Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Methodology for Screening Effective Substances of Chinese Herbal Medicine for Reducing Serum Uric Acid Level / 中国实验方剂学杂志

Gout is caused by the nucleation and growth of monosodium rate crystals in tissues and around joints, which is followed by long-standing hyperuricemia and serum urate of above the saturation threshold. It could cause a series of complications, such as cardiovascular, hypertension, and renal complications. Over the past two decades, the incidences of hyperuricemia and gout have been increasing due to the continuous improvement of living standards and the changes in dietary structure. The prime and most important therapy for hyperuricemia and gout is to reduce serum uric acid levels, but the western medicine for reducing uric acid in clinical application has serious toxic and side effects. With the rapid development of modern science and technology, the application and development of different screening methods for effective ingredients with a low toxicity and side effects from Chinese herbal medicines for reducing serum uric acid levels has attracted much attention in the research and development of drugs for the prevention and treatment of hyperuricemia and gout. In this study, the screening methods for extracts, fractions, active monomer components and other effective substances were reviewed and analyzed. According to the findings, the screening methods had a considerable progress both in vivo and in vitro. The results showed that the in vivo methods were mainly applied for studying the urate lowing effect and mechanisms of herbal extracts, while the studies for xanthine oxidase(XOD) inhibitors mainly depended on the in vitro methods. Molecular docking homology modeling and liquid chromatography-mass spectrometry have become a new trend for screening effective substances with XOD inhibitory activities and uric acid excretion activities, while cell model will open up a new way for screening effective substances for uric acid excretion. The review provides certain reference for effective components screening of hyperuricemia and gout.

Membrane permeability evaluation method of oral drugs and their application progress in Chinese materia medica / 中草药

Chinese materia medica is mostly taken orally. The permeability of a drug’s biofilm (e.g. cell membrane) reflects its ability of absorption and transportation in the body. It is of guiding significance to evaluate the membrane permeability of the active components of Chinese materia medica by using appropriate drug permeation model, so as to clarify, the oral absorption and transport mechanism of active ingredients, pharmacodynamic substance basis and dosage form design. The evaluation method of oral drug membrane permeability, as well as the application of various methods in Chinese medicine was summarized for reference in this review.

Research Progress on the Effective Substances and the Mechanism of Traditional Chinese Medicine Compound / 中国药学杂志

It is important to elucidate the effective substances and the mechanism of Traditional Chinese Medicine (TCM) compound in revealing the compatibility mechanism of TCM, completing the transformation of large varieties of TCM, modernizing TCM, and gaining international recognition. The research METHODS mainly include: the serum pharmacochemistry, network pharmacology, spectrum-effect relationship, high throughput screening, metabonomics and so on. The main research METHODS reviewed through domestic and foreign related literatures can provide the reference for elucidating the effective substances and the mechanism of TCM compound.

The Mechanism Study of Micro-substance of Chinese Medicine——The Discovery and Elucidation of Effective Substance and Mechanism of Chinese Medicine via the Theory of Synthetic Lethality / 世界科学技术-中医药现代化

The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.

Separation and Identification of Surface Preponderant Fungi on Citri Reticulatae Pericarpium and Its Influence on Effective Substance / 世界科学技术-中医药现代化

This paper studied the influence ofsurface preponderantfungi on main effective substances of CitriReticulatae Pericarpium (CRP).Spreading plate method was used to isolatepredominant strains from the surface of CRP.Besides,the method combining microscopic and molecular identification was also adopted.HPLC and UVspectrophotometric methods were used to determine the main effective substances in CRP.From thesurface of CRP,the advantage strain fungi were Aspergillusniger and A.Flavus.After the inoculation of A.Niger and A.flavus against CRP,the effective compositionwas changed.And different A.niger strains had differenceeffectiveness oneffective chemical components,especially one strain of A.niger.Compared withthe control group,contents of total flavonoids and hesperidin were significantly increased (P＜0.01);and five types of obvious new chemical compositions were produced.It was concluded that the metabolic transformation of fungi was related tochanges ofeffective substances of CRP,which played a significant role in the aging process of CRP.The growth and metabolism of fungi consumeeffeetive substances and producechanges of composition.From the perspective of microorganisms,"the older,the better" of CRP hasa better explanation.

Exploration and review on substance basis responsible for "Xuanfa" and its biological mechanisms about "Zhijie" / 中草药

Although the basic theory of "Xuanfa Sujiang" has been generally accepted by Chinese medicine practitioners, it is still controversial that traditional Chinese medicine (TCM) theory is combined with modern biology and interpreted by modern science. Based on relevant classical theories, prescriptions, pharmacological substance basis and biological mechanism, we put forward the following points in this paper: The effect and function of "Feiqi" governing organ movement depends on the difference about subtype or expression of adrenergic receptors on the post ganglionic fibers dominated autonomic effector. Coincidentally, TCM theory selected different types of natural effective molecules, such as phenylethylamine and its derivatived alkaloid, to achieve a good sympathetic regulation, and just meet the different needs of clinical treatment; The β-AR/cAMP/PKA signaling pathway is the core pathways for positive regulation; The concept of the "Zhijie" is closely related to the balance of myosin light chain phosphorylation and dephosphorylation levels; Prescription compatibility can effectively enhance the crosstalk between adrenergic receptor-related multiple signal pathways, and reflect the advantages of TCM for complex diseases treatment by multi-ingredients and multi-targets.

Study on anti-inflammatory components in Rosae Rugosae Flos based on bioactivity-integrated UPLC-Q/TOF method / 中草药

Objective: To investigate the anti-inflammatory effect of Rosae Rugosae Flos (RRF) and screen its bioactive components on nuclear factor-κappa B (NF-κB) inhibition by ultra-performance liquid chromatography coupled with quadrupole/time of flight mass spectrometry (UPLC-Q/TOF MS). Methods: The anti-inflammatory effect of RRF was assessed in Pseudomonas aeruginosa strain-induced acute lung infection mouse model. UPLC-Q/TOF MS coupled with NF-κB activity luciferase reporter assay system was applied to detect the potential anti-inflammatory components in RRF extract. Results: The administration of RRF extract could ameliorate the neutrophil infiltration and diminish the levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), and IL-8 in P. aeruginosa induced mice. Seven components were screened to have potential NF-κB inhibitory effects based on the bioactivity-integrated UPLC-Q/TOF assay system. Conclusion: RRF can contribute to the alleviation of inflammation in mice with acute lung infection induced by P. aeruginosa strain. Seven potentially active ingredients, such as gallic acid, 4-O-galloylquinic acid, methylgallate, centaureidin, strictinin, casuariin, and ellagic acid are found to have anti-inflammatory effects as NF-κB inhibitors.

Spectrum-effect relationship of Bupleurum chinense for hepatoprotective effect based on cluster analysis and typical correlation analysis / 中草药

Objective: To analyze the spectrum-effect relationship between the hepatoprotective effect and HPLC fingerprints of the n-butanol fraction extracted from Bupleurum chinense and to elucidate its effective substance. Methods: HPLC-ELSD was used to obtain the fingerprint peaks of n-butanol fraction of B. chinense; the levels of alanine transarninase (ALT) and aspartate aminotransferase (AST) in serum, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity in liver tissue of mice with acute hepatic injury induced by CCl4 were detected. Cluster analysis and typical correlation analysis were used to analyze the data of spectrum and efficacy. Results: Twelve common peaks which could show the features of B. chinense were isolated and there was statistical difference (P < 0.05) among the hepatoprotective effects of B. chinense from different origins. Saikoside a and saikoside d were proved to have linear relationship with the serum ALT level and liver tissue SOD activity in mice with acute liver injury in the treatment group by cluster analysis and typical correlation analysis. Conclusion: Saikoside a and saikoside d are the effective substances of B. chinense with hepatoprotective effect.

Bioethnopharmaceutical analytical pharmacology:a strategy for elucidating ethnoherbal absorbed bioactive compounds / 中草药

To review the background and advance of a strategy of bioethnopharmaceutical analytical pharmacology(BAP).BAP is an idea for elucidating absorbed bioactive compound(ABC)in traditional Chinese medicine(TCM)formula or herbal remedy.It is also a mode of active comparison between absorbed compounds and the parent formula including determination of ABC in blood,the ABC dosage identical to its content in formula,and the active comparison of ABC and the parent formula.The ABC of Guan-Xin-Er-Hao formula elucidated by BAP strategy has been reviewed and the significance of BAP strategy will be further discussed.