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1.
J Ethnopharmacol ; 300: 115723, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36115600

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs "taken orally after soaked with Chinese Baijiu" in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. AIM OF THE STUDY: To analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu". MATERIALS AND METHODS: Ultra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. RESULTS: The identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-ß-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-ß-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-ß-boswellic acid in XJP&B were relatively longer. CONCLUSION: This research proved that "taking XJPs orally after being soaked with Chinese Baijiu" can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu", which can provide a theoretical basis for the optimization of XJPs' clinical administration method.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Ácido Oleanólico , Aconitina/análise , Animais , Ácidos Araquidônicos , China , Cromatografia Líquida de Alta Pressão/métodos , Cicloparafinas , Medicamentos de Ervas Chinesas/química , Hiperplasia , Medicamentos sem Prescrição , Ácido Oleanólico/análise , Ratos , Triterpenos , Água
2.
J Ethnopharmacol ; 300: 115748, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162545

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: With high mortality and morbidity rates, lung cancer (LC) has become one of the major threats to human health. The treatment strategies for LC currently face issues, such as drug resistance and body tolerance. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity, and limited side effects. TCM includes a substantial number of biologically active ingredients, several of which are effective monomeric agents against LC. An increasing number of researchers are focusing their efforts on the discovery of active anti-cancer ingredients in TCM. AIM OF THE REVIEW: In this review, we summarized the anti-LC mechanisms of five types of TCM monomeric compounds. Our goal is to provide research ideas for the identification of new prospective medication candidates for the treatment of LC. MATERIALS AND METHODS: We collected reports on the anti-LC effects of TCM monomers from web databases, including PubMed, Science Direct, Web of Science, and Europe PubMed Central. Among the keywords used were "lung cancer," "traditional Chinese medicine," "pharmacology," and their combinations thereof. Then, we systematically summarized the anti-LC efficacy and related mechanisms of TCM monomers. RESULTS: Based on the available literature, this paper reviewed the therapeutic effects and mechanisms of five types of TCM monomers on LC. The characteristics of TCM monomers include the capabilities to suppress the tumor cell cycle, inhibit proliferation, induce apoptosis, promote autophagy, inhibit tumor cell invasion and metastasis, and enhance efficacy or reduce drug resistance when combined with cytotoxic agents and other methods to arrest the progression of LC and prolong the survival of patients. CONCLUSIONS: TCM contains numerous flavonoids, alkaloids, terpenoids, polyphenols, and other active compounds that are effective against LC. Given their chemical structure and pharmacological properties, these monomers are suitable as candidate drugs for the treatment of LC.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Citotoxinas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Estudos Prospectivos , Terpenos
3.
J Ethnopharmacol ; 300: 115751, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162550

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis leads to cardiac remodeling and dysfunction. Curcumae Rhizoma has been utilized in clinical trials to treat a variety of cardiovascular illnesses, although its role in myocardial fibrosis is unknown. AIM OF THE STUDY: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with Curcumae Rhizoma. MATERIALS AND METHODS: The chemical components in the aqueous extract from Curcumae Rhizoma were identified using GC-MS analysis. A prediction network describing the relationship between Curcumae Rhizoma and MF was established based on information collected from multiple databases. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate Curcumae Rhizoma targets acting on MF, which were further validated by vivo experiments. RESULTS: There were 444 targets obtained from the 39 active ingredients in Curcumae Rhizoma, and 5691 disease targets related to MF were identified. Then, 41 key targets were determined with the PPI interaction network, which was structured from 324 overlapping gene targets. GO and KEGG analyses revealed that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 signaling pathways might play crucial roles in the therapeutic mechanism of MF. According to the results of molecular docking, the binding activity between core components and targets was marvelous (affinity < -6 kcal/mol). Take it a step further, the experimental validation data affirmed that Curcumae Rhizoma substantially decreased myocardial fibrosis and recovered cardiac function in the ISO-induced rats. The associated proteins expression data implied that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways might be vital in the anti-fibrosis effect of Curcumae Rhizoma. CONCLUSION: The findings suggested that Curcumae Rhizoma diminished myocardial fibrosis by suppressing fibrosis multiplication and collagen deposition through inhibiting p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways, which might be a promising therapeutic medicament for alleviating myocardial fibrosis.


Assuntos
Medicamentos de Ervas Chinesas , Fator de Crescimento Transformador beta1 , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , Simulação de Acoplamento Molecular , NF-kappa B , Farmacologia em Rede , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno
4.
J Ethnopharmacol ; 300: 115724, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36115599

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI) is a renowned traditional Chinese medicine often used clinically to treat cardiovascular and cerebrovascular diseases. Studies have shown that DHI can significantly alter microRNA (miRNA) expression in the brain tissue. Therefore, exploring specific miRNAs' regulatory mechanisms during treatment with DHI is essential. AIM OF THE STUDY: To investigate DHI's regulatory mechanism on cerebral autophagy in rats with cerebral ischemia-reperfusion injury (CIRI). MATERIAL AND METHODS: Rats were randomly divided into the sham, middle cerebral artery occlusion (MCAO) model, and DHI-treatment groups. The extent of brain damage was evaluated using triphenyl tetrazolium chloride and hematoxylin-eosin staining. Hippocampal cell autophagy was observed using transmission electron microscopy. Autophagy-related proteins were analyzed using western blotting. Differentially expressed miRNAs were screened using high-throughput and real-time quantitative reverse transcription PCR. The relationship between miR-132-3p and ATG12 was confirmed using a dual-luciferase assay. The miR-132-3p mimics and inhibitors were transfected into PC12 cells subjected to oxygen-glucose deprivation (OGD) in vitro and MCAO model rats in vivo. RESULTS: DHI significantly altered the miRNA expression profile in rat brain tissues. The pathological changes in the brain tissues were improved, and the autophagic hippocampal cell vehicles were significantly reduced after DHI treatment. miRNA-132-3p, one of the miRNAs with a significantly different expression, was screened. Kyoto Encyclopedia of Genes and Genomes signal pathway analysis showed that its target genes were closely related to autophagy. Western blotting revealed that the p-PI3K, p-AKT, and mTOR expression increased significantly; AMPK, ULK1, ATG12, ATG16L1, and LC3II/I were downregulated in the DHI group. Dual-luciferase reporter gene experiments showed that miRNA-132-3p could target the ATG12 3'-UTR region directly. In vitro, miRNA-132-3p had a protective effect on OGD/R-induced oxidative stress injury in PC12 cells, improving cell viability, and affecting the expression of autophagy pathway-related proteins. In vivo transfection experiments showed that miR-132-3p could regulate ATG12 expression in CIRI rats' lateral brain tissue, affecting the autophagy signaling pathway. miR-132-3p overexpression reduces CIRI-induced autophagy and protects neurons. CONCLUSION: This study showed that DHI inhibits neuronal autophagy after cerebral ischemia-reperfusion. This may have resulted from miR-132-3p targeting ATG12 and regulating the autophagy signaling pathway protein expression.


Assuntos
Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Proteínas Quinases Ativadas por AMP , Animais , Apoptose , Autofagia , Proteína 12 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Isquemia Encefálica/metabolismo , Cloretos , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Glucose/farmacologia , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Infarto da Artéria Cerebral Média/patologia , MicroRNAs/metabolismo , Oxigênio/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ratos , Traumatismo por Reperfusão/metabolismo , Serina-Treonina Quinases TOR
5.
J Ethnopharmacol ; 300: 115680, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36058479

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome (MetS) is a cluster of disease centered on obesity, which is the result of stagnation of liver qi according to traditional Chinese medicine. Panax notoginseng is a traditional Chinese herbal medicine, entering liver and stomach meridians and dissipating blood stasis, in which panax notoginseng saponins (PNS) are the main active components. However, its effects and mechanism on metabolic syndrome has not been revealed yet. AIM OF STUDY: To evaluate the anti-MetS effect of PNS, including body weight and adiposity, glucose metabolism and non-alcoholic fatty liver disease (NAFLD), as well as to explore the mechanism and signaling pathway of PNS on MetS effect. MATERIALS AND METHODS: HPLC was utilized to affirm the percentages of saponins in PNS. In vivo, normal C57BL/6J mice and high-fat diet (HFD)-induced MetS mice were used to evaluate anti-MetS effect of PNS. Body weight, food and water intake were recorded. NMR imager was used for NMR imaging and lipid-water analysis. Blood glucose detection, glucose and insulin tolerance test were performed to evaluate glucose metabolism. Biochemical indexes analysis and histopathological staining were used to evaluate the effect on NAFLD. The expressions of mRNA and proteins related to thermogenesis in adipose tissue were determined using real-time PCR and Western blot. In silico, network pharmacology was utilized to predict potential mechanism. In vitro, matured 3T3-L1 adipocyte was used as subject to confirm the signaling pathway by Western blot. RESULTS: We determined the content of PNS component by HPLC. In vivo, PNS could improve metabolic syndrome with weight loss, reduction of adiposity, improvement of adipose distribution, correction of glucose metabolism disorder and attenuation of NAFLD. Mechanismly, PNS boosted energy exhaustion and dramatically enhanced thermogenesis in brown adipose tissue (BAT), induced white adipose tissue (WAT) browning. In silico, utilizing network pharmacology strategy, we identified 307 candidate targets which were enriched in MAPK signaling pathway specifically in liver tissue and adipocyte. In vitro validation confirmed ERK and p38MAPK mediated anti-MetS effects of PNS, not JNK signaling pathway. CONCLUSION: PNS exerted protective effect on metabolic syndrome through MAPK-mediated adipose thermogenic activation, which may serve as a prospective therapeutic drug for metabolic syndrome.


Assuntos
Medicamentos de Ervas Chinesas , Insulinas , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Panax notoginseng , Saponinas , Animais , Glicemia , Peso Corporal , Medicamentos de Ervas Chinesas/farmacologia , Glucose , Lipídeos , Síndrome Metabólica/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Panax notoginseng/química , RNA Mensageiro/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Água
6.
J Ethnopharmacol ; 300: 115677, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36064148

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bioactive substance identification is always the focal point and the main challenge in Chinese herbal medicine (CHM). Most CHM present multiple efficacies and multiple tropisms, which has improved the application accuracy of CHM, and is worthy of further study. In this article, the concept of "multi-tropism efficacy of CHM" has been proposed for the first time. In addition, it is hypothesized that the different components in CHM can be classified based on their efficacy status. AIM OF THE STUDY: The spectrum-effect relationship between the fingerprint and efficacy was established to identify the efficacy status of components. This provided a practical, efficient and accurate way to identify the bioactive substances from a complex CHM system. MATERIALS AND METHODS: The network pharmacology approach was applied to preliminarily analyze the potential antibacterial compounds and mechanisms of HQ. Furthermore, its chemical fingerprint was established and the characteristic peaks were identified by LC-MS/MS. The antibacterial and anti-inflammatory bioactivities of HQ were determined to evaluate its pharmacological effect of heat-clearing and detoxification, and its anticoagulation activity was determined to evaluate its heat-clearing and tocolysis effects. The spectrum-effect relationships were assessed by gray correlation analysis to discriminate the status of active components in HQ with different efficacies. RESULTS: Network pharmacology analysis revealed apigenin, wogonin, baicalein, acacetin, ß-sitosterol, baicalin, eugenol, moslosooflavone, palmitic acid, oroxylin-A 7-O-glucuronide, and scutevulin as the potential active compounds responsible for the efficacy of HQ against both E. coli and S. aureus. The spectrum-effect relationship was utilized to reveal the orientation activities, with the results as follows: 1) The main basic-efficacy components in HQ with antibacterial, anti-inflammatory, and anticoagulant effects were P5, P8, P9, P15, P18, P19, P20; while the general basic-efficacy components were P2, P3, P6, P7, P11, P14, P21, P22, P28. 2) The main efficacy-oriented components in HQ with antibacterial effects on E. coli were P1, P12, P17, while the general efficacy-oriented compound was P10, P24, P25, P26, P27; the main efficacy-oriented in HQ with antibacterial effects on S. aureus were P14 and the general efficacy-oriented components were P1, P12, P26, P29, P30, respectively. 3) The main efficacy-oriented components with anti-inflammatory activity were P14, P24, P25, P27, and P30, while the general efficacy-oriented components were P13, P23, P26. 4) The main efficacy-oriented compounds in HQ with effects on anticoagulation were P6 and P22; these acted by prolonging APTT through the intrinsic coagulation pathway and PT through the extrinsic coagulation pathway, respectively. 5) The pharmacodynamic status classification of Scutellaria baicalensis ingredients were confirmed by nine reference compounds exemplarily. CONCLUSION: This work established a novel strategy for active compound efficacy status identification in multi-tropism Chinese herbal medicine (Scutellaria baicalensis Georgi) based on multi-indexes spectrum-effect gray correlation analysis, the method is scientific feasible and can be applied to the effective substances identification and quality control of other CHM.


Assuntos
Medicamentos de Ervas Chinesas , Scutellaria baicalensis , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anticoagulantes , Apigenina , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Escherichia coli , Eugenol , Glucuronídeos , Ácido Palmítico , Piridinolcarbamato , Scutellaria baicalensis/química , Staphylococcus aureus , Espectrometria de Massas em Tandem , Tropismo
7.
J Ethnopharmacol ; 300: 115690, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.


Assuntos
Colite Ulcerativa , Fator 88 de Diferenciação Mieloide , Animais , Caspases/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Interleucina-6/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
J Ethnopharmacol ; 300: 115675, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075275

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L. (RP) and Coptis chinensis Franch. (CC), frequently used as herbal pair (HP) in clinical practicing of traditional Chinese medicine, exerted predominate efficacies in colitis treatment. However, the mechanism of their synergism lacks scientific explanation. AIM OF THE STUDY: By integrating network pharmacology and DSS-induced colitis model, the anti-colitis effects and synergistic molecular mechanisms of RP-CC combination was determined. MATERIALS AND METHODS: In vivo study, mice were divided into control, model, RP, CC and RP-CC (low, middle, high) groups, 2.5% DSS was administrated to induce colitis for consecutive 7 days, subsequently, the therapeutic effects were evaluated from body weight changes, disease activity index (DAI), and pathological conditions. After determining the shared and exclusive targets of RP and CC, respectively by network pharmacology, CETSA, WB, and qPCR were utilized to verify the action modes of RP and CC on specific targets. RESULTS: Compared to RP or CC used alone, RP-CC combination can significantly protect colon tissues from inflammatory damage in a dose-dependent manner via remarkably alleviating DAI and colon shortening. Network pharmacological analysis suggested that AKT1 would be the core target for RP-CC synergism since these two herbs could simultaneously but non-competitively bind to AKT1 at different sits. Furthermore, RP and CC could also influencing HIF and MAPK pathways, respectively, these additional actions attribute to more optimizing effectiveness towards colitis. CONCLUSION: In contrast to the mild therapeutic effects of RP or CC individually, RP-CC herb pair could exert strong and synergistic effects in treatment of colitis via non-competitive binding to AKT1 simultaneously, as well as exclusively influencing MAPK and HIF pathways. Our study not only provides the evidence for understanding the combined effect of RP and CC, but also brings up a new strategy and suggestive thoughts for the rationality of HP-based TCM formula.


Assuntos
Colite , Coptis , Medicamentos de Ervas Chinesas , Rheum , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Coptis/química , Coptis chinensis , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Camundongos , Farmacologia em Rede
9.
J Ethnopharmacol ; 301: 115773, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36191660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. AIM OF THE STUDY: To investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. MATERIALS AND METHODS: The extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. RESULTS: Thirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO3 sulfonation products and five H2SO3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. CONCLUSION: SF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation.


Assuntos
Medicamentos de Ervas Chinesas , Triptofano , Camundongos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Simulação de Acoplamento Molecular , Fumigação , Enxofre/toxicidade , Enxofre/química , Metabolômica , Medicamentos de Ervas Chinesas/química , Tirosina , Fenilalanina
10.
J Ethnopharmacol ; 301: 115770, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36191661

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular diseases are still the leading cause of death worldwide. Heart failure (HF), as the terminal stage of many cardiovascular diseases, has brought a heavy burden to the global medical system. Microvascular rarefaction (decreased myocardial capillary density) with reduced coronary flow reserve is a hallmark of HF and therapeutic myocardial angiogenesis is now emerging as a promising approach for the prevention and treatment in HF. Traditional Chinese medicine (TCM) has made remarkable achievements in the treatment of many cardiovascular diseases. Growing evidence have shown that their protective effect in HF is closely related to therapeutic angiogenesis. AIM OF THE STUDY: This review is to enlighten the therapeutic effect and pro-angiogenic mechanism of TCM in HF, and provide valuable hints for the development of pro-angiogenic drugs for the treatment of HF. MATERIALS AND METHODS: The relevant information about cardioprotective TCM was collected from electronic scientific databases such as PubMed, Web of Science, ScienceDirect, and China National Knowledge Infrastructure (CNKI). RESULTS: The studies showed that TCM formulas, extracts, and compounds from herbal medicines can provide therapeutic effect in HF with their pro-angiogenic activity. Their actions are achieved mainly by regulating the key angiogenesis factors particularly VEGF, as well as related regulators including signal molecules and pathways, non-coding miRNAs and stem cells. CONCLUSION: TCM and their active components might be promising in therapeutic angiogenesis for the treatment of HF.


Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Plantas Medicinais , Humanos , Medicina Tradicional Chinesa , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , China , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química
11.
J Ethnopharmacol ; 301: 115754, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195301

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis Rhizoma (ZR) and Zingiberis Rhizoma Carbonisata (ZRC), as two forms of ginger-based herbal drugs used in China for at least 2000 years, have been recorded in Chinese Pharmacopoeia and applied for specific indications in traditional Chinese medicine (TCM). AIM OF THE STUDY: The present study aimed to explore the underlying therapeutic and processing mechanism of the absorbed components of ZR and ZRC on deficiency-cold and hemorrhagic syndrome (DCHS) using network pharmacological technique combined with pharmacokinetics strategy. MATERIALS AND METHODS: In this study, a rapid and sensitive approach was conceived to simultaneously determine the seven components (zingiberone, 6-gingerol, 8-gingerol, 6-shogaol, 6-paradol, diacetyl-6-gingerol and 10-gingerol) in rat serum by HPLC-DAD-MS. The network pharmacological technique was employed to evaluate the effect of the absorbed components of ZR and ZRC on DCHS. Also, the vitro experiments were carried out to validate the functions of the seven compounds on coagulation and other major haematological effects. RESULTS: The values of intra-assay and inter-assay precision were determined to be less than 7.44%, with an accuracy value ranging from 83.64% to 107.99%. Analysis of rat plasma revealed that the extraction recoveries and matrix effects of the seven analytes were >85.76%. The method for validation following oral administration of ZR and ZRC to rats was proved to be a success in the pharmacokinetic study of the seven ingredients. Pharmacokinetics showed that ZR processing could enhance the absorption and utilization of 6-shogaol, 6-paradol and diacetyl-6-gingerol, meanwhile reduce the absorption of 6-gingerol, 8-gingerol, and 10-gingerol. Through the pathway enrichment analysis, it was found that the significant biological process of ZR and ZRC on DCHS was primarily associated with complement, coagulation cascades and platelet activation pathways. The vitro experiments indicated that zingiberone, 6-paradol and diacetyl-6-gingerol had a hemostatic effect by upregulating the expression of one or more targets such as TNF-α, FⅩa, FⅫ, FⅧ, ICAM-1, vWF and ITGB3. While 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol played a critical role in promoting blood circulation by increasing the expression of TM and/or PORC, and/or reducing the expression of ITGB3. CONCLUSION: In brief, network pharmacological technique in combination with pharmacokinetics strategy provided an applicable method for pharmacological mechanism study of ZR and ZRC, which, also, could be used as reference for quality control of the two drugs. In a broader sense, this combined strategy might even be valuable in uncovering the therapeutic and processing mechanism of Chinese herbs on a systematic level.


Assuntos
Diacetil , Medicamentos de Ervas Chinesas , Ratos , Animais , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacocinética
12.
J Ethnopharmacol ; 301: 115772, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36202164

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The 'cold' property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the 'cold' property herbs on heat syndrome has not been investigated. AIM OF THE STUDY: The study aimed to probe the activities of the four typical 'cold' property herbs on hyperthyroidism. MATERIALS AND METHODS: Firstly, the four typical 'heat' property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical 'cod' property herbs and the four typical 'heat' property herbs. H&E staining were used to confirmed the influence of the typical 'cold' property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical 'cold' property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na+/K+-ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot. RESULTS: It is proved that the four typical 'cold' property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical 'heat' property herbs showed no benefit. Moreover, the four typical 'cold' property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca2+ and MAPK signaling pathway. And the levels of UCP-1, Na+/K+-ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical 'cold' property herbs. CONCLUSION: The four typical 'cold' property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+/MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.


Assuntos
Medicamentos de Ervas Chinesas , Hipertireoidismo , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Ácido Araquidônico , Ácido Linoleico , Interleucina-6 , Receptores Ativados por Proliferador de Peroxissomo , Metabolômica , Taurina , Hormônios Tireóideos , Inflamação , Trifosfato de Adenosina , Glutationa
13.
J Ethnopharmacol ; 301: 115789, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36208822

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustri Lucidi Fructus (LLF) is one of the usual Chinese herbs that has long been used with high therapeutic and condition value. LLF is used for the treatment of dizziness and tinnitus, soreness and weakness of the waist and knees, premature greying of the hair, the darkness of the eyes, internal heat and thirst, bone steam and hot flashes and other symptoms. AIM OF THE STUDY: This review reviews botany, traditional uses, processing, phytochemistry, quality control, pharmacology, toxicity and pharmacokinetics to better understand its therapeutic potential. MATERIALS AND METHODS: The literature on LLF was obtained from Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WAN FANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS: So far, Multiple chemical components were isolated and identified from LLF, mainly including terpenoids and flavonoids. Modern studies have shown that LLF extracts and compounds have a wide range of pharmacological effects, including antitumor, liver protection, blood glucose, lipid-lowering, immune regulation, and other aspects. CONCLUSIONS: LLF occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant and its chemical composition, pharmacological activity, quality control, toxicity and pharmacokinetics.


Assuntos
Botânica , Medicamentos de Ervas Chinesas , Ligustrum , Ligustrum/química , Medicina Tradicional Chinesa , Fitoterapia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/farmacologia , Etnofarmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
14.
J Ethnopharmacol ; 301: 115801, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36216199

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The processed lateral root of Aconitum carmichaelii Debx. is known as Fuzi, an extensively used Traditional Chinese Medicine to treat cardiovascular diseases, rheumatism arthritis, bronchitis, pains, and hypothyroidism, etc. Although Chinese Pharmacopeia regulates the safe clinical dosage of Fuzi at 3-15 g/person/day, such recommendation not only lacks bench evidence but also does not differentiate Fuzi with different processing types, such as Heishunpian and Paofupian. AIM OF THE STUDY: The current study aimed to 1) determine No-Observed-Adverse-Effect-Levels of Heishunpian and Paofupian in rats and 2) investigate the related toxicity mechanisms for their safe clinical use. MATERIALS AND METHODS: After giving clinically relevant dosing regimen of Heishunpian/Paofupian to rats, we conducted toxicity assessments including ECG monitoring, histopathological changes and serum biomarkers to detect organ injury. Metabolomic study in the liver revealed changes in endogenous metabolite levels after two-week treatment of Fuzi preparations or its corresponding six toxic alkaloids mixtures. RESULTS: The NOAEL for both bolus and two-week treatments of Heishunpian and Paofupian in rats was designated to be 7.5 g/kg and 15 g/kg, respectively. Corresponding recommended doses in humans were 7.5-25 g/person/day for Heishunpian and 15-50 g/person/day for Paofupian. Metabolic profiles revealed more significant alterations in endogenous substances from rats receiving the two Fuzi preparations than their corresponding toxic alkaloids mixtures. Upregulation of bile acid pathway could be responsible for Fuzi induced liver injury. CONCLUSIONS: Compared to the current maximum recommended dose, our suggested upper limit of guided dose for Heishunpian was comparable, whereas that for Paofupian could be further elevated. Both C19-diterpenoid alkaloids and co-occurring components in Fuzi preparations contributed to their hepatotoxicity via upregulation of bile acid pathway.


Assuntos
Aconitum , Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Medicamentos de Ervas Chinesas , Humanos , Ratos , Animais , Aconitum/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides/metabolismo , Diterpenos/metabolismo , Medicina Tradicional Chinesa/efeitos adversos , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Raízes de Plantas/toxicidade
15.
J Ethnopharmacol ; 301: 115820, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36220511

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Yangshe granule is a characteristic Chinese preparation against cervical cancer used at Fudan University Shanghai Cancer Center, and it consists of Hedyotis Diffusae Herba, Solani Lyrati Herba, Rubiae Radix et Rhizoma, Echinopsis Radix, Angelicae Sinensis Radix, Codonopsis Radix and Atractylodis Macrocephalae Rhizoma. AIM OF THE STUDY: The objective of the current study was to investigate the preclinical efficacy of compound Yangshe granule against cervical cancer and elucidate the underlying mechanisms. MATERIALS AND METHODS: Antitumor effect of the preparation was investigated in U14 cells in vitro and subcutaneous xenograft mice in vivo. The underlying mechanisms were investigated by through network pharmacological analysis and identified by in vitro study. The components of compound Yangshe granule were collected from the Traditional Chinese Medicine Systems Pharmacology database, and the corresponding targets were predicted by the SwissTargetPrediction database. The targets involved in cervical cancer were collected from the GeneCards, Online Mendelian Inheritance in Man and DrugBank databases. A protein‒protein interaction network was constructed by using the String platform. The drug-disease-target network was plotted by Cytoscape software. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed to investigate hub targets. RESULTS: After treatment with 0.5-10 mg/mL compound Yangshe granule, the survival rates of U14 cells gradually declined to 53.32% for 24 h, 23.62% for 48 h, and 12.81% for 72 h. The apoptosis rates of U14 cells gradually increased to 15.52% for 24 h, 23.87% for 48 h, and 65.01% for 72 h after treatment with 2-10 mg/mL compound Yangshe granule. After oral administration of compound Yangshe granule by xenograft mice, the tumor inhibition rates reached 52.27%, 74.62%, and 82.70% in the low, middle, and high dose groups, respectively. According to the network pharmacological analysis, quercetin, luteolin and naringenin were the most bioactive ingredients of the preparation. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that compound Yangshe granule may combat cervical cancer through the PI3K/AKT pathway. CONCLUSION: In summary, network pharmacology combined with biological experiments demonstrated that the main bioactive components including quercetin, luteolin and naringenin could inhibit the tumor growth by regulating the PI3K/AKT pathway and Bcl-2 family. Thus, compound Yangshe granule may be a promising adjuvant therapy for cervical cancer.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias do Colo do Útero , Feminino , Humanos , Camundongos , Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Quercetina/farmacologia , Luteolina/farmacologia , Farmacologia em Rede , Transdução de Sinais , China , Medicina Tradicional Chinesa , Neoplasias do Colo do Útero/tratamento farmacológico , Simulação de Acoplamento Molecular
16.
J Ethnopharmacol ; 301: 115800, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36228890

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC). AIMS OF THIS STUDY: To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC. MATERIALS AND METHODS: The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking. RESULTS: The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II. CONCLUSIONS: For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Plantas Medicinais , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicina Tradicional Tibetana , Medicina Herbária , Medicamentos de Ervas Chinesas/farmacologia , Fator A de Crescimento do Endotélio Vascular , Farmacologia em Rede , Tibet
17.
J Ethnopharmacol ; 301: 115835, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252878

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated. AIM OF THE STUDY: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism. METHODS: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD. RESULTS: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats. CONCLUSION: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Humanos , Feminino , Ratos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ovariectomia/efeitos adversos , Transdução de Sinais , Metabolismo dos Lipídeos , Ácidos Graxos/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo
18.
J Ethnopharmacol ; 301: 115838, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36257343

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum carmichaelii Debeaux. (also known as Fuzi in Chinese) is a toxic Chinese medicine but widely used in clinical practice with remarkable effects. It is specifically used to treat cardiovascular diseases, rheumatoid arthritis, and other diseases, in Korea, Japan, and India. AIM OF THIS REVIEW: This study aimed to summarize and discuss the effects of drug processing on toxicity, chemical composition, and pharmacology of the lateral root of Aconitum carmichaelii Debeaux. This review could provide feasible insights for further studies. MATERIALS AND METHODS: Relevant information on phytochemistry, pharmacology, and toxicology of Fuzi was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and CNKI. RESULTS: More than 100 chemical compounds, including alkaloids, flavonoids, and polysaccharides were revealed. Modern pharmacological studies show that these chemical components have good effects on anti-inflammatory, anti-tumor, anti-aging, treatment of cardiovascular diseases, and improving immunity. Di-ester alkaloids are the main source of Fuzi toxicity. Increasing studies have shown that Fuzi can induce multiple organ damage, especially cardiotoxicity and neurotoxicity. At present, most of the Fuzi used in clinical practice are processed. The processing affects the chemical structure, pharmacology, and toxicology of Fuzi. Moreover, different processing methods have different effects on Fuzi. CONCLUSIONS: This review analyzed the effects of Fuzi processing methods on its toxicity and efficiency. The lateral roots of aconite are the known medicinal part of Fuzi; however, the aerial parts of aconite are understudied and require further research to expand its medicinal potential. Processing and compatibility are the primary means to reduce Fuzi toxicity. Nevertheless, establishing a reasonable unified safe dose range requires further discussion.


Assuntos
Aconitum , Alcaloides , Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Aconitum/química , Raízes de Plantas/química , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides/química , Medicina Tradicional Chinesa
19.
J Ethnopharmacol ; 301: 115847, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36272491

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ershiwuwei Zhenzhu Pill (EZP), a representative and classic formula in Tibetan medicine, is commonly used in the treatment of various cerebrovascular diseases, including ischemic stroke (IS). Nevertheless, their efficacy and potential mechanism in treating IS have yet to be investigated. AIM OF THE STUDY: This study aimed to investigate the potential mechanisms of EZP in the treatment of IS based on network pharmacology and experimental verification. MATERIALS AND METHODS: The chemical profile of EZP was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The targets related to the compounds in EZP were predicted by the Swiss Target Prediction and Target Net platform, and targets of IS were collected from the Gene Cards and OMIM databases. Subsequently, a protein-protein interaction (PPI) network of targets was constructed and analyzed by the STRING database and Cytoscape software, version 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed, and an ingredient-target-pathway network was constructed. Ultimately, the middle cerebral artery occlusion (MCAO) model was established to evaluate the anti-IS effects of EZP by detecting the neurological deficit score, HE, Nissl and TCC staining, and inflammatory factors, and the expression of key protein targets was detected by western blotting. RESULTS: A total of 129 components were identified in EZP. Network pharmacology revealed 3136 compound targets and 2826 disease-related targets, and 412 overlapping proteins were obtained as potential therapeutic targets. The PPI network results showed that 6 key targets (AKT1, SRC, VEGFA, TP53, TNF and EGFR) were core targets of EZP in the treatment of IS. Western blotting demonstrated that the expression levels of AKT1, VEGFA, TP53, SRC, TNF and EGFR in the brain tissue of MCAO rats were significantly changed after treatment with EZP compared to the model group. CONCLUSIONS: EZP ameliorated IS in MCAO rats. The underlying mechanism might be associated with inhibiting inflammation and apoptosis, promoting angiogenesis and protecting neurons by regulating multiple targets and pathways.


Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Animais , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Receptores ErbB , AVC Isquêmico/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Medicina Tradicional Tibetana
20.
J Ethnopharmacol ; 301: 115851, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36273748

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The external use of traditional Chinese medicine (TCM) to treat fractures has a long history of clinical application and theoretical basis, and is also one of the characteristic treatment methods of TCM with significant efficacy and many advantages. Among the commonly used external Chinese medicines, Tubiechong is noteworthy. AIM OF THE STUDY: To elucidate whether local patching of Tubiechong can promote fracture healing and explore its mechanism of action. MATERIALS AND METHODS: A rat tibia fracture model was constructed by the modified Einhorn modeling method. X-ray films were taken to evaluate the progress of fracture healing. Serum bone alkaline phosphatase (BALP), osteocalcin (BGP) and the C-terminal content of collagen type I (CTX-I) were analyzed by ELISA. CD31 immunohistochemistry was used to evaluate angiogenesis in the tibia segment. The effects of Tubiechong decoction (TD) on HUVEC proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell migration assay, respectively. RNA-seq was performed to identify differentially expressed genes (DEGs). Enrichment of functions and signaling pathway analysis were performed based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to study gene expression levels. Western blotting (WB) was used to detect the expression of relevant regulatory proteins. RESULTS: The healing time of rat tibia fractures in the three TD dose groups was shortened. The serum levels of BALP, BGP and CTX- I in the TD-treated group were higher than those in the NC group. The X-ray results showed that on the 7th day after surgery, the fracture healing degree of the high-dose TD group was significantly better than that of the NC group, and the fracture healing degrees of each TD treatment group were significantly higher than those of the NC group on the 14th, 17th, and 21st days after the operation. The CD31 immunohistochemistry results showed that the number of blood vessels and the vascular area in the TD treatment group were higher than those in the NC group. In vitro, TD promoted the proliferation, wound healing and migration of HUVECs. GO analysis of transcriptome sequencing results showed that TD significantly altered the expression of genes related to cell growth, metabolism, and motility. According to KEGG annotations, VEGFA was upregulated. Eight DEGs were enriched in the VEGFA-VEGFR2 signaling pathway, of which six were upregulated. KEGG signaling pathway analysis showed that the most abundant DEGs were in mitogen-activated protein kinase (MAPK) signaling pathway. qRT-PCR showed that VEGFA gene expression in HUVECs was 7.8 times that of the control group after 1 mg/mL TD treatment for 24 h, and WB experiments showed that its protein expression was 3 times that of the control group. WB results showed that the phosphorylated ERK gene was highly expressed, while the expression levels of phosphorylated P38 and phosphorylated JNK protein remained unchanged. CONCLUSION: Tubechong patching therapy promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.


Assuntos
Consolidação da Fratura , Fator A de Crescimento do Endotélio Vascular , Animais , Ratos , Sistema de Sinalização das MAP Quinases , Neovascularização Patológica/metabolismo , Transdução de Sinais , Tíbia/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Medicamentos de Ervas Chinesas
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