Zaninelli Tiago H, Martelossi-Cebinelli Geovana, Saraiva-Santos Telma, Borghi Sergio M, Fattori Victor, Casagrande Rubia, Verri Waldiceu A
Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Centre of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.
Center for Research in Health Sciences, University of Northern Londrina, Londrina, Brazil.
Expert Opin Ther Targets. 2023 Jul-Dec;27(8):679-703. doi: 10.1080/14728222.2023.2247559. Epub 2023 Sep 11.
Gout arthritis (GA) is an intermittent inflammatory disease affecting approximately 10% of the worldwide population. Symptomatic phases (acute flares) are timely spaced by asymptomatic periods. During an acute attack, redness, joint swelling, limited movement, and excruciating pain are common symptoms. However, the current available therapies are not fully effective in reducing symptoms and offer numerous side effects. Therefore, unveiling new drug targets and effector molecules are required in developing novel GA therapeutics.
This review discusses the pathophysiological mechanisms of GA and explores potential pharmacological targets to ameliorate disease outcome. In addition, we listed promising pre-clinical studies demonstrating effector molecules with therapeutical potential. Among those, we emphasized the importance of natural products, including traditional Chinese medicine formulas and their multitarget mechanisms of action.
In our search, we observed that there is a massive gap between pre-clinical and clinical knowledge. Only a minority (4.4%) of clinical trials aimed to intervene by applying natural products or current hot targets described herein. In this sense, we envisage four possibilities for GA therapeutics, which include the repurposing of existing therapies, ALX/FPR2 agonism for improvement in disease outcome, the use of multitarget drugs (e.g. natural products), and targeting the neuroinflammatory component of GA.
痛风性关节炎（GA）是一种间歇性炎症性疾病，影响着全球约10%的人口。症状期（急性发作）被无症状期适时隔开。急性发作期间，发红、关节肿胀、活动受限和剧痛是常见症状。然而，目前可用的治疗方法在减轻症状方面并不完全有效，且有许多副作用。因此，开发新型GA治疗药物需要揭示新的药物靶点和效应分子。
本综述讨论了GA的病理生理机制，并探索了改善疾病结局的潜在药理学靶点。此外，我们列出了有前景的临床前研究，这些研究证明了具有治疗潜力的效应分子。其中，我们强调了天然产物的重要性，包括中药配方及其多靶点作用机制。
在我们的研究中，我们观察到临床前知识和临床知识之间存在巨大差距。只有少数（4.4%）临床试验旨在通过应用本文所述的天然产物或当前热门靶点进行干预。从这个意义上说，我们设想了GA治疗的四种可能性，包括现有疗法的重新利用、ALX/FPR2激动作用以改善疾病结局、使用多靶点药物（如天然产物）以及针对GA的神经炎症成分。
