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2.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674061

RESUMO

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.


Assuntos
Anti-Inflamatórios , Quempferóis , Humanos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Transdução de Sinais/efeitos dos fármacos
3.
Molecules ; 29(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474647

RESUMO

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.


Assuntos
Aesculus , Camundongos , Animais , Aesculus/química , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa , Sementes/química , Lipopolissacarídeos/farmacologia , Óxido Nítrico/análise
4.
Fitoterapia ; 172: 105783, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38110127

RESUMO

Eight nitrogenous compounds including five undescribed ones, aeswilnitrousol A (1), aeswilnitrousosides BD (2-4), and 6-(2-hydroxy-3-methylbutylamino)-8-oxoadenine (5) were isolated from the seeds of Aesculus wilsonii. Their structures and absolute configurations were established based on spectroscopic determination, calculated electronic circular dichroism (ECD) analysis, as well as chemical reaction methods. Among the three known compounds, 7 and 8 were obtained from the Aesculus genus for the first time, and 6 was gained from this plant initially. The 13C NMR data of 7 and 8 were reported for the first time. Moreover, the inhibitory effect of all the isolates against LPS-induced nitric oxide production in RAW264.7 macrophages was evaluated. As a result, compounds 2 and 8 exhibited anti-inflammatory activity in a concentration-dependent manner at 10, 25, and 50 µM.


Assuntos
Aesculus , Estrutura Molecular , Aesculus/química , Compostos de Nitrogênio/análise , Anti-Inflamatórios/farmacologia , Sementes/química , Óxido Nítrico
5.
Int J Mol Sci ; 24(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38139367

RESUMO

Ulcerative colitis, an immune-mediated inflammatory disease of the gastrointestinal tract, places a significant financial burden on patients and the healthcare system. Recently, reviews of the pomegranate and the abundant medicinal applications of its ellagitannins, as well as its pharmacological action, phytochemicals, metabolism, and pharmacokinetics, have been completed. However, summaries on their anti-ulcerative colitis effects are lacking. Numerous preclinical animal investigations and clinical human trial reports demonstrated the specific therapeutic effects of pomegranate and the effect of its ellagitannins against ulcerative colitis. According to the literature collected by Sci-finder and PubMed databases over the past 20 years, this is the first review that has compiled references regarding how the rich ellagitannins found in pomegranate have altered the ulcerative colitis. It was suggested that the various parts of pomegranates and their rich ellagitannins (especially their primary components, punicalagin, and ellagic acid) can inhibit oxidant and inflammatory processes, regulate the intestinal barrier and flora, and provide an anti-ulcerative colitis resource through dietary management.


Assuntos
Colite Ulcerativa , Lythraceae , Punica granatum , Animais , Humanos , Colite Ulcerativa/tratamento farmacológico , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/uso terapêutico , Frutas/química
6.
Fitoterapia ; 171: 105694, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37778669

RESUMO

Twenty-four aromatic compounds including five novel ones, dolilabphenosides A (1), B1 (2), B2 (3), C1 (4), and C2 (5) were obtained from the seeds of Dolichos lablab L. Their structures were established based on spectroscopic analyses and chemical reactions. Among the known compounds, 9, 10, 14, 17, 19, and 22-24 were gained from the family Leguminosae for the first time, and 6, 8, 11-13, 15, 16, 18, 20, as well as 21 were firstly identified from Dolichos genus. Moreover, the inhibitory effect evaluation of all the isolates against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages suggested that compounds 1-3, 6, 7, 11-15, 17, 20, 21, 23, 24 exhibited anti-inflammatory activity in a concentration-dependent manner. Moreover, the novel compounds, dolilabphenosides A (1), B1 (2), B2 (3) were found to inhibit the secretion of inflammatory cytokine IL-1ß.


Assuntos
Dolichos , Fabaceae , Dolichos/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Sementes/química
7.
Phytochemistry ; 214: 113827, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37595774

RESUMO

In vitro cytotoxicity-guided isolation based on a MTT assay was conducted for Penthorum chinense Pursh. (Penthoraceae). In the active components (EtOAc extract of P. chinense), eight undescribed neolignans, penthoneolignans A-H (1-8), and two known analogs (9 and 10) were obtained and identified. Their absolute configurations were determined by experimental and computational comparison of electronic circular dichroism spectra analysis. The MTT experiment results of the obtained neolignans on HT29 and LoVo cells indicated previously undescribed neolignans, penthoneolignans A (1) and F (6), showed better cytotoxicity than the positive drug 5-fluorouracil. Then, functional technologies such as the 5-ethyny1-2'-deoxyridine, wound healing, Transwell, and Western blot assays indicated that they could significantly inhibit the proliferation of HT29 and Lovo cells, promote apoptosis by up-regulating Bax, and down-regulating B-cell CLL/lymphoma 2 and poly ADP-ribose polymerase. Furthermore, a Western blot assay combining the Dsh homolog 2 agonist IWP-L6 and the ß-catenin agonist MG132 suggested their mechanism of action was closely related to the inhibition of the Wnt/ß-catenin signaling pathway. In conclusion, previously undescribed neolignans, penthoneolignans A (1) and F (6), may intervene in the development and progression of colorectal cancer by inhibiting the Wnt/ß-catenin signaling pathway and have the potential to be drug candidates.


Assuntos
Neoplasias Colorretais , Lignanas , Humanos , Via de Sinalização Wnt , Apoptose , Dicroísmo Circular , Lignanas/farmacologia , Neoplasias Colorretais/tratamento farmacológico
8.
Int J Biol Macromol ; 238: 124165, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36963537

RESUMO

Colorectal cancer (CRC) is one of the three major malignant tumors in the world. The major treatments currently recommended for it are surgery, radiotherapy, and chemotherapy, all of which are frequently accompanied by a poor prognosis and high recurrence rate. To limit cell proliferation and metastasis, trigger cell apoptosis, and regulate tumor microenvironment (TME), researchers are focusing attention on investigating highly effective and non-toxic natural medicines. According to the research reported in 89 pieces of related literature, between 2018 and 2021, specialists extracted 48 different types of polysaccharides with CRC inhibitory actions from various plants, including Dendrobium officinale Kimura et Migo., Nostoc commune Vaucher, and Ganoderma lucidum (Leyss. ex Fr.) Karst. The novel founded mechanisms mainly include: inhibiting cancer cell proliferation by acting on IRS1/PI3K/Akt and IL-6/STAT3 pathways; inducing cancer cell apoptosis by acting on LncRNA HOTAIR/Akt mediated-intrinsic apoptosis, or regulating the TNF-α-mediated extrinsic apoptosis; inducing cancer cell autophagy by acting on endoplasmic reticulum stress or mTOR-TFEB pathway; inhibiting cancer cell metastasis by regulating Smad2/3 and TLR4/JNK pathways; regulating TME in CRC; and maintaining the intestinal barrier. This review will provide more novel research strategies and a solid literature basis for the application of polysaccharides in the treatment of CRC.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Proliferação de Células , Neoplasias Colorretais/patologia , Apoptose , Linhagem Celular Tumoral , Microambiente Tumoral
9.
Int J Mol Sci ; 24(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36768602

RESUMO

Colorectal carcinoma (CRC) is a kind of malignant tumor closely related to ulcerative colitis. Xanthone derivatives are one of the most promising therapeutic drugs which have been used in phase I/II clinical trials for cancer therapy. Our previous study indicated that the aerial parts of Gentianella acuta Michx. Hulten (GA) was rich in xanthones and showed a good therapeutic effect on ulcerative colitis in mice, suggesting that GA xanthones might have some therapeutic or ameliorative effects on CRC. However, no relevant study has been reported. This study aims to find the effective substances of GA inhibiting CRC and clarify their mechanism. Solvent extraction, column chromatographic separation, and LC-MS analysis were used to characterize the 70% EtOH extract of GA and track xanthones abundant fraction XF. MTT assay was carried out to clarify the activity of GA fractions; the result showed XF to be the main active fraction. LC-MS analysis was executed to characterize XF, 38 xanthones were identified. Network pharmacology prediction, in vitro activity screening, and molecular docking assay were combined to predict the potential mechanism; the PI3K/Akt/mTOR signaling pathway was found to be most important. Western blot assay on the main active xanthones 1,3,5-trihydroxyxanthone (16), 1,3,5,8-tetrahydroxyxanthone (17), 1,5,8-trihydroxy-3-methoxyxanthone (18), and 1,7-dihydroxy-3,8-dimethoxyxanthone (19) was used to verify the above prediction; these xanthones were found to inhibit the PI3K/Akt/mTOR signaling pathway, and 17 played a significant role among them through Western blot assay using PI3K/AKT/mTOR agonist IGF-1. In conclusion, this study demonstrated that GA xanthones were effective compounds of GA inhibiting CRC by regulating PI3K/Akt/mTOR signaling pathway transduction, at least. Importantly, 1,3,5,8-tetrahydroxyxanthone (17), the most abundant active xanthone in GA, might be a candidate drug for CRC.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Gentianella , Xantonas , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Gentianella/química , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Xantonas/farmacologia , Xantonas/química , Neoplasias Colorretais/tratamento farmacológico , Proliferação de Células
10.
Phytomedicine ; 110: 154639, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608502

RESUMO

BACKGROUND: Jujube, a popular fruit from the Rhamnaceae family, relieves colorectal inflammation caused by spleen deficiency and has been used in many formulas in clinical for decades to treat colorectal cancer (CRC). As of yet, the therapeutic substances and mechanism of their action are unknown. PURPOSE: The purpose of this study is to define the therapeutic substances of jujube and its mechanism of action in treating CRC. METHODS: The pharmacological effects of jujube extract and its fractions were evaluated in vivo using a CRC mouse model induced by AOM/DSS. The DAI value, colon length, mortality, tumor burden, and histological tumor size of the treated animals were compared. To explore the potential therapeutic substances, LC-MS analysis was conducted to characterize the serum migration components. A network pharmacology experiment was carried out for potential molecular targets. To verify the therapeutic substances as well as the molecular mechanism of jujube intervening CRC, cellular MTT assay of the serum migration components, Western blot and IHC tests were conducted. RESULTS: The in vivo pharmacological studies showed that compared to AOM/DSS treated mice, the mortality and DAI value, tumor burden, and histological tumor size of jujube extract and its fat-soluble fraction (mainly contained triterpenes) treated mice were significantly reduced, and their colon lengths were obviously longer than AOM/DSS treated mice. The targeted-LC/MS analysis supposed triterpenes 3, 7, 9, 11, 12, 14, 17 - 21, and 25 - 28 to be the serum migration components, which might be the potential therapeutic substances. In the network pharmacology experiment, the GO annotation and enrichment analysis of the KEGG pathway indicated that PI3K-Akt pathway and inflammatory reaction were important factors for jujube inhibiting CRC. Cellular MTT assay of serum migration components indicated that the potential effective substances from fat-soluble fraction to be triterpenes 3, 7, 17, 19, 20, and 25. The Western blot and IHC assays implied that the jujube extract, its fat-soluble fraction, and triterpenes 7, 17, and 20 showed inhibition on the expression of PI3K/Akt/NF-κB signaling pathway-related proteins. Additionally, it was noted in the pharmacodynamic experiment that ZJL's effectiveness was more apparent than ZJH and SQL in tumor burden rate, colon length, and spleen weight, which indicated that the efficacy of ZJ is contributed from CD and SQ, and they may have a synergistic effect on anti-CRC. CONCLUSION: These results for the first time provide evidence that jujube triterpenes possess an anti-CRC effect, their mechanism was involving the control of the PI3K/Akt/NF-κB signaling pathway. What's more, the potential synergistic effect of the fat-soluble and water-soluble components found in this study provided a solid foundation for our deep understanding of how jujube can ameliorate CRC.


Assuntos
Neoplasias Colorretais , Triterpenos , Ziziphus , Animais , Camundongos , Ziziphus/metabolismo , NF-kappa B/metabolismo , Triterpenos/farmacologia , Proteínas Proto-Oncogênicas c-akt , Frutas , Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/patologia
11.
Biomed Pharmacother ; 155: 113712, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36130420

RESUMO

Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.


Assuntos
Aterosclerose , Produtos Biológicos , Doenças Cardiovasculares , Plantas Medicinais , Placa Aterosclerótica , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Autofagia , Aterosclerose/tratamento farmacológico , Colesterol/farmacologia
12.
Molecules ; 27(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35889496

RESUMO

Punica granatum L. (Punicaceae) is a popular fruit all over the world. Owning to its enriched polyphenols, P. granatum has been widely used in treating inflammation-related diseases, such as cardiovascular diseases and cancer. Twenty polyphenols, containing nine unreported ones, named punicagranins A-I (1-9), along with eleven known isolates (10-20), were obtained from the peels. Their detailed structures were elucidated based on UV, IR, NMR, MS, optical rotation, ECD analyses and chemical evidence. The potential anti-inflammatory activities of all polyphenols were examined on a lipopolysaccharide (LPS)-induced inflammatory macrophages model, which indicated that enhancing nitric oxide (NO) production in response to inflammation stimulated in RAW 264.7 cells was controlled by compounds 1, 3, 5-8, 10, 11, 14 and 16-20 in a concentration-dependent manner. The investigation of structure-activity relationships for tannins 6-8 and 12-20 suggested that HHDP, flavogallonyl and/or gallagyl were key groups for NO production inhibitory activity. Western blotting indicated that compounds 6-8 could down-regulate the phosphorylation levels of proteins p38 MAPK, IKKα/ß, IκBα and NF-κB p65 as well as inhibit the levels of inflammation-related cytokines and mediators, such as IL-6, TNF-α, iNOS and COX-2, at the concentration of 30 µM. In conclusion, polyphenols are proposed to be the potential anti-inflammatory active ingredients in P. granatum peels, and their molecular mechanism is likely related to the regulation of the p38 MAPK and NF-κB signaling pathways.


Assuntos
Lythraceae , Punica granatum , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Células RAW 264.7 , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Opt Lett ; 47(4): 858-861, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35167543

RESUMO

Optical injection into a chaotic laser under feedback is investigated for dimension enhancement. Although injecting a solitary laser is known to be low-dimensional, injecting the laser under feedback is found to enhance the correlation dimension D2 in experiments. Using an exceptionally large data size with a very large reconstruction embedding dimension, efficient computation is enabled by averaging over many short segments to carefully estimate D2. The dimension enhancement can be achieved together with time-delay signature suppression. The enhancement of D2 as a fundamental geometric quantifier of attractors is useful in applications of chaos.

14.
Phytochemistry ; 196: 113076, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35007935

RESUMO

As one of raw materials, the rhizome of Imperata cylindrica var. major (Nees) C.E. Hubb. is used in kinds of preparations curing inflammation related diseases, while its effective substances are not yet clear. In this paper, its chemical constituents and their anti-inflammatory activities were investigated. As results, ten compounds, named as imperphenoside A (1), imperphenols B (2) and C (3), imperphenosides D-F (4-6), and imperlignanosides A-D (7-10), along with previously reported thirty-seven known ones (11-47) were obtained from it. Their structures were ascertained basing on the extensive spectroscopic methods and electronic circular dichroism data analysis. Meanwhile, compounds 4, 11, 12, 24, 27, 31, 32, 37, 43, 45, and 47 exhibited nitric oxide inhibitory effects in concentration dependent at 3, 10, and 30 µM on lipopolysaccharides induced RAW 264.7 cells. Moreover, the western blot analysis indicated that compounds 4, 11, 43, and 47 could restrain the phosphorylation of nuclear factor kappa-B kinase to down-regulate the protein expression of inflammatory cytokines such as inducible nitric oxide synthase, interleukin-6 and tumor necrosis factor-α. In conclusion, they might play the anti-inflammatory effects through regulating NF-κB signaling pathway.


Assuntos
Poaceae , Rizoma , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Poaceae/química , Células RAW 264.7 , Rizoma/química
15.
J Nat Med ; 76(1): 39-48, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34345982

RESUMO

25 phenolic acids, including four new isolates, eurylophenosides A-D (1-4) and 21 known ones (5-25) were isolated and identified from the stems of Oplopanax elatus Nakai. Among the known compounds 5-9, 11-13, 16, 18-25 were isolated from the genus for the first time; 17 was first obtained from the plant; and the NMR data of 22 was reported here first. Meanwhile, the UVB-induced photodamage model of HaCaT cells was used to study the prevent-photodamage abilities of compounds 1-2, 4-8, 11-13 and 15-25 with a nontoxic concentration at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds at the concentration of 10, 25, and 50 µM, respectively. Consequently, pretreatment with compounds 1, 16, 17, 19, 20, 22, 24 and 25 could suppress the cell viability decreasing induced by UVB irradiation in a concentration-dependent manner. These results indicated that phenolic acids were one kind of material basis with prevent-photodamage activity of O. elatus.


Assuntos
Oplopanax
16.
J Nat Med ; 76(1): 200-209, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34743295

RESUMO

One new compound, 3Z-1-O-ß-D-glucopyranosyl-3-hexene-1,5-diol (1), together with 26 known isolates (2-27) were obtained from the leaf of Morus alba var. multicaulis. Among the known compounds, 7, 11, 12, 14, 15, 18, 19, 23, and 24 were firstly obtained from the Morus genus; 2-5, 8, 10, 13, and 20 were firstly isolated from M. alba. var. multlcaulis. Meanwhile, the NMR data of 20 and 23 have been reported here for the first time. Moreover, compounds 1-11, 13, 21, and 23-27 showed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells. In mechanism, compound 1 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα) to accelerate the ß-oxidation of fatty acids via promoting the phosphorylation of acetyl-CoA carboxylase 1 and up-regulating carnitine palmitoyl-transferase 1A. Besides, compound 1 exerted lipolysis effect by activating hormone-sensitive lipase. In brief, compound 1 might play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acid ß-oxidation and lipolysis. 27 compounds were obtained from the leaf of Morus alba var. multicaulis. Among them, 18 showed inhibitory effects on TG accumulation in HepG2 cells. Moreover, the new compound, 3Z-1-O-ß-D-glucopyranosyl-3-hexene-1,5-diol (1), was found to play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acids ß-oxidation and lipolysis.


Assuntos
Morus , Proteínas Quinases Ativadas por AMP/metabolismo , Células Hep G2 , Humanos , Metabolismo dos Lipídeos , Folhas de Planta , Transdução de Sinais
17.
Front Chem ; 9: 766041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805098

RESUMO

In the process of continuing to investigate ultraviolet b (UVB) irradiation protective constituents from Oplopanax elatus stems, nine new sesquiterpenes, named as eurylosesquiterpenosides A-D (1-4), eurylosesquiterpenols E-I (5-9), and ten known ones (10-19) were gained. Their structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. In addition, UVB induced HaCaT cells were used to study their anti-photoaging activities and mechanism. The results consolidated that compounds 7, 11, and 14 could improve the survival rate of HaCaT cells in concentration dependent manner at 10, 25, and 50 µM. Furthermore, western blot assay suggested that all of them could inhibit the expression of matrix metalloproteinase-1 (MMP-1), and increase the level of type I collagen markedly. Compounds 11 and 14 could reduce the phosphorylation of extracellular signal-regulated kinase and p38, respectively. Besides, compounds 7, 11, and 14 could significantly down-regulate the expression of inflammation related protein, such as tumor necrosis factor-α and cyclooxygenase-2, which indicated that they played anti-photoaging activities by reducing MMP-1 expression via down-regulating the production of inflammatory mediators and cytokines in UVB-induced HaCaT cells.

18.
Fitoterapia ; 154: 105018, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34450202

RESUMO

Twenty-two flavonoids and stilbenes (1-22) were obtained from the leaf of Morus alba var. multicaulis. Among them, morusalbanosides A (1), B1 (2), and B2 (3) were new compounds. Moreover, compounds 1, 3, 4-11, 15-18, and 22 displayed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells in a concentration dependent manner. Furthermore, compounds 1, 3, 11, and 22 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα), reduce the synthesis of TG by inhibiting the expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). While, only compounds 1 and 11 could promote the phosphorylation of acetyl-CoA carboxylase 1 (ACC1) and accelerate the oxidation of fatty acids by up-regulating carnitine palmitoyltransferase 1A (CPT1A). In brief, this study found that most of the researched flavonoids and stilbenes could regulate TG metabolism in vitro. They might play the role by up-regulating phosphorylation of AMPKα, inhibiting TG biosynthesis, and promoting the oxidation of fatty acids.


Assuntos
Flavonoides/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Morus/química , Estilbenos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , China , Flavonoides/isolamento & purificação , Células Hep G2 , Humanos , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Estilbenos/isolamento & purificação , Triglicerídeos/metabolismo
19.
Food Funct ; 12(10): 4496-4503, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33885123

RESUMO

Twenty-nine triterpenes were obtained from the fruits of Ziziphus jujuba Mill. through various chromatography methods, and their stereo-structures were confirmed by spectroscopic methods. Among them, 2α,3ß,20-trihydroxylupane-28-oic acid (1) was identified as a new compound, and the 1H and 13C NMR data of 7, 8 and 23, as well as the 13C NMR data of 17 are reported here for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As results, compounds 2, 7, 10-13, 15, 16, 18-21, 26-29 were found to play important roles in suppressing NO production at 5 µM. The structure-activity relationships (SARs) on NO inhibition indicated that the ursolic and oleanolic acid skeletons, p-coumaroyl group substitution, six-membered A ring, and deoxygenation (loss of C[double bond, length as m-dash]O) in the C ring showed a more positive effect on the NO inhibitory activity of triterpenes, while the reduction of the A ring C[double bond, length as m-dash]O to OH was a negative factor. Moreover, it was found that compounds 15 and 19 could suppress the phosphorylation of IκBα and NF-κB/p65 to prevent it from shifting into the nucleus and downregulate the expression of inflammatory factors, such as iNOS, IL-6 and TNF-α. Our investigations revealed that the NO inhibitory effects of the active triterpenes obtained from Z. jujuba were mediated, at least in part, through the NF-κB signaling pathway.


Assuntos
Frutas/química , Inflamação/tratamento farmacológico , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Ziziphus/química , Animais , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ácido Oleanólico , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Molecules ; 25(17)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825257

RESUMO

Two new 12,23-epoxydammarane-type saponins, notoginsenosides NL-I (1) and NL-J (2), were isolated and identified from Panax notoginseng leaves through the combination of various chromatographies and extensive spectroscopic methods, as well as chemical reactions. Among them, notoginsenoside NL-J (2) had a new skeleton. Furthermore, the lipopolysaccharide (LPS)-induced RAW 264.7 macrophage model was used to identify the in vitro anti-inflammatory activity and mechanisms of compounds 1 and 2. Both of them exerted strong inhibition on nitric oxide (NO) productions in a concentration-dependent manner at 1, 10, and 25 µM. Moreover, these two compounds significantly decreased the secretion of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB/p65), and nitric-oxide synthase (iNOS) in LPS-activated RAW 264.7 cells.


Assuntos
Anti-Inflamatórios , Panax notoginseng/química , Folhas de Planta/química , Saponinas , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/biossíntese , Citocinas/biossíntese , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico Sintase Tipo II/biossíntese , Células RAW 264.7 , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Fator de Transcrição RelA/metabolismo
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