Carmen Avagliano

Bio: Carmen Avagliano is an academic researcher from University of Naples Federico II. The author has contributed to research in topics: Butyrate & Palmitoylethanolamide. The author has an hindex of 14, co-authored 25 publications receiving 657 citations.

Gut-brain Axis: Role of Lipids in the Regulation of Inflammation, Pain and CNS Diseases

Abstract: The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut–brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the bacteria-derived metabolites. Many studies have focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome (IBS) to neurodevelopmental disorders, such as autism, and to neurodegenerative diseases, such as Parkinson Disease, Alzheimer Disease etc. Based on this background, and considering the relevance of alteration of the symbiotic state between host and microbiota, this review focuses on the role and the involvement of bioactive lipids, such as the N-acylethanolamine (NAE) family whose main members are N-arachidonoylethanolamine (AEA), palmitoylethanolamide (PEA) and oleoilethanolamide (OEA), and short chain fatty acids (SCFAs), such as butyrate, belonging to a large group of bioactive lipids able to modulate peripheral and central pathologic processes. It is well established their effective role in inflammation, acute and chronic pain, obesity and central nervous system diseases. It has been shown a possible correlation between these lipids and gut microbiota through different mechanisms. Indeed, systemic administration of specific bacteria can reduce abdominal pain through the involvement of cannabinoid receptor 1 in rat; on the other hand, PEA reduces inflammation markers in a murine model of inflammatory bowel disease (IBD), and butyrate, producted by gut microbiota, is effective in reducing inflammation and pain in irritable bowel syndrome and IBD animal models. In this review, we underline the relationship among inflammation, pain, microbiota and the different lipids, focusing on a possible involvement of NAEs and SCFAs in the gut-brain axis and their role in central nervous system diseases.

The Protective Role of Butyrate against Obesity and Obesity-Related Diseases.

Abstract: Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.

Control of pain initiation by endogenous cannabinoids

Abstract: The potent analgesic effects of cannabis-like drugs and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord, indicate that endogenous cannabinoids such as anandamide may contribute to the control of pain transmission within the central nervous system (CNS). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor, exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CB2-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.

Current development of biodegradable polymeric materials for biomedical applications

Abstract: In the last half-century, the development of biodegradable polymeric materials for biomedical applications has advanced significantly. Biodegradable polymeric materials are favored in the development of therapeutic devices, including temporary implants and three-dimensional scaffolds for tissue engineering. Further advancements have occurred in the utilization of biodegradable polymeric materials for pharmacological applications such as delivery vehicles for controlled/sustained drug release. These applications require particular physicochemical, biological, and degradation properties of the materials to deliver effective therapy. As a result, a wide range of natural or synthetic polymers able to undergo hydrolytic or enzymatic degradation is being studied for biomedical applications. This review outlines the current development of biodegradable natural and synthetic polymeric materials for various biomedical applications, including tissue engineering, temporary implants, wound healing, and drug delivery.

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Abstract: Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system — known as the endocannabinoidome — that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma. In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.

Antibacterial and Anti-Inflammatory pH-Responsive Tannic Acid-Carboxylated Agarose Composite Hydrogels for Wound Healing.

Abstract: pH-sensitive hydrogels play an important role in controlled drug release applications and have the potential to impact the management of wounds. In this study, we report the fabrication of novel carboxylated agarose/tannic acid hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of tannic acid. The resulting hydrogels exhibited negligible release of tannic acid at neutral and alkaline pH and sustained release at acidic pH, where they also displayed maximum swelling. The hydrogels also displayed favorable antibacterial and anti-inflammatory properties, and a lack of cytotoxicity toward 3T3 fibroblast cell lines. In simulated wound assays, significantly greater cell migration and proliferation was observed for cells exposed to tannic acid hydrogel extracts. In addition, the tannic acid hydrogels were able to suppress NO production in stimulated human macrophages in a concentration-dependent manner, indicating effective anti-inflammatory activity. Taken together, the cytocompatibilit...