Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea

• Published in: BMC complementary and alternative medicine 2021-09, Vol.21 (1), p.234-17, Article 234
• Main Authors: Popoola, Temidayo D, Guetchueng, Stephanie T, Ritchie, Kenneth J, Awodele, Olufunsho, Dempster, Nicola M, Akinloye, Oluyemi, Sarker, Satyajit D, Fatokun, Amos A
• Format: Article
• Language: English
• Subjects: Analysis; Anti-inflammatory; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-inflammatory drugs; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antioxidant; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Assaying; Basic-Leucine Zipper Transcription Factors - drug effects; Cancer; Cancer therapies; Cell culture; Cell Survival - drug effects; Cells, Cultured - drug effects; Chemotherapy; Constituents; Cytotoxicity; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Experiments; GA-binding protein; Humans; Inflammation; Lipopolysaccharides; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Mitogens; Molecular modelling; Neoplasms - drug therapy; Nitric oxide; Olacaceae - chemistry; Olax subscorpioidea; Oxidative stress; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Roots - chemistry; Plants, Medicinal - chemistry; Prevention; Prostate cancer; Reactive oxygen species; Scientific equipment and supplies industry; Streptomyces - chemistry; Uvaria - chemistry; Uvaria chamae
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-021-03404-0

Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). Extracts up to 100 μg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC  > 200 μg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.