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Radix Astragali , a versatile traditional Chinese medicinal herb, has a rich history dating back to "Sheng Nong's herbal classic". It has been employed in clinical practice to address various ailments, including depression. One of its primary active components, total flavonoids from Astragalus (TFA), remains unexplored in terms of its potential antidepressant properties. This study delves into the antidepressant effects of TFA using a mouse model subjected to chronic unpredictable mild stress (CUMS). The study aimed to scrutinize how TFA influenced depressive behaviors, corticosterone and glutamate levels in the hippocampus, as well as myelin-related protein expression in CUMS mice. Additionally, it sought to explore the involvement of the Wnt/β-catenin/Olig2/Sox10 signaling axis as a potential antidepressant mechanism of TFA. Male C57BL/6 mice were subjected to CUMS to induce depressive behaviors. TFA were orally administered at two different doses (50 mg/kg and 100 mg/kg). A battery of behavioral tests, biochemical analyses, immunohistochemistry, UPLC-MS/MS, real-time PCR, and Western blotting were employed to evaluate the antidepressant potential of TFA. The role of the Wnt/β-catenin/Olig2/Sox10 signaling axis in the antidepressant mechanism of TFA was validated through MO3.13 cells. TFA administration significantly alleviated depressive behaviors in CUMS mice, as evidenced by improved sucrose preference, reduced immobility in tail suspension and forced swimming tests, and increased locomotor activity in the open field test. Moreover, TFA effectively reduced hippocampal corticosterone and glutamate levels and promoted myelin formation in the hippocampus of CUMS mice. Then, TFA increased Olig2 and Sox10 expression while inhibiting the Wnt/β-catenin pathway in the hippocampus of CUMS mice. Finally, we further confirmed the role of TFA in promoting myelin regeneration through the Wnt/β-catenin/Olig2/Sox10 signaling axis in MO3.13 cells. TFA exhibited promising antidepressant effects in the CUMS mouse model, facilitated by the restoration of myelin sheaths and regulation of corticosterone, glutamate, Olig2, Sox10, and the Wnt/β-catenin pathway. This research provides valuable insights into the potential therapeutic application of TFA in treating depression, although further investigations are required to fully elucidate the underlying molecular mechanisms and clinical relevance. TFA effectively alleviates depressive-like behaviors in CUMS model mice through various mechanisms, including the regulation of corticosterone and glutamate levels in the hippocampus, the enhancement of myelination, and the modulation of Olig2/Sox10 and the Wnt/β-catenin signaling pathways. [Display omitted] • TFA can improve depressive-like behavior in CUMS mice. • TFA can reduce hippocampal corticosterone and glutamate levels in depression mice. • TFA can improve hippocampal demyelination in CUMS depression mice. • TFA exert antidepressant effects by modulating the wnt/β-catenin/olig2/sox10 signaling axis. [ABSTRACT FROM AUTHOR]

Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey , Polygala tenuifolia , Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear. This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism. PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice. KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues. KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed ferroptosis in hippocampal neurons and myocardiocytes. [Display omitted] • KXS can improve learning and memory in mice with sleep deprivation. • KXS plays a cardioprotective role in mice with sleep deprivation. • KXS inhibits hippocampal neuron and cardiac ferroptosis in mice with sleep deprivation. [ABSTRACT FROM AUTHOR]

Radix Astragali is a traditional Chinese medicine with various pharmacological effects. Total astragalosides (TA), the main effective ingredients in Radix Astragali, exert properties including anti-oxidative stress, anti-neuroinflammation, and neuroprotection. We previously found that TA alleviated experimental autoimmune encephalomyelitis (EAE) progression, a widely used animal model of multiple sclerosis (MS). As a chronic demyelination disease, MS generally manifests myelin loss and fails to myelin regeneration. Regulation of oligodendrocyte progenitor cells (OPCs) differentiation and remyelination is the fundamental strategy for MS treatment. However, whether TA could directly promote OPCs differentiation and remyelination is still unknown. This study was aimed to investigate pro-differentiation and myelin regeneration effects of TA on OPCs and Cuprizone (CPZ)-induced demyelination mice, an animal model of MS, and to explore mechanism underlying from regulation of OPCs differentiation and maturation. Mice were orally given CPZ (400 mg/kg) daily for 4 weeks to induce myelin loss, and then treated with TA (25 and 50 mg/kg) daily for 1 week. Cell proliferation assay, Western blot, RT-PCR, immunocytochemistry and immunohistochemistry were performed to explore the mechanisms. The role of TA in oligodendrocyte differentiation and maturation was evaluated using MO3.13, a human oligodendrocytic hybrid cell line. TA was shown to mitigate behavioral impairment in CPZ-induced mice. It markedly ameliorated myelin loss and enhanced remyelination in the corpus callosum of mice, evidenced by increased expression of myelin basic protein (MBP) and the number of CC1+ newly generated oligodendrocytes (OLs). TA also enhanced the expression of MBP at both mRNA and protein levels in MO3.13 cells. In CPZ-induced mice and MO3.13 cells, TA remarkably promoted the activation of GSK3β, repressed the phosphorylation of β-catenin, reduced the expression of transcription factor 4 and inhibitor of DNA binding 2. The agonist of β-catenin, SKL2001, partially abolished the pro-differentiation effect of TA in MO3.13 cells. Taken together, we clarified that TA could effectively enhance the differentiation and maturation of OPCs and accelerate remyelination in CPZ-induced mice through inhibition of Wnt/β-catenin signaling pathway. This study provides new insight into the beneficial effect of TA in the treatment of MS. [Display omitted] • TA ameliorated myelin loss and accelerated remyelination in CPZ-induced mice. • TA increased expression of MBP and the number of CC1+ newly generated OLs. • TA enhanced the differentiation and maturation of OPCs by suppressing Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

In the long history of traditional Chinese medicine, Panax notoginseng has been used as a key herb for the treatment of blood diseases. Brain microvessels support adequate blood circulation to maintain normal physiological function, therefore, brain microcirculation disorder is an important therapeutic target for various brain diseases. However, the role of Xueshuantong (XST) injection composed of saponins from P. Notoginseng (PNS) in the amelioration of cerebral microcirculation disorder is unclear. Cerebral microcirculation disorder and inflammation play a vital role in stroke. Capillary endothelial cells and adjacent tight junctions are fundamental to the structure and function of cerebrovascule. XST injection has been used clinically in the treatment of stroke, but no studies have reported its indication in cerebral microcirculation disorder. This study is to explore the action and mechanism of XST injection in the alleviation of cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. MCAO/R rats and LPS-induced bEnd.3 cells were employed for the investigation of effect and mechanism of XST injection. Brain damages were evaluated by neurobehavioral assessment, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining (H&E), and Nissl staining. Morphology and density changes of cerebral microvessels were monitored by immunohistochemistry. Cell permeability was detected by measurement of trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. The mRNA and protein expressions of inflammatory cytokines, tight junction proteins, adhesion molecules, Janus kinase 2 (JAK2), signal transducer and activator of transcription-3 (STAT3), inhibitor of NF-κB (IκB), nuclear factor-κB (NF-κB) and c-jun N-terminal kinase (JNK) in brain microvessels and lipopolysaccharide (LPS)-induced bEnd.3 cells were measured by real-time PCR and Western blot, respectively. XST injection at 48 mg/kg significantly improved the neurological damage, inflammatory infiltration, and microvessel morphology, and increased microvessel density in brain of MCAO/R rats. The endothelial permeability was significantly mitigated by XST injection in LPS-induced bEnd.3 cells. Meanwhile, the tight junction proteins such as zona occludens 1 (ZO-1) and occludin were elevated remarkably in brain microvessel of MCAO/R rats and LPS-induced bEnd.3 cells. Moreover, the expression of inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), cycloocygenases 2 (COX-2), vascular cellular adhesion molecule-1 (VCAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 were inhibited by XST injection. In addition, XST injection suppressed the phosphorylation of JAK2, STAT3, IκB, NF-κB and JNK, which could be abolished by anisomycin, the JNK agonist. XST injection improved cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder. MCAO/R promotes microvascular endothelial cell activation and release of inflammatory mediators such as IL-1β, IL-6, TNF-α, VCAM-1 and MMP-9, and induces cerebral microcirculation disorder in rats. XST injection improves cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. [Display omitted] • XST injection improves cerebral microcirculation disorder in MCAO/R rats. • XST injection suppresses inflammatory response of the cerebral endothelial cells in MCAO/R rats. • XST injection inhibits the activation of JAK2/STAT3 and NF-κB signaling pathways by deactivation of JNK. [ABSTRACT FROM AUTHOR]

Artemisia annua L. (A. annua) is a traditional Chinese medicine that has been used since ancient times to treat malaria, eczema, dermatomycosis, jaundice, and boils. Modern pharmacological studies show that it has immunosuppressive and anti-inflammatory effects. However, the mechanism of A. annua in the treatment of atopic dermatitis (AD) remains unclear. This study was aimed to investigate the effect of A. annua water extract (AWE) on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model and tried to explore its possible underlying mechanisms. AD was induced in BALB/c mice by the topical repeated application of DNCB. Oral drug intervention of AWE and dexamethasone (DEX, positive control) began from the 7th day and continued for 13 consecutive days. The clinical skin score, ear thickness and the weight of ear and spleen were assessed. The ear tissue were stained with toluidine blue and hematoxylin and eosin (H&E) to detect inflammatory cell infiltration. IgE, terleukin (IL)-4 and IL-13 levels in the serum and IgE level in splenocytes were quantified by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-6, IL-13, IL-17, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP) were measured by quantitative real time polymerase chain reaction. The phosphorylation levels of mitogen-activated protein kinases (MAPKs)-p38 and nuclear factor (NF)-κB in ear tissue were detected by Western blot. Results demonstrated that AWE treatment significantly attenuated the AD-like symptoms in DNCB-induced BALB/c mice, including the skin dermatitis severity and ear edema. Further study disclosed that AWE treatment suppressed the expressions of IgE, IL-4, IL-6, IL-13, IL-17, TNF-α and TSLP at mRNA and protein levels. Moreover, AWE showed inhibitory effect on the phosphorylation of p38 MAPK and NFκB in ear tissues of AD mice. Collectively, our results suggested that AWE suppressed DNCB-induced AD in mice probably by restraining Th2 type inflammatory response. These findings might pave the road for the potential clinical application of AWE for AD treatment. [Display omitted] • AWE attenuated the AD-like lesions in DNCB-induced BALB/c mice. • AWE mitigated DNCB-induced mast cells and eosinophils infiltration. • AWE reduced Th2-related inflammatory responses in DNCB induced AD mice. • AWE inhibited the over-activation of p38MAPK/NFκB pathway in AD mice. [ABSTRACT FROM AUTHOR]

According to the Tang Dynasty classics Dietetic Material Medica and the Ming Dynasty classics Compendium of Materia Medica records, bear bile powder (BBP) has been used to treat a variety of diseases, such as febrile seizures, the pathogenesis of which is associated to neuroinflammation. However, the mechanism of BBP on alleviating neuroinflammation remains unclear. Microglia can be activated by peripheral lipopolysaccharide (LPS) and play an important role in the pathogenesis of neuroinflammation. The purpose of this study is to investigate the effects and mechanism of BBP in inhibiting LPS-induced microglia inflammation in vitro and in vivo. The anti-microglia inflammatory effects and mechanism of BBP were assessed in LPS-treated BV2 microglial cells and in LPS-treated mice. The mRNA expression levels of the inflammatory factor and the protein expressions of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), takeda G-protein coupled receptor 5 (TGR5), nuclear factor-κB (NF-κB), inhibitor of NF-κB (IκBɑ), protein kinase B (AKT) in BV2 cells, mouse hippocampus and cortex were detected. The NF-κB transcription activity and NF-κB nuclear translocation were observed. Our findings showed that BBP reduces branched process retraction and NO in LPS-treated BV2 cells, inhibits the protein expression of ionized calcium binding adaptor molecule 1 in the hippocampus of LPS-treated mice. Moreover, we observed that BBP decreases tumor necrosis factor α, interleukin (IL)-6 and IL-1β mRNA levels, deceases iNOS and COX-2 protein levels, increases TGR5 protein levels, suppresses the phosphorylation of AKT, NF-κB and IκBɑ protein in microglia both in vitro and in vivo. Further, we found that triamterene, the inhibitor of TGR5, abolishes the effects of BBP in LPS- treated BV2 cells. BBP inhibits LPS-induced microglia activation, and the mechanism of its action is partly through TGR5/AKT/NF-κB signaling pathway. Graphical abstract LPS induces significant amoebic morphorology of microglia. It inhibits the activation of the bile acid receptor TGR5. Meanwhile, LPS promotes the phosphorylation of AKT, NF-κB and IκBɑ and benefits NF-κB transcription activity, NF-κB nuclear translocation. However, BBP suppresses inflammatory reactions induced by activation of the AKT/NF-κB signaling pathway in LPS-treated microglia by activating and upregulating the expression of TGR5. [Display omitted] • Bear bile powder suppresses LPS-induced inflammatory responses in microglia. • Bear bile powder inhibits LPS-induced activation of AKT/NF-κB signaling pathway. • Bear bile powder activates the bile acid receptor TGR5 in microglia. [ABSTRACT FROM AUTHOR]

Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment. Image 1 [ABSTRACT FROM AUTHOR]