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1.
Phytother Res ; 37(10): 4607-4620, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37380363

RESUMO

Atractylenolide-III (AT-III) is well known as its role in antioxidant and anti-inflammatory. Present study was aimed to figure out its effects on osteoarthritis and potential mechanisms. Rat model, human osteoarthritis cartilage explants as well as rat/human chondrocyte cultures were prepared to test AT-III's effects on osteoarthritis progression and chondrocyte senescence. Potential targeted molecules of AT-III were predicted using network pharmacology and molecular docking, assessed by Western blotting and then verified with rescue experiments. AT-III treatment alleviated osteoarthritis severity (shown by OARSI grading score and micro-CT) and chondrocyte senescence (indexed by levels of SA-ß-gal, P16, P53, MMP13, ROS and ratio of healthy/collapsed mitochondrial membrane potentials). Network pharmacology and molecular docking suggested that AT-III might play role through NF-κB pathway. Further experiments revealed that AT-III reduced phosphorylation of IKKα/ß, IκBα and P65 in NF-κB pathway. As well as nuclear translocation of p65. Both in vivo and in vitro experiments indicated that AT-III's effects on osteoarthritis and anti-senescence were reversed by an NF-κB agonist. AT-III could alleviate osteoarthritis by inhibiting chondrocyte senescence through NF-κB pathway, which indicated that AT-III is a prospective drug for osteoarthritis treatment.

2.
Metabolites ; 13(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36984896

RESUMO

The dried root of Codonopsis pilosula (Franch.) Nannf., referred to as Dangshen in Chinese, is a famous traditional Chinese medicine. Polysaccharides, lobetyolin, and atractylenolide III are the major bioactive components contributing to its medicinal properties. Here, we investigated the dynamic changes of the main substances in annual Dangshen harvested at 12 time points from 20 May to 20 November 2020 (from early summer to early winter). Although the root biomass increased continuously, the crude polysaccharides content increased and then declined as the temperature fell, and so did the content of soluble proteins. However, the content of total phenolics and flavonoids showed an opposite trend, indicating that the carbon flux was changed between primary metabolism and secondary metabolism as the temperature and growth stages changed. The changes in the contents of lobetyolin and atractylenolide III indicated that autumn might be a suitable harvest time for Dangshen. The antioxidant capacity in Dangshen might be correlated with vitamin C. Furthermore, we analyzed the expression profiles of a few enzyme genes involved in the polysaccharide biosynthesis pathways at different growth stages, showing that CpUGpase and CPPs exhibited a highly positive correlation. These results might lay a foundation for choosing cultivars using gene expression levels as markers.

3.
Phytomedicine ; 104: 154289, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35785561

RESUMO

BACKGROUND: Hypothermia is a complex pathophysiological response that can be life-threatening in low-temperature environment because of impaired thermoregulation. However, there is currently no clinically effective drugs that can prevent or treat this disease. Brown adipose tissue (BAT) activation or browning of white adipose tissue (WAT) is a promising therapeutic strategy to prevent or treat hypothermia. Atractylodes macrocephala Koidz extract (AE) and its active compound Atractylenolide III (AIII) has been reported to regulate glycolipid metabolism, which might be relevant to BAT activation. However, the thermogenic effect and mechanism of AE and AIII on adipose tissues have not been explored yet. Therefore, this study firstly investigated the role of AE and AIII on hypothermia by promoting heat production of BAT and WAT. PURPOSE: To explore the anti-cold effect of AE and AIII in cold exposure model and explore their biological function and mechanism underlying thermogenesis. METHODS: The effect of thermogenesis and anti-hypothermia of AE and AIII on C57BL/6J mice were evaluated with several experiment in cold environment, such as toxicity test, cold exposure test, metabolism estimation, histology and immunohistochemistry, and protein expression. Additionally, BAT, inguinal WAT (iWAT) and brown adipocytes were utilized to explore the mechanism of AE and AIII on thermogenesis in vivo and in vitro. Finally, SIRT1 agonist and inhibitor in brown adipocytes to verify that AIII activated BAT through SIRT1/PGC-1α pathway. RESULTS: Both AE and AⅢ could significantly maintain the core body temperature and body surface temperature of mice during cold exposure. Besides, AE and AⅢ could significantly improve the capacity of total antioxidant and glucose, lipid metabolism of mice. In addition, AE and AIII reduced mitochondrial membrane potential and ATP content both in BAT and brown adipocytes, and decreased the size of lipid droplets. Moreover, AE and AⅢ promoted the expression of proteins related to heat production in BAT and iWAT. And AIII might activate BAT via SIRT1/PGC-1α pathway. CONCLUSION: AE and AⅢ were potential candidate drugs that treated hypothermia by improving the heat production capacity of the mice. Mechanistically, they may activate SIRT1/PGC-1α pathway, thus enhancing the function of BAT, and promoting the browning of iWAT, to act as anti-hypothermia candidate medicine.


Assuntos
Atractylodes , Sirtuína 1 , Tecido Adiposo Branco , Animais , Lactonas , Camundongos , Camundongos Endogâmicos C57BL , Sesquiterpenos , Transdução de Sinais , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo
4.
J Ethnopharmacol ; 288: 114968, 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35007681

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. AIM OF THE STUDY: Here, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. MATERIALS AND METHODS: First, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. RESULTS: A total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. CONCLUSIONS: Our study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.


Assuntos
Atractylodes/química , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/normas , Controle de Qualidade , Quimiometria , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Humanos , Espectrometria de Massas , Farmacologia em Rede , Análise de Componente Principal , Rizoma
5.
Chem Biodivers ; 18(8): e2001001, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34156157

RESUMO

The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mouse colitis model. TNBS-induced colitis was established in mice, which were treated with 8-ß-Hydroxyasterolide (Atractylenolide III) for 14 days. The body weight of the mice in the middle and high dose groups of Atractylenolide III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolide III, as determined by histological analysis. Moreover, Atractylenolide III downregulated the expression levels of the inflammatory factors interleukin-1ß and tumor necrosis factor-α, and greatly suppressed the levels of the pro-oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptor 1 (FPR1) and nuclear respiratory factor 2 (Nrf2) were upregulated in the colonic tissues of TNBS-treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS-induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lactonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lactonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
6.
Clin Exp Pharmacol Physiol ; 47(8): 1360-1367, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32196713

RESUMO

Paediatric asthma is a common inflammatory disease in children. Atractylenolide III is an active component of the Atractylodes rhizome, an herbal medicine that has been used as an asthma treatment. This study aimed to explore the effects and underlying mechanisms of atractylenolide III in IL-4-induced 16HBE cells and ovalbumin-induced asthmatic mice. The results showed that IL-4 stimulation significantly decreased, and atractylenolide III treatment increased, growth and apoptosis of 16HBE cells. In 16HBE cells, administration of atractylenolide III also significantly suppressed the IL-4-induced increases in the expression of cleaved caspase-1; apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC); and nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3). Moreover, the numbers of total leukocytes, neutrophils, eosinophils, and macrophages significantly increased in ovalbumin-induced mice, and then decreased after atractylenolide III treatment. In ovalbumin-induced asthmatic mice, atractylenolide III treatment also significantly inhibited NLRP3 inflammasome activation and restored the Th1/Th2 balance. These results indicate that atractylenolide III reduced NLRP3 inflammasome activation and regulated the Th1/Th2 balance in IL-4 induced 16HBE cells and ovalbumin-induced asthmatic mice, suggesting it has a protective effect that may be useful in the treatment of paediatric asthma.


Assuntos
Astenia/imunologia , Inflamassomos/metabolismo , Lactonas/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sesquiterpenos/farmacologia , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Astenia/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Humanos , Camundongos , Células Th1/citologia , Células Th2/citologia
7.
Artigo em Chinês | WPRIM | ID: wpr-846016

RESUMO

Objective: To establish HPLC-ELSD fingerprint of Zhenwu Decoction(ZWD), screen out the signature components of ZWD through chemical pattern recognition, so as to establish the content determination method of ZWD based on this index. Methods: The fingerprint of 16 batches of ZWD was established by HPLC-ELSD method. The similarity evaluation system of traditional Chinese medicine chromatographic fingerprint (2012 Version) was used for similarity evaluation to determine the common peaks and its attribution. Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to select the index components of ZWD. Results: The fingerprint of ZWD was established, 38 common peaks were confirmed, and the similarity was > 0.95. The results of CA, PCA and OPLS-DA were consistent and the samples were divided into three categories. Benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, polyporenic acid C, pachymic acid, atractylenolide II, atractylenolide III, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin were identified as the 11 index components with significant difference contribution in different batches of ZWD samples. 6-Gingerol and 6-shogaol were the main active components of ginger, so the above 13 components were taken as the index components of ZWD. The chromatographic peak separation degree and linear relationship were good. The average recovery rate was 96.46%-99.80%, RSD ≤ 3.15%. The mass fraction range of benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, polyporenic acid C, pachymic acid, atractylenolide II, atractylenolide III, oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, 6-gingerol, 6-shogaol in 16 batches were 283.93-576.86, 25.05-147.39, 62.96-303.37, 31.24-131.27, 9.76-44.04, 32.15-83.55, 76.55-333.13, 17.48-146.61, 456.58-1554.14, 3 322.48-5 590.01, 158.21-556.50, 525.85-582.92 and 68.52-74.73 mg/g, respectively. Conclusion: The fingerprint combined with PCA, CA and OPLS-DA can comprehensively evaluate the quality of ZWD. This method is stable and reliable, providing reference for the quality evaluation.

8.
Chin J Nat Med ; 17(4): 264-274, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31076130

RESUMO

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca2+ overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.


Assuntos
Apoptose/efeitos dos fármacos , Corticosterona/toxicidade , Lactonas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células PC12 , Fosforilação/efeitos dos fármacos , Ratos
9.
Phytomedicine ; 59: 152922, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981186

RESUMO

BACKGROUND: Inflammation is a major contributor to stroke pathology, making it a promising strategy for intervention. Microglia, the resident macrophages in the brain, play essential roles in both the generation and resolution of neuroinflammation. In particular, mitochondrial homeostasis is critical for microglial function and its dysregulation is involved in the pathogenesis of ischemic stroke. Atractylenolide III (A III), a sesquiterpene lactone found in Atractylodes macrocephala Koidz, has been shown to have an inhibitory effect on inflammation. However, its effect specifically on neuroinflammation and microglial mitochondrial homeostasis following stroke remains elusive. HYPOTHESIS: We hypothesized that A III protects against brain ischemia through inhibition of neuroinflammation mediated by JAK2/STAT3/Drp1-dependent mitochondrial fission. METHODS: The neuroprotective and anti-neuroinflammatory effects of A III were investigated in vivo in mice with transient occlusion to the middle cerebral artery (MCAO) and in vitro in oxygen glucose deprivation-reoxygenation (OGDR)-stimulated primary microglia from mice. RESULTS: A III and AG490, an inhibitor of JAK2, treatment reduced brain infarct size, restored cerebral blood flow (CBF), ameliorated brain edema and improved neurological deficits in MCAO mice. Furthermore, A III and AG490 inhibited mRNA and protein expressions of proinflammatory (IL-1ß, TNF-α, and IL-6) and anti-inflammatory cytokines in both MCAO mice and OGDR-stimulated primary microglia. The JAK2/STAT3 pathway was effectively suppressed by A III, similar to the effect of AG490 treatment. In addition, A III and AG490 treatments significantly decreased Drp1 phosphorylation, translocation and mitochondrial fission in primary microglia stimulated with OGDR for 24 h. CONCLUSION: Our study demonstrated that A III was able to reduce complications associated with ischemia through inhibiting neuroinflammation, which was mediated in part by JAK2/STAT3-dependent mitochondrial fission in microglia.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Dinaminas/metabolismo , Inflamação/tratamento farmacológico , Janus Quinase 2/metabolismo , Lactonas/farmacologia , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/farmacologia , Animais , Isquemia Encefálica/patologia , Citocinas/metabolismo , Dinaminas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Interleucina-1beta/metabolismo , Janus Quinase 2/genética , Masculino , Camundongos , Microglia/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo
10.
J Ethnopharmacol ; 210: 179-191, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28866044

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer. AIM OF THE STUDY: The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action. MATERIALS AND METHODS: NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways. RESULTS: 8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism. CONCLUSIONS: The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Sistema Imunitário/efeitos dos fármacos , Mitomicina/toxicidade , Animais , Biomarcadores/metabolismo , Masculino , Espectrometria de Massas , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-Dawley
11.
Food Chem Toxicol ; 106(Pt A): 78-85, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28545868

RESUMO

Atractylenolide III (ATL-III) is an active compound of Atractylodes lancea, which has been widely used for the treatment of cancer. Cancer is closely connected with inflammation, and many anti-inflammatory agents are also used to treat cancer. We investigated the influence of ATL-III on thymic stromal lymphopoietin (TSLP)-induced inflammatory reactions. Pretreatment with ATL-III suppressed murine double minute 2 levels and promoted p53 levels in TSLP-treated human mast cell, HMC-1 cells. Mast cell proliferation increased by TSLP or IL-3 stimulation was significantly decreased by ATL-III pretreatment. Interleukin (IL)-13 and phosphorylated signal transducer and activator of transcription 3, 5, and 6 levels in TSLP-treated HMC-1 cells were also decreased by ATL-III pretreatment. In addition, ATL-III decreased the TSLP-induced production of proinflammatory cytokines (IL-6, IL-1ß, tumor necrosis factor-α, and IL-8). ATL-III decreased the levels of Bcl2 and procaspase-3 and increased caspase-3 activation and cleaved PARP levels. Furthermore, ATL-III decreased TSLP-induced mast cell proliferation and the production of inflammatory cytokine by LAD2 cells. Taken together, these findings suggest that ATL-III plays a useful role as an anti-inflammatory agent and should be viewed as a potential anti-cancer agent.


Assuntos
Atractylodes/química , Proliferação de Células/efeitos dos fármacos , Citocinas/farmacologia , Lactonas/farmacologia , Mastócitos/citologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Anti-Inflamatórios/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Humanos , Interleucina-13/genética , Interleucina-13/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Linfopoietina do Estroma do Timo
12.
Phytother Res ; 30(1): 25-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26536846

RESUMO

Drug-metabolizing enzymes inhibition-based drug-drug interaction remains to be the key limiting factor for the research and development of efficient herbal components to become clinical drugs. The present study aims to determine the inhibition of uridine 5'-diphospho-glucuronosyltransferases (UGTs) isoforms by two important efficient herbal ingredients isolated from Atractylodes macrocephala Koidz, atractylenolide I and III. In vitro recombinant UGTs-catalysed glucuronidation of 4-methylumbelliferone was used to determine the inhibition capability and kinetics of atractylenolide I and III towards UGT2B7, and in silico docking method was employed to explain the possible mechanism. Atractylenolide I and III exhibited specific inhibition towards UGT2B7, with negligible influence towards other UGT isoforms. Atractylenolide I exerted stronger inhibition potential than atractylenolide III towards UGT2B7, which is attributed to the different hydrogen bonds and hydrophobic interactions. Inhibition kinetic analysis was performed for the inhibition of atractylenolide I towards UGT2B7. Inhibition kinetic determination showed that atractylenolide I competitively inhibited UGT2B7, and inhibition kinetic parameter (Ki) was calculated to be 6.4 µM. In combination of the maximum plasma concentration of atractylenolide I after oral administration of 50 mg/kg atractylenolide I, the area under the plasma concentration-time curve ration AUCi /AUC was calculated to be 1.17, indicating the highly possible drug-drug interaction between atractylenolide I and drugs mainly undergoing UGT2B7-catalysed metabolism.


Assuntos
Glucuronosiltransferase/antagonistas & inibidores , Lactonas/química , Sesquiterpenos/química , Interações Medicamentosas , Glucuronosiltransferase/metabolismo , Humanos , Himecromona/metabolismo , Cinética , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/metabolismo
13.
J Ethnopharmacol ; 178: 66-81, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26680587

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Neurodegenerative diseases (NDs) is a time-dependent course for a sequence of conditions that primarily impact the neurons in the human brain, ultimately, resulting in persistence and progressive degeneration and / or death of nerve cells and reduction of cognition and memory function. Currently, there are no therapeutic approaches to cure neurodegeneration, except certain medicines that temporarily alleviate symptoms, facilitating the improvement of a patients' quality of life. Danggui-shaoyao-san (DSS), as a famous Chinese herbal formula, has been widely used in the treatment of various illnesses, including neurodegenerative diseases. Although well-practiced in clinical medicine, the mechanisms involved in DSS for the treatment of neurodegenerative diseases remain elusive. MATERIALS AND METHODS: In the present study, a novel systems pharmacology approach was developed to decipher the potential mechanism between DSS and neurodegenerative disorders, implicated in oral bioavailability screening, drug-likeness assessment, target identification and network analysis. RESULTS: Based on a comprehensive systems approach, active compounds of DSS, relevant potential targets and targets associated with diseases were predicted. Active compounds, targets and diseases were used to construct biological networks, such as, compound-target interactions and target-disease networks, to decipher the mechanisms of DSS to address NDs. CONCLUSIONS: Overall, a well-understood picture of DSS, hallmarked by multiple herbs-compounds-targets-pathway-cooperation networks for the treatment of NDs, was revealed. Notably, this systems pharmacology approach provided a novel in silico approach for the development paradigm of traditional Chinese medicine (TCM) and the generation of new strategies for the management of NDs.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Disponibilidade Biológica , Células CACO-2 , Linhagem Celular Tumoral , Humanos , Medicina Tradicional Chinesa/métodos
14.
Neuroscience ; 290: 485-91, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25662510

RESUMO

Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury.


Assuntos
Lactonas/farmacologia , Deficiências da Aprendizagem/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Homocisteína , Deficiências da Aprendizagem/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Proteína Quinase C/metabolismo , Distribuição Aleatória , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Memória Espacial/efeitos dos fármacos
15.
J Ethnopharmacol ; 151(2): 791-9, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24296088

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes macrocephala (Compositae) is one of the most well-known traditional Chinese medicine in China, Japan and Korea, which has a long history of use for the treatment of splenic asthenia, edema, anorexia, and excessive perspiration, etc. As active compounds of anti-inflammatory activity of this medicinal plant have not been fully elucidated, the aim of this study was to isolate and identify the active constituents inhibiting nitric oxide (NO) production from the rhizomes of A. macrocephala. MATERIALS AND METHODS: Inhibitory activity against NO production in lipopolysaccharide-activated RAW264.7 macrophages was evaluated by Griess reaction. Fifteen polyacetylenes were isolated from the active ethyl acetate extract using activity-guided screening. The structures of all compounds were elucidated by spectroscopic methods and comparison with published data. The compounds were further tested for their inhibitory activity against NO production. RESULTS: Seven new polyacetylenes, named atractylodemaynes A-G (1-7), along with eight known ones (8-15) were isolated. Compound 14 was isolated for the first time from the rhizomes of A. macrocephala. The study showed that the tested compounds exhibited inhibitory activity against NO production in a dose-dependent manner. Among them, compounds 10, 11 and 12 had relatively stronger inhibitory effect with IC50 values of 28, 23 and 19µM, respectively. CONCLUSION: The results demonstrated that the polyacetylenes might greatly contribute to the anti-inflammatory activity of the rhizomes of A. macrocephala.


Assuntos
Anti-Inflamatórios/farmacologia , Atractylodes , Macrófagos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Poli-Inos/farmacologia , Rizoma/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , Extratos Vegetais/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-24211810

RESUMO

Rhizoma Atractylodis Macrocephalae (RAM) is a commonly used food and traditional Chinese medicine (TCM), which traditionally strengthens the spleen, benefits vital energy, eliminates dampness, and promotes hidroschesis. Its primary effective constituents are polysaccharides and volatile oil, whose main components are atractylenolide I and III. Fourier transform near-infrared spectroscopy (FT-NIR) is widely used in TCM research. However, determination of atractylenolides in RAM using FT-NIR has not been described. In this study, a new method for the determination of atractylenolides I and III in RAM by NIR was established. The spectral characteristics of atractylenolides I and III were obtained by second derivative multiple scattering correction, and its chart to the original absorbance spectra. Additionally, in combination with the partial least squares (PLS) algorithm, the calibration process was performed for the quantitation of the samples. The root mean square error of cross-validation of the PLS models for atractylenolides I and III was 0.0387 and 0.0358, and the determination coefficient of quantitative models was 96.63 and 96.16, respectively. This study demonstrated that NIR spectroscopy can be used to analyze quickly and efficiently the contents of atractylenolides I and III in RAM.


Assuntos
Antagonistas Colinérgicos/análise , Medicamentos de Ervas Chinesas/química , Lactonas/análise , Sesquiterpenos/análise , Análise dos Mínimos Quadrados , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos
17.
Chinese Pharmaceutical Journal ; (24): 1077-1080, 2012.
Artigo em Chinês | WPRIM | ID: wpr-860695

RESUMO

OBJECTIVE: To establish a novel and efficient method for enriching low content active components from traditional Chinese herbs. METHODS: The enrichment of atractylenolide III was taken as an example. First, molecular imprinting polymers (MIPs) of atractylenolide III were prepared by precipitation polymerization using 1-Vinylimidazole as functional monomer. Second, the atractylenolide III MIPs were packed into solid-phase column to separate atractylenolide III and its analogues from the exracts of Herba Atractylodes Macrocephaia and Codonopsis pilosula. Moreover, the adsorption performance of MIPs for the target components was also investigated. RESULTS: Enrichment factor (EF) of MIP-SPE and C18-SPE column were 78.90 and 51.56 μg · g-1 respectively, suggesting that MIPs had better adsorption property than C18; the precision and accuracy of the developed method were satisfactory with recoveries of 102.2% and LOD of 0.36 μg · mL-1. CONCLUSION These results demonstrate the feasibility of molecularly imprinted solid phase extraction for enriching low content active components in traditional Chinese herbs.

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