Advances in Azorella glabra Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization

Abstract

Azorella glabra Wedd. (AG) is traditionally used to treat gonorrhea or kidney’s problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of AG chloroform fraction (AG CHCl3) and of its ten sub-fractions (I-X) and to identify their possible bioactive compounds. We determined their in vitro antioxidant activity using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) and superoxide anion (SO) assays, and their phytochemical profile by spectrophotometric and LC-MS/MS techniques. I-X action on two acute myeloid leukemia (AML) cell lines viability, apoptosis and cell cycle were evaluated by MTS, western blotting and cytofluorimetric assays. Different polyphenol, flavonoid and terpenoid amount, and antioxidant activity were found among all samples. Most of I-X induced a dose/time dependent reduction of cell viability higher than parent extract. IV and VI sub-fractions showed highest cytotoxic activity and, of note, a negligible reduction of healthy cell viability. They activated intrinsic apoptotic pathway, induced a G0/G1 block in leukemic cells and, interestingly, led to apoptosis in patient AML cells. These activities could be due to mulinic acid or azorellane terpenoids and their derivatives, tentatively identified in both IV and VI. In conclusion, our data suggest AG plant as a source of potential anti-AML agents.

Advances and challenges in cancer treatment and nutraceutical prevention: the possible role of dietary phenols in BRCA regulation

“…As activated aromatic hydrocarbon receptor possesses a promiscuous binding site for many food-derived bioactive molecules, many officinal herb or foodderived compounds could act as antagonists, providing higher cancer prevention (Lamorte et al 2020). They include polyphenols, most of all flavonoids, but also carotenoids, as lutein and lycopene from carrots and tomatoes, and indoles, as indole-3-carbinol from cruciferous vegetables (Busbee et al 2013;Xue et al 2017).…”

How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?

“…Azorella glabra Mulinic acid, azorellane terpenoids G0/G1 cell cycle arrest and apoptosis in AML cell lines. A slight decrease in the survival of non-tumor cells [133] Ephedra chilensis Terpens and fatty acids IC50 of non-polar extracts for one breast cancer and three colon cell lines was at the level of doxorubicin; in vitro cytotoxicity for normal colon epithelium cells was less than doxorubicin.…”

Leishmanicidal and cytotoxic activities and 4D‐QSAR of 2‐arylidene indan‐1,3‐diones

“…[24,49] This activity is important, as studies attribute the antileukemia and leishmanicidal capacity of different substances to their antioxidative potential. [50][51][52] However, as already mentioned, little is known about the mechanisms of action of indandiones, and to better clarify the relationship between the activity and structure of the synthesized compounds investigated herein, QSAR models were performed and the results are presented in sequence.…”