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Natural Product Compounds from Plants in Neurodegenerative Diseases
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Priya Darshani, Md TanjimAlam, Prem P. Tripathi, V.S. Pragadheesh
Root ethanolic extract of Nardostachys jatamansi (D.Don) DC. delayed the neuronal injury induced in the 6-OHDA rat model of PD. Animals treated with this extract significantly attenuated the neurotoxin-induced lipid peroxidation led to the loss of catecholamine and increased the glutathione (GSH) content (Ahmad et al., 2006). Phytoconstituents like crocin and crocetin of Crocus sativus L. executed neuroprotective activity through antioxidant, anti-inflammatory and immunoregulatory pathways. Cannabinoids from the Cannabis sativa L. such as delta-9-tetrahydrocannabinol (THC) and cannabidiol showed neuroprotection through their antioxidant activity. Cannabinoid derivatives, namely AM404 and WIN-55212–2, showed therapeutic activity by recovering affected MAO dopaminergic neurons and constrain excitotoxicity, glial activation and oxidative injury that prevented the deterioration of nigrostriatal neurons. Additionally, cannabinoid compounds such as CE-178253, oleoylethanolamide, nabilone and HU210 have shown their consistent effects against bradykinesia and levodopa-induced dyskinesia in PD (Carrera and Cacabelos, 2019; Pertwee, 2015; Concannon et al., 2015).
Biocatalyzed Synthesis of Antidiabetic Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The G protein-coupled receptor 119 (GPR119), responsive to natural ligands oleoylethanolamide and monooleoylglycerol, is a recent potential target for the development of oral antidiabetic drugs (Overton et al., 2008; Ohishi and Yoshida, 2012; Ritter et al., 2016). In fact, more than 20 pharmaceutical companies have been developing GPR119 agonists, but many clinical candidates have been discontinued for different reasons not always explained (Buzard et al., 2012; Ritter et al., 2016). For instance, Bristol-Myers Squibb, after disclosing some pyridone, pyridazone, benzothiazole, dihydrobenzofuran, bicyclic pyrimidines and piperidinyl sulfone GPR-119 agonists (Wacker et al., 2014; Ye et al., 2014), is working now on some new pyrimidinylpiperidinyloxypyridone analogues 38 (Fig. 11.20) possessing chirality (Broekema et al., 2013), and for this purpose, an scalable synthesis of enantiomers of N-substituted 3-hydroxypyrrolidin-2-ones have been recently reported (Singh et al., 2015), as shown in Fig. 11.23. Enzymatic resolution of N-substituted 3-hydroxypyrrolidin-2-ones.
Endocannabinoid Role in Gut Health *
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
Other evidence supporting the endocannabinoid system’s role in modulating colonic inflammation was provided by rodent models showing that suppressing FAAH, leading to a rise in anandamide levels, stops the development of colitis.28,29 Likewise, inhibiting FAAH and the inflammatory enzyme cyclooxygenase (COX) in mice with colitis reduces the severity of the disease by elevating anandamide levels and acting on the CB1 receptor.30 Blocking FAAH and COX correlated with higher concentrations of the endocannabinoids palmitoylethanolamide (PEA) and oleoylethanolamide. In intestinal tissue from ulcerative colitis patients, PEA levels are 1.8-fold higher compared with healthy patients, likely a result of the PEA attempting to help heal the inflammation.31 PEA has pronounced anti-inflammatory properties that inhibit features of colitis in mice as well as the synthesis of inflammatory cytokines.32
A review on the reciprocal interactions between neuroinflammatory processes and substance use and misuse, with a focus on alcohol misuse
Published in The American Journal of Drug and Alcohol Abuse, 2023
Anny Gano, Terrence Deak, Ricardo Marcos Pautassi
At a more general level, an exciting avenue of research is the development of molecules that can inhibit the drug-induced activation of TLR4s. One of those, the bioactive lipid oleoylethanolamide, seems to act by protecting the intestinal barrier [reviewed in (60)]. In the current special issue Perez-Reytor & Karahanian review the “microbiota-gut-brain axis” concept, wherein they postulate that the intestinal microbiota can release factors that affect neuroinflammatory status of the brain (19). The authors highlight how this communication can take place, for instance by stimulation of the vagus nerve, and remark the value of dietary treatments high in fiber content. According to the authors, such a dietary regime would promote the production of short-chain fatty acids that protect the integrity of the intestine and prevent the neuroinflammatory signaling.
A comprehensive systematic review of the effectiveness of Akkermansia muciniphila, a member of the gut microbiome, for the management of obesity and associated metabolic disorders
Published in Archives of Physiology and Biochemistry, 2023
Neda Roshanravan, Sepideh Bastani, Helda Tutunchi, Behnam Kafil, Omid Nikpayam, Naimeh Mesri Alamdari, Amir Hadi, Simin Sotoudeh, Samad Ghaffari, Alireza Ostadrahimi
Similar to animal models, human studies demonstrated the effect of dietary factors on the intestinal A. muciniphila abundance (Ramnani et al.2010, Roshanravan et al.2018). In recent human trials, pomegranate fruit extract (PFX) significantly increased the genus of Akkermansia in stool samples of the individuals following PFX extract intervention (Li et al.2015, Henning et al.2017). In a systematic review in 2019, Verhoog et al. (2019) showed an energy-restricted diet, supplemented with resveratrol, polydextrose, yeast fermentate, sodium butyrate, and inulin-type fructans might elevate the A. muciniphila abundance. In contrast, a diet low in fermentable monosaccharides, disaccharides, oligosaccharides, and polyols reduced A. muciniphila abundance. Hooda et al. (2012) reported that polydextrose (PDX) supplementation increased A. muciniphila abundance in healthy individuals’ faecal samples. Whole grains (e.g. wheat, corn, and rice) are other dietary factors shown to affect faecal microbiota composition favourably. In 2016, Cooper et al. (2017) reported increases in the relative abundance of Akkermansia following whole grains consumption in healthy adults. Recently, a study in obese people indicated an increase in the A. muciniphila bacterium abundance following oleoylethanolamide (OEA) supplementation (Payahoo et al.2019).
Could serum endocannabinoid and N-acylethanolamine levels be important in bipolar disorder?
Published in The World Journal of Biological Psychiatry, 2023
Ruhan Deniz Topuz, Yasemin Gorgulu, Milkibar Kyazim Uluturk
Cannabinoids are chemicals that exert their effects through cannabinoid receptors (CB1 and CB2). Phytocannabinoids (natural cannabinoids found in the cannabis plant), synthetic cannabinoids and endogenous cannabinoids called endocannabinoids (anandamide [AEA], 2-arachidonyl glycerol [2-AG]). The endocannabinoid system (ECS; endocannabinoids, cannabinoid receptors, enzymes involved in their synthesis and degradation) plays a regulatory role in many physiological and pathological processes (Ulugöl 2014). CB1 receptors are more widely distributed in the central nervous system while CB2 receptors have restrictive distribution. CB1 receptors are widely expressed in the cerebellum, basal ganglia, hippocampus, cerebral cortex, hypothalamus, olfactory system and spinal cord (Pertwee 2015). Endocannabinoids stimulate transient receptor potential vanilloid 1 (TRPV1) channels and peroxisome proliferator activating receptor alpha (PPAR-α), besides CB1 and CB2 receptors (De Petrocellis and Di Marzo 2010). Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are N-acylethanolamines a group of endocannabinoid-like molecules that do not activate cannabinoid receptors; TRPV1 channels and PPAR-α appear to mediate their effects (Iannotti et al. 2016).