Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway

Abstract

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality rates. Pancreatic ductal cells are the most susceptible of all cell types that are exposed to the noxious stimuli of pancreatitis. Our previous studies demonstrated that emodin, a natural product extracted from Rheum palmatum L., protected pancreatic acinar cells from injutyh due to its anti-inflammatory activity. In the present study, in order to investigate the protective effects and molecular mechanisms of action of emodin on injured pancreatic ductal cells, an adenosine triphosphate (ATP)-induced model of cell injury was established using the human pancreatic ductal epithelial cell line, HPDE6-C7. The results revealed that emodin attenuated ATP-induced HPDE6-C7 cell injury by decreasing the levels of inflammatory factors, including interleukin (IL)-1β and IL-18. Furthermore, emodin significantly downregulated the protein levels of purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 in the injured HPDE6-C7 cells. The results also indicated that emodin attenuated HPDE6-C7 cell injury at least partially through the inhibition of the P2X7/NLRP3 signaling pathway. The protective effects of emodin were abrogated upon pre-treatment with P2X7 overexpression plasmid, which further confirmed that the P2X7 signaling pathway is the drug target of the effects of emodin against ATP-induced pancreatic ductal cell injury. Collectively, the findings of this study demonstrate that emodin attenuates ATP-induced pancreatic ductal cell injury in AP mainly through the inhibition of the P2X7/NLRP3 signaling pathway. This study suggests that emodin may be further developed for its application in future medical therapy.

What we already know about rhubarb: a comprehensive review

“…Feng et al treated acute pancreatitis (AP) rats with rhubarb decoction orally (150 mg/ kg) and found that rhubarb probably attenuated AP by inhibiting activation of MAPKs [49]. Our previous studies also proved that emodin alleviated AP via miRNA-30a-5p/HtrA serine peptidase 1/transforming growth factor-β (HTRA1/TGF-β) and purinergic receptor P2X, ligand-gated ion channel, 7/NLRP3 (P2X7/NLRP3) inflammatory signaling [50,51].…”

Burn Ointment Promotes Cutaneous Wound Healing by Modulating the PI3K/AKT/mTOR Signaling Pathway

“…Diels could reduce the liberation of proinflammatory cytokines, including IL-1β, IL-6, TNF-alpha, and IL-33 ( Kim et al, 2018b ; Shen et al, 2019 ). They have an anti-inflammatory and analgesic effect ( Wei et al, 2016 ), induce cell proliferation ( Gundogdu et al, 2019 ), and protect cells from injuries ( Zhang et al, 2019b ). But, the activity of BO in anti-inflammation, analgesia, and promoting skin wound healing, and its specific mechanism are still unclear.…”

Advances in the study of emodin: an update on pharmacological properties and mechanistic basis

“…Zhang et al found that emodin (60 mg/kg) significantly inhibited the expression levels of P2X7 and NLRP3, thus delaying 5.0% sodium taurocholate-induced inflammasome activation and severe acute pancreatitis (SAP) progress in rats [ 46 ]. On the other hand, in an in vitro ATP‑injured model of human pancreatic ductal epithelial cell line (HPDE6‑C7), this protective activity of emodin against SAP was abrogated after pretreatment with P2X7 overexpression plasmid, which further verified that P2X7/NLRP3 signaling was the target of emodin on regulating inflammasome activation [ 47 ]. Moreover, a recent study revealed that emodin (25 mg/kg) protected against SAP-associated acute lung injury (ALI) in rats through the inhibition of NLRP3 inflammasome and uncovered a novel mechanism.…”