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.
ABSTRACT
BACKGROUND: Diabetic peripheral neuropathy (DPN), due to its potential for causing morbidity and disability from foot ulcers and amputations, is increasingly becoming a source of concern in Saudi Arabia and worldwide. However, wide variability exists in the prevalence of DPN reported in previous studies in Saudi Arabia, limiting the utility of existing data in national public health policy. Therefore, the aim of this study was to systematically evaluate the magnitude of DPN in patients living with DM in Saudi Arabia in order to inform policymakers during the implementation of appropriate preventive and treatment strategies for DPN. METHODS: PubMed, Google Scholar, African Journals Online, Scopus, Web of Science, Embase, and Wiley Online Library were searched systematically to acquire relevant articles based on preset criteria. We evaluated heterogeneity and publication bias and employed a random-effects model to estimate the pooled prevalence of DPN from the included studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in conducting the meta-analysis. Analysis was performed using the STATA Version 12 software. RESULTS: Twelve studies with a total of 4,556 participants living with DM, of whom 2,081 were identified as having DPN were included in the meta-analysis. The overall prevalence of DPN was 39% (95% CI [30%, 49%]). Subgroup analysis based on diagnostic method showed that prevalence estimates for DPN using screening questionnaires and clinical examination were 48% (95% CI [46%, 50%]) and 40% (95% CI: [38%, 42%]), respectively, while the estimated prevalence using nerve conduction studies was 26% (95% CI [15%, 36%]). CONCLUSION: This study showed a high magnitude of DPN in Saudi Arabia (39%), thus highlighting the need for sustained efforts to reduce the prevalence of diabetes mellitus and DPN in the kingdom.
