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1.
J Ethnopharmacol ; 301: 115813, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36220513

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zerumbone (ZER) is a humulane sesquiterpenoid isolated from Syringa pinnatifolia Hemsl. (SP), its content accounts for 64.7% of volatile oil and 0.86% of total ethanol extract (TEE), representing one of characteristic ingredient of SP. As a representative Mongolian medicine with anti-"Khii", anti-asthma, and clearing-heat effects, SP has been used for the treatment of cardiovascular diseases, upset, insomnia, and other symptoms. AIM OF STUDY: Previous results showed that TEE has sedative effect, but the pharmacological substances and its sedative mechanism remains unclear. This study aims to determine whether ZER, as one of major and characteristic sesquiterpenoids of SP, contributes to the sedative effect of SP and its underlying mechanism. MATERIALS AND METHODS: Locomotor activity and threshold dose of pentobarbital sodium sleep experiments were used to evaluate the sedative effects in mice. ELISA assay was used to examine the level of GABA/Glu ratio in rats hippocampus, cortex and hypothalamus tissue. The binding ability of ZER with glutamic acid decarboxylase 67 (GAD67) and Gephyrin protein were predicted by molecular docking. Western blot and Immunohistochemistry assay were used to determine the expression of GABAergic nerve system related proteins (GAD67, Gephyrin) in rat's hypothalamus. ZER was co-administrated with flumazenil and bicuculline (GABAA antagonist) to determine whether it acts on GABAA receptor. Furthermore, MQAE assay was used to test the effect of ZER on the chloride ion concentration in cerebellar granule cells. RESULTS: Current data demonstrated that ZER dose-dependently (5-20 mg/kg) reduces the locomotor activity and sleep latency of mice, and extend sleeping time of mice. The results of ELISA showed that ZER increases the level of GABA/Glu in rats brain tissue, in particular in hypothalamus. Molecular docking results revealed that ZER has a strong affinity to GAD67 and Gephyrin protein. The Western blot and Immunohistochemistry data indicated that ZER up-regulates the expression of GAD67 and Gephyrin protein in rat's hypothalamus. Antagonism test results demonstrated that flumazenil and bicuculline reverse the effect of ZER on threshold dose of pentobarbital sodium sleep experiments. In addition, ZER also could dose-dependently (5-20 µM) increase the chloride ion concentration in cerebellar granule cell, suggesting that ZER induces the opening of chloride channel, exerts central inhibitory effect. CONCLUSION: ZER has a significant sedative effect in mice and rat, and the effect is associated with GABAergic nervous system. The present results suggest that ZER, as one of the major bioactive ingredients of SP, contributes to the sedative effect and provide substantial evidence for its traditional use of anti-"Khii" in clinic of Syringa pinnatifolia.


Assuntos
Sesquiterpenos , Syringa , Animais , Camundongos , Ratos , Syringa/química , Hipnóticos e Sedativos/farmacologia , Pentobarbital , Flumazenil , Bicuculina , Simulação de Acoplamento Molecular , Cloretos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/farmacologia , Ácido gama-Aminobutírico/metabolismo , Receptores de GABA-A/metabolismo , Sistema Nervoso/metabolismo
2.
J Ethnopharmacol ; 301: 115786, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36206869

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae) is rich in essential oil, distinguished by a predominance of monoterpenes and sesquiterpenes, it being widely used in traditional medicine for the treatment of inflammations. AIM OF STUDY: This study's objective was to investigate the chemical composition of the essential oil of S. terebinthifolia (EOST) collected in six states of Brazil, evaluate its anti-inflammatory effects in mice, and analyze the histochemistry and micromorphology of leaves and stems. MATERIALS AND METHODS: Aerial parts of S. terebinthifolia were collected in six states of Brazil, and the essential oil was extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The histochemistry and micromorphology of leaves and stems were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The EOST were evaluated for anti-inflammatory activity and hyperalgesia using the carrageenan-induced paw edema methodology. RESULTS: The EOST showed variation across the six states in its yield (0.40%-0.86%) and chemical composition: hydrocarbon monoterpenes (28.76%-47.73%), sesquiterpenes, (31.43%-41.76%), oxygenated monoterpenes (14.31%-19.57%), and oxygenated sesquiterpenes (4.87%-14.38%). Both α-pinene and limonene were predominant constituents of essential in five regions, except for one state where α-phellandrene and limonene were the dominant components. A comprehensive description of the leaf and stem micromorphology and histochemistry was performed. In the in vivo testing, all EOST samples exerted antiedematogenic and anti-hyperalgesic effects, when tested in a carrageenan-induced paw inflammation (mechanical and thermal hyperalgesia) model with oral doses of 30 mg/kg. CONCLUSION: Our results indicate that the EOST samples collected in six Brazilian states differed in their chemical composition but not their anti-inflammatory and antihyperalgesic effects, which was correlated with the synergistic effect of its components, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Also, micromorphology and histochemistry of leaves and stems presented in this study provide anatomical and microchemical information, which aids species identification.


Assuntos
Anacardiaceae , Óleos Voláteis , Sesquiterpenos , Camundongos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/análise , Limoneno/análise , Carragenina , Anacardiaceae/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/análise , Monoterpenos/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Folhas de Planta/química , Hiperalgesia , Inflamação/tratamento farmacológico
3.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364101

RESUMO

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A-J (1-10), were isolated from the roots of T. wilfordii, along with ten known analogues (11-20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9-16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 µg/mL, 8.75 µM, 0.74 µM, and 15.66 µM, respectively, and no influence on the cell viability at a concentration of 100 µg/mL (TA) or 100 µM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Humanos , Tripterygium/química , NF-kappa B , Células HEK293 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Piridinas/farmacologia , Piridinas/química , Imunossupressores/farmacologia
4.
Molecules ; 27(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364182

RESUMO

Lung cancer, especially adenocarcinoma, is the second most occurring and highest fatality-causing cancer worldwide. Many natural anticancer compounds, such as sesquiterpene lactones (SLs), show promising anticancer properties. Herein, we examined Lactucin, an SL from the plant Cichorium intybus, for its cytotoxicity, apoptotic-inducing, cell cycle inhibiting capacity, and associated protein expression. We also constructed a biotinylated Lactucin probe to isolate interacting proteins and identified them. We found that Lactucin stops the proliferation of A549 and H2347 lung adenocarcinoma cell lines while not affecting normal lung cell MRC5. It also significantly inhibits the cell cycle at G0/G1 stage and induces apoptosis. The western blot analysis shows that Lactucin downregulates the MAPK pathway, cyclin, and cyclin-dependent kinases, inhibiting DNA repair while upregulating p53, p21, Bax, PTEN, and downregulation of Bcl-2. An increased p53 in response to DNA damage upregulates p21, Bax, and PTEN. In an activity-based protein profiling (ABPP) analysis of A549 cell's protein lysate using a biotinylated Lactucin probe, we found that Lactucin binds PGM, PKM, and LDHA PDH, four critical enzymes in central carbon metabolism in cancer cells, limiting cancer cells in its growth; thus, Lactucin inhibits cancer cell proliferation by downregulating the MAPK and the Central Carbon Metabolism pathway.


Assuntos
Chicória , Neoplasias Pulmonares , Sesquiterpenos , Humanos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Carbono/metabolismo , Sesquiterpenos/farmacologia , Lactonas/farmacologia , Proliferação de Células , Neoplasias Pulmonares/metabolismo , Apoptose , Ciclinas/metabolismo , Linhagem Celular Tumoral
5.
Mar Drugs ; 20(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36355005

RESUMO

Euplotin C is a sesquiterpene of marine origin endowed with significant anti-microbial and anti-tumor properties. Despite the promising functional profile, its progress as a novel drug candidate has failed so far, due to its scarce solubility and poor stability in aqueous media, such as biological fluids. Therefore, overcoming these limits is an intriguing challenge for the scientific community. In this work, we synthesized ß-cyclodextrin-based nanosponges and investigated their use as colloidal carriers for stably complex euplotin C. Results obtained proved the ability of the carrier to include the natural compound, showing remarkable values of both loading efficiency and capacity. Moreover, it also allowed us to preserve the chemical structure of the loaded compound, which was recovered unaltered once extracted from the complex. Therefore, the use of ß-cyclodextrin-based nanosponges represents a viable option to vehiculate euplotin C, thus opening up its possible use as pharmacologically active compound.


Assuntos
Ciclodextrinas , Sesquiterpenos , beta-Ciclodextrinas , Ciclodextrinas/farmacologia , Ciclodextrinas/química , beta-Ciclodextrinas/química , Sesquiterpenos/farmacologia , Solubilidade
6.
Molecules ; 27(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36296633

RESUMO

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5ß,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC50 = 0.002 µg/mL. On the other hand, 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3) and 5ß,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC50 = 0.04 µg/mL and 69.5% at IC50 = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease.


Assuntos
Produtos Biológicos , Croton , Sesquiterpenos de Eudesmano , Sesquiterpenos , Simulação de Acoplamento Molecular , Sesquiterpenos/farmacologia , Peptídeo Hidrolases , Estrutura Molecular
7.
Chin J Nat Med ; 20(10): 737-748, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36307196

RESUMO

Sesquiterpenoids are comprised of three C5 units and derived from farnesyl diphosphate. In these C15 family of terpenoids, drimane-type sesquiterpenoids are unique as their chemical structure of decahydronaphthalene along with the methyl group decorations resemble the A/B rings of labdane derived diterpenoids and the eastern part of many meroterpenoids. In the past decades, based on their chemical structural features and diverse bioactivities, great efforts have been made to perform chemical and biological research on this family of natural products, leading to the characterization of a large of new compounds and a few biosynthetic pathways. In this review, we collected 164 new drimane-type sesquiterpenoids from fungi between January 2004 and October 2021 and classified them into three major subfamilies, so as to highlight their diverse chemical structures, biological activities, and biosynthetic pathways,.


Assuntos
Diterpenos , Sesquiterpenos , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Fungos , Terpenos/farmacologia , Terpenos/química
8.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234691

RESUMO

Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. ß-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases. A diet-induced obesity model was performed in 16-week-old C57BL/6 mice administered with BCP [50 mg/kg]. A reduction in the expression of Claudin-1 was observed in the group with a high-fat diet (HFD), which was caused by the administration of BCP; besides BCP, the phylaAkkermansia and Bacteroidetes decreased between the groups with a standard diet (STD) vs. HFD. Nevertheless, the use of BCP in the STD increased the expression of these phyla with respect to fatty acids; a similar effect was observed, in the HFD group that had a decreasing concentration that was restored with the use of BCP. The levels of endotoxemia and serum leptin increased in the HFD group, while in the HFD + BCP group, similar values were found to those of the STD group, attributing the ability to reduce these in conditions of obesity.


Assuntos
Gastroenteropatias , Sesquiterpenos , Infecções Sexualmente Transmissíveis , Animais , Claudina-1 , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/uso terapêutico , Leptina , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Infecções Sexualmente Transmissíveis/complicações
9.
Molecules ; 27(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36234725

RESUMO

The medicinal plant Artabotrys hexapetalus (synonyms: A.uncinatus and A. odoratissimus) is known as yingzhao in Chinese. Extracts of the plant have long been used in Asian folk medicine to treat various symptoms and diseases, including fevers, microbial infections, ulcers, hepatic disorders and other health problems. In particular, extracts from the roots and fruits of the plant are used for treating malaria. Numerous bioactive natural products have been isolated from the plant, mainly aporphine (artabonatines, artacinatine) and benzylisoquinoline (hexapetalines) alkaloids, terpenoids (artaboterpenoids), flavonoids (artabotrysides), butanolides (uncinine, artapetalins) and a small series of endoperoxides known as yingzhaosu A-to-D. These natural products confer antioxidant, anti-inflammatory and antiproliferative properties to the plant extracts. The lead compound yingzhaosu A displays marked activities against the malaria parasites Plasmodium falciparum and P. berghei. Total syntheses have been developed to access yingzhaosu compounds and analogues, such as the potent compound C14-epi-yingzhaosu A and simpler molecules with a dioxane unit. The mechanism of action of yingzhaosu A points to an iron(II)-induced degradation leading to the formation of two alkylating species, an unsaturated ketone and a cyclohexyl radical, which can then react with vital parasitic proteins. A bioreductive activation of yingzhaosu A endoperoxide can also occur with the heme iron complex. The mechanism of action of yingzhaosu endoperoxides is discussed, to promote further chemical and pharmacological studies of these neglected, but highly interesting bioactive compounds. Yingzhaosu A/C represent useful templates for designing novel antimalarial drugs.


Assuntos
Annonaceae , Antimaláricos , Aporfinas , Benzilisoquinolinas , Antagonistas do Ácido Fólico , Malária , Plantas Medicinais , Sesquiterpenos , Annonaceae/química , Antimaláricos/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aporfinas/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Dioxanos , Compostos Ferrosos , Flavonoides/uso terapêutico , Antagonistas do Ácido Fólico/uso terapêutico , Heme , Humanos , Ferro/uso terapêutico , Cetonas/uso terapêutico , Malária/tratamento farmacológico , Malária/parasitologia , Peróxidos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plasmodium falciparum , Sesquiterpenos/farmacologia
10.
Molecules ; 27(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36234934

RESUMO

Seven new sesquiterpenes, named croargoid A-G (1-7), were isolated from the bark of Croton argyratus. Compounds 1-4 were the first examples of eudesmane sesquiterpene lactones containing C5-OH group. Compound 7 was a highly degraded eudesmane sesquiterpene possessing a rare eleven-carbon skeleton. Their structures with stereochemistry were mainly elucidated by NMR analyses in combination with MS and ECD data. Cytotoxicities and NO inhibitions of all isolates were evaluated and only compound 5 showed moderate NO inhibitory activity.


Assuntos
Croton , Sesquiterpenos de Eudesmano , Sesquiterpenos , Carbono , Lactonas/farmacologia , Estrutura Molecular , Casca de Planta , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia
11.
J Agric Food Chem ; 70(41): 13279-13288, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36198678

RESUMO

In the present study, we demonstrated that whether the gut microbiota and related metabolites contribute to the therapeutic effect of total sesquiterpenoids (TSs) from loquat leaves on obesity. A 4-week high fat diet was used to induce obesity which was then treated with TSs for another 4 weeks. TSs remarkedly reduced the weight of body and white adipose and the levels of total cholesterol (TC) and triglyceride (TG) in serum. We also found that TSs restored the diversity and richness of gut microbiota. In addition, TSs administration affected the relative abundance of seven key genera. Meanwhile, TSs were determined to affect the metabolism of the host through detecting the metabolites in feces. By applying KEGG and the correlation analysis with gut microbiota, 10 differential metabolites were identified to be the key. The results in this work proved that TSs inhibited obesity by remodeling gut microbiota and related metabolites.


Assuntos
Eriobotrya , Obesidade , Folhas de Planta , Sesquiterpenos , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Eriobotrya/química , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/etiologia , Obesidade/prevenção & controle , Folhas de Planta/química , Sesquiterpenos/farmacologia , Triglicerídeos/sangue , Animais , Camundongos , Camundongos Endogâmicos C57BL
12.
Tissue Cell ; 79: 101914, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183441

RESUMO

PURPOSE: ß-elemene has a wide range of anticancer effects and can be used in a variety of cancer types. This study mainly explored its mechanism of action on TNBC cells and provided theoretical basis for the treatment of TNBC. METHODS: Firstly, TNBC cells were treated with different concentrations of ß-elemene, and screened out an appropriate concentration for subsequent research. Then, through the bioinformatics website, predicted genes that have a binding relationship with ß-elemene. Then, the overexpression vector of the selected gene was transfected into the cell. The effects of ß-elemene and its target genes on the proliferation and apoptosis of TNBC cells were detected by CCK-8, Edu assay, and flow cytometry, and the senescence of cells was determined by SA-ß-gal experiment. Western blotting was used to detect the expression of apoptosis and aging-related proteins. RESULTS: ß-elemene inhibited TNBC cell viability and proliferation in a concentration-dependent manner, and induces apoptosis and senescence. Through the screening of candidate genes, IGF1 was finally determined to be an effective target gene of ß-elemene. The expression level of IGF1 was decreased in cells treated with ß-elemene. Overexpression of IGF1 significantly alleviated ability of ß-elemene to inhibit cell viability, proliferation, and induced cell apoptosis and senescence. In addition, ß-elemene inhibited the expression of IGF1R and Bcl-2, and promoted the expression of Cleaved Caspase-3 and senescence-related proteins (p27, p16, p53 and p21), and these effects were reversed by overexpression of IGF1. CONCLUSION: ß-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.


Assuntos
Sesquiterpenos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Sesquiterpenos/farmacologia , Apoptose , Proliferação de Células , Fator de Crescimento Insulin-Like I , Receptor IGF Tipo 1/farmacologia
13.
Chem Biodivers ; 19(11): e202200856, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36193005

RESUMO

Two new germacrane sesquiterpenes, named nivalenoids A and B (1 and 2), along with four known sesquiterpenes (3-6), were isolated from the Rhododendron nivale. The structures of compounds 1 and 2 were elucidated by integrating spectroscopic analyses, including NMR, UV, IR, as well as HR-MS data. Anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells revealed that compared with the positive control dexamethasone (IC50 =2.50 µM), compounds 1 and 2 showed mild anti-inflammatory activity, with IC50 value of 27.55 µM and 53.26 µM, respectively.


Assuntos
Rhododendron , Sesquiterpenos , Camundongos , Animais , Rhododendron/química , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Células RAW 264.7 , Óxido Nítrico
14.
Aging (Albany NY) ; 14(20): 8346-8356, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36260873

RESUMO

We focus on investigating the role of Parthenolide (Par), a small sesquiterpenoid molecule, in hepatocellular carcinoma (HCC) and its effective target.Highly-metastatic HCC cells, MHCC97-H, were divided into the DMSO and the Par groups, of which the Par group was intervened at 5 and 10 mg/L doses. Cell viability was assessed by CCK-8 assay. Transwell chamber assay was performed to examine the metastatic and invasive abilities, while plate clone formation assay was conducted to detect the clone formation ability. For analysis of glucose uptake, glycolytic ability and lactate level, the glycolysis assay was employed. Brdu staining was performed to evaluate the cell proliferative potential. The P50 and HIF-1α levels were measured by immunofluorescence, while the expressions of p-P50 and HIF-1α were determined by Western-Blot. Small molecule-protein docking and Pull-down experiments were conducted to validate the Par-P50 binding model. After establishing the tumor-bearing mouse model, Par was administered by gavage to measure the tissue levels of P50 and HIF-1α, followed by plotting of tumor growth curves.Par could inhibit the metastatic, invasive and clone formation abilities of MHCC97-H cells, reduce the cell proliferative potential, and suppress the glycolysis, as manifested by down-regulated level of lactate and reduced oxygen consumption. Meanwhile, Par inhibited the HIF-1α expression. We found that after silencing P50, the HIF-1α was down-regulated, the glycolytic ability decreased drastically, and the cellular metastatic and invasive abilities were suppressed. After P50 knockout, the effect of Par intervention on the MHCC97-H cells was reduced. In HCC-bearing mice, Par also exhibited an excellent anti-tumor effect, decreasing the tissue levels of P50 and HIF-1α.This study discovers that Par can inhibit the HIF-1α-mediated glycolysis of HCC cells by targeting P50, thereby exerting an anti-tumor effect. P50 is a major effective target of Par.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sesquiterpenos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Sesquiterpenos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Lactatos , Linhagem Celular Tumoral
15.
Biomed Pharmacother ; 155: 113699, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36116253

RESUMO

Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts.


Assuntos
Medicamentos de Ervas Chinesas , Óleos Voláteis , Sesquiterpenos , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Transdução de Sinais
16.
Nat Prod Rep ; 39(11): 2096-2131, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36106498

RESUMO

Covering: up to December 2021Picrotoxane sesquiterpenoids are a special category of natural products known to have a picrotoxane skeleton and are characterised by a highly oxidised cis-hydrindene core, lactone rings, and epoxide functionalities. Ever since the first picrotoxane was isolated from Menispermum cocculus in the early 19th century, these compounds have long attracted the attention of natural product chemists, synthetic chemists, and pharmacologists for their particular structures and powerful biological activities. This review extensively summarizes a total of 132 naturally occurring picrotoxane sesquiterpenoids, taking into account their distributions, structural classifications, chemical and bio-synthetic researches, and bioactivities. It provides a comprehensive and in-depth perspective for further investigation on picrotoxane sesquiterpenoids.


Assuntos
Produtos Biológicos , Sesquiterpenos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Lactonas
17.
Chem Biodivers ; 19(11): e202200762, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36177989

RESUMO

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.


Assuntos
Ligularia , Sesquiterpenos , Camundongos , Animais , Sesquiterpenos Policíclicos , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Células RAW 264.7 , Óxido Nítrico
18.
Nutrients ; 14(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36079888

RESUMO

The aim of the study was to explain the effects of sesquiterpene lactones (SLs) from chicory (Cichorium intybus L.) root extracts as inhibitors of acetylcholinesterase (AChE) at the molecular level and to determine the inhibition of AChE activity by specific SLs (lactucin and lactucopicrin) and different chicory extracts. The obtained SLs-rich extracts were purified by the countercurrent partition chromatography (CPC) technique. AChE inhibitors were analyzed using two models: isothermal titration calorimetry (ITC) and docking simulation. The results of ITC analysis of the enzyme and the ligands' complexation showed strong interactions of SLs as well as extracts from chicory with AChE. In a test of enzyme activity inhibition after introducing acetylcholine into the model system with SL, a stronger ability to inhibit the hydrolysis of the neurotransmitter was observed for lactucopicrin, which is one of the dominant SLs in chicory. The inhibition of enzyme activity was more efficient in the case of extracts, containing different enzyme ligands, exhibiting complementary patterns of binding the AChE active site. The study showed the high potential of using chicory to decrease the symptoms of Alzheimer's disease.


Assuntos
Chicória , Sesquiterpenos , Acetilcolinesterase/metabolismo , Calorimetria , Chicória/química , Inibidores da Colinesterase/farmacologia , Lactonas/química , Lactonas/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia
19.
Molecules ; 27(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36144782

RESUMO

A new sesquiterpenoid (1) was obtained by hydrogenating Chlojaponilactone B. The structure of 1 was elucidated according to a combination of NMR, HRESIMS, and NOE diffraction data. The treatment of H2O2 in a PC12 cell model was used to evaluate the antioxidant activity of 1. An MMT assay showed that 1 had no cytotoxicity to the PC12 cell and rescued cell viability from the oxidative damage caused by H2O2. The treatment of 1 stabilized the mitochondria membrane potential (MMP), which decreased the intracellular ROS level and reduced cell apoptosis in the oxidative stress model. The activities of antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of intracellular glutathione (GSH) were significantly enhanced after the treatment of 1. In addition, the results of qRT-PCR showed that 1 treatment minimized the cell injury by H2O2 via the up-regulation of the expression of nuclear factor erythroid 2 (Nrf2) and its downstream enzymes Heme oxygenase 1 (HO-1), glutamate cysteine ligase-modifier subunit (GCLm), and NAD(P)H quinone dehydrogenase 1 (Nqo1). Based on the antioxidant activity of 1, we speculated its potential as a therapeutic agent for some diseases induced by oxidative damage.


Assuntos
Fármacos Neuroprotetores , Sesquiterpenos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/toxicidade , NAD/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Células PC12 , Quinonas/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Superóxido Dismutase/metabolismo
20.
Biomed Pharmacother ; 153: 113478, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076580

RESUMO

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.


Assuntos
Anti-Inflamatórios não Esteroides , Sesquiterpenos , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina/uso terapêutico , Ciclo-Oxigenase 2 , Edema/induzido quimicamente , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Histamina , Inflamação/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia
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