Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is called pharmacokinetics.
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation. Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection. Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.
Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. In this form, HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.
Disufenton sodium is a free radical trapping nitrone-based antioxidant compound that has been under development for several medical conditions.
Honokiol is a lignan isolated from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. It has been identified as one of the chemical compounds in some traditional eastern herbal medicines along with magnolol, 4-O-methylhonokiol, and obovatol.
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the UGT1A10 gene.
Dimethylaniline monooxygenase [N-oxide-forming] 1 is an enzyme that in humans is encoded by the FMO1 gene.
UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4 gene.
Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.
Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea. It has mixed effects on normal and cancer cells in in vitro and in vivo studies.
Rhynchophylline is an alkaloid found in certain Uncaria species (Rubiaceae), notably Uncaria rhynchophylla and Uncaria tomentosa. It also occurs in the leaves of Mitragyna speciosa (kratom), a tree native to Thailand. Chemically, it is related to the alkaloid mitragynine.
Leonurine is a pseudoalkaloid that has been isolated from Leonotis leonurus, Leonotis nepetifolia, Leonurus japonicus, Leonurus cardiaca (motherwort), Leonurus sibiricus, as well as other plants of family Lamiaceae. Leonurine is easily extracted into water.
Salidroside (rhodioloside) is a glucoside of tyrosol found in the plant Rhodiola rosea. It has been studied, along with rosavin, as one of the potential compounds responsible for the putative antidepressant and anxiolytic actions of this plant. Salidroside may be more active than rosavin, even though many commercially marketed Rhodiola rosea extracts are standardized for rosavin content rather than salidroside.
Clostridium sporogenes is a species of Gram-positive bacteria that belongs to the genus Clostridium. Like other strains of Clostridium, it is an anaerobic, rod-shaped bacterium that produces oval, subterminal endospores and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized animals, it has a mutualistic rather than pathogenic interaction with the host.
Tropoflavin, also known as 7,8-dihydroxyflavone, is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves. It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF). Tropoflavin is both orally bioavailable and able to penetrate the blood–brain barrier. A prodrug of tropoflavin with greatly improved potency and pharmacokinetics, R13, is under development for the treatment of Alzheimer's disease.
3-Indolepropionic acid (IPA), or indole-3-propionic acid, has been studied for its therapeutic therapeutic value in the treatment of Alzheimer's disease. As of 2022 IPA shows potential in the treatment of this disease, though the therapeutic effect of IPA depends on dose and time of therapy initiation.
Geniposide, the glycoside form of genipin, is a bioactive iridoid glycoside that is found in a wide variety of medicinal herbs, such as Gardenia jasminoides (fruits) . Geniposide shows several pharmacological effects including neuroprotective, antidiabetic, hepatoprotective, anti-inflammatory, analgesic, antidepressant-like, cardioprotective, antioxidant, immune-regulatory, antithrombotic and antitumoral activity. These pharmacology benefits arise through the modulating action of geniposide on several proteins and genes that are associated with inflammatory and oxidative stress processes.
Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary L-tryptophan that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.
A cerebroprotectant is a drug that is intended to protect the brain after the onset of acute ischemic stroke. As stroke is the second largest cause of death worldwide and a leading cause of adult disability, over 150 drugs tested in clinical trials to provide cerebroprotection.
