RESUMO
The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.
Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Dislipidemias , Microbioma Gastrointestinal , Camundongos , Animais , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversos , Farmacologia em Rede , RNA Ribossômico 16S , Diabetes Mellitus Tipo 2/complicações , Obesidade/tratamento farmacológico , Obesidade/genética , Peso Corporal , Lipídeos , Insulina , Fatores de Transcrição , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Camundongos Endogâmicos C57BLRESUMO
Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/d-GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases, and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hepatócitos/fisiologia , Fígado/metabolismo , Extratos Vegetais/uso terapêutico , Estilbenos/uso terapêutico , Animais , Apoptose , Células Cultivadas , Galactosamina/imunologia , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/imunologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos , Morus/imunologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
By introducing octyloxy to C-3 and alkyl groups to C-8 of jatrorrhizine, a series of 3-octyloxy-8-alkyljatrorrhizine derivatives were synthesized and their antimicrobial activities were evaluated in vitro. The results indicated that the derivatives exhibited high antimicrobial activities, especially against Gram-positive bacteria. The 3-octyloxy-8-butyljatrorrhizine displayed the highest antimicrobial activity in all compounds. Their structure-activity relationships were discussed.