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1.
Int J Mol Sci ; 22(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34639036

RESUMO

Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.


Assuntos
Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Endorribonucleases/antagonistas & inibidores , SARS-CoV-2/enzimologia , Sesquiterpenos/farmacologia , Tomatina/análogos & derivados , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/virologia , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Endorribonucleases/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2/efeitos dos fármacos , Tomatina/farmacologia , Proteínas não Estruturais Virais/metabolismo
2.
Acta Cir Bras ; 36(8): e360802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644770

RESUMO

PURPOSE: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. METHODS: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. CONCLUSIONS: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.


Assuntos
Amidoidrolases/antagonistas & inibidores , Proteína Forkhead Box O1/antagonistas & inibidores , Lesão Pulmonar , Sepse , Sesquiterpenos , Animais , Apoptose , Proteínas Ligadas por GPI/antagonistas & inibidores , Lactonas , Camundongos , Sepse/complicações , Sepse/tratamento farmacológico , Sesquiterpenos/farmacologia
3.
J Agric Food Chem ; 69(40): 11878-11889, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34605647

RESUMO

Fourteen eremophilane sesquiterpenoids (1-14), including nine new congeners, septoreremophilanes A-I (1-9), together with three known sesquiterpenes (15-17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1-6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1-9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 µM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 µM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.


Assuntos
Ascomicetos , Sesquiterpenos , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacologia
4.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3789-3796, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472251

RESUMO

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.


Assuntos
Diterpenos , Sesquiterpenos , Compostos Fitoquímicos/farmacologia , Plantas , Sesquiterpenos/farmacologia , Terpenos
5.
Chem Biol Interact ; 348: 109635, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506763

RESUMO

Aflatoxin B1 (AFB1) is a mycotoxin highly toxic and carcinogenic to humans due to its potential to induce oxidative stress. The Beta-caryophyllene (BCP) have been highlighted for its broad spectrum of pharmacological effects. The present study aimed to investigate the beneficial effects of BCP against the susceptibility of hepatic and renal tissues to AFB1 toxicity, in biochemical parameters to assess organ function, tissue oxidation, and the immunocontent of oxidative and inflammatory proteins. Male Wistar rats was exposed to AFB1 (250 µg/kg, i.g.) and/or BCP (100 mg/kg, i.p.) for 14 successive days. It was found that exposure to AFB1 did not change the measured renal toxicity parameters. Also, AFB1 increased liver injury biomarkers (gamma glutamyl transferase and alkaline phosphatase) and reduced levels of non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol), however did not cause changes in the lipid peroxidation levels. Moreover, AFB1 interfered in oxidative pathway regulated by Kelch-like ECH-associated protein (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2), overacting Glutathione-S-Transferase (GST) activity. Lastly, a main effect of AFB1 on the total interleukin 1 beta (IL-1ß) was observed. Remarkably, the associated treatment of AFB1 + BCP improved altered liver parameters. In addition, BCP and AFB1 + BCP groups showed an increase in the levels of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß). Thus, these results indicated that BCP has potential protective effect against AFB1 induced hepatotoxicity.


Assuntos
Aflatoxina B1/toxicidade , Citoproteção/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/citologia , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
6.
Chin J Nat Med ; 19(9): 693-699, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34561081

RESUMO

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 µmol·L-1, respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 µmol·L-1, respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.


Assuntos
Agaricales , COVID-19 , Polifenóis , Sesquiterpenos , Antioxidantes/farmacologia , Basidiomycota , COVID-19/tratamento farmacológico , Glucose , Humanos , Simulação de Acoplamento Molecular , Polifenóis/farmacologia , SARS-CoV-2 , Sesquiterpenos/farmacologia
7.
Int J Mol Sci ; 22(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34360675

RESUMO

In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 µg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 µg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena.


Assuntos
Benzoatos/farmacologia , Cicloeptanos/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Estresse Oxidativo , Sesquiterpenos/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular , Técnicas de Cocultura , Escherichia coli , Humanos , Inflamação/induzido quimicamente , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Substâncias Protetoras/farmacologia
8.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361731

RESUMO

Strigolactones (SLs) are a class of sesquiterpenoid plant hormones that play a role in the response of plants to various biotic and abiotic stresses. When released into the rhizosphere, they are perceived by both beneficial symbiotic mycorrhizal fungi and parasitic plants. Due to their multiple roles, SLs are potentially interesting agricultural targets. Indeed, the use of SLs as agrochemicals can favor sustainable agriculture via multiple mechanisms, including shaping root architecture, promoting ideal branching, stimulating nutrient assimilation, controlling parasitic weeds, mitigating drought and enhancing mycorrhization. Moreover, over the last few years, a number of studies have shed light onto the effects exerted by SLs on human cells and on their possible applications in medicine. For example, SLs have been demonstrated to play a key role in the control of pathways related to apoptosis and inflammation. The elucidation of the molecular mechanisms behind their action has inspired further investigations into their effects on human cells and their possible uses as anti-cancer and antimicrobial agents.


Assuntos
Antineoplásicos/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Lactonas/farmacologia , Micorrizas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Plantas/metabolismo , Sesquiterpenos/farmacologia , Adaptação Fisiológica , Agricultura/métodos , Agroquímicos/isolamento & purificação , Agroquímicos/metabolismo , Agroquímicos/farmacologia , Antibacterianos/biossíntese , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/metabolismo , Humanos , Inflamação/prevenção & controle , Lactonas/isolamento & purificação , Lactonas/metabolismo , Micorrizas/química , Neoplasias/tratamento farmacológico , Patentes como Assunto , Reguladores de Crescimento de Plantas/biossíntese , Reguladores de Crescimento de Plantas/isolamento & purificação , Plantas/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo , Estresse Fisiológico , Controle de Plantas Daninhas/métodos
9.
Phytochemistry ; 191: 112901, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34388663

RESUMO

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol), a sesquiterpene alcohol present in aromatic essential oils of numerous plants, has been reported to possess anticancer activity. The potential therapeutic effect of nerolidol on uterine fibroids (UF), the most common benign tumor of the uterus worldwide, is unknown. In this study, we examined the anti-UF potential of nerolidol in ELT3 cells, a rat leiomyoma cell line widely used as an in vitro model, to identify the potential therapeutic agents for UF. We observed that treatment with cis- or trans-nerolidol inhibited cell proliferation in a dose-dependent manner and induced cell cycle arrest in the G1 phase, which was accompanied by reduction in Akt phosphorylation and downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 protein expression. The proliferation-inhibiting activity of nerolidol correlated with the generation of intracellular reactive oxygen species (ROS), which was suppressed by N-acetyl-l-cysteine, a ROS inhibitor. Nerolidol treatment also increased the percentage of cells for which tail moment could be calculated using an alkaline comet assay, and induced p-γH2AXser139 expression, which indicated induction of DNA damage. We also observed downregulation of ATM and its phosphorylation after nerolidol treatment; furthermore, treatment with KU-55933, an ATM kinase inhibitor, mimicked the inhibitory effects of nerolidol treatment on cell proliferation and Akt phosphorylation. In conclusion, nerolidol displayed anti-UF activity in a leiomyoma cell model via ROS-induced DNA damage and G1 phase cell cycle arrest by inhibiting the expression and activation of the ATM/Akt pathway. Our data suggests that nerolidol is a potential therapeutic agent for UF.


Assuntos
Leiomioma , Sesquiterpenos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Dano ao DNA , Regulação para Baixo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia
10.
Phytochemistry ; 191: 112924, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34428668

RESUMO

Fifteen undescribed dimeric sesquiterpenoids, linderanoids A-O along with one known lindenane-type sesquiterpenoid dimer, lindenaneolide F, were isolated and identified from the roots of Lindera aggregata. Their structures and absolute configurations were elucidated using spectroscopy and electronic circular dichroism (ECD) analysis. All the isolated compounds were screened for transforming growth factor (TGF)-ß inhibitory activity, and the results showed that linderanoid E significantly inhibited the TGF- ß induced smad2 phosphorylation at a concentration of 25 µM.


Assuntos
Lindera , Sesquiterpenos , Raízes de Plantas , Sesquiterpenos/farmacologia
11.
J Nat Prod ; 84(8): 2385-2389, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34351742

RESUMO

The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (1-4), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic cadinane sesquiterpenoids inhibited the SARS-CoV-2 spike-ACE2 interaction, with IC50 values ranging from 64.5 to 99.1 µM. A molecular docking study showed the disruption of the interaction of compound 1 via hydrogen interactions with Arg403, Asp405, and Arg408 of SARS-CoV-2 RBD and Arg393 and His34 residues of ACE2. These results suggested that aromatic cadinane sesquiterpenoids might be useful in developing agents for COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/química , Antivirais/farmacologia , Carpóforos/química , Phellinus/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Humanos , Ligação de Hidrogênio/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Simulação de Acoplamento Molecular
12.
J Chem Ecol ; 47(8-9): 740-746, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347235

RESUMO

Aphids are destructive pests, and alarm pheromones play a key role in their chemical ecology. Here, we conducted a detailed analysis of terpenoids in the vetch aphid, Megoura viciae, and its host plant Pisum sativum using gas chromatography/mass spectrometry. Four major components, (-)-ß-pinene (49.74%), (E)-ß-farnesene (32.64%), (-)-α-pinene (9.42%) and ( +)-limonene (5.24%), along with trace amounts of ( +)-sabinene, camphene and α-terpineol) (3.14%) were found in the aphid. In contrast, few terpenoids were found in the host plant, consisting mainly of squalene (66.13%) and its analog 2,3-epoxysqualene (31.59%). Quantitative analysis of the four major terpenes in different developmental stages of the aphid showed that amounts of the monoterpenes increased with increasing stage, while the sesquiterpene amount peaked in the 3rd instar. (-)-ß-Pinene was the most abundant terpene at all developmental stages. Behavioral assays using a three-compartment olfactometer revealed that the repellency of single compounds varied in a concentration-dependent manner, but two mixtures [(-)-α-pinene: (-)-ß-pinene: (E)-ß-farnesene: ( +)-limonene = 1:44.4:6.5:2.2 or 1:18.4:1.3:0.8], were repellent at all concentrations tested. Our results suggest that (-)-α-pinene and (-)-ß-pinene are the major active components of the alarm pheromone of M. viciae, but that mixtures play a key role in the alarm response. Our study contributes to the understanding of the chemical ecology of aphids and may help design new control strategies against this aphid pest.


Assuntos
Afídeos/fisiologia , Ervilhas/química , Feromônios/química , Terpenos/química , Animais , Afídeos/química , Afídeos/crescimento & desenvolvimento , Comportamento Animal/efeitos dos fármacos , Monoterpenos Bicíclicos/isolamento & purificação , Monoterpenos Bicíclicos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Controle de Insetos/métodos , Estágios do Ciclo de Vida , Ervilhas/metabolismo , Ervilhas/parasitologia , Feromônios/análise , Feromônios/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Terpenos/análise , Terpenos/farmacologia
13.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361712

RESUMO

The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.


Assuntos
Alcaloides/química , Maitansina/análogos & derivados , Maytenus/química , Compostos Fitoquímicos/química , Sesquiterpenos/química , Triterpenos/química , Alcaloides/classificação , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Maitansina/isolamento & purificação , Maitansina/farmacologia , Maytenus/metabolismo , Estrutura Molecular , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais , Sesquiterpenos/classificação , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Triterpenos/classificação , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
14.
Cell Prolif ; 54(9): e13107, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34346124

RESUMO

OBJECTIVES: In recent years, cellular senescence has attracted a lot of interest in researchers due to its involvement in non-alcoholic fatty liver disease (NAFLD). However, the mechanism of cellular senescence is not clear. The purpose of this study was to investigate the effect of curcumol on hepatocyte senescence in NAFLD and the molecular mechanisms implicated. MATERIALS AND METHODS: LVG Golden Syrian hamsters, C57BL/6J mice and human hepatocyte cell line LO2 were used. Cellular senescence was assessed by analyses of senescence marker SA-ß-gal, p16 and p21, H3K9me3, γ-H2AX and telomerase activity. RESULTS: The results showed that curcumol could inhibit hepatocyte senescence in both in vivo and in vitro NAFLD models, and the mechanism might be related to its regulation of ferritinophagy and subsequent alleviation of iron overload. Moreover, overexpression of nuclear receptor coactivator 4 (NCOA4) weakened the effect of curcumol on ferritinophagy-mediated iron overload and cellular senescence. Furthermore, we demonstrated that curcumol reduced the expression of NCOA4 by Yes-associated protein (YAP). In addition, depression of YAP could impair the effect of curcumol on iron overload and cellular senescence. CONCLUSION: Our results clarified the mechanism of curcumol inhibition of hepatocyte senescence through YAP/NCOA4 regulation of ferritinophagy in NAFLD. These findings provided a promising option of curcumol to regulate cellular senescence by target YAP/NCOA4 for the treatment of NAFLD.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autofagia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Ferritinas/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Coativadores de Receptor Nuclear/metabolismo , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Hepatócitos/metabolismo , Humanos , Ferro/metabolismo , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
15.
Phytochemistry ; 190: 112850, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34217042

RESUMO

The phytochemical assessment of Cinnamomum migao H. W. Li fruits illustrated the isolation and identification of ten undescribed guaiane-type sesquiterpenoids "miganoids A-J″ and one undescribed sesquiterpene "7(S)-(hydroxypropanyl)-3-methyl-2-(4-oxopentyl) cyclohex-2-en-1-one". The extensive analysis of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD) analysis entirely corroborated the configuration and confirmation of these isolated compounds. Moreover, the anti-inflammatory properties of the reported compounds were established by determining the LPS induced nitric oxide production. In the current study, miganoid C is testified the most active compound with about 89% NO inhibition. Additionally, miganoids C, E, and G also exhibited moderate inhibitory effects against the pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). The IC50 values for miganoid C and miganoid G were determined as 19.4 and 14.5 µΜ against TNF-α mRNA, respectively.


Assuntos
Cinnamomum , Sesquiterpenos , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Óxido Nítrico , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano
16.
Phytochemistry ; 190: 112889, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34329938

RESUMO

Five undescribed (four guaianolide sesquiterpenes and a benzoate ester derivative) and seven known compounds were isolated from the aerial parts of S. orientalis L. Their chemical structures were determined by extensive analysis of HR-ESI-MS and NMR spectroscopic methods. Absolute configurations were elucidated by experimental and TD-DFT calculated ECD spectra. Twelve isolated compounds exhibited potential xanthine oxidase inhibitory activity with IC50 values ranging from 0.76 ± 0.17 µM to 31.80 ± 0.97 µM. Molecular docking studies predicted that the binding energies of all isolated compounds with xanthine oxidase were lower than that of the positive control allopurinol. Benzyl 2-hydroxy-6-O-ß-D-glucopyranosylbenzoate and benzyl 2-methoxy-6-O-ß-D-glucopyranosylbenzoate displayed not only the best docking score but also the highest in vitro xanthine oxidase inhibitory activity with IC50 values of 0.76 ± 0.17 µM and 0.98 ± 0.26 µM, respectively.


Assuntos
Sesquiterpenos , Xantina Oxidase , Benzoatos , Ésteres , Simulação de Acoplamento Molecular , Estrutura Molecular , Componentes Aéreos da Planta , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano
17.
Molecules ; 26(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299640

RESUMO

A series of cyclohumulanoids, i.e., tricocerapicanols A-C (1a-1c), tricoprotoilludenes A (2a) and B (3), tricosterpurol (4), and tricoilludins A-C (5-7) were isolated along with known violascensol (2b) and omphadiol (8) from the culture broth of Daedaleopsis tricolor, an inedible but not toxic mushroom. The structures were fully elucidated on the basis of NMR spectroscopic analysis, and the suggested relative structures were confirmed via density functional theory (DFT)-based chemical shift calculations involving a DP4 probability analysis. In the present study, the 1H chemical shifts were more informative than the 13C chemical shifts to distinguish the diastereomers at C-11. The absolute configurations of 1-5 were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. For 6 and 7, the same chirality was assigned according to their biosynthetic similarities with the other compounds. The successful assignment of some Cotton effects was achieved by utilizing DFT calculations using simple model compounds. The plausible biosynthesis of 1-7 was also discussed on the basis of the structural commonality and general cyclohumulanoid biosynthesis. Compounds 2a and 5 were found to simultaneously induce hyphal swelling and branching at 5.0 µg/mL against a test fungus Cochliobolus miyabeanus.


Assuntos
Meios de Cultura/química , Polyporaceae/crescimento & desenvolvimento , Sesquiterpenos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
18.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202590

RESUMO

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone's antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB1 receptor), SR144528 (CB2 receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB1, PPARα and PPARγ in zerumbone's action against mechanical allodynia, whereas only CB1 and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.


Assuntos
Neuralgia , PPAR alfa/antagonistas & inibidores , PPAR gama/antagonistas & inibidores , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Neuralgia/patologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo
19.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203809

RESUMO

Rhododendron (Ericaceae) extracts contain flavonoids, chromones, terpenoids, steroids, and essential oils and are used in traditional ethnobotanical medicine. However, little is known about the immunomodulatory activity of essential oils isolated from these plants. Thus, we isolated essential oils from the flowers and leaves of R. albiflorum (cascade azalea) and analyzed their chemical composition and innate immunomodulatory activity. Compositional analysis of flower (REOFl) versus leaf (REOLv) essential oils revealed significant differences. REOFl was comprised mainly of monoterpenes (92%), whereas sesquiterpenes were found in relatively low amounts. In contrast, REOLv was primarily composed of sesquiterpenes (90.9%), with a small number of monoterpenes. REOLv and its primary sesquiterpenes (viridiflorol, spathulenol, curzerene, and germacrone) induced intracellular Ca2+ mobilization in human neutrophils, C20 microglial cells, and HL60 cells transfected with N-formyl peptide receptor 1 (FPR1) or FPR2. On the other hand, pretreatment with these essential oils or component compounds inhibited agonist-induced Ca2+ mobilization and chemotaxis in human neutrophils and agonist-induced Ca2+ mobilization in microglial cells and FPR-transfected HL60 cells, indicating that the direct effect of these compounds on [Ca2+]i desensitized the cells to subsequent agonist activation. Reverse pharmacophore mapping suggested several potential kinase targets for these compounds; however, these targets were not supported by kinase binding assays. Our results provide a cellular and molecular basis to explain at least part of the beneficial immunotherapeutic properties of the R. albiflorum essential oils and suggest that essential oils from leaves of this plant may be effective in modulating some innate immune responses, possibly by inhibition of neutrophil migration.


Assuntos
Óleos Voláteis/química , Rhododendron/química , Flores/química , Células HL-60 , Humanos , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/metabolismo , Imunomodulação/efeitos dos fármacos , Monoterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Folhas de Planta/química , Receptores de Formil Peptídeo/efeitos dos fármacos , Receptores de Formil Peptídeo/metabolismo , Rhododendron/metabolismo , Sesquiterpenos/farmacologia
20.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203927

RESUMO

Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.


Assuntos
Artemisia/metabolismo , Flavonoides/farmacologia , Helicobacter pylori/efeitos dos fármacos , Animais , Antiulcerosos/farmacologia , Flavonoides/metabolismo , Gastrite/tratamento farmacológico , Masculino , Medicina Tradicional , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/farmacologia , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Úlcera Gástrica/tratamento farmacológico
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