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Métodos Terapêuticos e Terapias MTCI
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1.
Phytomedicine ; 115: 154817, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37121061

RESUMO

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Camundongos , Animais , NF-kappa B/metabolismo , Ácido Ursodesoxicólico/farmacologia , Transdução de Sinais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Traumatismo por Reperfusão/metabolismo , Citocinas
2.
Phytomedicine ; 109: 154609, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610141

RESUMO

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.


Assuntos
Terapias Complementares , Medicamentos de Ervas Chinesas , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Medicamentos de Ervas Chinesas/efeitos adversos , AVC Isquêmico/tratamento farmacológico , Medicina Tradicional , Acidente Vascular Cerebral/tratamento farmacológico , Medicina Tradicional Chinesa
3.
World J Gastrointest Oncol ; 15(1): 36-54, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36684050

RESUMO

Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

4.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6541-6550, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36604902

RESUMO

Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.


Assuntos
Canabidiol , Cannabis , Neoplasias , Humanos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose , Transtornos de Ansiedade/tratamento farmacológico , Microambiente Tumoral
5.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2251-2259, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359650

RESUMO

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-ß-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias Pulmonares/patologia , Nanopartículas , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Micelas , Tamanho da Partícula , Taxoides
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