Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways

Abstract

Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many mammalian bodies and promote tumor growth inhibition. Apigenin is a flavonoid with low toxicities and numerous bioactive properties due to which it has been considered as a traditional medicine for decades. Apigenin shows synergistic effects in combined treatment with sorafenib in the HepG2 human cell line (HCC) in less time and statistically reduces the viability of tumor cells, migration, gene expression and apoptosis. The combination of anti-cancerous drugs with apigenin has shown health promoting potential against various cancers. It can prevent cell mobility, maintain the cell cycle and stimulate the immune system. Apigenin also suppresses mTOR activity and raises the UVB-induced phagocytosis and reduces the cancerous cell proliferation and growth. It also has a high safety threshold, and active (anti-cancer) doses can be gained by consuming a vegetable and apigenin rich diet. Apigenin also boosted autophagosome formation, decreased cell proliferation and activated autophagy by preventing the activity of the PI3K pathway, specifically in HepG2 cells. This paper provides an updated overview of apigenin's beneficial anti-inflammatory, antibacterial, antiviral, and anticancer effects, making it a step in the right direction for therapeutics. This study also critically analyzed the effect of apigenin on cancer cell signaling pathways including the PI3K/AKT/MTOR, JAK/STAT, NF-κB and ERK/MAPK pathways.

Keywords: ROS; apigenin; apoptosis; flavonoid; signaling cascades.

Figure 1

Detailed mechanism of the pharmacological properties of apigenin. (A) Anti-inflammatory response; apigenin inhibits the activity of reactive oxygen species and cancer cell metastasis which further inhibits several cell signaling pathways. It promotes the growth and development of healthy cells and downregulates the expression of cancer cell metastasis. Moreover, it blocks the activity of the phospholipase A2 (PLA2) enzyme which releases from the plasma membrane. Generally, PLA2 induces arachidonic acid (AA), which is a precursor of eicosanoid. Apigenin inhibits the expression of AA and promotes anti-inflammatory response in the host body. (B) Anti-oxidant response; host body modulates the expression of ROS when exposed to external stimuli (UV, drugs and smoke, etc.) which stimulates P53 activity and promotes apoptosis and lipid peroxidation in the host (mice) body. Apigenin consumption can significantly improve the oxidative damage caused by enhanced apoptosis and lipid peroxidation. (C) Anti-bacterial response; apigenin induces ROS in the bacterial cell and causes DNA damage and disruption in its cell wall. Furthermore, it can block beta-barrel proteins, intracellular proteins and toxins which are released from the bacterial cell. (D) Anti-viral response; apigenin enhances the reduced expression of miR122 and blocks the viral entry sites, which ultimately prevents viral DNA translation and protein synthesis. (E) Hypoglycemic response; apigenin stimulates Ras and MEK activity and increased the production of glycogen in the muscle and liver of the host body.

Figure 2

Modulation of PI3K/AKT/MTOR pathway by apigein.

Figure 3

Inhibition of JAK/STAT pathway by apigenin.

Figure 4

Downregulation of NF-kB pathway by apigenin.

Figure 5

Inhibition of ERK/MAPK pathway by apigenin.