literature [ 5 , 6 , 7 ] can be potential therapeutic alternatives and/or adjuvants for anti-arthritic drugs currently in the market, which have unwanted side-effects associated with prolonged use. However, natural products, including triterpenoids, often suffer from poor absorption and low bioavailability due to extensive first-pass metabolism upon oral administration, and low water solubility, among other physicochemical characteristics ( Table S4, Supplementary Materials ) [ 6 , 8 , 9 ].…”

Lignan and Phthalide Derivatives from the Rhizome of Ligusticum chuanxiong (Rhizoma chuanxiong) and Evaluation of Their anti-Xanthine Oxidase Activities

“…Gout is one of the relatively common inflammatory diseases of the joints caused by the deposition of uric acid crystals in the tissues, in which uric acid is produced by xanthine oxidase (XO) acting on the purine bases hypoxanthine and xanthin . In developed countries, the prevalence of gout is 3–6% in males and 1–2% in females, with a strong impact on individual health and healthcare systems . Studies in recent years have shown that gout is an independent risk factor for chronic kidney disease, hypertension, cardiovascular and cerebrovascular diseases, diabetes, and an independent predictor of premature death. , …”