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1.
Metabolites ; 14(9)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39330497

RESUMO

Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient target of CRC. As natural products have garnered interest due to notable pharmacological effects and potential in counteracting chemoresistance, an increasing body of research is delving into the impact of these natural products on the metabolic reprogramming associated with CRC. In this review, we collected published data from the Web of Science and PubMed, covering the period from January 1980 to October 2023. This article focuses on five central facets of metabolic alterations in cancer cells, glucose metabolism, mitochondrial oxidative phosphorylation (OXPHOS), amino acid metabolism, fatty acid synthesis, and nucleotide metabolism, to provide an overview of recent advancements in natural product interventions targeting metabolic reprogramming in CRC. Our analysis underscores the potential of natural products in disrupting the metabolic pathways of CRC, suggesting promising therapeutic targets for CRC and expanding treatment options for metabolic-associated ailments.

2.
Chin J Integr Med ; 30(9): 826-834, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38990479

RESUMO

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.


Assuntos
Araquidonato 5-Lipoxigenase , Proliferação de Células , Glioma , Inibidores de Lipoxigenase , Simulação de Acoplamento Molecular , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/metabolismo , Glioma/enzimologia , Araquidonato 5-Lipoxigenase/metabolismo , Humanos , Inibidores de Lipoxigenase/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cálcio/metabolismo , Espectrometria de Massas em Tandem
3.
Arch Pharm Res ; 47(5): 410-441, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750332

RESUMO

The genus Tamarix in the Tamaricaceae family consists of more than 100 species of halophyte plants worldwide that are mainly used to improve saline-alkali land and for coastal windbreaks, sand fixation, and afforestation in arid areas. A considerable number of species in this genus are also used as traditional medicines to treat various human diseases, especially in Asian and African countries. This review presents a comprehensive summary of 655 naturally occurring compounds derived from the genus Tamarix, categorized into flavonoids (18.0%), phenols (13.9%), tannins (9.3%), terpenoids (10.5%), essential oils (31.0%), and others (17.3%). The investigation revealed that the crude extracts and phytochemicals of this genus exhibited significant therapeutic potential, including anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, antibacterial, and antifungal activities. Six species of Tamarix have anticancer effects by causing cancer cell death, inducing autophagy, and stopping cell division. Seven species from the same genus have the potential for treating diabetes by inhibiting α-glycosidase activity, suppressing human islet amyloid polypeptide, regulating blood glucose levels, and modulating autophagy or inflammation. The focus on antibacterial and antidiabetic effects is due to the presence of volatile oil and flavonoid components. Extensive research has been conducted on the biological activity of 30 constituents, including 15 flavonoids, 5 phenols, 3 terpenoids, 1 tannin, and 6 others. Therefore, future research should thoroughly study the mechanisms of action of these and similar compounds. This is the most comprehensive review of the phytochemistry and pharmacological properties of Tamarix species, with a critical assessment of the current state of knowledge.


Assuntos
Compostos Fitoquímicos , Tamaricaceae , Humanos , Tamaricaceae/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/química
4.
Heliyon ; 10(3): e24986, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333853

RESUMO

Malinzi is the dry ripe seed of Iris Lactea Pall. var. chinensis (Fisch.) Koidz and is a tradtional medicinal plant with significant development and utilization value. A total of 31 compounds from Malinzi have been reported, including flavonoids, quinones, oligostilbenes, and other constituents. Modern pharmacological studies have shown that Malinzi has good activities in anti-tumor, radio-sensitization, boost immunity, anti-oxidation, anti-fertility, and glucolipid metabolism. In this paper, by reviewing the domestic and foreign research literatures of Malinzi and summarizing its traditional uses, chemical constituents, and pharmacological activities, it is expected to provide theoretical reference for the subsequent in-depth research and application of Malinzi.

5.
J Adv Res ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37949300

RESUMO

BACKGROUND: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. AIM OF REVIEW: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. KEY SCIENTIFIC CONCEPTS OF REVIEW: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

6.
J Ethnopharmacol ; 308: 116273, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36822343

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex rotundifolia L. f. and Vitex trifolia L. belong to the genus Vitex, and Vitex rotundifolia L. f. evolved from Vitex trifolia L. Both are essential ethnic medicinal plants with a long history, commonly used to treat headaches, fever, diarrhea, hair loss, wound recovery, and other diseases. AIM OF THE REVIEW: The research status of Vitex trifolia L. and its relative species Vitex rotundifolia L. f. were reviewed from the aspects of traditional medicinal use, phytochemistry, and pharmacological activities, to provide a reference for the further development and utilization of Vitex rotundifolia L. f. and Vitex trifolia L. MATERIALS AND METHODS: In this paper, a comprehensive search of published literature was conducted through various books and online databases to obtain relevant information on Vitex rotundifolia L. f. and Vitex trifolia L. The search terms "(Vitex rotundifolia) OR (Vitex trifolia) OR (Fructus viticis)" were entered in PubMed, Web of Science, China national knowledge infrastructure (CNKI), Wanfang Data, Baidu Scholar, respectively. In addition to setting the year threshold of "2018-2022" on Baidu Scholar, other databases searched all fields and found 889, 283, 1263, 1023, and 147 articles, respectively. Among them, review, repetition, overlapping data, and other reasons were excluded, and finally, a total of 164 articles were included in the review study. RESULTS: A total of 369 compounds have been identified, including 159 terpenoids, 51 flavonoids, 83 phenylpropanoids, and 76 other compounds. Pharmacological studies have shown that Vitex rotundifolia L. f. and Vitex trifolia L. have a variety of pharmacological activities, such as anti-tumor, analgesic, antipyretic, anti-inflammatory, antioxidant, antibacterial, and estrogen-like activity. Modern clinical use for treating cold headaches, diarrhea dysentery, irregular menstruation, and other diseases. CONCLUSIONS: As traditional medicinal plants, Vitex rotundifolia L. f. and Vitex trifolia L. have wealthy chemical constituents and extensive pharmacological activities and are widely used in clinical practice from traditional to modern times. However, the research on the pharmacological activities of Vitex rotundifolia L. f. and Vitex trifolia L. is not in-depth, and the potential active components still need to be explored.


Assuntos
Plantas Medicinais , Vitex , Vitex/química , Medicina Tradicional , Anti-Inflamatórios/farmacologia , China , Compostos Fitoquímicos , Etnofarmacologia , Extratos Vegetais/farmacologia
7.
Food Chem ; 405(Pt B): 134968, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36442239

RESUMO

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1-14), eight phenolic acids (15-22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27-29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1-5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3-5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.


Assuntos
Chenopodiaceae , Polifenóis , Animais , Polifenóis/farmacologia , Verduras , Peixe-Zebra , Flavonoides/farmacologia
8.
Front Oncol ; 12: 905868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457514

RESUMO

The literature related to TMZ research in the Web of Science (WOS) database was analyzed using bibliometrics and visualization by Citespace and VOSviewer.The publication status (number of publications, institutions, and frequency of citations), collaborations, and research focus was analyzed to clarify the current situation of TMZ research. And the recent research on TMZ provides a detailed summary. Based on objective data analysis, this study provides a complete analysis portraying the progression of historical milestones in TMZ development and future research directions from various TMZ research domains.

9.
Pharmaceuticals (Basel) ; 15(5)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35631427

RESUMO

As one of the most characteristic ingredients of glandular trichome secretions from Nicotiana tabacum L. (tobacco), natural cembrenediols, namely, (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (α-cembrenediol/α-CBD) and its C-4 epimer (ß-cembrenediol/ß-CBD), have attracted considerable attention for their potent antitumor, neuroprotective, antimicrobial, and other activities. Many researchers are committed to exploring the possibility of utilizing these two cembrenediols and their derivatives both in human medicine and in agricultural fungicides. To the best of our knowledge, this review is the first to provide a comprehensive summary of the chemical modifications and bioactivities of α- and ß-CBD from their discovery to the present day; the review highlights their potential medicinal value for humans. The extensive references from 1962 to 2022 provided herein were systematically gathered from the SciFinder, Web of Science, and Google Scholar databases. We expect this review to assist in providing practical ideas for future drug development based on α- and ß-CBD and in further facilitating the utilization of the tobacco cembrenediols.

10.
Mol Pharm ; 19(7): 1927-1951, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35499303

RESUMO

Glioma is the most common and aggressive primary intracranial tumor within the central nervous system. The blood-brain barrier (BBB) has been a great hurdle for an effective glioma treatment. To effectively treat glioma, various strategies have been applied to deliver drugs to the brain by crossing the BBB. Nanocarrier-mediated drug delivery is emerging as an effective and noninvasive system to treat glioma, showing great potential in glioma therapy. In this review, we will provide a comprehensive overview on nanocarrier-mediated drug delivery and related glioma therapy. Following an initial overview of the BBB and blood-brain-tumor barrier (BBTB) structure and characteristics, nanocarrier-mediated drug delivery strategies (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, biomimetic nanoparticles, and exosomes) for crossing the BBB are discussed. Finally, nanotherapeutic techniques (imaging-mediated chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, immunotherapy, ferroptosis therapy, sonodynamic therapy, chemodynamic therapy, and combination therapy) in treating glioma are summarized. In addition, this review provides some perspectives on the clinical applications of nanomedicines.


Assuntos
Neoplasias Encefálicas , Glioma , Nanopartículas , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Lipossomos/uso terapêutico , Nanopartículas/química
11.
J Ethnopharmacol ; 289: 115084, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35134488

RESUMO

ETHNIC PHARMACOLOGICAL RELEVANCE: Plant materials are used as complementary and alternative therapies all over the world for the treatment of various diseases. Ulcerative colitis (UC), a chronic nonspecific inflammatory bowel disease listed as one of the modern refractory diseases by the World Health Organization, has a long course, is challenging to cure, and is prone to cause cancer. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) to UC. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of UC and reports the therapeutic effect of TCM on UC (including TCM prescriptions, single TCM, and treatments using TCM ingredients) to provide a theoretical basis for the use of TCM in treating UC. METHODS: We performed a collection and collation of relevant scientific articles from different scientific databases regarding TCM and its usefulness in treating UC. In this paper, the therapeutic effect of TCM is summarized and analyzed according to the existing experimental and clinical research. RESULTS: There are positive signs that TCM primarily regulates inflammatory cytokines, intestinal flora, and the immune system, and also protects the intestinal mucosa. Hence, it can play a role in treating UC. CONCLUSION: TCM has a definite curative effect in the treatment of UC. It can alleviate and treat UC in a variety of ways. We should take syndrome differentiation and treatment differentiation as the basis. With the help of modern medicine, TCM's clinical curative effects can be enhanced for the treatment of UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos
12.
J Mater Chem B ; 10(12): 1908-1922, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35212343

RESUMO

In recent years, nanodrug delivery systems have attracted increasing attention due to their advantages, such as high drug loading, low toxicity and side effects, improved bioavailability, long circulation time, good targeting and controlled drug release efficiency. Self-assembly technology has developed rapidly in recent decades and plays an important role in the research and development of nanoscience. The combination of nanometer drug delivery and self-assembly technology can realize the self-delivery process of drugs. The facile synthesis process and strong biological affinity can both effectively enhance the therapeutic efficacy and reduce the toxicity of drugs. This combination of technologies has received wide attention in the field of nanobiomedicine. In this review, we summarize the research progress and applications of different types of self-assembled nanodrug delivery systems (amphiphilic block copolymer-based self-assembled drug delivery system, carrier-free nanodrugs, peptide-based self-assembled delivery system, metal-polyphenol self-assembly and natural small-molecule self-assembled nanodrug delivery systems), which are expected to have potential therapeutic value in the field of biomedicine in the future.


Assuntos
Nanopartículas , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Nanopartículas/uso terapêutico , Peptídeos
13.
Mar Biotechnol (NY) ; 24(1): 68-81, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34982299

RESUMO

Deep sea water (DSW), as a noticeable natural resource, has been demonstrated to contain high levels of beneficial minerals and exert marked anti-diabetes effects. Epidemiological studies show that type 2 diabetes mellitus (T2DM) is closely related to high danger of Alzheimer's disease (AD); moreover, Akt/GSK-3ß signaling is the main underlying pathway that connects these two diseases. Besides, it has been demonstrated that minerals in DSW, such as Mg, Se, and Zn, could effectively treat cognitive deficits associated with AD. Herein, we first observed the protection of DSW against cognitive dysfunction in T2DM rats, then furtherly explored the neuroprotective mechanism in SH-SY5Y cell model. In T2DM rats, DSW obviously elevated the concentrations of elements Mg, V, Cr, Zn, and Se in brain and improved learning and memory dysfunction in behavior assays, including Morris water maze (MWM) and new object recognition (NOR). Western blot (WB) results demonstrated that DSW could stimulate PI3K/Akt/GSK-3ß signaling, arrest Tau hyperphosphorylation at serine (Ser) 396 and threonine (Thr)231, which was confirmed by immunohistochemistry (IHC). In order to further confirm the mechanism, we employed wortmannin to inhibit PI3K in SH-SY5Y cells; results showed that pretreatment with wortmannin almost abolished DSW-induced decreases in phosphorylated Tau. Taken together, these data elucidated that DSW could improve Tau hyperphosphorylation and cognitive impairment, which were closely related with the stimulation of Akt/GSK-3ß signaling, and the neuroprotective effects of DSW should be contributed to the synergistic effects of major and trace elements in it, such as Mg, V, Cr, Zn, and Se. These experimental evidence indicated that DSW may be explored as natural neuroprotective food for the prevention and treatment of AD.


Assuntos
Disfunção Cognitiva , Glicogênio Sintase Quinase 3 beta , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas tau , Animais , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Água do Mar , Transdução de Sinais , Proteínas tau/metabolismo
14.
J Ethnopharmacol ; 282: 114615, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509606

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen, the dried rhizome of Salvia miltiorrhiza Bge., is widely used to treat cardio-cerebrovascular diseases in China. However, its role in nourishing blood, which has been detailed in historical literature for thousands of years, is perpetually disputed in the academic field. Moreover, there is no systematic research on Danshen in treating anemia. This research aimed to investigate the effects and mechanisms of Danshen on anemia in a zebrafish model based on the results of a network pharmacology study. MATERIALS AND METHODS: The network pharmacology study was based on the screening of chemical components and related targets from TCMSP and SwissADME database. The genes associated with anemia were obtained from DisgeNet database, and the genes with the intersection of Danshen target genes were screened out. The Cytoscape 3.7.2 software package was used to construct the "ingredient-target-pathway" network. The exploration of target interaction by String system and the enrichment analysis by Metascape system, was used to discover the possible anti-anemia action mechanism of Danshen. Then, a zebrafish anemia model was induced by vinorelbine followed by the administration of aqueous/ethanol extract of Danshen in contrast to SiWu Decoction (SWD), which is generally acknowledged as a positive drug for tonifying blood. Afterward, the red blood cell signal, cardiac output, and blood flow velocity were detected to evaluate their blood-enriching effects. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the mRNA levels of hematopoietic-related factors, which were predicted in network pharmacology. RESULTS: Compounds and target screening hinted that 115 chemical targets from Danshen were related to anemia, KEGG pathway enrichment results suggested that the mechanism of Danshen in treating anemia was significantly related to the Jak-STAT signaling pathway. Pharmacodynamic results showed that aqueous extract of Danshen (DSAE) and ethanol extract of Danshen (DSEE) markedly enhanced the number of red blood cells, cardiac output, and blood flow velocity. Compared with DSAE, DSEE exerted anti-anemia effects at a lower dose; however, along with higher toxicity. PCR data demonstrated that DSAE and DSEE treatment both upregulated the mRNA expression of erythroid hematopoiesis-related factors in the Epo-JAK-STAT signaling pathway, such as Gata-1, Epo, EpoR, Jak2, STAT3, and STAT5. In general, DSAE exhibited higher activation of this signaling than DSEE. CONCLUSIONS: These results indicated that DSAE and DSEE both possess blood-enriching functions related with their ability to promote Jak-STAT signaling. DSAE exerted lower toxicity and attenuated anemia over a wider dose range than DSEE, which suggests that DSAE may be more suitable for the treatment for anemia. These results presented experimental evidence for the clinical use of Danshen as an intervention for anemia, especially in chemotherapy-induced anemia.


Assuntos
Anemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Farmacologia em Rede , Salvia miltiorrhiza/química , Animais , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fitoterapia , Peixe-Zebra
15.
Colloids Surf B Biointerfaces ; 208: 112046, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34419809

RESUMO

Subcellular localization of organelles can achieve accurate drug delivery and maximize drug efficacy. As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays an important role in protein synthesis, folding, and posttranslational modification; lipid biosynthesis; and calcium homeostasis. Observing the changes in various metal ions, active substances, and the microenvironment in the ER is crucial for diagnosing and treating many diseases, including cancer. Excessive endoplasmic reticulum stress (ERS) can have a killing effect on malignant cells and can mediate cell apoptosis, proper modulation of ERS can provide new perspectives for the treatment of many diseases, including cancer. Therefore, the ER is used as a new anticancer target in cancer treatment. This review discusses ER-targeting fluorescent probes and ERS-mediated nanoanticancer strategies.


Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Apoptose , Retículo Endoplasmático , Corantes Fluorescentes , Humanos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
16.
J Mater Chem B ; 8(30): 6333-6351, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32633311

RESUMO

There is growing acceptance of traditional Chinese medicines (TCMs) as potential sources of clinical agents based on the demonstrated efficacies of numerous bioactive compounds first identified in TCM extracts, such as paclitaxel, camptothecin, and artemisinin. However, there are several challenges to achieving the full clinical potential of many TCMs, particularly the generally high hydrophobicity and low bioavailability. Recently, however, numerous studies have attempted to circumvent the limited in vivo activity and systemic toxicity of TCM ingredients by incorporation into nanoparticle-based delivery systems. Many of these formulations demonstrate improved bioavailability, enhanced tissue targeting, and greater in vivo stability compared to the native compound. This review summarizes nanoformulations of the most promising and extensively studied TCM compounds to provide a reference for further research. Combining these natural compounds with nanotechnology-based delivery systems may further improve the clinical utility of these agents, in turn leading to more intensive research on traditional medicinal compounds.


Assuntos
Medicamentos de Ervas Chinesas/química , Nanocápsulas/química , Alcaloides/farmacologia , Animais , Disponibilidade Biológica , Composição de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Medicina Tradicional Chinesa , Polifenóis/farmacologia , Quinonas/farmacologia , Terpenos/farmacologia , Nanomedicina Teranóstica
17.
Antiviral Res ; 179: 104789, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32353383

RESUMO

Human adenoviruses (HAdVs) often cause mild respiratory infections. These infections, however, can potentially become fatal in immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for treatment of HAdV infections. In this study, a time-course transcriptome of HAdV-infected human lung epithelial cells (A549 cells) was performed and compared with perturbation datasets of 890 drug-treated A549 cells from the library of integrated network-based cellular signatures (LINCS) database to predict previously unknown therapeutic drug-HAdV relationships using a characteristic direction (CD) algorithm. We performed experiments to validate a prediction for the anti-diabetic drug rosiglitazone as a candidate drug for treatment of anti-HAdV both in vivo and in vitro. The Type I interferon (IFNs) signaling pathway was negatively regulated during the course of HAdV infection and rosiglitazone increased STAT1 phosphorylation for antiviral IFN response induction. Taken together, this study confirmed the prospect for re-exploitation of this FDA-approved drug as a potential therapeutic for HAdV infections.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Antivirais/uso terapêutico , Bases de Dados de Produtos Farmacêuticos , Reposicionamento de Medicamentos , Rosiglitazona/uso terapêutico , Replicação Viral/efeitos dos fármacos , Células A549 , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/fisiologia , Algoritmos , Animais , Antivirais/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Camundongos , Camundongos SCID , Rosiglitazona/farmacologia
18.
Int J Mol Sci ; 20(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842453

RESUMO

BACKGROUND: G-protein-coupled bile acid receptor (TGR5), a membrane bile acid receptor, regulates macrophage reactivity, and attenuates inflammation in different disease models. However, the regulatory effects of TGR5 in ischemia/reperfusion (I/R)-induced kidney injury and inflammation have not yet been extensively studied. Therefore, we hypothesize that Farnesiferol B, a natural TGR5 agonist, could alleviate renal I/R injury by reducing inflammation and macrophage migration through activating TGR5. METHODS: Mice were treated with Farnesiferol B before I/R or sham procedures. Renal function, pathological analysis, and inflammatory mediators were examined. In vitro, the regulatory effects of Farnesiferol B on the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in macrophages were investigated. RESULTS: After I/R, Farnesiferol B-treated mice displayed better renal function and less tubular damage. Farnesiferol B reduced renal oxidative stress and inflammation significantly. In vitro, Farnesiferol B treatment alleviated lipopolysaccharide (LPS)-induced macrophage migration and activation, as well as LPS-induced NF-κB activation through TGR5. CONCLUSIONS: Farnesiferol B could protect kidney function from I/R-induced damage by attenuating inflammation though activating TGR5 in macrophages. Farnesiferol B might be a potent TGR5 ligand for the treatment of I/R-induced renal inflammation.


Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/tratamento farmacológico , Animais , Biópsia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Camundongos , Modelos Biológicos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico
19.
Artigo em Inglês | MEDLINE | ID: mdl-31061667

RESUMO

OBJECTIVE: Cancer is one of the most dangerous diseases to human life and there is no radical cure for it. In this paper, we compiled quantities of case history to evaluate the current available evidence of herbal Danshen (Radix Salviae Miltiorrhizae, RSM) formulae for the treatment of cancer by means of the high-quality randomized controlled trials (RCTs). METHODS: English and Chinese electronic databases were searched from PubMed, the Cochrane Library, EMBASE, and the China National Knowledge Infrastructure (CNKI), VIP database, Wanfang database until September 2018. The methodological quality of the included studies was evaluated by using the method of Cocharne evidence-based medicine system evaluation, the quality was evaluated by screening the literature that met the requirements, and the Review Manager 5.3 was used for statistical analysis. The pooled odds ratio (OR) with 95% CIs was used to estimate the correlation between Danshen formulae and therapeutic effects. RESULTS: Thirteen RCTs with 1045 participants were identified. The studies investigated the lung cancer (n = 5), leukemia (n = 3), liver cancer (n = 3), breast or colon cancer (n = 1), and gastric cancer (n = 1). A total of 83 traditional Chinese medicines were used in all prescriptions and there were 3 different dosage forms. Meta-analysis suggested that Danshen formulae had a significant effect on RR (response rate) (OR 2.38, 95% CI 1.66-3.42), 1-year survival (OR 1.70 95% CI 1.22-2.36), 3-year survival (OR 2.78, 95% CI 1.62-4.78), and 5-year survival (OR 8.45, 95% CI 2.53-28.27). CONCLUSION: The current research results showed that Danshen formulae combined with chemotherapy for cancer treatment was better than conventional drug treatment plan alone.

20.
Artigo em Inglês | MEDLINE | ID: mdl-28191021

RESUMO

Traditional Chinese Marine Medicine (TCMM) represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA) displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms) via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1) Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, and Sargassum genus; (2) Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3) Holothuroidea class, Aspidochirotida order, and Holothuria genus. Our analyses showed that TCMMs with closer taxonomic relationship were more likely to possess anticancer bioactivity. We found that the cluster pattern of marine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species within Metazoa or Viridiplantae kingdom of cold nature were more likely to contain AA properties. We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources.

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