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...[ Read more ]

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.