Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP‑activated protein kinase (Review)

Abstract

AMP-activated protein kinase (AMPK) is an ubiquitously expressed serine/threonine kinase and an important regulator of energy metabolism. The decreased activity of AMPK induced by low-grade chronic inflammation has been implicated in several diseases, including type 2 diabetes and atherosclerosis. However, the activation of AMPK by natural and synthetic products can ameliorate these diseases through the inhibition of inflammation. For example, aged garlic extract (AGE) has been shown to enhance the phosphorylation of Thr172 of the α-subunit of AMPK in several tissues of disease model animals. In addition, AGE has been reported to suppress the progression of atherosclerotic plaque formation in an animal model of atherosclerosis. Moreover, AGE has been found to decrease the level of plasma glycated albumin and to improve hyperglycemia in an animal model of type 2 diabetes. These inhibitory effects of AGE are induced by the suppression of the inflammatory response. In the present review, we discuss the mechanisms through which AGE activates AMPK, as well as the mechanisms through which the activation of AMPK by AGE modulates the inflammatory response in disease models.

The effects of allium sativum on immunity within the scope of COVID-19 infection

“…Aged garlic extract suppresses the production of proinflammatory cytokines such as TNF-α and CRP in the liver [37]. In the hypothalamus, aged black garlic (ABG) treatment induced a decrease in leptin receptor (LepR) mRNA levels.…”

S‑1‑Propenylcysteine, a sulfur compound in aged garlic extract, alleviates cold‑induced reduction in peripheral blood flow in rat via activation of the AMPK/eNOS/NO pathway

“…AMPK is known to phosphorylate the specific serine residue (Ser1177) of eNOS that is essential for its activation (58,59). It was also shown that AGE activated AMPK in both diabetic model TSOD mice (39), and arteriosclerotic model ApoE-KO mice (36). In addition, S1PC enhanced the AMPK activity in mouse spleen cells in vitro (37).…”

“…Previous studies have demonstrated the beneficial effect of AGE on hypertension (8)(9)(10)(11)(12), atherosclerosis (13)(14)(15), metabolic syndrome (16), and gingivitis (17). Furthermore, recent studies have revealed that AGE and its constituents, SAC and S1PC, exert such desirable effects as anti-hypertension (18)(19)(20)(21)(22), cardioprotection (23), antioxidation (24)(25)(26)(27), antiaging (27,28), i m munomodulation (29)(30)(31), a nti-fatig ue (32,33), anti-stress (34,35), anti-inflammation (36)(37)(38)(39), and liver protection (40).…”

Aged Garlic Extract Reduces IL-6: A Double-Blind Placebo-Controlled Trial in Females with a Low Risk of Cardiovascular Disease

“…The present study concluded that 12 months of AGE treatment had a lowering effect on the inflammatory biomarker IL-6. AGE has in prior clinical and preclinical studies shown a beneficial effect on inflammation [ 22 , 23 ], with a significant lowering effect on IL-6; however, this is the first time it has been shown to have a lowering effect in a female cohort with a low risk of cardiovascular disease.…”

“…AGE ameliorates atherosclerosis and type 2 diabetes through the suppression of inflammation. AGE modulates the inflammatory response by enhancing the phosphorylation of AMP-activated protein kinase (AMPK) [ 23 ]. AMPK plays an important role in regulating the inflammatory response through the inhibition of the TLR signaling pathway.…”