Allicin inhibits oxidative stress-induced mitochondrial dysfunction and apoptosis by promoting PI3K/AKT and CREB/ERK signaling in osteoblast cells

Abstract

Abstract.Osteoporosis is a disease of the skeleton that is characterized by the loss of bone mass and degeneration of bone microstructure, resulting in an increased risk of fracture. Oxidative stress, which is known to promote oxidative damage to mitochondrial function and also cell apoptosis, has been recently indicated to be implicated in osteoporosis. However, there are few agents that counteract oxidative stress in osteoporosis. In the present study, the protective effects of allicin against the oxidative stress-induced mitochondrial dysfunction and apoptosis were investigated in murine osteoblast-like MC3T3-E1 cells. The results demonstrated that allicin counteracted the reduction of cell viability and induction of apoptosis caused by hydrogen peroxide (H 2 O 2 ) exposure. The inhibition of apoptosis by allicin was confirmed by the inhibition of H 2 O 2 -induced cytochrome c release and caspase-3 activation. Moreover, the inhibition of apoptosis by allicin was identified to be associated with the counteraction of H 2 O 2 -induced mitochondrial dysfunction. In addition, allicin was demonstrated to be able to significantly ameliorate the repressed phosphoinositide 3-kinase (PI3K)/AKT and cyclic adenosine monophosphate response element-binding protein (CREB)/extracellular-signal-regulated kinase (ERK) signaling pathways by H 2 O 2 , which may also be associated with the anti-oxidative stress effects of allicin. In conclusion, allicin protects osteoblasts from H 2 O 2 -induced oxidative stress and apoptosis in MC3T3-E1 cells by improving mitochondrial function and the activation of PI3K/AKT and CREB/ERK signaling. The present study implies a promising role of allicin in oxidative stress-associated osteoporosis.

Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration

“…Mechanistically, PDGF-BB upregulated periostin expression via inducing the phosphorylation of PDGFR-β, PI3K, AKT, and CREB. CREB is essential for enhanced osteogenic formation, which is modulated by PI3K/AKT signaling (55,56), but the downstream target of CREB in PDCs has not been well characterized. We showed that PDGF-BB could induce direct binding of pCREB to periostin promoter in ChIP assay.…”

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death

“…Oxidative stress, a biochemical imbalance between endogenous antioxidant and oxidant formation, has been thought to play an essential role in the pathogenesis of various diseases [26]. Furthermore, mitochondria, key organelles in eukaryotic cells, are essential for cellular energy Fig.…”

Dietary Allicin Improved the Survival and Growth of Large Yellow Croaker (Larimichthys crocea) Larvae via Promoting Intestinal Development, Alleviating Inflammation and Enhancing Appetite

“…The high energy consumption required for the rapid growth of marine fish larvae also makes them vulnerable to oxidative stress ( Liu et al, 2015 ). Early studies have shown that allicin can protect osteoblasts from H 2 O 2 -induced oxidative stress ( Ding et al, 2016 ), and allicin can scavenge oxygen free radicals and also affect the antioxidant capacity of animals ( Chung, 2006 ). Purportedly, allicin protects cells against oxidative stress by inducing the production of antioxidant enzymes ( El-Sheakh et al, 2016 ).…”