Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Anti-inflammatory and phytochemical evaluation of Combretum aculeatum Vent growing in Sudan Kamal M. Hamad a , Manal M. Sabry a,∗ , Sabah H. Elgayed a , Abdel-Rahman El Shabrawy a , Ahlam M. El-Fishawy a , Gehad A. Abdel Jaleel b a Department of Pharmacognosy, Faculty of Pharmacy Cairo University, Cairo, 11562, Egypt b Department of Pharmacology, National Research Centre, Dokki, Giza, Egypt ARTICLE INFO Keywords: Phytochemical Anti-inflammatory Combretum aculeatum Combretaceae ABSTRACT Ethnopharmacological relevance: Combretum aculeatum Vent was traditionally used in Sudan, Eretria and Ethiopia as anti-inflammatory in case of skin inflammation, catarrh, wounds, scorpion stings and snake bites. Nevertheless, there is no scientific information regarding this activity. Aim of study: The present study aimed to evaluate the phytochemical constituents and the scientific basis for the traditional use of Combretum aculeatum Vent through studying its anti-inflammatory properties for the first time to illustrate the putative mechanisms behind this bioactivity. Materials and methods: the ethanolic extract was partitioned by petroleum ether, methylene chloride, ethyl acetate, and n-butanol saturated with water. The petroleum ether fraction was saponified and the saponifiable and unsaponifiable fractions were analyzed on GC/MS. The different fractions were subjected to phytochemical investigation to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanolic extract was eval- uated using carrageenan induced rat paws edema method at doses of 200, 400 and 600 mg/kg and proved based on histopathological and biochemical parameters. Results: Five known compounds were isolated for the first time from the aerial parts of Combretum aculeatum Vent: quercetin, vitexin, isorhamnetin 3-O-β-glucoside, isovitexin and rutin, in addition to two previously iso- lated ones: β-sitosterol and its glucoside. The ethanolic extract evidenced in-vivo anti-inflammatory activity by oral intake of 400 mg/kg of the ethanolic extract significantly (P ≥ 0.05) decreased the paw edema (only 32 ± 1.9% increase in paw weight after 4 h) compared to indomethacin (28.6 ± 2.5%). Moreover, it sig- nificantly suppressed the serum malondialdehyde (MDA) and nitric oxide (NO) and increased the GSH to be 11.76 ± 0.85, 5.13 ± 0.62 μmol/mL and 5.66 ± 0.28 μM/mL, respectively. It diminished the serum cytokines TNF-α, IL-6 and IL-1β levels to be 39.1 ± 1.2, 32.6 ± 1.1 and 37.5 ± 1.2 pg/mL, respectively. Results are ac- companied by histopathological examination. Conclusion: Overall, the results herein presented significant anti-inflammatory properties traditionally ascribed to Combretum aculeatum Vent. Moreover, the biochemical mechanisms associated to this action were highlighted, introducing new prospects for the development of effective anti-inflammatory herbal medicinal products. 1. Introduction Combretaceae is a large family of herbs, shrubs and trees. It com- prises about 20 genera and 600 species with tropical distribution around the globe and centers of diversity in Africa and Asia. Some Combretum species are extensively used in traditional medicine against inflammation and various ailments (Muthu et al., 2006). Several Com- bretum species have been investigated for their phytochemistry: terpe- noids, phenolic acids, flavonoids, phenanthrene, stilbenes and tannins have been isolated (Asami et al., 2003; Bisoli et al., 2008; Eloff et al., 2005; Osborne and Pegel, 1984; Pettit et al., 1988; Rogers, 1995; Teles et al., 2015; Wang et al., 2014) and for their biological activity viz.; antibacterial, antifungal, antioxidant, anti-inflammatory and anti- protozoal (Asres et al., 2001; Mariod et al., 2006; Masoko et al., 2007; Gouveia et al., 2011; De Morais Lima et al., 2012; Simon et al., 2012). Combretum aculeatum Vent is widely distributed in Sudan, Eretria and Ethiopia, South America, and Asia (Jossang et al., 1996). Different plant parts are traditionally used: the roots as purgative and vermifuge and for treatment of gonorrhea and leprosy. In Sudan, bark, leaves and seeds extracts were taken to treat skin tuberculosis, fever, wounds, https://doi.org/10.1016/j.jep.2019.112052 Received 24 March 2019; Received in revised form 6 June 2019; Accepted 29 June 2019 ∗ Corresponding author. E-mail address: manal.sabry@pharma.cu.edu.eg (M.M. Sabry). Journal of Ethnopharmacology 242 (2019) 112052 Available online 29 June 2019 0378-8741/ © 2019 Published by Elsevier B.V. T