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Hypertension
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Malignant hypertension must be treated in an intensive care unit (ICU). The BP is slowly and continually reduced by using a short-acting titratable intravenous medication. Based on the involved target organ, drug choice and the method of BP reduction are varied. Usually, the goal is a 20%–25% reduction in mean arterial pressure over about 1 hour. Additional titration is used based on the patient’s symptoms. It is not necessary to achieve a normal BP quickly. First-line agents usually include fenoldopam, nitroprusside, labetalol, and nicardipine. Methyldopa, an aromatic-amino-acid decarboxylase inhibitor, is also used. Nitroglycerin used on its own is not as potent as these drugs. Oral drugs have varied onset and are difficult to titrate. Though short-acting nifedipine reduces BP quickly, it can cause potentially fatal cardiovascular and cerebrovascular events. Thiazide diuretics such as hydrochlorothiazide are also used. Cardiac glycosides include drugs such as digoxin.
Protecting Pancreatic β-cells from Metabolic Insults
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
An ethanol extract of aerial parts of Desmodium gangeticum (L.) DC. given orally to Sprague–Dawley rats at a dose of 200 mg/kg during oral glucose tolerance inhibited raise of glycemia compared with untreated animals.170 This extract given orally to streptozotocin-induced diabetic Sprague–Dawley rats at a dose of 200 mg/kg for 2 weeks lowered glycemia from 246.4 to 127.1 mg/dL, triglycerides from 181.2 to 101.2 mg/dL, total cholesterol from 119 to 82.1 mg/dL, and increased high-density lipoprotein from 29.8 to 80.7 mg/dL.170 The extract at a dose of 2 mg/mL induced the secretion of insulin by MIN6 cells in the presence of calcium chelator.170 The extract induced a transient and significant secretion of insulin by mouse MIN6 β-cells pseudoislets exposed to the extract (at a dose of 2 mg/mL).170 An interesting feature of Desmodium gangeticum (L.) DC. is the presence of 5-methoxy-N, N-dimethyltryptamine, N, N-dimethyltryptamine, N-methyl-tetrahydroharman and 6-methoxy-β-carbolinium as well as pterocarpanoids such as gangetin, gangetinin, and desmodin.171,172 The precise molecular basis of insulinotropic activity is unknown. Note that tryptophan at a single intraperitoneal dose of 750 mg/kg induced a profound hypoglycemia in both fed or starved rodents with maximum effect at 6 hours.173 This effect was abrogated with the tryptophane hydroxylase inhibitor p-chlorophenylalanine, the aromatic l-amino acid decarboxylase inhibitor MK-486, or methysergide and boosted by the monoamine oxidase inhibitor pargyline suggesting 5-hydroxytryptamine (serotonine) to be responsible for the aformentionned activity.173 In human, β-cells in Langerhans islets of the pancrease express serotonin receptors 5-hydroxytryptamin-1A, 5-hydroxytryptamin-1B, 5-hydroxytryptamin-1F, 5-hydroxytryptamin-2A, 5-hydroxytryptamin-6, and 5-hydroxytryptamin-7.126 5-Hydroxytryptamin-1A, 5-hydroxytryptamin-1B, and 5-hydroxytryptamin-1F receptor agonist sumatripan inhibit insulin, glucagon and somatostatin secretion in human.174 It would be therefore of interest to appraise the insulinotropic effect of 5-methoxy-N, N-dimethyltryptamine, N, N-dimethyltryptamine, N-methyl-tetrahydroharman, and 6-methoxy-β-carbolinium in rodent models of type 2 diabetes. As for gangetin, gangetinin, and desmodin, their pharmacological activities are unexplored yet. Rathi et al. (2004) provided evidence that administration of aqueous extract of aerial part of this plant at a dose of 20 mk/kg prevented carageenin-induced inflammation in rodents.175 One could speculate that the plant contains anti-inflammatory and/or antioxidant water soluble principles that would, at least partly, improve pancreatic function in streptozotocin-induced diabetic rodents. Such principles need to be identified and their mechanisms clarified.
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
Benserazide [15,41] (1–8) is an approved drug in the UK for the treatment of Parkinson’s disease. It is a peripheral aromatic L-amino acid decarboxylase inhibitor and is often combined with levodopa in clinical practice. Li et al. used a structure-based virtual ligand screening method to screen the FDA-approved drug database and found that 1–8 was a selective HK2 inhibitor [42] (Enzyme inhibition IC50: 5.52 ± 0.17 μM). As a clinically used drug, 1–8 has clear pharmacokinetics, pharmacodynamics, and low toxicity, which greatly facilitates the development of 1–8 and its derivatives as anti-tumor drugs. Moreover, 1–8 was found to reduce the glucose uptake rate, lactate production, and intracellular ATP levels of cancer cells, as well as depolarize the cancer cell mitochondrial membrane potential leading to apoptosis. These results suggested 1–8 might be a very promising anticancer drug candidate.