Role of Natural Agents in the Management of Diabetes
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Galega officinalis is a leguminous plant, which aerial parts have long been used in traditional and folk medicine to treat diabetes in Chile, Japan as well as Europe (Bailey and Day, 2004; Gunn and Farnsworth, 2013; Rios et al., 2015). This herb consists of two nitrogen guanidine constituents: galegin (syn. galegine) as isoamylene guanidine and hydroxygalegine prevalent in all parts during flowering and forming fruits. These bioactive substances possess pharmacological features as hypoglycemic and galactogenic factors. However, guanidine is excessively toxic for clinical treat; hence, the study focused on galegine, which turned out to be less toxic as an extract of G. officinalis. In the 1920s, the extract was specified as an antidiabetic formulation (Bailey and Day, 2004; Martínez-Larrañaga and Martínez, 2018).
Andrology
Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed in MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
NO is released either at non-adrenergic non-cholinergic nerve terminals (nitrergic) on the cavernous smooth muscle cell or on the endothelial cell lining of the sinusoids. Through membrane-bound G proteins, NO activates guanylate cyclase, which induces cleavage of guanosine triphosphate to 3′,5′-cyclic guanosine monophosphate (3′,5′-cGMP). The smooth muscle-relaxing effects of NO are mediated by this second messenger (cGMP). Cyclic GMP activates protein kinase G, which phosphorylates proteins at the so-called maxi-potassium channels. This results in an outflow of potassium ions into the extracellular space with subsequent hyperpolarisation, with inhibition of voltage-dependent calcium channels and therefore a decrease in intracellular calcium ion concentrations. The intracellular decline in calcium ions suppresses the activity of myosin light chain kinase and thus increases the intracellular content of dephosphorylated myosin light chain, which enables the smooth muscle cell to relax. The enzyme phosphodiesterase type 5 inactivates cGMP and thereby reduces relaxation. By inhibiting this enzyme, PDE5 inhibitors promote smooth muscle relaxation in the corpus cavernosum by increasing the cGMP concentration.
Nitric oxide precursors
Jay R Hoffman in Dietary Supplementation in Sport and Exercise, 2019
L-arginine is a semi-essential amino acid (C6H14N4O2) that is abundant in the diet, particularly in protein-rich foods such as meat, fish, dairy products and eggs (132). The mean daily L-arginine intake in humans is 4–6 g (72, 138). Despite its strong bitter and alkaline taste (112) orally-ingested L-arginine is generally well tolerated up to doses of 9 g (55), but side effects including gastrointestinal discomfort, vomiting, diarrhoea and headache have been reported in some studies when this dose has been exceeded (44, 55). After oral supplementation with 6 g L-arginine, L-arginine attains peak concentration in the plasma at approximately 90 min (range 60–150 min) post ingestion (19). Although circulating systemic and tissue [L-arginine] is several times higher than the Michaelis–Menten constant (Km) of the constitutively expressed NOS isoforms for L-arginine, L-arginine administration has been reported to increase NO synthesis in certain experimental conditions (20). This phenomenon is termed the L-arginine paradox (20) and has prompted numerous studies attempting to enhance NOS-derived NO through oral L-arginine supplementation.
RGS7 silence protects palmitic acid-induced pancreatic β-cell injury by inactivating the chemokine signaling pathway
Published in Autoimmunity, 2023
Yurong Zhu, Jun Li, Tao Ba, Yuan Sun, Xiangyun Chang
Regulators of guanine nucleotide binding protein (G protein) signaling (RGSs) are originally identified as guanosine triphosphate (GTP)-activating proteins of Gα subunit of heterotrimer G protein [11]. Presently, more than 30 RGS proteins have been identified [12]. Of these, RGS7 is evolutionarily conservative in all animals and plays a key role in many processes and organ systems [13,14]. More importantly, RGS proteins were reported to play a key role in regulating insulin sensitivity in vivo [11,15–17]. RGS16 reconstitution substantially exacerbated insulin resistance in mice [18]. RGS7 is highly expressed in the brain, especially in the hypothalamus, and may be involved in regulating the hypothalamic–pituitary–adrenal axis in response to different stresses and stimuli [19]. Previous studies have provided evidence that RGS7 may constitute an obesity locus in humans [19,20]. Based on these findings, we speculated that RGS proteins may provide a new therapeutic opportunity for T2D.
Opioid MOP receptor agonists in late-stage development for the treatment of postoperative pain
Published in Expert Opinion on Pharmacotherapy, 2022
Qiu Qiu, Joshua CJ Chew, Michael G Irwin
All opioid receptors are inhibitory G-protein coupled receptors (GPCRs). Although the clinical effects can differ, the signaling mechanism of inhibitory GPCRs are the same. When an opioid agonist binds to the receptor, the receptor complex undergoes a conformational change. The α subunit exchanges its bound guanosine diphosphate (GDP) for guanosine triphosphate (GTP). Subsequently, the α-GTP and βγ subunit dissociate and proceed to interact with effector proteins such as adenylate cyclase and modulate ion channels. With inhibitory GPCRs, agonism causes the inhibition of adenylyl cyclase, leading to the reduction in formation of intracellular adenosine monophosphate (cAMP). The βγ subunit activates G protein-coupled inwardly rectifying potassium channels and inhibits voltage gated calcium channels. This results in hyperpolarisation and decreased neurotransmitter release. Agonism also leads to the recruitment of GPCR kinase which phosphorylates the GPCR. The phosphorylated GPCR subsequently binds β-arrestin, and this family of cytosolic proteins has been implicated in causing respiratory depression, tolerance and constipation. Phosporylated GPCRs can be recycled to the cell membrane or undergo lysosomal degradation [12–15] (Figure 1). Reduced available receptors via this mechanism is how the receptor is negatively regulated, and leads to decreased sensitivity and tolerance [16].
Effect of Curcumin and Its Derivates on Gastric Cancer: Molecular Mechanisms
Published in Nutrition and Cancer, 2021
Afsane Bahrami, Gordon A. Ferns
The US National Cancer Institute have not reported any side effects of CUR in rats, monkeys or dogs at doses up to 3.5 g/kg/BW prescribed for up to three months (163). In several preclinical studies, no toxicity has been observed from 0.2% dietary CUR (about 300 mg/kg BW) for 14 weeks supplemented to mice or from 2% dietary CUR (about 1.2 g/kg BW) for 14 day supplemented to rats (164). Moreover, clinical studies also showed that it is safe and well tolerated at maximum doses 8 g/day. Although these investigations have reported that administration CUR at doses of about 0.9-3.6 g/day for one to four months may be responsible for some side effects such as nausea and diarrhea and elevation in serum lactate dehydrogenase and alkaline phosphatase. Indeed, chest tightness, gastrointestinal upset, skin rashes, and inflamed skin have observed; however, it may be happen at high doses (165). Cai et al. report the toxicity of CUR elevated when the compound dose was more than 30 M (10–30 M was moderate). Oral CUR 1.2–2.1 g daily for two to six weeks to patients with rheumatoid arthritis stating did not cause any adverse events (166). Two manifestations of gastrointestinal side effects were recorded by patients, which were possibly associated to CUR supplementation: one patient received 0.45 g daily one month and one patient received 3.6 g daily four months after treatment developed diarrhea. In one patient receiving 0.9 g CUR daily occurrence nausea (162). While a few clinical studies reported any discernible toxicity of oral CUR, further studies are warranted to investigate its safety.
Related Knowledge Centers
- Cyclic Guanosine Monophosphate
- Glycosidic Bond
- Guanosine Diphosphate
- Nucleic Acid
- Nucleoside
- Purine
- Phosphorylation
- Guanine
- Guanosine Monophosphate
- Guanosine Triphosphate