Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis

Lee, Jin Hwan; An, Chun San; Yun, Bok Sun; Kang, Kum Suk; Lee, Young Ae; Won, Sun Mi; Gwag, Byoung Joo; Cho, Sung Ig; Hahm, Ki‐Baik

doi:10.1016/j.ejphar.2012.04.048

Cited by 17 publications

(12 citation statements)

References 65 publications

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“…Indeed, ROS act as inflammatory mediator in this model so it was used in the current study. In this model, cerulein causes liver complications with extensive lipid peroxidation, producing some metabolites such as MDA (Lee et al 2012). Cerulein can also cause systemic diseases in organs such as the lungs, heart, kidneys, and liver as well (Korkmaz et al 2014).…”

Section: Discussionmentioning

confidence: 99%

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

et al. 2015

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Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 lg/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein ? CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSHPx. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitisinduced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP ? CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p \ 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction.

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Section: Discussionmentioning

confidence: 99%

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

et al. 2015

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“…It has been traditionally used to treat disorders of the liver, upper respiratory tract diseases, dyspepsia, chronic diarrhea, and scorpion sting [3]. Picroside II (h-D-glucopyranoside,1a,1b,2,5a,6,6a-hexahydro-6-[(4-hydroxy-3-methoxybenzoyl)oxy]-1a(hydroxymethyl)oxirenocyclopenta[1,2-c]pyran-2-yl) is one of the most effective components extracted from Picrorhiza scrophulariiflora (Figure 1) [4].…”

Section: Introductionmentioning

confidence: 99%

“…TNF- α is thought to induce a cascade of other inflammatory cytokines and activate various immune cells, thus inducing the proinflammatory response [17, 18]. It has been confirmed that serum IL-6 level is a very good discriminator of SAP and can be used as an early marker of SAP [3]. TNF- α and IL-6 aggravate SAP and increase plasma extravasation and induce leukocyte adherence, result in SIRS (the systemic inflammatory response syndrome) and MODS (the multiple organ dysfunction syndrome) [19].…”

Section: Introductionmentioning

confidence: 99%

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Piao¹,

Liu

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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Picroside II, from the herb Picrorhiza scrophulariiflora Pennell, has antioxidant and anti-inflammatory activities. However, its function on severe acute pancreatitis (SAP) and molecular mechanism remains unknown. The effects of picroside II on the SAP induced by cerulean were investigated. SAP rats were treated with picroside II (25 mg/kg). The severity of SAP was evaluated by using biochemical and histological analyses. Pancreatic cancer cell PANC-1 was transfected with ptfLC3 (an indicator of autophagic activity), pcDNA3.1-NF-κB (nuclear factor kappa B), and pTZU6+1-NF-κB-shRNA and then treated with picroside II. Relative molecules related with NF-κB-dependent autophagy were detected by using Western blot. Autophagic activities were observed by phase-contrast and fluorescent microscopes. Acetylated LC3 was detected by immunoprecipitation. The results showed that picroside II treatment reduced the level of ALT, AST, NF-κB, IL-1β, IL-6, TNF-α, and SIRT1 (NAD+-dependent deacetylase) and increased the level of SOD and GSH. The autophagic activity was reduced when NF-κB was silenced, and the levels of TNF-α and SIRT1 were reduced. In contrast, the overexpression of NF-κB increased autophagic activity and the level of TNF-α, which activated SIRT1. SIRT1 deacetylated LC3 and increased autophagic activities. Picroside II ameliorates SAP by improving antioxidant and anti-inflammtory activities of SAP models via NF-κB-dependent autophagy.

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“…(i) Caerulein‐induced pancreatitis: 6‐ to 8‐week‐old female mice (13–17 g) were fasted from solid food for 12–16 h (but were allowed water ad libitum) and then received seven‐hourly intraperitoneal injections of phosphate‐buffered saline or 50 μg/kg caerulein (50 μg/kg in 0.2 mL of phosphate‐buffered saline, Sigma, St Louis, MO, USA) . (ii) Choline‐deficient supplemented with ethionine diet (CDE) induced pancreatitis: 3‐ to 4‐week‐old female mice (11–16 g) were fasted as mentioned previously, were fed CDE (MP, Irvine, CA, USA) chow for 3 days then switched to a normal diet . For the caerulein‐induced models, the mice were examined at different time point, then anesthetized and euthanized.…”

Section: Methodsmentioning

confidence: 99%

β‐Arrestin1 alleviates acute pancreatitis via repression of NF‐κBp65 activation

Lin

Tan

et al. 2018

J of Gastro and Hepatol

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Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis

Cited by 17 publications

References 65 publications

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

β‐Arrestin1 alleviates acute pancreatitis via repression of NF‐κBp65 activation

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