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Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin Ⅴ-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a dose- and time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.
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Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin V-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a doseand time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.
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Objective: To investigate the chemical constituents of the leaves of Phyllanthus acidus. Methods: All compounds were isolated by silica gel and Sephadex LH-20 gel column chromatographies as well as semi-preparative HPLC, and their structures were elucidated on the basis of physicochemical properties and spectral data. Results: Ten compounds were isolated and identified as 3α-cinnamoyloxyurs-20(29)-en-18β-ol (1), phyllanthol (2), maslinic acid (3), ovoideal E (4), quercetin-3-rhamnoside (5), 4-hydroxybenzoic acid (6), methyl 4-hydroxyphenylacetate (7), 4-O-(β-glucopyranosyloxy)-benzoic acid (8), thioacetic anhydride (9), L-pyroglutamic acid (10). Conclusion: Compound 1 is a new compound named as phyllanacidol B, and compounds 3-10 are obtained from P. acidus for the first time.
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Objective: To investigate the effects of maslinic acid (MA) on the proliferation and autophagy in nasopharyngeal carcinoma CNE2 cells and to elucidate the regulatory role of PI3K/Akt/mTOR pathway in this process. Methods: The effect of MA on the proliferation of CNE2 cells was assessed by CCK-8. MDC staining of autophagic vacuoles was performed for autophagy analysis. Additionally, the levels of autophagy-and PI3K/Akt/mTOR-associated proteins were examined using western blot analysis. Results: MA significantly inhibited the proliferation of CNE2 cells in a dose-and time-dependent manner. MA displayed autophagy-inducing effect, as shown by the increased MDC-labeled vacuoles, up-regulated LC3-II/LC3-I ratio and Atg5, as well as the down-regulated p62 level after MA treatment. Moreover, we observed that MA inhibited the expression of PI3K-p110α and the phosphorylation of Akt and mTOR. Conclusion: MA inhibits the proliferation and induces the autophagy of CNE2 cells, the mechanism may be related to the PI3K/Akt/mTOR signaling pathway. These results imply that MA may be a potential anti-cancer agent for use in the treatment of nasopharyngeal carcinoma.
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Objective: To study the chemical constituents of Empetrum nigrum var. japonicum. Methods: The chemical constituents were isolated by silica gel column chromatography and HPLC, and its structure was identified by their spectral data and physicochemical properties analysis. Results: Twenty-two compounds were isolated from ethyl acetate extracts of E. nigrum var. japonicum with the structures identified as 3,4-dihydroxybenzoic acid (1), 3-methoxy-4-hydroxybenzoic acid (2), methyl-3,4-dihydroxybenzoate (3), dihydroconiferyl alcohol (4), (6S,9R)-vomifoliol (5), (6R,9R)-9-hydroxy-3-one-α-ionol (6), phenylpropionic acid (7) quercetin-3-O-(6″-benzoyl)-β-D-galactoside (8), daucosterol (9), quercetin-3-O-β-D-glucopyranoside (10), phenylpropyl-O-β-D-glucopyranoside (11), maslinic acid (12), rutinum (13), quercetin-3-O-β-D-galactoside (14), benzyl-(6-O- α-L-arabinofuranosyl)-O-β-D-glucopyranoside (15), cinnamol-O-(6-O-α-L-arabinopyranosyl)-β-D-glucopyranoside (16), quercetin-3- O-neohesperidoside (17), kaempferol-3-O-neohesperidoside (18), 2α,3β-dihydroxyurs-12-en- 28-oic acid (19), foliachinenoside A2 (20), kaempferol-3-O-rutinoside (21) and isorhamnetin-3-O-rutinoside (22). Conclusion: Compounds 1-6, 8, 11-13, 15-22 were isolated from E. nigrum var. japonicum for the first time.
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Objective: To investigate chemical constituents from Isodon coetsa distributed in Guizhou. Methods: Chemical constituents were isolated and purified by chromatography with silica gel, Sephadex LH-20, and semi-preparative HPLC, and their structures were identified by analysis of spectroscopic evidences and physicochemical properties as well as relevant references. Results: A total of 19 compounds were isolated from plant material extracted with 95% aqueous methanol, which were elucidated as β-sitosterol (1), stigmasterol (2), β-daucosterol (3), methyl linolenat (4), 9,12-octadecadienoic acid-2-hydroxy-1,3-propanedinyl ester (5), ursolic acid (6), oleanoic acid (7), 3β-hydroxy-urs-20-en-28-oic acid (8), betulinic acid (9), kurarinone (10), maslinic acid (11), 2α-hydroxy ursolic acid (12), 2α,3α-dihydroxy-urs-12-en-28-oic acid (13), 2α,3α,24-trihydrxyolean-12-en-28-oic acid (14), 2α,3β,24- trihydroxyolean-12-en-28-oic acid (15), formononetin (16), emodin (17), uracil (18), and sucrose (19). Conclusion: Compounds 2, 4, 5, 9, 11, 13-19 are isolated from this plant for first time, and compounds 11, 17, 19 are isolated from the genus of Isodon for the first time.
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Objective To study the protective effect and mechanism of maslinic acid (MA) on acute liver injury (ALI) in rats.Methods Fifty BALB/c mice were randomly divided into control group,model group,and low (12.5 mg/kg),medium (25.0 mg/kg) and high doses (50.0 mg/kg) of MA,with 10 rats in each group.The control group was intraperitoneally injected with normal saline.The other groups were intraperitoneally injected with lipopolysaccharide (LPS) (50 mg/kg) and D-Gal N (500 mg/kg) to prepare mouse AL[model.The MA groups were administered with 12.5,25.0,50.0 mg/kg MA 1 h before model establishment,respectively.All the mice were sacrificed 6 h after model establishment,and serum and liver tissues were collected.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured.Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue.Thiobarbituric acid method was used to determine malondialdehyde (MDA).H2O2 reaction product colorimetric was used to determine the content of myeloperoxidase (MPO).The tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue was detected by enzyme-linked immunosorbent assay,respectively.Western Blot was conducted to detect the expression of nuclear factor E2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1) and the activation of nuclear factor-kappa B (NF-κB) pathway.Results Compared with the model group,the liver histopathology in the low,medium and high doses MA groups was significantly improved.The serum ALT and AST levels were decreased,and the differences were statistically significant (all P＜0.05).The contents of MDA and MPO in liver tissues were decreased,and the differences were statistically significant (all P＜0.05).The protein contents of Nrf2 and HO-1 were increased,the differences were statistically significant (all P＜0.05).The NF-κB pathway was inhibited,and the differences were statistically significant (all P＜0.05).The levels of TNF-α and IL-6 in serum and liver tissues were decreased,and the differences were statistically significant (all P＜0.05).Conclusions MA has a protective effect on LPS/D-Gal N-induced ALI,and its mechanism is related to inhibition of NF-κB pathway and activation of Nrf2/HO-1 pathway.
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Objective: To study the chemical constituents from the herb of Salvia plebeian. Methods: The constituents were isolated and purified by silica gel, Sephadex LH-20, and ODS column chromatography, and preparative TLC. The structures of the isolated compounds were elucidated by spectroscopic analysis and physicochemical properties. Results: Eleven compounds were isolated and purified from the ethanol extract of S. plebeia. They were identified as 5,6-dihydroxy-7,4'-dimethoxyflavone (1), 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (2), nepetin (3), homoplantaginin (4), apigenin (5), cirsiliol (6), 6-methoxynaringenin (7), emodin (8), maslinic acid (9), isorosmanol (10), and (-)-epiloliolide (11). Conclusion: Among them, compound 11 is isolated from the plants of Salvia L. firstly, and compounds 1, 2, 6, 9, and 10 are isolated from S. plebeian for the first time.
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AIM@#To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.@*METHOD@#HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).@*RESULTS@#The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.@*CONCLUSION@#The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
Subject(s)
Animals , Humans , Male , Mice , Diabetes Mellitus , Drug Therapy , Genetics , Metabolism , Drugs, Chinese Herbal , Enzyme Inhibitors , Glycogen , Metabolism , Glycogen Phosphorylase , Genetics , Metabolism , Hep G2 Cells , Insulin , Metabolism , Mice, Inbred C57BL , Signal Transduction , TriterpenesABSTRACT
The aim of this study was to establish an analytical method to detect the presence of the responsible triterpenoids of the anti-inflammatory activity of the leaves of Ugni molinae (murtilla). Successive leaves extracts of EtOAc (EAE) and ethanol (TEE) were prepared, obtaining for the first time from TEE a triterpenoid-rich sub-fraction (TF). The topical anti-inflammatory activity of TF was assessed (43.3 percent at 1 mg/ear) by means of the TPA-induced mouse ear oedema model, which was compared to EAE (83.1 +/- 3.2 percent) and TEE (78.3 +/- 11.8 percent) activities, both previously evaluated by us. These extracts were characterized in their triterpenoids by HPLC-UV and HPLC-ESI-MS. We demonstrated that TF has triterpenoids responsible in part of the anti-inflammatory activity, among them, madecassic and maslinic acids. These two compounds have been reported for the first time for this species. ED50 for madecassic and alphitolic acids are also here reported.
El objetivo de este trabajo fue establecer un método analítico para determinar la presencia de los triterpenoides responsables de la actividad anti-inflamatoria de las hojas de Ugni molinae (murtilla). Fueron preparados los extractos seriados de EtOAc (EAE) y etanólico (TEE) desde sus hojas, obteniendo desde el TEE por primera vez una sub-fracción rica en triterpenoides (TF). Se demostró la actividad anti-inflamatoria tópica del TF por el modelo de edema de oreja de ratón inducida por TPA (43,3 por ciento a 1 mg/oreja), la cual fue comparada con las de los EAE (83,1 +/- 3,2 por ciento) y TEE (78,3 +/- 11,8 por ciento) determinadas en nuestros estudios previos. Dichos extractos fueron caracterizados en sus triterpenoides por CLAE-UV y CLAE-IES-MS. Demostramos que el TF contiene triterpenoides responsables en parte de la actividad anti-inflamatoria, entre ellos, los ácidos madecásico y maslínico, reportados por primera vez para esta especie. Se informan además las DE50 para los ácidos madecásico y alfitólico.
Subject(s)
Animals , Rats , Anti-Inflammatory Agents , Plant Extracts/pharmacology , Plant Leaves/chemistry , Myrtaceae/chemistry , Triterpenes/isolation & purification , Triterpenes/analysis , Chile , Chromatography, High Pressure Liquid , Spectrometry, Mass, Electrospray Ionization , Triterpenes/pharmacologyABSTRACT
Objective: To study the chemical constituents of Ostryopsis nobilis and their anti-oxidant activities. Methods: The chemical constituents were isolated and purified by various column chromatographic methods. Their structures were identified by physicochemical properties and spectral analyses. Results: Twenty-three compounds were isolated from the 95% ethanol extract and identified as loliolide (1), maslinic acid (2), vanillic acid (3), 3β-(3, 4-dihydroxycinnamoyl)-erythrodiol (4), dammarenediol II 3-caffeate (5), pinoresinol (6), quercetin (7), daucosterol (8), kaempferol (9), 3, 5-dihydroxy-1, 7-bis (4H-hydroxyphenyl) heptane (10), alnusdiol (11), casuarinondiol (12), quercetin-3-O-α-L-arabinoside (13), isoquercetin (14), 2, 3-dihydroxylbenzoic acid (15), isoquercetin-6″-butyl acetate (16), isoquercetin-6″-benzoate (17), 4″-trans-p-coumaroyl-kaempferol-3-O-α-L-rhamnoside (18), 4″-cis-p-coumaroyl-kaempferol-3-O-α-L-rhamnoside (19), maslinic acid-28-O-β-D-glucoside (20), gallic acid (21), betulatetraol (22), and L-chiroinositol (23). Conclusion: All the compounds are isolated from the plants in this genus for the first time. Diarylheptanoid compounds and other ten monomer compounds exhibit the good scavenging activities against 2, 2-diphenyl-1-picryhydrazyl (DPPH), and O. nobilis extracts show moderate anti-oxidant effects.
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Objective: To develop a quantitative analysis of multi-components by single-marker (QAMS) method for the simultaneous determination of six triterpene acid (euscaphic acid, tormentic acid, maslinic acid, corosolic acid, oleanolic acid, and ursolic acid) contents in the effective fraction of Eriobotryae Folium. Methods: Ursolic acid was used as the internal reference substance, and the relative correlation factors (RCF) of euscaphic acid, tormentic acid, maslinic acid, corosolic acid, and oleanolic acid were determined by HPLC-ELSD with good reproducibility. The contents of the five components were calculated according to the RCF, respectively. The contents of these six triterpene acids in 15 batches of effective fraction were determined by the external standard method. The rationality, feasibility, and repeatability of the QAMS method were verified by comparing the results obtained from the two different methods. Results: For the six triterpene acids, there was no significant difference between the quantitative results with the two different methods in the 15 batches. Conclusion: The method established in this research is accurate and feasible that it just needs to assay single-marker (ursolic acid) for the determination of six triterpene acids in the effective fraction of Eriobotryae Folium simultaneously. Therefore, this method could provide a new reference for the quality assess of multi components in Chinese materia medica.