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1.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638752

RESUMO

Alzheimer's disease (AD) is characterized by the deposition of ß-amyloid peptide (Aß). There are currently no drugs that can successfully treat this disease. This study first explored the anti-inflammatory activity of seven components isolated from Antrodia cinnamonmea in BV2 cells and selected EK100 and antrodin C for in vivo research. APPswe/PS1dE9 mice were treated with EK100 and antrodin C for one month to evaluate the effect of these reagents on AD-like pathology by nesting behavior, immunohistochemistry, and immunoblotting. Ergosterol and ibuprofen were used as control. EK100 and antrodin C improved the nesting behavior of mice, reduced the number and burden of amyloid plaques, reduced the activation of glial cells, and promoted the perivascular deposition of Aß in the brain of mice. EK100 and antrodin C are significantly different in activating astrocytes, regulating microglia morphology, and promoting plaque-associated microglia to express oxidative enzymes. In contrast, the effects of ibuprofen and ergosterol are relatively small. In addition, EK100 significantly improved hippocampal neurogenesis in APPswe/PS1dE9 mice. Our data indicate that EK100 and antrodin C reduce the pathology of AD by reducing amyloid deposits and promoting nesting behavior in APPswe/PS1dE9 mice through microglia and perivascular clearance, indicating that EK100 and antrodin C have the potential to be used in AD treatment.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide/metabolismo , Maleimidas , Microglia/metabolismo , Placa Amiloide , Polyporales/química , Presenilina-1/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Linhagem Celular , Maleimidas/química , Maleimidas/farmacologia , Camundongos , Camundongos Transgênicos , Microglia/patologia , Placa Amiloide/tratamento farmacológico , Placa Amiloide/genética , Placa Amiloide/metabolismo , Presenilina-1/genética
2.
Molecules ; 26(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34684816

RESUMO

The cultivation of one actinobacteria strain, Herbidospora yilanensis, was isolated from sediment samples collected from Yilan County City in Taiwan, resulting in the isolation of five previously undescribed compounds: herbidosporayilanensins A-E (1-5), and four compounds isolated from nature for the first time: herbidosporayilanensins F-I (6-9). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR experiments with those of known analogues, and on the basis of HR-EI-MS mass spectrometry, their antimycobacterial activities were also evaluated.


Assuntos
Actinobacteria/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Actinobacteria/isolamento & purificação , Antibacterianos/farmacologia , Antituberculosos/química , Antituberculosos/metabolismo , Antituberculosos/farmacologia , Sedimentos Geológicos/microbiologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Microbiologia do Solo , Taiwan
3.
Molecules ; 26(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34641311

RESUMO

Phytochemical investigation and chromatographic separation of extracts from one new actinobacteria strain Amycolatopsis taiwanensis that was isolated from soil of Yilan township, in the north of Taiwan, led to the isolation of nine new compounds, amycolataiwanensins A-I (1-9, resp.), and one new natural product, namely amycolataiwanensin J (10). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3, 5, 7 and 8 exhibited potent anti-NO production activity, with IC50 values of 17.52, 12.31, 17.81 and 13.32 µM, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.94 µM. This is the first report on indole metabolite from the genus Amycolatopsis.


Assuntos
Anti-Inflamatórios/química , Produtos Biológicos/química , Lipopolissacarídeos/efeitos adversos , Amycolatopsis/química , Amycolatopsis/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Metabolismo Secundário , Microbiologia do Solo , Taiwan
4.
Antioxidants (Basel) ; 10(9)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34573062

RESUMO

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3ß-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.

5.
Food Sci Nutr ; 9(9): 4758-4769, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34531989

RESUMO

Liver diseases, including viral hepatitis, liver cirrhosis, and liver cancer, mostly remain silent until the late stages and pose a continuing threat to millions of people worldwide. Liver transplantation is the most appropriate solution in the case of liver failure, but it is associated with hepatic ischemia and reperfusion (I/R) injury which severely reduces the prognosis of the patients. In order to ameliorate I/R injury, we investigated the potential of bracteanolide A, from the herb Tradescantia albiflora Kunth in protecting the liver from I/R injury. We first determined the protective effect of bracteanolide A against oxidative stress and DNA damage using HepG2 hepatocyte cell line and then assessed the levels of inflammatory cytokines and antioxidant proteins in response to hepatic insult using an animal model of hepatic I/R injury. The results showed bracteanolide A greatly enhanced cell survival and decreased reactive oxygen species (ROS) production under H2O2 induction. It also upregulated the expression of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and its downstream cytoprotective proteins NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Bracteanolide A effectively reduced the severity of liver lesions in I/R-injured rats revealed by histological analysis and significantly decreased the levels of alanine transaminase (ALT), aspartate transaminase (AST), cyclooxygenase-2, and inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Bracteanolide A preconditioning effectively protected the liver from I/R damage in the animal model, and this easily applied procedure may provide a new means to ameliorate hepatic I/R injury during liver surgeries.

6.
Nat Prod Res ; : 1-9, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519597

RESUMO

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

7.
Molecules ; 26(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34577123

RESUMO

Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify bioactive compounds from bitter melon leaf. Ethanolic extract of bitter melon leaf was separated into five subfractions by open column chromatography. Subfraction-5-3 significantly inhibited P. gingivalis-induced interleukin (IL)-8 and IL-6 productions in human monocytic THP-1 cells and then was subjected to separation and purification by using different chromatographic methods. Consequently, 5ß,19-epoxycucurbita-6,23(E),25(26)-triene-3ß,19(R)-diol (charantadiol A) was identified and isolated from the subfraction-5-3. Charantadiol A effectively reduced P. gingivalis-induced IL-6 and IL-8 productions and triggered receptors expressed on myeloid cells (TREM)-1 mRNA level of THP-1 cells. In a separate study, charantadiol A significantly suppressed P. gingivalis-stimulated IL-6 and tumor necrosis factor-α mRNA levels in gingival tissues of mice, confirming the inhibitory effect against P. gingivalis-induced periodontal inflammation. Thus, charantadiol A is a potential anti-inflammatory agent for modulating P. gingivalis-induced inflammation.


Assuntos
Monócitos , Porphyromonas gingivalis , Animais , Anti-Inflamatórios/farmacologia , Temperatura Alta , Camundongos , Momordica charantia , Periodontite
8.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500769

RESUMO

Ergosta-7,9(11),22-trien-3ß-ol (EK100) was isolated from the Taiwan-specific medicinal fungus Antrodia camphorata, which is known for its health-promotion and anti-aging effects in folk medicine. Alzheimer's disease (AD) is a major aging-associated disease. We investigated the efficacy and potential mechanism of ergosta-7,9(11),22-trien-3ß-ol for AD symptoms. Drosophila with the pan-neuronal overexpression of human amyloid-ß (Aß) was used as the AD model. We compared the life span, motor function, learning, memory, oxidative stress, and biomarkers of microglia activation and inflammation of the ergosta-7,9(11),22-trien-3ß-ol-treated group to those of the untreated control. Ergosta-7,9(11),22-trien-3ß-ol treatment effectively improved the life span, motor function, learning, and memory of the AD model compared to the untreated control. Biomarkers of microglia activation and inflammation were reduced, while the ubiquitous lipid peroxidation, catalase activity, and superoxide dismutase activity remained unchanged. In conclusion, ergosta-7,9(11),22-trien-3ß-ol rescues AD deficits by modulating microglia activation but not oxidative stress.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Drosophila , Humanos , Microglia/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Polyporales/química
9.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443495

RESUMO

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A-C (1-3, respectively), and three new natural products, namely (2S)-5,7,3',4'-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4-6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.


Assuntos
Actinobacteria/química , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Misturas Complexas , Flavonoides/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7
10.
Biomed Pharmacother ; 142: 112028, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34399201

RESUMO

Acute kidney disease due to renal ischemia/reperfusion (I/R) is a major clinical problem without effective therapies. The injured tubular epithelial cells may undergo epithelial-mesenchymal transition (EMT). It will loss epithelial phenotypes and express the mesenchymal characteristics. The formation of scar tissue in the interstitial space during renal remodeling is caused by the excessive accumulation of extracellular matrix components and induced fibrosis. This study investigated the effect of caffeic acid ethanolamide (CAEA), a novel caffeic acid derivative, on renal remodeling after injury. The inhibitory role of CAEA on EMT was determined by western blotting, real-time PCR, and immunohistochemistry staining. Treating renal epithelial cells with CAEA in TGF-ß exposed cell culture successfully maintained the content of E-cadherin and inhibited the expression of mesenchymal marker, indicating that CAEA prevented renal epithelial cells undergo EMT after TGF-ß exposure. Unilateral renal I/R were performed in mice to induce renal remodeling models. CAEA can protect against I/R-induced renal remodeling by inhibiting inflammatory reactions and consecutively inhibiting TGF-ß-induced EMT, characterized by the preserved E-cadherin expression and alleviated α-SMA and collagen expression, as well as the alleviated of renal fibrosis. We also revealed that CAEA may exhibits biological activity by targeting TGFBRI. CAEA may antagonize TGF-ß signaling by interacting with TGFBR1, thereby blocking binding between TGF-ß and TGFBR1 and reducing downstream signaling, such as Smad3 phosphorylation. Our data support the administration of CAEA after I/R as a viable method for preventing the progression of acute renal injury to renal fibrosis.

11.
Chem Biodivers ; 18(8): e2100211, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34323355

RESUMO

Cultivation of the actinobacteria strain Isoptericola chiayiensis, a mangrove-derived actinobacteria that was isolated from a mangrove soil collected in Chiayi County, resulted in the isolation of one new 2-furanone derivative, isopterfuranone (1), one new sesquiterpenoid, isopterchiayione (2), one new benzenoid derivative, isopterinoid (3), five new flavonoids, chiayiflavans A-E (4-8), and 4 metabolites isolated for the first time from nature source, methyl 3-(4-methyl-2,5-dioxopyrrolidin-3-yl)propanoate (9), 3-ethyl-4-methylpyrrolidine-2,5-dione (10), chiayiensol (11) and chiayiensic acid (12). Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. Most of the isolates showed potent inhibitory effects on NO production in LPS-stimulated RAW 264.7 murine macrophages cells with IC50 values ranging from 9.36 to 40.02 µM. Of these isolates, 4 and 5 showed NO inhibitory activity with IC50 values of 17.14 and 9.36 µM, stronger than the positive control quercetin (IC50 =36.95 µM). This is the first report on flavan metabolites from the genus Isoptericola.


Assuntos
Actinobacteria/química , Flavonoides/química , Sesquiterpenos/química , Actinobacteria/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Microbiologia do Solo
12.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204506

RESUMO

Ergosta-7, 9 (11), 22-trien-3ß-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-κB reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (IκB)/NF-κB signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-κB reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-κB inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila.


Assuntos
Anti-Inflamatórios/farmacologia , Drosophila/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Antígeno 96 de Linfócito/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Receptores de Lipopolissacarídeos/química , Lipopolissacarídeos/química , Lipopolissacarídeos/imunologia , Antígeno 96 de Linfócito/química , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Ligação Proteica , Relação Estrutura-Atividade , Receptor 4 Toll-Like/química
13.
Molecules ; 26(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067678

RESUMO

Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3ß-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Ergosterol/análogos & derivados , Ergosterol/farmacologia , Animais , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Ciclo-Oxigenase 2/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Polyporales/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
J Nat Prod ; 84(7): 1898-1903, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34185528

RESUMO

Theissenia cinerea 89091602 is a previously reported plant-derived bioactive fungal strain, and the active principles separated from the extracts of its submerged culture were shown to exhibit potent anti-neuroinflammatory activities in both cellular study and animal testing. In a continuation of our previous investigation on the bioactive entities from this fungus, solid state fermentation was performed in an attempt to diversify the bioactive secondary metabolites. In the present study, five previously unreported polyketides, theissenophenol (1), theissenepoxide (2), theissenolactone D (3), theissenone (4), and theissenisochromanone (5), together with the known theissenolactone B (6), theissenolactone C (7), and arthrinone (8), were isolated and characterized through spectroscopic analysis and comparison with the literature data. The configurations of theissenepoxide (2) and theissenisochromanone (5) were further corroborated by single-crystal X-ray diffraction data analysis. Theissenone (4), theissenolactone B (6), theissenolactone C (7), and arthrinone (8) exhibited potent nitric oxide production inhibitory activities in murine brain microglial BV-2 cells with IC50 values of 5.0 ± 1.0, 4.5 ± 0.6, 1.1 ± 0.1, and 3.2 ± 0.3 µM, respectively, without any significant cytotoxic effects.

15.
Biochem Biophys Rep ; 26: 101020, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34041372

RESUMO

Alzheimer's disease (AD) is characterized by accumulation of ß-amyloid (Aß) in senile plaques, contributing to oxidative stress, mitochondrial diseases, and synaptic atrophy, consequently leading to the deterioration of brain function. Adlay (Coix lacryma-jobi L.) is an annual botanical. Here, a 95% ethanol extract of adlay hull (AHEE) was partitioned by ethyl acetate (AHEAE), n-butanol (AHBUE), and water (AHWE), and the effects of these extracts on lipopolysaccharide (LPS)-induced RAW264.7 cells and Aß-induced PC12 cells, as experimental models of neurotoxicity, were evaluated. The expression of anti-inflammatory and antiapoptosis-related proteins was investigated and AHEE, AHEAE, and AHWE were found to exert anti-inflammatory effects. AHWE exhibited antiapoptotic effects and inhibited inducible nitric oxide synthase expression and nitric oxide production. We investigated the protective effects of AHWE against Aß-induced neurotoxicity in dPC12 cells and explored the underlying mechanism. Pretreatment with AHWE significantly attenuated cell death and Aß-mediated increase in B cell lymphoma (Bcl)-2/Bax ratio. AHWE significantly inhibited Aß and enhanced protein kinase B (Akt) level in dPC12 cells, suggesting that its protective effect against Aß-induced apoptosis in dPC12 cells was mediated through upregulation of the phosphoinositide 3-kinases (PI3K)/Akt signaling pathway. These extracts and its bioactive compound K36-21 may be potentially useful to treat neurodegenerative disorders.

16.
Prev Nutr Food Sci ; 26(1): 58-66, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33859960

RESUMO

Hepatic ischemia/reperfusion (IR) injury is a complication that occurs during liver surgery, whereby hepatic tissue is injured by oxygen deficiency during ischemia, then further damaged by a cascade of inflammatory and oxidative insults when blood is resupplied during reperfusion. Antrodia camphorata is an indigenous fungus in Taiwan and an esteemed Chinese herbal medicine with various bioactivities. This study examined the effect of ergostatrien-3ß-ol (EK100), an active compound found in both the fruiting body and mycelia of A. camphorata, on IR injury pathologies in rats and cell models of oxidative and inflammatory stress. Male Sprague-Dawley rats were randomly assigned to receive a vehicle or 5 mg/kg EK100 prior to hepatic IR injury induced by 1 h ischemia followed by 24 h reperfusion, or a sham operation. RAW 264.7 murine macrophages and HepG2 hepatocytes were pretreated with EK100, then inflammation was induced with lipopolysaccharides in the former and oxidative stress was induced with hydrogen peroxide in the latter. EK100 decreased IR-induced elevation in serum levels of alanine aminotransferase and aspartate aminotransferase and lowered levels of the inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß. In addition, EK100 significantly reduced hepatic mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, as well as nitrite production and iNOS gene expression in both hepatocyte and macrophage cell lines. We demonstrated that EK100 exhibits potent protec-tion against hepatic IR injury, which may be used to design strategies to ameliorate liver damage during liver surgery.

17.
Plants (Basel) ; 10(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917957

RESUMO

Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and superoxide anion (O2-•), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities.

18.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802228

RESUMO

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3ß), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics.


Assuntos
Ácidos Cafeicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Epiderme/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanócitos/metabolismo , Melanossomas/metabolismo , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases/genética , Melanossomas/genética
19.
Nat Prod Res ; 35(12): 2028-2036, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31496280

RESUMO

One new naturally occurring quinone, 3',4'-dihydroxy-1,2,6-trimethoxy-[1,1'-biphenyl]-4(1H)-one (1), one new diarylpropane, emarginone A (2), and one new neolignan, emarginone B (3), along with eighteen known compounds have been isolated from the chemical investigation of the EtOAc-soluble fraction of the Vaccinium emarginatum whole plant methanolic extract. The new structures were elucidated by combined analysis of spectroscopic analytical methods and comparison with the literature data obtained from known analogues. In addition, the cytotoxicity of compounds 2, 4, and 14-20 against Du145 and PC-3 prostate cancer cell lines using MTT cell proliferation assay was evaluated. Compounds 2 and 19 showed most potent cytotoxicity against Du145 with IC50 values of 7.53 and 6.63 µg/mL, respectively. Furthermore, compounds 2, 17, and 19 also exhibited significant cytotoxicity against PC-3 with IC50 values ranging from 3.44-6.64 µg/mL.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Vaccinium/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Células PC-3 , Fenilpropionatos/química , Fenilpropionatos/farmacologia , Extratos Vegetais/química , Neoplasias da Próstata/patologia , Quinonas/química , Quinonas/farmacologia
20.
Molecules ; 25(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172041

RESUMO

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4-15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial ß-Glucuronidase (ßG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-ßG inhibitors with no effect on human ßG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-ßG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial ßG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial ßG but not human ßG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucuronidase/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/metabolismo , Glucuronidase/metabolismo , Humanos , Lauraceae/química , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
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