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

BMC Complement Med Ther. 2021 Sep 18;21(1):234. doi: 10.1186/s12906-021-03404-0.

Abstract

Background: 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.

Methods: 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).

Results: Extracts up to 100 μg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 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.

Conclusion: 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.

Keywords: Anti-inflammatory; Antioxidant; Olax subscorpioidea; Uvaria chamae; cancer.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Basic-Leucine Zipper Transcription Factors / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured / drug effects
  • Doxorubicin / pharmacology*
  • Doxorubicin / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Olacaceae / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Plant Roots / chemistry
  • Plants, Medicinal / chemistry
  • Streptomyces / chemistry
  • Uvaria / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Basic-Leucine Zipper Transcription Factors
  • Plant Extracts
  • Doxorubicin