New Perspectives on the Therapeutic Potentials of Bioactive Compounds from Curcuma longa: Targeting COX-1 & 2, PDE-4B, and Antioxidant Enzymes to Counteract Oxidative Stress and Inflammation

Abstract

Background Inflammations, oxidative stress, and pains underlie the pathogenesis of non-communicable diseases (NCDs) like respiratory disorders and cancer; however, they are scientifically treated with Curcuma longa. Therefore, the pharmacological screening (antioxidant, anti-inflammatory, and analgesic) of the plant's rhizome, isolation and characterization of its compounds, as well as their in silico profiling with cyclooxygenases, phosphodiesterase, superoxide dismutase, glutathione peroxidase, and catalase could yield lead compounds with better benefit-to-risk ratio against oxidative stress and inflammation. Methods The collection of the plant's rhizomes , extract preparation, anti-inflammatory, analgesic, and antioxidant studies, retrieval of target proteins, GC-MS, ADME, and docking analyses were done using standard protocols. Results Curcuma longa's percentage edema inhibition and analgesic potentials were better than aspirin in both acute and sub-acute inflammations as well as chemical and thermal-induced pains; moreover, its antioxidant activities were better than vitamin C. Moreover, twenty compounds with anti-inflammatory, analgesic, and antioxidant activities were unraveled from the GC-MS analysis. Ar-tumerone, curcumin, γ-sitosterol, α-tocopherol, isocurcumenol, adamantane, and curdione were the lead compounds based on their binding affinities (for PDE-4B, COX-1, COX-2, SOD, CAT, GPx), lower molecular weights, non-permeation of blood brain barrier, bioavailability profiles, non-inhibition of metabolizing enzymes, faster renal clearance, and non-violation of Lipinski's rules. Conclusion Adamantane, α-tocopherol, and γ-sitosterol reported for the first time in the plant's rhizome could mitigate oxidative stress and inflammation as mediators of apoptosis, cytotoxic impaired autophagy, DNA damages, and mitochondrial dysfunction that contributes to the progression of non-communicable diseases (NCDs).