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  1. Article: [Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on AngⅡ-induced cardiomyocyte hypertrophy].

    Wang, Xiang / Mo, Jia-Jia / Tang, Tong-Juan / Ding, Rui / Huang, Jin-Ling

    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

    2024  Volume 49, Issue 3, Page(s) 754–762

    Abstract: This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro ... ...

    Abstract This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 μmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.
    MeSH term(s) Rats ; Animals ; Myocytes, Cardiac ; Cells, Cultured ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism ; Atrial Natriuretic Factor/genetics ; Atrial Natriuretic Factor/metabolism ; Angiotensin II/adverse effects ; Angiotensin II/metabolism ; Natriuretic Peptide, Brain/metabolism ; Hypertrophy/metabolism ; Cardiomegaly/chemically induced ; Cardiomegaly/drug therapy ; Cardiomegaly/genetics
    Chemical Substances Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Atrial Natriuretic Factor (85637-73-6) ; Angiotensin II (11128-99-7) ; Natriuretic Peptide, Brain (114471-18-0)
    Language Chinese
    Publishing date 2024-03-11
    Publishing country China
    Document type English Abstract ; Journal Article
    ZDB-ID 1004649-5
    ISSN 1001-5302 ; 0254-0029
    ISSN 1001-5302 ; 0254-0029
    DOI 10.19540/j.cnki.cjcmm.20231020.401
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: [Effect of Linggui Zhugan Decoction-containing serum on mitochondrial oxidative stress in cardiomyocytes: an exploration based on Nrf2/BNIP3 signaling pathway].

    Tang, Tong-Juan / Wang, Xiang / Zhou, Peng / Wang, Liang / Shi, Hui / Huang, Jin-Ling

    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

    2022  Volume 47, Issue 12, Page(s) 3303–3311

    Abstract: This study aimed to explore the effect of Linggui Zhugan Decoction(LGZGD)-containing serum on mitochondrial oxidative stress in cardiomyocytes based on the NF-E2-related factor2(Nrf2)/Bcl-2/adenovirus E1 B 19 kDa interacting protein(BNIP3) signaling ... ...

    Abstract This study aimed to explore the effect of Linggui Zhugan Decoction(LGZGD)-containing serum on mitochondrial oxidative stress in cardiomyocytes based on the NF-E2-related factor2(Nrf2)/Bcl-2/adenovirus E1 B 19 kDa interacting protein(BNIP3) signaling pathway. After the preparation of LGZGD-containing serum and blank serum, H9 c2 cardiomyocytes were exposed to H_2O_2 for inducing oxidative stress in vitro. The H9 c2 cells were divided into four groups, namely normal control group, H_2O_2 model group, 20% blank serum group, and 20% LGZGD-containing serum group. After the cells were pre-treated with different types of serum for 12 h and cultured with 100 μmol·L~(-1 )H_2O_2 for 6 h, the reactive oxygen species(ROS) level in each group was detected by DCFH-DA, and the openness of mitochondrial permeability transition pore(mPTP) was measured using a calcein AM fluorescent probe. The expression levels of cytoplasmic cytochrome C(CytC), mitochondrial CytC, cytoplasmic and nuclear Nrf2, and BNIP3 were detected by Western blot. Nrf2-silenced H9 c2 cells were prepared by transfecting them with siRNA-Nrf2 for investigating the efficacy of LGZGD-containing serum in regulating ROS, mPTP, cytoplasmic and mitochondrial CytC, and BNIP3. The results showed that compared with the normal control group, H_2O_2 significantly increased the ROS content and mPTP openness(P<0.01), and the expression of Nrf2, BNIP3, and cytoplasmic CytC(P<0.01), and decreased the expression of mitochondrial CytC(P<0.01), without causing obvious change in cytoplasmic Nrf2. LGZGD-containing serum significantly lowered ROS content(P<0.01), inhibited mPTP openness(P<0.01), down-regulated the expression of cytoplasmic CytC and BNIP3(P<0.01), up-regulated mitochondrial CytC expression(P<0.01), and promoted Nrf2 nuclear translocation(P<0.05). However, after Nrf2 silencing, the reduced ROS production, diminished BNIP3 expression, and inhibited mPTP openness and CytC release induced by LGZGD-containing serum were reversed(P<0.01). These results have suggested that LGZGD-containing serum is able to alleviate the mitochondrial oxidative stress injury of cardiomyocytes by regulating the Nrf2/BNIP3 signaling pathway.
    MeSH term(s) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology ; Apoptosis ; Myocytes, Cardiac ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Signal Transduction
    Chemical Substances NF-E2-Related Factor 2 ; Reactive Oxygen Species ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (9P21XSP91P)
    Language Chinese
    Publishing date 2022-07-18
    Publishing country China
    Document type Journal Article
    ZDB-ID 1004649-5
    ISSN 1001-5302 ; 0254-0029
    ISSN 1001-5302 ; 0254-0029
    DOI 10.19540/j.cnki.cjcmm.20220111.401
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Systematic investigation of the multi-scale mechanisms of herbal medicine on treating ventricular remodeling: Theoretical and experimental studies.

    Yang, Yinfeng / Xu, Yuan / Qian, Shanna / Tang, Tongjuan / Wang, Kangyong / Feng, Jie / Ding, Ran / Yao, Juan / Huang, Jinling / Wang, Jinghui

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Volume 112, Page(s) 154706

    Abstract: Background: To explore the underlying molecule mechanism of herbal medicine in preventing ventricular remodeling (VR), we take a herbal formula that is clinically effective for preventing VR as an example, which composed of Pachyma hoelen Rumph, ... ...

    Abstract Background: To explore the underlying molecule mechanism of herbal medicine in preventing ventricular remodeling (VR), we take a herbal formula that is clinically effective for preventing VR as an example, which composed of Pachyma hoelen Rumph, Atractylodes macrocephala Koidz., Cassia Twig and Licorice. Due to multi-components and multi-targets in herbal medicine, it is extremely difficult to systematically explain its mechanisms of action.
    Methods: An innovative systematic investigation framework which combines with pharmacokinetic screening, target fishing, network pharmacology, DeepDDI algorithm, computational chemistry, molecular thermodynamics, in vivo and in vitro experiments was performed for deciphering the underlying molecular mechanisms of herbal medicine for treating VR.
    Results: ADME screening and SysDT algorithm determined 75 potentially active compounds and 109 corresponding targets. Then, systematic analysis of networks reveals the crucial active ingredients and key targets in herbal medicine. Additionally, transcriptomic analysis identifies 33 key regulators during VR progression. Moreover, PPI network and biological function enrichment present four crucial signaling pathways, i.e. NF-κB and TNF, PI3K-AKT and C-type lectin receptor signaling pathways involved in VR. Besides, both molecular experiments at animal and cell levels reveal the beneficial effect of herbal medicine on preventing VR. Finally, MD simulations and binding free energy validate the reliability of drug-target interactions.
    Conclusion: Our novelty is to build a systematic strategy which combines various theoretical methods combined with experimental approaches. This strategy provides a deep understanding for the study of molecular mechanisms of herbal medicine on treating diseases from systematic level, and offers a new idea for modern medicine to explore drug interventions for complex diseases as well.
    MeSH term(s) Animals ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Drugs, Chinese Herbal/chemistry ; Phosphatidylinositol 3-Kinases ; Reproducibility of Results ; Ventricular Remodeling ; Plants, Medicinal ; Molecular Docking Simulation ; Medicine, Chinese Traditional/methods
    Chemical Substances Drugs, Chinese Herbal ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2023-02-08
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.154706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Systematic investigation of the multi-scale mechanisms of herbal medicine on treating ventricular remodeling: theoretical and experimental studies

    Yang, Yinfeng / Xu, Yuan / Qian, Shanna / Tang, Tongjuan / Wang, Kangyong / Feng, Jie / Ding, Ran / Yao, Juan / Huang, Jinling / Wang, Jinghui

    Phytomedicine. 2023 Feb. 08, p.154706-

    2023  , Page(s) 154706–

    Abstract: To explore the underlying molecule mechanism of herbal medicine in preventing ventricular remodeling (VR), we take a herbal formula that is clinically effective for preventing VR as an example, which composed of Pachyma hoelen Rumph, Atractylodes ... ...

    Abstract To explore the underlying molecule mechanism of herbal medicine in preventing ventricular remodeling (VR), we take a herbal formula that is clinically effective for preventing VR as an example, which composed of Pachyma hoelen Rumph, Atractylodes macrocephala Koidz., Cassia Twig and Licorice. Due to multi-components and multi-targets in herbal medicine, it is extremely difficult to systematically explain its mechanisms of action. An innovative systematic investigation framework which combines with pharmacokinetic screening, target fishing, network pharmacology, DeepDDI algorithm, computational chemistry, molecular thermodynamics, in vivo and in vitro experiments was performed for deciphering the underlying molecular mechanisms of herbal medicine for treating VR. ADME screening and SysDT algorithm determined 75 potentially active compounds and 109 corresponding targets. Then, systematic analysis of networks reveals the crucial active ingredients and key targets in herbal medicine. Additionally, transcriptomic analysis identifies 33 key regulators during VR progression. Moreover, PPI network and biological function enrichment present four crucial signaling pathways, i.e. NF-κB and TNF, PI3K-AKT and C-type lectin receptor signaling pathways involved in VR. Besides, both molecular experiments at animal and cell levels revealing the beneficial effect of herbal medicine on preventing VR. Finally, MD simulations and binding free energy validate the reliability of drug-target interactions. Our novelty is to build a systematic strategy which combines various theoretical methods combined with experimental approaches. This strategy provides a deep understanding for the study of molecular mechanisms of herbal medicine on treating diseases from systematic level, and offers a new idea for modern medicine to explore drug interventions for complex diseases as well.
    Keywords Atractylodes macrocephala ; Cassia ; Gibbs free energy ; algorithms ; animals ; branches ; chemistry ; herbal medicines ; lectins ; licorice ; medicine ; pharmacokinetics ; transcriptomics ; Herbal Medicine ; Ventricular Remodeling ; Mechanisms of Action ; MD simulations ; Experimental Validation ; AMI ; ADME ; BS ; C-T ; C-T-F ; C-T-D ; DL ; FL ; GZ ; GC ; MD ; MM-PBSA ; MLR ; OB ; PLS ; R2 ; RF ; SVR ; SEE ; SVM ; VR ; WGCNA
    Language English
    Dates of publication 2023-0208
    Publishing place Elsevier GmbH
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.154706
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Exploring the Mechanism of Ling-Gui-Zhu-Gan Decoction in Ventricular Remodeling after Acute Myocardial Infarction Based on UPLC and

    Zhou, Peng / Zhang, Meng / Zhao, Xiao-Ni / Tang, Tong-Juan / Wang, Xiang / Huang, Lu-Lu / Kong, Qi / Wang, Liang / Huang, Jin-Ling

    Evidence-based complementary and alternative medicine : eCAM

    2022  Volume 2022, Page(s) 8593176

    Abstract: Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical ... ...

    Abstract Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical treatment and basic research of cardiovascular diseases (CVDs), such as myocardial infarction, heart failure, and angina pectoris. However, the mechanism of LGZGD against VR after AMI remains unclear. Ultra-performance liquid chromatography (UPLC) was applied to investigate the major constituents of LGZGD, and molecular docking was used to predict the targets on the NLRP3/Caspase-1/GSDMD signaling pathway.
    Language English
    Publishing date 2022-05-16
    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 10.1155/2022/8593176
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Virtual screening analysis of natural flavonoids as trimethylamine (TMA)-lyase inhibitors for coronary heart disease.

    Zhou, Peng / Zhao, Xiao-Ni / Ma, Yao-Yao / Tang, Tong-Juan / Wang, Shu-Shu / Wang, Liang / Huang, Jin-Ling

    Journal of food biochemistry

    2022  , Page(s) e14376

    Abstract: Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut ... ...

    Abstract Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut microbiota plays a vital role in the beginning and progression of CHD. The gut microbial metabolite, trimethylamine-N-oxide (TMAO), is intimately linked to the pathophysiology of CHD. TMAO is formed when trimethylamine (TMA) is converted by flavin-containing monooxygenases in the hepatocytes. Therefore, inhibition of TMA production is essential to reduce TMAO levels. Flavonoids may reduce the risk of death from cardiovascular disease. In this article, we reviewed and evaluated twenty-two flavonoids for the therapy of CHD based on their inhibition of TMA-lyase by molecular docking. Docking results revealed that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had a good binding effect with TMA-lyase. This indicates that these chemicals were the most active and could be used as lead compounds for structural modification in the future. PRACTICAL APPLICATIONS: Flavonoids are a large class of polyphenolic compounds found in fruits, vegetables, flowers, tea, and herbal medicines, which are inexorably metabolized and transformed into bioactive metabolites by α-rhamnosidase, β-glucuronidase, β-glucosidase, and nitroreductase produced by the gut microbiota, which plays a beneficial role in the prevention and treatment of cardiovascular diseases. Because flavonoids protect the cardiovascular system and regulate the gut microbiota, and the gut microbiota is directly connected to TMAO, thus, reducing TMAO levels involves blocking the transition of TMA to TMAO, which may be performed by reducing TMA synthesis. Molecular docking results found that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had good binding effects on TMA-lyase, which were the most active and could be used as lead compounds for structural modification.
    Language English
    Publishing date 2022-08-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 433846-7
    ISSN 1745-4514 ; 0145-8884
    ISSN (online) 1745-4514
    ISSN 0145-8884
    DOI 10.1111/jfbc.14376
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Liquiritin inhibits H2O2‐induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF‐κB signaling pathway

    Tang, Tong‐Juan / Wang, Xiang / Wang, Liang / Chen, Ming / Cheng, Jing / Zuo, Meng‐Yu / Gu, Jin‐Fan / Ding, Rui / Zhou, Peng / Huang, Jin‐Ling

    Journal of Food Biochemistry. 2022 Oct., v. 46, no. 10 p.e14351-

    2022  

    Abstract: Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has ... ...

    Abstract Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has antioxidant and anti‐inflammatory properties, but the mechanism against oxidative stress in cardiomyocytes has not been reported. Establishment of oxidative damage model in H9c2 cells by hydrogen peroxide (H₂O₂). Liquiritin (5, 10, 20 μmol/L) could significantly prevent the loss of cell viability and decrease the apoptosis rate. It can reduce the levels of reactive oxygen species (ROS), malonedialdehyde (MDA), lactate dehydrogenase (LDH), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and increase the activity of ATP, superoxidedismutase (SOD), glutathione peroxide (GSH‐px), glutathione reductase (GR) and catalase (CAT) to alleviate oxidative stress and inflammation in a dose‐dependent manner. Liquiritin was found to be related to AMP‐Activated Protein Kinase (AMPK) pathway by molecular docking. Western blotting (WB) and quantitative reverse transcription PCR (RT‐qPCR) confirmed that liquiritin could promote AMPKα phosphorylation and sirtuin 1 (SIRT1) protein expression, and inhibit phosphorylation of nuclear factor kappa B p65 (NF‐κB p65). Compound C, EX 527, and PDTC can reverse the effects of liquiritin, indicating that its antioxidant effect is achieved by regulating AMPK/SIRT1/NF‐κB signaling pathway. PRACTICAL APPLICATIONS: Heart failure is one of the most common cardiovascular diseases, and its treatment remains a worldwide problem. Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM). Liquiritin is one of the main active components of licorice, which has antioxidant and anti‐inflammatory pharmacological effects. This study revealed the mechanism of licorice against oxidative damage of H9c2 cardiomyocytes, and provided a scientific basis for liquiritin as an antioxidant in the treatment of heart failure.
    Keywords AMP-activated protein kinase ; Oriental traditional medicine ; antioxidant activity ; apoptosis ; cardiomyocytes ; catalase ; cell viability ; dietary supplements ; dose response ; glutathione ; glutathione-disulfide reductase ; heart failure ; hydrogen peroxide ; inflammation ; ingredients ; interleukin-6 ; lactate dehydrogenase ; licorice ; models ; mortality ; oxidative stress ; phosphorylation inhibition ; protein synthesis ; reverse transcriptase polymerase chain reaction ; sirtuins ; transcription factor NF-kappa B ; tumor necrosis factor-alpha
    Language English
    Dates of publication 2022-10
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 433846-7
    ISSN 1745-4514 ; 0145-8884
    ISSN (online) 1745-4514
    ISSN 0145-8884
    DOI 10.1111/jfbc.14351
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Virtual screening analysis of natural flavonoids as trimethylamine (TMA)‐lyase inhibitors for coronary heart disease

    Zhou, Peng / Zhao, Xiao‐Ni / Ma, Yao‐Yao / Tang, Tong‐Juan / Wang, Shu‐Shu / Wang, Liang / Huang, Jin‐Ling

    Journal of Food Biochemistry. 2022 Dec., v. 46, no. 12 p.e14376-

    2022  

    Abstract: Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut ... ...

    Abstract Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut microbiota plays a vital role in the beginning and progression of CHD. The gut microbial metabolite, trimethylamine‐N‐oxide (TMAO), is intimately linked to the pathophysiology of CHD. TMAO is formed when trimethylamine (TMA) is converted by flavin‐containing monooxygenases in the hepatocytes. Therefore, inhibition of TMA production is essential to reduce TMAO levels. Flavonoids may reduce the risk of death from cardiovascular disease. In this article, we reviewed and evaluated twenty‐two flavonoids for the therapy of CHD based on their inhibition of TMA‐lyase by molecular docking. Docking results revealed that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had a good binding effect with TMA‐lyase. This indicates that these chemicals were the most active and could be used as lead compounds for structural modification in the future. PRACTICAL APPLICATIONS: Flavonoids are a large class of polyphenolic compounds found in fruits, vegetables, flowers, tea, and herbal medicines, which are inexorably metabolized and transformed into bioactive metabolites by α‐rhamnosidase, β‐glucuronidase, β‐glucosidase, and nitroreductase produced by the gut microbiota, which plays a beneficial role in the prevention and treatment of cardiovascular diseases. Because flavonoids protect the cardiovascular system and regulate the gut microbiota, and the gut microbiota is directly connected to TMAO, thus, reducing TMAO levels involves blocking the transition of TMA to TMAO, which may be performed by reducing TMA synthesis. Molecular docking results found that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had good binding effects on TMA‐lyase, which were the most active and could be used as lead compounds for structural modification.
    Keywords atherosclerosis ; baicalin ; cardiovascular system ; coronary disease ; death ; flavin-containing monooxygenase ; hepatocytes ; hesperidin ; intestinal microorganisms ; metabolites ; myocardial infarction ; myricetin ; naringin ; nitroreductases ; pathophysiology ; risk reduction ; tea ; therapeutics ; trimethylamine
    Language English
    Dates of publication 2022-12
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note REVIEW
    ZDB-ID 433846-7
    ISSN 1745-4514 ; 0145-8884
    ISSN (online) 1745-4514
    ISSN 0145-8884
    DOI 10.1111/jfbc.14376
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Ling-Gui-Zhu-Gan Decoction Protects H9c2 Cells against H

    Wang, Xiang / Tang, Tongjuan / Zhai, Mengting / Ge, Ruirui / Wang, Liang / Huang, Jinling / Zhou, Peng

    Evidence-based complementary and alternative medicine : eCAM

    2020  Volume 2020, Page(s) 8860603

    Abstract: Objectives: Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of ... ...

    Abstract Objectives: Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of oxidative stress response is still unknown. This study was aimed to investigate the protective effect of LGZGD-containing serum on H
    Methods: Eighteen rats were randomly divided into two groups: the blank control group and LGZGD group. The LGZGD group rats were administrated with 8.4 g/kg/d LGZGD for seven consecutive days through gavage, while the blank control group rats were given an equal volume of saline. The serum was extracted from all the rats. To investigate the efficacy and the underlying mechanism of LGZGD, we categorized the H9c2 cells into groups: the control group, model group, normal serum control (NSC) group, LGZGD group, LGZGD + all-trans-retinoic acid (ATRA) group, and ATRA group. Malonedialdehyde (MDA) and superoxide dismutase (SOD) were used as markers for oxidative stress. Dichlorodihydrofluorescin diacetate (DCFH-DA) staining was used to measure the levels of reactive oxygen species (ROS). The apoptosis rate was detected using flow cytometry. The expression levels of pro-caspase-3, cleaved-caspase-3, Bcl-2, Bax, Keap1, Nrf2, and HO-1 were measured using western blotting. The mRNA levels of Keap1, Nrf2, and HO-1 were measured using RT-qPCR.
    Results: The LGZGD attenuated injury to H9c2 cells and reduced the apoptosis rate. It was also found to upregulate the SOD activity and suppress the formation of MDA and ROS. The expression levels of pro-caspase-3 and Bcl-2 were significantly increased, while those of cleaved-caspase-3 and Bax were decreased in the LGZGD group compared with the model group. As compared with the model group, the LGZGD group demonstrated decreased Keap1 protein expression and significantly increased Nrf2 nuclear expression and Nrf2-mediated transcriptional activity. ATRA was found to reverse the LGZGD-mediated antioxidative and antiapoptotic effect on injured H9c2 cells induced by H
    Conclusion: Our results demonstrated that LGZGD attenuated the H
    Language English
    Publishing date 2020-11-30
    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 10.1155/2020/8860603
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pharmacokinetic evaluation of 24 representative components of Ling-Gui-Zhu-Gan decoction in acute myocardial infarction model rats via a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry method.

    Li, Jing / Ge, Ruirui / Wang, Feng / Gu, Jinfan / Zuo, Mengyu / Tang, Tongjuan / Ge, Xinru / Niu, Yingchao / Wang, Liang / Huang, Jinling / Chen, Jian

    Rapid communications in mass spectrometry : RCM

    2023  Volume 37, Issue 19, Page(s) e9620

    Abstract: Rationale: Ling-Gui-Zhu-Gan decoction (LGZGD), one of the 100 herbal classic formulas, is clinically used to treat chronic heart failure with remarkable curative effect. However, LGZGD pharmacokinetic parameters in pathological model rats are poorly ... ...

    Abstract Rationale: Ling-Gui-Zhu-Gan decoction (LGZGD), one of the 100 herbal classic formulas, is clinically used to treat chronic heart failure with remarkable curative effect. However, LGZGD pharmacokinetic parameters in pathological model rats are poorly understood, in particular for special components. As physicochemical properties are specific to each representative component, no standard sample preparation is available for absolute quantification of representative components of LGZGD in rat plasma.
    Methods: A specific, sensitive and high-throughput ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method capturing 24 representative components was developed and applied to evaluate the pharmacokinetic parameters of LGZGD in acute myocardial infarction (AMI) rat plasma after intragastric administration (2.4, 4.8 and 9.6 g/kg). Precipitation and extraction were selected and optimized for plasma preparation, and isopropanol precipitation could offer higher recovery and broader coverage.
    Results: It was expected that AMI could cause less absorption and slower elimination of most of active components of LGZGD. Most of newly reported special components absorbed quickly and eliminated slowly. The average elimination half-life of the 24 representative components was 10.09 h, which is consistent with the dosage of LGZGD (twice daily).
    Conclusions: The specificity, linearity, precision and accuracy, recovery, matrix effect and stability were validated according to Food and Drug Administration guidance. The validation results demonstrated that the method could be applied to evaluate the pharmacokinetic parameters of LGZGD in AMI rats. The pharmacokinetic parameters showed substantial improvement in quality research of LGZGD, thereby laying the groundwork for preclinical and clinical trials in chronic heart failure clinical efficacy.
    MeSH term(s) United States ; Animals ; Rats ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Heart Failure ; Myocardial Infarction/drug therapy
    Chemical Substances ling-gui-zhu-gan decoction
    Language English
    Publishing date 2023-09-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 58731-x
    ISSN 1097-0231 ; 0951-4198
    ISSN (online) 1097-0231
    ISSN 0951-4198
    DOI 10.1002/rcm.9620
    Database MEDical Literature Analysis and Retrieval System OnLINE

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