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1.
J Ethnopharmacol ; : 113571, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181282

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sparganii Rhizoma (SR), a traditional Chinese medicine (TCM), is the rhizome of Sparganium stoloniferum Buch.-Ham. mainly distributed in East Asia. It has been used for eliminating blood stasis, promoting the flow of Qi, removing the retention of undigested food and relieving pain in China for hundreds of years. AIM OF THE REVIEW: This review summarizes comprehensive information in traditional clinical application, processing, phytochemistry, pharmacology, quality control and toxicity of SR, in exploring future scientific and therapeutic potentials. MATERIALS AND METHODS: Pertinent information was systematically collected from several electronic scientific databases (e.g., Web of Science, PubMed, China Knowledge Resource Integrated, Springer, Elsevier, ScienceDirect, and Google Scholar), PhD and MS dissertations, and classic Chinese medical books. RESULTS: SR is a gynecological drug which is often used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM. Two kinds of processed products of SR are included in Chinese Pharmacopoeia, which have better pharmacological effects than the crude herb. Approximately 180 compounds have been identified from SR, including phenylpropanoids, flavonoids, anthraquinones, organic acids, alkaloids, steroids, volatile oils, diarylheptanes, etc. The crude extracts and isolated components of SR have been reported to have anti-tumor, antithrombotic, estrogen antagonistic , anti-inflammatory, analgesic, antioxidant, anti organ fibrosis and other pharmacological activities. SR also has reproductive toxicity. CONCLUSIONS: As an important TCM, SR has been demonstrated by modern pharmacological researches to have significant bioactivities, especially on anti-tumor, antithrombotic, and estrogen antagonistic activities. These activities provide prospects for the development of new drugs and therapeutics for future applications. Nevertheless, quality control and evaluation, in-depth pharmacological mechanism, and toxicological effect of SR require further detailed research.

2.
Sci Rep ; 10(1): 11280, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647188

RESUMO

Chemical profile and antioxidant potency of essential oils (EOs) of Thymus quinquecostatus Celak. (thyme oils) obtained from Loess Plateau in China had been studied. 130 constituents of thyme oils were determined using gas chromatography-mass spectrometry (GC-MS) and carvacrol ethyl ether was firstly reported as a new natural product, which has been used as a synthetic flavoring substance with no safety concern. The thyme oils showed the anti-oxidant activity using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) and conferred protection against oxidative stress in zebrafish. In addition, a class of carvacrol analogues was found to develop as potential natural antioxidant products of thyme oils from Loess Plateau by the correlation analysis. YL-thyme oil performed the best antioxidant activity in this research, which could be recommended as preferred sources of thyme oils. Furthermore, YL-thyme oil exhibited a potent antioxidant capacity by reactive oxygen species (ROS) scavenging, enhancing the endogenous antioxidant system, inhibiting lipid peroxidation and activation of Keap1/Nrf2 pathway in zebrafish.

3.
J Ethnopharmacol ; 250: 112465, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31821851

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) are the classical herbal couple for activating blood circulation and treating tumor in clinics. AIM OF THE STUDY: To investigate the anti-tumor activity and to clarify the bioactive ingredients of herbal couple CR-SR and the single herbs Curcumae Rhizoma (CR) and Sparganii Rhizoma (SR). MATERIALS AND METHODS: The active fractions of CR-SR decoction were fractioned by column chromatography. And isolated compounds were characterized by IR, ESI-MS, 1D and 2D-NMR techniques. Detecting linear-diarylheptanoids in CR-SR, CR and SR was realized through UPLC-LTQ-Orbitrap MSn, based on the fragmentation pathways established in this study, comparison with MS data of isolated compounds and references. The anti-tumor activities of different solvent fractions from CR-SR, CR and SR, as well as isolated ingredients were tested by CCK-8 method. RESULTS: Ultimately, a new compound (1), having a sulfonic acid group at C-3, named demethoxyshogasulfonic acid, along with another structurally similar 17 known linear-diarylheptanoids were isolated. These linear-diarylheptanoids (1-18) were divided into 12 categories based on the differences of substituents at C-3 and C-5 on the straight chain of seven carbons. Six fragmentation pathways were established by summarizing MS data of the 18 isolated compounds collected from UPLC-MS. Based on that, and retention times and MS fragmentation ions, 47 linear-diarylheptanoids were identified in CR-SR and CR, in which 12 linear-diarylheptanoids were also detected in SR. Most importantly, 5 sulfonated linear-diarylheptanoids were new compounds detected in CR and CR-SR. And the biological assay indicated that compounds 1-4 and 12-15 significantly reduced the proliferation and inhibited colony formation of MCF-7 and HepG2 cells. CONCLUSION: The new compound (1) exhibited good anti-cancer activity, which suggests that a great effort has to be paid to investigate the bioactivity of sulfonated compounds. The fractions of CR-SR decoction exhibited stronger anti-tumor activities than that of CR and SR against 5 different cancer cells. As for chemical composition, it is the first time to report that diarylheptanoids are in Sparganiaceae and the sulfonated compounds in Zingiberaceae. Moreover, the linear-diarylheptanoids found in SR which being tested to possess good anti-tumor activity, plus those compounds in CR enhance the capacity of CR-SR. It shows importance of TCM compatibility.


Assuntos
Antineoplásicos/farmacologia , Curcuma , Diarileptanoides/farmacologia , Extratos Vegetais/farmacologia , Rizoma , Typhaceae , Linhagem Celular Tumoral , Humanos
4.
J Pharm Biomed Anal ; 175: 112791, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31398629

RESUMO

The anti-rheumatic fraction (ARF), is responsible for the anti-inflammatory and analgesic effects of Dianbaizhu derived from the aerial part of Gaultheria leucocarpa var. yunnanensis (Ericaceae). The gastrointestinal metabolism of ARF was investigated in vitro through simulating a series of models-gastric juice, intestinal juice, and human intestinal bacteria, analyzed by HPLC-DAD and UPLC-LTQ-Orbitrap-MSn. ARF includes three categories: methyl salicylate glycosides, organic acids and the others. The primordial and metabolic components of ARF bio-transformed by simulated gastric fluid (36 and 13), intestinal fluid (29 and 7) and two human fecal bacteria (34 and 34, 40 and 25) were characterized, respectively. The methyl salicylate glycosides, MSTG-B, MSTG-A and gaultherin, with terminal-xylosyl-moiety in sugar chain were always being found in the whole gastrointestinal incubation processing. The metabolites were formed through hydrolysis of ester and glucosidic bond, as well as methylation, hydroxylation, acetylation, sulfation, reduction, decarboxylation, deglycosylation and glucuronidation. The metabolic conversion effect of the four index compounds, MSTG-B, MSTG-A, gaultherin, and chlorogenic acid by human intestinal bacteria exhibited much stronger. Those markers' variation in content-time curve in volunteer A gut flora were faster than that in volunteer B's. These results indicate that ARF is relatively stable in the gastrointestinal tract.


Assuntos
Antirreumáticos/metabolismo , Líquidos Corporais/metabolismo , Suco Gástrico/metabolismo , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Gaultheria/metabolismo , Intestinos/fisiologia , Anti-Inflamatórios/metabolismo , Bactérias/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ericaceae/metabolismo , Fezes/química , Fezes/microbiologia , Suco Gástrico/microbiologia , Trato Gastrointestinal/microbiologia , Glucosídeos/metabolismo , Glicosídeos/metabolismo , Humanos , Intestinos/microbiologia
5.
J Neurol Sci ; 396: 247-253, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30529802

RESUMO

Glioblastoma (GBM) is a typical malignant tumor, and there are no effective drugs capable of improving patient survival. Docosahexaenoic acid (DHA), a nutrient essential to animal health and neurodevelopment, exerts an anticancer effect in several types of cancer. However, the function of DHA in GBM is still unclear. Here, we showed that DHA could repress the migration and invasion of GBM U251 cells and promote their apoptosis in a dose- and time-dependent manner, indicating that DHA has an anticancer effect on GBM cells. Whole-transcriptome analysis indicated that DHA treatment mainly regulates the genes associated with receptor binding, oxidoreductase activity, organic acid transmembrane transporter activity, and carboxylic acid transmembrane transporter activity. Long non-coding RNAs (LncRNAs) involved in the regulation network of DHA were also identified, and their targets were assigned to the Gene Ontology (GO) categories. In silico analysis was conducted to predict the pathways related to the differentially expressed genes by DHA treatment. Our findings suggest that DHA acts as an antitumor agent in GBM, which may provide a suitable means of improving the efficacy of GBM treatment in the future.


Assuntos
Antineoplásicos/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Sequenciamento Completo do Exoma/métodos , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Biologia Computacional , Relação Dose-Resposta a Droga , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Glioblastoma/patologia , Humanos , Invasividade Neoplásica , RNA Mensageiro/metabolismo , Fatores de Tempo , Cicatrização/efeitos dos fármacos
6.
Dis Model Mech ; 11(10)2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305304

RESUMO

Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoEm/m ) and frameshift mutations (ApoE-/- ) were simultaneously produced. ApoE-/- pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE-/- pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/patologia , Animais , Animais Geneticamente Modificados , Apolipoproteínas E/genética , Aterosclerose/sangue , Sequência de Bases , Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Colesterol/sangue , Dieta Hiperlipídica , Comportamento Alimentar , Feto/citologia , Fibroblastos/metabolismo , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/patologia , Mutação INDEL/genética , Técnicas de Transferência Nuclear , Fenótipo , RNA Guia/metabolismo , Suínos , Porco Miniatura , Triglicerídeos/sangue
7.
J Biomed Res ; 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-30007952

RESUMO

Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to remove the major antigens [Gal, Neu5Gc, and Sd(a)] present on pig cells and tissues. Triple gene (GGTA1, CMAH, and ß 4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.

8.
Molecules ; 23(4)2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29671816

RESUMO

Thymus quinquecostatus Celak is a species of thyme in China and it used as condiment and herbal medicine for a long time. To set up the quality evaluation of T. quinquecostatus, the response surface methodology (RSM) based on its 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was introduced to optimize the extraction condition, and the main indicator components were found through an UPLC-LTQ-Orbitrap MSn method. The ethanol concentration, solid-liquid ratio, and extraction time on optimum conditions were 42.32%, 1:17.51, and 1.8 h, respectively. 35 components having 12 phenolic acids and 23 flavonoids were unambiguously or tentatively identified both positive and negative modes to employ for the comprehensive analysis in the optimum anti-oxidative part. A simple, reliable, and sensitive HPLC method was performed for the multi-component quantitative analysis of T. quinquecostatus using six characteristic and principal phenolic acids and flavonoids as reference compounds. Furthermore, the chemometrics methods (principal components analysis (PCA) and hierarchical clustering analysis (HCA)) appraised the growing areas and harvest time of this herb closely relative to the quality-controlled. This study provided full-scale qualitative and quantitative information for the quality evaluation of T. quinquecostatus, which would be a valuable reference for further study and development of this herb and related laid the foundation of further study on its pharmacological efficacy.


Assuntos
Plantas Medicinais/metabolismo , Thymus (Planta)/metabolismo , Cromatografia Líquida de Alta Pressão , Estresse Oxidativo , Plantas Medicinais/química , Análise de Componente Principal , Thymus (Planta)/química
9.
Acta Biomater ; 72: 196-205, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29631050

RESUMO

Bioprosthetic heart valves (BHVs) originating from pigs are extensively used for heart valve replacement in clinics. However, recipient immune responses associated with chronic calcification lead to structural valve deterioration (SVD) of BHVs. Two well-characterized epitopes on porcine BHVs have been implicated in SVD, including galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) whose synthesis are catalyzed by α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Ac hydroxylase (encoded by the CMAH gene), respectively. It has been reported that BHV from αGal-knockout pigs are associated with a significantly reduced immune response by human serum. Moreover, valves from αGal/Neu5Gc-deficient pigs could further reduce human IgM/IgG binding when compared to BHV from αGal-knockout pigs. Recently, another swine xenoantigen, Sd(a), produced by ß-1,4-N-acetyl-galactosaminyl transferase 2 (ß4GalNT2), has been identified. To explore whether tissue from GGTA1, CMAH, and ß4GalNT2 triple gene-knockout (TKO) pigs would further minimize human antibody binding to porcine pericardium, TKO pigs were successfully produced by CRISPR/Cas9 mediated gene targeting. Our results showed that the expression of αGal, Neu5G and Sd(a) on TKO pigs was negative, and that human IgG/IgM binding to pericardium was minimal. Moreover, the analysis of collagen composition and physical characteristics of porcine pericardium from the TKO pigs indicated that elimination of the three xenoantigens had no significant impact on the physical proprieties of porcine pericardium. Our results demonstrated that TKO pigs would be an ideal source of BHVs. STATEMENT OF SIGNIFICANCE: Surgical heart valve replacement is an established lifesaving treatment for diseased heart valve. Bioprosthetic heart valves (BHVs) made from glutaraldehyde-fixed porcine or bovine tissues are widely used in clinics but exhibit age-dependent structural valve degeneration (SVD) which is associated with the immune response against BHVs. Three major xenoantigens present on commercial BHVs, Galactosea α1,3 galactose (αGal), N-glycolylneuraminic acid (Neu5Gc) and glycan products of ß-1,4-N-acetyl-galactosaminyl transferase 2 (ß4GalNT2) are eliminated through CRISPR/Cas9 mediated gene targeting in the present study. The genetically modified porcine pericardium showed reduced immunogenicity but comparable collagen composition and physical characteristics of the pericardium from wild-type pigs. Our data suggested that BHVs from TKO pigs is a promising alternative for currently available BHVs from wild-type pigs.


Assuntos
Animais Geneticamente Modificados , Antígenos Heterófilos/genética , Bioprótese , Galactosiltransferases/genética , Deleção de Genes , Próteses Valvulares Cardíacas , Oxigenases de Função Mista/genética , N-Acetilgalactosaminiltransferases/genética , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/imunologia , Antígenos Heterófilos/imunologia , Galactosiltransferases/imunologia , Humanos , Oxigenases de Função Mista/imunologia , N-Acetilgalactosaminiltransferases/imunologia , Suínos
10.
Molecules ; 22(8)2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28825681

RESUMO

The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus. Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo. This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references.


Assuntos
Alnus/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Humanos
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