14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats

Mandal, Samir; Nelson, Vinod K.; Mukhopadhyay, Sibabrata; Bandhopadhyay, Sukdeb; Maganti, Lakshmi; Ghoshal, Nanda; Sen, Gargi; Biswas, Tanmay

doi:10.1016/j.fct.2013.05.056

Cited by 20 publications

(11 citation statements)

References 59 publications

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“…Since PKA activates HIF-1 α through cAMP response element-binding protein (CREB) [ 25 ] and AC is reported to be the target of other hepatoprotective agents [ 26 ], we then considered that the AC/cAMP/PKA pathway might be repressed by M30 to downregulate the activity of HIF-1 α . To test this hypothesis, AC activator forskolin and inhibitor SQ22536 were used to treat BRL-3A cells in the presence or absence of ethanol and M30.…”

Section: Resultsmentioning

confidence: 99%

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

Xiao

Lin

et al. 2015

Oxidative Medicine and Cellular Longevity

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The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1α) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1α/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1α pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure.

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Section: Resultsmentioning

confidence: 99%

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

Xiao

Lin

et al. 2015

Oxidative Medicine and Cellular Longevity

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“…The beneficial effect of cAMP signaling via activation of adenylate cyclase (AC) and the PDE3 inhibitor, Cilostazol, on liver injury has also been demonstrated in both in vivo and in vitro ALD models [ 124 , 125 , 126 ]. Treatment of ethanol-fed rats for the last four weeks of an eight-week study with 14-deoxyandrographolide (14-DAG) attenuated ethanol-induced hepatic apoptosis, oxidative stress and lipid peroxidation via activating AC [ 126 ]. Cilostazol decreased ethanol-induced oxidative stress and prevented mitochondrial pathway-mediated apoptosis in hepatocytes [ 124 ].…”

Section: Camp Signaling In Aldmentioning

confidence: 99%

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

et al. 2020

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The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.

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“…ANDRO is a diterpenoid, like neoandrographolide (NEO), 14-deoxyandrographolide (14DAP), and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). These compounds have antioxidant and anti-inflammatory properties [ 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

et al. 2020

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Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

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14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats

Cited by 20 publications

References 59 publications

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

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