Development of a systematic strategy for the global identification and classification of the chemical constituents and metabolites of Kai‐Xin‐San based on liquid chromatography with quadrupole time‐of‐flight mass spectrometry combined with multiple data‐processing approaches

Abstract

To rapidly identify and classify complicated components and metabolites for traditional Chinese medicines, a liquid chromatography with quadrupole time-of-flight mass spectrometry method combined with multiple data-processing approaches was established. In this process, Kai-Xin-San, a widely used classic traditional Chinese medicine preparation, was chosen as a model prescription. Initially, the fragmentation patterns, diagnostic product ions and neutral loss of each category of compounds were summarized by collision-induced dissociation analysis of representative standards. In vitro, the multiple product ions filtering technique was utilized to identify the chemical constituents for globally covering trace components. With this strategy, 108 constituents were identified, and compounds database was successfully established. In vivo, the prototype compounds were extracted based on the established database, and the neutral loss filtering technique combined with the drug metabolism reaction rules was employed to identify metabolites. Overall, 69 constituents including prototype and metabolites were characterized in rat plasma and nine constituents were firstly characterized in rat brain, which may be the potential active constituents resulting in curative effects by synergistic interaction. In conclusion, this study provides a generally applicable strategy to global metabolite identification for the complicated components in complex matrix and a chemical basis for further pharmacological research of Kai-Xin-San.

Novel applications of mass spectrometry‐based metabolomics in herbal medicines and its active ingredients: Current evidence

“…), Poria, and Acori Tatarinowii Rhizoma (dried rhizoma of Acortw tatarinowii Schott), is mainly used to treat neurasthenia and Alzheimer's disease (Liu et al, ; Chu et al, ). Wang et al () applied a ultra‐high performance liquid chromatography‐quadrupole time of flight mass spectrometry (UHPLC‐Q‐TOF MS) method to screen the effective chemical constituents of Kaixin San in vitro and in vivo . One hundred and eight compounds were identified in vitro and 69 components were characterized in vivo , of which were 47 prototype and 22 metabolites.…”

“…), Poria, and Acori Tatarinowii Rhizoma (dried rhizoma of Acortw tatarinowii Schott), is mainly used to treat neurasthenia and Alzheimer's disease (Liu et al, 2015a;Chu et al, 2016). Wang et al (2018) applied a ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF MS) method to FIGURE 3. Histogram of metabolomics manuscripts engaged in the study of herbal ingredients with the keywords ("herbal chemical composition" OR "herbal components" OR "phytoconstituents" OR "herbal constituents" OR "herbal ingredients" OR "ingredients of Chinese herbal medicine" OR "components of Chinese herbal medicines" OR "components of Chinese herb") in their abstracts were extracted from PubMed from January 2000 to December 2018. screen the effective chemical constituents of Kaixin San in vitro and in vivo.…”

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer’s Disease Based on Systems Biology

“…Wolf (PO), and Acorus tatarinowii Schott (AT) [20]. Recent researches of KXS were mainly focused on component identification or mechanism exploration, and most pathological studies were related to single pathway neurotransmitter regulation, which could not completely explain the therapeutic mechanism of KXS and the synergistic effects among the four single herbs [21,22]. Therefore, there is an urgent need to explain the multidimensional beneficial effects and synergism of KXS with systems biology methods.…”

Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

“…Wolf (PO), and Acorus tatarinowii Schott (AT) [6]. Based on literatures to date, researches of KXS were mainly focused on component identification or mechanism dissection, and most pathological studies were related to neurotransmitter regulation that involved a single pathway, which could not comprehensively elaborate therapeutic effects of KXS and the scientificity of AD treatment [7, 8]. Therefore, there is an urgent need for explaining multidimensional beneficial effects of KXS with modern biological methods.…”