AUTHOR=Jeelani Mohammed , Fouotsa Hugues , Mohammed Osama A. , Alfaifi Jaber , Adebayo Salmon , Ahmed Mohammad Muzammil , Yahia Amar Ibrahim Omer , Eissa Hanan , Bahashwan Emad , Mohammed Nahid Ahmed , Alotaibi Yousef Ayesh , Asiri Ashwaq Yahya , Rezigallah Assad , Alharthi Muffarah Hamid , Dzoyem Jean Paul , Isa Adamu Imam 

TITLE=Naturally occurring benzophenones and xanthones from Garcinia smeathmannii (Planch. & Triana) Oliv. displayed anti-inflammatory effects by modulating the activities of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1370073

DOI=10.3389/fphar.2024.1370073

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds’ anti-inflammatory effects. In this study, four xanthones ananixanthone (<bold>1</bold>), smeathxanthone A (<bold>2</bold>), smeathxanthone B (<bold>3</bold>), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (<bold>4</bold>); and three benzophenones guttiferone O (<bold>5</bold>), guttiferone M (<bold>6</bold>), and aristophenone A (<bold>7</bold>) from <italic>Garcinia smeathmannii</italic> (Planch. &amp; Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages.</p><p><bold>Methods:</bold> The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer.</p><p><bold>Results:</bold> All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (<bold>6</bold>), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (<bold>5</bold>) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10).</p><p><bold>Conclusion:</bold> This observation supports future exploration of ananixanthone (<bold>1</bold>), guttiferone O (<bold>5</bold>), and guttiferone (<bold>6</bold>) as potential candidates for the development of anti-inflammatory drugs.</p>