Simultaneous Determination of Seven Lipophilic and Hydrophilic Components in Salvia miltiorrhiza Bunge by LC-MS/MS Method and Its Application to a Transport Study in a Blood-Brain-Barrier Cell Model.

Hui Wang,Mingyong Zhang,Yifeng Chai,Min Liu,Zhanying Hong,Yuzhen He,Jiahao Fang

doi:10.3390/molecules27030657

Abstract

Salvia miltiorrhiza Bunge (SM) has been extensively used in Alzheimer’s disease treatment, the permeability through the blood-brain barrier (BBB) determining its efficacy. However, the transport mechanism of SM components across the BBB remains to be clarified. A simple, precise, and sensitive method using LC-MS/MS was developed for simultaneous quantification of tanshinone I (TS I), dihydrotanshinone I (DTS I), tanshinone IIA (TS IIA), cryptotanshinone (CTS), protocatechuic aldehyde (PAL), protocatechuic acid (PCTA), and caffeic acid (CFA) in transport samples. The analytes were separated on a C18 column by gradient elution. Multiple reaction monitoring mode via electrospray ionization source was used to quantify the analytes in positive mode for TS I, DTS I, TS IIA, CTS, and negative mode for PAL, PCTA, and CFA. The linearity ranges were 0.1–8 ng/mL for TS I and DTS I, 0.2–8 ng/mL for TS IIA, 1–80 ng/mL for CTS, 20–800 ng/mL for PAL and CFA, and 10–4000 ng/mL for PCTA. The developed method was accurate and precise for the compounds. The relative matrix effect was less than 15%, and the analytes were stable for analysis. The established method was successfully applied for transport experiments on a BBB cell model to evaluate the apparent permeability of the seven components.

Highlights

Alzheimer’s disease (AD) is the leading cause of dementia and one of the significant healthcare challenges of the 21st century [1]
The results demonstrated that the water-soluble analytes in the negative ionization mode expressed high intensity and good sensitivity of precursor and product ions
The results showed no significant differences in the retention time among these conditions, while the column pressure at 0.400 mL/min was increased

Summary

Introduction

Alzheimer’s disease (AD) is the leading cause of dementia and one of the significant healthcare challenges of the 21st century [1]. AD is an age-related neurodegenerative disorder characterized by progressive cognitive decline and memory loss [2]. Research since the discoveries of amyloid β (Aβ) and tau protein, the main components of senile plaque (SP), and neuro-fibrillary tangles (NFT), respectively, has provided detailed information about molecular pathogenetic events of AD [3]. Oxidative stress, mitochondrial dysfunction, excessive reactive oxygen species production, lipid peroxidation, proteasomal dysfunction, microglial activation, neurotransmitter alteration, and neuroinflammation have been implicated in AD pathology [4]. The cause of AD is poorly known, and there are no curative treatments despite the major expenditure of research and money over many decades [5]. Current treatment strategies only provide symptomatic relief. The common drugs, including cholinesterase inhibitors, N-methyl-D-aspartic acid (NMDA)

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