RESUMO
Peony pollen contains multiple nutrients and components and has been used as a traditional Chinese medicine with a long history, but the effect of the treatment of primary dysmenorrhea remains to be clarified. The aim of this study is to investigate the therapeutic effect of peony pollen on primary dysmenorrhea mice and the potential mechanism. A uterus contraction model in vitro and primary dysmenorrhea mice were used to evaluate the treatment effect of peony pollen on primary dysmenorrhea. The primary dysmenorrhea mice were treated with 62.5 mg/kg, 125 mg/kg, or 250 mg/kg of peony pollen, and the writhing response, latency period, histopathological changes in the uterus, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) levels, and infiltration of neutrophils and macrophages were investigated. Protein expression of interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase 1 (mPGEs-1), BCL2-Associated X (Bax), B-cell lymphoma-2 (BCL-2), caspase-3, and cleaved caspase-3 were detected by Western blot, and the oxidative stress related marker malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were evaluated. Peony pollen could attenuate spontaneous or oxytocin-induced uterus contractions in vitro. Moreover, peony pollen decreased the writhing times, prolonged the writhing latency, and reduced the pathological damage of uterine tissues. Furthermore, the inflammatory cell infiltration and the protein expression of IL-1ß, IL-6, and NLRP3 were decreased. The COX-2/PGE2 pathway was inhibited; oxidative stress and apoptosis in the uterus also improved in the uterus of primary dysmenorrhea mice. Peony pollen exerts a positive effect on primary dysmenorrhea by inhibiting the inflammatory response and modulating oxidative stress and apoptosis by regulating the COX-2/PGE2 pathway.
Assuntos
Dinoprostona , Paeonia , Humanos , Feminino , Camundongos , Animais , Dinoprostona/metabolismo , Dismenorreia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Caspase 3 , Paeonia/metabolismo , Interleucina-6/efeitos adversos , Dinoprosta/metabolismoRESUMO
Neurodegenerative diseases are explained by progressive defects of cognitive function and memory. These defects of cognition and memory dysfunction can be induced by the loss of brain-derived neurotrophic factors (BDNF) signaling. Paeonia lactiflora is a traditionally used medicinal herb in Asian countries and some beneficial effects have been reported, including anti-oxidative, anti-inflammatory, anti-cancer activity, and potential neuroprotective effects recently. In this study, we found that suffruticosol A is a major compound in seeds of Paeonia lactiflora. When treated in a SH-SY5 cell line for measuring cell viability and cell survival, suffruticosol A increased cell viability (at 20 µM) and recovered scopolamine-induced neurodegenerative characteristics in the cells. To further confirm its neural amelioration effects in the animals, suffruticosol A (4 or 15 ng, twice a week) was administered into the third ventricle beside the brain of C57BL/6 mice for one month then the scopolamine was intraperitoneally injected into these mice to induce impairments of cognition and memory before conducting behavioral experiments. Central administration of suffruticosol A into the brain restored the memory and cognition behaviors in mice that received the scopolamine. Consistently, the central treatments of suffruticosol A showed rescued cholinergic deficits and BDNF signaling in the hippocampus of mice. Finally, we measured the long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse to figure out the restoration of the synaptic mechanism of learning and memory. Bath application of suffruticosol A (40 µM) improved LTP impairment induced by scopolamine in hippocampal slices. In conclusion, the central administration of suffruticosol A ameliorated neuronal effects partly through elevated BDNF signaling.
Assuntos
Paeonia , Escopolamina , Camundongos , Animais , Escopolamina/farmacologia , Paeonia/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Aprendizagem em LabirintoRESUMO
Seed oil not only provides energy for seed postgermination development but also provides essential nutrients and raw materials for human products. However, the transcriptional regulatory mechanism controlling seed oil accumulation remains largely unknown. Tree peony (Paeonia rockii) is an emerging woody oilseed crop in China that is known for its high-quality seed oil. Here, we revealed that a tree peony nuclear factor Y transcription factor, PrNF-YC2, is expressed predominantly in developing seeds and functions as an essential positive regulator of seed oil accumulation. PrNF-YC2 promoted oil accumulation in both transient ectopic overexpression Nicotiana benthamiana leaves and stable transgenic Arabidopsis thaliana seeds, globally upregulating the expression of genes involved in oil accumulation. In contrast, PrNF-YC2-silenced tree peony leaves using a virus-induced gene silencing system showed reduced oil content and expression of oil synthesis-related genes, including four master positive regulators contributing to oil accumulation, namely, LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and WRINKLED1 (WRI1). We demonstrated that PrNF-YC2 directly activates PrLEC1 and PrABI3 alone and indirectly activates PrFUS3 and PrWRI1 by interacting with PrLEC1. Moreover, interaction with PrLEC1 also enhances the activation capacity of PrNF-YC2. The activation of these four master positive regulators by PrNF-YC2 triggered the upregulation of numerous oil synthesis-related genes, thus promoting oil accumulation. These findings provide new insights into the regulatory mechanism of seed oil accumulation and manipulation of PrNF-YC2 may be beneficial for enhancing oil yield in tree peony and other oilseed crops.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Paeonia , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Paeonia/genética , Paeonia/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Sementes/metabolismo , Óleos de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMO
Suffruticosol B (Suf-B) is a stilbene found in Paeonia suffruticosa ANDR., which has been traditionally used in medicine. Stilbenes and their derivatives possess various pharmacological effects, such as anticancer, anti-inflammatory, and anti-osteoporotic activities. This study aimed to explore the bone-forming activities and mechanisms of Suf-B in pre-osteoblasts. Herein, >99.9% pure Suf-B was isolated from P. suffruticosa methanolic extracts. High concentrations of Suf-B were cytotoxic, whereas low concentrations did not affect cytotoxicity in pre-osteoblasts. Under zero levels of cytotoxicity, Suf-B exhibited bone-forming abilities by enhancing alkaline phosphatase enzyme activities, bone matrix calcification, and expression levels with non-collagenous proteins. Suf-B induces intracellular signal transduction, leading to nuclear RUNX2 expression. Suf-B-stimulated differentiation showed increases in autophagy proteins and autophagosomes, as well as enhancement of osteoblast adhesion and transmigration on the ECM. These results indicate that Suf-B has osteogenic qualities related to differentiation, autophagy, adhesion, and migration. This also suggests that Suf-B could have a therapeutic effect as a phytomedicine in skeletal disorders.
Assuntos
Paeonia , Estilbenos , Osteogênese , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteoblastos/metabolismo , Autofagia , Paeonia/metabolismo , Estilbenos/farmacologia , Diferenciação CelularRESUMO
OBJECTIVE: The mechanism of action and potential targets of Paeoniae RadixAlba (Baishao, B) in the treatment of adjuvant-induced arthritis (AIA) rats are explained using metabolomics and network pharmacology techniques, and the research evidence for the development of anti-rheumatoid arthritis (RA) drugs is enriched. METHODS: The rats were injected with Freund's complete adjuvant (CFA) to induce arthritis. We then measured the general physical characteristics, examined their X-rays and histopathology to evaluate the pathological condition of the inflammation models, and conducted metabolomics studies on the change in urine metabolism caused by CFA. The lyophilized powder of B at a dose of 2.16 g/kg was orally administered to the rats continuously for 28 days, and the therapeutic effect was evaluated. Network pharmacology prediction shows that B contains the target action of the ingredient, and the simulation of the target molecular docking, in combination with the metabolomics analysis results, shows that B has a potential role in the treatment of AIA rats. RESULTS: B can reduce the paw swelling and pathological changes in rats caused by CFA, reverse the levels of 12 urine biomarkers, and regulate histidine metabolism, phenylalanine metabolism, arginine, proline metabolism, pyrimidine metabolism, etc. The prediction of the active ingredient target in B indicates that it may act as an inflammatory signaling pathway in anti-RA, among them being paeoniflorin, palbinone, beta-sitosterol, kaempferol, and catechin, which are the significant active ingredients. CONCLUSION: The metabolomics results revealed the markers and metabolic mechanisms of urinary metabolic disorders in rats with AIA, demonstrated the efficacy of the therapeutic effect of B, and identified the key ingredients in B, providing theoretical support for the subsequent development and utilization of B.
Assuntos
Artrite Experimental , Artrite Reumatoide , Catequina , Medicamentos de Ervas Chinesas , Paeonia , Ratos , Animais , Paeonia/metabolismo , Quempferóis/uso terapêutico , Simulação de Acoplamento Molecular , Catequina/uso terapêutico , Pós , Histidina , Farmacologia em Rede , Metabolômica/métodos , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Biomarcadores/metabolismo , Arginina/uso terapêutico , Fenilalanina/uso terapêutico , Pirimidinas/uso terapêutico , ProlinaRESUMO
Cut flower quality is severely restrained by stem bending due to low stem strength. Melatonin has been shown to function in many aspects of plant growth and development, yet whether it can enhance stem strength, and the corresponding underlying mechanisms remain unclear. We investigated the role of melatonin in enhancement of stem strength in herbaceous peony (Paeonia lactiflora Pall.) by applying exogenous melatonin and changing endogenous melatonin biosynthesis. Endogenous melatonin content positively correlated with lignin content and stem strength in various P. lactiflora cultivars. Supplementation with exogenous melatonin significantly enhanced stem strength by increasing lignin content and the S/G lignin compositional ratio, up-regulating lignin biosynthetic gene expression. Moreover, overexpression of TRYPTOPHAN DECARBOXYLASE GENE (TDC) responsible for the first committed step of melatonin biosynthesis in tobacco, significantly increased endogenous melatonin, which further increased the S/G ratio and stem strength. In contrast, silencing PlTDC in P. lactiflora decreased endogenous melatonin, the S/G ratio and stem strength. Finally, manipulating the expression of CAFFEIC ACID O-METHYLTRANSFERASE GENE (COMT1), which is involved in both melatonin and lignin biosynthesis, showed even greater effects on melatonin, the S/G ratio and stem strength. Our results suggest that melatonin has a positive regulatory effect on P. lactiflora stem strength.
Assuntos
Melatonina , Paeonia , Descarboxilases de Aminoácido-L-Aromático/genética , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Lignina/metabolismo , Melatonina/metabolismo , Paeonia/metabolismo , Plantas/metabolismoRESUMO
PURPOSE: Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. METHODS: Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6 weeks. RESULTS: PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. CONCLUSIONS: It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.
Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Paeonia , Animais , Cricetinae , Masculino , Colesterol , Mesocricetus , Paeonia/metabolismo , Óleos de Plantas/metabolismo , Óleos de Plantas/farmacologiaRESUMO
Paeonia ostii is an authorized novel vegetable oil crop due to its seeds rich in unsaturated fatty acids (UFAs) especially α-linolenic acid (ALA), which overweight the current available edible oil. However, little is known on the regulation mechanism of UFAs biosynthesis during its seed development. Here, we used transcriptome and proteome data combining phytochemistry means to uncover the relationship between abscisic acid (ABA) signaling and UFAs biosynthesis during P. ostii seed development. Based on transcriptome and proteome analysis, two desaturases of omega-6 and omega-3 fatty acid, named as PoFAD2 and PoFAD3 responsible for ALA biosynthesis were identified. Then, an ABSCISIC ACID-INSENSITIVE 5 (ABI5) proteins was identified as an upstream transcriptional factor, which activated the expression of PoFAD3 instead of PoFAD2. Moreover, silencing of PoABI5 repressed the response of PoFAD3 to ABA. This study provides the first view on the connection between the function of ABA signaling factors and ALA biosynthesis in the P. ostii seed, which lays the foundation for studies on the regulatory mechanism of ABA signaling involved in the UFAs synthesis during seeds development, meanwhile, it will shed light on manipulation of ALA content for satisfying human demands on high quality of edible oil or healthy supplement.
Assuntos
Ácidos Graxos Ômega-3 , Paeonia , Ácido Abscísico/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/análise , Paeonia/metabolismo , Sementes/metabolismoRESUMO
Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.
Assuntos
Antioxidantes/farmacologia , Paeonia/química , Compostos Fitoquímicos/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Glutationa Peroxidase/metabolismo , Humanos , Malondialdeído/metabolismo , Espectrometria de Massas/métodos , Paeonia/metabolismo , Fenóis/química , Compostos Fitoquímicos/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estações do Ano , Superóxido Dismutase/metabolismoRESUMO
Paeonia ostii var. lishizhenii has emerged as a valuable oil-producing crop with splendid characteristic of high α-linolenic acid (C18:3, ALA) content in its seed oil for healthy food supplement, but the molecular mechanism for seed ALA accumulation remains enigmatic. In our previous report, a PoSAD gene encoding stearoyl-ACP desaturase had been cloned and functional charactered for the first desaturation procedure involved in ALA biosynthesis pathway in P. ostii var. lishizhenii endosperms, while other participants have not been identified to date. In this study, full-length cDNAs of PoFAD2 (1489 bp), PoFAD6 (1638 bp), and PoFAD3 (1709 bp) were isolated based on our recent transcriptome sequencing data. Bioinformatic analyses revealed that the PoFADs were closest to their counterparts from Paeoniaceae species P. ludlowii, P. rockii, and P. suffruticosa in phylogenetic tree, which shared highly conserved histidine boxes (HXXXH, HXXHH, and HXXHH), exhibiting typical characters of membrane-bound desaturases in higher plants. Additionally, the PoFAD2 and PoFAD3 were specifically expressed and highly associated with LA and ALA accumulation in developing endosperms, whereas PoFAD6 expression has no significantly difference during whole seed developing stages. The catalytic function of these PoFADs were further analyzed by heterologous expression in Saccharomyces cerevisiae and Arabidopsis thaliana. The results showed that PoFAD2 and PoFAD6 could catalyze linoleic acid (C18:2) synthesis, while PoFAD3 had ability to produce ALA. This study functional identified three PoFAD genes, which indicates their critical roles in ALA biosynthesis pathway in P. ostii var. lishizhenii, and is of great theoretical and practical meaning on breeding and cultivating new tree peony varieties to promote human health and nutrition supplement.
Assuntos
Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Paeonia/genética , Paeonia/metabolismo , Sementes/genética , Sementes/metabolismo , Ácido alfa-Linolênico/biossíntese , Ácido alfa-Linolênico/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Vias Biossintéticas , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Paeonia/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimentoRESUMO
KEY MESSAGE: After cryopreservation, the NO content in pollen increased, inducing programmed cell death as a key reason for reduced viability. Low recovery of biomaterials after cryopreservation is a bottleneck that limits the application of this technology. At present, the mechanism of viability decline after cryopreservation is not fully understood. In this study, the effects of nitric oxide (NO) on programmed cell death (PCD) and its relationship with viability were investigated, using Paeonia lactiflora 'Fen Yu Nu' pollen with significantly decreased viability after cryopreservation. The results showed that: the activity of caspase-3-like and caspase-9-like protease and the apoptosis rate of pollen cells were significantly increased, the expression level of the promoting PCD (pro-PCD) genes was up-regulated, while the expression level of the inhibiting PCD (anti-PCD) genes was down-regulated after preservation in liquid nitrogen (LN); the NO content in pollen cells increased significantly after LN exposure. The correlation analysis showed that NO was significantly correlated with pollen viability and all indicators of PCD. The addition of a NO carrier SNP after LN storage reduced pollen viability, increased endogenous NO content, decreased mitochondrial membrane potential level, activated caspase-3-like and caspase-9-like protease in pollen cells, and increased cell apoptosis rate. The expression levels of pro-PCD genes PDCD2 and ATG8CL were significantly up-regulated, while the expression levels of anti-PCD genes DAD1, BI-1 and LSD1 were significantly down-regulated. The addition of NO scavenger c-PTIO improved pollen viability, and produced the opposite effect of sodium nitroferricyanide (III) dihydrate (SNP), but did not change the mitochondrial membrane potential. These results suggest that NO induced PCD during the cryopreservation of pollen, which was one of the reasons for the significant decrease of pollen viability after cryopreservation.
Assuntos
Criopreservação/métodos , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Pólen/citologia , Pólen/metabolismo , Apoptose/genética , Caspases/metabolismo , Regulação da Expressão Gênica de Plantas , Potencial da Membrana Mitocondrial , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Paeonia/citologia , Paeonia/efeitos dos fármacos , Paeonia/genética , Proteínas de Plantas/metabolismo , Pólen/química , Pólen/genéticaRESUMO
The plant transcription factor WRINKLED1 (WRI1), a member of AP2/EREBP, is involved in the regulation of glycolysis and the expression of genes related to the de novo synthesis of fatty acids in plastids. In this study, the key regulator of seed oil synthesis and accumulation transcription factor gene PoWRI1 was identified and cloned, having a complete open reading frame of 1269 bp and encoding 422 amino acids. Subcellular localization analysis showed that PoWRI1 is located at the nucleus. After the expression vector of PoWRI1 was constructed and transformed into wild-type Arabidopsis thaliana, it was found that the overexpression of PoWRI1 increased the expression level of downstream target genes such as BCCP2, KAS1, and PKP-ß1. As a result, the seeds of transgenic plants became larger, the oil content increased significantly, and the unsaturated fatty acid content increased, which provide a scientific theoretical basis for the subsequent use of genetic engineering methods to improve the fatty acid composition and content of plant seeds.
Assuntos
Regulação da Expressão Gênica de Plantas , Paeonia/genética , Paeonia/metabolismo , Óleos de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Sequência de Bases , Vias Biossintéticas/genética , Clonagem Molecular , Ácidos Graxos/metabolismo , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Transporte Proteico , Sementes/genética , Sementes/metabolismo , Análise de Sequência de DNARESUMO
Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (ß2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.
Assuntos
Artéria Basilar/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/metabolismo , Glycyrrhiza , Ligantes , Masculino , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Paeonia/metabolismo , Panax/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologiaRESUMO
We aimed to compare the estrogenic activities of compounds isolated from Moutan Cortex Radicis (MRC, Paeonia suffruticosa Andrews) and identify their potential use in hormone replacement therapy. We quantified seven marker components (gallic acid, oxypaeoniflorin, paeoniflorin, ethyl gallate, benzoic acid, benzoylpaeoniflorin, and paeonol) in MRC using a high-performance liquid chromatography simultaneous analysis assay. To investigate the estrogenic activity of MRC and the seven marker components, an E-screen assay was conducted using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line. Among them, ethyl gallate caused cell proliferation in a concentration-dependent manner at concentrations above 25 µM and was clearly suppressed by combination treatment with the ER antagonist ICI 182,780. Therefore, ethyl gallate may be a compound of MRC that can increase the estrogenic effect in ER-positive MCF-7 cells.
Assuntos
Estrona/química , Ácido Gálico/análogos & derivados , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Estrogênios , Ácido Gálico/química , Ácido Gálico/farmacologia , Glucosídeos/química , Terapia de Reposição Hormonal , Humanos , Monoterpenos/química , Paeonia/química , Paeonia/metabolismo , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action. METHODS: Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro. The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1. RESULTS: TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells. CONCLUSIONS: In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats. In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.
Assuntos
Apoptose , Glucosídeos/metabolismo , Integrina beta1/metabolismo , Rim/patologia , MicroRNAs/metabolismo , Paeonia/metabolismo , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Proliferação de Células/genética , Sobrevivência Celular , Creatinina/sangue , Medicamentos de Ervas Chinesas , Células Epiteliais/citologia , Inflamação/tratamento farmacológico , Masculino , Medicina Tradicional Chinesa , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , TransfecçãoRESUMO
A research was performed to determine and compare the physicochemical properties, chemical compositions and in vitro antioxidant activities of Paeonia lactiflora Pall seed oils with ultrasonic-assisted solvent extraction, pressing and supercritical fluid extraction. Paeonia lactiflora Pall seed oil contained a high percentage of polyunsaturated fatty acids and monounsaturated fatty acids, especially oleic (31.62-32.88%) and α-linolenic acids (37.55-39.95%). The beneficial multiple dietary phytochemicals (tocopherol, phytosterols and squalene) and in vitro antioxidant activity were significantly influenced by the hull and processing method (Pï¼0.05). However, higher tocopherol (596.67-738.76 mg/kg) and phytosterols (5775.01-6055.62 mg/kg) contents were found in supercritical fluid extraction oils. Additionally, ten individual polyphenols were quantified, and significantly influenced by the hull and processing method (Pï¼0.05), with the content of benzoic acid and several individual flavonoids being the higher. According to the results, pressing might be the best process for extracting oil with a high number of polyphenols.
Assuntos
Paeonia/metabolismo , Óleos de Plantas/química , Cromatografia com Fluido Supercrítico , Sequestradores de Radicais Livres/química , Fitosteróis/química , Fitosteróis/isolamento & purificação , Extratos Vegetais/química , Óleos de Plantas/isolamento & purificação , Sementes/química , Sementes/metabolismo , Sonicação , Tocoferóis/química , Tocoferóis/isolamento & purificaçãoRESUMO
Parkinson disease is one of the most common neurological movement disorders affecting geriatric population. Biosynthesized gold nanoparticles are the ideal alternatives spotlighted by many researchers to treat various diseases. In the present study we synthesized gold nanoparticles using the root extract of Paeonia mountan, woody trees which are used in traditional Chinese medicine to be prescribed for diverse diseases. The synthesis of gold nanoparticles was confirmed with UV-Vis spectroscopic analysis and characterized using FTIR, HR-TEM, EDAX and XRD analysis. The cytotoxicity property of synthesized gold nanoparticles was assessed using MTT assay in the murine microglial BV2 cells. The neuroprotective effect of synthesized gold nanoparticles in inflammatory agent lipopolysaccharides triggered murine microglial BV2 cells was evaluated using nitric oxide, prostaglandin E2 and inflammatory cytokines assays such as IL-6&IL-1ß. Further to confirm in vivo effect of synthesized nanoparticles, the nanoparticles were treated to Parkinson induced C57BL/6 mice. Behavioral, biochemical and molecular analysis were performed to estimate the potency of synthesized gold nanoparticles against the Parkinson induction in mice model. Our characterization results prove the gold nanoparticles synthesized using Paeonia mountan fulfills the requirement of ideal nanodrug and it potentially inhibited the inflammation in in vitro murine microglial BV2. The results of in vivo experiments authentically confirm gold nanoparticles synthesized using Paeonia mountan alleviates the neuroinflammation and improves the motor coordination in Parkinson induced mice.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Fármacos Neuroprotetores/química , Paeonia/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Química Verde , Lipopolissacarídeos/farmacologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Raízes de Plantas/química , Raízes de Plantas/metabolismoRESUMO
Paeonol extracted from the Moutan Cortex, possesses hepatoprotective activity against epirubicin (EPI)-induced liver damage. This study evaluated the protective effect of paeonol on EPI-induced hepatotoxicity and explored the underlying metabolomic mechanism. Breast tumor-bearing mice were randomly divided into three groups: control, EPI, and EPI + paeonol treatment. Mice received a tail i.v. injection of EPI every other day for 3 cycles or/and intragastrically (i.g.) administered paeonol daily for 6 days. Hematoxylin-eosin (HE) staining and biochemical detection were used to determine the degree of damage. A gas chromatography-mass spectrometry (GC-MS) technique was established to determine the metabolites. PLS-DA and PCA were used to investigate metabolic changes. HE staining and biochemical detection results showed that EPI caused serious liver damage while paeonol ameliorated it. The results of mass spectrogram, partial least squares-discriminate analysis (PLS-DA), and principal component analysis (PCA) demonstrated that lipid, amino acid, and energy metabolism involving seven metabolites were obviously changed by EPI and reversed by paeonol. Additionally, paeonol inhibited EPI-induced activation of adenosine monophosphate activated protein kinase/mammalian target of Rapamycin (AMPK/mTOR) signalling pathway. Our results demonstrated the hepatoprotective effect of paeonol on EPI-induced hepatotoxicity in mice, provided potential biomarkers for early assessment of EPI-induced liver injury and illuminated the metabolic mechanism underlying paeonol-related hepatic protection.
Assuntos
Acetofenonas/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Epirubicina/efeitos adversos , Fígado/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Análise dos Mínimos Quadrados , Fígado/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Paeonia/efeitos dos fármacos , Paeonia/metabolismo , Análise de Componente Principal , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 105 km2 is suitable for growing P. ostii, accounting for 21.16% of the country's total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.
Assuntos
Conservação dos Recursos Naturais/métodos , Ecossistema , Modelos Teóricos , Paeonia/crescimento & desenvolvimento , Óleos de Plantas/metabolismo , Altitude , China , Mudança Climática , Geografia , Concentração de Íons de Hidrogênio , Paeonia/metabolismo , Chuva , Estações do Ano , Solo/química , TemperaturaRESUMO
Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson's disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.