The anti-depression effect and potential mechanism of the petroleum ether fraction of CDB: Integrated network pharmacology and metabolomics.

The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.

Traditional Chinese medicine and mitophagy: A novel approach for cardiovascular disease management.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, imposing an enormous economic burden on individuals and human society. Laboratory studies have identified several drugs that target mitophagy for the prevention and treatment of CVD. Only a few of these drugs have been successful in clinical trials, and most studies have been limited to animal and cellular models. Furthermore, conventional drugs used to treat CVD, such as antiplatelet agents, statins, and diuretics, often result in adverse effects on patients' cardiovascular, metabolic, and respiratory systems. In contrast, traditional Chinese medicine (TCM) has gained significant attention for its unique theoretical basis and clinical efficacy in treating CVD. PURPOSE: This paper systematically summarizes all the herbal compounds, extracts, and active monomers used to target mitophagy for the treatment of CVD in the last five years. It provides valuable information for researchers in the field of basic cardiovascular research, pharmacologists, and clinicians developing herbal medicines with fewer side effects, as well as a useful reference for future mitophagy research. METHODS: The search terms "cardiovascular disease," "mitophagy," "herbal preparations," "active monomers," and "cardiac disease pathogenesis" in combination with "natural products" and "diseases" were used to search for studies published in the past five years until January 2024. RESULTS: Studies have shown that mitophagy plays a significant role in the progression and development of CVD, such as atherosclerosis (AS), heart failure (HF), myocardial infarction (MI), myocardial ischemia/reperfusion injury (MI/RI), cardiac hypertrophy, cardiomyopathy, and arrhythmia. Herbal compound preparations, crude extracts, and active monomers have shown potential as effective treatments for these conditions. These substances protect cardiomyocytes by inducing mitophagy, scavenging damaged mitochondria, and maintaining mitochondrial homeostasis. They display notable efficacy in combating CVD. CONCLUSION: TCM (including herbal compound preparations, extracts, and active monomers) can treat CVD through various pharmacological mechanisms and signaling pathways by inducing mitophagy. They represent a hotspot for future cardiovascular basic research and a promising candidate for the development of future cardiovascular drugs with fewer side effects and better therapeutic efficacy.

The extraction, purification, structural features, bioactivities, and applications of Schisandra chinensis polysaccharides: A review.

Schisandra chinensis, as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo, including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields.

Potential therapeutic effects of Chinese herbal medicine in postpartum depression: Mechanisms and future directions.

ETHNOPHARMACOLOGICAL RELEVANCE: Postpartum depression (PPD) is a common psychiatric disorder in women after childbirth. Per data from epidemiologic studies, PPD affects about 5%-26.32% of postpartum mothers worldwide. Biological factors underlying this condition are multiple and complex and have received extensive inquiries for the roles they play in PPD. Chinese herbal medicine (CHM), which is widely used as a complementary and alternative therapy for neurological disorders, possesses multi-component, multi-target, multi-access, and low side effect therapeutic characteristics. CHM has already shown efficacy in the treatment of PPD, and a lot more research exploring the mechanisms of its potential therapeutic effects is being conducted. AIM OF THE REVIEW: This review provides an in-depth and comprehensive overview of the underlying mechanisms of PPD, as well as samples the progress made in researching the potential role of CHM in treating the disorder. MATERIALS AND METHODS: Literature was searched comprehensively in scholarly electronic databases, including PubMed, Web of Science, Scopus, CNKI and WanFang DATA, using the search terms "postpartum depression", "genetic", "hormone", "immune", "neuroinflammation", "inflammation", "neurotransmitter", "neurogenesis", "brain-gut axis", "traditional Chinese medicine", "Chinese herbal medicine", "herb", and an assorted combination of these terms. RESULTS: PPD is closely associated with genetics, as well as with the hormones, immune inflammatory, and neurotransmitter systems, neurogenesis, and gut microbes, and these biological factors often interact and work together to cause PPD. For example, inflammatory factors could suppress the production of the neurotransmitter serotonin by inducing the regulation of tryptophan-kynurenine in the direction of neurotoxicity. Many CHM constituents improve anxiety- and depression-like behaviors by interfering with the above-mentioned mechanisms and have shown decent efficacy clinically against PPD. For example, Shen-Qi-Jie-Yu-Fang invigorates the neuroendocrine system by boosting the hormone levels of hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes, regulating the imbalance of Treg/T-helper cells (Th) 17 and Th1/Th2, and modulating neurotransmitter system to play antidepressant roles. The Shenguiren Mixture interferes with the extracellular signal-regulated kinase (ERK) pathway to enhance the number, morphology and apoptosis of neurons in the hippocampus of PPD rats. Other herbal extracts and active ingredients of CHM, such as Paeoniflorin, hypericin, timosaponin B-III and more, also manage depression by remedying the neuroendocrine system and reducing neuroinflammation. CONCLUSIONS: The pathogenesis of PPD is complex and diverse, with the main pathogenesis not clear. Still, CHM constituents, like Shen-Qi-Jie-Yu-Fang, the Shenguiren Mixture, Paeoniflorin, hypericin and other Chinese Medicinal Formulae, active monomers and Crude extracts, treats PPD through multifaceted interventions. Therefore, developing more CHM components for the treatment of PPD is an essential step forward.

Saikosaponin a activates tet1/dll3/notch1 signalling and promotes hippocampal neurogenesis to improve depression-like behavior in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri, also named "Chaihu" in Chinese, is a substance derived from the dry roots of Bupleurum chinense DC. [Apiaceae] and Bupleurum scorzonerifolium Willd. [Apiaceae]. Radix Bupleuri was initially recorded as a medicinal herb in Shen Nong Ben Cao Jing, the earliest monograph concerning traditional Chinese medicine (TCM). Ever since, Radix Bupleuri has been broadly used to alleviate exterior syndrome, disperse heat, modulate the liver-qi, and elevate yang-qi in TCM. Radix Bupleuri has also been utilized as an important component in Xiaoyaosan, a classical formula for relieving depression, which was originated from the famous Chinese medical book called "Tai Ping Hui Min He Ji Ju Fang" in Song Dynasty. Currently, many valuable pharmacological effects of Radix Bupleuri have been explored, such as antidepressant, neuroprotective activities, antiinflammation, anticancer, immunoregulation, etc. Former studies have illustrated that Saikosaponin A (SSa), one of the primary active components of Radix Bupleuri, possesses potential antidepressant properties. However, the underlying mechanisms still remain unknown. AIM OF THE STUDY: We used a chronic social defeat stress (CSDS) mouse model to explore the ameliorative effects and potential mechanisms of SSa in depressive disorder in vivo. MATERIALS AND METHODS: The CSDS mouse model was established and mice underwent behavioral studies using assays such as the social interaction test (SIT), sucrose preference test (SPT), forced-swim test (FST), tail suspension test (TST), and open field test (OFT). Western blotting, immunofluorescence, and Golgi staining were performed to investigate signaling pathway activity, and alterations in synaptic spines in the hippocampus. To model the anticipated interaction between SSa and Tet1, molecular docking and microscale thermophoresis (MST) techniques were employed. Finally, sh-RNA Tet1 was employed for validation via lentiviral transfection in CSDS mice to confirm the requirement of Tet1 for SSA efficacy. RESULTS: SSa dramatically reduced depressed symptoms, boosted the expression of Tet1, Notch, DLL3, and BDNF, encouraged hippocampus development, and enhanced the dendritic spine density of hippocampal neurons. In contrast, Tet1 knockdown in CSDS mice dampened the beneficial effects of SSa on depressive symptoms. CONCLUSIONS: Therefore, our results suggest that SSa significantly activates the Tet1/Notch/DLL3 signaling pathways and promotes hippocampal neurogenesis to exert antidepressant effects in the CSDS mouse model in vivo. The present results also provide new insight into the importance of the Tet1/DLL3/Notch pathways as potential targets for novel antidepressant development.

The antidepressant-like effects of Danzhi Xiaoyao San and its active ingredients.

BACKGROUND: Depression is a severe mental illness that endangers human health. Depressed individuals are prone to sleep less and to the loss of appetite for food; their thinking and cognition processes, as well as mood, may even be affected. Danzhi Xiaoyao San (DXS), documented in the Internal Medicine Summary, has been used for hundreds of years in China and is widely applied traditionally to treat liver qi stagnation, liver and spleen blood deficiency, menstrual disorders, and spontaneous and night sweating. DXS can also clear heat and drain the liver. Presently, it is used frequently in the treatment of depression based on its ability to clear the liver and alleviate depression. PURPOSE: To summarize clinical and preclinical studies on the antidepressant-like effects of DXS, understand the material basis and mechanisms of these effects, and offer new suggestions and methods for the clinical treatment of depression. METHODS: "Danzhi Xiaoyao", "Danzhixiaoyao", "Xiaoyao", "depression" and active ingredients were entered as keywords in PubMed, Google Scholar, CNKI and WANFANG DATA databases in the search for material on DXS and its active ingredients. The PRISMA guidelines were followed in this review process. RESULTS: Per clinical reports, DXS has a therapeutic effect on patients with depression but few side effects. DXS and its active ingredients allegedly produce their neuroprotective antidepressant-like effects by modulating monoamine neurotransmitter levels, inhibiting the hypothalamic-pituitary-adrenal (HPA) axis hyperfunction, reducing neuroinflammation and increasing neurotrophic factors. CONCLUSION: Overall, DXS influences multiple potential mechanisms to exert its antidepressant-like effects thanks to its multicomponent character. Because depression is not caused by a single mechanism, probing the antidepressant-like effects of DXS could further help understand the pathogenesis of depression and discover new antidepressant drugs.

Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity.

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-ß-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

[Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research].

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.

Jing-Fang n-butanol extract and its isolated JFNE-C inhibit ferroptosis and inflammation in LPS induced RAW264.7 macrophages via STAT3/p53/SLC7A11 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has accumulated valuable experience in the treatment of inflammatory diseases caused by Ferroptosis. Jing Jie and Fang Feng are two warm acrid exterior-resolving medicinal herbs that play an important role in the prevention and treatment of inflammatory diseases. The pairing of the two forms a drug pair (Jing-Fang) that shows significant advantages in fighting oxidative stress and inflammation. Whereas, the underlying mechanism needs to be further improved. AIM OF THE STUDY: In this study, the anti-inflammatory effect of Jing-Fang n-butanol extract (JFNE) and its isolate C (JFNE-C) on LPS-induced RAW264.7 cells and the regulation effect on ferroptosis were investigated, and also the mechanism of STAT3/p53/SLC7A11 signal pathway-related to ferroptosis. MATERIALS AND METHODS: Jing-Fang n-butanol extract (JFNE) and its active isolate (JFNE-C) were extracted and isolated. LPS-induced inflammation model in RAW264.7 cells was established to assess the anti-inflammatory effect and ferroptosis mechanism of JFNE and JFNE-C. The levels of interleukin 6 (IL-6), interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were measured. The activity levels of antioxidant substances such as glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were measured. Flow cytometry, immunofluorescence and transmission electron microscopy were used to assess ROS level, ferrous iron content and mitochondrial morphological changes. Through administration of Ferrostatin-1 (Fer-1), an ferroptosis inhibitor, to verify the role of JFNE and JFNE-C in regulating ferroptosis in resistance to the inflammatory response. Western blotting was used to determine whether the JFNE and JFNE-C exerted effectiveness by modulating the STAT3/p53/SLC7A11 signaling pathway. In addition, the important role of STAT3/p53/SLC7A11 signaling pathway in drug regulation of ferroptosis and inflammatory response was further validated by administration of S3I-201 (STAT3 inhibitor). Finally, high performance liquid chromatography-mass spectrometry (HPLC-MS) was used to determine the major active components of JFNE and JFNE-C. RESULTS: The results showed that treated with JFNE-C significantly reduced the contents of interleukin 6 (IL-6), interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in the supernatant of LPS-induced RAW264.7 cells. The pretreatment with JFNE and JFNE-C significantly decreased intracellular oxidative stress levels, including reductions of ROS and MDA levels, and increases of GSH-Px, SOD and GSH levels. In addition, JFNE and JFNE-C obviously reduced intracellular ferrous iron level, and JFNE-C was effective in alleviating mitochondrial damage which includes mitochondrial shrinkage, increase of mitochondrial membrane density and reduction and absence of cristae. Further results indicated that JFNE-C showed a reduction of p53 and p-p53 protein levels in LPS-induced RAW264.7 cells, while significantly increasing the protein expression levels of STAT3, p-STAT3, SLC7A11 and GPX4. Besides, JFNE-C contains key active substances such as 5-O-Methylvisammioside, Hesperidin and Luteolin. Remarkably, this is different from JFNE, which is rich in nutrients such as sucrose, choline and various amino acids. CONCLUSION: These results suggest that JFNE and JFNE-C may exert anti-inflammatory effect through activating the STAT3/p53/SLC7A11 signaling pathway to inhibit ferroptosis.

[Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine].

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

[Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang"].

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1ß(IL-1ß), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1ß, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1ß in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

[Mechanism of essential oil from Schizonepeta tenuifolia in treatment of depression based on network pharmacology and experimental verification].

This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1ß was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1ß and pro IL-1ß in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, and cyclic adenosine monophosphate(cAMP) signaling pathway. Biological processes such as synaptic signal transduction, G-protein coupled receptor signaling pathway, and chemical synaptic transmission were involved. Molecular functions such as neurotransmitter receptor activity, RNA polymerase Ⅱ transcription factor activity, and heme binding were involved. In mice experiments, the results showed that EOST at 100 mg·kg~(-1) and 50 mg·kg~(-1) significantly shortened the immobility time in TST and FST as well as the feeding latency in NSFT compared with the model group, decreased the levels of serum IL-1ß and NO, and reduced the protein expression levels of IL-1ß and pro IL-1ß in the hippocampus. In conclusion, EOST shows a good antidepressant effect in a multi-component, multi-target, and multi-pathway manner. The mechanism may be attributed to the fact that EOST can down-regulate the protein expression levels of IL-1ß and pro IL-1ß, decrease the release of inflammatory factors, and reduce neuroinflammation response.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Dietary replacement of soybean meal by fermented feedstuffs for aged laying hens: effects on laying performance, egg quality, nutrient digestibility, intestinal health, follicle development, and biological parameters in a long-term feeding period.

This study aimed to investigate the effects of dietary supplementation with fermented soybean meal (FSM) or fermented miscellaneous meal (FMM, cottonseed meal: coconut meal = at a 1:1 ratio) on the intestinal health, laying performance, egg quality, and follicle development of laying hens. A total of 1,008 54-wk-old laying hens were randomly divided into 7 treatment groups and fed a corn-soybean base diet in addition to 2%, 4%, and 8% FSM or FMM. The results showed that fermentation increased the contents of crude protein, amino acids (Ser, Gly, Cys, Leu, Lys, His, and Arg), and organic acids (butyric acid, citric acid, succinic acid) and decreased the contents of neutral and acid detergent fiber in the soybean and miscellaneous meals (P < 0.05). Compared with the results found for the control group, feeding with 4% FSM increased the egg production, egg mass and average daily feed intake (ADFI), and feeding with 4% FMM increased the ADFI of laying hens (P < 0.05). Furthermore, feeding with 8% FMM reduced the productive performance and laying performance, supplementation with 4% FSM increased the eggshell strength and weight, and 2 to 4% FSM increased the egg albumen height and Haugh unit (P < 0.05). Moreover, 2 to 8% FSM or 2 to 4% FMM enhanced the apparent digestibility of dry matter, crude protein, and NDF for laying hens (P < 0.05). The relative weight, villus height, crypt depth, and villus:crypt ratio of the jejunum were higher in the 4% FSM- and FMM-fed groups (P < 0.05). Moreover, diamine oxidase (DAO) activity, transepithelial electrical resistance (TEER), and the expression of tight junction proteins (ZO-1, Occluding, and Claudin1), the intestinal stem cell marker Lgr5, and the proliferation cell marker proliferating cell nuclear antigen (PCNA) was upregulated in the jejunum of laying hens fed 4% FSM and FMM (P < 0.05). The relative weight of the ovaries, and the number of small yellow follicles and large white follicles were elevated after 4% FSM or FMM supplementation. Furthermore, the levels of serum follicle-stimulating hormone and luteinizing hormone were increased in the 4% FSM and FMM groups (P < 0.05). In conclusion, the supplementation of laying hen feed with FSM and FMM improved the laying performance, egg quality, intestinal barrier function, and follicle development of aged laying hens, and 4% FSM supplementation was optimal.

Isolation, structure and bioactivity of polysaccharides from Atractylodes macrocephala: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Polysaccharides from Atractylodes macrocephala are important components isolated and extracted from the traditional Chinese medicine named Atractylodes macrocephala Koidz. Traditionally, A. macrocephala has been used to strengthen the spleen, benefit qi, dry dampness and promote water circulation, and prevent miscarriage. As the main components, polysaccharides from A. macrocephala have a variety of related pharmacological activities, such as the ability to regulate the gastrointestinal tract, protect the liver and so on. AIM OF THE REVIEW: This review aims to compile the extraction and purification methods, structural characteristics and pharmacological activities of polysaccharides from A. macrocephala and the mechanisms of actions to explore the future application potential of polysaccharides from A. macrocephala. MATERIALS AND METHODS: Valid and comprehensive relevant information was collected from China National Knowledge Infrastructure, Web of Science, Pubmed and so on. RESULTS: More than 20 polysaccharides have been extracted from A. macrocephala, different extraction and purification methods have been described, and the composition structures and pharmacological activities of polysaccharides from A. macrocephala have been reviewed. Polysaccharides, as important components of A. macrocephala, were mainly extracted by four methods such as water decoction, ultrasonic-assisted extraction, complex enzyme method and microwave-assisted extraction, and then were obtained through decolorization, deproteinization and separation and purification by various chromatographic columns. The chemical compositions and structures of polysaccharides from A. macrocephala show diversification, and three structural formulae have been confirmed at this stage. Polysaccharides from A. macrocephala have a variety of pharmacological activities, such as immunomodulation, antitumor, antioxidant, hepatoprotection, gastrointestinal mucosa protection, neuroprotection, hypoglycemia, growth promotion and so on. CONCLUSIONS: There is a diversity in the compositional structures of polysaccharides from A. macrocephal, which have multiple biological activities and promising applications. Therefore, further understanding of the relationship between structures and functions of polysaccharides from A. macrocephaly, and potential synergistic effects with other substances is especially important for its development and utilization.

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis.

Objectives: Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney. Conclusion: Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

The antitumour activity of C21 steroidal glycosides and their derivatives of Baishouwu: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Baishouwu has been used in China for thousands of years since it was first discovered in the late Tang Dynasty and flourished in the Song and Ming Dynasties. The Chinese herbal medicines named Baishouwu include Cynanchum auriculatum Royle ex Wight., Cynanchum bungei Decne. and Cynanchum wilfordii Hemsl. It is described in the Sign of Materia Medica as "sweet, bitter, reinforce liver and kidney, and non-toxic". It is widely used for nourishing the blood to expel wind, reinforcing liver and kidney, strengthening bones and muscles. AIM OF THE REVIEW: In this review, the current research status of the C21 steroidal glycosides and their derivatives of Baishouwu for malignant tumours and their anti-tumour mechanisms are discussed. This may lay the ground for potential application of Baishouwu and its active ingredients in the treatment of tumours. MATERIALS AND METHODS: Scientific databases, including PubMed, Elsevier, Science Direct, Google Scholar, CNKI, WANFANG DATA and VIP were searched to gather data about Baishouwu and its C21 steroidal glycosides and their derivatives. RESULTS: Prior literature indicates that Baishouwu has important biological activities such as anti-tumour, anti-epileptic, reducing cholesterol, protection of liver and kidney and immunomodulatory, which are of increasing interest, especially its anti-tumour activity. Recent studies demonstrate that the C21 steroidal glycosides of Baishouwu, which have prominent antitumour efficacy, are one of its main active ingredients. Presently, a variety of C21 steroidal glycosides have been isolated from Baishouwu medicinal part, the tuberous root. This review summarizes the various antitumour activities of the C21 steroidal glycosides and their derivatives of Baishouwu. CONCLUSIONS: In this review, the antitumour effects and mechanisms of total C21 steroidal glycosides and monomers and derivatives of Baishouwu in vitro and in vivo were summarized. Baishouwu can inhibit tumourigenesis by blocking tumour cell cycle progression, regulating numerous signaling pathways, promoting apoptosis, inhibiting tumour cells proliferation and metastasis, improving immunity and so on. This review provides a theoretical basis for inheriting and developing the medical heritage of the motherland, exploring the resources of traditional Chinese medicine for ethnic minorities and clinical rational drug use.

Traditional uses, phytochemical constituents and pharmacological properties of Osmanthus fragrans: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Osmanthus fragrans Lour., is a medicinal plant distributed widely in some Asian countries including Japan and Korea and southwestern China. It has been used traditionally for the treatment of weakened vision, halitosis, panting, asthma, cough, toothache, stomachache, diarrhea, rheumatism, physique pain and hepatitis. AIM OF THE REVIEW: Recent advances in traditional uses, botanical characteristics, distribution, taxonomy, phytochemical constituents, biological effects as well as the toxicities of O. fragrans are comprehensively presented and critically evaluated, and the underlying mechanism associated with the bioactivities of extracts, essential oil and components from this plant is also well summarized. In order to provide comprehensive scientific basis for the medical application and help interested researchers discover food and medicinal natural products from O. fragrans. MATERIALS AND METHODS: All information was systematically gathered from globally accepted scientific databases by Internet databases, including Elsevier, ScienceDirect, PubMed, Web of Science, Wiley, Springer, SciFinder, ACS Publications, CNKI, WanFang, Google Scholar, Baidu Scholar, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations). All published contributions on O. fragrans different languages were included and cited. The chemical structures of all isolated compounds were drawn by using ChemBioDraw Ultra 14.0 software. RESULTS: To date, more than 183 compounds were isolated and structurally identified from different plant parts of O. fragrans. Among them, ionone, ionol, flavonoids, polyphenols and iridoids, as the major bioactive substances, have been extensively studied and displayed the best bioactivity. Pharmacological studies demonstrated that O. fragrans and its active components had a wide range of biological activities, such as antioxidant, antitumor, anti-inflammatory, anti-hyperglycemic, anti-thrombotic, anti-melanogenesis, neuroprotective, and hepatoprotective activities, etc. CONCLUSION: O. fragrans, as a food and medicinal resource, has a good health care function and important edible and medicinal value, and thus has good prospects for utilization. However, many studies on biological activities were mainly based on extracts and the bioactive ingredients of this plant, and the mechanism responsible for these extracts and ingredients have not been well identified and there is a gap in research regarding clinical effect and safety. Therefore, the detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more clinical studies are encouraged to be conducted to ensure safety and effectiveness of the plant for human use.

Piperazine ferulate attenuates gentamicin-induced acute kidney injury via the NF-κB/NLRP3 pathway.

BACKGROUND: Piperazine ferulate (PF) is widely used in chronic nephritis and nephrotic syndrome in clinic. PF can improve diseases related inflammation by inhibiting the activation of nuclear factor kappa-B (NF-κB) signal. Acute kidney injury (AKI) is usually associated with the occurrence and development of renal inflammation. However, the nephroprotective effect and anti-inflammatory mechanisms of PF on AKI are not clear. PURPOSE: This study aimed to investigate the nephroprotective effects of PF on gentamicin (GM) induced AKI in rats and its potential mechanisms. METHODS: Male Sprague Dawley (SD) rats were intraperitoneally injected with GM (100 mg/kg/day) with or without PF (50 and 100 mg/kg/day) for 7 consecutive days. In vitro, the NRK-52e cells were exposed to GM (7 mg/ml) with or without PF (62.5 µg/ml) treatment. The renal injury and cell damage were assessed subsequently. RESULTS: Our findings showed that PF treatment can significantly improve renal function, reduce renal pathological changes, and attenuate inflammatory response in rats treated with gentamicin. Besides, PF could significantly reduce the cell damage and cellular inflammatory response. In terms of mechanisms, our study revealed that PF can evidently inhibit the activation of NF-κB and nod-like receptor family pyrin domain protein 3 (NLRP3) inflammasome. Meanwhile, it could down regulate the expressions of protein and gene of p-IKKα, p-IKKß, p-p65, p65, p50, p105, NLRP3 and IL-1ß. CONCLUSION: Our findings showed that PF may improve inflammation by inhibiting the NF-κB/NLRP3 pathway, so as to attenuate AKI.

Cinnamic acid preserves against myocardial ischemia/reperfusion injury via suppression of NLRP3/Caspase-1/GSDMD signaling pathway.

BACKGROUND: Cinnamic acid (CA) is an active organic acid compound extracted from Cinnamomi ramulus that has various biological activities. There is growing studies have shown that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome significantly contributes to sterile inflammatory response and pyroptosis in myocardial ischemia/reperfusion injury (MI/RI). However, whether CA has any influence on NLRP3 inflammasome and pyroptosis during MI/RI are not fully elucidated. PURPOSE: In the present study, we investigated whether NLRP3 inflammasome activation and pyroptosis were involved in the cardioprotective effect of CA against MI/RI. METHODS: Male Sprague-Dawley rats were intragastrically administered either with CA (75 and 150 mg/kg, daily) or vehicle for 7 successive days prior to ligation of coronary artery, and then rats were subjected to ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min to evoke MI/RI. RESULTS: Our results demonstrated that CA could significantly improve cardiac diastolic function, decrease cardiac infarct size and myocardial injury enzymes, inhibit cardiomyocyte apoptosis, attenuate cardiac structure abnormality, and mitigate oxidative stress and inflammatory response. We also found that MI/RI activate NLRP3 inflammasome as evidenced by the upregulation levels of NLRP3, pro-caspase-1, caspase-1, and ASC proteins and mRNA. More importantly, MI/RI trigger pyroptosis as indicated by increased DNA fragmentation, membrane pore formation, and mitochondrial swelling as well as increased levels of pyroptosis-related proteins and mRNA, including GSDMD, N-GSDMD, IL-18, and IL-1ß. As expected, all these deleterious alterations were prominently reversed by CA pretreatment. CONCLUSIONS: These findings indicate that CA effectively protected cardiomyocytes against MI/RI by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway, and it is worthy of more investigations for its therapeutic potential for extenuating ischemic heart disease.