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1.
Phytomedicine ; 62: 152952, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132754

RESUMO

BACKGROUND: Although rubrofusarin-6-ß-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated. PURPOSE: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG. STUDY DESIGN: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model. METHODS: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis. RESULTS: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver. CONCLUSION: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cromonas/farmacologia , Glucosídeos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipogenia/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Serina-Treonina Quinases TOR/metabolismo
2.
Molecules ; 23(4)2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29671829

RESUMO

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed based on the inhibitory activities with α-glucosidase (IC50 13.01 µM), α-amylase (IC50 30.81 µM), and PTP1B (IC50 16.39 µM). Acankoreagenin showed better anti-diabetic effects. Then, an investigation was performed to analyze the insulin secretion effects of the insulin-secreting cell line in RIN-m5F cells. It was found that acankoreagenin could increase the insulin release in RIN-m5F cells. It was also found that acankoreagenin reduced NO production, activity of caspase-3, and the reactive oxygen species levels in the cells injured by processing of cytokines. In western blotting, inactivation of NF-κB signaling was confirmed. Acankoreagenin (20 µM) showed a higher I-κBα expression and lower NF-κB expression than the control group and showed a better expression than the positive control L-NAME (1 mM) (p < 0.05). This study demonstrates the anti-diabetic effects of acankoreagenin in vitro and suggests acankoreagenin might offer therapeutic potential for treating diabetes mellitus.


Assuntos
Eleutherococcus/química , NF-kappa B/metabolismo , Folhas de Planta/química , Triterpenos/farmacologia , Animais , Humanos , Hipoglicemiantes/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
3.
Molecules ; 23(1)2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301264

RESUMO

The phytochemical study on the leaves of Acanthopanax gracilistylus (Araliaceae) resulted in the discovery of a new lupane-triterpene compound, acangraciligenin S (1), and a new lupane-triterpene glycoside, acangraciliside S (2), as well as two known ones, 3α,11α-dihydroxy-lup-20(29)-en-23,28-dioic acid (3) and acankoreoside C (4). Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The chemical structures of the new compounds 1 and 2 were determined to be 1ß,3α-dihydroxy-lup-20(29)-en-23, 28-dioic acid and 1ß,3α-dihydroxy-lup-20(29)-en-23,28-dioic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl] ester, respectively. The anti-neuroinflammatory activity of the selective compounds, 1 and 3, were evaluated with lipopolysaccharide (LPS)-induced BV2 microglia. The tested compounds showed moderate inhibitory effect of nitric oxide (NO) production.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Eleutherococcus/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Avaliação Pré-Clínica de Medicamentos/métodos , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estrutura Molecular , Óxido Nítrico/metabolismo , Folhas de Planta/química
4.
Mol Med Rep ; 16(6): 9149-9156, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039503

RESUMO

Acanthopanax gracilistylus (AGS) has long been used in traditional Chinese medicine for the treatment of various inflammatory diseases. 3­O­ß­D­glucopyranosyl 3α, 11α­dihydroxylup­20(29)­en­28­oic acid, acantrifoside A, acankoreoside D, acankoreoside B and acankoreoside A are major lupane­type triterpenoid saponins derived from AGS. In the present study, these five saponins were isolated from AGS by chromatography and their anti­inflammatory activities were investigated in lipopolysaccharide (LPS)­treated RAW264.7 macrophages. Cell viability was evaluated by MTT assay. Tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and NF­κB p65 were measured by ELISA. The gene expression levels of TNF­α and IL­1ß was detected by reverse­transcription polymerase chain reaction. And high­mobility group box 1 (HMGB1) were analyzed by western blotting. The results demonstrated that these five saponins significantly suppressed LPS­induced expression of TNF­α and IL­1ß at the mRNA and protein level in RAW264.7 cells. Further analysis revealed that acankoreoside A and acankoreoside B were able to reduce the secretion of HMGB1 and NF­κB activity induced by LPS in RAW264.7 macrophages. Taken together, these results suggested that the anti­inflammatory activity of AGS­derived saponins may be associated with the downregulation of TNF­α and IL­1ß, and the 'late­phase' proinflammatory cytokine HMGB1, via negative regulation of the NF­κB pathway in RAW264.7 cells.


Assuntos
Proteína HMGB1/biossíntese , Interleucina-1beta/biossíntese , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Saponinas/farmacologia , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Interleucina-1beta/genética , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética
5.
Biosci Biotechnol Biochem ; 81(7): 1305-1313, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28345393

RESUMO

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.


Assuntos
Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/química , Proteína HMGB1/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Expressão Gênica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Inibidor de NF-kappaB alfa/antagonistas & inibidores , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Fosforilação/efeitos dos fármacos , Triterpenos/isolamento & purificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Zhong Yao Cai ; 34(12): 1894-7, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22500427

RESUMO

OBJECTIVE: To study the fat-soluble components in different parts of Pileostegia viburnoides. METHODS: The fat-soluble components in different parts of Pileostegia viburnoides were extracted by Herbal Blitzkrieg Extractor (HBE), and its constituents were analyzed by GC-MS. RESULTS: 37 compounds from the stems, 14 compounds from the leaves were separated and identified. The ratios of identification of total compounds were 90. 63% and 81.61%, respectively. CONCLUSION: This result provides the scientific basis for ex-ploiting resources of Miao ethnomedicine Pileostegia viburnoides.


Assuntos
Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saxifragaceae/química , Tecnologia Farmacêutica/métodos , Ésteres/análise , Gorduras/análise , Ácido Linoleico/análise , Medicina Tradicional , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Ácido Palmítico/análise , Folhas de Planta/química , Caules de Planta/química
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