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1.
Front Endocrinol (Lausanne) ; 13: 891714, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784537

RESUMO

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioral stress in vertebrate and urochordate models. There is little information for invertebrates regarding the existence or function of a TCAP. This study used the Sydney rock oyster (SRO) as a molluscan model to characterize an invertebrate TCAP, from molecular gene analysis to its physiological effects associated with hemocyte phagocytosis. We report a single teneurin gene (and 4 teneurin splice variants), which encodes a precursor with TCAP that shares a vertebrate-like motif, and is similar to that of other molluscan classes (gastropod, cephalopod), arthropods and echinoderms. TCAP was identified in all SRO tissues using western blotting at 1-2 different molecular weights (~22 kDa and ~37kDa), supporting precursor cleavage variation. In SRO hemolymph, TCAP was spatially localized to the cytosol of hemocytes, and with particularly high density immunoreactivity in granules. Based on 'pull-down' assays, the SRO TCAP binds to GAPDH, suggesting that TCAP may protect cells from apoptosis under oxidative stress. Compared to sham injection, the intramuscular administration of TCAP (5 pmol) into oysters modulated their immune system by significantly reducing hemocyte phagocytosis under stress conditions (low salinity and high temperature). TCAP administration also significantly reduced hemocyte reactive oxygen species production at ambient conditions and after 48 h stress, compared to sham injection. Transcriptomic hemocyte analysis of stressed oysters administered with TCAP demonstrated significant changes in expression of genes associated with key metabolic, protective and immune functions. In summary, this study established a role for TCAP in oysters through modulation of physiological and molecular functions associated with energy conservation, stress and cellular defense.


Assuntos
Hemócitos , Ostreidae , Acetofenonas , Animais , Ostreidae/genética , Peptídeos , Filogenia , Transcriptoma
2.
Int Immunopharmacol ; 108: 108901, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35729834

RESUMO

Memory loss is the most common occurrence of dementia in the elderly population. Evidence shows 1,2-Diacetylbenzene (DAB) can exacerbate cerebral dysfunction. The molecular mechanisms involved in DAB actions in the hippocampus have not been well elucidated to date. qPCR, western blot, Morris water maze, and RNAseq analysis were used to identify the association between inflammation and hyperphosphorylated tau in male DAB-treated mice (1 or 5 mg/kg/day), rats (3 mg/kg/day), in vitro BV2 microglial cells (1 or 5 µM), and the hippocampal transcriptome of male DAB-treated rats. We found that DAB induces memory deficits by activating pro-inflammatory cytokines as well as down-regulating memory and learning genes. Several genes involved in learning, memory, and behavior induced by DAB (e.g., PRL, Pit-1, PRLR, Ttr, Notch2, Ntsr1, C5ar2, Cd74) were not changed or downregulated in young rats, but upregulated in old rats. Detoxification pathways were upregulated in young rats treated with DAB, whereas prolactin (PRL) signaling pathways were upregulated in old DAB-treated rats. Further work is needed to gain a better understanding of the roles of PRL during aging.


Assuntos
Citocinas , Prolactina , Acetofenonas/farmacologia , Idoso , Animais , Citocinas/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/metabolismo , Camundongos , Prolactina/metabolismo , Prolactina/farmacologia , Ratos , Receptor da Anafilatoxina C5a/metabolismo
3.
J Oleo Sci ; 71(6): 853-861, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35661067

RESUMO

Coronavirus is one of the RNA viruses with the largest genome; It is a group of viruses known to infect humans very little until the end of the 20th century, generally causing infection in animals (bird, cat, pig, mouse, horse, bat). It is the causative agent of 15-30% of seasonal lower and upper respiratory tract infections, and may rarely cause gastrointestinal and nervous system infections. We have obtained results for the collagenase and elastase enzymes were at the micromolar level. We obtained IC50 results for the collagenase enzyme for 6-hydroxy-4-methylcoumarin 257.22 ± 34.07 µM and for 2,5-dihydroxyacetophenone 74.46 ± 8.61 µM. 6-Hydroxy-4-methylcoumarin and 2,5-dihydroxyacetophenone were considered good inhibitors for elastase enzyme. Additionally, these compounds significantly decreased human pancreatic cancer cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in human pancreatic cancer cell viability. IC50 results (IC50: 10-50 µM) were better than control. In the otherwords, the docking results suggest that both compounds tend to have lower efficacy on the main protease targets of SARS-CoV-2 than standard compounds, (NL-1 and NL-2). The reason for this is that the standard compounds interact strongly and more frequently with the target proteins, and the surface areas they cover on the active surface are much larger than the small ligand molecules studied.


Assuntos
COVID-19 , Neoplasias Pancreáticas , Acetofenonas , Animais , COVID-19/tratamento farmacológico , Colagenases , Flavonoides , Cavalos , Camundongos , Elastase Pancreática , Neoplasias Pancreáticas/tratamento farmacológico , SARS-CoV-2 , Suínos
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121495, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35700610

RESUMO

Herein, we examined the modulatory effects ofApocynum (APO) on Monosodium Glutamate (MSG)-induced oxidative damage on the brain tissue of rats after long-term consumption of blood serum components by biochemical assays, Fourier transform infrared spectroscopy(FTIR), and machine learning methods. Sprague-Dawley male rats were randomly divided into the Control, Control + APO, MSG, and MSG + APO groups (n = 8 per group). All administrations were made by oral gavage saline, MSG, or APO and they were repeated for 28 days of the experiments. Brain tissue and blood serum samples were collected and analyzed for measurement levels ofmalondialdehyde (MDA),glutathione (GSH),myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and Spectroscopic analysis. After 29 days, the results were evaluated using machine learning (ML). The levels of MDA and MPO showed changes in the MSG and MSG + APO groups, respectively. Changes in the proteins and lipids were observed in the FTIR spectra of the MSG groups. Additionally, APO in these animals improved the FTIR spectra to be similar to those in the Control group. The accuracy of the FTIR results calculated by ML was 100%. The findings of this study demonstrate that Apocynin treatment protectsagainst MSG-induced oxidative damage by inhibitingreactive oxygen speciesand upregulatingantioxidant capacity, indicating its potential in alleviatingthe toxic effects of MSG.


Assuntos
Estresse Oxidativo , Glutamato de Sódio , Acetofenonas , Animais , Encéfalo/metabolismo , Glutationa/metabolismo , Aprendizado de Máquina , Masculino , Ratos , Ratos Sprague-Dawley , Glutamato de Sódio/metabolismo , Glutamato de Sódio/farmacologia
5.
J Neuroinflammation ; 19(1): 142, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690821

RESUMO

BACKGROUND: It has been demonstrated that reactive astrocytes can be polarized into pro-inflammatory A1 phenotype or anti-inflammatory A2 phenotype under neurotoxic and neurodegenerative conditions. Microglia have been suggested to play a critical role in astrocyte phenotype polarization by releasing pro- and anti-inflammatory mediators. In this study, we examined whether trimethyltin (TMT) insult can induce astrocyte polarization in the dentate gyrus of mice, and whether protein kinase Cδ (PKCδ) plays a role in TMT-induced astrocyte phenotype polarization. METHODS: Male C57BL/6 N mice received TMT (2.6 mg/kg, i.p.), and temporal changes in the mRNA expression of A1 and A2 phenotype markers were evaluated in the hippocampus. In addition, temporal and spatial changes in the protein expression of C3, S100A10, Iba-1, and p-PKCδ were examined in the dentate gyrus. Rottlerin (5 mg/kg, i.p. × 5 at 12-h intervals) was administered 3-5 days after TMT treatment, and the expression of A1 and A2 transcripts, p-PKCδ, Iba-1, C3, S100A10, and C1q was evaluated 6 days after TMT treatment. RESULTS: TMT treatment significantly increased the mRNA expression of A1 and A2 phenotype markers, and the increased expression of A1 markers remained longer than that of A2 markers. The immunoreactivity of the representative A1 phenotype marker, C3 and A2 phenotype marker, S100A10 peaked 6 days after TMT insult in the dentate gyrus. While C3 was expressed evenly throughout the dentate gyrus, S100A10 was highly expressed in the hilus and inner molecular layer. In addition, TMT insult induced microglial p-PKCδ expression. Treatment with rottlerin, a PKCδ inhibitor, decreased Iba-1 and C3 expression, but did not affect S100A10 expression, suggesting that PKCδ inhibition attenuates microglial activation and A1 astrocyte phenotype polarization. Consistently, rottlerin significantly reduced the expression of C1q and tumor necrosis factor-α (TNFα), which has been suggested to be released by activated microglia and induce A1 astrocyte polarization. CONCLUSION: We demonstrated the temporal and spatial profiles of astrocyte polarization after TMT insult in the dentate gyrus of mice. Taken together, our results suggest that PKCδ plays a role in inducing A1 astrocyte polarization by promoting microglial activation and consequently increasing the expression of pro-inflammatory mediators after TMT insult.


Assuntos
Astrócitos , Complemento C1q , Acetofenonas , Animais , Astrócitos/metabolismo , Benzopiranos , Complemento C1q/metabolismo , Giro Denteado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fenótipo , RNA Mensageiro/metabolismo , Compostos de Trimetilestanho
6.
Front Immunol ; 13: 896874, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686124

RESUMO

Developing quorum-sensing (QS) based anti-infection drugs is one of the most powerful strategies to combat multidrug-resistant bacteria. Paeonol has been proven to attenuate the QS-controlled virulence factors of P. aeruginosa by down-regulating the transcription of QS signal molecules. This research aimed to assess the anti-virulence activity and mechanism of paeonol against P. aeruginosa infection in vitro and in vivo. In this study, paeonol was found to reduce the adhesion and invasion of P.aeruginosa to macrophages and resist the cytotoxicity induced by P.aeruginosa. Paeonol reduced the expression of virulence factors of P.aeruginosa by inhibiting QS, thereby reducing the LDH release and damage of P.aeruginosa-infected macrophages. Paeonol can inhibit bacterial virulence and enhance the ability of macrophages to clear P.aeruginosa. In addition, paeonol exerts anti-inflammatory activity by reducing the expression of inflammatory cytokines and increasing the production of anti-inflammatory cytokines. Paeonol treatment significantly inhibited the activation of TLR4/MyD88/NF-κB signaling pathway and decreased the inflammation response of P. aeruginosa-infected macrophages. Paeonol also significantly reduced the ability of P.aeruginosa to infect mice and reduced the inflammatory response. These data suggest that paeonol can inhibit the virulence of P.aeruginosa and decrease the inflammation response in P.aeruginosa-infected macrophages and mice, which can decrease the damage induced by P.aeruginosa infection and enhance the ability of macrophages to clear bacteria. This study supports the further development of new potential anti-infective drugs based on inhibition of QS and virulence factors.


Assuntos
Pseudomonas aeruginosa , Fatores de Virulência , Acetofenonas , Animais , Anti-Inflamatórios/farmacologia , Citocinas , Inflamação/tratamento farmacológico , Camundongos , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência/metabolismo
7.
Front Cell Infect Microbiol ; 12: 884793, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669114

RESUMO

Fungal populations are commonly found in natural environments and present enormous health care challenges, due to increased resistance to antifungal agents. Paeonol exhibits antifungal activities; nevertheless, the antifungal and antibiofilm activities of paeonol against Candida albicans and Cryptococcus neoformans remain largely unexplored. Here, we aimed to evaluate the antifungal and antibiofilm activities of paeonol against C. albicans and/or C. neoformans (i.e., against mono- or dual-species). The minimum inhibitory concentrations (MICs) of paeonol for mono-species comprising C. albicans or C. neoformans were 250 µg ml-1, whereas the MIC values of paeonol for dual-species were 500 µg ml-1. Paeonol disrupted cell membrane integrity and increased the influx of gatifloxacin into cells of mono- and dual-species cells, indicating an antifungal mode of action. Moreover, paeonol at 8 times the MIC damaged mono- and dual-species cells within C. albicans and C. neoformans biofilms, as it did planktonic cells. In particular, at 4 and 8 mg ml-1, paeonol efficiently dispersed preformed 48-h biofilms formed by mono- and dual-species cells, respectively. Paeonol inhibited effectively the yeast-to-hyphal-form transition of C. albicans and impaired capsule and melanin production of C. neoformans. The addition of 10 MIC paeonol to the medium did not shorten the lifespan of C. elegans, and 2 MIC paeonol could effectively protect the growth of C. albicans and C. neoformans-infected C. elegans. Furthermore, RNA sequencing was employed to examine the transcript profiling of C. albicans and C. neoformans biofilm cells in response to 1/2 MIC paeonol. RNA sequencing data revealed that paeonol treatment impaired biofilm formation of C. albicans by presumably downregulating the expression level of initial filamentation, adhesion, and growth-related genes, as well as biofilm biosynthesis genes, whereas paeonol inhibited biofilm formation of C. neoformans by presumably upregulating the expression level of ergosterol biosynthesis-related genes. Together, the findings of this study indicate that paeonol can be explored as a candidate antifungal agent for combating serious single and mixed infections caused by C. albicans and C. neoformans.


Assuntos
Criptococose , Cryptococcus neoformans , Acetofenonas , Animais , Antifúngicos/farmacologia , Biofilmes , Caenorhabditis elegans , Candida albicans , Testes de Sensibilidade Microbiana
8.
Int J Pharm ; 623: 121916, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35714817

RESUMO

The cyclodextrin (CD) was grafted onto hyaluronic acid (HA) to form a topical delivery carrier (HACD) in which Paeonol was loaded in its CD cavity and self-assemble into the polymeric micelles (HACD-PAE) for the treatment of atopic dermatitis. Fluorescence microscope observed that HACD could fast penetrate into the skin and remain stable within 12 h. In vitro penetration test (IVPT) results showed the PAE retentions of HACD-PAE group in the stratum corneum and dermis were 3.35 and 1.78 times improvement than that of PAE group. ATR-FTIR and H&E staining assays indicated HACD could increase the gap of keratinocytes by interacting with corneum lipids and loosening the keratin. Furthermore, HACD-PAE showed the best therapeutic effect on atopic dermatitis mice. Thus HACD could be a promising skin-specific delivery carrier, not only promoting the drug penetrating but increasing its remaining in the skin and play the skin disease therapy and skin-care role.


Assuntos
Ciclodextrinas , Dermatite Atópica , Acetofenonas/farmacologia , Animais , Ciclodextrinas/farmacologia , Dermatite Atópica/tratamento farmacológico , Ácido Hialurônico , Camundongos , Pele
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(4): 289-294, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35583056

RESUMO

Objective This study is aimed to investigate the effect of paeonol on inflammation of BV2 microglia induced by lipopolysaccharide (LPS), and the underlying mechanism. Methods Mouse BV2 microglia was cultured in vitro. BV2 microglia was pretreated with paeonol of different concentration for 24 hours, then stimulated by LPS for 12 hours. Cell viability was detected by CCK-8 assay. Morphological changes of microglia were monitored by microscopy. The mRNA expression of TNF-α, IL-1ß, IL-12 and IL-6 by BV2 microglia was measured by real time quantitative-PCR. The protein expression of NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) was determined by Western blot analysis. Results Paeonol treatment improved cell viability, and inhibited over-activation of BV2 microglia challenged by LPS. Paeonol treatment concentration-dependently suppressed LPS induced mRNA expression of inflammatory cytokines including TNF-α, IL-1ß, IL-6, and IL-12 by BV2 microglia. Phosphorylation of NF-κB p65, but not protein level of NF-κB p65, was suppressed by paeonol treatment in a concentration-dependent manner. Conclusion Paeonol inhibits LPS induced phosphorylation of NF-κB p65 and transcription of downstream proinflammatory cytokines in BV2 microglia.


Assuntos
Lipopolissacarídeos , Microglia , Acetofenonas , Animais , Citocinas/metabolismo , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Eur J Pharmacol ; 927: 175057, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35636525

RESUMO

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.


Assuntos
Hipertensão , Vasodilatação , Acetofenonas , Animais , Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Endotélio Vascular , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR
11.
Sci Total Environ ; 837: 155558, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35504386

RESUMO

Fine particulate matter (PM2.5) has been consistently linked to cardiovascular diseases, and cardiac fibrosis plays a crucial role in the occurrence and development of heart diseases. It is reported that NOX4-dependent redox signaling are responsible for TGFß-mediated profibrotic responses. The current study was designed to explore the possible mechanisms of cardiac fibrosis by PM2.5 both in vitro and in vivo. Female C57BL/6 mice received PM2.5 (3 mg/kg b.w.) exposure with/without NOX4 inhibitor (apocynin, 25 mg/kg b.w.) or ROS scavenger (NALC, 50 mg/kg b.w.), every other day, for 4 weeks. H9C2 cells were incubated with PM2.5 (3 µg/mL) with/without 5 mM NALC, TGFß inhibitor (SB431542, 10 µM), or siRNA-NOX4 for 24 h. The results demonstrated that PM2.5 induced evident collagen deposition and elevated expression of fibrosis biomarkers (Col1a1 & Col3a1). Significant systemic inflammatory response and cardiac oxidative stress were triggered by PM2.5. PM2.5 increased the protein expression of TGFß1, NOX4, and P38 MAPK. Notably, the increased effects of PM2.5 could be suppressed by SB431542, siRNA-NOX4 in vitro or apocynin in vivo, and NALC. The reverse verification experiments further supported the involvement of the TGFß/NOX4/ROS/P38 MAPK signaling pathway in the myocardial fibrosis induced by PM2.5. In summary, the current study provided evidence that PM2.5 challenge led to cardiac fibrosis through oxidative stress, systemic inflammation, and subsequent TGFß/NOX4/ROS/P38 MAPK pathway and may offer new therapeutic targets in cardiac fibrosis.


Assuntos
Sistema de Sinalização das MAP Quinases , Miocárdio , NADPH Oxidase 4 , Espécies Reativas de Oxigênio , Proteínas Quinases p38 Ativadas por Mitógeno , Acetofenonas/farmacologia , Animais , Feminino , Fibrose , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , NADPH Oxidase 4/antagonistas & inibidores , NADPH Oxidase 4/metabolismo , Estresse Oxidativo , Material Particulado/toxicidade , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Chemosphere ; 302: 134750, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35504468

RESUMO

Increasing water pollution is a severe problem in densely industrialized countries. Nanomaterials provide strong potentials for the efficient elimination of organic pollutants due to their beneficial properties. Advancement in water purification is required to more efficiently remove the emerging organic contaminants, especially in pharmaceuticals wastes such as acetophenone, which shows high solubility in industrial wastewaters. Bismuth ferrite-based nanostructures were fabricated using a novel double solvent sol-gel method. The phase purity and crystallinity of bismuth ferrite were confirmed using XRD and further endorsed by TEM analysis. The SEM and XPS were used to study the particle sizes and presence of co-dopants on the Bi and Fe-sites of bismuth ferrite. After co-doping, the band-gap engineering of pure bismuth ferrites was accomplished by reducing it from 2.06 eV to 1.45 eV, likely attributing to the creation of shallow traps for the incoming photo-generated charge carriers. In particular, the Bi0.90Gd0.10Fe0.95Sn0.05 and Bi0.95Sm0.05Fe0.75Mn0.25 successfully eliminated up to 98% of acetophenone from polluted water in 3 h by irradiation of visible-light. These results reveal the suitability of the co-doped bismuth ferrites photocatalysts for the practical removal of pharmaceutical contaminants in hazardous industrial wastewater. The photodegradation of acetophenone by bismuth ferrite nanostructures with potentially long-lasting reusability demonstrate its potential as an advanced photocatalyst for wastewater treatment.


Assuntos
Bismuto , Nanoestruturas , Acetofenonas , Bismuto/química , Catálise , Compostos Férricos , Resíduos Industriais , Luz , Nanoestruturas/química , Águas Residuárias , Água
13.
Pest Manag Sci ; 78(8): 3442-3455, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35567371

RESUMO

BACKGROUND: Paeonol is extracted and isolated as a rich and sustainable natural bioresource from the root bark of Paeonia suffruticosa, the derivatives of which exhibit numerous biological activities. It is well known that ester compounds play a very important role in pest control, such as organophosphorus, carbamate and pyrethroid pesticides. RESULTS: To discover biorational natural product-based pesticides, three series of (60) paeonol ester derivatives (7a-t, 8g,p, 9g,p, 10g-j,n-u, 11g,u, 12g,u, 13a-p, 14b,c, and 15b,c) were prepared by structural modification of paeonol, and their structures were well characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 nuclear magnetic resonance (13 C-NMR), high-resolution mass spectrometry (HRMS), and melting point. Furthermore, we assessed the compounds as insecticidal, nematicidal, and anti-oomycete agents against three serious agricultural pests, Mythimna separata, Heterodera glycines, and Phytophthora capsici. Among all tested compounds: (i) compound 8p showed more significant insecticidal activity than toosendanin, and the final mortality rates of 8p and toosendanin against M. separata (1 mg mL-1 ) were 70.4%, and 51.9%, respectively; (ii) compound 7a exhibited more promising nematicidal activity than paeonol, and the median lethal concentration (LC50 ) values of 7a and 1 against H. glycines were 15.47 and 50.80 mg L-1 , respectively; (iii) compounds 7n and 13m displayed more significant anti-oomycete activity compared to zoxamide against Phytophthora capsici, and the median effective concentration (EC50 ) values of 7n, 13m, and zoxamide were 23.72, 24.51, and 26.87 mg L-1 , respectively; and the protective effect of the compounds against Phytophthora capsici in vivo further confirmed the effectiveness of the agents. CONCLUSION: This study suggested that the introduction of a nitro at the C5 or C3 position of paeonol could improve its bioactivity against M. separata, H. glycines, and Phytophthora capsici. © 2022 Society of Chemical Industry.


Assuntos
Inseticidas , Mariposas , Praguicidas , Acetofenonas , Animais , Antinematódeos/farmacologia , Ésteres/farmacologia , Inseticidas/química , Estrutura Molecular , Praguicidas/farmacologia
14.
Molecules ; 27(10)2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35630811

RESUMO

Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite-1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime - 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite-1) or synthetized (oxime-1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10-5 M oxime-1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC50 to KCl significantly (p < 0.01) increased in the presence of oxime-1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime-1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10-7 to 10-5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10-5 M), oxime-1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime-1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite-1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite-1 and oxime-1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions.


Assuntos
Produtos Biológicos , Senécio , Acetofenonas/farmacologia , Animais , Aorta Torácica , Produtos Biológicos/farmacologia , Endotélio Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Oximas/farmacologia , Fenilefrina/farmacologia , Ratos , Vasodilatadores/química , Vasodilatadores/farmacologia
15.
Biomater Adv ; 133: 112604, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35527157

RESUMO

Acute skin injury should be treated in time, due to many factors will affect the normal healing process of wounds, hinder tissue regeneration, and eventually form chronic wounds. Herein, an injectable, in-situ gel-forming hydrogel has been fabricated. The hydrogel is stabilized by dynamic Schiff base and composed of gelatin (Gel), oxidized dextran (Odex) and apocynin (Apo). In vitro studies have shown that this hydrogel has good injectability, plasticity, self-healing and efficient hemostatic properties. The hydrogel has good cytocompatibility with HaCaT and L929 cells by the Live/Dead cell staining. Furthermore, in vivo studies have shown that hydrogel loaded with APO can accelerate angiogenesis and skin tissue regeneration by reducing wound inflammation. Therefore, the injectable Gel/Odex/Apo hydrogel has the advantages of simple preparation process, convenient use and multifunction, etc., it is a promising wound dressing for full-thickness skin repair and has great potential in the field of skin tissue regeneration.


Assuntos
Gelatina , Hidrogéis , Acetofenonas , Dextranos/farmacologia , Gelatina/farmacologia , Hidrogéis/farmacologia , Cicatrização
16.
Org Biomol Chem ; 20(18): 3742-3746, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35438123

RESUMO

A series of Bpin-containing acetophenone derivatives were reduced by asymmetric transfer hydrogenation (ATH), using Noyori-Ikariya catalysts, with formic acid/triethylamine, to alcohols in high ee when the Bpin is in the para- or meta-position. Substrates containing ortho-Bpin groups were reduced in lower ee, with formation of a cyclic boron-containing group. The products were converted to substituted derivatives using Pd-catalysed coupling reactions. The results represent the first examples of ATH of Bpin-containing ketones.


Assuntos
Ácidos Borônicos , Ésteres , Acetofenonas , Glicóis , Hidrogenação , Estereoisomerismo
17.
Int Immunopharmacol ; 108: 108736, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35364429

RESUMO

1,2 diacetyl benzene (DAB) penetrates the blood-brain barrier, causing neuroinflammation, tau hyperphosphorylation, and cognitive impairment. Converging evidence supports the anti-inflammatory effects of B vitamins on cognitive impairment, but the effects of B vitamins on cognitive impairment induced by DAB remain unclear. Here, we investigated the anti-inflammatory properties of B vitamins in DAB-stimulated human neuroblastoma SH-SY5Y cells. In this in-silico analysis, we investigated the genes, transcription factors, miRNAs, and sponges linked with DAB, B vitamins and the pathogenesis of cognitive impairment. We found vitamins B1, B2, and B3 had anti-inflammatory properties in DAB-stimulated SH-SY5Y cells, possibly via inhibiting NF-κB activation. Furthermore, vitamins B1, B2, and B3 inhibited GSK-3ß, ß-amyloid, and tau hyperphosphorylation in SH-SY5Y cells. These vitamins can also modulate genes induced by DAB (IL1B, IL6, IL10, iNOS, COX2, NFκB, GSK3B, TNF, and APP) in SH-SY5Y cells. In silico analyses, inflammatory response related pathways, "Alzheimer's disease", "pathways of neurodegeneration-multiple disease", and "prolactin signaling pathway", were highlighted. Additionally, we explored a network-based approach to identify key genes, transcription factors, miRNAs, and pathways in cognitive impairment. The transcription factors NFKB2 and BATF3 were shown to be the most important in regulating genes. We also found eight significant miRNAs related to cognitive impairment, and these miRNAs were also validated by qPCR. Finally, we developed and tested in silico miRNA sponge sequences for these miRNAs.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , MicroRNAs , Neuroblastoma , Complexo Vitamínico B , Acetofenonas/efeitos adversos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular Tumoral , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Neuroblastoma/genética , Fosforilação , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêutico , Proteínas tau/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-35378299

RESUMO

Paeonol (2'-hydroxy-4'-methoxyacetophenone) is a phenol that exhibits antioxidant and anti-inflammatory capabilities. In this study, the underlying mechanism of paeonol against LPS-induced oxidative stress and inflammatory responses in gibel carp was investigated. Three hundred healthy gibel carp were divided into five groups (n = 9), intraperitoneally injected with LPS and thereafter treated with paeonol (16 mg/kg and 64 mg/kg). Fish were anesthetized with MS-222 (100 mg/L), and samples were collected at 72 h to investigate plasma biochemical indexes, liver histopathology, antioxidant enzymatic activity, and TLR receptor-related gene expression. Fish injected with LPS (20 mg/kg) exhibited significantly increased plasma aminotransferase (ALT), aminotransferase (AST), lactate dehydrogenase (LDH), glucose (GLU), diamine oxidase (DAO), and alkaline phosphatase (ALP) levels (P < 0.05). In addition, LPS challenge significantly enhanced myeloperoxidase (MPO) and malondialdehyde (MDA) contents, whereas those of catalase (CAT) and glutathione peroxidase (GSH-Px) decreased (P < 0.05). However, treatment with paeonol attenuated these LPS-induced changes (P < 0.05). The mRNA expression of TLR4, TIRAP, MyD88, TRAF6, NF-κB, TNF-α, IL-1ß, and IL-8, which were activated by LPS challenge (P < 0.05), were downregulated by paeonol. Additionally, histopathological examination demonstrated that paeonol alleviates LPS-induced hepatic tissue lesions in fish. Taken together, the results suggest that paeonol mitigates LPS-induced liver oxidative stress and inflammation in gibel carp.


Assuntos
Carpa Dourada , Lipopolissacarídeos , Acetofenonas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Carpa Dourada/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Transaminases
19.
Mol Med Rep ; 25(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35475506

RESUMO

It has been reported that oxidative stress plays a prominent role in diabetic macrovascular diseases. 3,4­Dihydroxyacetophenone (3,4­DHAP) has been found to have a variety of biological activities. However, few studies have assessed the antioxidant capacity of 3,4­DHAP and the underlying mechanisms. Thus, the aim of the present study was to explore the effects of 3,4­DHAP on oxidative stress in human umbilical vein endothelial cells (HUVECs). HUVECs were pre­treated with 3,4­DHAP and then exposed to high glucose conditions. Cell viability and cytotoxicity were measured using an MTT assay. Reactive oxygen species (ROS) levels were measured using an inverted fluorescence microscope and a fluorescent enzyme labeling instrument. Protein expression levels of nuclear factor E2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), microtubule­associated protein 1A/1B­light chain 3 (LC3) and poly ADP­ribose polymerase­1 (PARP­1) were measured using western blotting, and mRNA expression of Nrf2 and HO­1 were measured through reverse transcription­quantitative PCR (RT­qPCR). Nrf2 nuclear translocation was evaluated using immunofluorescence analysis and autophagosomes were observed using transmission electron microscope (TEM). The results of the present study demonstrated that compared with the control group, cell viability of the high glucose group was reduced and cell cytotoxicity of the high glucose group was increased. ROS production in the high glucose group was clearly enhanced. In addition, high glucose upregulated Nrf2 and HO­1 protein and mRNA expression levels. Nuclear translocation of Nrf2 in the high glucose group was also increased. The formation of autophagosomes in the high glucose group was also higher than that in the control group. Furthermore, LC3­II/LC3­I and PARP­1 protein expression levels were increased after treatment with high glucose. However, compared to the high glucose group, 3,4­DHAP (10 µmol/l) significantly enhanced cell viability. 3,4­DHAP markedly decreased the production of ROS, increased Nrf2 and HO­1 protein and mRNA expression levels, and promoted nuclear translocation of Nrf2 in HUVECs. In addition, 3,4­DHAP promoted the formation of autophagosomes, and notably increased the protein expression levels of LC3­II/LC3­I and PARP­1. Moreover, it was determined that compared to the 3,4­DHAP group, treatment with 3,4­DHAP and ML385 enhanced cell viability, and decreased ROS production, Nrf2 and HO­1 protein and mRNA expression levels, nuclear translocation of Nrf2, and LC3­II/LC3­I and PARP­1 protein expression levels. Collectively, the results of the present study showed that 3,4­DHAP protected HUVECs against oxidative stress via regulation of the Nrf2/HO­1 pathway, by increasing autophagy and promoting DNA damage repair.


Assuntos
Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Acetofenonas , Glucose/metabolismo , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
Pharm Biol ; 60(1): 562-569, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35249458

RESUMO

CONTEXT: Paeonol (PAE) is the main phytochemical from Cortex Moutan. Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. OBJECTIVE: The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. RESULTS: Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 µm2; PAE50: 576.0 ± 53.5 µm2). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. DISCUSSION AND CONCLUSIONS: Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.


Assuntos
Acetofenonas/farmacologia , Cardiomegalia/prevenção & controle , Cardiotônicos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Animais , Aorta/fisiopatologia , Apoptose/efeitos dos fármacos , Constrição Patológica/complicações , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
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