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Nanostructures for Improving the Oral Bioavailability of Herbal Medicines
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Much research is still required to completely understand the mechanism by which the phytochemicals are absorbed from the GI tract (Rice-Evans et al., 2000). As with any other drug products, to get absorbed into systemic circulation, the phytochemicals must dissolve in the fluids of the GI tract, survive the harsh pH environment, and not get degraded or metabolized by intestinal enzymes such as the glycosidases, esterases, oxidases, and hydrolases. After dissolution in the GI tract fluid, the dissolved drug has to be partitioned through the phospholipid-based biological membrane into systemic circulation. Many plant bioactives, such as most polyphenols, are probably too hydrophilic, exhibiting poor partitioning properties, to penetrate the gut wall by passive diffusion, however, the membrane carriers that could be involved in polyphenol absorption have not been identified (Manach et al., 2004). In contrast, paclitaxel, a diterpenoid pseudoalkaloid extracted from the bark of Taxus brevifolia exhibits a poor aqueous solubility (<1 µg/ml) resulting in low oral bioavailability (<2%) (Yang et al., 2015).This low oral bioavailability of paclitaxel has been attributed to its poor aqueous solubility, low permeability restricted by P-glycoprotein (P-gp), and metabolism by P450 enzymes like CYP3A4 (Iqbal et al., 2011; Yang et al., 2015). In most of the cases, all flavonoids, except flavanols, are found in glycosylated forms in foods, and this glycosylation influences absorption. Only aglycones and some glucoside forms of the drug can be absorbed in the small intestine, whereas polyphenols linked to a rhamnose sugar must reach the colon and be hydrolyzed by rhamnosidases of the microflora before absorption (Manach et al., 2004). Hollman et al. (1995) suggested that glucosides could be transported into enterocytes by the sodium-dependent glucose transporter SGLT1. Another pathway involves the lactase phloridzine hydrolase, a glucosidase of the brush border membrane of the small intestine that catalyzes extracellular hydrolysis of some glucosides, which is followed by diffusion of the aglycone across the brush border. Another reason for the poor bioavailability of many phytochemicals is their rapid conjugation, especially by glucuronidation in the intestine and liver, which is mediated by uridine diphosphate-glucuronosyl transferases (UDP-UGTs), and together with reactions of cytochrome P450 enzymes they represent more than 80% of the pathways by which compounds are metabolized (Aqil et al., 2013).
Sodium-glucose transporter (SGLT2) inhibition: A potential target for treatment of type-2 Diabetes Mellitus with Natural and Synthetic compounds
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Shubham Batra, Prabhjeet Kaur Bamrah, Manjusha Choudhary
In GIT(gastrointestinal tract), SGLT1 is a vital transporter for glucose uptake but the effect in kidneys is less significant whereas SGLT2 serves as important transporter (reabsorbs 90% glucose) in kidneys which causes hyperglycemia in diabetes mellitus. Thus, this transporter (SGLT2) has gained interest in the treatment for the T2DM. Especially in hypoglycemic patients SGLT2 inhibitors oppose the effects of SGLT2 transporter, thereby increasing glucosuria and decreasing serum glucose levels. SGLT2 inhibitors have been demonstrated to improve CVS outcomes and provided much-needed advantages for type −2 diabetes mellitus. SGLT2 inhibition is therefore considered a strategy for the treatment of diabetes mellitus [8]. This review encapsulates the first plant-derived SGLT inhibitory compound, Phlorizin, and a description of phlorizin-derived synthetic SGLT2 inhibitors which are commercially available and it also summarizes active constituents with SGLT2 inhibitory effects from natural plants.
The effect of calcium co-ingestion on exogenous glucose oxidation during endurance exercise in healthy men: A pilot study
Published in European Journal of Sport Science, 2021
Ben J. Narang, Gareth A. Wallis, Javier T. Gonzalez
The typical intestinal glucose absorption pathway consists of an active component mediated by SGLT1 at the apical membrane of the enterocyte, followed by the passive transport of glucose across the basolateral membrane via GLUT2 (Röder et al., 2014). When luminal glucose concentrations are high, transport across the brush border membrane is thought to be facilitated by apical GLUT2 insertion (Chaudhry et al., 2012), resulting in a greater capacity for glucose uptake into the enterocyte. Thus, any factor that can influence apical GLUT2 expression has the potential to alter the absorption and subsequent metabolism of exogenous glucose. The putative role for calcium in apical GLUT2 insertion relates to both cytoskeletal rearrangement of the enterocyte (Turner, 2000) and SGLT1-dependent expression of PKC βII (Hug & Sarre, 1993). Morgan, Mace, Affleck, and Kellett (2007) demonstrated the necessity of calcium for myosin light chain kinase (MLCK) activity in isolated rate intestine, and in turn showed a facilitative role for MLCK activity in intestinal glucose absorption. Furthermore, these authors demonstrated a decrease in PKC βII expression in a calcium-deplete rat intestine (Mace et al., 2007; Morgan et al., 2007). However, despite the putative effect of calcium on intestinal glucose absorption, the present study shows that the addition of high-dose calcium to 1.2 g min−1 glucose does not enhance exogenous carbohydrate oxidation during endurance exercise.