Downregulating PI3K/Akt/NF-κB signaling with allicin for ameliorating the progression of osteoarthritis:in vitroandvivostudies

Abstract

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1β (IL-1β) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1β-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy

“…The allicin treatment decreased both proinflammatory cytokines and these effects were exerted at the systemic and tissue levels. In vitro and in vivo allicin modulates the production of IL-1β, IL-6 and TNF-α at both the mRNA and protein levels [ 24 , 25 , 26 ]. Other studies described that allicin has anti-inflammatory effects [ 27 ] and suppresses both oxidative stress and proinflammatory cytokines [IL-1, TNF-α and Monocyte Chemoattractant Protein-1 (MCP-1)] [ 26 , 28 ].…”

“…On the other hand, allicin reduces the activation of NFκβ, the nuclear translocation and the phosphorylation of Iκβ induced by IL-1 [ 25 ]. Moreover, allicin suppresses IL-1β-induced phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) phosphorylation, a pathway involved in the regulation of NFκβ [ 25 ].…”

“…On the other hand, allicin reduces the activation of NFκβ, the nuclear translocation and the phosphorylation of Iκβ induced by IL-1 [ 25 ]. Moreover, allicin suppresses IL-1β-induced phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) phosphorylation, a pathway involved in the regulation of NFκβ [ 25 ]. In fructose-fed diabetic rats, the administration of garlic homogenate decreases cardiac hypertrophy, NFκβ activity and oxidative stress through the PI3K/AKT/Nrf2-Keap1-dependent pathway [ 30 ].…”

High follicle‐stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF‐κB pathway

“…For example, inhibition of PI3K/AKT/mammalian target of rapamycin pathway could induce articular chondrocyte autophagy and suppress inflammatory processes in OA rats [14]. Allicin alleviates the progression of OA by inactivating the PI3K/AKT/NF-jB pathway [15]. Blocking PI3K/AKT signaling can reduce post-traumatic OA or tumor necrosis factor-a-induced OA [16,17].…”

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

“…Similarly, Arellano Buendia et al (2018) had revealed that the allicin treatment decrease proinflammatory cytokines ( il-1 β and il-6 ) showing the same effect on both systemic and tissue levels of diabetic rats. Moreover, both in vitro and in vivo , allicin has been reported to modulate the production of il-1 β, il-6 and tnfα at both the mRNA and protein levels ( Alam et al, 2018 ; Qian et al, 2018 ). Therefore, these results suggested that allicin supplementation could enhance immunity and alleviate inflammation of large yellow croaker larvae.…”