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      Protopanaxatriol Ginsenosides Inhibit Glucose Uptake in Primary Cultured Rabbit Renal Proximal Tubular Cells by Arachidonic Acid Release


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          Ginsenosides are involved in protective action against renal dysfunction and the regulation of renal functions. However, the effects of ginsenosides on glucose reabsorption are not yet known in renal proximal tubular cells. The aim of this study was to examine the effects of ginsenosides, protopanaxadiol (PD) saponin and protopanaxatriol (PT) saponin, on α–methyl–D–glucopyranoside (α–MG) uptake and its mechanism of action in primary cultured rabbit renal proximal tubular cells (PTCs). The α–MG uptake was inhibited by 90% by 0.5mM phloridizin and by removal of Na<sup>+</sup> in the PTCs. These are typical characteristics described for the proximal tubule. To determine the time– and dose–dependent effects of PD and PT saponins on α–MG uptake, PTCs were incubated with different concentrations of PD and PT saponins (10–100 μg/ml) and for different time periods (from 10 min to 24 h). PT saponin (≥50 μg/ml) from 30 min inhibited α–MG uptake; however, PD saponin did not alter the α–MG uptake at any doses and time periods. In the kinetic analysis of α–MG uptake, PT saponin produced a significant decrease in V<sub>max</sub>. The PT saponin induced inhibition of α–MG uptake was blocked by mepacrine, a phospholipase A<sub>2</sub> inhibitor. In addition, PT saponin increased [<sup>3</sup>H] arachidonic acid release by 218% of that of control, and this effect was also completely blocked by mepacrine. In conclusion, PT saponin inhibited, in part, α–MG uptake through the phospholipase A<sub>2</sub> signal pathway in primary cultured rabbit renal PTCs.

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          Panax ginseng pharmacology: a nitric oxide link?

          Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to cope with fatigue and physical stress. Major active components are the ginsenosides, which are mainly triterpenoid dammarane derivatives. The mechanisms of ginseng actions remain unclear, although there is an extensive literature that deals with effects on the CNS (memory, learning, and behavior), neuroendocrine function, carbohydrate and lipid metabolism, immune function, and the cardiovascular system. Reports are often contradictory, perhaps because the ginsenoside content of ginseng root or root extracts can differ, depending on the method of extraction, subsequent treatment, or even the season of its collection. Therefore, use of standardized, authentic ginseng root both in research and by the public is to be advocated. Several recent studies have suggested that the antioxidant and organ-protective actions of ginseng are linked to enhanced nitric oxide (NO) synthesis in endothelium of lung, heart, and kidney and in the corpus cavernosum. Enhanced NO synthesis thus could contribute to ginseng-associated vasodilatation and perhaps also to an aphrodisiac action of the root. Ginseng is sold in the U.S. as a food additive and thus need not meet specific safety and efficacy requirements of the Food and Drug Administration. Currently, such sales amount to over $300 million annually. As public use of ginseng continues to grow, it is important for this industry and Federal regulatory authorities to encourage efforts to study the efficacy of ginseng in humans by means of appropriately designed double-blind clinical studies.
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            Recent advances on ginseng research in China

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              Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium

              Primary cultures of rabbit-kidney epithelial cells derived from purified proximal tubules were maintained without fibroblast overgrowth in a hormone-supplemented serum-free medium (Medium RK-1). A hormone- deletion study indicated that the primary cultures derived from purified rabbit proximal tubules required all of the three supplements in Medium RK-1 (insulin, transferrin, and hydrocortisone) for optimal growth but did not grow in response to EGF and T3. In contrast, the epithelial cells in primary cultures derived from an unpurified preparation of rabbit kidney tubules and glomeruli grew in response to EGF and T3, as well as insulin, transferrin, and hydrocortisone. These observations suggest that kidney epithelial cells derived from different segments of the nephron grow differently in response to hormones and growth factors. Differentiated functions of the primary cultures derived from proximal tubules were examined. Multicellular domes were observed, indicative of transepithelial solute transport by the monolayers. The proximal tubule cultures also accumulated alpha- methylglucoside (alpha-MG) against a concentration gradient. However, little or no alpha-MG accumulation was observed in the absence of Na+. Metabolic inhibitor studies also indicated that alpha-MG uptake by the primaries is an energy-dependent process, and depends upon the activity of the Na+/K+ ATPase. Phlorizin at 0.1 mM significantly inhibited 1 mM alpha-MG uptake whereas 0.1 mM phloretin did not have a significant inhibitory effect. Similar observations have been made concerning the Na+-dependent sugar-transport system located on the lumenal side of the proximal tubule, whereas the Na+-independent sugar transporter on the peritubular side is more sensitive to inhibition by phloretin than phlorizin. The cultures also exhibited PTH-sensitive cyclic AMP synthesis and brush-border enzymes typical of proximal cells. However, the activities of the enzymes leucine aminopeptidase, alkaline phosphatase, and gamma-glutamyl-transpeptidase were lower in the cultures than in purified proximal-tubule preparations from which they are derived.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                25 June 1999
                : 22
                : 3
                : 114-120
                aCollege of Veterinary Medicine and bHormone Research Center, Chonnam National University, Kwangju, Korea
                25916 Kidney Blood Press Res 1999;22:114–120
                © 1999 S. Karger AG, Basel

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                Page count
                Figures: 6, References: 21, Pages: 7
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/25916
                Self URI (text/html): https://www.karger.com/Article/FullText/25916
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                Ginsenosides,Na+/glucose cotransport,Arachidonic acid,Kidney
                Cardiovascular Medicine, Nephrology
                Ginsenosides, Na+/glucose cotransport, Arachidonic acid, Kidney


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