Saponins isolated from the leaves of Panax notoginseng protect against alcoholic liver injury via inhibiting ethanol-induced oxidative stress and gut-derived endotoxin-mediated inflammation

Abstract

Available online A B S T R A C TEffects of saponins from leaves of Panax notoginseng (LPNS) against alcoholic liver injury were evaluated, and their probable molecular mechanisms were further elucidated in a mouse model of chronic-plus-single-binge ethanol feeding. Alcohol exposure dramatically increased plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacylglycerol (TG) and endotoxin; these elevations were attenuated by treatment with LPNS at a dose of 100 or 300 mg/kg. LPNS was also found to suppress thiobarbituric acid reactive substances (TBARS) production, enhance glutathione (GSH) level and superoxide dismutase (SOD) activity in liver. The protective of LPNS against oxidative stress was associated with down-regulation of hepatic cytochrome P450 2E1 (CYP2E1), and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1). Additionally, LPNS ameliorated gut leakiness via upregulating the expressions of tight junction proteins, and suppressed endotoxin-mediated inflammation via down-regulating toll-like receptor-4 (TLR-4), CD14 and p-NF-κB p65. These results demonstrate that treatment with LPNS effectively protects against alcoholic liver injury through reducing ethanol-induced oxidative stress and ameliorating gut-derived endotoxin-mediated inflammation. Alcoholic liver injurySaponins from the leaves of Panax notoginseng Oxidative stress Gut-derived endotoxin Inflammation Abbreviations: ALD, alcoholic liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BW, body weight; CYP2E1, cytochrome P450 2E1; GSH, glutathione; H2O2, hydrogen peroxide; HO-1, haem oxygenase-1; HPLC, high performance liquid chromatography; HRP, horseradish peroxidase; IL-6, interleukin 6; LBP, lipopolysaccharide-binding protein; LPNS, saponins from leaves of Panax

Analisis Kemiripan 20 Aksesi Temu Ireng (Curcuma aeruginosa Roxb.) Berdasarkan Warna Rimpang, Hasil Ekstrak, dan Kandungan Fitokimia

“…Adanya kandungan terpenoid dan saponin menjadikan temu ireng berpotensi sebagai obat. Wang et al (2015) menunjukkan saponin berkhasiat sebagai antioksidan dan hepatoprotektor. Beberapa penelitian lain menunjukkan bahwa saponin berkhasiat juga sebagai antikanker (Man et al, 2015;Yuan et al, 2013), meningkatkan imunitas pada unggas (Yu et al, 2015a), antitumor (Yu et al, 2015b), dan imunomodulator (Nalbantsoy et al, 2012).…”

Polydatin Protects Rat Liver against Ethanol‐Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF‐κB p65 Pathway

“…The early stage of ALD is reflected as fatty liver, but it is finally progressing into more severe forms, such as inflammation, fibrosis, and cirrhosis [ 2 ]. Nowadays, ALD has become one of the leading causes of chronic diseases and death in the world [ 3 ]. Hence, it is necessary to unmask the pathological mechanisms of ALD and to look for potential therapeutic agents.…”

“…Many studies indicate that steatosis, oxidative stress, inflammatory factors, and mitochondrial dysfunction are involved in ALD [ 5 ]. And it is widely accepted that oxidative stress and inflammation are key mechanisms underlying the pathogenesis of ALD [ 3 ]. Reactive oxygen species (ROS), a highly reactive species of free radical, are known to play a dual role in living systems [ 6 ].…”

<b><i>Panax notoginseng</i></b> Saponins Ameliorate Leukocyte Adherence and Cerebrovascular Endothelial Barrier Breakdown upon Ischemia-Reperfusion in Mice

“…Likewise, pretreatment with PNS at the dosage of 45 mg/kg, but not 22.5 mg/kg, significantly increased ZO-1, occludin, and claudin-5 protein levels in the ischemic brain. Interestingly, it was reported that in a rat model of alcoholic liver disease, a high dosage of PNS remarkably normalized the degradation of ZO-1 and occludin in the intestine barrier [24]. It does indicate an internal consistency in the results since the fence-like tight junction disruption was usually initiated by leukocyte-endothelial interactions either in the gut [25] or in the brain [26].…”