Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

Abstract

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis.

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

“…The types of death in acinar cells during SAP include apoptosis, necrosis, and pyroptosis (4). When acinar cells are mainly apoptotic, the clinical manifestations are mild edematous pancreatitis, which has good prognosis (5). When damaged by pyroptosis, acinar cells are ruptured and release the cellular contents and inflammatory factors, such as tumor necrosis factor alpha (TNF-α) and IL-1β, aggravating the inflammatory response (6).…”

Current trends in pharmacological approaches for treatment and management of acute pancreatitis – a review

“…These compounds also possess antioxidant activity. [41] Apart from that, cell therapies involving mesenchymal stem cells (MSCs) can reduce acute inflammatory response with the help of their immunomodulatory effects such as suppression of pro-inflammatory cytokines, secretion of anti-inflammatory cytokines and regulation of immune cell activation and proliferation. [42] Hence, these approaches may serve as a potential treatment method for AP in future.…”

“…These compounds maintain the balance between necrosis and apoptosis via either activating apoptosis by mechanisms such as upregulation of FasL gene expression, inhibition of X-linked inhibitor of apoptotic proteins or inhibiting necrosis resulting in significant decrease in the severity of the disease. [41] They also have antioxidant activity and exhibit specific protective activity such as suppression of neutrophil infiltration and inflammasome inhibition. The various potent phytochemicals to treat pancreatitis and their mechanism of action are described in Table 1.…”

Targeting Cancer with Phytochemicals via Their Fine Tuning of the Cell Survival Signaling Pathways

“…Glabridin causes apoptosis in oral cancer cells via the JNK1/2 pathway, which with NF-κB is involved in cell survival, apoptosis, inflammation and angiogenesis [ 110 , 111 ]; hesperedin induces apoptosis in endometrial carcinoma by downregulating the estrogen receptor relationship via the ERK/MAPK pathway [ 112 ]; apigenin triggers apoptosis and autophagy in hepatocellular carcinoma cells via the PI3K/Akt/mTOR signaling pathway [ 113 ]; chrysin and other fundamental components of propolis, such as the phenolic acids caffeic, ferulic and α-coumaric acid, induce a proline dehydrogenase/proline oxidase-dependent apoptosis in human tnongue squamous cell carcinoma [ 114 ]. The panoply of different targets by which flavonoids induce apoptosis may be a consequence of their modulatory role in balancing the apoptosis/necrosis ratio [ 115 ].…”