Background: Bipolar disorder (BD) is a deleterious psychiatric disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine-associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders such as schizophrenia and substance user disorders. However, it is unknown whether TAAR1 is involved in the pathogenesis of BD. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of ouabain (OUA)-induced BD.
Methods: Intracerebroventricular (ICV) administration of OUA-induced BD model was established. The in vitro cell-based cAMP assay was used to examine TAAR1 agonism of PCC0105004. The receptor specificity of PCC0105004 was determined by an off-target panel assay that included radioligand binding and enzymatic assays. The effects of PCC0105004 on manic-like and depressive-like behaviors were evaluated in the rat BD model. TAAR1-mediated signaling and oxidative stress parameters were biochemically determined in the prefrontal cortex and the hippocampus of rats.
Results: Western blotting revealed reduced TAAR1 expression level in the prefrontal cortex but unchanged in the hippocampus in model rats. PCC0105004, a TAAR1 agonist with the agonism EC₅₀ value of 0.06182 μM, attenuated the manic-like behaviors on the 7th day and the depressive-like behaviors on the 14th day at doses that did not affect locomotor activity in the BD rats. Mechanistically, PCC0105004 exerted its behavioral effects via the reduction of ROS damage through the phosphorylation activation of the TAAR1/Akt/GSK3β/BDNF signaling pathway.
Conclusion: These results demonstrated the potential antimanic-like and antidepressant-like efficacy of a novel TAAR1 agonist PCC0105004 in rats and revealed its underlying molecular basis, which supports the possibility of TAAR1 agonists as candidate pharmacotherapeutics for BD.

Objective: Bipolar disorder (BD) affects more than 1% of the global population with limited therapeutic options. The neurokinin B (NKB)-neurokinin B receptor (NK3R) is involved in a variety of emotional activities. This study explored the role of NK3 receptor signaling in bipolar disorder.
Materials and methods: In this study, a model of intracerebroventricular (ICV) administration of OUA-induced BD was used to investigate the possible role of NK3R signaling in BD. The involvement of NK3R in the expression of OUA-induced BD was assessed by genetically knocking down the NK3R-encoding TACR3 gene with shRNA approach in the hippocampus and systemic administration of a NK3R antagonist ESN364,. Biochemical techniques were used to examine the NK3R-associated signaling changes and the oxidative stress parameters in the hippocampus of BD rats.
Results: The NK3R expression level was elevated in the hippocampus BD rats. Both TACR3 knockdown in the hippocampus and ESN364 treatment reversed the manic-like and depression-like behaviors in BD rats Inhibition of the NK3R signaling reversed oxidative stress-induced damage via upregulating the BDNF signaling pathway in the hippocampus.
Conclusion: These results demonstrated that NK3R signaling plays a key role in the pathogenesis of BD and that pharmacological antagonist of NK3R such as ESN364 could represent a novel therapeutic strategy for the management of BD.

Objective: Fuyuekang Lotion (FYKL) is an improved traditional Chinese medicine (TCM) prescription widely used to treat acute eczema (AE). However, the mechanism of action remains unclear. This study aimed to explore the therapeutic mechanism of FYKL in AE.
Methods: We revealed the underlying mechanism by utilizing a network pharmacology approach, molecular docking studies, and in vitro verification. The active compounds in FYKL were identified, and their targets were predicted. These targets were subsequently mapped to a component-target interaction network, with their therapeutic mechanisms predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to verify protein-binding efficacy. Potential key targets of FYKL against AE were further confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: The study identified 59 potential active compounds of FYKL, with quercetin, luteolin, and gallic acid suggested as critical active ingredients. Our findings suggest that these ingredients could exert their effects mainly by modulating the inflammatory immune response and promoting epidermal repair. FYKL was found to be a multi-target, multi-component drug that could potentially regulate the inflammatory immune response in AE through numerous pathways.
Conclusions: The findings from this study provide a scientific basis for further research into the therapeutic effects and mechanisms of FYKL in treating AE, underscoring the potential of TCM in modern therapeutics.

Background: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. The traditional China herb pairs such as Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian showed therapeutic effects on AS by clearing heat and resolving phlegm, invigorating blood and removing blood stasis, as well as aromatic resuscitation, respectively. However, the common and specific mechanisms of these pairs against the same disease are elusive.
Objective: This study aimed to explore the molecular mechanisms of 3 herb pairs treating AS by network pharmacology, molecular modeling and mechanism experiments.
Methods: The components and their corresponding targets of 3 herb pairs, as well as AS-related targets, were collected from multiple databases and literature. Then the protein-protein interaction network was built to identify the key components and targets associated with AS. The pathway enrichment analysis using KEGG was carried out for analyzing the common mechanisms of 3 herb pairs against AS. Finally, the binding modes of the key components and targets were analyzed by molecular docking and molecular dynamic simulation.
Results: The PPI network indicated that the common targets of 3 herb pairs focused on four pathways, including regulated vascular shear stress, TNF, ARE-RAGE, and IL-17 pathways. The molecular docking analysis indicated that the key component quercetin showed highest docking score with PTGS2 in comparison to other targets. Molecular dynamics simulations revealed that quercetin stably anchored to the active pocket of PTGS2 by forming hydrogen bonds with Thr175, Asn351, and Trp356.
Conclusion: The molecular mechanism of Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian against AS was preliminarily expounded, and we wish to provide a theoretical instruction for clinical treatment of AS.