Chinese Medicine Cistanche Deserticola Chemical Composition And Analysis Of Components in The Body

ABSTRACT

Cistanches Herba is a famous traditional Chinese medicine with a complex chemical composition. Traditional analytical methods are usually focused on phenylethanoid glycosides and it is difficult to achieve comprehensive quality control for the herba. Cistanches Herba has extremely high medicinal value for its treatment of anti-dementia, and anti-parkinsonism, protecting cerebral ischemia, and improving learning and memory. Cistanche glycosides are the main active ingredients which widely used in clinical to prevent and treat vascular dementia.However, the effective substances and action mechanisms of Cistanche Herba invivo have not been clearly defined, which seriously restricts its clinical application and further development.

To clarify the chemical components and improve the quality control system of Cistanches Herba, the chemical components of Herba were qualitatively and quantitatively characterized.1. Aiming to analyze the chemical profile of Cistanche herba (CH), the in-lab database was established and fragmentation pathways of primary chemical types were summarized based on literature data. Structural identification wasefficientlyaccurately identified for the main constituents via HPLC-IT-TOF-MS, a total of 45 compounds were assigned in negative mode.

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2. The contents of 23 hydrophilic and hydrophobic substances which spanned wide polarity(-3.326<cLogP<1.421)were quantified in 20 batches of ofCistanche herba using serially coupled reverse phase-hydrophilic interaction chromatography-tandem mass spectrometry (RPLC-HILIC-MS/MS), including three organic acids (ie. nicotinic acid, succinic acid, and ferulic acid), four nucleosides (i.e. uridine, adenosine, inosine, guanosine), two carbohydrates (i.e.mannitol and sucrose), one amino acid (i.e. phenylalanine), one benzyl-glucoside(i.e.cistanoside F), two lignans (i.e.alaschaniosideAandpinoresinol-β-D-glucopyranoside), seven phenylethanoid glycosides (i.e.salidroside, echinacoside, cistanoside A, tableside A, acetonide, isoacteoside.and 2'-acetylacteoside) and three iridoids (i.e. glucoside, 6-deoxycatalpol and8-epi-organic acid). On the other side, inferior parameters rather than the optimal ones were applied for those abundant ingredients to advance the upper limits of quantitation, such as echinacoside (1.35-387.50 mg/g), mannitol(13.45-110.00mg/g), and acetonide (0.75-85.90 mg/g), in mass spectrometer domain. Simultaneous quantification of the analytes that spanned a wide content range(more than 5 orders of magnitude) was achieved

RPLC-HILIC-MS/MS was configured the for simultaneous determination of components with wide polarity and content ranges in CH, which provided a basis for the quality standard ascension of CH and contributed to comprehensively understanding the metabolome of plants.

To elucidate the effective substances and action mechanism, the chemical composition of Cistanche Herba in vivo was qualitatively and quantitatively characterized.

1. To elucidate effective material basis and metabolic pathways of CH invivo, an in-lab database, and fragmentation pathways were built based on literature data,45 compounds assigned in CH, and extensive phase I and phase Ilmetabolic pathways. Metabolites in plasma, urine, and feces of rats were systematically characterized after oral administration of CH water extract by HPLC-IT-TOF-MS. A total of 82 prototypes and metabolites were tentatively identified, including 35 in plasma, 36 in urine, and 60 in feces, respectively. The results indicated that the main compounds of CH were easily hydrolyzed and metabolized into degradation products (i.e. caffeic acid, hydroxytyrosol and phenolic acid derivatives). Deglycosylation, sulfation, methylation, acetylationhydroxylation, hydrolysis, oxidation, reduction, and glucuronidation were considered as the primary metabolic pathways for the main constituents of CH. Moreover, sulfation, hydroxylation, and degradation mainly occurred in plasma.  Sulfation and glucuronidation almost occurred in urine while most compounds found in feces were the prototypes.

2. To illustrate the pharmacokinetic characteristics of constituents migrating in blood, pharmacokinetic profiles of19 compounds including endogenous components, and drug-derived components were researched in rather oral administration of CH using RPLC-HILIC-MS/MS, and concentration-time curves and pharmacokinetic parameters were obtained. This research preliminarily elucidated the chemical constituents, metabolic pathways in vivo and pharmacokinetic characteristics of componentscommigrating in the blood of CH, which provided a reference for CH efficacy material basis research, action mechanism, and clinical use.

KEY WORDS :Cistanches Herba;control;comprehensive qualityRPLC-HILIC-MS/MS; Pharmacokinetics; Endogenous components