Abstract
Human health may benefit from the study of natural compounds and phytoconstituents that can protect from inflammation. We investigated Nimbin (N1), a member of the ring C Seco-tetranortriterpenoids family, and its semi-natural analog deacetyl Nimbin namely N2 and N3 for their anti-inflammatory properties. As key findings, N1, N2, and N3 were able to improve wound healing by cell proliferation in a period of 24 h and were able to reduce the reactive oxygen species (ROS) production in Madin-Darby Canine Kidney cells which were screened using dichloro-dihydro fluorescein diacetate (DCF-DA) staining. When the zebrafish larvae were subjected to DCF-DA assay N1, N2, and N3 were able to substantially reduce the ROS levels in a dose-dependent manner. In zebrafish larvae, the cell death indicates the fluorescent intensity due to acridine orange staining that was found to be dramatically decreasing upon the treatment of N1, N2, and N3. The cell membrane lipid peroxidation levels were also reduced in a dose-dependent manner upon the treatment of Nimbin and its analogs indicating lesser blue fluorescent levels. Among the Nimbin and its analogs, N2 was subjected to have better activity. To confirm the activity of N1, N2, and N3, in silico characterization was performed using Density functional theory and molecular docking. As a result, N2 exhibited the lowest electronegative value and highest binding energy when docked with anti-inflammatory and antioxidant proteins CAT, COX, GP, IL-1, and MPO. Furthermore, the therapeutic potential of N2 must be explored at the molecular level as well as in clinical studies for the treatment of inflammation-associated diseases.