Structure of pyridindolol, inhibitor of beta-galactosidase.

Pyridindolol is a product of a streptomyces and exhibits inhibitory activity against bovine liver beta-galactosidase. The structure of pyridindilol, 1-[1(R), 2-dihydroxyethyl]-3-hydroxymethyl-9H-pyrido[3,4-b] indole, has been established by spectroscopic analyses and an X-ray structure determination.     

Metabolites of microorganisms. 242 pyridindolol glucosides from Streptomyces parvulus

From a new strain of Streptomyces, Streptomyces parvulus, strain Tü 2480 three glucosides of the alkaloid pyridindolol were isolated. The structure elucidation is based on spectroscopic investigations and degradation to pyridindolol and alpha,D-methyl glucoside.     

Inhibitory effect of dioctyl sodium sulfosuccinate on trypsin activity.

The inhibitory effect of dioctyl sodium sulfosuccinate on the proteolytic activity of trypsin was investigate over the pH 6-8 range. The antitryptic activity was determined using two different substrates: casein and N,alpha-benzoyl-DL-arginine-p-nitroanilide hydrochloride. The mechanistic studies revealed the substrate-inhibitor interaction to be the overall major mechanism of inhibition. This interaction was shown to involve substrate depletion, probably involving some primary sites of the natural substrate casein. Some inhibition was also shown to be due to an interaction between the enzyme and the inhibitior molecules. The interactions of the inhibitor with the enzyme and the substrate were irreversible. The possible therapeutic significance of the inhibitory effect of the surfactant is discussed.     

Inhibitory effects of fruit juices on CYP3A activity.

There have been very limited reports on the effects of commercial fruit juices on human CYP3A activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum, and wild grape. White grapefruit, pomegranate, and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC(50) values of all fruit juices tested were reduced after preincubation with microsomes in the presence of the NADPH-generating system, suggesting that a mechanism-based inhibitory component was present in these fruit juices, as in the case of grapefruit. The results suggest that, like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant.     

石杉碱乙的抗胆碱酯酶作用

目的：测试石杉碱乙的抗胆碱酯酶作用并与他克林进行比较,方法：比色法用于测定胆碱酶活性。结果：石杉碱乙和他克林对ＢｕＣｈＥ和ＡＣｈＥ抑制的ＩＣ５０值的比率分别为６５．８和０．５４,石杉碱乙对乙酰胆碱酯酶有更强的选择性抑制作用。石杉碱乙灌胃对脑内ＡＣｈＥ的抑制作用明业强于他克林,而他克林对ＢｕＣｈＥ的抑制作用强于石杉碱乙,并有严重副反应,单次灌胃石杉碱乙在４小时内对脑内ＡＣｈＥ产生较对稳定的抑制作用,     

Inhibitory activity of Plantago major L. on angiotensin I-converting enzyme

Eight compounds were isolated from methanol extract of Plantago major L. leaves and investigated for their ability to inhibit angiotensin I-converting enzyme activity. Among them, compound 1 showed the most potent inhibition with rate of 28.06 ± 0.21% at a concentration of 100 μM. Compounds 2 and 8 exhibited weak activities. These results suggest that compound 1 might contribute to the ability of P. major to inhibit the activity of angiotensin I- converting enzyme.     

Inhibitory effects of plant secondary metabolites on cytotoxic activity of polymorphonuclear leucocytes.

The inhibitory effects of 151 natural products, representing most of the frequently occurring types, on the cytotoxicity to MM2 tumor cells of polymorphonuclear leucocytes (PMN) induced by TAK, a polysaccharide immunomodulator, were examined. Forty-two compounds inhibited the TAK-induced activation of PMN. Among them, some naturally occurring quinones and various alkaloids (nicotine, Cinchona alkaloids, isoquinoline alkaloids such as cepharanthine, and indole alkaloids such as ajmaline) exhibited potent inhibitory effects. Using the inhibition assay for monitoring, the extracts of Hydrangea Dulcis folium, Scopoliae rhizoma, Cinchona cortex, Magnoliae cortex, Stephania tuber, and Rauwolfia radix were analysed to characterize the active constituents.     

Inhibitory effects of beta-hydroxyethyl 2,4-dinitrophenyl disulphide on rat brain cholinesterase activity.

Hydrolysis of 1-6 mM AChJ by rat brain homogenates in TRIS-HCl buffer, pH 7-8, supplemented with NaCl and MgCl2, was found to be suppressed by a half by pretreatment with 0-3 mM beta-hydroxyethyl 2,4-dinitrophenyl disulphide (HEDD), a reagent for SH groups. This effect has been shown to be due to partial inhibition of a Phg-sensitive esterase which has been characterized as AChE on the ground of experiments with MeCh and BuCh. Similar inhibition of AChJ hydrolysis was also noted on pretreatment of brain homogenates with 0-05 M N-ethylmaleinimide (NEM). The inhibition degree has turned out to depend upon either AChJ concentration (0-1--4-8 mM) and duration of contact of the tissue with HEDD before addition of the substrate. The AChE activity revealed in 0-2 mM AChJ was found to be particularly sensitive to HEDD. Sensitivity of rat brain AChE to either HEDD and NEM may indicate for occurring of SH in some one its isozyme. No less, other mechanisms of the inhibition, particularly possibility of interaction of HEDD with a disulphide group must be also considered.     

甘草提取物对酪氨酸酶活性的抑制作用

目的研究甘草提取物对酪氨酸酶活性的抑制作用。方法用50%(V/V)乙醇提取甘草中的有效成分,分别以L-酪氨酸、邻苯二酚为底物,在475、390nm处测定溶液的吸光度,观察甘草提取物对单酚酶、双酚酶活性的影响。结果50%(V/V)乙醇甘草提取物对酪氨酸酶有明显的抑制作用(IC50分别为1.94、2.94mg·ml-1)。结论甘草提取物对酪氨酸酶单酚酶、双酚酶的活性均有抑制作用;以邻苯二酚为底物的双酚酶活性测定体系可较好地应用于酪氨酸酶活性的研究。     

Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.     

Inhibitory profiles of captopril on matrix metalloproteinase-9 activity

To investigate the inhibitory profiles of angiotensin-converting enzyme (ACE) inhibitors on matrix metalloproteinase-9 (MMP-9) activity, the inhibitory activity and molecular interaction of captopril on human MMP-9 were studied. Plasma MMP-9 and ACE activities in samples from patient with acute myocardial infarction were similarly inhibited by captopril. Molecular models showed that captopril directly bound to the MMP-9 active center. Compared with the other ACE inhibitors, the compact structure of captopril seemed to make the inhibitory profiles on the MMP-9 active site.     

Hydroxypropyl-beta-cyclodextrin inhibits spray-drying-induced inactivation of beta-galactosidase.

The single-step, fast spray-drying process may represent a valuable alternative to the multistep, time-consuming freeze-drying process in the area of formulation and processing of biopharmaceuticals. In this study, we tested the use of sucrose and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as stabilizing excipients in the spray-drying of a model protein, beta-galactosidase. The solutions were processed using a Büchi 190 cocurrent Mini Spray Dryer at an outlet temperature of 61 +/- 2 degrees C. The powders were redissolved and analyzed for catalytic activity, aggregation, chemical decomposition, and thermal susceptibility as observed by high-resolution calorimetry. Spray-drying significantly inactivated beta-galactosidase. Spray-drying beta-galactosidase in the presence of sucrose did not prevent inactivation. However, after spray-drying beta-galactosidase in the presence of HP-beta-CD, or HP-beta-CD and sucrose, full catalytic activity was exhibited on reconstitution. Furthermore, the reconstituted product was unchanged in terms of molecular weight, charge, and thermal stability. These findings are consistent with a hypothesis that the change responsible for inactivation of beta-galactosidase was mainly a monomolecular, noncovalent change, i. e., the formation of incorrect structures, that arose from surface denaturation. This study clearly demonstrates that cyclodextrins can be useful stabilizing excipients in the preparation of spray-dried protein pharmaceuticals.     

Inhibitory effect of methylmercury on the activity of glutathione peroxidase

Inhibitory effect of methylmercuric chloride (MMC) on the activity of glutathione peroxidase was studied using 100,000g supernatant of the liver homogenate from 10 male SPF Wistar rats in vitro. Marked inhibition of glutathione peroxidase activity was observed between concentrations of 5 × 10^?6 and 5 × 10^?5m MMC, but the activity was hardly inhibited at concentrations less than 5 × 10^?6m MMC; inhibition was almost complete at concentrations greater than 5 × 10^?5m MMC.     

Inhibitory activity of Cinnamomum Cassia extract on hypersensitivity in mice

OBJECTIVE Cinnamomum cassia has been used in traditional medicine in East Asian countries to treatallergic disease.Previous studies have demonstrated that C.cassiainhibits the development of mite antigen-induced skin lesions in NC/Nga mice by suppressing the Thelper 2cell response.The objective of this study is to investigate whether C.cassia has an efficient inhibition on systemic anaphylaxis and contact hypersensitivity in mice.METHODS To induce systemic anaphylaxis,mice were injected intraperitoneally with compound 48/80.Mortality was monitored for 1h after the injection.Contact hypersensitivity reaction was induced by topical application of 2,4-dinitrofluorobenzene(DNFB)to the ears of mice.After DNFBchallenge,ear thickness was measured 0,24 and 48h.RESULTS We discovered that C.cassia significantly inhibited compound 48/80-induced anaphylaxis and DNFB-induced ear swelling.Compound 48/80-induced anaphylaxiswas completely inhibited at the dose of 60mg·kg-1 body weight.Ear swelling at 24 h after DNFB-challenge was significantly less than that in the control group(0.16±0.03 vs.0.32±0.03 mm,P<0.01),while C.cassia was administered at the dose of 200mg·kg-1.CONCLUSION These findings indicate that C.cassiasuppresses allergic reactions,thus has potential value for mitigation of atopic dermatitis.     

Inhibitory effects of huperzine B on cholinesterase activity in mice

目的：测试石杉碱乙的抗胆碱酯酶作用并与他克林进行比较．方法：比色法用于测定胆碱酯酶活性．结果：石杉碱乙和他克林对ＢｕＣｈＥ和ＡＣｈＥ抑制的ＩＣ５０值的比率分别为６５８和０５４．石杉碱乙对乙酰胆碱酯酶有更强的选择性抑制作用．石杉碱乙灌胃对脑内ＡＣｈＥ的抑制作用明显强于他克林．而他克林对ＢｕＣｈＥ的抑制作用强于石杉碱乙,并有严重副反应．单次灌胃石杉碱乙在４小时内对脑内ＡＣｈＥ产生较为稳定的抑制作用．结论：与他克林比较石杉碱乙是乙酰胆碱酯酶的高选择性抑制剂,灌胃时药效高,毒性低．     

白术挥发油抗实体瘤的作用研究

目的　研究白术挥发油对动物移植性肿瘤的作用。方法　以动物移植性肿瘤肝癌H2 2 、肉瘤S180 为模型 ,以环磷酰胺为阳性对照 ,观察白术挥发油的抗肿瘤作用。结果　白术挥发油 2 5 0mg/kg对小鼠肝癌H2 2 、肉瘤S180 的抑制率分别为 5 1 6 %、5 3 2 %。结论　白术挥发油对小鼠移植性肿瘤肝癌H2 2 及肉瘤S180 有显著抑制作用