Modulatory role of the endocannabinoidome in the pathophysiology of the gastrointestinal tract

Lian, Jerome; Casari, Ilaria; Falasca, Marco

doi:10.1016/j.phrs.2021.106025

Cited by 22 publications

(15 citation statements)

References 288 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An intercommunication system has been found to exist between the gut microbiota and the endocannabinoid system [285,298,[397][398][399][400][401][402]. The gut microbiota, representing more than 100 trillion microorganisms, including at least 1000 distinct species, lives in symbiosis with the host and assists in controlling the metabolic health of the host by degrading nutrients that the host is unable to digest and by providing a whole battery of small signaling molecules, metabolites, and nutrients beneficial for the host physiology [298,403].…”

Section: Dialog Between the Gut Microbiota And The Endocannabinoid Sy...mentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

View full text Add to dashboard Cite

Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.

show abstract

Section: Dialog Between the Gut Microbiota And The Endocannabinoid Sy...mentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Increasing evidence demonstrated that the response to cannabinoids is mediated not only by the canonical receptors CB1 and CB2 but also by other G-protein coupled receptors, such as GPR55 and GPR119, transient receptor potential vanilloid (TRPV) channels, such as TRPV1, and peroxisome proliferator-activated receptors (PPARs). These receptors, alongside emerging bioactive lipids and enzymes regulating their synthesis and degradation, are collectively known as the “expanded cannabinoid system” or “endocannabinoidome” [ 87 , 90 ]. The endocannabinoidome is a complex system whose knowledge is in constant evolution, developed particularly in the central nervous system but also spread in the periphery of the body and in the gut, where it participates in the regulation of the enteroendocrine system’s functions [ 90 ].…”

Section: Cannabinoids In Pancreatic Cancer Treatmentmentioning

confidence: 99%

“…These receptors, alongside emerging bioactive lipids and enzymes regulating their synthesis and degradation, are collectively known as the “expanded cannabinoid system” or “endocannabinoidome” [ 87 , 90 ]. The endocannabinoidome is a complex system whose knowledge is in constant evolution, developed particularly in the central nervous system but also spread in the periphery of the body and in the gut, where it participates in the regulation of the enteroendocrine system’s functions [ 90 ].…”

Section: Cannabinoids In Pancreatic Cancer Treatmentmentioning

confidence: 99%

Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

Selvaggi

Melchiorre

Casari

et al. 2022

Cancers

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the dynamic interaction between pancreatic cancer cells and nerves. This reciprocal interface leads to perineural invasion (PNI), defined as the ability of cancer cells to invade nerves, similar to vascular and lymphatic metastatic cascade. Targeting PNI in pancreatic cancer might help ameliorate prognosis and pain relief. In this review, the modern knowledge of PNI in pancreatic cancer has been analysed and critically presented. We focused on molecular pathways promoting cancer progression, with particular emphasis on neuropathic pain generation, and we reviewed the current knowledge of pharmacological inhibitors of the PNI axis. PNI represents a common hallmark of PDAC and correlates with recurrence, poor prognosis and pain in pancreatic cancer patients. The interaction among pancreatic cancer cells, immune cells and nerves is biologically relevant in each stage of the disease and stimulates great interest, but the real impact of the administration of novel agents in clinical practice is limited. It is still early days for PNI-targeted treatments, and further advanced studies are needed to understand whether they could be effective tools in the clinical setting.

show abstract

“…Hence, the term “endocannabinoidome” was devised in order to classify these novel endogenous lipid mediators, enzymes and receptors, as a broader “ome”, meaning a completed set [ 44 ]. Altogether, the eCBome system is greatly expressed across the body, including the CNS, adipose and inflammatory tissue, the GI tract and the pancreas [ 45 ]. Therefore, understanding the eCBome poses a significant value for the pharmacological treatment of a multitude of pathological conditions including neuropsychiatric diseases such as anxiety and depression, neurological disorders such as multiple sclerosis, nausea induced by chemotherapy, inflammatory and autoimmune diseases, obesity and type 2 diabetes, and cancers, such as pancreatic cancer.…”

Section: Endocannabinoidomementioning

confidence: 99%

Targeting the Endocannabinoidome in Pancreatic Cancer

Falasca

2022

Biomolecules

Self Cite

View full text Add to dashboard Cite

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic efficacy. The existing therapeutic approaches such as FDA-approved chemotherapeutics, gemcitabine, abraxane and folfirinox, prolong survival marginally and are accompanied by adverse effects. Several studies suggest the role of cannabinoids as anti-cancer agents. Cannabinoid receptors are known to be expressed in pancreatic cells, with a higher expression reported in pancreatic cancer patients. Therefore, pharmacological targeting of the endocannabinoid system might offer therapeutic benefits in pancreatic cancer. In addition, emerging data suggest that cannabinoids in combination with chemotherapy can increase survival in transgenic pancreatic cancer murine models. This review provides an overview of the regulation of the expanded endocannabinoid system, or endocannabinoidome, in PDAC and will explore the potential of targeting this system for novel anticancer approaches.

show abstract

Modulatory role of the endocannabinoidome in the pathophysiology of the gastrointestinal tract

Cited by 22 publications

References 288 publications

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

Targeting the Endocannabinoidome in Pancreatic Cancer

Contact Info

Product

Resources

About