Saireito and Saikosaponin D Prevent Urinary Protein Excretion via Glucocorticoid Receptor in Adrenalectomized WKY Rats with Heterologous-Phase Anti-GBM Nephritis

Abstract

Aims: In order to clarify the antinephritic mechanisms of saireito, the glucocorticoid receptor agonistic effect of saireito was evaluated in adrenalectomized rats with anti-glomerular basement membrane (anti-GBM) nephritis.Methods: Rats with anti-GBM nephritis were subjected to adrenalectomy to exclude the effects of endogenous steroid hormones to investigate effects of saireito on the nephritis. The suppressive effects of saireito and saikosaponin D on the production of cytokines were investigated in vitro andin vivo. Results: Administration of saireito or saikosaponin D significantly suppressed the increase of urinary protein excretion and histopathological changes in adrenalectomized nephritic rats. Coadministration of saireito or saikosaponin D and RU-38486, a glucocorticoid receptor antagonist, did not suppress the increase of urinary protein excretion. Saikosaponin D inhibited the glucocorticoid receptor binding of [³H]dexamethasone in anin vitro assay (IC₅₀ ratio 5.8 µmol/l). The IC₅₀ values of saikosaponin D for the release of IL-2 and IL-10 were 13.4 and 12.3 µmol/l, respectively. Administration of saireito and saikosaponin D prevented an increase in IL-2 levels in the renal cortex of anti-GBM nephritic rats. Conclusion: These results suggest that the antinephritic effects of saireito may be partly attributable to an agonistic action on the glucocorticoid receptor by saikosaponin D, a component of saireito.

Saikosaponin-D Enhances Radiosensitivity of Hepatoma Cells under Hypoxic Conditions by Inhibiting Hypoxia-Inducible Factor-1a

“…Saikosaponin-d (SSd), an extract from a traditional Chinese herb, Bupleurum chinensis DC, exhibits various pharmacological properties, such as anti-inflammation [14,15], hepatocyte injury prevention [16], angiogenesis inhibition [17], and anti-cancer [18,19]. In our preliminary experiments, SSd and radiation are administered to treat liver cancer; the results have revealed that this combined treatment is more effective than either of these treatments administered alone.…”

Saikosaponin-d suppresses the expression of cyclooxygenase-2 through the phospho-signal transducer and activator of transcription 3/hypoxia-inducible factor-1α pathway in hepatocellular carcinoma cells

“…Numerous traditional Chinese plants have been identified to possess biological activities with potential therapeutic applications. Saikosaponin-d (SSD), a saponin derivative extracted from several species of Bupleurum (Umbelliferae), has been traditionally used in the treatment of infectious diseases due to its anti-inflammatory, antipyretic and analgesic effects (4,5). Previous studies have demonstrated that SSD also has hepatoprotective, antifibrotic (6,7) and immunomodulatory (8,9) activities.…”

Metabolism of Saikosaponin a in Rats: Diverse Oxidations on the Aglycone Moiety in Liver and Intestine in Addition to Hydrolysis of Glycosidic Bonds

“…Saikosaponins, the major bioactive ingredients of the genus Bupleurum with a long history of medicinal use, exert significant pharmacological activities, including antitumor (targeting various cancer cells) (Motoo and Sawabu, 1994;Ahn et al, 1998;Hsu et al, 2000;Tsai et al, 2002;Wen-Sheng, 2003;Hsu et al, 2004;Kim and Hong, 2011), chemosensitizing (Wang et al, 2010a), anti-inflammatory (Yokoyama et al, 1981;Nose et al, 1989a;Bermejo Benito et al, 1998), immunomodulatory (Kumazawa et al, 1989;Leung et al, 2005;Sun et al, 2009), hepatoprotective (Abe et al, 1980;Fan et al, 2007;Wu et al, 2008), antinephritic Chen et al, 2008;Hattori et al, 2008), antibacterial and antiviral (Kumazawa et al, 1990;Chiang et al, 2003;Cheng et al, 2006), estrogenic (Wang et al, 2010b), and promoting amylase secretion in rat pancreatic acini (Yu et al, 2002). On the other hand, saikosaponins have also been reported to be responsible for toxicity induced by their hemolytic action (Abe et al, 1978a, b;Nose et al, 1989b).…”