New drug targets for the treatment of gout arthritis: what's new?

被引:4
|
作者
Zaninelli, Tiago H. [1 ]
Martelossi-Cebinelli, Geovana [1 ]
Saraiva-Santos, Telma [1 ]
Borghi, Sergio M. [1 ,2 ]
Fattori, Victor [1 ,3 ]
Casagrande, Rubia [4 ]
Verri Jr, Waldiceu A. [1 ,5 ]
机构
[1] Univ Estadual Londrina, Ctr Biol Sci, Dept Pathol, Lab Pain Inflammat Neuropathy & Canc, Londrina, PR, Brazil
[2] Univ Northern Londrina, Ctr Res Hlth Sci, Londrina, Brazil
[3] Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Karp Res Bldg, Boston, MA USA
[4] Univ Estadual Londrina, Ctr Hlth Sci, Dept Pharmaceut Sci, Lab Antioxidants & Inflammat, Londrina, Brazil
[5] Univ Estadual Londrina, Dept Ciencias Patol, Rodovia Celso Garcia Cid Km480 PR445,POB, BR-86057970 Londrina, PR, Brazil
关键词
natural products; antioxidants; multitargeting drug; specialized pro-resolving lipid mediators; microbiota; neuroimmune interactions; drug repurposing; MONOSODIUM URATE CRYSTALS; NLRP3 INFLAMMASOME ACTIVATION; URIC-ACID; RECEPTOR STIMULATION; HYDROGEN-PEROXIDE; SYNOVIAL-FLUID; UP-REGULATION; MURINE MODEL; SUBSTANCE-P; IN-VIVO;
D O I
10.1080/14728222.2023.2247559
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
IntroductionGout 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.Areas coveredThis 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.Expert opinionIn 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.
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页码:679 / 703
页数:25
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