Phenolic metabolites of thioridazine in man

After oral administration of thioridazine or mesoridazine to man, faecal extracts contained mainly unconjugated 7-hydroxy-thioridazine and its demethylated analogue, together with some 3-hydroxy-thioridazine, and 7-hydroxy derivatives of sulphoridazine and desmethyl sulphoridazine. In contrast, urine contained free 7-hydroxy-mesoridazine, and no free 7-hydroxy-thioridazine was detectable. Conjugates of all these phenols were also found. After oral sulphoridazine administration (thioridazine side-chain sulphone), urine contained mainly 7-hydroxy-sulphoridazine and faeces both 7-hydroxy-sulphoridazine and its desmethyl analogue. Sulphoridazine metabolism is therefore much simpler than that of thioridazine. This different elimination pattern in faeces and urine may be due to reduction of sulphoxides but not sulphones by intestinal bacteria.     

Phenylpropanoid glycosides from Orobanche caerulescens

Two new phenylpropanoid glycosides, caerulescenoside ( 1), and 3'-methyl crenatoside ( 2), as well as five known phenylpropanoid glycosides [acteoside ( 3), isoacteoside ( 4), campneoside II ( 5), crenatoside ( 6), and desrhamnosyl acteoside ( 7)] were isolated from the whole plant of Orobanche caerulescens. The antioxidative effects of compounds 1 - 7 on human low-density lipoprotein were evaluated. All these compounds suppress concentration-dependently conjugated diene formation with IC (50) values of 1.25 +/- 0.06, 2.97 +/- 0.31, 0.31 +/- 0.01, 1.01 +/- 0.05, 1.15 +/- 0.04, 1.69 +/- 0.15, and 0.64 +/- 0.03 microM, respectively. Comparison of their antioxidative activities with that of resveratrol (IC (50) : 6.75 +/- 1.05 microM), a natural phenolic antioxidant isolated from grape, demonstrated that the prolonged effect on lag-time and the damping effect on oxidative rate by compounds 1 - 7 were all more potent.     

Phenolic metabolites of chlorprothixene in man and dog

From urine and feces of dogs and urine of patients given chlorprothixene (CPT) per os, metabolites were extracted without or with enzymatic deconjugation and separated by repeated TLC. Purified compounds were characterized by UV, NMR, and mass spectrometry, by color reactions, and by chemical interconversions. Both species excreted 6- and 7-hydroxy-CPT besides the sulfoxide and demethylated analogues. In urine, the phenols were largely present as conjugates. The major metabolites in dog feces were 5-hydroxy-CPT and its demethylated derivative, whereas 5-hydroxylation was not detected in man. Dog excrete also contained 6-hydroxy-7-methoxy (or 7-hydroxy-6-methoxy)-CPT; further, a 5-hydroxy compound was detected in which the exocyclic double bond was hydrated. In the other metabolites, the Z-configuration of CPT had been retained, but small quantities of E-isomers were formed during isolation. According to preliminary quantitative data, phenols accounted for a small part of extractable metabolites in human urine, whereas they predominated in dog feces.     

Flavonoid glycosides from Alchemilla speciosa

The new flavonol glycosides quercetin 3- O-beta-(2'- O-alpha- L-rhamnopyranosyl)-glucopyranoside uronic acid and kaempferol 3- O-beta-(2'- O-alpha- L-rhamnopyranosyl)-glucopyranoside uronic acid were isolated from the leaves of Alchemilla speciosa Buser together with 13 known flavonol and flavone glycosides and (+)-catechin. The structures were determined by spectroscopic methods.     

牛大力的化学成分研究

目的 研究牛大力Millettia speciosa Champ.的化学成分.方法 对牛大力的乙醇提取物进行色谱分离,用波谱方法和理化性质鉴定各化合物的结构.结果 分离得到14个化合物,分别鉴定为3β,11α-二羟基-6(7),12(13)-二烯-乌苏烷(Ⅰ)、3β,11α-二羟基-12(13)-烯-乌苏烷(Ⅱ)、异甘草素(Ⅲ)、美迪紫檀素(Ⅳ)、2',4,4',α-四羟基二氢查耳酮(Ⅴ)、2',4-二羟基-4'-甲氧基查耳酮(Ⅵ)、高丽槐素(Ⅶ)、3',4'-二羟基-7-甲氧基异黄酮(Ⅷ)、4-羟基-2',4-二甲氧基查耳酮(Ⅸ)、2',4',α-三羟基-4-甲氧基二氢查耳酮(Ⅹ)、毛蕊异黄酮(Ⅺ)、8-hydroxypinoresinol(Ⅻ)、甘草异黄醇(Ⅻ)、3',4',7-三羟基异黄酮(ⅩⅣ).结论 除化合物Ⅲ、Ⅳ、Ⅶ外,其余11个均为首次从该植物中分离得到.     

Phenolic metabolites of amitriptyline and nortriptyline in rat bile

Anesthetized bile fistula rats received amitriptyline (AT), its N-oxide (AT-NO), or nortriptyline (NT) at doses of 72 mumol/kg ip, and bile was collected for 6-9 hr. Isolation of metabolites was achieved by enzymic deconjugation and repeated TLC of extracted aglycones. Purified compounds were characterized by UV, NMR, and mass spectrometry, by color reactions, and by chemical interconversions. Besides the alcohols E-10-hydroxy-AT and 10,11-dihydroxy-AT, the phenol E-2-hydroxy-AT occurred as a major AT metabolite, while 2,10- and 2,11-dihydroxy-AT, 2,10,11-trihydroxy-AT, and 2-hydroxy-3-methoxy (or 3-hydroxy-2-methoxy)-AT were present in smaller quantities. Further minor metabolites were 2-hydroxy-11-oxo-AT, 3-hydroxy-AT, 3,11-dihydroxy-AT, and its dehydration product 3-hydroxy-10,11-dehydro-AT. The exact position of the functional groups was elucidated by the nuclear Overhauser effect (NOE) in NMR spectroscopy and by analyzing metabolite patterns in the bile of rats given E- or Z-10-hydroxy-AT. Administration of AT-NO led to a larger proportion of methylated catechols and a smaller one of 10-hydroxy metabolites. Besides the tertiary amines, rats given AT or AT-NO excreted the demethylated analogues of some of the hydroxylation products. The latter also occurred as metabolites of NT, the ratio of aromatic and aliphatic hydroxylation being lower than with AT or AT-NO. Urine of rabbits treated orally with AT contained mono- and dihydroxylated metabolites resulting from attack at positions 2, 3, 10, and/or 11 and the same methylated catechols as rat bile.     

Terpenoids and sterols from Lagerstroemia speciosa

The leaves of Lagerstroemia speciosa afforded a new natural product, 31-norlargerenol acetate (4), along with known compounds 24-methylenecycloartanol acetate (1), its 31-nor analog (2), largerenol acetate (3), tinotufolins C (5) and D (6), lutein, phytol, sitosterol and sitosterol acetate. The structure of 4 was elucidated by 1D and 2D NMR and mass spectroscopy.     

Excretion of catecholamine metabolites following intraventricular injection of 6-hydroxydopamine in the Macaca speciosa

Seven non-human primates (Macaca speciosa) were stereotaxically implanted with Kopf cannulae with the tip being placed at the junction of the lateral and third ventricles. Following a recovery period, 2 24-hr baseline urine specimens were collected from each animal. 4 of the animals were given intraventricular (i. vent.) injections of 1, 2, 4 and 8 mg of 6-hydroxy-dopamine?HBr (6-OH-DA?HBr) at 12-hr intervals ( in 1 ml of artifical CSF) and 7 days later a final injection of 16 mg of 6-OH-DA?HBr. 3 control animals were given artificial CSF + equimolar NaBr injections on a similar schedule. Following the i. vent. injections 24-hr urine specimens were collected at periodic intervals. Urines were assayed for normetanephrine (NM), metanephrine (M), 3-methoxy-4-hydroxy-mandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). All animals were sacrificed 16 days after the final i. vent. injections and 14 areas of brain, adrenal gland, heart, and thoracic sympathetic chain were removed and assayed for norepinephrine (NE). It has been found that it is possible with this schedule of injection of 6-OH-DA to produce animals which have significantly reduced levels of brain NE (70% depletion) without decreasing NE in tissues outside the CNS. Such experimental animal preparations should be of particular use in studies in which a separation of peripheral from central noradrenergic systems is desirable. No differences in the excretion of NM, M, VMA, and MHPG between baseline and post-injection periods were found in those animals which were injected with artificial CSF only. In all animals which were given intraventricular 6-OH-DA and in which there was a decrement in brain NE without a depletion of NE in tissues outside the central nervous system, there was a significant decrement in urinary MHPG between the baseline and post-injection periods while no differences in the excretion of NM, M, or VMA were found. Based upon these data calculations were made which suggest that a significant fraction of urinary MHPG has its origin in metabolism of NE in brain.     

弯管列当多糖最佳提取工艺研究

目的 优选弯管列当多糖的最佳提取工艺.方法 以多糖提取率为评价指标,采用四因素三水平正交试验优选最佳提取工艺.结果 四因素对弯管列当多糖提取率的影响大小依次为提取次数＞提取温度＞料液比＞提取时间.最佳提取工艺为料液比1∶15,提取温度80℃,提取2次,每次提取1h.结论 优化工艺可为弯管列当多糖的深入研究和利用奠定基础.     

木瓜总黄酮抗肿瘤活性研究

目的:研究木瓜总黄酮抗肿瘤活性。方法:通过乙醇-正丁醇萃取方法提取木瓜总黄酮;通过分子药物筛选模型、酶联免疫法检测木瓜总黄酮对免疫共刺激分子程序性死亡因子(PD)-1与其配体(PD-L1)结合的抑制作用。通过H22肿瘤细胞模型小鼠,观察木瓜总黄酮对模型小鼠体内肿瘤体积与存活时间的影响;流式细胞仪测定小鼠腹水中肿瘤细胞及淋巴细胞表面相关分子的表达。结果:正丁醇馏分中木瓜总黄酮占85%。木瓜总黄酮具有抑制PD-1和PD-L1结合的作用,且抑制效率具有剂量依赖性。木瓜总黄酮在复制模型10 d后对模型小鼠体内肿瘤有明显抑制作用;对S180细胞表面PD-L1表达具有明显抑制作用,对体内淋巴细胞侵润有明显增强作用。结论:木瓜总黄酮可以抑制PD-1与PD-L1的结合,同时可降低肿瘤细胞表面PD-L1的表达从而促进机体对肿瘤的免疫应答,最终达到抑制肿瘤生长,提高肿瘤鼠存活率的作用。     

Phenolic metabolites,biological activities,and isolated compounds of Terminalia muelleri extract

Context: Terminalia muelleri Benth. (Combretaceae), is rich with phenolics that have antioxidant and cytotoxic activities. No screening studies were published before on T. muelleri.

Objective: The study focused on isolation and identification of secondary metabolites from aqueous methanol leaf extract of T. muelleri and evaluation of its biological activities.

Materials and methods: The n-butanol extract was chromatographed on polyamide 6, and eluted with H₂O/MeOH mixtures of decreasing polarity, then separated by different chromatographic tools that yielded 10 phenolic compounds. The antioxidant activity of the extract was evaluated by investigating its total phenolic and flavonoid content and DPPH scavenging effectiveness. The extract and the two acylated flavones were evaluated for their anticancer activity towards MCF-7 and PC3 cancer cell lines. Molecular docking study of the acylated flavones was performed against topoisomerase enzyme.

Results and discussion: Two acylated flavonoids, apigenin-8-C-(2″-O-galloyl) glucoside 1 and luteolin-8-C-(2″-O-galloyl) glucoside 2, were isolated and identified for the second time in nature, with eight tannins (3–10), from the leaves of T. muelleri. The extract and compound 10 showed the most significant antioxidant activity (IC₅₀?=?3.55 and 6.34?μg/mL), respectively. The total extract and compound 2 demonstrated cytotoxic effect against MCF-7 with IC₅₀?=?29.7 and 45.2?μg/mL respectively, while compound 1 showed cytotoxic effect against PC3 (IC₅₀?=?40.8?μg/mL). The docking study of compounds 1 and 2 confirmed unique binding mode in the active site of human DNA topoisomerase enzyme.

Conclusions: Terminalia muelleri is a promising medicinal plant as it possesses high antioxidant activity and moderate cytotoxic activity against MCF-7.     

Phenolic glycosides from Lavandual angustifolia

Abstract

Four new phenolic glycosides (1–4), together with 12 known ones (5–16), were isolated from the essential oil extraction waste of Lavandula angustifolia. Their structures were unequivocally determined by extensive spectroscopic analysis (1D and 2D NMR, HR-ESI-MS, UV, and optical rotation), chemical method, and comparison with data reported in the literature. The antioxidant activities of all compounds and new compounds’ influence on melanin content in B16 melanoma cells were examined, which indicated that compounds 1, 8, 13 had a certain degree of DPPH free radical scavenging activities, while only compound 2 could increase the melanin content with a dose-dependent manner.     

Phenolic compounds from Eucalyptus maculata

From the chloroformic extract of the resinous exudate of the stems of Eucalyptus maculata, four phenolic constituents have been isolated. A new di-cinnamic acid glucose ester was isolated, in addition to cinnamic acid, 7-methyl aromadendrin and sakuranetin. The isolated compounds were elucidated using UV, IR, 1D and 2D NMR and MS.     

Phenolic glycosides from Rhodohypoxis baurii

Three new phenolic glycosides (1–3), together with a known glycoside (4), were isolated from the bulbs of Rhodohypoxis baurii (Hypoxidaceae). The structures of the new glycosides (1–3) were determined on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses.     

Phenolic glycosides from Glycosmis pentaphylla

Three new phenolic glycosides, named as glycopentosides A–C (1–3), along with nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis pentaphylla. Their structures were determined by using spectroscopic and chemical methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide production in lipopolysaccharides-stimulated RAW 264.7 cells with IC₅₀ value of 12.14 μM.