Activation of AMPK by Buddleja officinalis Maxim. Flower Extract Contributes to Protecting Hepatocytes from Oxidative Stress

Abstract

The Buddleja officinalis Maxim. flower is used in traditional Chinese and Korean medicine to treat inflammation, vascular diseases, headache, and stroke, as well as enhance liver function. This research investigated the effects of B. officinalis Maxim. flower extract (BFE) on hepatotoxicity. The cytoprotective effects and mechanism of BFE against severe mitochondrial dysfunction and H2O2 production in hepatotoxicity induced by coadministration of arachidonic acid (AA) and iron were observed in the HepG2 cell line. In addition, we performed blood biochemical, histopathological, and histomorphometric analyses of mice with carbon tetrachloride- (CCl4-) induced acute liver damage. BFE inhibited the AA + iron-mediated hepatotoxicity of HepG2 cells. Moreover, it inhibited mitochondrial dysfunction, H2O2 production, and glutathione depletion mediated by AA + iron in the same cells. Meanwhile, the cytoprotective effects of BFE against oxidative stress were associated with the activation of AMP-activated protein kinase (AMPK). In particular, based on the histopathological observations, BFE (30 and 100 mg/kg) showed clear hepatoprotective effects against CCl4-induced acute hepatic damage. Furthermore, it inhibited 4-hydroxynonenal and nitrotyrosine immunoreactivity in hepatocytes. These results provide evidence that BFE has beneficial hepatoprotective effects against hepatic damage via the activation of AMPK pathway. Accordingly, BFE may have therapeutic potential for diverse liver disorders.

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“…It is an effective strategy to prevent IR and type 2 diabetes by regulating AKT and AMPK. [28][29][30] For example, AMPK can regulate the activity of PI3K and AKT by combining IRS-1 (insulin receptor substrate-1). 31 The AMPK is a serine/threonine protein kinase that is highly conserved in higher eukaryotes.…”

Sipjeondaebo-tang Alleviates Oxidative Stress‐Mediated Liver Injury through Activation of the CaMKK2‐AMPK Signaling Pathway

“…Because we and others have reported several medicinal herbs and natural products that prevent oxidative stress via AMPK activation [ 4 , 7 – 10 ], we first monitored the effect of SDT (300 μ g/mL) on the temporal responses of AMPK and ACC (a representative downstream substrate of AMPK) phosphorylation. Based on immunoblot results, maximal increases in AMPK and ACC phosphorylation were observed at 0.5 h after SDT treatment, after which the levels gradually decreased.…”

“…AA induces mitochondria-dependent apoptosis of hepatocytes [ 3 ]. Moreover, in the presence of iron, AA promotes ROS generation in cells and mitochondria, depletes reduced glutathione (GSH), induces mitochondrial membrane leakage, and accelerates apoptosis of hepatocytes [ 3 , 4 ].…”

“…Because the mitochondrion is an essential subcellular organelle for accelerating oxidative stress, maintaining mitochondrial integrity and homeostasis via AMPK provides a prosurvival signal against oxidative stress. Several medicinal herbs and isolated natural products that protect against oxidative stress via AMPK activation have been identified [ 4 , 7 – 10 ].…”

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“…(Loganiaceae) [1]. Buddleja officinalis grows many regions of China and is commonly used in traditional Chinese medicine for the treatment of ophthalmologic diseases, conjunctivitis, hepatic asthenia, stroke, and headache [2‐5]. In addition, it has also been used as a natural food dye to color yellow rice in southwestern China [6].…”