Nardosinone

J Huazhong Univ Sci Technolog Med Sci. 2013 Dec;33(6):822-6.

Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy.[Pubmed: 24337842]

Pathological cardiac hypertrophy induced by angiotensin II (AngII) can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots of Nardostachys chinensis, a well-known traditional Chinese medicine.
METHODS AND RESULTS:
In order to investigate the effects of Nardosinone on AngII-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with Nardosinone (25, 50, 100, and 200 μmol/L) or AngII (1 μmol/L). Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with Nardosinone could significantly inhibit the enlargement of cell surface area induced by AngII. The mRNA expression of ANP, BNP and β-MHC was obviously elevated in AngII-treated H9c2 cells, which could be effectively blocked by Nardosinone at the concentration of 100 μmol/L. Further study revealed that the protective effects of Nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways.
CONCLUSIONS:
It was suggested that the inhibitory effect of Nardosinone on Ang II-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

PLoS One. 2014 Mar 10;9(3):e91260.

Nardosinone improves the proliferation, migration and selective differentiation of mouse embryonic neural stem cells.[Pubmed: 24614893]

In this study, we investigated the impact of Nardosinone, a bioactive component in Nardostachys root, on the proliferation and differentiation of neural stem cells.
METHODS AND RESULTS:
The neural stem cells were isolated from cerebrums of embryonic day 14 CD1 mice. The proliferation of cells was monitored using the cell counting kit-8 assay, bromodeoxyuridine incorporation and cell cycle analysis. Cell migration and differentiation were investigated with the neurosphere assay and cell specific markers, respectively. The results showed that Nardosinone promotes cells proliferation and increases cells migration distance in a dose-dependent manner. Nardosinone also induces the selective differentiation of neural stem cells to neurons and oligodendrocytes, as indicated by the expression of microtubule-associated protein-2 and myelin basic protein, respectively. Nardosinone also increases the expression of phospho-extracellular signal-regulated kinase and phospho-cAMP response element binding protein during proliferation and differentiation.
CONCLUSIONS:
In conclusion, this study reveals the regulatory effects of Nardosinone on neural stem cells, which may have significant implications for the treatment of brain injury and neurodegenerative diseases.

Brain Res Dev Brain Res. 2003 Nov 12;145(2):177-83.

Nardosinone, the first enhancer of neurite outgrowth-promoting activity of staurosporine and dibutyryl cyclic AMP in PC12D cells.[Pubmed: 14604758]

Nardosinone was isolated as an enhancer of nerve growth factor (NGF) from Nardostachys chinensis [Neurosci. Lett. 273 (1999) 53].
METHODS AND RESULTS:
Nardosinone (0.1-100 microM) enhanced dibutyryl cyclic AMP (dbcAMP, 0.3 mM)- and staurosporine (10 nM)-induced neurite outgrowth from PC12D cells in a concentration-dependent manner. PD98059 (20 microM), a potent mitogen-activated protein (MAP) kinase kinase inhibitor, partially blocked enhancements of dbcAMP (0.3 mM)- or staurosporine (10 nM)-induced neurite outgrowth by Nardosinone. Nardosinone alone had no effect on the phosphorylation of MAP kinase. The dbcAMP-induced increase in phosphorylation of MAP kinase was not affected by Nardosinone. Staurosporine almost unaffected the phosphorylation of MAP kinase, and Nardosinone potentiated the staurosporine-induced neurite outgrowth without stimulation of the phosphorylation of MAP kinase. Since it is known that MAP kinase signaling is required for neurite outgrowth in PC12D cells, these results suggest that Nardosinone enhances staurosporine- or dbcAMP-induced neurite outgrowth from PC12D cells, probably by amplifying both the MAP kinase-dependent and -independent signaling pathways of dbcAMP and staurosporine. It is also suggested that Nardosinone enhances a downstream step of MAP kinase in the MAP kinase-dependent signaling pathway.
CONCLUSIONS:
Nardosinone is the first enhancer of the neuritogenic action of dbcAMP and staurosporine and may become a useful pharmacological tool for studying the mechanism of action of not only NGF but also both the neuritogenic substances.

Yao Xue Xue Bao. 2013 Sep;48(9):1422-9.

[Nardosinone reduces neuronal injury induced by oxygen-glucose deprivation in primary cortical cultures].[Pubmed: 24358776]

The aim of the study is to investigate the effect of Nardosinone (Nar) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from embryos at gestational day 14.
METHODS AND RESULTS:
MTT method was used to determine the dosage regimen of Nar in primary neuronal cultures and observe the influence of Nar on the neurons suffering OGD; Western blotting analysis was used to detect expressions of protein kinase A (PKA), Ras related protein 1 (Rap1), mitogen-activated protein kinase kinase 1 (MEK1) and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) of OGD-injured or uninjured primary cultured neurons after Nar treatment. Results showed that Nar (50 and 100 micromol x L(-1)) improved the cell viability during OGD damage (P < 0.01) and increased the expression of PKA, Rap1, MEK1 and p-ERK1/2 in injured neurons. Additionally, elevations of PKA, Rapl, MEK1 and p-ERK1/2 in uninjured neurons were caused by Nar (50, 100 and 200 micromol x L(-1)) with a dose-dependent tenclency as well (P < 0.01).
CONCLUSIONS:
In conclusion, Nar could protect against the neuronal injury exposed to OGD, which may be relevant to the promotion of PKA and ERK signaling pathway.