Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

Effects of Silage Diet on Meat Quality through Shaping Gut Microbiota in Finishing Pigs.

With increasing demand for high-quality pork, development of green and healthy feed for finishing pigs is urgently needed. In this study, the effects and mechanisms of mulberry and paper mulberry silages on growth performance, meat quality, and intestinal health of finishing pigs were explored. Intestinal microbiota were profiled, and microbially produced short-chain fatty acids (SCFAs) were measured. The average daily gain (ADG) and feed conversion rate (FCR) with mulberry and paper mulberry silages were not significantly different from those of the control. Meat quality as measured by pork marbling and fatty acids in the longissimus dorsi was better with mulberry silage. The highest concentration of SCFAs was also with mulberry silage. According to 16S rRNA sequencing, Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae, which are important in SCFA production, were biomarkers of mulberry silage. PICRUSt functional analysis of intestinal microbes indicated that galactose metabolism, starch and sucrose metabolism, and carbohydrate digestion and absorption decreased significantly in silage treatments but increased in the control. Correlations between intestinal microbes and SCFAs and fatty acids indicated Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA and fatty acid contents. The results indicated that mulberry silage could increase SCFA content through shaping intestinal microbes to affect the deposition of fatty acids, which laid a solid theoretical foundation for improving pork quality. IMPORTANCE To avoid competition between people and animals for food, it is essential to develop nontraditional feeds. In this study, the effects of the silages of the unconventional feed resources mulberry and paper mulberry on meat quality of finishing pigs were examined. With mulberry silage in the diet, meat quality improved as indicated by meat color, marbling score, and beneficial fatty acids in the longissimus dorsi muscle. Pigs fed mulberry silage had the highest concentrations of short-chain fatty acids (SCFAs), and 16S rRNA sequencing identified Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae as biomarkers, which are important in SCFA production. Functions of intestinal microbes in the two silage groups primarily involved amino acid metabolism and SCFA production. Correlations between intestinal microbes and SCFAs and fatty acids indicated that Clostridium_sensu_stricto-1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA contents in the intestine and fatty acids in the longissimus dorsi.

Dietary alfalfa powder supplementation improves growth and development, body health, and meat quality of Tibetan sheep.

The application of alfalfa powder (AP) in Tibetan sheep to explore its healthy effects and meat quality improvement potential has not been reported. Our study found that AP improved the growth performance, serum metabolism, and antioxidation of Tibetan sheep. The edible quality, sensory quality, and nutritional quality of longissimus dorsi (LD) were analyzed. We observed lower drip loss and hue angle of meat after AP supplementation. AP also increased the cooked meat percentage, pH24h, a*24h, chroma24h, and the contents of protein and fat. The targeted metabolomics profiling revealed that the contents of essential amino acids and flavor amino acids in mutton increased by AP treatments. AP also promoted the deposition of MUFA and PUFA. Therefore, as a promising botanical supplement, AP has a positive effect on the growth, development, and body health of Tibetan sheep, and is also conductive to providing healthy and nutritious high-quality livestock products.

Shema Oral Liquid Ameliorates the Severity of LPS-Induced COPD via Regulating DNMT1.

Background: Chronic obstructive pulmonary disease (COPD) is the most common respiratory disease with high morbidity and mortality. Shema oral liquid (Shema) is a traditional Chinese medicine (TCM) approved for the treatment of respiratory diseases. Clinical applications have shown that Shema has antitussive, expectorant, and anti-asthmatic effects, but its definite efficacy to COPD is still unclear. This study aimed to explore the therapeutic capacity and potential mechanism of Shema in treatment of COPD. Methods: Network pharmacology was used to investigated the possible pharmacological mechanism of Shema against COPD. A rat model of lipopolysaccharide (LPS)-induced COPD was established to determine pulmonary ventilatory function, serum inflammatory cytokines, and pulmonary pathological change. Subsequently, tandem mass tag (TMT)-based quantitative proteomics was used to further reveal the therapeutic targets related with Shema against COPD. Western blot was finally performed to validate the expression of targeted proteins screened by proteomics research. Results: Network pharmacology analysis indicated that Shema against COPD mainly inhibited the inflammation and affected the immune system. The animal experiment demonstrated that Shema treatment protected the lung tissue from LPS induced injury, inhibited the levels of serum inflammatory cytokines such as interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and improved the respiratory ventilatory function by upregulating forced expiratory volume in 0.1 s (FEV0.1), FEV0.3, forced vital capacity (FVC), and the ratios of FEV0.1 (0.3)/FVC. Proteomic analysis and western blot both proved that Shema inhibited the expression of DNA methyltransferase 1 (DNMT1) in the lung tissue. Conclusion: The therapeutic mechanism of Shema in treatment of COPD may involve inhibiting inflammatory response, improving pulmonary ventilatory function, and alleviating LPS-induced lung injury through regulating the expression of DNMT1. This study also shed light on the development of therapeutic strategies in treating COPD by intervening DNMT-related pathways.

Effect of Yiqi Huayu Pinggan Zishen Formula Combined with Valsartan in the Treatment of Hypertension and Its Effect on MMP-9, Ang II, and MCP-1.

Objective: To explore the effect of Yiqi Huayu Pinggan Zishen recipe combined with valsartan in the treatment of hypertension and its effect on MMP-9, Ang II, and MCP-1. Methods: About 100 patients with hypertension treated in our hospital from March 2020 to April 2021 were enrolled. All patients were arbitrarily assigned to the control group and the study group. The former group was cured with valsartan, and the latter group was cured with Yiqi Huayu Pinggan Zishen recipe combined with valsartan. The curative effect, blood pressure level, renal function index, serum matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), angiotensin II (Ang II) level, traditional Chinese medicine (TCM) syndrome score, and the incidence of adverse reactions were compared. Results: First of all, we compared the curative effects; the study group exhibited remarkably effective in 44 cases and effective in 6 cases, and the effective rate was 100.00%, while in the control group, 24 cases were markedly effective, 16 cases were effective, and 5 cases were ineffective; the effective rate was 90.00%. The curative effect in the study group was higher (P < 0.05). Secondly, we compared the blood pressure level. Before treatment, there was no remarkable difference (P > 0.05). After treatment, the blood pressure of the two groups decreased. The systolic blood pressure and diastolic blood pressure of the study group were lower (P < 0.05). In terms of renal function indexes, the levels of blood urine nitrogen (BUN), Cr, and ß 2-MG in the study group were lower, while the level of eGFR in the study group was higher (P < 0.05). The serum levels of MMP-9, MCP-1, and Ang II decreased. Of note, the levels of serum MMP-9, MCP-1, and Ang II in the study group were lower (P < 0.05). After treatment, the TCM syndrome scores decreased, and the study group was lower (P < 0.05). Finally, we compared the incidence of adverse reactions. The incidence of adverse reactions in the study group was lower (P < 0.05). Conclusion: Yiqi Huayu Pinggan Zishen recipe combined with valsartan in the treatment of hypertension can remarkably reduce the clinical symptoms, enhance the renal function, strengthen the therapeutic effect, promote the ability of independent movement, and reduce the levels of serum MMP-9, MCP-1, and Ang II with high safety, which has the value of clinical application.

Protective effects of alfalfa saponins on oxidative stress-induced apoptotic cells.

As is known, alfalfa saponins can be used as a feed additive in a pig's diet and the addition of alfalfa saponins to a pig's diet could improve its antioxidant capacity. However, the mechanism by which alfalfa saponins exert their antioxidant effects has not been studied. To address this issue, H2O2-induced rat intestinal epithelial cells were used to establish an oxidative stress model to explore the protective mechanism of alfalfa saponins in this study. The results demonstrated that alfalfa saponins could rescue the cell proliferation activity, elevate the amount of antioxidant enzymes and downregulate the release of MDA and LDH in H2O2-induced cells. The antioxidant activity of alfalfa saponins was achieved by restoring GSH homeostasis. Further results demonstrated that alfalfa saponins could inhibit cell apoptosis through activating the MAPK signaling pathway. These results elucidated the mechanism by which alfalfa saponins exert their antioxidant effects and provided a potential strategy for alleviating oxidative stress in monogastric animals.

[Marker genes of geniposide-induced hepatotoxicity based on genomic strategy].

The aim of this paper was to screen out relevant genes of geniposide-induced hepatotoxicity based on genomics,in order to provide a scientific basis for the non-clinical evaluation of drugs containing Gardeniae Fructus and geniposide. Fifty-five SD rats were randomly divided into normal control group,24 h group and 72 h group. The changes of appearance,behavior and weight of rats were observed after administration by gavage for 3 days. The activities of ALT and AST were detected. Molecular mechanism of geniposideinduced hepatotoxicity was investigated by Affymetrix miRNA 4. 0 and Affymetrix Rat Gene 2. 0 to examine the gene expression levels in Sprague-Dawley rat livers at 24 h and 72 h after administration of overdose-geniposide( 300 mg·kg-1 daily),and then verified by Realtime quantitative PCR. Compared with the normal control group,the activities of ALT and AST were markedly increased. In addition,experimental results indicated that 324 genes were differentially expressed,among which 259 were up-regulated and 65 down-regulated.Nine candidate genes were verified by qRT-PCR,including Bcl2,Il1 b,Tpm3,MMP2,Col1α1,Ifit1,Aldob,Nr0 b2,Cyp2 c23. And Bcl2,Col1α1,Aldob,Nr0 b2 and Cyp2 c23 were found to be correlated with geniposide-induced hepatotoxicity. This study provides an important clue for mechanism of geniposide-induced hepatotoxicity.

Integrated UPLC-Q/TOF-MS Technique and MALDI-MS to Study of the Efficacy of YiXinshu Capsules Against Heart Failure in a Rat Model.

Background: Yixinshu Capsules (YXSC) are widely used in Chinese medicine for the treatment of cardiovascular diseases. However, the therapeutic mechanisms of action are not well understood. Method: In this study, a metabonomic approach based on integrated UPLC-Q/TOF-MS technique and MALDI-MS was utilized to explore potential metabolic biomarkers that may help increase the understanding of heart failure (HF) and in order to assess the potential mechanisms of YXSC against HF. Plasma metabolic profiles were analyzed by UPLC-Q/TOF-MS with complementary hydrophilic interaction chromatography and reversed-phase liquid chromatography. Moreover, time-course analysis at the 2nd, 4th, and 10th week after permanent occlusion was conducted. In an effort to identify a more reliable potential metabolic marker, common metabolic markers of the 2nd, 4th, and 10th week were selected through multivariate data analysis. Furthermore, MALDI-MS was applied to identify metabolic biomarkers in the blood at apoptotic positions of heart tissues. Results: The results showed that HF appeared at the fourth week after permanent occlusion based on echocardiographic assessment. Clear separations were observed between the sham and model group by loading plots of orthogonal projection to latent structure discrimination analysis (OPLS-DA) at different time points after permanent occlusion. Potential markers of interest were extracted from the combining S-plots, variable importance for the projections values (VIP > 1), and t-test (p < 0.05). Twenty-one common metabolic markers over the course of the development and progression of HF after permanent occlusion were identified. These were determined to be mainly related to disturbances in fatty acids, phosphatidylcholine, bile acids, amino acid metabolism, and pyruvate metabolism. Of the metabolic markers, 16 metabolites such as palmitoleic acid, arachidonic acid, and lactic acid showed obvious changes (p < 0.05) and a tendency for returning to baseline values in YXSC-treated HF rats at the 10th week. Moreover, four biomarkers, including palmitoleic acid, palmitic acid, arachidonic, acid and lactic acid, were further validated at the apoptotic position of heart tissue using MALDI-MS, consistent to the variation trends in the plasma. Conclusions: Taken in concert, our proposed strategy may contribute to the understanding of the complex pathogenesis of ischemia-induced HF and the potential mechanism of YXSC.

One-Pot Synthesis of Aza-Morita-Baylis-Hillman Adducts via Zinc-Mediated Allylation of 4-Bromocrotonates and Imines.

An approach to the synthetically valuable ß-substituted aza-Morita-Baylis-Hillman (MBH) type products, through zinc-mediated allylation of imines with 4-bromocrotonates followed by subsequent isomerization of the double bond, was developed. Complementary to classical MBH reaction, this reaction utilizes easily available 4-bromocrotonates as the reaction partners, providing a rapid alternative to the traditional use of α,ß-unsaturated carbonyl compounds. The short reaction time, one-pot operation, broad substrate scopes, gram-scale synthesis, and synthetic application exemplified the utility and practicability of this method.

Proteomic Investigations of Transcription Factors Critical in Geniposide-Mediated Suppression of Alcoholic Steatosis and in Overdose-Induced Hepatotoxicity on Liver in Rats.

Alcoholic steatosis is one of the most prevalent forms of liver disease, and appropriate insight and application of anti-steatosis drugs must be considered. Geniposide, the major active constituent of the Gardenia jasminoides (Ellis) fruit, has been commonly used as a traditional herbal medicine for the treatment of liver diseases. However, its hepatoprotective effect on alcoholic steatosis has not been reported. Moreover, geniposide overdose-induced hepatotoxicity was demonstrated. Hence, its therapeutic effects and overdose-induced hepatotoxicity in rat models along with corresponding targets, especially the targets of transcription factors (TFs), were systematically investigated in this study by using a concatenated tandem array of consensus TF response elements. The results indicate that geniposide can attenuate alcoholic steatosis and liver injury by enhancing the transcriptional activities of peroxisome proliferator-activated receptor-α and hepatocyte nuclear factors 1α and 4α, while geniposide overdose perturbs other TFs. In addition, therapeutic doses and overdoses of geniposide have differentiated target TFs. This study is the first to provide a systematic insight into the difference of critical transcription factors between the actions of therapeutic doses and overdoses of geniposide, as well as much-needed attention to the important topic of alcoholic liver disease therapy.

BAOXIN Granules Protected Mouse Model With Elevated Afterload From Cardiac Hypertrophy by Suppressing Both Inflammatory Reaction and Collagen Deposition.

BAOXIN Pill was reported to be effective clinically for chronic heart failure based on the principles of traditional Chinese medicine (TCM), invigorating qi and activating blood. The present study evaluated preclinically the effects of the improved dosage form, BAOXIN Granules, on cardiac hypertrophy. Transverse aortic constriction (TAC) was performed in mice to model cardiac hypertrophy by aortic stenosis for 4 weeks. The sham and TAC group were intragastrically administrated with saline as the controls. Two treatment groups were administrated orally with 10 mg/kg⋅d Enalapril (positive control) or 0.77 g/kg⋅d BAOXIN Granules for 4 weeks respectively. The effects were evaluated by echocardiography, morphology, and biological markers for cardiac function. The specific genes involved in inflammation and fibrosis were also examined for their expressions to investigate the pathways involved in early heart failure. Just as Enalapril, BAOXIN Granules administration markedly attenuated left ventricular hypertrophy and improved heart function as evidenced by echo cardiography, morphology. Accordingly, the biomarkers of the early stage heart failure, ANP, BNP and ß-MHC, were decreased in the two treatment groups. We also found that mRNA expressions of some inflammatory factors and fibrosis associated genes were down-regulated in the tissue of heart after treatment. BAOXIN Granules may protect the heart from myocardial hypertrophy caused by increasing left ventricular afterload. It can suppress both inflammatory reaction and collagen deposition during pressure overload. BAOXIN Granules is advised to be tested in clinical trials for heart failure in the future.

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia.

Functional dyspepsia (FD) is one of the most prevalent functional gastrointestinal disorders, and more and more multicomponent drugs represented by traditional Chinese medicines have provided a favorable therapeutic effect in its treatment. However, their precise localization in the clinic, as well as corresponding mechanism, is ambiguous, thus hindering their widespread use. To meet this requirement, a precise and systematic approach based on a restriction of special disease-related molecules and the following network pharmacology analysis was developed and applied to a multicomponent conventional drug, XiaoErFuPi (XEFP) granules. Experimental verification of the results indicates that this approach can facilitate the prediction, and the precise and systematic efficacy of XEFP could be easily revealed, which shows that XEFP has an advantage over the positive control drug on lactate, gastrin, interleukin 4 and calcitonin gene-related peptide. Moreover, by the proteomics analysis, its superposition of multi-target effects was revealed and a new candidate target for the treatment of FD, striatin, was obtained and verified. This study provides a practicable precise approach for the investigation of the efficacy of multicomponent drugs against FD and offers a promising alternative for the systematical management of FD.

A Metabonomics Investigation into the Therapeutic Effects of BuChang NaoXinTong Capsules on Reversing the Amino Acid-Protein Interaction Network of Cerebral Ischemia.

BACKGROUND: Amino acids (AAs) in cerebrospinal fluid (CSF) play a pivotal role in cerebral ischemia (CI). BuChang NaoXinTong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. METHODS: In order to investigate the therapeutic effects and pharmacological mechanisms of BNC on reversing CI from a system level, an amino acid-protein interaction imbalanced network of CI containing metabolites of AAs, key regulatory enzymes, and proteins was constructed for the first time. Furthermore, a novel method for detecting the ten AAs in CSF was developed by UPLC-QQQ-MS in an effort to validate the imbalanced networks and the therapeutic effects of BNC via analysis of metabolites. RESULTS: Based on a middle cerebral artery occlusion (MCAO) rat model, the dynamic levels of amino acids in CSF 3, 6, 12, and 24 h after MCAO were analyzed. Up to 24 h, the accumulated nine AA biomarkers were found to significantly change in the MCAO group compared to the sham group and exhibited an obvious tendency for returning to baseline values after BNC treatment. In addition, based on the imbalanced network of CI, four key enzymes that regulate the generation of BNC-mediated AA biomarkers were selected and validated using an enzyme-linked immunosorbent assay and western blotting. Finally, aromatic-L-amino-acid decarboxylase (AADC) was found to be one of the putative targets for BNC-mediated protection against CI. CONCLUSION: This study provides new strategies to explore the mechanism of cerebral ischemia and help discover the potential mechanism of BNC.

TCM-ADMEpred: A novel strategy for poly-pharmacokinetics prediction of traditional Chinese medicine based on single constituent pharmacokinetics, structural similarity, and mathematical modeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanhu Zhitong prescription (YZP) is a commonly used and relatively simple clinical herb preparation recorded in the China Pharmacopoeia. It contains Corydalis yanhusuo (Chinese name, Yanhusuo [YH]) and Angelica dahurica (Hoffm.) (Chinese name, Baizhi [BZ]), and has a long history of use in traditional Chinese medicine (TCM) for the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea. AIM OF THE STUDY: A TCM-ADMEpred method is developed for novel strategy for poly-pharmacokinetics prediction of TCM. To predict the pharmacokinetic characteristics of the main YZP constituents in rat plasma using in silico models, based on the theory that structurally similar constituents show similar pharmacokinetic properties. This approach may facilitate in silico prediction of the pharmacokinetics of TCM. MATERIALS AND METHODS: A robust platform using ultra-performance liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for simultaneous determination of seven active YZP constituents in rat plasma. These seven compounds were divided into two structural classes, alkaloids and coumarins. The correlation between AUC profiles within a structural class was expressed as Γ+, and this variable was used to develop two novel in silico models to predict constituent AUC values. The pharmacokinetics of tetrahydropalmatine, tetrahydroberberine, and corydaline following YZP administration were predicted using the Γ+-values of α-allocryptopine observed following YH administration, while those of imperatorin and isoimperatorin following BZ administration were predicted using the Γ+-values of byakangelicin observed following YZP administration. RESULTS: The UPLC-ESI-MS/MS method was successfully used to evaluate pharmacokinetic parameters after oral YZP, YH, or BZ administration. Our findings showed that co-administration of YH and BZ increased the AUC of four alkaloid constituents and reduced the AUC of three coumarin constituents, which might provide a scientific rationale for co-administering these herbs clinically as a YZP preparation, thus increasing their efficacy and reducing toxicity. The AUC values of imperatorin and isoimperatorin were predicted 3 h after oral BZ administration, with the bias ratios between the theoretical values and the observed experimental values ranging from 0.61% to 11.4%, and average bias ratios of 5.8% and 8.0%, respectively. The AUC values of tetrahydropalmatine, tetrahydroberberine, and corydaline were predicted 3 h after oral YZP administration, with bias ratios ranging from 3.7% to 46.4%, and average bias ratios of 23.8%, 15.4%, and 25.8%, respectively. CONCLUSION: The UPLC-ESI-MS/MS method was successfully applied to pharmacokinetic evaluations after oral administration of YZP, YH, and BZ to rats. The Γ+ variable was used to express the correlation between the AUC profiles of structurally similar compounds. This facilitated the development of an in silico model that was used to predict the AUC of three alkaloids in YZP and of two coumarins in BZ. Calculation of the bias ratios between the predicted and experimental values suggested that this in silico model provided a viable approach for the prediction of TCM pharmacokinetics.

Signature-oriented investigation of the efficacy of multicomponent drugs against heart failure.

Increasing attention has been paid to the application of precision medicine in heart failure (HF), and biomarker-based personalized medical care has shown great progress in HF management. Additionally, multicomponent drugs represented by traditional Chinese medicine (TCM) are demonstrating safety and efficacy in the management of HF. However, the potential mechanism is unclear, and the ambiguous clinical locations of TCM remain a hindrance to its extensive application. To meet this requirement, a precise investigation on the efficacy of multicomponent drugs against HF using the signature biomarkers-oriented approach was developed and applied to a conventional drug for cardiac disease, YiXinShu (YXS). On the basis of in vitro and in vivo efficacy evaluation of YXS against HF, and with the aid of proteomics and network pharmacology approaches, specific signatures regulated by YXS against HF were identified. YXS may show distinctive treatment features for those HF patients showing the elevation of fatty acid-binding protein 3 and cytoskeleton-associated protein 5, as well as other classic HF biomarkers. This study provides the first precise investigation of the efficacy of multicomponent drugs against HF and offers a practicable and low-cost approach for personalized management of HF.-Wei, J., Guo, F., Zhang, M., Xian, M., Wang, T., Gao, J., Wu, H., Song, L., Zhang, Y., Li, D., Yang, H., Huang, L. Signature-oriented investigation of the efficacy of multicomponent drugs against heart failure.

[Molecular mechanism of Tibetan medicine Rhodiola crenulata prevents oxidative stress through network pharmacology].

In this study, a computer-based network pharmacology approach was applied to investigate the potential mechanism and important components of Rhodiola crenulata in the protection of H9c2 cells against hydrogen peroxide (H2O2)-induced oxidative stress. The intestinal absorption liquid of R. crenulata enhanced the cell viability, maintained cell morphology and inhibited cell apoptosis in the H2O2-induced oxidative stress in H9c2. Then, computer-based network pharmacology was used to analyze the relevant mechanism. A total of 133 oxidative stress-related compounds were screened out; and 26 of them occupied the top 20%, and all of the compounds enriched in 43 oxidative stress-related key targets. Finally, a "compound-target-pathway-function" network was constructed. Based on the analysis of the network pharmacology, R. crenulata protected H9c2 cells against H2O2-induced oxidative stress probably by affecting apoptosis-related processes, such as cell death, nitric oxide metabolism, oxidative stress, mitochondrial mechanism, redox process, redox-related enzyme activty and other oxidative stress-related process. And salidroside, ethyl gallate and catechins, which were the main components of R. crenulata, played an important role in this process. Therefore, the potential mechanism and important components of R. crenulata revealed the protective effect on oxidative stress. This study shows a multi-component, multi-target and overall regulation effect of R. crenulata on the oxidative stress, and provides a reliable reference for subsequent systematic experimental studies for the pharmacodynamic material foundation and mechanism of action R. crenulata.

[Compatibility law of Baizhi formulae and molecular mechanism of core herbal pair "Baizhi-Chuanxiong"].

By using the traditional Chinese medicine inheritance support system (TCMISS) in this study, the prescription rules of Baizhi formulae were analyzed and the core herbal pair "Baizhi-Chuanxiong" was obtained. Through the systemic analysis of prescription rules of "Baizhi-Chuanxiong" and combined with the pharmacology thinking of "Baizhi-Chuanxiong" in treating headache, the paper was aimed to find out the combination rules containing Baizhi andits molecular mechanisms for treating headaches, and provide the theory basis for further research and reference of Baizhi and its formula. Totally 3 887 prescriptions were included in this study, involving 2 534 Chinese herbs. With a support degree of 20% in analysis, 16 most commonly used drug combinations were screened, which were mainly used to treat 15 types of diseases. Baizhi was often used to treat headache, and the core combination "Baizhi-Chuanxiong" was also often used to treat, consistent with ancient record. A chemical database was established; then the headache and migraine disease targets were retrieved and added in the database to build up the "compounds-targets-pathways "core network of "Baizhi-Chuanxiong" by the internet-based computation platform for IP of TCM (TCM-IP). TCM-IP was then applied to study the molecular mechanism of "Baizhi-Chuanxiong" treatment of headache. The results suggested that37 chemical compounds in the core combination "Baizhi-Chuanxiong" were closely related with headache treatment by adjusting serotonin levels or applying to inflammation-related targets and energy metabolism pathways such as purine metabolism, pyruvate metabolism, fatty acid degradation, carbon metabolism and gluconeogenesis.

[Study on Yueju Wan for "different diseases with same treatment" based on integrative pharmacology].

The traditional Chinese medicine prescription Yueju Wan has the function of regulating qi-flowing for activating stagnancy and resolving food stagnation, which is now used for the treatment of depression and gastrointestinal related diseases. In this study, an integrative pharmacological method was adopted to predict the targets and pathways of Yueju Wan and explore its molecular mechanism for depression and gastrointestinal dysfunction with the same treatment. First, disease targets were collected from Human Phenotype Ontology database, 201 targets related to depression and 474 targets related to gastrointestinal dysfunction, including 95 common targets of these two. Then, the integrative pharmacology platform of traditional Chinese medicine (TCMIP) was used to predict and analyze the drug targets, GO function, KEGG pathway, core targets network of Yueju Wan and heterogeneous network of TCM-chemical components-key drug targets-pathway. According to the integrative analysis, it is found that ATP1A1, KRAS, and PRKAA1 were key targets, and neuron apoptotic process, neurotrophin signaling pathway, serotonergic synapse and regulation of nitric-oxide synthase activity were key pathways which played important roles in molecular mechanism of Yueju Wan for depression and gastrointestinal dysfunction. In conclusion, speculated serotonergic synapse and regulation of nitric-oxide synthase activity maybe the common process in depression and gastrointestinal dysfunction. This paper provided an overall understanding on Yueju Wan based on TCMIP, helping to elucidate the mechanism of the same treatment for different diseases, depression and gastrointestinal dysfunction.

Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap, ADME prediction and network target analysis.

BACKGROUND: Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription. PURPOSE: To identify potential Q-markers of XSNC against arrhythmia. STUDY DESIGN: An integrative pharmacology-based investigation was performed. METHODS: Ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) was performed to identify the preliminary chemical profile of XSNC in a rapid and high-throughput manner. Then, in silico Absorption-Distribution-Metabolism-Excretion (ADME) models were utilized to screen candidate active chemical compounds characterized by drug-likeness features. In addition, drug target-disease gene interaction network was constructed, and network features were calculated to identify key candidate targets and the potential Q-markers of XSNC against arrhythmia. RESULTS: A total of 41 chemical compounds with good drug-likeness and more chances to be absorbed into body were identified as the candidate bioactive chemical compounds which might offer contributions to the therapeutic effects of XSNC against arrhythmia in vivo. Following the prediction of 921 XSNC putative targets and the construction of XSNC putative target-known therapeutic target of arrhythmia interaction network, 315 hub nodes with high connectivity were selected. Functionally, the hub nodes were involved into modulation of cardiac sympatho-vagal balance, regulation of energy production and metabolism, as well as angiogenesis and vascular circulation during the development and progression of arrhythmia. Moreover, 63 major hubs with network topological importance were chosen as XSNC candidate targets against arrhythmia. Furthermore, berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone hitting the corresponding XSNC candidate targets were screened out to be the potential Q-markers of XSNC against arrhythmia. CONCLUSION: Our integrative pharmacology-based approach combining UHPLC-LTQ-Orbitrap, in silico ADME prediction and network target analysis may be efficient to identify potential Q-markers of TCM prescriptions. Our data showed that berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone might function as candidate markers for qualitative evaluation of XSNC.