Cherry leaf decoction inhibits NMDAR expression and thereby ameliorates CUMS- induced depression-like behaviors through downregulation of α2δ-1.

Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl-d-aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.

An UPLC-Q-TOF/MS-Based Analysis of the Differential Composition of Dendrobium officinale in Different Regions.

Dendrobium officinale (D. officinale) is a valuable traditional Chinese herbal medicine with high commercial value. In Chinese Pharmacopoeia (Ch.P., 2020 edition), the quality of D. officinale is mainly evaluated by its polysaccharide content. However, varying growth and production conditions, such as cultivation environment, origin, harvesting process, or processing methods, resulting in highly variable yields, quality, and composition. The aim of this study was to investigate whether the content of secondary metabolites in D. officinale from different origins is consistent with the polysaccharide content. The results showed that the polysaccharide content and pass rate were ranked as GX > AH > GZ > YN. Based on the nontargeted metabolomics approach, we searched for differential components in 22 different regions of D. officinale, including amides, bibenzyls, disaccharide, flavonoids, organic nitrogenous compounds, and phenolic glycosides. The overall expression was opposite to the polysaccharide, and the most expressed was YN, followed by GZ, AH, and GX. These results indicated that the current quality standard for evaluating the quality of D. officinale by polysaccharide content alone is imperfect, and small molecule compounds need to be included as quality markers.

Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop.

Cherry leaves (Prunus pseudocerasus Lindl. [Rosaceae]), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABAA and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop.

Liquiritigenin protects against myocardial ischemic by inhibiting oxidative stress, apoptosis, and L-type Ca2+ channels.

Liquiritigenin (Lq) offers cytoprotective effects against various cardiac injuries, but its beneficial effects on myocardial ischemic (MI) injury and the related mechanisms remain unclear. In the in vivo study, an animal model of MI was induced by intraperitoneal injection of isoproterenol (Iso, 85 mg/kg). ECG, heart rate, serum levels of CK and CK-MB, histopathological changes, and reactive oxygen species (ROS) levels were all measured. In vitro, H9c2 cells were divided into four groups and treated for 24 hr with liquiritigenin (30 µmol/L and 100 µmol/L) followed with CoCl2 (800 µmol/L) for another 24 hr. Cell viability, apoptosis, mitochondrial membrane potential, and intracellular Ca2+ concentration ([Ca2+ ]i ) were then assessed. The L-type Ca2+ current (ICa-L ) was detected using a patch clamp technique on isolated rat ventricular myocytes. The myocyte contraction and Ca2+ transients were measured using an IonOptix detection system. The remarkable cardiac injury and generation of intracellular ROS induced by Iso were alleviated via treatment with Lq. CoCl2 administration induced cell apoptosis, mitochondrial dysfunction, and Ca2+ overload in H9c2; Lq reduces these deleterious effects of CoCl2 . Meanwhile, Lq blocked ICa-L in a dose-dependent manner. The half-maximal inhibitory concentration of Lq was 110.87 µmol/L. Lq reversibly reduced the amplitude of cell contraction as well as the Ca2+ transients. The results show that Lq protects against MI injury by antioxidation, antiapoptosis, counteraction mitochondrial dysfunction, and inhibition of ICa-L , thus damping intracellular Ca2+ .

Protective effect of baicalin against arsenic trioxide-induced acute hepatic injury in mice through JAK2/STAT3 signaling pathway.

Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.