Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression of p38 and Erk MAPK pathways

International Journal of Molecular Medicine

Liu

et al. 2017

Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti-inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg). Then the mice were treated by intragastric administration of resveratrol (80 mg/kg) every 12 h immediately after the second injection of L-arginine. Mice with ANP showed increased apoptosis of pancreatic acinar cells, pancreatic myeloperoxidase activity, serum lactate dehydrogenase activity, amylase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels as well as decreased serum IL-10 level, pancreatic expression of heat shock factor 1 (HSF1), sirtuin 1 (SIRT1) and p53, but the ratio of acetylated HSF1 and p53 was markedly increased. Resveratrol enhanced the survival rate of mice with ANP from 47.8 to 71.4% and obviously restored the changes in mice with ANP as mentioned above. Additionally, interactions between SIRT1 and p53 and between SIRT1 and HSF1 in the pancreas of the mice were confirmed by co-immunoprecipitation. These data suggest that resveratrol protects against L-arginine-induced ANP, which may be related to the enhancement of SIRT1-mediated deacetylation of p53 and HSF1.

Section: Discussionmentioning

confidence: 99%

Resveratrol protects against L-arginine-induced acute necrotizing pancreatitis in mice by enhancing SIRT1-mediated deacetylation of p53 and heat shock factor 1

Wang

International Journal of Molecular Medicine

Liu

et al. 2017

“…Ligustrazine (tetramethylpyrazine, Figure 3F ) (Chen et al, 2016) and honokiol (3,5′-diallyl-4,2′-dihydroxybiphenyl, Figure 3G ) (Weng et al, 2012) possess special pharmacological activities associated with the acceleration of acinar cell apoptosis at an early phase of AP. Thus, they may soon join the list of candidate drugs in the treatment of AP besides the above-mentioned natural products.…”

Section: Pleiotropic Natural Productsmentioning

confidence: 99%

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Xiang

et al. 2017

Front. Pharmacol.

Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.

“…Ligustrazine has been shown to effectively induce pancreatic acinar cell apoptosis and prevent the apoptosis of cells in the liver and kidneys, which decreased the pathological score of these organs in SAP rats[65]. The mechanism of ligustrazine may operate by suppressing the p38 and ERK/MAPK pathways[66]. Moreover, ligustrazine has been shown to effectively decrease serum amylase levels and inflammatory cytokines and alleviate pathological changes in the pancreas, liver, kidney, small intestinal mucosa, thymus and spleen, which protect the body from multiple organ injuries[66,67].…”

Section: Tcm Monomersmentioning

confidence: 99%

“…The mechanism of ligustrazine may operate by suppressing the p38 and ERK/MAPK pathways[66]. Moreover, ligustrazine has been shown to effectively decrease serum amylase levels and inflammatory cytokines and alleviate pathological changes in the pancreas, liver, kidney, small intestinal mucosa, thymus and spleen, which protect the body from multiple organ injuries[66,67]. …”

Section: Tcm Monomersmentioning

confidence: 99%

Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis

Zhou

et al. 2017

WJG

Acute pancreatitis (AP) is one of the most common diseases. AP is associated with significant morbidity and mortality, but it lacks specific and effective therapies. Traditional Chinese medicine (TCM) is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of AP. The current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on AP. This review summarizes the widely used formulas, single herbs and monomers that are used to treat AP and the potential underlying mechanisms of TCM. Because of the abundance, low cost, and safety of TCM as well as its ability to target various aspects of the pathogenesis, TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.