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AIMS: Abiraterone acetate, a prodrug of abiraterone (ABI), provides an efficient therapeutic option for metastatic castration-resistant prostate cancer patients. ABI undergoes extensive metabolism in vivo and is transformed into active metabolites Δ4 -abiraterone and 3-keto-5α-abiraterone as well as inactive metabolites abiraterone sulfate and abiraterone N-oxide sulfate. We aimed to examine the effect of polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on the pharmacokinetics of ABI and its metabolites. METHODS: In this study, 81 healthy Chinese subjects were enrolled and divided into 2 groups for fasted (n = 45) and fed (n = 36) studies. Plasma samples were collected after administering a 250 mg abiraterone acetate tablet followed by liquid chromatography-tandem mass spectrometry analysis. Genotyping was performed on a MassARRAY system. The association between SLCO2B1, CYP3A4, UGT1A4 genotype and pharmacokinetic parameters of ABI and its metabolites was assessed. RESULTS: Food effect study demonstrated high fat meal remarkedly increased systemic exposure of ABI and its metabolites. The geometric mean ratio and 90% confidence interval of area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t ) and maximum plasma concentration (Cmax ) of ABI in fed state vs. fasted state were 351.64% (286.86%-431.04%) and 478.45% (390.01%-586.94%), respectively, while the corresponding results were ranging from 145.11% to 269.42% and 150.10% to 478.45% for AUC0-t and Cmax of ABI metabolites in fed state vs. fasted state, respectively. The SLCO2B1 rs1077858 had a significant influence on AUC0-t and Cmax , while 7 other SLCO2B1 variants prolonged half-life of ABI under both fasted and fed conditions. As for ABI metabolites, the systemic exposure of Δ4 -abiraterone, abiraterone sulfate and abiraterone N-oxide sulfate as well as the elimination of 3-keto-5α-abiraterone were significantly affected by SLCO2B1 polymorphisms. Polymorphisms in CYP3A4 and UGT1A4 did not significantly affect pharmacokinetics of ABI and its metabolites. CONCLUSION: Polymorphisms in SLCO2B1 were significantly related to the pharmacokinetic variability of ABI and its metabolites under both fasted and fed conditions.
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Androstenos , Citocromo P-450 CYP3A , Transportadores de Anión Orgánico , Farmacocinética , Androstenos/metabolismo , Androstenos/farmacocinética , Humanos , Transportadores de Anión Orgánico/genética , Citocromo P-450 CYP3A/genética , Glucuronosiltransferasa/genética , Neoplasias de la Próstata , Polimorfismo de Nucleótido Simple , Pueblos del Este de Asia , Masculino , Voluntarios , Adulto , Ayuno , AlimentosRESUMEN
BACKGROUND: Gastric carcinoma (GC) treatment needs to be developed rapidly. Compound Kushen Injection (CKI), a formula from traditional Chinese medicine, has been used clinically in combination with chemotherapy to treat GC with satisfactory results. However, the molecular mechanism by which CKI acts to cure GC is still unclear. METHODS: In the present study, in vivo and in vitro experiments were used to assess the efficacy of CKI. Using ceRNA microarray and TMT technologies, the molecular mechanism of CKI was further investigated at the transcriptional and protein levels, and a bioinformatics approach was employed to investigate and functionally validate key CKI targets in GC. RESULTS: When combined with cisplatin (DDP), CKI significantly increased its efficacy in preventing the proliferation and metastasis of GC cells and malignant-looking tumors in mice. High-throughput sequencing data and bioinformatics analysis showed that CKI regulated the TNF signaling pathway, epithelial-mesenchymal transition (EMT), with VCAM1 as a key target. The transcription factors CEBPB, JUN, RELA, NFKB1, the EMT mesenchymal-like cell markers N-cadherin and vimentin, as well as the expression of VCAM1 and its upstream signaling driver TNF, were all downregulated by CKI. In contrast, the expression of the EMT epithelial-like cell marker E-cadherin was upregulated. CONCLUSION: CKI can effectively inhibit GC growth and metastasis, improve body's immunity, and protect normal tissues from damage. The molecular mechanism by which CKI inhibits metastasis of GC is by regulating VCAM1 induced by the TNF signaling pathway to inhibit EMT of GC. Our results provide an important clue to clarify precisely the multi-scale molecular mechanism of CKI in the treatment of GC.
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Antineoplásicos , Carcinoma , Neoplasias Gástricas , Animales , Ratones , Transición Epitelial-Mesenquimal , Antineoplásicos/farmacología , Transducción de Señal , Neoplasias Gástricas/genética , Cadherinas , Línea Celular TumoralRESUMEN
In the synthesis of larotaxel, a new-generation toxoid, eleven related impurities were detected. In this study, Impurity-I, II, III, IV, VII, IX, X and XI were synthesized, and Impurity-VI, VIII were isolated with the help of preparative high-performance liquid chromatography (HPLC). The structures of all impurities were characterized using high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectral data, and the possible origins of them were explained. Furthermore, a sensitive and accurate HPLC method was developed for the determination of larotaxel and its eleven impurities. The method was validated to fulfill the requirements of the International Conference on Harmonisation (ICH) guidelines, including specificity, sensitivity, precision, accuracy, linearity, and robustness. The validated method can be applied for routine quality control analysis of larotaxel.
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Contaminación de Medicamentos , Taxoides , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de MasasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen injection (CKI) is a representative medication of Chinese herbal injection and is often used in the adjuvant treatment of nasopharyngeal carcinoma (NPC), but its antitumor mechanism is poorly understood. AIM OF THE STUDY: To preliminarily elucidate the effects and possible mechanisms of CKI on NPC. METHODS: In this work, we explored the possible molecular mechanisms of CKI against NPC by using network pharmacology and molecular docking. In addition, proteomics was used to explore the localization and quantitative information of protein in NPC C666-1 cells after the intervention of CKI, and enrichment analysis was used to obtain the potential targets and pathways. Finally, the effect and the core targets of CKI in the intervention of NPC were explored in vitro experiments. RESULTS: Network pharmacology analysis identified three active components of CKI and 13 key targets. Molecular docking analysis showed that TNF, PTEN, CCND1, MAPK3, IL6, HIF1A, MYC had high affinity with corresponding components. Then the key pathway, cell cycle and the core targets MYC, CCND1, and P15 related to the key pathway were obtained. The results of in vitro experiments showed that CKI could inhibit the proliferation, migration, and invasion of NPC 5-8F cells and C666-1 cells, induce apoptosis of C666-1 cells, and arrest cell cycle G0/G1 phase. In addition, RT-qPCR and western blot showed that the expression of P15 was up-regulated and E2F4, E2F5, c-Myc, CCND1, and P107 was down-regulated in 5-8F cells and C666-1 cells intervened by CKI. CONCLUSION: The key pathway, cell cycle and the corresponding core targets MYC, CCND1, and P15 were obtained from network pharmacology, molecular docking, and proteomics. CKI could inhibit the proliferation, migration, and invasion of NPC cells, induce apoptosis of C666-1 cells. Especially CKI may arrest cell cycle G0/G1 phase through regulating targets MYC/P15/CCND1 of cell cycle pathway.
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Antineoplásicos , Medicamentos Herbarios Chinos , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Antineoplásicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Transducción de Señal , Neoplasias Nasofaríngeas/tratamiento farmacológico , Ciclina D1/genéticaRESUMEN
Background: Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. Methods: A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. Results: CKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8+ T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8+ T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro. Conclusions: The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.
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Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Ratones , Animales , Linfocitos T CD8-positivos/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , ARN , Microambiente TumoralRESUMEN
Xuanfu Daizhe Decoction, first seen in Zhang Zhongjing's Treatise on Cold Damage Diseases, was composed of seven medicinal materials: Inulae Flos, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma Recens, Haematitum, Pinelliae Rhizoma and Jujubae Fructus. It was used to treat gastric fullness and hardness and belching due to the wrong treatment of typhoid fever and sweating. With detailed records and description in ancient medical books, Xuanfu Daizhe Decoction was widely adopted in clinical practice by physicians of later generations, which expanded its main therapeutic functions. By comprehensive collation of ancient and modern literature on Xuanfu Daizhe Decoction, this paper systematically explored the historical evolution of the prescription from the source, composition, dosage, processing, clinical application, function interpretation and decocting method. It was found that the composition and processing method of the prescription in the past dynasties were relatively consistent, and there was a gradual decrease in dosage in clinical application. In ancient times, Xuanfu Daizhe Decoction was mainly used to treat nausea, vomiting, hiccups, constipation, etc., while modern clinicians mainly used it for digestive diseases such as reflux esophagitis and gastritis. Through the analysis and textual research, the composition, dosage, processing, function evolution and decocting method of this prescription were determined, which provided reference for the research and development of compound preparations of Xuanfu Daizhe Decoction.
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Medicamentos Herbarios Chinos , Triterpenos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Extractos Vegetales , RizomaRESUMEN
This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.
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Antineoplásicos , Neoplasias , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Antineoplásicos/farmacología , Medicamentos Herbarios Chinos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones , Neoplasias/tratamiento farmacológico , Dolor/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-bcl-2 , Factor A de Crecimiento Endotelial Vascular , Pez CebraRESUMEN
Gastric carcinoma (GC) is a severe tumor of the digestive tract with high morbidity and mortality and poor prognosis, for which novel treatment options are urgently needed. Compound Kushen injection (CKI), a classical injection of Chinese medicine, has been widely used to treat various tumors in clinical practice for decades. In recent years, a growing number of studies have confirmed that CKI has a beneficial therapeutic effect on GC, However, there are few reports on the potential molecular mechanism of action. Here, using systems pharmacology combined with proteomics analysis as a core concept, we identified the ceRNA network, key targets and signaling pathways regulated by CKI in the treatment of GC. To further explore the role of these key targets in the development of GC, we performed a meta-analysis to compare the expression differences between GC and normal gastric mucosa tissues. Functional enrichment analysis was further used to understand the biological pathways significantly regulated by the key genes. In addition, we determined the significance of the key genes in the prognosis of GC by survival analysis and immune infiltration analysis. Finally, molecular docking simulation was performed to verify the combination of CKI components and key targets. The anti-gastric cancer effect of CKI and its key targets was verified by in vivo and in vitro experiments. The analysis of ceRNA network of CKI on GC revealed that the potential molecular mechanism of CKI can regulate PI3K/AKT and Toll-like receptor signaling pathways by interfering with hub genes such as AKR1B1, MMP2 and PTGERR3. In conclusion, this study not only partially highlighted the molecular mechanism of CKI in GC therapy but also provided a novel and advanced systems pharmacology strategy to explore the mechanisms of traditional Chinese medicine formulations.
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BACKGROUND: Liver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-ß (TGF-ß) is a critical mediator of chronic liver fibrosis, targeting TGF-ß isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-ß/Smad7 signaling. METHODS: A meta-analysis was performed to evaluate CKI intervention on viral hepatitis-induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl4 ) injection or methionine-choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF-ß/Smad signaling and typical fibrosis-related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT-PCR, Western blotting, RNA-seq, immunofluorescence, and immunohistochemistry. RESULTS: Based on meta-analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF-ßR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI. CONCLUSIONS: Our results unveil the approach of CKI in rebalancing TGF-ß/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.
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Medicamentos Herbarios Chinos/farmacología , Transducción de Señal/efectos de los fármacos , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Tetracloruro de Carbono/toxicidad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular , Medicamentos Herbarios Chinos/uso terapéutico , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/metabolismo , Humanos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Medicina Tradicional China , Metaanálisis como Asunto , Ratones , Ratones Endogámicos C57BL , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteína smad7/antagonistas & inhibidores , Proteína smad7/genéticaRESUMEN
BACKGROUND: There is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Immunotherapy is promising especially when combined with traditional therapies. This study aimed to investigate the immunomodulatory function of an approved Chinese medicine formula, compound kushen injection (CKI), and its anti-HCC efficiency in combination with low-dose sorafenib. METHODS: Growth of two murine HCC cells was evaluated in an orthotopic model, a subcutaneous model, two postsurgical recurrence model, and a tumor rechallenge model with CKI and low-dose sorafenib combination treatment. In vivo macrophage or CD8+ T cell depletion and in vitro primary cell coculture models were used to determine the regulation of CKI on macrophages and CD8+ T cells. RESULTS: CKI significantly enhanced the anticancer activity of sorafenib at a subclinical dose with no obvious side effects. CKI and sorafenib combination treatment prevented the postsurgical recurrence and rechallenged tumor growth. Further, we showed that CKI activated proinflammatory responses and relieved immunosuppression of tumor-associated macrophages in the HCC microenvironment by triggering tumor necrosis factor receptor superfamily member 1 (TNFR1)-mediated NF-κB and p38 MAPK signaling cascades. CKI-primed macrophages significantly promoted the proliferation and the cytotoxic ability of CD8+ T cells and decreased the exhaustion, which subsequently resulted in apoptosis of HCC cells. CONCLUSIONS: CKI acts on macrophages and CD8+ T cells to reshape the immune microenvironment of HCC, which improves the therapeutic outcomes of low-dose sorafenib and avoids adverse chemotherapy effects. Our study shows that traditional Chinese medicines with immunomodulatory properties can potentiate chemotherapeutic drugs and provide a promising approach for HCC treatment.
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Carcinoma Hepatocelular/tratamiento farmacológico , Sinergismo Farmacológico , Medicamentos Herbarios Chinos/farmacología , Terapia de Inmunosupresión , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Sorafenib/farmacología , Macrófagos Asociados a Tumores/inmunología , Animales , Antineoplásicos/farmacología , Apoptosis , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Células Tumorales Cultivadas , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Through the multi-dimensional mining and analysis of launched anti-influenza proprietary Chinese medicines,this paper explores the study of the prescriptions and pharmacodynamics of traditional Chinese medicines for influenza. We established a standardized database by collecting and excavating the launched Chinese patent medicines that clearly describe the treatment of influenza. Frequency analysis and association rules were used to analyze the frequency of Chinese patent medicines for the treatment of influenza in the aspects of dosage form,category and prescription drugs. The network module partitioning method was used to excavate the core drug combination for influenza. The relationship between functional nouns was used to construct a network of functional terminology and analyze the relationship between its main functions. The pharmacological characteristics quantitative method was used to analyze the pharmacological characteristics of three heat-clearing and detoxifying type Chinese patent medicines for influenza. This article shows the traditional Chinese medicine syndrome differentiation ideas and medication rules for influenza treatment in many aspects and from multiple perspectives,so as to provide a certain reference for the clinical application of proprietary Chinese medicines for influenza and the development of new influenza drugs.
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Minería de Datos , Medicamentos Herbarios Chinos/uso terapéutico , Gripe Humana/tratamiento farmacológico , Prescripciones de Medicamentos , Humanos , Medicina Tradicional China , Medicamentos sin PrescripciónRESUMEN
Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Gefitinib/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Autofagia/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Medicamentos Herbarios Chinos/administración & dosificación , Gefitinib/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Transducción de Señal , Regulación hacia ArribaRESUMEN
Allergic reactions caused by traditional Chinese medicine injections (TCMIs) become a greatest concern in the clinic application safety. The integral animal evaluation method commonly used in the preclinical evaluation for allergic reactions of TCMIs was not sensitive, specific, quick and objective in observation indexes. Therefore, more researchers have paid attention to the in vitro test method for evaluating allergic reactions induced by TCMIs. Currently, the methods for evaluating allergic reactions induced by TCMIs are mainly targeted at type I allergic reaction and anaphylactic reaction, with only a few in vitro methods for evaluating type II allergic reaction. In this paper, researchers summarized relevant literatures published about evaluation methods for allergic reactions induced by TCMIs in recent years.
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Hipersensibilidad a las Drogas/etiología , Medicina Tradicional China/efectos adversos , Animales , Activación de Complemento , Hipersensibilidad a las Drogas/diagnóstico , Humanos , InyeccionesRESUMEN
Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.
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Antineoplásicos Fitogénicos/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Medicina Tradicional China/métodos , Neoplasias/tratamiento farmacológico , Alcaloides/administración & dosificación , Animales , Antineoplásicos Fitogénicos/análisis , Medicamentos Herbarios Chinos/análisis , Humanos , Inyecciones , Neoplasias/metabolismo , Neoplasias/patología , Quinolizinas/administración & dosificación , Resultado del Tratamiento , MatrinasRESUMEN
The objective of the present studies was to determine the localization of epidermal growth factor (EGF) and the epidermal growth factor receptor (EGFR) in testicular tissue collected from male alpacas at 12 and 24 months of age. In the testes of 12-month-old alpacas, positive staining for EGF was not detected. EGFR was localized to Leydig cells within the 12-month-old alpaca testis, but staining was absent within seminiferous tubules. At 24 months of age, EGF was localized to Leydig cells, peritubular myoid cells, Sertoli cells and germ cells of the alpaca testis, with a preferential adluminal compartment staining within the seminiferous tubules. EGFR was also localized to the Leydig cells, peritubular myoid cells, Sertoli cells and germ cells within the 24-month-old alpaca testis, but staining within the tubules was primarily within the basal compartment. Results indicate distinct temporal and spatial regulation of EGF and EGFR in the alpaca testis and support a potential role for EGF and its related ligands in alpaca testis development and spermatogenesis.