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Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.
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Animais , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Chumbo , Simulação de Acoplamento Molecular , Neoplasias/genética , Transdução de SinaisRESUMO
In view of the current inadequate standards for Gleditsiae Spina in the Chinese Pharmacopoeia, this study put forward some new items of the quality standards of Gleditsiae Spina. Thin-layer chromatography(TLC) was performed for identification with the reference substance of taxifolin and the reference material of Gleditsiae Spina as the control. According to the general principles of the Chinese Pharmacopoeia(2020 edition, Vol. 4), the moisture, total ash content, and alcohol-soluble extract of medicinal materials and decoction pieces of Gleditsiae Spina were determined. The content determination method for medicinal materials and decoction pieces of Gleditsiae Spina was established using high-performance liquid chromatography(HPLC), with taxifolin as the quality control index. Based on the determination results of 30 batches of samples of Gleditsiae Spina from different habitats, the draft quality standards of Gleditsiae Spina were developed, which provided suggestions for the revision of the quality standards of Gleditsiae Spina in the Chinese Pharmacopoeia.
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Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Controle de Qualidade , Padrões de ReferênciaRESUMO
Depression is a kind of emotional and mental disorder, which is related to many pathogenic factors, such as abnormal metabolism of monoamine neurotransmitters, immune inflammatory reaction, neuroendocrine disorder and so on. it has the characteristics of high disability rate and high recurrence rate, which is seriously harmful to human health. It brings huge economic burden to patients and their families. At present, the commonly used antidepressants in clinic are monoamine oxidase inhibitors, tricyclic antidepressants and selective 5-hydroxytryptamine reuptake inhibitors. Long-term use causes adverse reactions such as cardiovascular, urinary and digestive dysfunction. The multi-target, multi-pathway and multi-mechanism of traditional Chinese medicine has played a great role in the treatment and rehabilitation of depression. At the same time, traditional Chinese medicine has gradually become a hot spot in the research and development of antidepressants because of its small side effects and good drug compliance. Especially the ZHANG Zhong-jing's classical formulae with precise medication and rigorous prescription has unique advantages in the treatment of depression. For thousands of years, it has been used clinically by countless doctors in the treatment of various types of depression, with definite curative effects and few side effects. In recent years, clinical research, experimental research, and pharmacological research around ZHANG Zhong-jing's classical formulae for depression have been continuously expanded and deepened. This article reveals the rules of medication of the treatment of depression with ZHANG Zhong-jing's classical formulae from three aspects of Bupleurum class prescription, Gardenia class prescription, and other prescriptions, which is reflected in the study on the composition of prescription, the etiology, and pathogenesis and the symptoms of the treatment. Integrating and classifying ZHANG Zhong-jing's classical formulae's experience in the treatment of depression, mainly expounded from two aspects, clinical research and pharmacological research, summarizing the research perspective and progress of Zhongjing prescription medicine in the treatment of depression in recent years, to excavate, inherit and develop ZHANG Zhong-jing's classical formulae, and provide experience and reference for the treatment of depression from multiple angles and ideas.
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Objective:To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway of hippocampus in rats with depression. Method:A total of 120 SD rats were randomly divided into normal group,model group, and low, middle and high-dose Chaihu Jia Longgu Mulitang groups(3.25,6.5,13 g·kg-1), and fluoxetine group, with 20 rats in each group. Except normal group, the depression model was prepared through chronic unpredictable mild stimulation(CUMS). The normal group and the model group were given normal saline with 6.5 g·kg-1 by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75,6.5,13 g·kg-1, while fluoxetine group was intragastrically given fluoxetine 10 mg·kg-1 for 21 days, once a day. Then the depressive behaviors of rats were observed by sucrose preference test (SPT) and forced swimming test (FST). Western blot was used to detect the protein expressions of PI3K,Akt,GSK3β and phosphorylation level. Result:Compared with normal group,the sucrose preference index was decreased significantly,while the immobility time in FST was increased significantly(P<0.01), the protein expressions of PI3K, p-PI3K p110, p-PI3K p85 were decreased significantly (P<0.01), and expressions of Akt, p-Akt Thr308,p-Akt Ser473, p-GSK3β Ser9 and β-catenin were decreased significantly(P<0.01), while the level of GSK3β, p-GSK3β Tyr216 were increased significantly in model group(P<0.05,P<0.01). Compared with model group,Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST(P<0.01), the protein expressions of PI3K p110 and PI3K p85 was increased significantly (P<0.01), levels of Akt Thr308,Akt Ser473, p-GSK3β Ser9, β-catenin were increased significantly (P<0.01), whereas levels of GSK3β, and GSK3β Tyr216 were decreased significantly. Conclusion:Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus, activate Akt, inhibit GSK3β kinase activity and prevent β-catenin from degradation, so as to increase PI3K/Akt pathway activity in rat hippocampus, and protect hippocampal neurons.
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Objective:To study the effect of modified Suanzaoren Tang on the expression of excitatory amino acids receptor(EAARs) in hippocampus of rats with chronic depression, and to explore the anti-depressant mechanism of modified Suanzaoren Tang based on excitatory amino acids receptor. Method:Sixty SD rats were randomly divided into normal group,model group,and low,middle and high-dose modified Suanzaoren Tang groups,and ketamine group,with 10 rats in each group.Except normal group,the depression model of rats was prepared by using chronic restraint stress(CRS).The normal group and model group were intragastrically(ig) given normal saline.the modified Suanzaoren Tang groups were intragastrically given corresponding herbal drugs 6,12,24 g·kg-1, ketamine group group were given ketamine 0.015 g·kg-1 through intraoeritoneal injection,for 21 days,once a day.Then the depressive behaviors of rats were observed by Morris water maze and novelty feeding experiment.Western blot was used to detect the levels of DAR1,NMDAR2A,NMDAR2B,GluR1,mGluR1,CaMKⅡα and CaMKⅡβ protein expression in rat hippocampus tissue. Result:Compared with normal group,the time of novel ingestion and escape latencywere prolonged significantly(P<0.01), and the time of space exploration was shortened significantly(P<0.01).The levels of NMDAR1,NMDAR2A,NMDAR2B,mGluR1 and CaMKⅡβ expression were increased significantly(P<0.01),while the levels of GluR1 and CaMKⅡα expression were decreased significantly(P<0.01)in model group. Compared with model group,the time of novel ingestion and escape latency were shortened significantly (P<0.01), and the time of space exploration was prolonged significantly(P<0.01).The levels of NMDAR1,NMDAR2A,NMDAR2B,mGluR1 and CaMKⅡβ protein expression were decreased significantly(P<0.01),but the levels of GluR1 and CaMKⅡα expression were increased decreased significantly(P<0.01)in middle and high-dose modified Suanzaoren Tang groups. Conclusion:Modified Suanzaoren Tang can improve the behavior of chronic depression rats effectly. Its mechanism may be related with reduction the expression of NMDAR1,NMDAR2A,NMDAR2B,mGluR1 and CaMKⅡβ protein ,increase the expression of GluR1and CaMKⅡα protein.
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Objective:To study the effect of modified Xiao Chaihutang on the expressions of excitatory amino acid transporters(EAATs) and vesicle glutamate transporters(VGLUTs)in hippocampus of rats with chronic depression, in order to explore the anti-depressant mechanism of modified Xiao Chaihutang based on glutamate transport. Method:A total of 120 SD rats were randomly divided into normal group, model group, and low, middle and high-dose modified Xiaochaihutang groups (6.5, 13, 26 g·kg-1) and riluzole group, with 20 rats in each group.Except normal group, the depression model of rats was prepared through Chronic restraint stress(CRS). The normal group and the model group were intragastrically (ig) given normal saline. The modified Xiao Chaihutang groups were intragastrically given corresponding herbal drugs (6.5, 13, 26 g·kg-1), and the Riluzole group was given Riluzole 20 mg·kg-1 through intraoeritoneal injection for 21 days, once a day. Then the depressive behaviors of rats were observed by forced swimming test (FST) and tail suspension test (TST). The level of glutamic acid (Glu) in rats hippocampus was determined by high performance liquid chromatography (HPLC). The mRNA expressions of EAAT1, EAAT2 and EAAT3 in hippocampus were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR)method. Western blot was used to detect the protein expressions of EAAT1, EAAT2, EAAT3, VGLUT1 and VGLUT2 in rat hippocampus tissue. Nissl staining was used to observe the morphology of hippocampal neurons in rats. Immunohistochemical(IHC)S-P method were used to detect the location expressions of EAAT1, EAAT2 and NeuN proteins in rat hippocampal CA1 region tissue. Result:The immobility times in FST and TST were increased significantly(P<0.01), the mRNA and protein expressions of EAAT1,EAAT2,EAAT3 were decreased significantly (P<0.01), and as well as the expressions of VGLUT1 and NeuN were decreased significantly(P<0.01), while the level of Glutamate and the expression of VGLUT2 were increased significantly(P<0.01) in model group, compared with normal group. Compared with model group,the immobility times in FST and TST were decreased significantly(P<0.05, P<0.01), mRNA and protein expressions of EAAT1,EAAT2,EAAT3 were increased significantly(P<0.01), and expressions of VGLUT1 and NeuN were increased significantly(P<0.01). However, the level of Glutamate and the expression of VGLUT2 were decreased significantly(P<0.01), and the damage of hippocampal neurons in rats was mild in middle and high-dose modified Xiao Chaihutang groups. Conclusion:Modified Xiao Chaihutang has an anti-depressive effect. Its mechanism may be related to its up-regulation of expressions of EAAT1, EAAT2, EAAT3 genes and VGLUT1 protein in the hippocampus of depression model rats.
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Homology of medicine and food is an important content in Chinese medicine and also works as the basis for guiding the development of compound health food containing Chinese materia medica. The top products,supplements,health care prescriptions,and medicinal meals in traditional herbal texts are the theoretical treasures of Chinese medicine compound health foods. With the implementation of the National Healthy China 2030,China's major health industry faces with tremendous opportunities. It is necessary to develop a batch of compound health food containing Chinese materia medica with Chinese medicine characteristics,in line with the needs of the country and society. Domestic research on compound health food containing Chinese materia medica mainly focuses on the extraction of functional components,preparation molding processes,quality standards,and efficacy evaluation. However,there are still some deficiencies in the related characteristics of traditional Chinese medicine(TCM) theory and function,evaluation criteria of efficacy and safety,new product R&D evaluation system and R&D platform. Based on a large number of previous studies by this laboratory,the views in nature,flavor and efficacy relationship were put forward in this paper. Based on the establishment of the Chinese medicine function-pharmacology-clinical application database system,the Chinese medicine compatibility database system,the Chinese medicine nature and flavor modern research database system,and the evaluation platform for animal models of Chinese medicine; the efficacy study,safety evaluation system,new product research and development evaluation system as well as research and development platform were established,providing a basis for the development and evaluation of compound health food containing Chinese materia medica. The modern scientific connotation of the core efficacy of compound health food containing Chinese materia medica was explained as well,helpful to promote the research and development of compound health food containing Chinese materia medica and play an important role in general health.
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China , Mineração de Dados , Alimentos , Materia Medica , Medicina Tradicional ChinesaRESUMO
With the development of social economy,people's demand for health services is growing rapidly. As health resource with Chinese characteristics,health food containing Chinese materia medica have broad prospect and great market space for development.However,at present,there are still many problems of health food containing Chinese materia media in the research,development,evaluation and market application. In addition,due to lack of theoretical support of traditional Chinese medicine(TCM) in the research and development of health food containing Chinese materia media,blurred boundaries between health food containing Chinese materia media and other health products as well as TCM are present,lacking of TCM characteristics. In the evaluation process of health food containing Chinese materia media,the construction of functional food laws,regulations and evaluation norms is relatively lagging behind,which can't meet the needs of health food containing Chinese materia media research and development,severely restricting the development of health food containing Chinese materia media. Based on the research and evaluation of health food containing Chinese materia media,the existing problems were reviewed and the reasons for the deficiencies were analyzed in this paper. Guided by the theory of TCM,based on the constitution identification in TCM,and combined with modern scientific and technological means,a new research and development mode of functional food was put forward in this paper to distinguish health food containing Chinese materia media from TCM as well as general health products. Nevertheless,we should ensure the vitality of Chinese medicine health products with original thinking and scientific and technological connotations,and accelerate the harmonious,rapid and sustainable development of Chinese medicine health industry.