Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in pancreatic acinar cells

Abstract

AIMTo investigate the effects of combined use of emodin and baicalein (CEB) at the cellular and organism levels in severe acute pancreatitis (SAP) and explore the underlying mechanism.METHODSSAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol (1,4,5)-trisphosphate receptor (IP3R) expression were investigated to assess the mechanism of CEB.RESULTSPancreatic histopathology score (2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05) and serum amylase activity (2866.2 ± 617.7 vs 5241.3 ± 1410.0, P < 0.05) were significantly decreased in the CEB (three doses) treatment group compared with the SAP group (2.07 ± 1.20 vs 6.84 ± 1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6 (466.82 ± 48.55 vs 603.50 ± 75.53, P < 0.05) and TNF-α (108.04 ± 16.10 vs 215.56 ± 74.67, P < 0.05) and increased the level of the anti-inflammatory cytokine IL-10 (200.96 ± 50.76 vs 54.18 ± 6.07, P < 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 mRNA expression compared with those in the SAP group (P < 0.05). There was a trend towards decreased IP3R protein in the CEB treatment group; however, it did not reach statistical significance (P > 0.05).CONCLUSIONThese results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.

Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis

“…9,10 To elucidate their therapeutic roles in the treatment of SAP, the ingredients of the herbs have been extensively assessed via in silico, in vitro, and in vivo experiments. Emodin, as a predominant compound of rhubarb, has been reported to inhibit vacuole formation in the acinar cells, 11 attenuate autophagy response, 12 and protect against the oxidative stress and inflammasome signals in SAP. 13,14 However, the role of emodin in the intestinal barrier injury and immune response caused by SAP is still limited.…”

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway

“…Out of the active compounds of CQCQD, baicalein, baicalin, chrysin, honokiol, magnolol, and salidroside, all demonstrated marked potential for high affinity binding to AKT1, with chrysin being the most potent. While previous studies have reported that some of these compounds can improve AP in the in vivo or in vitro models ( Li et al, 2018 ; Pu et al, 2019 ), the evidence that CQCQD components modulate oxidative stress or the PI3K/Akt pathway is marginal. In different diseases, honokiol was used as an inhibitor of Akt activation ( Zhai et al, 2005 ), and chrysin was postulated to modulate the PI3K/Akt pathway ( Zhou et al, 2021 ).…”

A New Role for the Spleen

“…As anti-inflammatory mediators, IL-4 and IL-10 have been suggested to be valuable treatment strategies for SAP. 38,39 However, the expression of IL-4 and IL-10 was down-regulated in the serum and spleen of SAP rats, but this pattern could be inverted by splenectomy. In addition, the 13 differentially expressed cytokines were significantly enriched in the GO terms inflammatory response, positive regulation of major histocompatibility complex class II biosynthetic process, positive regulation of B-cell proliferation and immune response, and the KEGG pathways cytokine-cytokine receptor interaction, TNF signaling, and JAK-STAT signaling.…”