Saikosaponin C

Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by suppressing caspase-3 activation and subsequent degradation of focal adhesion kinase in human umbilical vein endothelial cells.[Pubmed: 24565837]

Biochem Biophys Res Commun. 2014 Mar 14;445(3):615-21.

Bacterial lipopolysaccharide (LPS) is an important mediator of inflammation and a potent inducer of endothelial cell damage and apoptosis. In this study, we investigated the protective effects of Saikosaponin C (SSc), one of the active ingredients produced by the traditional Chinese herb, Radix Bupleuri, against LPS-induced apoptosis in human umbilical endothelial cells (HUVECs).
METHODS AND RESULTS:
LPS triggered caspase-3 activation, which was found to be important in LPS-induced HUVEC apoptosis. Inhibition of caspase-3 also inhibited LPS-induced degradation of focal adhesion kinase (FAK), indicating that caspase-3 is important in LPS-mediated FAK degradation as well as in apoptosis in HUVECs. SSc significantly inhibited LPS-induced apoptotic cell death in HUVECs through the selective suppression of caspase-3. SSc was also shown to rescue LPS-induced FAK degradation and other cell adhesion signals. Furthermore, the protective effects of SSc against LPS-induced apoptosis were abolished upon pretreatment with a FAK inhibitor, highlighting the importance of FAK in SSc activity.
CONCLUSIONS:
Taken together, these results show that SSc efficiently inhibited LPS-induced apoptotic cell death via inhibition of caspase-3 activation and caspase-3-mediated-FAK degradation. Therefore, SSc represents a promising therapeutic candidate for the treatment of vascular endothelial cell injury and cellular dysfunction.

Saikosaponin C induces endothelial cells growth, migration and capillary tube formation.[Pubmed: 15581913]

Life Sci. 2004 Dec 31;76(7):813-26.

Saikosaponin C is one of the saikosaponins that are consisted in a Chinese herb, Radix Bupleuri. Recently, saikosaponins have been reported to have properties of cell growth inhibition, inducing cancer cells differentiation and apoptosis. However, Saikosaponin C had no correlation with cell growth inhibition. In this study, we investigated the role of Saikosaponin C on the growth of endothelial cells and angiogenesis.
METHODS AND RESULTS:
We found that Saikosaponin C yielded a potent effect on inducing human umbilical vein endothelial cells (HUVECs) viability and growth. In addition to inducing endothelial cells growth, Saikosaponin C also induced endothelial cells migration and capillary tube formation. The gene expression or activation of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF) and the p42/p44 mitogen-activated protein kinase (MAPK, ERK) that correlated with endothelial cells growth, migration and angiogenesis were also induced by Saikosaponin C.
CONCLUSIONS:
From these results, we suggest that Saikosaponin C may have the potential for therapeutic angiogenesis but is not suitable for cancer therapy.

Metabolism of saikosaponin c and naringin by human intestinal bacteria.[Pubmed: 18982483]

Arch Pharm Res. 1997 Oct;20(5):420-4.

METHODS AND RESULTS:
By human intestinal bacteria, Saikosaponin C was transformed to four metabolites, prosaikogenin E1 (E1) prosaikogenin E2 (E2), prosaikogenin E3 (E3) and saikogenin E. Metabolic time course of Saikosaponin C was as follows; in early time, Saikosaponin C was converted to E1 and E2, and then these were transformed to saikogenin E via E3. Also, this metabolic pathway was similar to the metabolism of Saikosaponin C by rat intestinal bacteria.Bacteroides JY-6 andBacteroides YK-4, the bacteria isolated from human intestinal bacteria, could transform saiko-saponin c to E via E1 (or E2) and E3. However, these bacteria were not able to directly transform E1 and E2 to saikogenin E.
CONCLUSIONS:
Naringin was mainly transformed to naringenin by human intestinal bacteria. The minor metabolic pathway transformed naringin to naringenin via prunin. By JY-6 or YK-4, naringin was metabolized to naringenin only via prunin.

Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species.[Pubmed: 14531019]

Planta Med. 2003 Aug;69(8):705-9.

Saikosaponins, the main active constituents of Bupleurum spp., have been shown to possess immunomodulatory, hepatoprotective, anti-tumor and anti-viral activities. In this study, saikosaponins a, c and d were evaluated for cytotoxicity and anti-hepatitis B virus ( HBV) activities.
METHODS AND RESULTS:
Results showed that, with the exception of saikosaponins a and d, HBV-transfected human hepatoma cells (2.2.15 cells) cultured with Saikosaponin C showed a significantly lower level of HBeAg in culture medium. Saikosaponin C also possessed activity in inhibiting HBV DNA replication; this inhibitory effect was not due to the cytotoxicity of Saikosaponin C or its effect on 2.2.15 cell proliferation. Although saikosaponin d exhibited cytotoxicity on 2.2.15 cells, it failed to inhibit HBV multiplication. The cytotoxicity of saikosaponin d against HepG2 human hepatocellular carcinoma cells was due to the induction of apoptosis through the activation of caspases 3 and 7, which subsequently resulted in poly-ADP-ribose-polymerase (PARP) cleavage. DNA fragmentation was clearly noted at more than 6 h after HepG2 cells exposure to saikosaponin d.
CONCLUSIONS:
The present study concludes that Saikosaponin C exhibits anti-HBV activity and saikosaponin d possesses potent cytotoxicity against human hepatocellular carcinoma cells.

Molecules. 2016 Jan 28;21(2):153.

Binding between Saikosaponin C and Human Serum Albumin by Fluorescence Spectroscopy and Molecular Docking.[Pubmed: 26828474 ]

Saikosaponin C (SSC) is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese) that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries.
METHODS AND RESULTS:
The binding of SSC to human serum albumin (HSA) was explored by fluorescence, circular dichroism (CD), UV-vis spectrophotometry, and molecular docking to understand both the pharmacology and the basis of the clinical use of SSC/Chaihu. SSC produced a concentration-dependent quenching effect on the intrinsic fluorescence of HSA, accompanied by a blue shift in the fluorescence spectra. The Stern-Volmer equation showed that this quenching was dominated by static quenching. The binding constant of SSC with HSA was 3.72 × 103 and 2.99 × 103 L·mol(-1) at 26 °C and 36 °C, respectively, with a single binding site on each SSC and HSA molecule. Site competitive experiments demonstrated that SSC bound to site I (subdomain IIA) and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for SSC-HSA association. The energy transfer efficiency and binding distance between SSC and HSA was calculated to be 0.23 J and 2.61 nm at 26 °C, respectively.
CONCLUSIONS:
Synchronous fluorescence and CD measurements indicated that SSC affected HSA conformation in the SSC-HSA complex. Molecular docking supported the experimental findings in conformational changes, binding sites and binding forces, and revealed binding of SSC at the interface between subdomains IIA-IIB.