Chromolaena odorata flavonoids attenuate experimental nephropathy: Involvement of pro-inflammatory genes downregulation.

Nephropathy is a serious complication comorbid with a number of life-threatening diseases such as diabetes. Flavonoids are well known cytoprotective phytochemicals. Here, nephropathy associated with streptozotocin (STZ) treatment in experimental animals was challenged by flavonoids (CoF) isolated from Chromolaena odorata. Experimental animals were divided into control (n = 5), STZ (40 mg/kg b.w. i.p. n = 5) and STZ-CoF (CoF = 30 mg/kg b.w. oral, 60 days, n = 7) groups. Blood urea nitrogen (BUN) and serum creatinine (SC) levels were quantified using ELISA. Kidney function, inflammatory marker, and antioxidant gene expression levels were also evaluated using reverse-transcription and polymerase chain reaction protocols. Histological assessment was also performed using Haematoxylin and Eosin (H&E) staining protocols. CoF improved kidney function by restoring BUN/SC levels to pre-STZ treatment states. KIM-1, TNF-α, and MCP-1 but not TNF-R and IL-10 genes were significantly downregulated in STZ-CoF treated group in comparison with STZ-treated group (p < 0.05). Anti-oxidant genes (GPx-1, CAT) significantly (p < 0.05 vs. control) upregulated in STZ-treatment did not respond to CoF treatment. STZ treatment associated Bowman's space enlargement, thickened basement membrane, and glomerulosclerosis were completely reversed in STZ-CoF group. Finally, CoF has demonstrable anti-nephropathic via downregulation of proinflammatory genes and may represent new management option in clinical nephropathy.

Flavones scaffold of Chromolaena odorata as a potential xanthine oxidase inhibitor: Induced Fit Docking and ADME studies.

Introduction: Gout is a type of painful inflammation initiated by the interactions between monosodium urate crystals and connective tissue. Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine, then to uric acid. The primary treatments for gout include XO inhibitors. At present, allopurinol is the most used XO inhibitor for the treatment of gout. However, it can cause adverse effects commonly known as allopurinol hypersensitivity syndrome, thereby limiting its usage. Consequently, it is necessary to develop potent and less toxic inhibitors of XO. Chromolaena odorata is one of such plants under investigation for its diverse health benefits. Methods: Phytochemicals of C. odorata were screened against XO receptor, using molecular docking. The top five hit compounds of glide docking yield flavones scaffold which were subjected to induced fit docking (IFD) and absorption, distribution, metabolism, and excretion (ADME) studies. Results: The result showed that flavones scaffold of C. odorata can bind with higher affinity and lower free energy values when compared to that of the standard, allopurinol. The IFD scores of the flavones scaffold range from -1525.25 to -1527.99 kcal/mol. Conclusion: Our results have shown that flavones scaffold might have the potential to act as an effective drug candidate when compared to allopurinol in treating and/or preventing gout and some inflammatory condition.