SBC (Sanhuang Xiexin Tang combined with Baihu Tang plus Cangzhu) alleviates NAFLD by enhancing mitochondrial biogenesis and ameliorating inflammation in obese patients and mice.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.

Effects of Selenium Yeast on Egg Quality, Plasma Antioxidants, Selenium Deposition and Eggshell Formation in Aged Laying Hens.

Internal egg and eggshell quality are often deteriorated in aging laying hens, which causes huge economic losses in the poultry industry. Selenium yeast (SY), as an organic food additive, is utilized to enhance laying performance and egg quality. To extend the egg production cycle, effects of selenium yeast supplementation on egg quality, plasma antioxidants and selenium deposition in aged laying hens were evaluated. In this study, five hundred and twenty-five 76-week-old Jing Hong laying hens were fed a selenium-deficient (SD) diet for 6 weeks. After Se depletion, the hens were randomly divided into seven treatments, which included an SD diet, and dietary supplementation of SY and sodium selenite (SS) at 0.15, 0.30, and 0.45 mg/kg to investigate the effect on egg quality, plasma antioxidant capacity, and selenium content in reproductive organs. After 12 weeks of feeding, dietary SY supplementation resulted in higher eggshell strength (SY0.45) (p < 0.05) and lower shell translucence. Moreover, organs Se levels and plasma antioxidant capacity (T-AOC, T-SOD, and GSH-Px activity) were significantly higher with Se supplementation (p < 0.05). Transcriptomic analysis identified some key candidate genes including cell migration inducing hyaluronidase 1 (CEMIP), ovalbumin (OVAL), solute carrier family 6 member 17 (SLC6A17), proopiomelanocortin (POMC), and proenkephalin (PENK), and potential molecular processes (eggshell mineralization, ion transport, and eggshell formation) involved in selenium yeast's effects on eggshell formation. In conclusion, SY has beneficial functions for eggshell and we recommend the supplementation of 0.45 mg/kg SY to alleviate the decrease in eggshell quality in aged laying hens.

Microbiome and ileum transcriptome revealed the boosting effects of selenium yeast on egg production in aged laying hens.

The declines in laying performance during the late production period have adverse effects on the length of the production cycle. Improving the nutrition of laying hens is a crucial measure to reverse this declination. This study investigated the effect of selenium yeast (SY) on egg production, ileal gene expression and microbiota, as well as elucidating their associations in aged laying hens. A total of 375 Jinghong laying hens at 76 weeks old were randomly assigned into 5 dietary treatments, which included a selenium-deficient basal diet based on corn-soybean meal, and dietary supplementation of SY at 0.15, 0.30 and 0.45 mg/kg, and sodium selenite at 0.45 mg/kg. The results showed that SY ameliorated the depression in aged laying performance in the 0.30 mg/kg group (P < 0.01). Selenium yeast significantly increased ileum selenium concentration (P < 0.05), and SY groups had higher selenium deposition efficiency than the sodium selenite group. Functional enrichment and Short Time-series Expression Miner (STEM) analysis indicated that SY activated metabolic progress (e.g., glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism), immune response and oxidative stress response. Four hub genes including thioredoxin reductase 1 (TXNRD1), dihydrolipoamide dehydrogenase (DLD), integrin linked kinase (ILK) and leucine zipper tumor suppressor 2 (LZTS2) were involved in intestinal metabolism which was closely associated with selenium deposition/status. Moreover, the relative abundance of Veillonella, Turicibacter and Lactobacillus was significantly increased, but the relative abundance of Stenotrophomonas was significantly decreased by SY supplementation. Multi-omics data integration and Canonical correspondence analysis (CCA) showed that both the ileum selenium content and the laying rate were highly correlated with pathways and bacteria enriched in metabolism and immune response. Meanwhile, the "switched on" gene prostate stem cell antigen (PSCA) had a positive relationship with Veillonella and a negative relationship with the opportunistic pathogens Stenotrophomonas. Overall, our study offered insight for the further exploration of the role of SY on boosting egg production and balancing ileum intestinal flora in aged laying hens.

MiR-30c-5p mediates the effects of panax notoginseng saponins in myocardial ischemia reperfusion injury by inhibiting oxidative stress-induced cell damage.

Myocardial ischemia reperfusion (MI/R) injury is a severe pathological process that threatens human health all over the world. The role of microRNAs (miRNAs) in the pathogenesis of MI/R injury has been increasingly recognized in recent years. Here, we conducted a miRNA profiling of the hearts of MI/R injured rat model, and identified 46 miRNAs which were differentially expressed between the MI/R injury and the control groups. With a special focus on one of the most significantly changed miRNA, miR-30c-5p, we demonstrated its protective role against cardiomyocyte injury in tBHP-treated H9c2 cells. Overexpression of miR-30c-5p increased cell viability, decreased LDH release, and reduced cell apoptosis of cardiomyocytes after tBHP stimulation, accompanied with downregulated p53 expression. Noticeably, the level of miR-30c-5p was markedly upregulated in MI/R injury cells treated with panax notoginseng saponins (PNS), a traditional Chinese Medicine with significant clinical effects in the treatment of human MI/R injury. Moreover, miR-30c-5p inhibitor is sufficient to block the protection of PNS, as well as its active ingredient ginsenoside Re, against tBHP induced cardiomyocyte injury. The expression of p53 protein was also reduced in PNS treated cells. In summary, our study identified novel miRNA hits of MI/R injury, revealed a pivotal role of miR-30c-5p in cardiomyocyte damage and apoptosis after MI/R, and illustrated a miR-30c-5p-dependent therapeutic mechanism of PNS of this pathologic process. Future studies are warranted to examine the endogenous significance of miR-30c-5p, along with multiple other miRNA hits, in the pathogenesis and treatment of MI/R injury.

Integrating candidate metabolites and biochemical factors to elucidate the action mechanism of Xue-sai-tong injection based on (1)H NMR metabolomics.

A strategy of integrating candidate metabolites with crucial biochemical factors was proposed in this study to discover relevant biological functions for interpreting the action mechanism of Traditional Chinese Medicines (TCM). This approach was applied to Xue-Sai-Tong injection (XST) to reveal the action mechanism based on the metabolic response in an ischemia/reperfusion (I/R) rat model by analyzing NMR profile. Partial least squares discriminate analysis (PLS-DA) was used to compare metabolic profiles of serum samples and revealed nine metabolites altered by I/R injury could be restored to normal status (sham-operated group) under the therapy of XST. The pathway enrichment analysis suggested the metabolic changes were mainly involved in pyruvate metabolism, glycolysis, and citrate cycle. The functional roles of the candidate metabolites were further identified by Pearson correlation analysis with the key biochemical factors in serum. The results indicated pyruvate, succinate, acetate and lysine showed significant associations with the oxidative stress factors. Elevated level of pyruvate was found as an essential metabolic response for the major effect of XST against I/R injury by enhancing glycolysis and overcoming the induced reactive oxygen species (ROS). This metabolomics approach provides a better understanding of the mechanisms of TCM and helps to develop a holistic view of TCM efficacy.

Evaluating the antidiabetic effects of Chinese herbal medicine: Xiao-Ke-An in 3T3-L1 cells and KKAy mice using both conventional and holistic omics approaches.

BACKGROUND: Xiao-Ke-An (XKA) is a Chinese medicine widely used for treating type 2 diabetes mellitus (T2D). It is composed of eight herbal medicines traditionally used for T2D, including Rehmannia glutinosa Libosch, Anemarrhena asphodeloides Bunge, Coptis chinensis Franch, etc. The aim of the present study was to investigate the antidiabetic effects of XKA with both conventional and holistic omics approaches. METHODS: The antidiabetic effect of XKA was first investigated in 3T3-L1 cells to study the effect of XKA on adipogenesis in vitro. Oil Red O staining was performed to determine the lipid accumulation. The intracellular total cholesterol (TC) and triglyceride (TG) contents in XKA treated 3T3-L1 cells were also evaluated. The therapeutic effects of XKA was further evaluated in KKAy mice with both conventional and holistic omics approaches. Body weight, fasting and non-fasting blood glucose, and oral glucose tolerance were measured during the experiment. At the time of sacrifice, serum was collected for the measurement of TG, TC, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). The liver, kidney, spleen, pancreas, heart and adipose tissues were harvested and weighted. The liver was used for further microarray experiment. Omics approaches were adopted to evaluate the holistic rebalancing effect of XKA at molecular network level. RESULTS: XKA significantly inhibited adipogenic differentiation, lowered the intracellular TC and TG contents in 3T3-L1 cells. XKA improved the glucose homeostasis and lipid metabolism, ameliorated insulin resistance in KKAy mice. Furthermore, XKA also exhibited effective therapeutic effects by reversing the molecular T2D disease network from an unbalanced state. CONCLUSIONS: This study investigated the antidiabetic effects of XKA with both conventional and holistic omics approaches, providing both phenotypic evidence and underlying action mechanisms for the clinical use of XKA treating T2D.

Dissecting Xuesaitong's mechanisms on preventing stroke based on the microarray and connectivity map.

Elucidating action mechanisms of Chinese medicines has remained a challenging task due to the chemical and biological complexity that needs to be resolved. In this study we applied a gene expression data and connectivity map (CMAP) based approach to study action mechanisms of a Chinese medicine Xuesaitong injection (XST) on preventing cerebral ischemia-reperfusion injury. XST is a standardized patent Chinese medicine of Panax notoginseng roots and it has long been used for the effective prevention and treatment of stroke in China. However, more research is needed to understand the mechanisms underlying its effects against ischemic stroke. We first evaluated the effect of XST against ischemic stroke in an ischemia-reperfusion rat animal model and dissected its mechanisms based on gene expression data of injured brain. The results showed that treatment with XST significantly attenuated infarct area and histological damage. Based upon pathway analysis and the CMAP query of microarray data, anti-inflammatory response and anti-platelet coagulation were found as the major mechanisms of XST against stroke, which were further validated in vitro and with pharmacological assays of serum. We demonstrated the feasibility of applying the combination of the microarray with the CMAP in identifying mechanisms of Chinese medicine.

[Study on main pharmacodynamic effects for Schisandra lignans based upon network pharmacology].

In this study, we focused on the study of pharmacodynamic effects for 6 major bioactive lignans of Schisandra chinensis, namely deoxyschizandrin, schisandrin B, schisandrin C, schisandrin, schizandrol B and schisantherin A. A compound-gene-pathway network, which contained 124 related genes and 88 pathways, was constructed by collecting drug genes through mining relevant literatures and network pharmacology analysis. Based on the network analysis, 32 pathways and 80 related genes were associated with inflammation, which implied that anti-inflammatory might be the major pharmacodynamic effects of these compounds. All lignans except schizandrol B reduced LPS-induced NO production in RAW264.7 cells, which validated the anti-inflammatory hypothesis generated from network analysis. Furthermore, we investigated the effects of deoxyschizandrin, schisandrin C, schisandrin and schisantherin A on the secretion of inflammatory cytokines TNF-α, IL-1ß, IL-6, PGE2 and protein expressions of iNOS, COX-2. As a result, deoxyschizandrin showed the strongest anti-inflammatory activity with inhibitory effect on all 4 inflammatory cytokines secretions and protein expressions of iNOS, COX-2. This study provided evidences for systematic exploration on the pharmacolgical actions and mechanisms of schisandra.

[Network pharmacology study of mechanism on xuesaitong injection against retinal vein occlusion].

Retinal vein occlusion (RVO) is a common clinical disease causing vision loss. Risk factors such as diabetes, atherosclerosis are closely associated with RVO. Xuesaitong injection is used extensively in clinical treatment of RVO, however the mechanism is still unclear. In this study, we investigated the protective effect of Xuesaitong injection on RVO rat model. Using a compound-target network of Xuesaitong on anti-RVO constructed by literature mining, we aim to elucidate the multi-compound, multi-target effect of Xuesaitong injection. Fifteen potential targets of Xuesaitong injection associated with inflammation, angiogenesis, apoptosis, and coagulation were identified in this study. VEGF, IL-1beta and IL-6, three important targets in the compound-target network were further experimentally validated. This study provided experimental evidence for Xuesaitong injection being effective in treating RVO and a network view on its anti-RVO mode of action through a multi-compound and multiple-target mechanism.

A network pharmacology study of Chinese medicine QiShenYiQi to reveal its underlying multi-compound, multi-target, multi-pathway mode of action.

Chinese medicine is a complex system guided by traditional Chinese medicine (TCM) theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA) are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ), on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang). Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD)-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.

Dissecting active ingredients of Chinese medicine by content-weighted ingredient-target network.

Chinese medicine has been widely used in clinical practice, but its mode of action often remains obscure. This has seriously hindered further development and better clinical applications of Chinese medicine. Among the most critical questions to be addressed, the identification of active ingredients is an important one requiring more research. Existing methods are only concerned the potential pharmacological effects of the individual purified chemical ingredients without consideration of the contents of these ingredients, which is critical to the comprehensive effect of Chinese medicine. A novel approach was proposed here to integrate network pharmacology analysis and ingredient content in Chinese medicine to identify active ingredients. The therapeutic action of Xuesaitong (XST) injection on myocardial infarction was analyzed as an example in this study. Firstly, we built a cardiovascular disease (CVD) related protein-protein interaction (PPI) network. Secondly, the potential targets of the ingredients of XST were identified by integrating microarray data, text mining and pharmacophore model-based prediction. The target-ingredient relationships were then mapped to the network. Topological attributes related to the targets of these ingredients, together with the ingredients' contents, were combined to calculate a composition-weighted index for integrative evaluation of ingredient efficacy. Our results indicated that major active ingredients in XST were notoginsenoside R1, ginsenoside Rg1, Rb1, Rd and Re, which was further validated on myocardial infarction rat models. In conclusion, this study presented a novel approach to identify active ingredients in Chinese medicine.

A network study of chinese medicine xuesaitong injection to elucidate a complex mode of action with multicompound, multitarget, and multipathway.

Chinese medicine has evolved from thousands of years of empirical applications and experiences of combating diseases. It has become widely recognized that the Chinese medicine acts through complex mechanisms featured as multicompound, multitarget and multipathway. However, there is still a lack of systematic experimental studies to elucidate the mechanisms of Chinese medicine. In this study, the differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with Xuesaitong Injection (XST), a Chinese medicine consisting of the total saponins from Panax notoginseng (Burk.) F. H. Chen (Chinese Sanqi). A network-based approach was developed to combine DEGs related to cardiovascular diseases (CVD) with lines of evidence from the literature mining to investigate the mechanism of action (MOA) of XST on antimyocardial infarction. A compound-target-pathway network of XST was constructed by connecting compounds to DEGs validated with literature lines of evidence and the pathways that are functionally enriched. Seventy potential targets of XST were identified in this study, of which 32 were experimentally validated either by our in vitro assays or by CVD-related literatures. This study provided for the first time a network view on the complex MOA of antimyocardial infarction through multiple targets and pathways.

[Prediction of multi-target of Aconiti Lateralis Radix Praeparata and its network pharmacology].

OBJECTIVE: To predict multi-targets by multi-compounds found in Aconiti Lateralis Radix Praeparata and construct the corresponding multi-compound-multi-target network. METHOD: Based on drug-target relationships of FDA approved drugs, a model for predicting targets was established by random forest algorithm. This model was then applied to predict the targets of Aconiti Lateralis Radix Praeparata and construct the multi-compound-multi-target network. RESULT: The predicted targets of 22 compounds of Aconiti Lateralis Radix Praeparata are validated by literature. Each compound in the established network was correlated with 16. 3 targets on average, while each target was correlated with 4. 77 compounds on average, which reflects the "multi-compound and multi-target" characteristic of Chinese medicine. CONCLUSION: The proposed approach can be used to find potential targets of Chinese medicine.