Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test / 中国中药杂志

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.

Pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus Herb-pair Extract, in kidney-yin deficiency model

Abstract To investigate the pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus herb-pair in kidney-yin deficiency model, which was made by continuously oral gavage of thyroxine. A simple and rapid LC-MS/MS method was developed and validated for the determination of loganin and morroniside in rat plasma and used for the pharmacokinetics study. The kidney-yin deficiency significantly changed the AUC(0-∞), Cmax and CLz/F of loganin and morroniside. The T1/2z of morroniside increased significantly in the kidney-yin deficiency rats. For the pharmacodynamics study, the liver index, kidney index, and ALT, TBIL, UREA, CREA level in the kidney-yin deficiency mice were examined. The herb-pair had been proved to be effective for the treatment of kidney-yin deficiency by affecting the liver, kidney, ALT, UREA and CREA, which showed positively correlated with the dose. The pharmacokinetics and pharmacodynamics studies in the pathological status could offer more valuable information for the future application of Astragali Radix-Corni Fructus herb-pair.

Effect of Asari Radix et Rhizoma-Zingiberis Rhizoma Herb Pair on Lung and Liver Lipid Metabolism in Rats with COPD Based on Metabolomics and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair （XGHP） on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease （COPD）. MethodForty SD male rats were divided into a normal group （10 rats） and a model group （30 rats）. The method of cigarette smoke + tracheal injection of lipopolysaccharide（LPS） + cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung. A COPD group， a XGHP group （5.4 g·kg-1·d-1）， and an aminophylline group （0.5 g·kg-1·d-1） were established after successfully inducing the model， with 10 rats in each group. After treatment， the serum triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels of rats in each group were measured. Gas chromatography-mass spectrometer （GC-MS） was used to detect the differential metabolites in the lung and liver tissues of rats in each group， and the relevant targets of the differential metabolites were predicted by network pharmacology. Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology. The mRNA and protein expression levels of peroxisome proliferator-activated receptor α （PPARα） and fatty acid binding protein 4 （FABP4） in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction （PCR） and Western blot. ResultXGHP significantly increased the levels of TG， TC， and LDL-C in serum （P<0.05）， and decreased the level of HDL-C （P<0.05） in rats with COPD. GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group. Network pharmacology predicted 59 common targets for the two differential metabolites， mainly enriched in the PPAR signaling pathway. Molecular docking results showed that the main components in XGHP were well combined with both PPARα and FABP4. Real-time PCR showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 mRNA （P<0.05）， and Western blot showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 proteins （P<0.05） in lung and liver tissues of rats with COPD. ConclusionXGHP effectively improves the blood lipid levels of rats with COPD， which may be related to the increase of the expression levels of PPARα and FABP4 mRNA and proteins in the PPAR signaling pathway， thus regulating lung and liver lipid metabolism.

Effect of Asari Radix et Rhizoma-Zingiberis Rhizoma Herb Pair on Lung and Liver Lipid Metabolism in Rats with COPD Based on Metabolomics and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair （XGHP） on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease （COPD）. MethodForty SD male rats were divided into a normal group （10 rats） and a model group （30 rats）. The method of cigarette smoke + tracheal injection of lipopolysaccharide（LPS） + cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung. A COPD group， a XGHP group （5.4 g·kg-1·d-1）， and an aminophylline group （0.5 g·kg-1·d-1） were established after successfully inducing the model， with 10 rats in each group. After treatment， the serum triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels of rats in each group were measured. Gas chromatography-mass spectrometer （GC-MS） was used to detect the differential metabolites in the lung and liver tissues of rats in each group， and the relevant targets of the differential metabolites were predicted by network pharmacology. Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology. The mRNA and protein expression levels of peroxisome proliferator-activated receptor α （PPARα） and fatty acid binding protein 4 （FABP4） in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction （PCR） and Western blot. ResultXGHP significantly increased the levels of TG， TC， and LDL-C in serum （P<0.05）， and decreased the level of HDL-C （P<0.05） in rats with COPD. GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group. Network pharmacology predicted 59 common targets for the two differential metabolites， mainly enriched in the PPAR signaling pathway. Molecular docking results showed that the main components in XGHP were well combined with both PPARα and FABP4. Real-time PCR showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 mRNA （P<0.05）， and Western blot showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 proteins （P<0.05） in lung and liver tissues of rats with COPD. ConclusionXGHP effectively improves the blood lipid levels of rats with COPD， which may be related to the increase of the expression levels of PPARα and FABP4 mRNA and proteins in the PPAR signaling pathway， thus regulating lung and liver lipid metabolism.

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy / 中国天然药物

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

Comparative Study in Situ on Rat Intestinal Absorption Mechanism of Paeoniflorin in Single Herb, Herb-pair, and Complicated Chinese Herbal Formula / 中国药学杂志

OBJECTIVE: To investigate the absorption mechanism of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis and Siwu Decoction. METHODS: The circulatory perfusion technique was used in this study, the concentrations of paeoniflorin and phenol red in intestinal absorption circulation were respectively determined by HPLC and UV. The effects of pH value, drug concentration, absorption site and P-gp on the absorption of paeoniflorin were investigated separately. RESULTS: By comparing the absorption of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis, and Siwu Decoction, it was found that in the sample solution at the same absorption site, pH value and concentration (based on the concentration of paeoniflorin), the absorption, Ka and cumulative absorption of paeoniflorin in compound Siwu decoction group were significantly increased compared with the other groups (P<0.05), while t1/2 was significantly decreased (P<0.05). When combined with the inhibitor and inducer of P-gp, the absorption of paeoniflorin showed significant increase or decrease in the amount of absorption, Ka and cumulative absorption% compared with the control group (P<0.05), and t1/2 also showed significant decrease or increase (P<0.05). CONCLUSION: The absorption of paeoniflorin could be affected by P-gp, and under the same conditions, the absorption of paeoniflorin in complicated Chinese herbal formula is better than that in the single herb and herb-pair.

Advances in Research on Different Compatibility Ratios of Coptidis Rhizoma-Evodia Fructus / 中国实验方剂学杂志

Coptidis Rhizoma-Evodia Fructus is a classic herb pair in traditional Chinese medicine prescriptions, the famous prescription is called Zuojinwan, which comes from Danxi Xinfa, is composed of Coptidis Rhizoma-Evodia Fructus (6∶1). In this formula, Coptidis Rhizoma has the effect of clearing heat and drying diuresis, purging fire to remove toxin and clearing heart. Evodia Fructus has the effects of expelling cold and alleviating pain, checking upward adverse flow of Qi tostop vomiting, and assisting yang to stop diarrhea. Coptidis Rhizoma has the properties of bitter and cold, and Evodia Fructus has the properties of pungent and calidus. Pungent drugs have divergent effects, and bitter drugs have sedimentation effect, when used in combination, they can clear the liver and purge fire, calm the adverse-rising energy and stop vomiting. On the basis of Zuojinwan, Coptidis Rhizoma-Evodia Fructus medicine has derived different compatibility ratios. Different ratios are different in terms of efficacy, usage, clinical application. Although with the application of modern analytical instruments and the development of molecular pharmacology theory, the chemical constituents and Pharmacological effects of Coptidis Rhizoma and Evodia Fructus have been fully studied, as to the principle of compatibility, and the study of pharmacological effects and chemical constituents after the compatibility of the two drugs in different proportions, there is still no comprehensive system summary. This article makes a systematic and comprehensive explanation of Coptidis Rhizoma-Evodia Fructus from the aspects of famous literature, chemical composition, pharmacological effects and clinical applicationthrough querying literature and ancient books. In order to make this herb pair more standardized, and provide reference materials for further research and development for this herb pair.

Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-glycoprotein / 药物分析学报

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

The mechanism of the anti-depression effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair determined by liver metabolomics / 药学学报

This study analyzed the effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair on endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression by using LC-MS liver metabolomics. Rats were randomly divided into 5 groups: a normal control group, a CUMS model group, a venlafaxine-positive group, and a high-low dose group for the Radix Bupleuri-Radix Paeoniae Alba herb pair, with continuous modeling and administration over 28 days. The efficacy of Radix Bupleuri-Radix Paeoniae Alba herb pair was evaluated by measuring traditional pharmacodynamic indicators of depression (body weight, open field test, sucrose preference test and forced swimming test). Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036). Liver metabolic profiles were obtained by the UHPLC-Q Exactive Orbitrap-MS metabolomics technique. The results show that the Radix Bupleuri-Radix Paeoniae Alba herb pair can significantly decrease depression-like behavior of rats in the CUMS model group. Increases in 25 depression-related metabolites were identified by LC-MS metabonomics, and the Radix Bupleuri-Radix Paeoniae Alba herb pair could significantly decrease 16 of them. Metabolic pathway analysis showed that D-glutamine and D-glutamate metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism were the main metabolic pathways altered by this herb pair in CUMS model rats.

Research progress of traditional Chinese antidepressant herb-pair / 药学学报

@#Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

Comparative study on the effect of Danggui-Chuanxiong herb pair on vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats using PLS-DA and multi-attribute comprehensive index methods / 药学学报

We evaluated the effects of Danggui-Chuanxiong (GX) herb pair with different proportions (1∶0, 3∶2, 1∶1, 2∶3, 0∶1) and preparation methods (water extract W, alcohol extract A, and water-alcohol extracts WA) on vasoactive substances and endothelial cell adhesion molecules in the serum of acute blood stasis in rats. An acute blood stasis model was co-replicated by ice water bath and subcutaneous injection of epinephrine hydrochloride in rats. The expressions of vasoactive substances (arachidonic acid metabolites, coagulation-fibrin system index) and adhesion molecules in the serum were detected by enzyme linked immunosorbent assay method; the Spearman method was used to analyze the correlation of those detection indicators; the partial least squares-discriminant analysis and multi-attribute comprehensive index method were used to comprehensively evaluate the total effect of GX herb pair samples with different proportions and preparation methods on vasoactive substances and adhesion molecules. The experimental scheme was approved by the Animal Experimental Ethics Committee of the First Affiliated Hospital of Henan University of Chinese Medicine. The results showed that GX 1∶1_WA had the strongest effect on the improvement of vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats (the total effect value was 6.96). When extraction method was same, the overall effect of GX 1∶1 had better effect than that of other proportions; when the proportion of GX was same, the total effects of GX_WA and GX_A were better than GX_W. The combination of Danggui and Chuanxiong can significantly improve the expressions of vasoactive substances and adhesion molecules in the serum of blood stasis in rats. But the action strength of GX herb pairs was different when the proportions and preparations of GX herb pair were different. These findings provide a basis for clinical rational application of GX herb pair, and lay the foundation for in-depth research on GX herb pair for treatment of blood stasis related diseases.

Modern research approaches and strategies for compatibility effects and efficacy components of herbal pairs / 药学学报

The herb pair is the simple and exquisite experience summary accumulated by generations of traditional Chinese medicine (TCM) experts in the process of long-term herbal prescription for curing diseases. Although it is only a combination of two herbs, it is cleverly matched and properly proportioned, which can well interpret TCM characteristics of "great combination and artful application". Moreover, the herb pair is an intermediate point between single herb and several TCM formulae, which implicates certain regularity and some connotation of many TCM formulae for diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Our team has long been focusing on the complexity of drug interactions and the diversity of TCM components to carry out systematic research on herb pair by using modern scientific and technological knowledge and approaches. As results, a series of modern research approaches and strategies formed for the compatibility effect and bio-active components of the herb pair. By representing the principles and application characteristics of these approaches, this paper provides important support for elucidating scientific connotation of compatibility regularity of herb pairs and application of formulae optimization, as well as explorative ideas and approaches for modern research on other herb pairs.

The improving effect of Zhimu-Huangbai herb pair on insulin resistance / 中国药理学通报

Aim To explore the effects of Zhimu-Huangbai herb pair( ZB) on insulin resistance. Methods The rat model of experimental T2DM was induced by intraperitoneal injection of streptozotocin after feeding with high fat and sucrose forage. Rats with T2DM were randomly divided into normal group, model group, metformin group and high-, low-dose ZB group(4. 5, 1. 5 g • kg"1) , with corresponding drugs administered orally by gastric gavage once a day for four weeks. The body weight, fasting blood glucose ( FBG ) , serum insulin level ( FINS ) and triglyceride content(TG) were measured, and the insulin sensitivity index(ISI) and insulin resistance index ( Homa-IR) were calculated. The HepG2 cells were treated with palmitate and oleate to induce insulin resistance, then divided into six groups: Control group, model group, metformin group and high-, middle-, low-dose ZB group(384, 192, 96 mg • L'1). Glucose consumption and TG content were assayed 24 h after administration. Results ZB not only markedly lowered the level of FBG, FINS, TG content (P <0. 05) and insulin resistance index ( P < 0. 01 ) , increased insulin sensitivity index(P <0. 05) in rats with T2DM, but also significantly decreased TG content (P <0. 05) and increased glucose consumption ( P < 0. 05 ) in HepG2 cell model with insulin resistance. Conclusions ZB can promote glucolipid metabolism and improve the insulin resistance by increasing insulin sensitivity.

Herb pair Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma: Mechanism analysis by systemic pharmacology approach / 中草药

Objective To study the functional material basis of herb pair Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma and analyze their mechanism of action by the systematic pharmacological method based on the platform of traditional Chinese medicine systematic pharmacological analysis (TCMSP) and the big data of traditional Chinese medicine. Methods TCMSP was used to search for the chemical constituents of the two Chinese herbal medicines, “Baishao” and “Gancao”. The molecular descriptors of the components were compared by the two tailed Mann-Whitney U test method, and the oral bioavailability (OB) and drug-likeness (DL) were used as indicators to screen the active components, targets and related diseases of the herb pair. The “component-target-disease” and PPI network models were constructed, and bioprocess and metabolic pathway were analyzed to explore the drug-based material basis and mechanism of action. Results Through the OB and DL parameters screening, 49 active pharmaceutical ingredients, 100 targets and 230 related diseases were obtained. The active ingredients with higher degree were formononetin, naringenin, and vestitol; The higher degree of targets were prostaglandin g/H synthase 2 (PTGS2), estrogen receptor (ESR1), and calmodulin (CALM); The higher-grade related diseases were unspecific cancer, inflammation, cardiovascular disease, unspecified, Alzheimer’s disease, and Parkinson’s disease, mainly involving 16 categories of diseases such as cancer, nervous system diseases, endocrine, nutritional and metabolic diseases and certain infectious diseases and parasitic diseases. Target proteins are involved in bioprocess including signal transduction, drug response, cell proliferation, RNA polymerase II promoter regulation, positive regulation of ERK1 and ERK2 cascades, regulating metabolic pathways such as PI3K-Akt and 5-hydroxytryptamine synapses. Conclusion This study preliminarily verified the basic pharmacological effects and mechanisms of the Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma herb pair, and explored new ideas for the study of the herb pair and related traditional Chinese medicine prescriptions.

Interaction of Scutellaria-Coptis herb pair in improvement of glucose and lipid metabolism of type 2 diabetes rats based on response surface method / 药学学报

The response surface method was used to evaluate the concentration range, property and degree of Scutellaria (HQ) and Coptis (HL) herb pair on improvement of glucose and lipid metabolism in this paper. Type 2 diabetes mellitus (T2DM) was induced in rats by low a dose of streptozotocin (STZ) in combination with high-fat diet feeding. The rats were administered with HQ-HL extract pairs at different ratio (1:0, 3:1, 2:1, 3:2, 1:1, 2:3, 1:2, 1:3, 0:1). To investigate the influence of herb pair extracts on glucose and lipid metabolism of T2DM rats, the multi index synthetic index method was adopted to integrate the indexes, then the response surface method was applied to analyze the integration results. The ratio of HQ and HL from 3:1 to 1:3 showed a synergistic effect (with the value between -0.2 and -0.8). Especially, when the proportion was between 3:2 and 1:3, herb pair extracts possessed stronger synergistic effects (value:-0.8). The high dose of HQ-HL with the ratio of 1:1 exhibited the strongest synergistic effect.

Antipyretic Effect of Herba Ephedrae-Ramulus Cinnamomi Herb Pair on Yeast-Induced Pyrexia Rats: A Metabolomics Study / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats.</p><p><b>METHODS</b>Totally 30 qualified male SD rats were randomly assigned to the normal control (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling.</p><p><b>RESULTS</b>Compared with the NC group, rectal temperatures were significantly higher in the model group (P<0.01), while 3 treatment groups decreased significantly compared with the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software.</p><p><b>CONCLUSION</b>The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.</p>

Discussion on Character of Xiaoqinglong Decoction Based on HPLC Fingerprints of Single Herb and Herb-pair / 世界科学技术-中医药现代化

Xiaoqinglong decoction,first recorded by Zhang Zhongjing in traditional Chinese medicine (TCM) classic text Shang Han Lun (Treatise on Cold Damage Diseases),has eight herbal components including Herb Ephedrae (Mahuang),Radix Paeoniae Alba (Shaoyao),Radix Asari (Xixin),Rhizoma Zingiberis (Ganjiang),Glycyrrhiza Uralensis (Gancao),Ramulus Cinnamomi (Cuizhi),Rhizoma Pinelliae (Banxia) and Fructus Schisandrae (Wuweizi).Fingerprints of HPLC for single herb and herb-pair including Mahuang-Gancao,Mahuang-Guizhi,Shaoyao-Guizhi,Shaoyao-Gancao,Wuweizi-Xixin were analyzed.Based on the HPLC of single herb and herbal pair,we discussed the character of the Xiaoqinglong decoction and explored the scientific connotation of the compatibility of medicines in prescription.

Origin of lifting and lowering theory and its herb pair study / 中国中药杂志

Lifting and lowering theory is one of the important basis for guiding clinical medication. Through the study of ancient books and literature, we learned that lifting and lowering theory was originated in Huangdi Neijing, practiced more in the Shanghan Zabing Lun, established in Yixue Qiyuan, and developed in Compendium of Materia Medica and now. However, lifting and lowering theory is now mostly stagnated in the theoretical stage, with few experimental research. In the clinical study, the guiding role of lifting and lowering theory to prescriptions?mainly includes opposite?role?of lift and lower medicine property, mutual promotion of lift and lower medicine property, main role of lift medicine property and main role of lower medicine property. Under the guidance of lifting and lowering theory, the herb pair compatibility include herb combination of lift medicine property, herb combination of lift and lower medicine property and herb combination of lower medicine property. Modern biological technology was used in this study to carry out experimental research on the lifting and lowering theory, revealing the scientific connotation of it, which will help to promote clinical rational drug use.