RESUMO
BACKGROUND: Using a thread for wound closure promotes healing and minimizes contamination by foreign substances. Threads have also been employed in esthetic surgery; however, functional threads that can improve wrinkles and rejuvenate the skin are required. OBJECTIVE: To evaluate the suitability of polydioxanone threads coated with polyethylene glycol, hyaluronic acid, and amino acids for use in the medical field because such formulations are expected to promote regeneration and collagen synthesis. MATERIALS AND METHODS: Physical properties (diameter [ n = 20], tensile strength [ n = 20], strength retention rate [ n = 10], and scanning electron microscopy images) and cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays) of polydioxanone threads coated with polyethylene glycol, hyaluronic acid, and amino acids were assessed and compared with those of uncoated polydioxanone threads. Analyses were performed using IBM SPSS Statistics (Statistical significance; p values <.05). RESULTS: The size standards for tensile strength (≥63.5 N) and diameter (average 0.570-0.610 mm) were met. There were no differences in the physical properties of the coated and uncoated threads; however, the biocompatibility of coated threads was high owing to low cytotoxicity. CONCLUSION: Threads coated with materials that can promote regeneration are suitable for use in the medical field.
Assuntos
Polidioxanona , Ritidoplastia , Humanos , Ácido Hialurônico , Ritidoplastia/métodos , Aminoácidos , Polietilenoglicóis , SuturasRESUMO
BACKGROUND: Sexually transmitted infections (STIs) can have serious consequences, and the global STI incidence remains high. However, there is little information on the frequency of STIs with multiple pathogens according to age. Accordingly, we conducted a study to determine the trends of coinfection with sexually transmitted pathogens according to age in the Republic of Korea from 2018 to 2020. METHODS: From January 2018 to December 2020, 65,191 samples of swab, urine, and other types submitted for STI screening were obtained from U2Bio Co. Ltd. (Seoul, Republic of Korea). Multiplex polymerase chain reaction, a sensitive and rapid method for simultaneous detection of STIs caused by multiple different pathogens, was performed using an AccuPower STI4C-Plex Real-Time PCR kit, AccuPower STI8A-Plex Real-Time PCR kit, and AccuPower STI8B-Plex Real-Time PCR kit with an Exicycler 96 Real-Time Quantitative Thermal Block. RESULTS: Of the 65,191 samples tested, 35,366 (54.3%) tested positive for one or more sexually transmitted pathogens. The prevalence of coinfections with two or more sexually transmitted pathogens was inversely proportional to age. Furthermore, the rates of coinfection with sexually transmitted pathogens and age distribution differed according to sex and the sexually transmitted pathogen type. CONCLUSION: This study confirmed that a significant proportion of patients with STIs are coinfected with multiple pathogens. Public health managers could use these results to recognize and prevent STIs according to age.
Assuntos
Coinfecção , Infecções Sexualmente Transmissíveis , Coinfecção/epidemiologia , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
Previously, we isolated six heterocyclic compounds (1-6) from the fruits of mulberry trees (Morus alba L.) and determined that loliolide affords rat pancreatic islet ß-cell (INS-1) protection against streptozotocininduced cytotoxicity. In the present study, we further investigated the effect of the six heterocyclic compounds (1-6) on glucose-stimulated insulin secretion (GSIS) in INS-1 cells. Among them, (R)5hydroxypyrrolidin2one(1) and indole (6) increased GSIS without inducing cytotoxicity. Additionally, compounds 1 and 6 enhanced the phosphorylation of total insulin receptor substrate-2, phosphatidylinositol 3-kinase, and Akt, and activated pancreatic and duodenal homeobox-1, which play a crucial role in ß-cell functions related to insulin secretion. Collectively, these findings indicate that (R)5hydroxypyrrolidin2one(1) and indole (6), isolated from M. alba fruits, may be beneficial in managing type 2 diabetes.
Assuntos
Glucose/antagonistas & inibidores , Compostos Heterocíclicos/farmacologia , Hipoglicemiantes/farmacologia , Secreção de Insulina/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucose/farmacologia , Compostos Heterocíclicos/química , Hipoglicemiantes/química , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
Hepatic fibrosis is a chronic liver disease characterized by the accumulation of extracellular matrix (ECM). Activation of hepatic stellate cells (HSCs) after repetitive liver damage is a key event in hepatic fibrogenesis. As part of ongoing research projects to identify pharmacologically effective natural products, the phytochemical investigation of a MeOH extract of Centipeda minima led to the isolation of a sesquiterpene lactone, brevilin A, which was explored to elucidate potential anti-fibrotic effects by reversing HSC activation. First, we observed that transforming growth factor (TGF)-ß1 treatment significantly increased the expression levels of HSC activation marker, α-smooth muscle actin (α-SMA), and ECM protein such as collagen and fibronectin. Then, we demonstrated that brevilin A reversed the TGF-ß1-induced increase in protein and mRNA expression levels of α-SMA and collagen. To investigate the underlying molecular mechanism of brevilin A, we evaluated the effects of brevilin A on the STAT3 signaling pathway. STAT3 phosphorylation, increased by TGF-ß1 treatment, was strongly inhibited by brevilin A; the expression levels of fibronectin and connective tissue growth factor were also significantly decreased by brevilin A. The present study indicated that brevilin A has a preventive and therapeutic potential against hepatic fibrosis.
Assuntos
Crotonatos/farmacologia , Desenho de Fármacos , Cirrose Hepática/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Sesquiterpenos/farmacologia , Crotonatos/química , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Estrutura Molecular , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Bioactivity-driven LC/MS-based phytochemical analysis of the root bark extract of Ulmus davidiana var. japonica led to the isolation of 10 compounds including a new coumarin glycoside derivative, ulmusakidian (1). The structure of the new compound was elucidated using extensive spectroscopic analyses via 1D and 2D NMR spectroscopic data interpretations, HR-ESIMS, and chemical transformation. The isolated compounds 1-10 were tested for their antifungal activity against human fungal pathogens Cryptococcus neoformans and Candida albicans. Compounds 9 and 10 showed antifungal activity against C. neoformans, with the lowest minimal inhibitory concentration (MIC) of 12.5-25.0 µg/mL, whereas none of the compounds showed antifungal activity against C. albicans.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Ulmus/química , Antifúngicos/química , Antifúngicos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Relação Estrutura-AtividadeRESUMO
Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC50 = 32 ± 1.06 µM) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.
Assuntos
Resistência à Insulina/fisiologia , Florizina/farmacologia , Proteínas Tirosina Fosfatases não Receptoras/antagonistas & inibidores , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Células 3T3 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Camundongos , Palmitatos/farmacologia , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Pinus koraiensis pinecones are considered an undesired waste by-product of the processing of seeds. However, recent studies of the potential anti-tumor effects of the pinecones have led to increasing interest in their chemical constituents. The present study examined the potential antiangiogenic effects of the constituents of pinecones and further characterized their underlying mechanisms of action. Chemical investigation of a water extract of P. koraiensis pinecones led to the isolation and identification of the eight main components including five diterpenoids (1-5), two monoterpenes (6,7) and a phenolic acid (8). The structure of the compounds was determined by spectroscopic analysis of NMR spectra and LC/MS analysis. Of the isolated compounds, 7α,15-dihydroxydehydroabietic acid (5) significantly inhibited the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5 inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK signaling pathways. These results provide experimental evidence of a novel biological activity of 7α,15-dihydroxydehydroabietic acid (5) as a potential antiangiogenic substance. This study also suggests that compound 5 could potentially be a useful adjuvant therapeutic substance for cancer prevention and treatment.
Assuntos
Abietanos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Pinus/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Abietanos/síntese química , Abietanos/química , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Estrutura Molecular , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The fruit of the white mulberry tree (Morus alba L.) is a multiple fruit with a sweet flavor commonly consumed around the world. Chemical investigation of the fruits led to the isolation of two indole acetic acid derivatives (1â¯-2) including a new compound, which turned out to be an isolation artifact, 3S-(ß-D-glucopyranosyloxy)-2,3-dihydro-2-oxo-1H-indole-3-acetic acid butyl ester (1), along with five known compounds (3â¯-7). Compounds 2 and 7 were newly identified from mulberry fruit. The new isolation artifact (1) exhibited cytotoxic effect on human cervical cancer Hela cells in a dose-dependent manner. Compound 1 activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Simultaneous alterations in protein expression of mitochondrial factors Bax, BID and Bcl-2 were also observed. A comparison between compounds 1 and 2 led to a structure-activity relationship analysis of the cytotoxic effect. These results suggest that compound 1 could be beneficial in human cervical cancer treatment, and provide a theoretical basis for further application of compound 1.
Assuntos
Antineoplásicos/farmacologia , Glucosídeos/farmacologia , Ácidos Indolacéticos/farmacologia , Morus/química , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Caspase 8/metabolismo , Caspase 9/metabolismo , Feminino , Frutas/química , Glucosídeos/química , Glucosídeos/isolamento & purificação , Células HeLa , Humanos , Ácidos Indolacéticos/química , Ácidos Indolacéticos/isolamento & purificação , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Guggulsterone derivatives were prepared using [3+2] click chemistry with aryl and alkyl acetylene. The series of derivatives were evaluated for their cellular protective effects on cisplatin-treated cultured LLC-PK1 kidney epithelial cells. Among the guggulsterone-triazole derivatives, compound 6g, which contains a hydroxyl methyl group, was the most active of all the derivatives. In an additional study, we determined that inhibition of the mitogen-activated protein kinase/caspase-3 signaling cascade by 6g mediates its protective effects against cytotoxicity in cultured LLC-PK1 cells.
Assuntos
Apoptose/efeitos dos fármacos , Pregnenodionas/química , Substâncias Protetoras/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Caspase 3/química , Caspase 3/metabolismo , Cisplatino/farmacologia , Química Click , Rim/citologia , Rim/efeitos dos fármacos , Rim/metabolismo , Células LLC-PK1 , Microscopia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Pregnenodionas/farmacologia , Substâncias Protetoras/química , Transdução de Sinais/efeitos dos fármacos , SuínosRESUMO
Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner.
Assuntos
Antineoplásicos/farmacologia , Taninos Hidrolisáveis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Taninos Hidrolisáveis/síntese química , Taninos Hidrolisáveis/química , Células MCF-7 , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3ß-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100µM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These results indicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.
Assuntos
Apoptose/efeitos dos fármacos , Basidiomycota/química , Cisplatino/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Triterpenos/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Estrutura Molecular , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Relação Estrutura-Atividade , Suínos , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Calvatia species, also known as puffball mushrooms, are common sources of food worldwide. Calvatia nipponica (Agaricaceae) is one of the most rare species in the Calvatia genus. It was first validated in 2008. Due to its scarcity, C. nipponica has never been chemically investigated. Its recent discovery in Korea allowed to conduct this study, and using bioactivity-guided fractionation for antiangiogenic activity, chemical investigation of the MeOH extract of the fruiting bodies of C. nipponica led to the isolation of five alkaloids (1-5) and two phenolic compounds (6-7). This is the first study to report the chemical investigation of C. nipponica, and compound 1 was previously reported as chemically synthesized only until our report of its isolation and identification from natural sources. The structure of 1 was determined by spectroscopic analysis by 1D and 2D NMR spectra and HR-MS. All compounds (1-7) were tested for inhibition of angiogenesis using human umbilical vein endothelial cells (HUVECs). Compounds 2, 4 and 5 significantly inhibited the promotion of angiogenesis in HUVECs. Compound 5 showed the most potent inhibition via downregulation of VEGF, p38 and ERK signaling pathways. These results suggested that the rare mushroom C. nipponica might be beneficial in antiangiogenesis therapy for cancer treatment.
Assuntos
Agaricales/química , Inibidores da Angiogênese/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Neovascularização Patológica/patologia , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3pro) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship. RESULTS: ZIKV NS2B-NS3pro was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K m of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3pro was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3pro by 6.2-88%. Seven polyphenol compounds had IC50 ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3pro protease. Its IC50 value was 22 ± 0.2 µM with a K i value of 8.9 ± 1.9 µM. CONCLUSION: The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3pro can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3pro.
Assuntos
Flavonoides/química , Flavonoides/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Zika virus/enzimologia , Eletroforese em Gel de Poliacrilamida , Polifenóis/química , Polifenóis/farmacologia , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/metabolismoRESUMO
The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (1-3), a sesquiterpene (4), two steroids (5-6), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 1-3 had IC50 values <10 µM. Treatment of LPS-stimulated RAW264.7 cells with compounds 1-3 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 1-3 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 1-3 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 1-3 could be promising lead compounds for the development of novel anti-inflammatory agents.
Assuntos
Fungos/química , Fenóis/química , Animais , Anti-Inflamatórios , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7RESUMO
CONTEXT: Antiacetylcholinesterase (AChE) drugs have been a main therapeutic treatment for Alzheimer's disease because increased AChE levels play a key role in reducing neurotransmission. OBJECTIVES: Extracts from 35 Korean plants were selected and screened for antioxidant and anti-cholinesterase activity to explore new sources derived from Korean natural resources that could be used as AD therapeutic agents. MATERIALS AND METHODS: The antioxidant effect of extracts from 35 selected Korean plants was determined using two most common free radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS). Additionally, the effect of extracts, identified as antioxidants, on acetylcholinesterase inhibition was assessed by an acetylcholinesterase assay kit. RESULTS: Out of 36 extracts of 35 plants tested, Oenothera biennis L. (9.09 µg/mL), Saururus chinensis (Lour.) Baill. (9.52 µg/mL) and Betula platyphylla var. japonica (9.85 µg/mL) showed strong DPPH scavenging activity. Twelve other extracts also exerted moderate free radical scavenging activities with IC50 values ranging from 10 to 50 µg/mL. Antioxidant capacity detected by ABTS assay was only significant in O. biennis (23.40 µg/mL), while the other extracts were weak or unable to reduce the production of ABTS. Based on the antioxidant activities of these plant extracts, 19 extracts with IC50 values less than 100 µg/mL in DPPH assay were selected for further AChE inhibition assay. Among the extracts tested, the IC50 value for Prunella vulgaris var. lilacina NAKAI (18.83 µg/mL) in AChE inhibitory activity was the lowest, followed by O. biennis (20.09 µg/mL) and Pharbitis nil Chosy (22.79 µg/mL). CONCLUSIONS: Considering complex multifactorial etiology of AD, the extracts of P. vulgaris var. lilacina (aerial part), O. biennis (seed) and P. nil (seed) may be safe and ideal candidates for future AD modifying therapies.
Assuntos
Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Acetilcolinesterase/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Técnicas In Vitro , Concentração Inibidora 50 , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , República da CoreiaRESUMO
Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 µM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.
Assuntos
Berberidaceae/química , Ácidos Cafeicos/química , Endotélio/efeitos dos fármacos , Frutas/química , Glucosídeos/química , Lipopolissacarídeos , Extratos Vegetais/farmacologia , Animais , Ácidos Cafeicos/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio/imunologia , Glucosídeos/farmacologia , Humanos , Inflamação/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Veratrum nigrum is recognized as a medicinal plant used for the treatment of hypertension, stroke, and excessive phlegm. Chemical investigation of the roots and rhizomes led to the isolation of five new steroidal alkaloids, jervine-3-yl formate (1), veramarine-3-yl formate (2), jerv-5,11-diene-3ß,13ß-diol (3), (1ß,3ß,5ß)-1,3-dihydroxyjervanin-12(13)-en-11-one (4), and veratramine-3-yl acetate (5). Compounds 1 and 5 exhibited potent inhibitory activity (11.3 and 4.7 µM, respectively) against protein tyrosine phosphatase 1B (PTP1B), which has emerged as a viable target for treatment of type 2 diabetes mellitus. On the basis of their PTP1B inhibitory activity, the compounds were evaluated for their potential to enhance glucose uptake in C2C12 skeletal muscle cells. The insulin-stimulated glucose uptake was enhanced upon treatment with compounds 1 and 5 (10 µM) by 49.9 ± 6.5% and 56.0 ± 9.7%, respectively, in a more potent manner than that with the positive control rosiglitazone (47.3 ± 3.4% at 30 µM). These results suggest that steroidal alkaloids serve as practical antidiabetes mellitus leads capable of enhancing glucose uptake.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Glucose/metabolismo , Plantas Medicinais/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Veratrum/química , Alcaloides/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estrutura Molecular , Músculo Esquelético/metabolismo , Raízes de Plantas/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , República da Coreia , Rizoma/química , Rosiglitazona , Estereoisomerismo , Esteroides/química , Tiazolidinedionas/farmacologiaRESUMO
Neuraminidase (NA) is one of the two glycoproteins on the surface of influenza virus, which cleaves terminal sialic acid residues and facilitates the release of virions from infected cells. The recombinant NA from H5N1 influenza virus strain A/Vietnam/1203/04 was expressed in Pichia pastoris X33 as a 45 kDa protein that displayed a K m of 9.96 ± 1.26 µM with fluorogenic substrate, 2'-(4-methylumbelliferyl)-α-D-N-acetyl neuraminic acid. Partially purified NA was used for the inhibition and kinetic assays with eight flavonoid compounds and gallic acid. Among them, gallocatechin gallate (GCG) showed the best inhibition against NA with the IC50 of 8.98 ± 0.46 µM and showed a competitive inhibition pattern with K i value of 8.34 ± 0.25 µM. In molecular docking experiments, GCG displayed a binding energy of -13.71 kcal/mol to the active site of NA and the galloyl moiety was required for NA inhibition activity.
RESUMO
Introduction: The coronavirus disease 2019 (COVID-19) pandemic may have influenced the prevalence and seasonality of acute respiratory viral infections. The aim of the study was to investigate the prevalence of all viruses causing acute viral respiratory infections before and after social distancing measures were lifted. Methods: Cross-sectional study where outpatients and inpatients at Kyunghee University Hospital were examined. From January 2021 to December 2022, respiratory samples were analyzed using multiplex reverse transcriptase real-time polymerase chain reaction. Results: Of 3953 samples obtained, 412 (10.42%) were positive for acute respiratory viral infection, and 502 viruses were detected. The number of viral infections increased from 184 in 2021 to 318 in 2022. Human metapneumovirus was detected from August to November 2022. Human bocavirus (HBoV) was frequently detected from April to June 2021; however, in 2022, HBoV was frequently detected from July to October. Human parainfluenza virus 3 was rarely detected after its initial frequent detection from October to December 2021 but was continuously observed after frequent detection in September 2022. Co-infection occurred in 78 (18.9%) cases. The most common combination of simultaneous infections was human rhinovirus-HBoV (n = 30, 38.5%). Conclusions: During the COVID-19 pandemic, the incidence of acute respiratory viral infection decreased significantly but increased in 2022 when measures were lifted. The prevalence and seasonality of respiratory viral infections have changed since the pandemic. Our findings contribute to the prediction of an effective response to changes in the prevalence of respiratory viruses.
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STUDY DESIGN: A retrospective, single-center study. OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a newly developed extensive dome-like laminoplasty using en bloc resection of the C2 inner lamina in patients with severe cord compression behind the C2 body. SUMMARY OF BACKGROUND DATA: A surgery for severe cord compression behind C2 body is challenging for spinal surgeons. To date, there has been no established solution for severe cord compression behind the C2 body. MATERIALS AND METHODS: Patients with severe cord compression behind the C2 body who underwent posterior surgery consecutively were enrolled. Extensive dome-like laminoplasty that was newly developed was performed to remove en bloc removal of the C2 inner lamina were performed. Preoperative and postoperative canal diameters behind the C2 and mean removed area of the C2 inner lamina were measured using MRI and CT scan. Clinical and radiographic parameters were assessed preoperative and postoperative periods. In addition, perioperative complications were analyzed. RESULTS: A total of 36 patients underwent extensive dome-like laminoplasty and their diagnoses were ossification of the posterior longitudinal ligament (OPLL, 66.7%) and congenital stenosis with spondylosis (33.3%). The mean canal diameter behind the C2 increased from 9.85 (2.28) mm preoperatively to 19.91 (3.93) mm at the last follow-up ( P <0.001). Clinically, neck and arm visual analog scale, Japanese Orthopaedic Association score, and neck disability index significantly improved at postoperative 1 month ( P <0.05), and the scores were maintained until the last follow-up. No meaningful radiographic changes occurred after the surgeries. During the procedures, there were no particular complications, but one patient showed deteriorated myelopathic symptoms and underwent additional C1-C2 decompressive surgery. CONCLUSIONS: After extensive dome-like laminoplasty, surgical outcomes are satisfactory, and complications are rare. This technique may be a viable option for patients with severe cord compression behind the C2 body. LEVEL OF EVIDENCE: Level IV.