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1.
Biochem Biophys Res Commun ; 671: 246-254, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37307708

RESUMO

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.


Assuntos
Disfunção Cognitiva , Demência Vascular , Fármacos Neuroprotetores , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Demência Vascular/tratamento farmacológico , Demência Vascular/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Autofagia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Disfunção Cognitiva/metabolismo , Hipóxia/tratamento farmacológico
2.
Int J Mol Sci ; 24(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37762645

RESUMO

Surface staining has emerged as a rapid technique for applying external stains to trace cellular identities in diverse populations. In this study, we developed a distinctive aptamer with selective binding to cell surface nucleolin (NCL), bypassing cytoplasmic internalization. Conjugation of the aptamer with a FAM group facilitated NCL visualization on live cell surfaces with laser confocal microscopy. To validate the aptamer-NCL interaction, we employed various methods, including the surface plasmon resonance, IHC-based flow cytometry, and electrophoretic mobility shift assay. The G-quadruplex formations created by aptamers were confirmed with a nuclear magnetic resonance and an electrophoretic mobility shift assay utilizing BG4, a G-quadruplex-specific antibody. Furthermore, the aptamer exhibited discriminatory potential in distinguishing between cancerous and normal cells using flow cytometry. Notably, it functioned as a dynamic probe, allowing real-time monitoring of heightened NCL expression triggered by a respiratory syncytial virus (RSV) on normal cell surfaces. This effect was subsequently counteracted with dsRNA transfection and suppressed the NCL expression; thus, emphasizing the dynamic attributes of the probe. These collective findings highlight the robust versatility of our aptamer as a powerful tool for imaging cell surfaces, holding promising implications for cancer cell identification and the detection of RSV infections.

3.
Molecules ; 28(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37241980

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1ß-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs.


Assuntos
Artrite Experimental , Artrite Reumatoide , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Colágeno Tipo II , Simulação de Acoplamento Molecular , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , DNA/uso terapêutico
4.
Chem Biodivers ; 19(11): e202200414, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36200645

RESUMO

A pair of new lignan conformers (1-2), one new flavonoid glycoside (3), as well as nineteen known compounds were purified from the twigs and leaves of Cajanus cajan (L.) Millsp.. The planar structures of the unknown compounds were determined via NMR and high-resolution mass spectrometry, while their absolute configurations were elucidated via comparison between their experimental and calculated electronic circular dichroism (ECD) values. All the isolated compounds were assayed for their α-glucosidase inhibitory activities. The results demonstrated that compounds 8-12, 15-16, 18-19, 21-22 had strong inhibition activities, with compound 10 (IC50 =0.4±0.21 µM) most active. The structure-activity relationships were preliminarily summarized. Enzyme kinetics showed that compounds 8, 9, 15-16, 18-19, 21-22 were non-competitive inhibitors and compounds 10-12 were anti-competitive ones.


Assuntos
Flavonoides , Inibidores de Glicosídeo Hidrolases , Lignanas , alfa-Glucosidases , Cajanus/química , Flavonoides/química , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Lignanas/química , Lignanas/farmacologia , Folhas de Planta/química
5.
J Asian Nat Prod Res ; 23(10): 938-954, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33111547

RESUMO

1,8-Cineole (also known as eucalyptol) is mostly extracted from the essential oils of plants, which showed extensively pharmacological properties including anti-inflammatory and antioxidant mainly via the regulation on NF-κB and Nrf2, and was used for the treatment of respiratory diseases and cardiovascular, etc. Although various administration routes have been used in the application of 1.8-cineole, few formulations have been developed to improve its stability and bioavailability. This review retrospects the researches on the source, biological activities, mechanisms, and application of 1,8-cineole since 2000, which provides a view for the further studies on the application and formulations of 1,8-cineole.


Assuntos
Cicloexanóis , Monoterpenos , Anti-Inflamatórios , Cicloexanóis/farmacologia , Eucaliptol , Estrutura Molecular , Monoterpenos/farmacologia
6.
Molecules ; 25(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971833

RESUMO

G-quadruplexes are non-canonical four stranded secondary structures possessing great biological importance. Controlling G-quadruplex conformation for further regulating biological processes is both exciting and challenging. In this study, we described a method for regulating G-quadruplex conformation by click chemistry for the first time. 8-ethynyl-2'-deoxyguanosine was synthesized and incorporated into a 12-nt telomere DNA sequence. Such a sequence, at first, formed mixed parallel/anti-parallel G-quadruplexes, while it changed to anti-parallel after reaction with azidobenzene. Meanwhile, the click reaction can give the sequence intense fluorescence.


Assuntos
Química Click , Quadruplex G , Desoxiguanosina/química
7.
Biomed Chromatogr ; 32(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28991393

RESUMO

Fructus Alpiniae zerumbet is widely used in Guizhou province as a miao folk herb with anti-inflammatory, analgesic, protection against cardiovascular diseases, antihypertension and antioxidant activities. To further investigate the chemical material basis, the spectrum-effect relationship was established using gray relational analysis between the chromatographic fingerprint and its bioactivities. Herein, the fingerprints of essential oils from Fructus Alpiniae zerumbet (EOFAZ) from various sources were determined by gas chromatography mass spectrometry, and the analgesic and anti-inflammatory bioactivities were investigated using the mouse model of acetic acid-induced writhing test and dimethylbenzene-induced mouse ear edema test. Finally, 17 common peaks were identified from nine batches of A. zerumbet, by comparison with the standard mass spectra in Nist2005, Wiley275 library. Meanwhile, the results showed significant analgesic and anti-inflammatory effects in all of the different sources of EOFAZ. In particularly, peak 1 (α-pipene), peak 3 (ß-pinene), peak 9 (camphor) and peak 16 (α-cadinol) might be the main bioactive ingredients for analgesic and anti-inflammatory activities. The model of the spectrum-effect relationships of EOFAZ was successfully discovered, which provided a novel platform for finding the bioactive components, a theoretical foundation for its further study and helping to establish quality control of Fructus A. zerumbet.


Assuntos
Alpinia/classificação , Analgésicos/análise , Analgésicos/farmacologia , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Óleos Voláteis/química , Analgésicos/química , Animais , Anti-Inflamatórios/química , Comportamento Animal/efeitos dos fármacos , Edema , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos
8.
Zhong Yao Cai ; 39(1): 138-42, 2016 Jan.
Artigo em Zh | MEDLINE | ID: mdl-30080016

RESUMO

Objective: To optimize the polymer material and process condition for preparation of tanshinone Ⅱ_A microspheres by orthogonal design. Methods: The microspheres were prepared by emulsion solvent evaporation method. The optimum polymer material and preparation process were clarified by the comprehensive weighted score which was evaluated with the drug loading, encapsulation efficiency, and yield. The quality characterization of the tanshinone Ⅱ_A microspheres were assayed by SEM, laser particle size analyzer, TGDSC,and XRD. Results: The drug loading and encapsulation rate of microspheres prepared by PLLA was significantly higher than that of other polymer material. The surface of TA-PLLA-MS was round with porous structure, average particle size was( 96. 95 ± 1. 7) µm, the drug loading was( 30. 43 ± 0. 04) %,the entrapment efficiency was( 82. 72 ± 1. 51) %,and the yield was( 94. 10 ± 1. 60) %. The drug crystal form was still in the microspheres from the results of TG-DSC and XRD. Conclusion: The PLLA tanshinone Ⅱ_A microspheres were prepared by emulsion solvent evaporation method which was simple,stable,and enough loaded drug.


Assuntos
Microesferas , Abietanos , Emulsões , Ácido Láctico , Tamanho da Partícula , Solventes
9.
Zhong Yao Cai ; 39(2): 329-30, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-30080369

RESUMO

Objective: To study the chemical constituents from Periploca forrestii. Methods: The constituents were separated by column chromatography and their structures were elucidated by spectroscopic methods. Results: Seven compounds were isolated from Periploca forrestii and identified as wogonin( 1),negletein( 2),vanilline( 3),isovanilline( 4),periplocoside L( 5),ß-sitosterol( 6) and ß-daucosterol( 7). Conclusion: Compounds 1 and 2 are obtained from this genus for the first time,and compounds 3 ~ 5 are isolated from this plant for the first time.


Assuntos
Periploca , Plantas Medicinais , Sitosteroides
10.
Zhongguo Zhong Yao Za Zhi ; 40(11): 2168-73, 2015 Jun.
Artigo em Zh | MEDLINE | ID: mdl-26552175

RESUMO

OBJECTIVE: To investigate the inhibitory effects of OMT on TGF-ß1-induced CFBs proliferation, and then explore the mechanism. METHOD: The experiment was randomly divided into 6 groups as following: control group (serum free DMEM), model group (20 µg x L(-1) TGF-ß1), OMT low dose group (1.89 x 10(-4) mol x L(-1) + 20 µg x L(-1) TGF-ß1), OMT medium dose group (3.78 x 10(-4) mol x L(-1) + 20 µg x L(-1) TGF-ß1), OMT high dose group (7.56 x 10(-4) mol x L(-1) + 20 µg x L(-1) TGF-ß1), SB203580 group (p38MAPK blocking agent, 1 x 10(-5) mol x L(-1) + 20 µg x L(-1) TGF-ß1). Vimentin of CFBs was identified by immunocytochemical methods, α-SMA of myFBs as well. Inhibitory effects of OMT on CFBs proliferation was detected by the MTT assay. Picric acid Sirius red staining was analyzed collagen type I and collagen type III deposition. Western blot was determined the expression of p38MAPK, p-p38MAPK, collagen type I and collagen type III. RESULT: MTT results showed that OMT significantly inhibited CFBs proliferation induced by TGF-ß1 (P < 0.01) α-SMA immunocytochemical experiments suggested that OMT could protect against the CFBs proliferation. OMT could significantly decrease the deposition of collagen type I and collagen type III by Western bloting and picric acid Sirius red staining. Western blot results showed that TGF-ß1 enhanced p38MAPK phosphorylation, however OMT attenuated the phosphorylation of p38MAPK induced by TGF-ß1 (P < 0.01). CONCLUSION: OMT can inhibit the CFBs proliferation induced by TGF-ß1, and its mechanism may be involved in inhibiting p38MAPK phosphorylation.


Assuntos
Alcaloides/farmacologia , Coração/efeitos dos fármacos , Quinolizinas/farmacologia , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Regulação para Baixo , Feminino , Fibroblastos/efeitos dos fármacos , Técnicas In Vitro , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Zhong Yao Cai ; 37(7): 1213-7, 2014 Jul.
Artigo em Zh | MEDLINE | ID: mdl-25566659

RESUMO

OBJECTIVE: To investigate the ameliorated effect of CVB-D on oxidative stress and energy metabolism in experimental cardiac injuried rats induced by sympathetic overactivity in vivo. METHODS: SD rats were randomly divided into five groups as following: control group, model group, Vitamin E 150 mg/kg group, CVB-D low dose and high dose groups, respectively. The rat experimental cardiac injury model was established by exposed to norepinephrine (NE) 3 mg/kg by ip for 16 d. The drugs were administrated to rat for 16 d by ig. The body weight of rats were monitored during all of the experimental period. At the designing ending-time point the indexes were assayed as following: cardiac index, hydroxyproline, histopathologically examination, oxidative stress ( MDA, SOD, CAT, GSH-Px and T-AOC) and energy metabolism indicatricle ( Na+, K(+) -ATPase, and Ca2+, Mg(2+) -ATPase). RESULTS: After exposed with NE for 16 d, the rats of model group was appeared dysfunction of oxidative stress and energy metabolism such as decreasing body weight, increasing cardiac index and hydroxyproline in cardiac tissue, decreasing Na+, K(+) -ATPase and Ca(2+), Mg(2+) -ATPase activities, and deteriorating the oxidative stress. Treated with CVB-D could ameliorate all of the exacerbated indexes. CONCLUSION: CVB-D has protective effect against oxidative stress and energy metabolism in rats of experimental myocardial injury induced by sympathetic overactivity.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Adenosina Trifosfatases , Animais , Traumatismos Cardíacos , Ratos , Ratos Sprague-Dawley , Vitamina E
12.
Zhong Yao Cai ; 37(9): 1632-5, 2014 Sep.
Artigo em Zh | MEDLINE | ID: mdl-25857166

RESUMO

OBJECTIVE: To investigate the protective effect of CVB-D on cardiac myocytes injury induced by high sympathesis activity and its relationship with oxidative stress. METHODS: Primary culture cardiac myocyte of new-born rat was injuried by NE and then incubated with VE and CVB-D (10 and 50 micromol/L). Indexes of cardiac myoctye injury were assayed by morphologic change, MTT, and LDH leakage ratio. The activity of SOD and the content of MDA were investigated to identify oxidation and antioxygen. RESULTS: CVB-D (10 and 50 micromol/L) significantly increased the cell survival rate,and reduced the LDH leakage rate. CVE-D (50 micromol/L) significantly increased the activity of SOD, and decreased content of MDA in injuried cell. CONCLUSION: CVB-D has protective effect against myocardial injury induced by high sympathesis activity, the mechanism involves in ameliorating oxidative stress.


Assuntos
Miócitos Cardíacos , Animais , Sobrevivência Celular , Células Cultivadas , Traumatismos Cardíacos , Estresse Oxidativo , Ratos
13.
Phytomedicine ; 123: 155227, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128398

RESUMO

BACKGROUND: Atherosclerosis (AS) is a progressive chronic disease. Currently, cardiovascular diseases (CVDs) caused by AS is responsible for the global increased mortality. Yanshanjiang as miao herb in Guizhou of China is the dried and ripe fruit of Fructus Alpinia zerumbet. Accumulated evidences have confirmed that Yanshanjiang could ameliorate CVDs, including AS. Nevertheless, its effect and mechanism on AS are still largely unknown. PURPOSE: To investigate the role of essential oil from Fructus Alpinia zerumbet (EOFAZ) on AS, and the potential mechanism. METHODS: A high-fat diet (HFD) ApoE-/- mice model of AS and a oxLDL-induced model of macrophage-derived foam cells (MFCs) were reproduced to investigate the pharmacological properties of EOFAZ on AS in vivo and foam cell formation in vitro, respectively. The underlying mechanisms of EOFAZ were investigated using Network pharmacology and molecular docking. EOFAZ effect on PPARγ protein stability was measured using a cellular thermal shift assay (CETSA). Pharmacological agonists and inhibitors and gene interventions were employed for clarifying EOFAZ's potential mechanism. RESULTS: EOFAZ attenuated AS progression in HFD ApoE-/- mice. This attenuation was manifested by the reduced aortic intima plaque development, increased collagen content in aortic plaques, notable improvement in lipid profiles, and decreased levels of inflammatory factors. Moreover, EOFAZ inhibited the formation of MFCs by enhancing cholesterol efflux through activiting the PPARγ-LXRα-ABCA1/G1 pathway. Interestingly, the pharmacological knockdown of PPARγ impaired the beneficial effects of EOFAZ on MFCs. Additionally, our results indicated that EOFAZ reduced the ubiquitination degradation of PPARγ, and the chemical composition of EOFAZ directly bound to the PPARγ protein, thereby increasing its stability. Finally, PPARγ knockdown mitigated the protective effects of EOFAZ on AS in HFD ApoE-/- mice. CONCLUSION: These findings represent the first confirmation of EOFAZ's in vivo anti-atherosclerotic effects in ApoE-/- mice. Mechanistically, its chemical constituents can directly bind to PPARγ protein, enhancing its stability, while reducing PPARγ ubiquitination degradation, thereby inhibiting foam cell formation via activation of the PPARγ-LXRα-ABCA1/G1 pathway. Simultaneously, EOFAZ could ameliorates blood lipid metabolism and inflammatory microenvironment, thus synergistically exerting its anti-atherosclerotic effects.


Assuntos
Alpinia , Aterosclerose , Óleos Voláteis , Placa Aterosclerótica , Animais , Camundongos , PPAR gama/metabolismo , Óleos Voláteis/farmacologia , Frutas , Simulação de Acoplamento Molecular , Transdução de Sinais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Apolipoproteínas E , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Receptores X do Fígado/metabolismo
14.
Phytomedicine ; 128: 155369, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38547618

RESUMO

BACKGROUND: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. PURPOSE: This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. METHODS: A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate mitochondrial transcription factor A (TFAM) was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. RESULTS: GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated TFAM, mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. CONCLUSION: The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.


Assuntos
Álcoois Benzílicos , Demência Vascular , Glucosídeos , Mitocôndrias , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Sirtuína 3 , Sirtuínas , Animais , Glucosídeos/farmacologia , Demência Vascular/tratamento farmacológico , Sirtuína 3/metabolismo , Álcoois Benzílicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Acetilação , Fármacos Neuroprotetores/farmacologia , Camundongos , Fatores de Transcrição/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ratos , Modelos Animais de Doenças , Linhagem Celular , Resveratrol/farmacologia , Gastrodia/química
15.
Nat Prod Res ; : 1-8, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683975

RESUMO

A new labdane diterpene (1), two new norsesquiterpenoids (2-3), as well as eight known terpenoids (4-11) were isolated from the seeds of Alpinia galanga (Zingiberaceae). Their structures and absolute configurations were elucidated by 1D, 2D NMR, MS, and comparison of their experimental and calculated electronic circular dichroism (ECD). The acetylcholinesterase (AChE) inhibitory activities of all the isolated compounds (1-11) were evaluated and the result showed that compounds 6 and 9 had inhibitory activity against AChE, with IC50 values at 295.70 and 183.91 µM, whereas other compounds did not show any inhibitory activity.

16.
Phytochemistry ; 225: 114197, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945281

RESUMO

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7-8), and fourteen known compounds (9-22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3-8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 µM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.


Assuntos
Alpinia , Antineoplásicos Fitogênicos , Proliferação de Células , Diarileptanoides , Ensaios de Seleção de Medicamentos Antitumorais , Monoterpenos , Sementes , Alpinia/química , Humanos , Diarileptanoides/química , Diarileptanoides/farmacologia , Diarileptanoides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Sementes/química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Relação Estrutura-Atividade , Chalconas/química , Chalconas/farmacologia , Chalconas/isolamento & purificação , Chalcona/química , Chalcona/farmacologia , Chalcona/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular
17.
Front Microbiol ; 14: 1140190, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37089547

RESUMO

During an investigation of Diatrypaceae from southern China, 10 xylariales-like taxa have been collected. Morphological and multi-gene analyses confirmed that these taxa reside in Diatrypaceae and represent eight novel taxa and two new records belonging to six genera (viz., Allocryptovalsa, Diatrype, Diatrypella, Paraeutypella, Peroneutypa, and Vasilyeva gen. nov.). Vasilyeva gen. nov. was proposed to accommodate Vasilyeva cinnamomi sp. nov. Among the other collections, seven new species were introduced (viz., Diatrype camelliae-japonicae sp. nov., Diatrype rubi sp. nov., Diatrypella guiyangensis sp. nov., Diatrypella fatsiae-japonicae sp. nov., Paraeutypella subguizhouensis sp. nov., Peroneutypa hainanensis sp. nov., and Peroneutypa qianensis sp. nov.), while two were reported as new records from China (Allocryptovalsa rabenhorstii and Diatrype enteroxantha). For Diatrypaceae, the traditional taxonomic approach based on morphology may not be applicable.

18.
Int J Biol Macromol ; 245: 125443, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37353131

RESUMO

ABCA1 has been found to be critical for cholesterol efflux in macrophages. Understanding the mechanism regulating ABCA1 expression is important for the prevention and treatment of atherosclerosis. In the present study, a G-quadruplex (G4) structure was identified in the ABCA1 promoter region. This G4 was shown to be essential for ABCA1 transcription. Stabilizing the G4 by ligands surprisingly upregulated ABCA1 expression in macrophages. Knocking out the G4 remarkably reduced ABCA1 expression, and abolished the increase of ABCA1 expression induced by the G4 ligand. By pull-down assays, the protein NONO was identified as an ABCA1 G4 binder. Overexpression or repression of NONO significantly induced upregulation and downregulation of ABCA1 expression, respectively. ChIP and EMSA experiments showed that the G4 ligand promoted the binding between the ABCA1 G4 and NONO, which led to more recruitment of NONO to the promoter region and enhanced ABCA1 transcription. Finally, the G4 ligand was shown to significantly reduce the accumulation of cholesterol in macrophages. This study showed a new insight into the regulation of gene expression by G4, and provided a new molecular mechanism regulating ABCA1 expression in macrophages. Furthermore, the study showed a possible novel application of the G4 ligand: preventing and treating atherosclerosis.


Assuntos
Aterosclerose , Macrófagos , Humanos , Ligantes , Macrófagos/metabolismo , Colesterol/metabolismo , Fatores de Transcrição/genética , Aterosclerose/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo
19.
BMC Complement Altern Med ; 12: 174, 2012 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-23039037

RESUMO

BACKGROUND: The essential oil from Fructus Alpiniae zerumbet (FAZ) is its principal bioactive ingredient, and is widely used in Miao folk herbs in Guizhou province for the treatment of gastrointestinal and cardiovascular diseases. Several studies have confirmed that FAZ ameliorates hyperlipidemia and atherosclerosis. Because endothelial dysfunction often accompanies cardiovascular diseases, especially hyperlipidemia and atherosclerosis, the present study concentrated on evaluating the endothelial protective effects of the essential oil from FAZ (EOFAZ) on oxidized low-density lipoprotein (ox-LDL)-induced injury of cultured human umbilical vein endothelial cells (HUVECs) and on the regulation of oxidative stress. METHODS: Cell viability was analyzed with the MTT assay and trypan blue exclusion staining (TBES). Cell injury was assessed by lactate dehydrogenase (LDH) release. Biochemical enzymatic methods were used to evaluate the oxidative stress, including the lipid peroxidation product, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). RESULTS: The redox status of HUVECs was significantly exacerbated after exposure to ox-LDL. EOFAZ protected HUVECs against ox-LDL injury as assessed by the MTT assay, TBES and LDH release. Furthermore, EOFAZ ameliorated the oxidative stress by elevating the activities of SOD, CAT and GSH-Px, and increasing the GSH levels, in addition to attenuating the MDA contents. CONCLUSIONS: The present data provide the first experimental evidence that EOFAZ protects endothelial cells against ox-LDL-induced injury, and indicate that this protection involves ameliorating the redox status.


Assuntos
Alpinia , Antioxidantes/farmacologia , Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Lipoproteínas LDL/efeitos adversos , Óleos Voláteis/farmacologia , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Frutas , Células Endoteliais da Veia Umbilical Humana , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Óleos Voláteis/uso terapêutico , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia
20.
Phytother Res ; 26(2): 159-67, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21928391

RESUMO

Atherosclerosis (AS) is a systemic cardiovascular disease with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Increasing lines of evidence have questioned the statins-dominated treatment for AS, including their dangerous side-effects such as the breakdown of muscle when taken in larger doses. A multifaceted approach that addresses all major risk factors or pathological targets may provide an ideal treatment for AS. Studies of the herbal remedies on the prevention and treatment of AS have received much attention in recent years. This review summarizes some important experimental findings regarding their mechanisms of action on AS. Using the pre-set PUBMED searching syntax and inclusion criteria, representative citations published in English concerning the experimental studies of 14 herbal materials were included. We found that many extracts and (or) single compounds from these herbal materials, such as Salvia miltiorrhiza, Curcuma longa, Rheum undulatum and Panax notoginseng, could regulate multiple key targets involved in the initiation and propagation of AS. Some important findings about the effects of herbal formulations on AS were also reviewed. Given the complicated nature of AS and the holistic, combinational approach of herbal remedies, we propose that mixed herbal preparations with multiple active ingredients may be preferable for the prevention and treatment of AS. Further rigorously designed pharmacological evaluation and multi-centred clinical trials are warranted.


Assuntos
Aterosclerose/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Curcuma , Humanos , Panax notoginseng , Rheum , Salvia miltiorrhiza
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