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1.
Zhongguo Zhong Yao Za Zhi ; 49(3): 754-762, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621879

RESUMO

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.


Assuntos
Miócitos Cardíacos , ATPase Trocadora de Sódio-Potássio , Ratos , Animais , Células Cultivadas , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Angiotensina II/efeitos adversos , Angiotensina II/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Hipertrofia/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/genética
2.
Inflammopharmacology ; 31(4): 1715-1729, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37261627

RESUMO

Cardiovascular diseases (CVDs) are a leading cause of global mortality and have a high incidence rate worldwide. The function of inflammasomes in CVDs has received a lot of attention recently, and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome may be a new target for the prevention and treatment of CVDs. Flavonoids, which are found in food and plant extracts, inhibited inflammation in CVDs by regulating the NLRP3 inflammasome. CB-Dock was used to investigate whether 34 flavonoids from natural products acted on NLRP3 inflammasome. In brief, the PDB format of NLRP3 was selected as a protein file, and 34 flavonoids in SDF format were selected as the ligand file, and then input to CB-Dock for molecular docking. The docking results showed that epigallocatechin-3-gallate (EGCG), amentoflavone, baicalin, scutellarin, vitexin, silibinin, and puerarin had good binding affinities to NLRP3, which could be used as NLRP3 inhibitors, and aid in the discovery of lead compounds for the design and development of CVDs.


Assuntos
Doenças Cardiovasculares , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Simulação de Acoplamento Molecular , Flavonoides/farmacologia
3.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3303-3311, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851124

RESUMO

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.


Assuntos
Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Apoptose , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Poro de Transição de Permeabilidade Mitocondrial
4.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4436-4445, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36046873

RESUMO

This study aims to investigate the effect of atractylenolide Ⅲ(ATL-Ⅲ) on hydrogen peroxide(H_2O_2)-induced endoplasmic reticulum stress and apoptosis of H9 c2 cells via the ROS/GRP78/caspase-12 signaling pathway.The binding activity of ATL-Ⅲ to GRP78 was determined by molecular docking.The result showed that ATL-Ⅲ had a good binding activity to GRP78, and the binding activity of ATL-Ⅲ was stronger than that of its specific inhibitor.The endoplasmic reticulum stress model of H9 c2 was established by H_2O_2(100 µmol·L~(-1)) treatment.Five groups were designed: blank control group, model group, and ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) groups.Apoptosis was detected by Hoechst/PI double staining and flow cytometry.The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and lactate dehydrogenase(LDH) were measured by colorimetry.The levels of reactive oxygen species(ROS) and calcium(Ca~(2+)) in cytoplasm were determined by the fluorescence probe DCFH-DA and the calcium fluorescence probe Flou-4, respectively.The protein levels of GRP78, caspase-12, and caspase-3 were determined by Western blot, and the mRNA levels of GRP78 and caspase-12 by RT-qPCR.N-acetyl-L-cysteine(NAC) and 4-phenylbutyric acid(4-PBA) were respectively used to inhibit ROS and GRP78, and then the mechanism of ATL-Ⅲ in protecting the cells from endoplasmic reticulum stress induced by H_2O_2 were deduced.ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) decreased the apoptosis rate and ROS, MDA, and LDH levels(P<0.01), increased the SOD activity(P<0.01), and down-regulated the protein levels of GRP78, caspase-12, and caspase-3 and the mRNA levels of GRP78 and caspase-12(P<0.05).The addition of NAC decreased the apoptosis rate and ROS, MDA, GRP78, caspase-12, and caspase-3 levels(P<0.01), while it elevated the SOD level(P<0.01).The addition of 4-PBA also decreased the apoptosis rate and the levels of GRP78, caspase-12, caspase-3, and Ca~(2+)(P<0.01).The effect of inhibitors were consistent with that of ATL-Ⅲ.In conclusion, ATL-Ⅲ can protect H9 c2 cardiomyocytes by regulating ROS/GRP78/caspase-12 signaling pathway to inhibit H_2O_2-induced endoplasmic reticulum stress and apoptosis.


Assuntos
Cálcio , Chaperona BiP do Retículo Endoplasmático , Apoptose , Cálcio/farmacologia , Caspase 12/genética , Caspase 12/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Estresse do Retículo Endoplasmático , Lactonas , Simulação de Acoplamento Molecular , RNA Mensageiro , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos , Transdução de Sinais , Superóxido Dismutase/metabolismo
5.
BMC Biotechnol ; 21(1): 24, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722223

RESUMO

BACKGROUND: The ability to clone DNA sequences quickly and precisely into plasmids is essential for molecular biology studies. The recent development of seamless cloning technologies has made significant improvements in plasmid construction, but simple and reliable tools are always desirable for time- and labor-saving purposes. RESULTS: We developed and standardized a plasmid cloning protocol based on a universal MCS (Multiple Cloning Site) design and bacterial in vivo assembly. With this method, the vector is linearized first by PCR (Polymerase Chain Reaction) or restriction digestion. Then a small amount (10 ~ 20 ng) of this linear vector can be mixed with a PCR-amplified insert (5× molar ratio against vector) and transformed directly into competent E. coli cells to obtain the desired clones through in vivo assembly. Since we used a 36-bp universal MCS as the homologous linker, any PCR-amplified insert with ~ 15 bp compatible termini can be cloned into the vector with high fidelity and efficiency. Thus, the need for redesigning insert-amplifying primers according to various vector sequences and the following PCR procedures was eliminated. CONCLUSIONS: Our protocol significantly reduced hands-on time for preparing transformation reactions, had excellent reliability, and was confirmed to be a rapid and versatile plasmid cloning technique. The protocol contains mostly mixing steps, making it an extremely automation-friendly and promising tool in modern biology studies.


Assuntos
Clonagem Molecular/métodos , Escherichia coli/genética , Plasmídeos/genética , Primers do DNA/genética , Escherichia coli/metabolismo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase
6.
Inflammopharmacology ; 28(1): 19-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894515

RESUMO

Cardiovascular disease (CVDs) is a chronic disease with the highest morbidity and mortality in the world. Previous studies have suggested that preventing inflammation serves an efficient role in protection against cardiovascular diseases. Modulation of IKK-ß activity can be used to treat and control CVDs associated with chronic inflammation, which targets the phosphorylation of IκB following the release of the RelA complex, and then translocates to the nucleus, eventually triggering the transcription of several genes that induce chemokines, cytokines, and adhesion molecules. Most importantly, the IκB kinase (IKK) complex is involved in transcriptional activation by phosphorylating the inhibitory molecule IkBα, enabling activation of NF-κB. Phenolic compounds possess cardioprotective potential that may be related to modulating inflammatory responses involved in CVDs. The SystemsDock analysis was used to explore whether 38 active compounds inhibit IKK-ß activity based on literature. Docking results showed that the top docking score of three chemical compounds were icariin, salvianolic acid B, and plantainoside D in all compounds. Icariin, salvianolic acid B, and plantainoside D are the most promising IKKß inhibitors. These phytochemicals could be helpful to find the lead compounds on designing and developing novel cardioprotective agents.


Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Quinase I-kappa B/antagonistas & inibidores , Inflamação/tratamento farmacológico , Fenóis/farmacologia , Fenóis/uso terapêutico , Animais , Humanos , Inflamação/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1779-1788, 2020 Apr.
Artigo em Zh | MEDLINE | ID: mdl-32489061

RESUMO

To investigate the mechanism of Coptidis Rhizoma-Pinelliae Rhizoma in the treatment of gastric cancer based on syste-matic pharmacology and data mining. The chemical constituents of Coptidis Rhizoma and Pinelliae Rhizoma were obtained from Traditio-nal Chinese Medicine Systems Pharmacology Database(TCMSP) and Shanghai Institute of Organic Chemistry database of Chinese Academy of Sciences by data mining. Then the active ingredients were screened by ADME, and the targets of the active ingredients were predicted by chemometrics. Molecular docking and free energy analysis were used to verify and screen the targets, so as to obtain the therapeutic targets of Coptidis Rhizoma and Pinelliae Rhizoma for gastric cancer. The biological functions, diseases and related signal pathways corresponding to the targets were further analyzed, and then the multi-component, multi-target and multi-channel mechanism of Coptidis Rhizoma and Pinelliae Rhizoma for gastric cancer were elaborated. Finally, MTT, Scratch, Transwell and Western blot experiments were carried out to verify the inhibitory effect of Coptidis Rhizoma and Pinelliae Rhizoma on human gastric cancer cell line MKN-45. A total of 46 active ingredients of Coptidis Rhizoma and Pinelliae Rhizoma were screened, as well as 77 corresponding targets, 38 targets related to gastric cancer and its complications, top 8 related signaling pathways, and top 20 target molecular functions by GO analysis. Cell experiments also proved that Coptidis Rhizoma and Pinelliae Rhizoma could effectively inhibit the proliferation, invasion and migration ability of gastric cancer cells and inhibit TGF-ß1-induced Wnt/ß-catenin signaling pathway activation. Coptidis Rhizoma and Pinelliae Rhizoma drug pair has many active ingredients, which can regulate nervous and mental system, cell cycle, cell differentiation and metastasis, and enhance anti-inflammatory and immune functions, playing a synergistic anti-cancer role in gastric cancer and its complications and providing new ideas for the follow-up clinical treatment of gastric cancer.


Assuntos
Medicamentos de Ervas Chinesas , Pinellia , Neoplasias Gástricas , China , Humanos , Simulação de Acoplamento Molecular
8.
Pak J Pharm Sci ; 33(4): 1459-1464, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33583775

RESUMO

Ling-Gui-Zhu-Gan decoction (LGZGD) is a classic Chinese herbal formula, which has been used to prevent and treat chronic heart failure (HF). Reliable therapeutics of LGZGD has also been confirmed in clinical practice. In this study, molecular docking has explored the mechanism of LGZGD as an effective treatment for heart failure. Twenty-one known active compounds of LGZGD in serum were screened based on twelve key receptors involved in myocardial damage. There were fourteen active molecules of LGZGD combined strongly with five or more than five protein targets after molecular docking, only seven active molecules of LGZGD combined strongly with ten or more than ten protein targets. The molecular docking provided a forceful tool for searching material foundation and the mechanism of action of TCM formula.


Assuntos
Doença Crônica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Miocárdio/patologia
9.
Zhongguo Zhong Yao Za Zhi ; 44(23): 5159-5165, 2019 Dec.
Artigo em Zh | MEDLINE | ID: mdl-32237353

RESUMO

Diabetic cardiomyopathy( DCM) is one of the major cardiovascular complications of diabetes mellitus. Based on the clinical efficacy of Danzhi Jiangtang Capsules( DJC) in the prevention and treatment of diabetes and its cardiovascular complications,both in vivo and in vitro methods were adopted to investigate its effect and underlying mechanism of protecting myocardial injury induced by diabetes. The type 2 diabetic rats were prepared by feeding high-energy food combined with streptozotin( STZ) injection,and the effects of DJC were observed by blood sugar,blood lipid,hemodynamic index,cardiac weight index and the change of cardiac pathological morphology. The protein expressions of TLR4,MyD88 and NF-κB p65 in myocardial tissue were detected and the possible mechanism was preliminarily analyzed. Besides this,DJC containing serum was prepared,H9 c2 cardiomyocyte induced by high sugar were studied to investigate the mechanism of TLR4/MyD88/NF-κB signaling pathway regulating cardiomyocyte injury and the therapeutic effect of DJC. The results demonstrated that fasting blood sugar,glycosylated hemoglobin,total cholesterol and glycerol triglyceride were significantly reduced( P<0. 01,P<0. 05). Cardiac weight index,left ventricle weight index,LVEDP and the protein expressions of TLR4,MyD88 and NF-κB p65 were significantly reduced( P<0. 01,P<0. 05). LVSP,+dp/dtmaxand-dp/dtmaxincreased significantly( P<0. 01,P< 0. 05). Moreover,the pathological damage of myocardial tissue in rats improved significantly. Meanwhile,the protein expressions of TLR4,MyD88 and NF-κB p65 in cardiomyocytes induced by high sugar were significantly inhibited( P<0. 01).It showed that DJC were effective in preventing and treating myocardial injury induced by diabetes and its mechanism may be related to the over-expression of TLR4/MyD88/NF-κB signaling pathway induced by high sugar.


Assuntos
Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Glicemia , Cápsulas , Diabetes Mellitus Experimental/induzido quimicamente , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 40(7): 1388-91, 2015 Apr.
Artigo em Zh | MEDLINE | ID: mdl-26281566

RESUMO

OBJECTIVE: The study aimed to test if Paridis Rhizoma total saponins (PRTS) could induce apoptosis of human gastric cancer cell MKN-45. METHOD: Based on the previous researches, PRTS was set by different concentrations to treat human gastric cancer cell for 12 h (5, 10, 20 mg x L(-1)). Fluorescent staining methods were adopted to observe apoptotic morphological changes of MKN-45. The apoptosis rates were analyzed by flow cytometry with Annexin V-FITC/PI staining. The enzymatic activities of caspase-3 and caspase-8 were measured by ELISA. The protein levels of Fas and FasL were detected by Western blotting. RESULT: Under a fluorescence microscope, MKN-45 treated by PRTS was seen typical apoptotic morphological features. PRTS significantly increased the rate of apoptosis. Compared with the control group, there exsited significant differences in apoptosis rate of PRTS concentration of 20 mg x L(-1) (P < 0.01); besides, the enzymatic activities of caspase-3 and caspase-8 were promoted obviously after the effect of PRTS on MKN-45 cells for 12 h (P < 0.01). The protein levels of Fas and FasL in the MKN-45 were upgraded significantly. CONCLUSION: PRTS can induce apoptosis of human gastric cancer cell MKN-45 , which is concerned with caspase-3 and caspase-8 and upgraded Fas and FasL.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína Ligante Fas/metabolismo , Magnoliopsida/química , Saponinas/farmacologia , Neoplasias Gástricas/metabolismo , Receptor fas/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Humanos , Rizoma/química , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/fisiopatologia
11.
Ying Yong Sheng Tai Xue Bao ; 35(1): 247-254, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38511462

RESUMO

In the context of the national ecological security development strategy, constructing regional ecological networks centered on protected areas and ecological corridors has become an urgent issue in protected areas system development of China. We focused on strengthening ecological connections between protected areas in Guangzhou, identified the ecological resource patches, ecological corridors, and ecological nodes by using Invest model, connectivity analysis, circuit theory models, and graph-theoretical network structure evaluation, and constructed an ecological network for the Guangzhou with nature reserves as the core. The results showed that 52 ecological resource patches were identified in the study area, covering a total area of 1450.01 km2. Nature reserves accounted for 76.4% of the total area, forming the main part of the ecological resource patches. 115 ecological corridors were identified, with a total length of 900.56 km and an average length of 7.83 km. Furthermore, 72 ecological key points were identified, covering a total area of 17.57 km2, and 81 ecological breakpoints, with a total area of 35.9 km2. The network structure indices (α=0.65, ß=2.21, and γ=0.77) indicated a reasonably structured and well-connected network. By exploring pathways for constructing regional ecological networks under the protected areas system and enriching the application of circuit theory models in ecological network construction, this study provides scientific basis for regional ecological security and biodiversity conservation.


Assuntos
Ecologia , Ecossistema , Conservação dos Recursos Naturais , Biodiversidade , China
12.
J Pharm Pharmacol ; 76(4): 405-415, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38241142

RESUMO

OBJECTIVE: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. METHODS: In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. KEY FINDINGS: In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. CONCLUSIONS: LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.


Assuntos
Ferroptose , Extratos Vegetais , Ratos , Animais , Ciclo-Oxigenase 2 , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Doxorrubicina/toxicidade
13.
Mol Phylogenet Evol ; 69(3): 1093-100, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23994356

RESUMO

To examine the phylogenetic relationships of Koenigia sensu lato (Polygonaceae), 43 samples representing all species of Koenigia and closely related taxa (e.g., Aconogonon, Bistorta, and Persicaria) were sequenced for nuclear ITS and four plastid regions (trnL-F, atpB-rbcL, rbcL, and rpl32-trnL((UAG))). Phylogenetic analyses indicate that Koenigia recognized by Hedberg is paraphyletic and that the basal species K. delicatula should be reassigned to a separate new genus. Based on these findings, we further propose that the genus Koenigia sensu lato be circumscribed to include five species. Ancestral state reconstruction showed that the pollen apertures likely evolved in parallel in the Aconogonon-Koenigia-Bistorta clade and Persicaria clade and that tricolpate pollen is most likely to be the ancestral state. Quincuncial aestivation likely evolved during the early evolution of Koenigia and its close relatives. Our findings suggest that the uplift of the Himalayas has played an important role in promoting species diversification of Koenigia. Koenigia islandica expanded its range during Pleistocene glacial cycles by tracking changes in newly available habitats.


Assuntos
Evolução Molecular , Filogenia , Polygonaceae/classificação , Teorema de Bayes , China , DNA de Cloroplastos/genética , DNA de Plantas/genética , DNA Espaçador Ribossômico/genética , Funções Verossimilhança , Modelos Genéticos , Pólen/anatomia & histologia , Polygonaceae/anatomia & histologia , Polygonaceae/genética , Análise de Sequência de DNA
14.
Zhonghua Nan Ke Xue ; 19(5): 446-50, 2013 May.
Artigo em Zh | MEDLINE | ID: mdl-23757970

RESUMO

OBJECTIVE: To study the effects of Wuzi Yanzong Pills (WYP) on sperm mitochondrial membrane potential (MMP) and its ultrastructure in oligo-asthenozoospermia model rats. METHODS: Oligo-asthenozoospermia models were made in 50 male rats weighing 200 - 220 g by intragastric administration of Tripterygium Glucosides at 30 mg per kg per d for 8 weeks, and then equally allocated to a model control, a Huangjing Zanyu Capsule (HZC) control, a low-dose WYP, a medium-dose WYP, and a high-dose WYP group. Another 10 age-matched normal male rats were included as normal controls. The rats in the model and normal control groups were given intragastrically distilled water at 10 ml/kg, those in the HZC group administered HZC at 3.01 g/kg, and those in the low-, medium- and high-dose WYP groups medicated with WYP at 2.30, 4.60 and 9.20 g/kg, respectively, once daily for 30 days. At 30 minutes after the last administration, we detected the sperm MMP by JC-1 fluorescent staining and flow cytometry, and examined the sperm ultrastructure under the JEM-1230 transmission electron microscope. RESULTS: JC-1 + % and its fluorescence intensity were (33.77 +/- 6.19)% and 1 468 +/- 496 in the model control, (56.34 +/- 10.35)% and 3 277 +/- 895 in the HZC control, (40.80 +/- 10.40)% and 2 016 +/- 767 in the low-dose WYP, (59.40 +/- 6.51)% and 3 897 +/- 643 in the medium-dose WYP, and (60.71 +/- 7.81)% and 3 371 +/- 647 in the high-dose WYP group, significantly reduced in comparison with (70.80 +/- 4.92)% and 4 360 +/- 945 in the normal control group (P < 0.05), but remarkably higher in the medium- and high-dose WYP groups than in the model controls (P < 0. 05). After modeling, the sperm membrane was loose and degenerated, the mitochondria swelling, variously sized and with incomplete membrane, and the axonemal structure unclear or ruptured. After 30 days of WYP administration, compared with the model control group, the rats exhibited integrated sperm membrane and mitochondrial membrane, reduced mitochondrial swelling and basically normal axonemal and microtubular structures. CONCLUSION: Tripterygium Glucosides could decrease the sperm mitochondrial membrane potential and damage the mitochondrial structure, while WYP could significantly increase the sperm mitochondrial membrane potential and reduce the sperm mitochondrial structure damage. The protection of the integrity of sperm mitochondrial structure and function is one of the mechanisms of WYP acting on oligo-asthenozoospermia.


Assuntos
Astenozoospermia , Medicamentos de Ervas Chinesas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Oligospermia , Espermatozoides/efeitos dos fármacos , Animais , Astenozoospermia/patologia , Astenozoospermia/fisiopatologia , Masculino , Oligospermia/patologia , Oligospermia/fisiopatologia , Ratos , Ratos Sprague-Dawley , Espermatozoides/fisiologia , Espermatozoides/ultraestrutura
15.
Front Public Health ; 10: 989540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504956

RESUMO

The urban-rural difference in poverty is an important issue in China, particularly for people with disabilities. The extra costs of disability render this population susceptible to falling into poverty, where this can exacerbate the inequality among people with disabilities between urban and rural areas of the country. Previous studies have provided empirical evidence for the extra costs of disabilities in certain countries, but little scholarly attention has been devoted to the urban-rural gap in the costs of disability, particularly in countries like China that have a dual urban-rural system. This study explores changes in the extra costs of disability in China between urban and rural households with disabled members from 2008 to 2018 by using the standard of living approach. We apply the Foster-Greer-Thorbecke Poverty Index to measure the rates of poverty in urban and rural households with disabilities after considering the costs of disability. The results reveal that the costs of disability were not always lower for rural households than for urban households. At the same time, many rural households with disabled people were found to suffer from severe poverty owing to the high costs of their disabilities. The difference in health insurance and rehabilitation services between urban and rural China have led to an urban-rural gap in the costs of disability. This suggests that supplying more goods and services for disabled people in rural areas, especially free services, and raising the reimbursement due to them from their health insurance can help improve their standard of living.


Assuntos
Pessoas com Deficiência , Pobreza , Humanos , China/epidemiologia , Seguro Saúde
16.
Artigo em Inglês | MEDLINE | ID: mdl-35615687

RESUMO

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. In vivo, histological changes in the myocardium were visualized using HE staining and Masson staining, and cardiomyocyte apoptosis was detected using TUNEL. IL-1ß activity in rat serum was determined by ELISA. Finally, NLRP3, Caspase-1, and GSDMD expressions were analyzed through RT-qPCR and Western blotting. The results showed that 8 authentic reference substances have been detected in LGZGD. Molecular docking showed that the major chemical constituents of LGZGD had a good binding activity with NLRP3, Caspase-1, and GSDMD. Our results showed that LGZGD treatment markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, reduced IL-1ß activity, and regulated the expression of genes and proteins related to the NLRP3/Caspase-1/GSDMD signal pathway. These results suggest that LGZGD protects against VR after AMI through NLRP3/Caspase-1/GSDMD signal pathway.

17.
J Food Biochem ; 46(12): e14376, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35945702

RESUMO

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, ß-glucuronidase, ß-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.


Assuntos
Doença das Coronárias , Hesperidina , Liases , Humanos , Simulação de Acoplamento Molecular , Flavonoides
18.
Artigo em Inglês | MEDLINE | ID: mdl-36159560

RESUMO

The objective of this study was to determine the effect of atractylenolide III (ATL-III) on endoplasmic reticulum stress (ERS) injury, H9c2 cardiomyocyte apoptosis induced by tunicamycin (TM), and the GRP78/PERK/CHOP signaling pathway. Molecular docking was applied to predict the binding affinity of ATL-III to the key proteins GRP78, PERK, IREα, and ATF6 in ERS. Then, in vitro experiments were used to verify the molecular docking results. ERS injury model of H9c2 cells was established by TM. Cell viability was detected by MTT assay, and apoptosis was detected by Hoechst/PI double staining and flow cytometry. Protein expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, and Caspase-3 were detected by Western blot. And mRNA levels of GRP78, CHOP, PERK, eIF2α, and ATF4 were detected by RT-qPCR. Moreover, the mechanism was further studied by using GRP78 inhibitor (4-phenylbutyric acid, 4-PBA), and PERK inhibitor (GSK2656157). The results showed that ATL-III had a good binding affinity with GRP78, and the best binding affinity was with PERK. ATL-III increased the viability of H9c2 cells, decreased the apoptosis rate, downregulated Bax and Caspase-3, and increased Bcl-2 compared with the model group. Moreover, ATL-III downregulated the protein and mRNA levels of GRP78, CHOP, PERK, eIF2α, and ATF4, consistent with the inhibition of 4-PBA. ATL-III also decreased the expression levels of PERK, eIF2α, ATF4, CHOP, Bax, and Caspase-3, while increasing the expression of Bcl-2, which is consistent with GSK2656157. Taken together, ATL-III could inhibit TM-induced ERS injury and H9c2 cardiomyocyte apoptosis by regulating the GRP78/PERK/CHOP signaling pathway and has myocardial protection.

19.
J Food Biochem ; 46(10): e14351, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35929638

RESUMO

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 (H2 O2 ). 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-1ß (IL-1ß), 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.


Assuntos
Insuficiência Cardíaca , NF-kappa B , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/farmacologia , Trifosfato de Adenosina/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Flavanonas , Glucosídeos , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lactato Desidrogenases/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Zhong Xi Yi Jie He Xue Bao ; 9(10): 1045-50, 2011 Oct.
Artigo em Zh | MEDLINE | ID: mdl-22015182

RESUMO

In this article, the authors firstly summarized the number of applications submitted to and projects supported by the National Natural Science Foundation of China (NSFC) in the field of traditional Chinese medicine research in 2010. Then they described the district distribution, research direction layout and allotment of the approved projects in the three primary disciplines (traditional Chinese medicine, Chinese materia medica and integrated traditional Chinese and Western medicine) and their 43 subdisciplines. The targeting suggestions for improvement were given respectively by concluding the reason of disapproved projects from the point of view of applicants and supporting institution, and by stating the common problems existing in the review process from the perspectives of fund managers and evaluation experts. Lastly, the major funding fields in the near future were predicted in the hope of providing guidance for applicants.


Assuntos
Fundações , Medicina Tradicional Chinesa , Apoio à Pesquisa como Assunto , China
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