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

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

doi:10.3389/fphar.2024.1370073

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

Front Pharmacol. 2024 Jun 3:15:1370073. doi: 10.3389/fphar.2024.1370073. eCollection 2024.

Authors

Mohammed Jeelani¹, Hugues Fouotsa², Osama A Mohammed³, Jaber Alfaifi⁴, Salmon Adebayo⁵, Mohammad Muzammil Ahmed⁶, Amar Ibrahim Omer Yahia⁷, Hanan Eissa³, Emad Bahashwan⁸, Nahid Ahmed Mohammed¹, Yousef Ayesh Alotaibi⁹, Ashwaq Yahya Asiri¹⁰, Assad Rezigallah¹¹, Muffarah Hamid Alharthi¹², Jean Paul Dzoyem¹³, Adamu Imam Isa¹

Affiliations

¹ Department of Physiology, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
² Department of Engineering Process, National Higher Polytechnic School of Douala, University of Douala, Douala, Cameroon.
³ Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
⁴ Department of Child Health College of Medicine, University of Bisha, Bisha, Saudi Arabia.
⁵ Neoteriks Health Research and Innovation, Avon, IN, United States.
⁶ Department of Basic Medical Sciences, Faculty of Medicine, Majmaah University, Al Majma'ah, Saudi Arabia.
⁷ Department of Pathology College of Medicine University of Bisha, Bisha, Saudi Arabia.
⁸ Department of Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
⁹ Department of Surgery, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
¹⁰ Department of Ophthalmology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
¹¹ Department of Anatomy, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
¹² Department of Community and Family Medicine, College of Medicine University of Bisha, Bisha, Saudi Arabia.
¹³ Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.

Abstract

Introduction: 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 (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & 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. Methods: 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. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

Keywords: benzophenone; cyclooxygenase; cytokines; lipoxygenase; nitric oxide; xanthone.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.