| In vitro: |
| Biochem Biophys Res Commun. 2014 Mar 14;445(3):615-21. | | 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] | 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. | | Life Sci. 2004 Dec 31;76(7):813-26. | | Saikosaponin C induces endothelial cells growth, migration and capillary tube formation.[Pubmed: 15581913] | 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. | | J Neurochem . 2016 Mar;136(6):1232-1245. | | A potential therapeutic effect of saikosaponin C as a novel dual-target anti-Alzheimer agent[Pubmed: 26710244] | | Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disease and the risk of developing it increases with advancing age. In this study, we investigated the protective effects of Saikosaponin C (SSc), one of the main bioactive components produced by the traditional Chinese herb, radix bupleuri, the root of Bupleurum falcatum, against AD in various neuronal models. Interestingly, we found that SSc has dual effects on AD by targeting amyloid beta (Aβ) and tau, two key proteins in AD. SSc significantly suppressed the release of both Aβ peptides 1-40 and 1-42 into cell culture supernatants, though it does not affect BACE1 activity and expression. SSc also inhibited abnormal tau phosphorylation at multiple AD-related residues. Moreover, SSc seems to have beneficial effects on cellular tau function; it accelerated nerve growth factor-mediated neurite outgrowth and increased the assembly of microtubules. In addition, SSc increased synaptic marker proteins such as synaptophysin and PSD-95. Considering its various biological activities, our results suggest that SSc might be a novel therapeutic tool for treating human AD and other neurodegenerative diseases. Tau and amyloid beta are two key features in Alzheimer's disease. Saikosaponin C, an active component of Bupleuri Radix, inhibits abnormal tau phosphorylation and amyloid beta production, thereby promoting synaptic integrity. Saikosaponin C also prevents amyloid beta-induced apoptosis in brain vascular endothelial cells. Therefore, Saikosaponin C may provide a new therapeutic strategy for treatment of neurodegenerative diseases, including Alzheimer's disease.
Keywords: Alzheimer's disease; amyloid beta; neurodegenerative diseases; Saikosaponin C; tau; therapeutic tool. |
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