Abstract

Propolis, also known as bee-glue, is a resinous substance produced by honeybees from materials collected from plants they visit. It contains mixtures of wax and bee enzymes and is used by bees as a building material in their hives and by humans for different purposes in traditional healthcare practices. Although the composition of propolis has been shown to depend on its geographic location, climatic zone, and local flora; two largely studied types of propolis: (i) New Zealand and (ii) Brazilian green propolis have been shown to possess Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC) as the main bioactive constituents, respectively. We have earlier reported that CAPE and ARC possess anticancer activities, mediated by abrogation of mortalin-p53 complex and reactivation of p53 tumor suppressor function. Like CAPE, Artepillin C (ARC) and the supercritical extract of green propolis (GPSE) showed potent anticancer activity. In this study, we recruited low doses of GPSE and ARC (that did not affect either cancer cell proliferation or migration) to investigate their antistress potential using in vitro cell based assays. We report that both GPSE and ARC have the capability to disaggregate metal- and heat-induced aggregated proteins. Metal-induced aggregation of GFP was reduced by fourfold in GPSE- as well as ARC-treated cells. Similarly, whereas heat-induced misfolding of luciferase protein showed 80% loss of activity, the cells treated with either GPSE or ARC showed 60–80% recovery. Furthermore, we demonstrate their pro-hypoxia (marked by the upregulation of HIF-1α) and neuro-differentiation (marked by differentiation morphology and upregulation of expression of GFAP, β-tubulin III, and MAP2). Both GPSE and ARC also offered significant protection against oxidative stress and, hence, may be useful in the treatment of old age-related brain pathologies.

Highlights

  • Propolis is a complex mixture of resinous material, produced by bees by mixing their saliva with botanical sources they live on

  • We experimentally prove this hypothesis using a variety of cell-based stress readouts including protein aggregation and misfolding, oxidative stress, and hypoxia

  • We examined if Green Propolis Supercritical Extract (GPSE) and Artepillin C (ARC) could upregulate hypoxia signaling at the molecular level

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Summary

Introduction

Propolis is a complex mixture of resinous material, produced by bees by mixing their saliva with botanical sources they live on. It is an important structural component of beehives and chemical weapon of bees. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid, ARC) as pre-dominant bioactive compounds [10,11,12] Besides these major bioactives, a large variety of constituents including flavonoids, phenolic acids, esters, terpenoids, steroids, amino acids, and cinnamic acid derivatives have been identified in propolis and are considered as popular pharmacological research material [10,13]. Molecular studies on the anticancer activity have revealed that the phenolic acid components of propolis including

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