Modulation of HIF-1α and TNF-α in pre-osteoblasts treated with alcohol extract of propolis: Implications for cellular response and signaling pathways

Abstract

Numerous studies have demonstrated the significant role of propolis in various biological processes, including inflammation and the repair of endothelial and bone tissues. The cascade of inflammation, proliferation, and tissue remodeling characterizes the injury site. Remarkable progress has been made in the field of alternative medicine with the utilization of propolis. In this study, we specifically investigated the effects of alcoholic extract of propolis on cell adhesion, survival, remodeling, and differentiation pathways in osteoblasts. Our findings revealed the activation of survival proteins such as AKT, ERK, and phosphorylated ERK during the adhesion phase, while interleukins, specifically IL-6 and TNF, exhibited increased expression during cell differentiation. Furthermore, treatment with propolis extract led to enhanced activity of metalloproteinases (MMP9 and MMP2) and HIF-1α, a crucial activator of angiogenesis and bone remodeling. It was observed that the alcoholic propolis extract stimulated cell proliferation, differentiation, and repair, with key molecules involved in these processes including pro-inflammatory factors IL-6 and TNFα, as well as HIF-1, MMP2, and BMP7 proteins. Collectively, these factors induced an initial state of proliferation followed by differentiation and repair. Therefore, the alcoholic extract of propolis holds promise as a potential therapeutic agent, particularly in cases involving tissue repair. Nevertheless, further comprehensive in vitro and in vivo studies targeting this area are necessary to advance our understanding.