“The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the ligands of G protein-coupled receptor 55 (GPR55), on experimental acute pancreatitis (AP) were investigated. Cannabidiol or O-1602 treatment significantly improved the pathological changes of mice with AP and decreased the enzyme activities, IL-6 and tumor necrosis factor α; levels, and the myeloperoxidase activities in plasma and in the organ tissues. G protein-coupled receptor 55 mRNA and protein expressed in the pancreatic tissue, and the expressions were decreased in the mice with AP, and either CBD or O-1602 attenuated these changes to a certain extent.
Monthly Archives: February 2017
Cannabinoids Ameliorate Pain and Reduce Disease Pathology in Cerulein-Induced Acute Pancreatitis
“The endocannabinoid system has been identified as a major regulator of physiological and pathological processes, such as pain, inflammation, cell growth, cell death, and as a regulator of diverse gastrointestinal functions, such as intestinal motility and secretion. Although cannabinoid-induced analgesia was initially primarily attributed to the activation of cannabinoid receptor 1 (CB1) in the nervous system, later studies demonstrated a contribution of cannabinoid receptor 2 (CB2), localized peripherally on immune cells as well as in the nervous system. A complex interplay between endogenously released cannabinoids, such as anandamide or 2-arachidonoylglycerol, and their receptors both on inflammatory cells and neurons is involved in modulation of inflammatory pain. In this article, we demonstrate the in vivo significance and therapeutic potential of cannabinoids in inflammation and pain associated with pancreatitis using human specimens and mouse models as test systems. Our results are more in line with a recent study reporting a protective role for the endogenous cannabinoid system against colonic inflammation in a mouse model of experimental colitis. Consistent with the above, we now show that acute pancreatitis, a visceral inflammatory disease in humans, is associated with an activation of the endocannabinoid system. In humans, acute pancreatitis is associated with up-regulation of ligands as well as receptors of the endocannabinoid system in the pancreas. Furthermore, our results suggest a therapeutic potential for cannabinoids in abolishing pain associated with acute pancreatitis and in partially reducing inflammation and disease pathology in the absence of adverse side effects. Because management of visceral inflammatory diseases should ideally include antinociceptive as well as anti-inflammatory components, our results lay a basis for testing the therapeutic value of cannabinoids as supplements to conventional analgesic therapy.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268094/]]>
Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells
“While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.
The activity of the endocannabinoid system was evaluated in human chronic pancreatitis (CP) tissues.
Augmentation of the endocannabinoid system via exogenously administered cannabinoid receptor agonists specifically induces a functionally and metabolically quiescent pancreatic stellate cell phenotype and may thus constitute an option to treat inflammation and fibrosis in chronic pancreatitis.
Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis
“Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance.
Trans-resveratrol (trans-3,5,4′-trihydroxystilbene) is a natural phenolic derivative of the stilbenoid family found in skins of red grapes, berries and peanuts. As a renowned antioxidant used in a number of preclinical and clinical studies, its remarkable antioxidant activities are often related to its nature as a potent Sirtuin1 activator.
Aside from being detected as a colonic metabolite of trans-resveratrol, dihydro-resveratrol is indeed produced by a number of plant species including Orchidaceae and Cannabis sativa L. as a phytoalexin against abiotic and biotic stress factors.
In the present study, we aimed to examine whether dihydro-resveratrol, as a remedial agent, attenuates oxidative damage in pancreatic tissues of rats with cerulein-induced acute pancreatitis and to delineate its underlying molecular actions.
Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains.
In conclusion, we suggest that dihydro-resveratrol may serve as a therapeutic or an adjuvant agent for the management of acute pancreatitis, in particular to patients who have microbial restriction in metabolizing trans-resveratrol and received unresponsiveness.”
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Cannabinoids and Cystic Fibrosis
“Cannabis stimulates appetite and food intake. This property has been exploited to benefit AIDS and cancer patients suffering from wasting disease, by administering the whole plant or its major active ingredient ?-tetrahydrocannabinol (THC). Endogenous cannabinoids (“endocannabinoids”) are found in maternal milk. We have recently shown that endocannabinoids are critical for milk ingestion and survival of newborns because blocking CB1 receptors resulted in death from malnutrition. Lack of appetite resulting in malnutrition is a contributing factor to mortality in many Cystic Fibrosis (CF) patients. It is proposed here for the first time, to administer THC to CF patients. It is hoped that the cannabinoid will alleviate malnutrition and thus help prevent wasting in CF patients. Recent findings suggest that a lipid imbalance (high arachidonic acid/low DHA) is a primary factor in the etiology of CF and that defective CFTR (CF transmembrane conductor regulator) that characterizes the CF condition is responsible for the dysregulation. Endocannabinoids are all fatty acid derivatives. Therefore, it is further proposed here that the CFTR gene product also modulates endocannabinoid synthesis, through regulation of fatty acid biosynthesis. According to this hypothesis, CF patients display decreased levels of endocannabinoids and by elevating these levels, symptoms may improve. Indeed, a number of physiological mechanisms of cannabinoids and endocannabinoids coincide with the pathology of CF. Thus it is suggested that potential benefits from THC treatment, in addition to appetite stimulation, will include antiemetic, bronchodilating, anti-inflammatory, anti-diarrheal and hypo-algesic effects.” https://www.researchgate.net/publication/233294071_Cannabinoids_and_Cystic_Fibrosis