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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
The main therapeutic approach for PD involves the administration of L-Dopa, the precursor of dopamine to elevate its level in the brain, inhibition of monoamine oxidase (MAO), and catechol-O-methyltransferase (COMT). Ayurveda, the traditional Indian system of medicine, describes the use of four plants—Mucuna pruriens (L.) DC, Hyoscyamus reticulatus L. seeds, Withania somnifera (L.) Dunal, and Sida cordifolia L. roots—as a concoction in cow’s milk for the treatment of PD (Figure 16.2). The concoction has been reported to contain compounds like L-Dopa, neuroactive agents like hyoscyamine, somniferin and ephedrine. A prospective clinical study demonstrates the efficacy of Ayurveda treatment, in which 18 patients of PD received a mixture of warm cow’s milk (200 mL) and powdered M. pruriens (4.5 g), H. reticulatus seeds (0.75 g), W. somnifera (14.5 g) and S. cordifolia roots (14.5 g). The symptoms like tremor, bradykinesia, stiffness and cramp-like pain were improved by 61.5%, 69.2%, 100% and 75%, respectively, in patients who followed the Ayurvedic treatment (Nagashayana et al., 2000).
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
Levodopa is a naturally occurring amino acid, most of which is metabolized by catechol-O-methyltransferase (COMT) to form an inactive metabolite, and some of which is decarboxylated by an aromatic amino acid decarboxylase to form dopamine (Figure 16.51). It is still the gold standard drug for PD, after 30 years of use, for improving the cardinal features of the illness. Currently, many formulations exist on the market (Table 16.7).
Cannabis
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Overall, studies and clinical experience, including the clinical experience of the author, suggest that adolescent brains may be particularly vulnerable to developing psychotic disorders associated with cannabis use and that some adolescents may be particularly vulnerable to the effects of THC. It has been speculated that this vulnerability may have a genetic basis and that it may be due to a variation in the gene that encodes catechol-O-methyltransferase (COMT), an enzyme that is involved in the breakdown of dopamine in the synapses (Caspi et al., 2005). However, the finding was not replicated in more recent research (Zammit et al., 2011). It is definitely more likely that multiple variations within multiple genes – rather than one single genetic polymorphism – may render a person vulnerable to developing psychosis after cannabis use (Henquet et al., 2008).
In vitro and in vivo characterization of Entacapone-loaded nanostructured lipid carriers developed by quality-by-design approach
Published in Drug Delivery, 2022
Yogeeta Agrawal, Kiran Patil, Hitendra Mahajan, Mrugendra Potdar, Pratiksha Joshi, Kartik Nakhate, Charu Sharma, Sameer N. Goyal, Shreesh Ojha
Entacapone, a nitro catechol compound (Figure 1), has been approved for clinical use in patients with PD. It inhibits the degradation of dopamine and levodopa by blocking the enzyme Catechol-O-Methyl Transferase (COMT) (Najib, 2001). It enhances the action of dopamine and reduces the onset of motor complications to a certain extent. It is used along with carbidopa-levodopa therapy to overcome the ‘wear-off’ symptoms (Antonini et al., 2018; Müller, 2020). But Entacapone is a BCS class IV drug with low aqueous solubility and low permeability (Bommaka et al., 2018). Moreover, the bioavailability may also be affected by high lipophilicity, pre-systemic clearance in the gastrointestinal mucosa, and the P-GP efflux mechanism (Garg et al., 2020). Therefore, the major challenge is to formulate the drug delivery system that possibly tackles all these problems and increases the bioavailability and residence of the drug.
Comparative examination of levodopa pharmacokinetics during simultaneous administration with lactoferrin in healthy subjects and the relationship between lipids and COMT inhibitory activity in vitro
Published in Nutritional Neuroscience, 2022
Masahiro Nagai, Madoka Kubo, Rina Ando, Masayuki Ikeda, Hiroshi Iwamoto, Yasuhiro Takeda, Masahiro Nomoto
Catechol-O-methyltransferase (COMT) is an enzyme that metabolizes biologically active substances, including catechols and methylated hydroxyl groups using S-adenosylmethionine as a methyl donor. It is widely distributed in living tissues and metabolizes biologically active substances, including the neurotransmitters dopamine and noradrenaline [4]. COMT is expressed as a membrane-bound and soluble isoform, and neurotransmitters are inactivated at neuronal synapses by these enzymes. COMT inhibitors, such as entacapone, have been studied for a long time and are used for the treatment of Parkinson’s disease (PD) [5]. As natural derivatives, epigallocatechin gallate and quercetin are known to exhibit COMT inhibitory effects [6,7]. COMT inhibitors inhibit the metabolism of levodopa in the treatment of PD and are used in combination with carbidopa and benserazide aromatic amino acid decarboxylase inhibitors (DCI) to enhance the brain entry (Figure 1).
Detection of altered methylation of MB-COMT promotor and DRD2 gene in cannabinoid or synthetic cannabinoid use disorder regarding gene variants and clinical parameters
Published in Journal of Addictive Diseases, 2021
Yasemin Oyaci, Hasan Mervan Aytac, Ozge Pasin, Pinar Cetinay Aydin, Sacide Pehlivan
Catechol-O-methyltransferase (COMT) is the critical enzyme responsible for the metabolism of dopamine in the brain’s cortical regions.14 The COMT gene is placed on chromosome 22q11.21, has eight exons, and produces 271 amino acids, which metabolize catecholamines.15 COMT gene polymorphisms are associated with the enzyme activity: higher activity is related to the COMT Val (valine) allele, and lower activity is associated with the COMT Met allele.16,17 In codon 158 (in the rs4680 polymorphism) of the COMT gene, the Met allele’s low enzymatic activity, which provides metabolic inactivation of dopamine, may be related to SUD. While COMT gene variants affect COMT activity, epigenetic modifications, especially DNA methylation of the COMT gene, may influence gene expression. Indeed, increased COMT gene methylation was related to decreased gene expression, and tobacco use disorder (TUD)18 and alcohol use disorder (AUD)2 were found to be related to higher membrane-bound catechol-O-methyltransferase (MB-COMT) promoter methylation, suggesting lower COMT gene activity.