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  1. Article ; Online: Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats.

    Wang, Chao / Jiang, Shengyu / Zheng, Haoyu / An, Yiming / Zheng, Wenxue / Zhang, Jiaqi / Liu, Jianming / Lin, Hongqiang / Wang, Guoqiang / Wang, Fang

    Journal of ethnopharmacology

    2023  Volume 319, Issue Pt 3, Page(s) 117294

    Abstract: Ethnopharmacological relevance: Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used ...

    Abstract Ethnopharmacological relevance: Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined.
    Aim of the study: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism.
    Materials and methods: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease.
    Results: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats.
    Conclusion: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.
    MeSH term(s) Male ; Rats ; Animals ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy ; Gastrointestinal Microbiome ; Rats, Wistar ; Metabolome ; Acetic Acid
    Chemical Substances Acetic Acid (Q40Q9N063P)
    Language English
    Publishing date 2023-10-14
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.117294
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Zhi-Zi-Chi Decoction Reverses Depressive Behaviors in CUMS Rats by Reducing Oxidative Stress Injury

    Zhang, Yin / Fang, Yi-Chao / Cui, Li-Xun / Jiang, Yue-Tong / Luo, Yu-Sha / Zhang, Wen / Yu, De-Xun / Wen, Jun / Zhou, Ting-Ting

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 887890

    Abstract: ... As a traditional Chinese medicine, Zhi-zi-chi decoction is utilized to regulate and improve depression. However, the research ... on the antidepressant mechanism and efficacy material basis of Zhi-zi-chi decoction has not been reported ... yet. Our previous research has found that Zhi-Zi-chi decoction can reduce glutamate-induced oxidative stress damage ...

    Abstract Depression is one of the main diseases that lead to disability and loss of ability to work. As a traditional Chinese medicine, Zhi-zi-chi decoction is utilized to regulate and improve depression. However, the research on the antidepressant mechanism and efficacy material basis of Zhi-zi-chi decoction has not been reported yet. Our previous research has found that Zhi-Zi-chi decoction can reduce glutamate-induced oxidative stress damage to PC 12 cells, which can exert a neuroprotective effect, and the antidepressant effect of Zhi-Zi-chi decoction was verified in CUMS rat models. In this study, the animal model of depression was established by chronic unpredictable mild stimulation combined with feeding alone. The brain metabolic profile of depressed rats was analyzed by the method of metabolomics based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass. 26 differential metabolites and six metabolic pathways related to the antidepressant of Zhi-zi-chi decoction were screened and analyzed. The targeted metabolism of the glutathione metabolic pathway was analyzed. At the same time, the levels of reactive oxygen species, superoxide dismutase, glutathione reductase, glutathione peroxidase in the brain of depressed rats were measured. Combined with our previous study, the antioxidant effect of the glutathione pathway in the antidepressant effect of Zhi-zi-chi decoction was verified from the cellular and animal levels respectively. These results indicated that Zhi-zi-chi decoction exerted a potential antidepressive effect associated with reversing the imbalance of glutathione and oxidative stress in the brain of depressed rats.
    Language English
    Publishing date 2022-04-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.887890
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Butyrate emerges as a crucial effector of Zhi-Zi-Chi decoctions to ameliorate depression via multiple pathways of brain-gut axis.

    Liu, Jialin / Fang, Yichao / Cui, Lixun / Wang, Zhongzhao / Luo, Yusha / Gao, Congcong / Ge, Wen / Huang, Taohong / Wen, Jun / Zhou, Tingting

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2022  Volume 149, Page(s) 112861

    Abstract: Gut microbiota has emerged as a crucial target of gut-brain axis to influence depression. Zhi-Zi ...

    Abstract Gut microbiota has emerged as a crucial target of gut-brain axis to influence depression. Zhi-Zi-Chi decoctions (ZZCD), as a classic oral formula in clinic, is widely applied in depression treatment nowadays. However, the underlying mechanism in the antidepressant activity of ZZCD remains unknown. A classic depression model of chronic mild unpredictable stress (CUMS) was established in rats based on the results of behavioral tests and hippocampal histomorphology. 16S rRNA sequencing analysis indicated that ZZCD could increase short-chain fatty acid-producing and anti-inflammatory bacteria and reduce inflammatory and tryptophan-metabolizing bacteria. Furthermore, ZZCD reversed the alterations of BDNF, TNF-α, pro-inflammatory cytokines and neurotransmitters in the gut, blood and brain along the brain-gut axis and restored the decrease of butyrate in cecal content caused by CUMS. Then, butyrate was utilized to validate its ameliorative effect on pathological characteristics of depressive rats. Taken together, these results show that ZZCD exhibits antidepressant effect through modulating gut microbiota to facilitate the production of butyrate, which further regulate anti-inflammation, neurotransmitters, endocrine and BDNF along the gut-brain axis. Hence, this study fills the gap of the antidepressive mechanism of ZZCD in the light of the brain-gut axis and established a multi-targets and multi-levels platform eventually for further research into the mechanism of other TCM efficacy.
    MeSH term(s) Animals ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Brain-Derived Neurotrophic Factor ; Brain-Gut Axis ; Butyrates/pharmacology ; Depression/metabolism ; Drugs, Chinese Herbal ; RNA, Ribosomal, 16S ; Rats ; Stress, Psychological/metabolism
    Chemical Substances Antidepressive Agents ; Brain-Derived Neurotrophic Factor ; Butyrates ; Drugs, Chinese Herbal ; RNA, Ribosomal, 16S
    Language English
    Publishing date 2022-03-23
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2022.112861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Quantitative multicomponent analysis of a single marker-based simultaneous determination and quality assessment of nucleoside analogs from Qi Zhi capsules.

    Bai, Biwei / Wang, Xijun / Yang, Le / Song, Hongwei / Yan, Guangli / Han, Ying / Fang, Heng / Sun, Hui

    Biomedical chromatography : BMC

    2022  Volume 37, Issue 3, Page(s) e5560

    Abstract: Qi Zhi capsule (QZC) is approved by the State Drug Administration of China. The QZC consists ...

    Abstract Qi Zhi capsule (QZC) is approved by the State Drug Administration of China. The QZC consists of nine crude drugs, including astragalus, leeches, ground beetles, curcuma zedoary, hawthorn, semen cassiae, rhizoma sparganii, polygonum multiflorum, and peach kernel, of which leeches and ground beetles are Traditional Chinese Medicine of animal origin. Nucleosides are animal substances with pharmacological effects that are easy to extract and quantify. Different nucleoside analogs in distinct animal-based formulations can be used to characterize animal-based medicines. However, the quality control of a single indicator does not reflect the overall quality of Chinese medicine. Here, we developed a method to simultaneously determine the nucleoside analogs uracil, xanthine, hypoxanthine, uridine, guanine, and uric acid in QZCs using high-performance liquid chromatography. Hypoxanthine was used as an internal reference to determine relative correction factors for the other five components. The six components were determined in ten different batches of QZCs. There was no significant difference between the quantitative multicomponent analysis of a single marker and the external standard method. The relative standard deviation of total nucleosides analogs of 10 batches of samples was 7%. This method can be applied to simultaneously determine multiple active components in QZCs and other nucleoside analog drugs, enabling multi-indicator quality control.
    MeSH term(s) Animals ; Drugs, Chinese Herbal/chemistry ; Nucleosides/analysis ; Qi ; Chromatography, High Pressure Liquid/methods ; Hypoxanthines
    Chemical Substances Drugs, Chinese Herbal ; Nucleosides ; Hypoxanthines
    Language English
    Publishing date 2022-12-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 632848-9
    ISSN 1099-0801 ; 0269-3879
    ISSN (online) 1099-0801
    ISSN 0269-3879
    DOI 10.1002/bmc.5560
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2166: Show issues Location:
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  5. Article ; Online: Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression.

    Gao, Fang-Yuan / Chen, Xue-Feng / Cui, Li-Xun / Zhai, Yu-Jia / Liu, Jia-Lin / Gao, Cong-Cong / Fang, Yi-Chao / Huang, Tao-Hong / Wen, Jun / Zhou, Ting-Ting

    Journal of ethnopharmacology

    2022  Volume 302, Issue Pt B, Page(s) 115934

    Abstract: Ethnopharmacological relevance: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases ...

    Abstract Ethnopharmacological relevance: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases", is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied.
    Aim of the study: To explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD.
    Materials and methods: A new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as "DIET" was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, β-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-β -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD.
    Results: The antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of β-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of β-glucosidase and sulfotransferases.
    Conclusions: It is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.
    MeSH term(s) Animals ; Rats ; Cellulases ; Chromatography, Liquid ; Depression/drug therapy ; Gastrointestinal Microbiome ; Iridoids ; Precision Medicine ; RNA, Ribosomal, 16S ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology
    Chemical Substances Cellulases (EC 3.2.1.-) ; Iridoids ; RNA, Ribosomal, 16S ; Drugs, Chinese Herbal
    Language English
    Publishing date 2022-11-19
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2022.115934
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  6. Article ; Online: Rapid discovery and identification of the anti-inflammatory constituents in Zhi-Shi-Zhi-Zi-Chi-Tang.

    Wang, Hai-Qiang / Zhu, Yun-Xiang / Liu, Yi-Ning / Wang, Ruo-Liu / Wang, Shu-Fang

    Chinese journal of natural medicines

    2019  Volume 17, Issue 4, Page(s) 308–320

    Abstract: The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT ...

    Abstract The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT), a traditional Chinese medicine formula, were predicted and identified using an approach based on activity index, LC-MS, semi-preparative LC and NMR. Firstly, the whole extract of ZSZZCT was analyzed using liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) and liquid chromatography - ion trap mass spectrometry (LC-IT-MS), 79 constituents were detected and 39 constituents were identified unambiguously or tentatively. Subsequently, the whole extract of the formula was separated into multiple components and the activity index method was used to calculate index values of the 79 constituents by integrating the chemical and pharmacological information of multiple components. Four polymethoxyl flavones were predicted as the major active constituents according to the activity index values. Furthermore, three polymethoxyl flavones were prepared using the strategy with semi-preparative LC guided by LC-MS, and their anti-inflammatory activities were validated. The results show that three polymethoxyl flavones with higher positive index values, i.e., 3, 5, 6, 7, 8, 3', 4'-heptamethoxyflavone, 3-hydroxynobiletein and tangeretin had significant anti-inflammatory effects. In conclusion, the predicted results indicated that the activity index method is feasible for the accurate prediction of active constituents in TCM formulae.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/isolation & purification ; Anti-Inflammatory Agents/pharmacology ; Drugs, Chinese Herbal/chemistry ; Drugs, Chinese Herbal/pharmacology ; Flavones/chemistry ; Flavones/isolation & purification ; Flavones/pharmacology ; Lipopolysaccharides/toxicity ; Macrophages/drug effects ; Macrophages/metabolism ; Medicine, Chinese Traditional ; Mice ; Molecular Structure ; Nitric Oxide/metabolism ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plants, Medicinal/chemistry ; RAW 264.7 Cells
    Chemical Substances Anti-Inflammatory Agents ; Drugs, Chinese Herbal ; Flavones ; Lipopolysaccharides ; Plant Extracts ; Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2019-05-10
    Publishing country China
    Document type Journal Article
    ZDB-ID 2192577-X
    ISSN 1875-5364 ; 2095-6975 ; 1672-3651
    ISSN (online) 1875-5364
    ISSN 2095-6975 ; 1672-3651
    DOI 10.1016/S1875-5364(19)30035-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mechanical Study of Jian-Gan-Xiao-Zhi Decoction on Nonalcoholic Fatty Liver Disease Based on Integrated Network Pharmacology and Untargeted Metabolomics.

    Cao, Yong-Jun / Li, Han-Zhou / Zhao, Jie / Sun, Yu-Meng / Jin, Xiao-Wen / Lv, Shu-Quan / Luo, Jun-Yu / Fang, Xi-Xing / Wen, Wei-Bo / Liao, Jia-Bao

    Evidence-based complementary and alternative medicine : eCAM

    2022  Volume 2022, Page(s) 2264394

    Abstract: Jian-Gan-Xiao-Zhi decoction (JGXZ) has demonstrated beneficial effects on nonalcoholic fatty liver ...

    Abstract Jian-Gan-Xiao-Zhi decoction (JGXZ) has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms by which JGXZ improve NAFLD are still unclear.
    Language English
    Publishing date 2022-07-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171158-6
    ISSN 1741-4288 ; 1741-427X
    ISSN (online) 1741-4288
    ISSN 1741-427X
    DOI 10.1155/2022/2264394
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  8. Article ; Online: Zhi-Zi-Hou-Po decoction alleviates depressive-like behavior and promotes hippocampal neurogenesis in chronic unpredictable mild stress induced mice via activating the BDNF/TrkB/CREB pathway.

    Ye, Zhaoyi / Wang, Jinwen / Fang, Fei / Wang, Yaya / Liu, Zhebin / Shen, Chunfeng / Hu, Yue

    Journal of ethnopharmacology

    2023  Volume 319, Issue Pt 3, Page(s) 117355

    Abstract: Ethnopharmacological relevance: Zhi-Zi-Hou-Po decoction (ZZHP), a traditional Chinese medicine ...

    Abstract Ethnopharmacological relevance: Zhi-Zi-Hou-Po decoction (ZZHP), a traditional Chinese medicine (TCM) classic recipe, has been extensively applied for the remedy of depression. However, the underlying mechanism of ZZHP hasn't been fully elucidated and it needs to be further clarified.
    Aim of study: The aim of the study is to uncover the mechanisms of ZZHP's effect on depression.
    Materials and methods: C57BL/6 mice were employed to establish Chronic Unpredictable Mild Stress (CUMS) models. Behavioral tests were conducted for evaluating the antidepressant effects of ZZHP. Then, the monoamine neurotransmitters in the hippocampus through High Performance Liquid Chromatography Electrochemical Detection (HPLC-ECD) were utilized to assess the effect of ZZHP on the maintenance of monoamine neurotransmitter homeostasis. Immunofluorescence staining and Golgi staining were detected to analyze the effects of ZZHP on neuroplasticity in the hippocampus. Western Blot (WB) was utilized to examine the effects of ZZHP on BDNF/TrkB/CREB pathways. Finally, behavioral tests, WB and immunofluorescence staining were repeated after TrkB receptor antagonist was added to further confirm the underlying mechanism.
    Results: Our results shown that ZZHP attenuated depressive-like symptoms in CUMS mice. Moreover, ZZHP remarkably reversed the reduction and maintained the homeostasis of monoamine neurotransmitters in the hippocampus. Simultaneously, ZZHP protected neuronal synaptic plasticity and promoted hippocampal neurogenesis. Furthermore, ZZHP stimulated the BDNF/TrkB/CREB pathway in the hippocampus. The addition of TrkB receptor antagonist inhibited the antidepressant effects of ZZHP, suggesting that ZZHP could not work without triggering the BDNF/TrkB/CREB pathway.
    Conclusion: This study demonstrates that ZZHP can alleviate depressive-like behavior and promote hippocampal neurogenesis in CUMS mice via activating the BDNF/TrkB/CREB pathway.
    MeSH term(s) Mice ; Animals ; Depression/drug therapy ; Depression/metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Receptor, trkB/metabolism ; Mice, Inbred C57BL ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Antidepressive Agents/metabolism ; Hippocampus ; Neurogenesis ; Neurotransmitter Agents/metabolism ; Stress, Psychological/drug therapy ; Stress, Psychological/metabolism ; Disease Models, Animal
    Chemical Substances Brain-Derived Neurotrophic Factor ; Receptor, trkB (EC 2.7.10.1) ; Antidepressive Agents ; Neurotransmitter Agents
    Language English
    Publishing date 2023-10-27
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.117355
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  9. Article ; Online: Discovery of the toxicity-related quality markers and mechanisms of Zhi-Zi-Hou-Po decoction based on Chinmedomics combined with differentially absorbed components and network pharmacology.

    Wan, Shulin / Xie, Xiaoxia / Yang, Gongjun / Feng, Fang

    Journal of ethnopharmacology

    2023  Volume 320, Page(s) 117408

    Abstract: Ethnopharmacological relevance: Zhi-Zi-Hou-Po decoction (ZZHPD), as a representative ...

    Abstract Ethnopharmacological relevance: Zhi-Zi-Hou-Po decoction (ZZHPD), as a representative traditional Chinese medicine (TCM) formula for the treatment of depression, has frequently triggered hepatorenal toxicity in recent years. However, its toxic effect, material basis, and underlying mechanisms have not been fully elucidated.
    Aim of the study: To explore the hepatorenal toxicity-material basis-quality markers (Q-markers) and multiple mechanisms of ZZHPD.
    Materials and methods: ZZHPD-induced rat model of toxicity was evaluated by behavioral indicators, biochemical parameters, and histopathological sections. Then, UHPLC-Q-Exactive Orbitrap-MS combined with multivariate data analysis was utilized to identify the endogenous differential metabolites and the prototype components of ZZHPD in the plasma. A comprehensive strategy integrating in-house library, diagnostic ions, Compound Discover software, and network databases was constructed to identify the chemical constituents of ZZHPD. Additionally, the differentially absorbed components of ZZHPD were screened out based on the spectrum-effect relationship (toxic state and normal state), feature extraction of exogenous components, and variable influence on projection (VIP). Further, Chinmedomics and network pharmacology oriented by differentially absorbed components were performed to predict toxicity-related Q-markers and core targets, as well as relevant pathways. Finally, the binding ability between components and targets was predicted using molecular docking, and the mRNA expression of core target genes was determined by real-time qPCR experiment.
    Results: ZZHPD exerted significant hepatotoxicity and nephrotoxicity in rats accompanied by body weight loss, abnormal biochemical indicators, and pathologic characteristics with mild inflammation and cell damage. The results of plasma metabolomics indicated that 22 differential metabolites interfered by ZZHPD mainly involved in primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism and biosynthesis, sphingolipid metabolism, pyrimidine and purine metabolism. Firstly, 106 chemical substances of ZZHPD were identified, 44 of them were absorbed into the blood, mainly including 7 iridoid glycosides, 15 flavonoids, 5 lignans, and others. Then, the correlation analysis results suggested that 12 of 19 differentially absorbed constituents were highly correlated with 22 differential metabolites and recognized as potential Q-markers. Finally, 9 toxicity-related Q-markers were predicted and confirmed with better binding ability to 5 core targets (PTGS2, CASP3, TNF, PPARG, HMOX1), including 3 flavonoids (naringin, hesperidin, and neohesperidin), 2 iridoid glycosides (geniposide and genipin-1-β-D-gentiobioside), 2 lignans (honokiol and magnolol), organic acid (chlorogenic acid), and crocin (crocetin). The real-time qPCR results showed that the mRNA levels of CASP3, TNF-α, and PPARG significantly increased in the damaged liver. Combining metabolomics and network pharmacology results, the multiple mechanisms of toxicity might involve in oxidative damage, inflammation, and apoptosis pathways.
    Conclusion: Taken together, the toxicity-related Q-markers of ZZHPD screened for the first time in this work were reliable, and the holistic intervention for hepatorenal toxicity further revealed the multi-component, multi-target, and multi-pathway features in TCM. The integrated approach provides a novel perspective for the discovery of toxicity/efficacy-related substances and mechanistic studies in TCM.
    MeSH term(s) Rats ; Animals ; Rats, Sprague-Dawley ; Caspase 3 ; Drugs, Chinese Herbal/chemistry ; Molecular Docking Simulation ; Network Pharmacology ; PPAR gamma ; Iridoid Glycosides ; Lignans ; Flavonoids ; Inflammation ; RNA, Messenger
    Chemical Substances Caspase 3 (EC 3.4.22.-) ; Drugs, Chinese Herbal ; PPAR gamma ; Iridoid Glycosides ; Lignans ; Flavonoids ; RNA, Messenger
    Language English
    Publishing date 2023-11-14
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.117408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Recombinant ling zhi-8 enhances Tregs function to restore glycemic control in streptozocin-induced diabetic rats.

    Xiao, Hongyu / Fang, Zhi / He, Xueling / Ding, Ping / Cao, Yongkai / Chan, Shamyuen / Hou, Shaozhen / Liang, Jian

    The Journal of pharmacy and pharmacology

    2020  Volume 72, Issue 12, Page(s) 1946–1955

    Abstract: Objectives: To explore the effect of recombinant LZ-8 (rLZ-8) on streptozocin (STZ)-induced diabetic rats and further illustrate its underlying mechanism.: Methods: Rats were intraperitoneally injected with single-dose STZ 50 mg/kg for induction of ... ...

    Abstract Objectives: To explore the effect of recombinant LZ-8 (rLZ-8) on streptozocin (STZ)-induced diabetic rats and further illustrate its underlying mechanism.
    Methods: Rats were intraperitoneally injected with single-dose STZ 50 mg/kg for induction of type 1 diabetes (T1D), and then, the diabetic rats were treated with rLZ-8 for 3 months. The clinical symptoms, fasting blood glucose, insulin, cytokines, histopathology, flow cytometry and immunofluorescence were used to evaluate the therapeutic effect and underlying mechanism of rLZ-8 on alleviating diabetes mellitus (DM).
    Key findings: Treatment with rLZ-8 obviously alleviated the clinical symptoms of T1D and dose-dependently reduced the levels of blood glucose, blood lipid and haemoglobin A1c (HbA1c) in diabetic rat model. Meanwhile, rLZ-8 markedly increased insulin secretion and protected against STZ-induced pancreatic tissue injury. Additionally, rLZ-8 dramatically inhibited the levels of TNF-α and IL-1β, and obviously increased the level of IL-10 in serum and pancreas. Further investigation indicated that rLZ-8 treatment significantly increased the number of regulatory T cells (Tregs) and up-regulated the expression of Foxp3 to restore balance between anti-inflammatory and inflammatory cytokines.
    Conclusions: These data suggest that rLZ-8 can antagonize STZ-induced T1D, and its mechanism may be related to inhibit inflammation and enhance Tregs generation.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/pharmacology ; Biomarkers/blood ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; Cytokines/blood ; Diabetes Mellitus, Experimental/blood ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/immunology ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/chemically induced ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/immunology ; Fungal Proteins/pharmacology ; Glycemic Control ; Hypoglycemic Agents/pharmacology ; Inflammation Mediators/blood ; Male ; Rats, Sprague-Dawley ; Recombinant Proteins/pharmacology ; Streptozocin ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
    Chemical Substances Anti-Inflammatory Agents ; Biomarkers ; Blood Glucose ; Cytokines ; Fungal Proteins ; Hypoglycemic Agents ; Inflammation Mediators ; Recombinant Proteins ; LZ-8 protein, Ganoderma lucidum (127187-71-7) ; Streptozocin (5W494URQ81)
    Language English
    Publishing date 2020-08-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 3107-0
    ISSN 2042-7158 ; 0022-3573 ; 0373-1022
    ISSN (online) 2042-7158
    ISSN 0022-3573 ; 0373-1022
    DOI 10.1111/jphp.13360
    Database MEDical Literature Analysis and Retrieval System OnLINE

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