Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition in cerebrovessels occurs in many AD patients and results in cerebral amyloid angiopathy (AD/CAA). Since Aβ can be transported across blood–brain barrier (BBB), aberrant Aβ trafficking across BBB may contribute to Aβ accumulation in the brain and CAA development. Expression analyses of 273 BBB-related genes performed in this study showed that the drug transporter, ABCG2, was significantly upregulated in the brains of AD/CAA compared with age-matched controls. Increased ABCG2 expression was confirmed by Q-PCR, Western blot, and immunohistochemistry. Abcg2 was also increased in mouse AD models, Tg-SwDI and 3XTg. Aβ alone or in combination with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial cells; however, conditioned media from Aβ-activated microglia strongly induced ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and coimmunoprecipitated with Aβ. Overexpression of hABCG2 reduced drug uptake in cells; however, interaction of Aβ_1–40with ABCG2 impaired ABCG2-mediated drug efflux. The role of Abcg2 in Aβ transport at the BBB was investigated in Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled Aβ_1–40or scrambled Aβ_40–1. Optical imaging analyses of live animals and their brains showed that Abcg2-null mice accumulated significantly more Aβ in their brains than wild-type mice. The finding was confirmed by immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at the BBB to prevent blood Aβ from entering into brain. ABCG2 upregulation may serve as a biomarker of CAA vascular pathology in AD patients.

Baizhu Shaoyao San (BSS) is a crucial traditional Chinese medicinal formula widely applied for the treatment of painful diarrhea, diarrhea-predominant irritable bowel syndrome, ulcerative colitis, and some other gastrointestinal diseases. Corresponding to the clinical medication, the three medicinal herbs (Atractylodis Macrocephalae Rhizoma, Paeoniae Radix Alba, and Citri Reticulatae Pericarpium) included in BSS should be processed using some specific methods of stir-frying. To find the underlying correlations between serum chemical profiles and curative effects of crude and processed BSS on ulcerative colitis rats, and further explore for the effective material basis of processing, an UHPLC/Q-TOF-MS/MS technique coupled with gray correlation analysis (GCA) was developed. A total of 134 compounds were identified in rat sera after oral administration of BSS, among which 24 compounds were prototypes and 110 compounds were metabolites. Meanwhile, an ulcerative colitis model was established in rats by enema with 2,4,6-trinitrobenzene sulfonic acid, and the pharmacodynamic indicators for drug efficacies were evaluated as well. According to the results, processed BSS showed better efficacy than crude BSS. The top 10 potential effective components with high degree of correlation were identified based on GCA results, which were thought to be the crucial compounds that contributed to the enhancement of therapeutic effects in BSS after processing.

Sinisan has been widely used to treat depression. However, its pharmacologically-effective constituents are largely unknown, and the pharmacological effects and clinical efficacies of Sinisan-containing processed medicinal herbs may change. To address these important issues, we developed an ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method coupled with multiple statistical strategies to analyze the compound profiles of Sinisan, including individual herb, herb-pair, and complicated Chinese medicinal formula. As a result, 122 different constituents from individual herb, herb-pair, and complicated Chinese medicinal formula were identified totally. Through the comparison of three progressive levels, it suggests that processing herbal medicine and/or altering medicinal formula compatibility could change herbal chemical constituents, resulting in different pharmacological effects. This is also the first report that saikosaponin h/i and saikosaponin g have been identified in Sinisan.

In Chinese medicine, the effect of promoting blood circulation and removing stasis could be enhanced after Chuanxiong Rhizoma is processed by wine. However, the relevant mechanism remains unclear. In this manuscript, a rapid and sensitive quantification method employing ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated to simultaneously determine butylidenephthalide, ligustilide, senkyunolide A and ferulic acid in rat plasma after oral administration of raw Chuanxiong Rhizoma (RCR) and wine-processed Chuanxiong Rhizoma (WCR) respectively. All analytes were extracted from plasma by proteins precipitation with methanol. Chromatographic separation was carried out on a Hypersil GOLD C₁₈ column by using a gradient mobile phase system of acetonitrile and water with 0.01% formic acid, the flow rate was 0.3 mL/min. For exact mass detecting, quick switching mode was used, positive and negative ions could be detected in one injection. The pharmacokinetic profiles of four components in the two groups were evaluated and compared. The results showed that, compared to the RCR group, the V_d and AUC_0→t values of four active compounds were increased and decreased respectively in WCR group, which revealed the effect of wine processing to Chuanxiong Rhizoma: the stronger the effect, the wider the distribution.