Acetyl-α-boswellic acid and Acetyl-β-boswellic acid protects against caerulein-induced pancreatitis via down-regulating MAPKs in mice
Introduction
Acute pancreatitis (AP) is a common acute abdomen that caused by autodigestion of pancreas. The pathological changes include pancreatic edema, hemorrhage and necrosis while it manifested as abdominal pain, vomiting, fever as well as elevated serum urease and amylase in clinic. Recently, epidemiological studies revealed that the incidence of pancreatitis increases each year [1], and the total mortality rate reaches 5% to 10% now [2]. Severe acute pancreatitis (SAP) accounts for 15%–20% of acute pancreatitis [3], which usually complicates with systemic inflammatory response or, acute respiratory distress syndrome or acute renal insufficiency and liver function damage. Uncontrolled SAP could lead to multiple organ failure [4], [5] with mortality as high as 36% to 50%. Although recent progressions in pathogenesis and treatment of AP, its incidence still increase and the mortality remains high [2], [6], [7]. AP remains a major threat to human health due to its high morbidity, mortality and treatment limitations. The pathogenesis of AP is complex and not fully understood, however inflammation theory is now considered to be one of the main culprits in its pathogenesis, and a large number of inflammatory factors are associated with the pathological process of pancreatitis [8].
Frankincense, an aromatic resin used in incense and perfumes from Boswellia carteri, is also used to treat a variety of inflammatory diseases in traditional medicine. The main components of frankincense include various boswellic acids, volatile oils, terpenes, arabinose and so on.
Previous studies showed that Boswellia extracted and its triterpenoids boswellic acid compounds include Acetyl-α-boswellic acid (α-ABA), Acetyl-β-boswellic acid (β-ABA) (Fig. 1), 11-keto-β-boswellic acid (KBA) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA) have anti-inflammatory activity against a variety of acute and chronic inflammatory models [9], [10]. Up to now, most studies on active compounds of Frankincense are regarding to AKBA and KBA. However, oral administration of boswellic acid resulted in several times higher Cmax values of α-ABA and β-ABA in plasma than those of KBA and AKBA [11], and the concentration of α-ABA and β-ABA in mice brain were also higher than those of KBA and AKBA [12]. Therefore, this study was to investigate whether the mixture of α-ABA and β-ABA (α/β-ABA) pose anti-inflammatory effect against LPS-activated proinflammatory cytokines and caerulein-induced acute pancreatitis in RAW 264.7 macrophages.
Section snippets
Reagents
α-ABA and β-ABA were both provided by Prof. Yan-ru Deng from Tianjin University of Traditional Chinese Medicine. Fetal bovine serum (FBS) was obtained from Biological Industries. Dulbecco’s modified Eagle's medium (DMEM) was obtained from Corning. Dimethyl sulfoxide (DMSO), radio-immunoprecipitation assay (RIPA) lysis buffer, nuclear protein extraction kit and primary antibody against Lamin B1 (Cat.K200032M) were obtained from Beijing Solarbio Life Sciences. Lipopolysaccharides (LPS) Ecoli.
Effect of acetyl-α, β-boswellic acid mixture on inflammation in RAW264.7 cell
As shown in Fig. 2, upon LPS stimulation (model group), the expressions of some cytokines: GM-CSF, RANTES, TNF-α, IL-6, MCP-1, sTNF R1, Eotaxin-2, IL-10 and GCSF were obviously increased. And administration of α/β-ABA at final concentration of 8 μM attenuates these increased cytokines in the treatment group.
Effects of acetyl-α, β-boswellic acid mixture on LPS-stimulated TNF-α, IL-1β, IL-10 and IL-6 production in RAW264.7
As shown in Fig. 3A, addition of α/β-ABA at final concentration of 20, 40, 80, 160 and 320 μM significantly reduced cell viability to 76.4%, 52.3%, 25.3%, 8.7% and 6.7% respectively.
Discussion
Macrophage plays an important role in the progression of pancreatitis by enhancing local damaged or inducing systemic complications. In the early stages of pancreatic injury, several enzymes and inflammatory mediators are released from damaged acinar cells, then the activated immune cells produce a series of cytokines and chemokines to initiate inflammatory cascades [14]. Clinical and experimental studies have demonstrated that SAP is associated with the number of macrophages mobilized in the
CRediT authorship contribution statement
Pan-Yang Zhang: Investigation, Data curation, Methodology, Writing - original draft. Bin Yu: Writing - review & editing. Wei-Jie Men: Investigation, Data curation. Ru-Yu Bai: Investigation, Methodology. Meng-Ying Chen: Writing - review & editing, Data curation. Zhao-Xin Wang: Data curation. Tao Zeng: Funding acquisition, Investigation. Kun Zhou: Conceptualization, Funding acquisition, Writing - review & editing.
Declaration of Competing Interest
The authors declare no conflicts of interest.
Acknowledgement
The authors are grateful to Ya-nan Bi, Hua Tian, Prof. Yan-ru Deng and Prof. Li-kang Sun for the help in this work. This research was funded by National Natural Science Foundation of China (No. 81673826) and Tianjin Innovation and Entrepreneurship Training Project for College Student (CXJJ2019YC01).
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