Studies on the Antinephritic Effect of Plant Components (4): Reduction of Protein Excretion by Berberine and Coptisine in Rats with Original-Type Anti-GBM Nephritis

Abstract

-The present study was conducted to investigate the antinephritic effects of berberine and coptisine, which are contained in Coptidis rhizoma, on original-type anti-GBM nephritis in rats. Ber berine and coptisine at the doses of 0.5, 1.0 and 5.0 mg/kg/day, i.p. were effective in inhibiting urinary protein excretion, elevation of serum cholesterol and creatinine contents as well as glomerular histo pathological changes. In addition, berberine at 20 mg/kg/day, p.o. also inhibited urinary protein excre tion throughout the experimental periods. Berberine and coptisine inhibited platelet aggregation in both in vitro and in vivo assays, and berberine inhibited the decline of renal blood flow. Although berberine inhibited an increase in thromboxane B2 formation, it increased the formation of 6-keto-prostaglandin Fl,, in platelets and isolated glomeruli. These results indicate that the antinephritic effects of berberine and coptisine may be partly due to antiplatelet action and improved renal hemodynamics via changing prostanoid synthesis. Keywords:Nephritis, Proteinuria, Berberine, Coptisine, Coptidis rhizomaIt is well-known that Coptidis rhizoma, which is ex tracted from Coptidis japonica MAKINO (Raunucu laceae), has been used as a bitter stomachic drug in Japanese-Chinese herbal medicine prescriptions. Coptidis rhizoma has also been prescribed for the purpose of providing antiphlogistic, analgestic and sedative action. However, it remains unclear which of the components composing Coptidis rhizoma exhibit the pharmacologi cal actions. Recently, Ohtsuka et al. (1) reported on the effects of constituents in the rhizomes of Coptidis japonica MAKING by means of several inflammatroy models. They demonstrated that the principal inhibitory elements acting against an inflammatory response such as granulation tissue formation were berberine and cop tisine.We have reported that TJ-8014, a new Japanese herb al medicine (2-6), and Coptidis rhizoma extract, one of eight crude drugs which constitute TJ-8014 (7), were effective in inhibiting the urinary protein excretion as well as glomerular histopathological changes in several renal diseases. However, it is unclear which compo nents of TJ-8014 have the antinephritic action.Therefore, to clarify the antinephritic effect of ber berine and coptisine, we investigated the effects of ber berine and coptisine on original-type anti-GBM nephri tis in rats in comparison with the effects of dipyrida mole. In the second experiment, the effects of berber ine and coptisine on platelet aggregation and renal blood flow of nephritic control rats were examined to elucidate the antinephritic mechanisms of these compo nents. In the third experiment, we investigated the effects of berberine and coptisine on thromboxane A2 (TXA2) and prostaglandin 12 (PGI2) formations in platelets and isolated glomeruli to determine the mechanisms by which these drugs exert their anti platelet action and improve renal blood flow. MATERIALS AND METHODS AnimalsMale Sprague-Dawley strain SPF rats, weighing approx...

Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats

“…Reductions of plasma TAG by BBR were also observed in other studies in rats with diabetes and nephritis [42,43,47]. Results from several in vitro studies have demonstrated that BBR decreases TAG levels through regulating fatty acid metabolism toward the downregulation of adipogenesis [51][52][53].…”

“…This discrepancy may have resulted from the differences in the diet composition, especially dietary cholesterol and fat levels, bile acid supplementation, and the time of BBR administration between the present study and previous studies [13,26,42,43]. It could also be due to the differences in cholesterol metabolism between humans and animal species [44][45][46].…”

“…The cholesterol-lowering property of BBR was initially observed in atherosclerotic human aortic intimal cells [41] and later in rodents [13,26,42,43] and humans [13].H o wever, the current study did not reveal a significant effect of BBR on plasma cholesterol in rats fed a semi-synthetic, high-cholesterol and high-fat diet for 1.5 months. This discrepancy may have resulted from the differences in the diet composition, especially dietary cholesterol and fat levels, bile acid supplementation, and the time of BBR administration between the present study and previous studies [13,26,42,43].…”

“…It could also be due to the differences in cholesterol metabolism between humans and animal species [44][45][46]. In addition, it should be noted that the effect of BBR on blood cholesterol in rats was previously examined only in disease models such as diabetes or nephritis [42,43,47]. Response of plasma lipids to BBR treatment in these disease models may be different from that in healthy animal models.…”

Selective Regulation of Multidrug Resistance Protein in Vascular Smooth Muscle Cells by the Isoquinoline Alkaloid Coptisine

“…In particular, the major medically important isoquinoline alkaloid, berberine, has been extensively studied [1][2][3][4][5][6][7][8][9] and recently reported to display beneficial effects in the treatment of diabetes, obesity and hyperlipidemia, [10][11][12] while both coptisine and palmatine have been reported to exhibit a limited number of biological activities compared with berberine. [13][14][15][16][17][18] These three isoquinoline alkaloids possess the same tetracyclic structure but differ in the nature of the substituents on the benzo ring, comprising methylene dioxy and/or dimethoxy substituents (Fig. 1).…”