Acori Tatarinowii Rhizoma (ATR, the dried rhizome of Acorus tatarinowii
Schott) has long been one of the most important traditional herbal medicines in
Asian countries. Several lines of evidence have suggested the application of ATR
and its main ingredients, i.e. α-asarone and β-asarone, in treatment of
neurological disorders. However, the action mechanisms of ATR have not been
done. Due to the clinical and bioactive properties of ATR, the neuro- beneficial
and neuro-protective function of α-asarone, β-asarone and volatile oil from ATR
were studied in different cell models.
Authentication of ATR was investigated by different methods, including
macroscopic and microscopic identification, chemical profiling and DNA
authentication. The quality control parameters of ATR were const...[
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Acori Tatarinowii Rhizoma (ATR, the dried rhizome of Acorus tatarinowii
Schott) has long been one of the most important traditional herbal medicines in
Asian countries. Several lines of evidence have suggested the application of ATR
and its main ingredients, i.e. α-asarone and β-asarone, in treatment of
neurological disorders. However, the action mechanisms of ATR have not been
done. Due to the clinical and bioactive properties of ATR, the neuro- beneficial
and neuro-protective function of α-asarone, β-asarone and volatile oil from ATR
were studied in different cell models.
Authentication of ATR was investigated by different methods, including
macroscopic and microscopic identification, chemical profiling and DNA
authentication. The quality control parameters of ATR were constructed by
measuring the amount of α-asarone and β-asarone, as well as the establishment
of HPLC fingerprint chromatogram. The total amount of volatile oil was measured
and the chemical composition of volatile oil was analyzed by GC-MS, and more
than 40 compounds were identified. α-Asarone and β-asarone accounted for
more than 95% of the total volatile oil. Here, we recommended a standardized
ATR extract should contain at least 1.06 and 6.65 mg of α-asarone and β-asarone
in 1 g of dried herb; and at least 1% (v/w) of total volatile oil by weight of dried
herb.
The application of α-asarone, β-asarone, or ATR oil, potentiated the nerve
growth factor (NGF)-induced neurite outgrowth as well as the neurofilaments
(NFs) expressions in PC12 cells. The application of H89, a protein kinase A (PKA)
inhibitor, partially blocked the asarone/ATR oil-induced neurite outgrowth and
neurofilament expression. In addition, the induction of cAMP responsive element
binding protein (CREB) phosphorylation was observed in asarone/ATR oil-treated
cultures, and the effect of which was fully blocked by H89. Moreover,
asarone or ATR oil was found to stimulate the expressions of synaptic proteins in
cultured neurons. Asarone or ATR oil stimulated the synthesis and secretion of
the neurotrophic factors, i.e. NGF, brain-derived neurotrophic factor (BDNF) and
glial cell-derived neurotrophic factor (GDNF). These results supported the neuro-beneficial
role of α-asarone, β-asarone or ATR oil on the brain.
In neuro-protective function, application of asarone or ATR oil dose-dependently
reduced tBHP-induced cell death as well as intracellular reactive
oxygen species (ROS) formation. Besides, α-asarone, β-asarone or ATR oil
increased the transcriptional activity of pARE-Luc in dose-dependent manner. In
addition, α-asarone, β-asarone, or ATR oil, activated the phosphorylation of Akt.
The treatment of LY294002, an Akt inhibitor, significantly inhibited the
asarone/ATR oil-mediated ARE transcriptional activity, as well as the
asarone/ATR oil mediated cell protective effect. On the other hands, α-asarone,
β-asarone or ATR oil markedly inhibited the processing of Aβ
1-42 from its
monomeric form into fibrils. Furthermore, a significant reduction of cytotoxicity
was observed in cortical neurons which were treated with asarone/ATR oil-modified
Aβ aggregates. Asarone or ATR oil exerted their strong neuro-protection
by blocking the apoptosis induced by Aβ, and/or activating Akt survival pathway
in neurons.
The results provided by this thesis have achieved four different aspects of
ATR and its active ingredient: (i) authentication and chemical standardization; (ii)
neuronal differentiation; (iii) synaptogenesis and neurotrophic factor regulation;
and (vi) neuro-protection. Overall, the proposed chemical standardization
parameters could be applied for the quality control of ATR; and this standardized
ATR might be considered as the good candidates in developing potential drugs,
in treating, or preventing different neurological disorders.
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