| Summary: | The objective of the current study was to evaluate the phytochemical and pharmacological potential of the <i>Cornus macrophylla</i>. <i>C. macrophylla</i> belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of <i>C. macrophyll</i> were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of <i>C. macrophylla</i> was studied by 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the <i>C. macrophylla</i> were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of <i>C. macrophylla</i> confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC<sub>50</sub> values of 09.54 μg/mL and 7.8 μg/mL against ABTS and DPPH assay respectively. Among all the fractions of <i>C. macrophylla</i>, Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC<sub>50</sub> values were 93.35 μg/mL against COX-2 and 75.64 μg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of <i>C. macrophylla. C. macrophylla</i> has promising potential as a source for the development of new drugs against inflammation in the future.
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