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1.
Danshen is one of the most famous herbs in the world, and more and more danshen–prescribed drugs interactions have been reported in recent years. Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen–drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver–Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver–Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0.4 and 1.7 μM, respectively. Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen–propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol.  相似文献   

2.
Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructus schisandrae which has been widely used as a tonic in traditional Chinese medicine for many years. Inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb–drug interaction. The aim of the present study is to investigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGT isoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM of deoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligible inhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin A were demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC50 value of 10.8 ± 0.4 μM and 12.5 ± 0.5 μM, respectively. Dixon and Lineweaver–Burk plots showed that inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, and inhibition kinetic parameter (Ki) was calculated to be 0.48 μM. Inhibition of UGT1A3 by schisantherin A gave the best fit for types of noncompetitive inhibition, and the results showed Ki to be 11.3 μM. All these experimental data suggested that herb–drug interaction might occur when deoxyschizandrin or schisantherin A containing herbs were co-administered with drugs which mainly undergo UGT1A3-mediated metabolism. However, given that many in vivo factors could influence the in vitro–in vivo extrapolation (IVIVE), these in vitro inhibitory parameters should be considered with caution.  相似文献   

3.
Sour jujube is a common fruit and traditional medicine in China. Bioactivity-guided fractionation of sour jujube was used to determine the chemical identity of potent antiproliferative and antioxidant constituents. Four novel ursane-type triterpenoids, together with 8 known were isolated and identified. The new triterpenoids were elucidated to be 2α,3β,13β,23-tetrahydroxy-urs-11-en-28-oic acid (3), 2α,3β-dihydroxy-urs-20(30)-en-28-oic acid (9), 2α,3β,28-trihydroxy-urs-20(30)-ene (10), and 3β,12β,13β-trihydroxy-ursan-28-oic acid (11). Among the triterpenoids isolated, 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (7), 9 and 10 showed high potent inhibitory activity toward the proliferation of HepG2 cells, which the IC50 values were lower than 5 μM. Compounds 9 and 10 also exhibited pronounced activity against MCF-7 cells, with IC50 value of 0.8 ± 0.03 and 1.5 ± 0.1 μM, respectively. Compound 10 showed high antioxidant activity with an EC50 of 0.8 ± 0.02 μM, which was 18.9 times higher than ascorbic acid in antioxidant capacity.  相似文献   

4.
Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-β -D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β -D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC50 values of 15.02 μM (SI = 111.3), 9.00 μM (SI = 185.9) and 12.01 μM (SI = 139.2).  相似文献   

5.
Four new lignans (1, 7–9), together with nine known ones, were isolated from the anti-osteoporosis fraction of the extract of Sambucus williamsii Hance which was eluted by 50% and 95% aqueous ethanol over D101 macroporous resin column. Their structures were elucidated by NMR spectroscopic analyses, and the absolute configurations of all compounds were determined by application of circular dichroism method. All the compounds were reported for the first time from the Sambucus genus and firstly studied for their proliferation effects on osteoblastic-like UMR 106 cell. The data showed that compounds 2–9 significantly promoted cell proliferation in some dose, especially compounds 2, 3, 4, 5, and 7 increased osteoblastic cell numbers by 31.3%, 28.3%, 25.6%, 25.1% and 26.0% at 10− 10 M, 10− 10 M, 10− 7 M, 10− 10 M and 10− 10 M, respectively, which suggested that lignans were the components accounting for the bone protective effects of SWH.  相似文献   

6.
Four new isocoumarins (1–4), along with three known ones (5–7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3–5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC50 values in the ranges 6.41–23.91 μM and 6.67–39.07 μM, respectively.  相似文献   

7.
Three new cycloartane triterpenoids (1–3) and two known compounds (4, 5) were isolated from the whole plant of Beesia calthaefolia. Their structures were elucidated by 1D and 2D NMR, HRESIMS and optical rotation spectral data. All isolates were investigated for their inhibitory effects on the classical pathway of the complement system. Among them, compound 4 showed stronger inhibitory activity (IC50 136.7 μM) than positive control (Rosmarinic acid, IC50 181.8 μM) while compounds 2 and 3 were moderately active with IC50 value of 206 μM and 200.9 μM. Chemical compound studied in this article: Rosmarinic acid (PubChem CID: 5281792).  相似文献   

8.
A phytochemical study on the ethanolic extract of the stem barks of Uncaria laevigata leads to the isolation and characterization of 18 triterpenoid compounds. Ten of these are new, including one novel heptanortriterpenoid (1), four ursane triterpenes (2–4, 10), and five oleanane triterpenes (5–9). Their structures were established by spectroscopic methods, especially by 2D-NMR and MS analyses. All these isolates were evaluated for their inhibitory effects on α-glucosidase: ursolic acid and 3 showed potent activities with IC50 values of 16 ± 2.2 and 49 ± 3.7 μM, respectively.  相似文献   

9.
Two new alkaloids, named stenine A (1) and stenine B (2), along with the known compounds neostenine (3), stenine (4) and neotuberostemonine (5), were isolated from the roots of Stemona sessilifolia. Their structures were elucidated by 1D- and 2D-NMR spectra and X-ray single-crystal diffraction experiment. Anti-acetylcholinesterase (AChE) activity of compounds 1–5 were also tested. Compounds 2 and 4 showed significant anti-acetylcholinesterase activities, with IC50 values of 2.1 ± 0.2 μM and 19.8 ± 2.5 μM, resp. The mode of AChE inhibition by Compound 2 (the most potential AChE inhibitor) was reversible and competitive. In addition, molecular modeling was performed to explore the binding mode of compound 2 with AChE.  相似文献   

10.
The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p < 0.01). On human PBMC, globularifolin at 6.25 and 12.5 μM concentrations showed a stimulatory effect, while at 12.5–200 μM it suppressed response of PBMC to stimulation with phytohemagglutinin (PHA). Globularifolin (50–200 μM) enhanced neopterin formation dose-dependently, whereas tryptophan breakdown was not influenced. At 50–200 μM in unstimulated PBMC in THP-1 cells, globularifolin induced a significant expression of nuclear factor-κB (NF-κB) as was quantified by Quanti-Blue assay. By contrast, in lipopolysaccharide (LPS)-stimulated cells, the higher concentrations of globularifolin suppressed NF-κB expression dose-dependently and a significant decrease was observed at 200 μM concentration. A positive correlation was found between increased neopterin and NF-κB activity (p < 0.01). Similarly, a positive correlation was observed between neopterin levels in mitogen-induced cells and NF-κB activity in LPS-stimulated cells after treatment with globularifolin (p = 0.001). The free radical scavenging capacity of globularifolin evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay showed relative ORAC values of 0.36 ± 0.05 μmol Trolox equivalent/μmol. All together, results show that natural antioxidant globularifolin might represent a potential immunomodulatory as well as proliferative agent, which deserves further in vitro and in vivo studies.  相似文献   

11.
Four new C14-polyacetylene glycosides, namely coreosides A–D (1–4), were isolated from the capitula of Coreopsis tinctoria, a Snow chrysanthemum or Snow tea that is used as a folk tea for prevention of cardiovascular disease in southern Xinjiang, China. Coreosides A–D feature a long chain structure as its aglycon with two acetylenes on C-8 and C-10 and two olefinics on C-6 and C-12 sites, which construct a large conjugate system. The structures were elucidated on the basis of spectroscopic evidences and hydrolysis. Compounds 1–4 exhibited significant inhibition against cyclooxygenase-2 at the concentration of 1 × 10− 6 mol/L, with its IC50 values of 0.22–8.8 × 10− 2 μmol/L.  相似文献   

12.
Five new mexicanolide-type limonoids, carapanolides C–G (1–5), together with two new phragmalin-type limonoids, carapanolides H–I (6, 7), were isolated from the oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the P388 (IC50 17.9 μM in 1, 15.8 μM in 3) and L1210 cell lines (IC50 13.3 μM in 1, 18.1 μM in 3, 16.9 μM in 7). On the other hand, Carapanolide D (2) exhibited a strong inhibitory effect in the HL-60 cell line (IC50 11.0 μM), Carapanolides F (4) showed inhibitory activity in the L1210 cell line (IC50 15.9 μM), and the cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.  相似文献   

13.
Plants belonging to the Amaryllidaceae contain an exclusive group of alkaloids, known as sources of important biological activities. In the present work, Pancratium illyricum L., a species belonging to this family and endemic of Sardinia (Italy), was investigated for its alkaloid content. Fresh bulbs and leaves were processed separately. Standard extraction and purification procedures were applied to obtain fractions and compounds for GC–MS and NMR analysis. In addition to eight already known alkaloids (1–8), 11α-hydroxy-O-methylleucotamine (9) was isolated for the first time and its structure completely determined by one and two-dimensional 1H and 13C NMR spectroscopy. This new galanthamine-type compound exhibited a pronounced in vitro acetylcholinesterase (AChE) inhibitory activity (IC50 = 3.5 ± 1.1 μM) in comparison to the reference standard galanthamine hydrobromide (IC50 = 1.5 ± 0.2 μM).  相似文献   

14.
Four new triterpenoids, indicalilacols A-D (1–4), were isolated from the MeOH extract of the fruits of Azadirachta indica, including a new 19(10 → 9β)abeo-tirucallane derivative, two new tirucallane-type triterpenoids, and a new euphane-type triterpenoid, along with three known tirucallane-type triterpenoids. Their structures were elucidated on the basis of spectroscopic analyses. The absolute configuration of 2 was elucidated by the chemical conversion of 2 into 21-oxo-melianodiol 24,25-acetonide. Compounds 2, 6–8 exhibited moderate cytotoxicity against three human cancer cell lines, including multidrug-resistant (MDR) cancer cells (KB-C2). Although compound 5 was not cytotoxic against any of the tested cancer cell lines, 5 showed cytotoxicity against KB-C2 cells in the presence of 2.5 μM colchicine, suggesting that 5 might have an MDR-reversal effect.  相似文献   

15.
Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses – namely diarrhoea, inflammation, liver disorders, snake bite and fever – are linked – at least in part – to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50 ≅ 10 μg/mL), COX-1(IC50 ≅ 50 μg/mL), and 12-LOX (IC50 ≅ 170 μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2 is not probable, but the extract induced the synthesis of the anti-inflammatory eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided fractionation of the crude extract led to the isolation of ziniolide, a known 12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the n-hexane extract (IC50 = 69 μM). Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NFκB activation, a key regulator of the arachidonic pathway.  相似文献   

16.
Two new lanostanoids, 3α-acetoxy-22-oxo-5α-lanosta-8,24-dien-21-oic acid, named tsugaric acid D (1) and 16α-hydroxy-3-oxo-5α-lanosta-6,8,24(241)-trien-21-oic acid, named tsugaric acid E (2) were isolated from the fruit bodies of Ganoderma tsugae. The structures 1 and 2 were determined by spectroscopic methods. Compound 1 and known compounds 3 and 6 exhibited significant inhibitory effects on xanthine oxidase (XO) activity with an IC50 values of 90.2 ± 24.2, 116.1 ± 3.0, and 181.9 ± 5.8 μM, respectively. Known compound 5 was able to protect human keratinocytes against damage induced by UVB light, which showed 5 could protect keratinocytes from photodamage. The 1 and 5 μM 1 combined with 5 μM cisplatin, respectively, enhanced the cytotoxicity induced by cisplatin. It suggested that 1 and 5 μM 1 combined with low dose of cisplatin may enhance the therapeutic efficacy of cisplatin and reduce side effect and cisplatin resistant.  相似文献   

17.
Five novel compounds — three sesquiterpene coumarin derivatives, ferulin A (1), B (2), and C (3), and two sesquiterpene chromone derivatives, ferulin D (4) and E (5), together with eleven known compounds (6–16) have been isolated from the roots of Ferula ferulaeoides (Steud.) Korov. Their structures were established by comprehensive spectroscopic analysis. The biosynthetic pathways leading to these compounds were proposed. The cytotoxicity of all these isolates against HepG2, MCF-7, and C6 cancer cell lines was evaluated and compound 7 displayed the highest potency against HepG2, MCF-7, and C6 with IC50 values 39.9 μM, 37.7 μM, and 16.0 μM, respectively.  相似文献   

18.
Three new cleistanthane diterpenes named tomocinon (1), tomocinol A (2), and tomocinol B (3), were isolated from the EtOAc extract of the seed of Caesalpinia sappan. Their structures were determined by extensive NMR spectroscopic analysis. The absolute stereochemistry of tomocinon (1) has been established by CD spectroscopic analysis. Cleistanthane diterpenes (1–3) represents the novel class of antiausterity agents having preferential cytotoxicity against PANC-1 human pancreatic cancer cell line under nutrient deprived condition with PC50 value of 34.7 μM, 42.4 μM and 39.4 μM, respectively.  相似文献   

19.
It is well known that hyperglycaemia is the initiating cause of tissue damage associated with type 2 diabetes mellitus and that enhanced hepatic gluconeogenesis may account for the increase in blood glucose levels. The purpose of this work was to investigate the possible actions and mechanisms of three related citrus flavanones, namely hesperidin, hesperetin and naringenin, on hepatic gluconeogenesis and related parameters using isolated perfused rat liver. Hesperetin and naringenin (but not hesperidin) inhibited gluconeogenesis from lactate plus pyruvate, alanine and dihydroxyacetone. The inhibitory effects of these flavanones on gluconeogenesis from lactate and pyruvate (hesperetin IC50 75.6 μM; naringenin IC50 85.5 μM) as well as from alanine were considerably more pronounced than those from dihydroxyacetone. The main cause of gluconeogenesis inhibition is the reduction of pyruvate carboxylation by hesperetin (IC50 134.2 μM) and naringenin (IC50 143.5 μM) via inhibition of pyruvate transport into the mitochondria. Secondary causes are likely inhibition of energy metabolism, diversion of glucose 6-phosphate for glucuronidation reactions and oxidation of NADH by flavanone phenoxyl radicals. The influence of the structural differences between hesperetin and naringenin on their metabolic effects was negligible. Analytical evidence indicated that the presence of a rutinoside moiety in hesperidin noticeably decreases its metabolic effects, confirming that hesperetin and naringenin interact with intracellular enzymes and mitochondrial or cellular membranes better than hesperidin. Thus, the inhibition of the gluconeogenic pathway by citrus flavanones, which was similar to that of the drug metformin, may represent an attractive novel treatment strategy for type 2 diabetes.  相似文献   

20.
BackgroundSafflor yellow A (SY) has been demonstrated to be beneficial to cardiovascular system. Our previous study showed that hydroxysafflor yellow A (HSYA), a main component of SY, could increase peroxisome proliferator-activated receptor γ mRNA expression. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes.MethodsThe proliferation and adipogenesis of 3T3-L1 cells treated with HSYA was studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining and intracellular triglyceride assay methods. HSL mRNA expression and promoter activity were studied by real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods.ResultsHSYA (0.1 mg/L) significantly inhibited the proliferation of 3T3-L1 cells when compared with control cells in 8 h. This effect was further enhanced with the extension time (24 to 96 h) and an increase of concentration of HSYA (1–10 mg/L). The maximal inhibitory action was observed at 0.1 mg/L HSYA in 72 h (86 ± 11.8% vs. 100 ± 4.1%, p < 0.01). HSYA notably reduced the amount of intracellular lipid and triglyceride content in adipocytes to 85% (1 mg/L) and 75% (100 mg/L) on Day 4 following the differentiation, respectively, while increased HSL mRNA expression and promoter activities to 2.7 fold and 1.55 fold, respectively (p < 0.01), in differentiated 3T3-L1 adipocytes.ConclusionsHSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.  相似文献   

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