Emerging potential of natural products for targeting mucins for therapy against inflammation and cancer

Abstract

Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy.

Effects of chlorogenic acid, epicatechin gallate, and quercetin on mucin expression and secretion in the Caco‐2/HT29‐MTX cell model

“…In the human intestine, MUC2 is the major secreted mucin of the mucosal layer (Hews et al, 2017). Recently, therapeutic approaches have focused on mucin regulation during inflammation and cancer in order to use mucins as therapeutic targets (Macha et al, 2015). Recently, therapeutic approaches have focused on mucin regulation during inflammation and cancer in order to use mucins as therapeutic targets (Macha et al, 2015).…”

“…Mucins are characterized by a defined pattern of expression that can be modified by environmental factors and thereby involve an alteration of gene expression (Hollingsworth & Swanson, 2004). Recently, therapeutic approaches have focused on mucin regulation during inflammation and cancer in order to use mucins as therapeutic targets (Macha et al, 2015).…”

MUC4 mucin- a therapeutic target for pancreatic ductal adenocarcinoma

“…Due to their ability to target signaling pathways involved in inflammation, several natural products have been demonstrated to modulate mucin expression [89]. In PDAC models, several natural compounds have been shown to exhibit therapeutic effects that are putatively mediated by downregulation of MUC4 [89].…”

“…In PDAC models, several natural compounds have been shown to exhibit therapeutic effects that are putatively mediated by downregulation of MUC4 [89]. Guggulsterone (GS) [(4,17(20)-pregnadiene-3,16-dione], a plant polyphenol derived from Commiphora mukul , has been traditionally used as a remedy for obesity, hypertension, and atherosclerosis.…”

Natural small molecule FMHM inhibits lipopolysaccharide-induced inflammatory response by promoting TRAF6 degradation via K48-linked polyubiquitination

“…Natural products have played a major role in discovering novel drugs for the pathobiology of infection and inflammatory diseases 18 19 . Bioactive small molecules from medicinal herbs form a treasury that supplies candidate drugs with structure-function diversity 20 .…”