Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (−)-syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

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Valeriana jatamansi Jones is an important medicinal plant and its quality is closely related to its region of origin. In the current study, we utilized a flexible and powerful strategy for comprehensive evaluation of the quality diversity for 15 regions in China. The method was based on a hybrid linear ion trap-Orbitrap mass spectrometry platform. For structure characterization, fragmentation patterns were detected by analyzing a series of standard compounds using data dependent multistage mass spectrometry acquisition. A fragment ion database for valepotriates was established, and the acquired data were high throughput filtered by fragment ion search for compound identification. For quantitative purposes, we normalized the mass spectrometry data of 15 samples using SIEVE 2.0 and the differences in composition were analyzed using principal component analysis combined with hierarchical clustering analysis. The results identified a total of 92 compounds from Valeriana jatamansi Jones. Samples from Dali, Kunming, and Baoshan have better qualities and concentrations of the main active constituents. To verify our strategy, we compared the valtrate, acevaltrate, and baldrinal contents using high-performance liquid chromatography with diode array detector. We developed and validated a comprehensive qualitative and quantitative analytical method to achieve quality control of Valeriana jatamansi Jones.

Background Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. Results The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. Conclusions The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Purpose: XTR004 is a novel 18F-labeled myocardial perfusion imaging tracer that can be clinically used to assess myocardial ischemia from coronary artery disease. This study aimed to evaluate imaging characteristics of XTR004 after a single injection at rest in humans. Methods: Eleven healthy subjects (man=8) received an intravenous injection of 239-290 MBq (6.5-7.8 mCi) XTR004 and imaged with nine whole-body positron emission tomography (PET) scans within 4.7 h. Collection of blood and urine samples was concurrently performed for 7.25 h. Image processing utilized 3D registered PET and CT images to derive %ID and then calculated the radiation dose using a Hermes workstation with the embedded OLINDA/EXM program. The radioactive count profile was measured for whole-blood, plasma, and urine to characterize pharmacokinetics with the metabolic correction. The safety profile was evaluated during the day of dosing and three follow-up visits, including physical examination, vital signs, laboratory tests and adverse event observation. Results: Myocardial uptake of XTR004 was rapid, high, and stable throughout the PET imaging period. In the 0-12 min PET images, the top five organs of %ID were liver (26.81±4.01), kidney (11.43±2.49), lung (6.75±1.76), myocardium (4.72±0.67) and spleen (3.1±0.84). Mean values of Cmax, Tmax, t1/2, and AUC0-last calculated by the non-compartment model in corrected plasma were 0.0013896 %ID/g, 2.543 min, 45.171 min, and 0.03314 min* (%ID/g), respectively. Whole-body effective dose per unit of injected activity was 0.0165 mSv/MBq. Cumulative urine excretion (Cum Ae) was 8.18%. Treatment‐related adverse events occurred in seven subjects (63.6%) and were overall reported as stimulated pain at the injection site. No severe adverse event was collected. Conclusions: XTR004 having a favorable safety profile with rapid, high, and stable myocardial uptake in humans demonstrated an excellent potential for PET MPI. Further exploration of XTR004 PET MPI to detect myocardial ischemia can be warranted. (A Study of XTR004 PET Radiotracer in Healthy Volunteers, ClinicalTrials.gov number NCT05195879.)