Alcohol hangover and Liv.52

Summary Ethanol and acetaldehyde levels in blood and urine have been evaluated in 9 volunteers following administration of Liv.52 and placebo on the evening of the study and on the following morning. On the following morning the volunteers scored their symptoms and completed visual analogue scales. Single dose and multiple dose studies were done.Liv.52 produced a considerable reduction in blood and urine levels of ethanol and acetaldehyde after 12 h. It is possible that Liv.52 prevents the binding of acetaldehyde, bringing about higher initial blood levels followed by rapid elimination. It reduced the hangover symptoms.     

PADMA-28, a traditional tibetan herbal preparation inhibits the respiratory burst in human neutrophils, the killing of epithelial cells by mixtures of oxidants and pro-inflammatory agonists and peroxidation of lipids

Both aqueous and methanolic fractions derived from the Tibetan preparation PADMA-28 (a mixture of 22 plants) used as an anti-atherosclerotic agent, and which is non-cytolytic to a variety of mammalian cells, were found to strongly inhibit (1) the killing of epithelial cells in culture induced by ‘cocktails’ comprising oxidants, membrane perforating agents and proteinases; (2) the generation of luminol-dependent chemiluminescence in human neutrophils stimulated by opsonized bacteria; (3) the peroxidation of intralipid (a preparation rich in phopholipids) induced in the presence of copper; and (4) the activity of neutrophil elastase. It is proposed that PADMA-28 might prove beneficial for the prevention of cell damage induced by synergism among pro-inflammatory agonists which is central in the initiation of tissue destruction in inflammatory and infectious conditions.     

Analysis of multiple constituents in a Chinese herbal preparation Shuang-Huang-Lian oral liquid by HPLC-DAD-ESI-MSn

A high-performance liquid chromatography/mass spectrometry (HPLC-MS) method for the quality control of Shuang-Huang-Lian oral liquid, an antimicrobial and antipyretic herbal preparation, has been developed. Pure compounds are subjected to tandem mass spectrometry (MS(n)) analysis to clarify their fragmentation rules. Then, the sample of Shuang-Huang-Lian was analyzed by on-line LC-MS(n). A total of 27 compounds, including seven phenylethanoid glycosides, three lignans, seven quinic acids, six saponins and four flavonoids, in the extract of Shuang-Huang-Lian oral liquid have been identified or tentatively characterized. It is expected to develop a comprehensive quality control method of this commonly used herbal preparation.     

Incorporation of the genetic control of alcohol dehydrogenase into a physiologically based pharmacokinetic model for ethanol in humans.

The assessment of the variability of human responses to foreign chemicals is an important step in characterizing the public health risks posed by nontherapeutic hazardous chemicals and the risk of encountering adverse reactions with drugs. Of the many sources of interindividual variability in chemical response identified to date, hereditary factors are some of the least understood. Physiologically based pharmacokinetic modeling linked with Monte Carlo sampling has been shown to be a useful tool for the quantification of interindividual variability in chemical disposition and/or response when applied to biological processes that displayed single genetic polymorphisms. The present study has extended this approach by modeling the complex hereditary control of alcohol dehydrogenase, which includes polygenic control and polymorphisms at two allelic sites, and by assessing the functional significance of this hereditary control on ethanol disposition. The physiologically based pharmacokinetic model for ethanol indicated that peak blood ethanol levels and time-to-peak blood ethanol levels were marginally affected by alcohol dehydrogenase genotypes, with simulated subjects possessing the B2 subunit having slightly lower peak blood ethanol levels and shorter times-to-peak blood levels compared to subjects without the B2 subunit. In contrast, the area under the curve (AUC) of the ethanol blood decay curve was very sensitive to alcohol dehydrogenase genotype, with AUCs from any genotype including the ADH1B2 allele considerably smaller than AUCs from any genotype without the ADH1B2 allele. Furthermore, the AUCs in the ADH1C1/C1 genotype were moderately lower than the AUCs from the corresponding ADH1C2/C2 genotype. Moreover, these simulations demonstrated that interindividual variability of ethanol disposition is affected by alcohol dehydrogenase and that the degree of this variability was a function of the ethanol dose.     

Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats

The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52.     

A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal preparation used for menopausal symptoms, in healthy female volunteers

Objectives Many patients use herbal medicines to relieve menopausal symptoms. Keishi‐bukuryo‐gan contains five herbal components, and has been used for treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian countries. In this study, we investigated the potential herb–drug interactions of keishi‐bukuryo‐gan in healthy female subjects. Methods Thirty‐one healthy females (20–27 years) were studied to evaluate their baseline activity of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N‐acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8‐h urine sample collected after a 150‐mg dose of caffeine and a 30‐mg dose of dextromethorphan, and also the urinary excretion ratio of 6β‐hydroxycortisol to cortisol. Thereafter, the subjects received 3.75 g of keishi‐bukuryo‐gan twice daily for seven days, and underwent the same tests on post‐dose day 7. Key findings The geometric mean phenotypic index for CYP1A2 significantly decreased by 16% on day 7 compared with the baseline (P = 0.026). Keishi‐bukuryo‐gan did not alter the indices for CYP2D6, CYP3A, XO and NAT2. Conclusions Keishi‐bukuryo‐gan may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen metabolism. However, TJ‐25 is unlikely to participate in herb–drug interactions involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2.     

Effect of linolenic acid/ethanol or limonene/ethanol and iontophoresis on the in vitro percutaneous absorption of LHRH and ultrastructure of human epidermis

The effect of enhancer(s) (e.g. ethanol (EtOH), 5% linolenic acid/EtOH, and 5% limonene/EtOH) and iontophoresis was investigated on the in vitro percutaneous absorption of luteinizing hormone releasing hormone (LHRH) and ultrastructure of human epidermis by transmission electron microscopy (TEM). 5% linolenic acid/EtOH or 5% limonene/EtOH significantly enhanced (P<0.05) the passive flux of LHRH through human epidermis in comparison to the control (no enhancer treated epidermis). Iontophoresis further increased the flux of LHRH through enhancer(s) treated epidermis. Iontophoretic flux of LHRH through 5% linolenic acid/EtOH and 5% limonene/EtOH treated epidermis was significantly (P<0.05) enhanced in comparison to iontophoretic flux through the control epidermis. TEM is the most efficient way to visualize the ultrastructure of the stratum corneum (SC). TEM results reveal that iontophoresis in combination with enhancers (e.g. linolenic acid/EtOH or and limonene/EtOH) transformed the highly compact cells of the SC into a looser network of filaments, disrupted the keratin pattern, and resulted in swelling of SC cell layers of human epidermis. Thus, linolenic acid/EtOH or limonene/EtOH in combination with iontophoresis increased the flux of LHRH through human epidermis by disrupting keratin pattern as well as loosening and swelling of SC cell layers.     

Effect of guar gum,a fibre preparation,on digoxin and penicillin absorption in man

Summary The effect of guar gum on the absorption of digoxin and phenoxymethyl penicillin was studied in a double blind study in 10 healthy volunteers. Guar gum reduced serum digoxin concentration during the early absorption period, but a similar amount of digoxin was found in 24 h urine whether given with or without guar gum. Both the peak penicillin concentration and the area under the serum curve were significantly reduced by the gum.     

中药“洗一号”涂膜剂定性、定量质量研究

目的建立中药"洗一号"涂膜剂中主药成分的定性、定量研究方法。方法采用薄层色谱法(TLC)分析制剂中的成分,主要包括黄柏、大黄、黄芪和黄连药材,采用高效液相色谱法(HPLC)测定制剂中大黄素和大黄酸的含量,色谱柱为Diamonsil C18,流动相为甲醇-体积分数0.1%磷酸溶液,流速为1.0 mL·min-1,检测波长为254 nm,柱温为40℃,进样量为20μL。结果大黄、黄连、黄芩和黄柏药材的TLC图点清晰,分离度好,阴性对照无干扰。大黄酸、大黄素检测质量浓度线性范围为0.16μg~0.49μg(r=0.9999)、0.17μg~0.51μg(r=0.9999);定量限为0.096 mg;加样回收率为95.0%~105.0%(RSD为1.2%,n=6);进样精密度、稳定性、重复性试验的RSD均小于2%。结论该研究所建标准可用于中药"洗一号"涂膜剂的质量控制。     

Effect of cyanamide on the metabolism of ethanol and acetaldehyde and on gluconeogenesis by isolated rat hepatocytes

Previous experiments demonstrated that acetaldehyde stimulated glucose production from pyruvate, whereas gluconeogenesis from glycerol, xylitol and sorbitol was inhibited [A.I. Cederbaum and E. Dicker, Archs Biochem. Biophys. 197, 415 (1979)]. To determine the mechanism whereby acetaldehyde affects glucose production from these precursors, and to evaluate the role of acetaldehyde in the actions of ethanol, experiments with cyanamide were carried out. The oxidation of acetaldehyde by isolated rat liver cells was inhibited by cyanamide after a brief incubation period. Associated with this inhibition of acetaldehyde oxidation was an inhibition of ethanol oxidation by cyanamide and an increase in the amount of acetaldehyde which arose during the oxidation of ethanol. Ethanol oxidation was decreased because of the ineffective removal of acetaldehyde in the presence of cyanamide. Cyanamide had no effect on hepatic oxygen uptake. The increase in the β-hydroxybutyrate/acetoacetate ratio produced by acetaldehyde was completely prevented by cyanamide, whereas the slight increase in the lactate/pyruvate ratio was not prevented by cyanamide. Cyanamide partially reversed the ethanol-induced increase in the lactate/pyruvate ratio, but it completely prevented the ethanol-induced increase in the β-hydroxybutyrate/acetoacetate ratio. The ethanol-induced change in the mitochondrial redox state may, therefore, be due primarily to the mitochondrial oxidation of the acetaldehyde which arises during the oxidation of ethanol. The inhibitory effects of acetaldehyde on gluconeogenesis from glycerol, xylitol and sorbitol, as well as the stimulation of acetaldehyde of glucose production from pyruvate, were completely prevented by cyanamide. These results indicate that the effects of acetaldehyde on gluconeogenesis represent metabolic effects, rather than direct effects of acetaldehyde. Changes in the cellular NADH/NAD^? ratio as a consequence of acetaldehyde metabolism are postulated to be responsible for these actions of acetaldehyde. Ethanol stimulated glucose production from pyruvate, while inhibiting gluconeogenesis from glycerol, xylitol and sorbitol. Cyanamide, which prevented the effects of acetaldehyde on gluconeogenesis, also prevented the effects of ethanol on gluconeogenesis. This prevention by cyanamide may be suggestive for a role for acetaldehyde in the actions of ethanol on gluconeogenesis. The possibility cannot be ruled out, however, that the prevention of the effects of ethanol by cyanamide may be due to the partial inhibition of ethanol oxidation by cyanamide. These results indicate that cyanamide is an effective inhibitor of acetaldehyde oxidation by isolated liver cells and therefore can be used to determine the mechanism whereby acetaldehyde affects metabolic function. Depending on the reaction under investigation, acetaldehyde can have direct or indirect effects on cellular metabolism.     

A comparison of the effect of lorazepam on memory in heavy and low social drinkers

The cognitive deficits, particularly memory impairment, observed in association with organic brain damage caused by chronic alcohol ingestion, are consistent with the profile of benzodiazepine-induced amnesia. This study examined the cognitive capabilities of a group of heavy social drinkers (n=11) and a group of low social drinkers (n=11) under the influence of a pharmacological challenge (lorazepam 2 mg) and a placebo treatment. Lorazepam impaired visual memory and verbal learning in both groups, but the effect of lorazepam was exacerbated in the heavy social drinkers for delayed recall of verbal material. Heavy social drinkers had lower verbal fluency scores and were less able to copy complex figures than low social drinkers whether or not the pharmacological challenge was present. Lorazepam induced deficits, in both groups, which conformed to the classic profile of those observed in benzodiazepine-induced amnesia. The deficits, both in the absence and presence of lorazepam, shown by heavy social drinkers suggest that changes may have occurred in their brain functioning.     

Effect of epinephrine and alprenolol on ethanol metabolism, liver cell respiration and mitochondrial function.

Chronic administration of epinephrine to adult male rats resulted in a significant increase in the rate of ethanol elimination, when given alone or together with the beta-adrenergic blocker alprenolol. This effect was observed concomitantly with an increased hepatic oxygen utilization and no changes in mitochondrial respiratory functions. Epinephrine given acutely did not modify the rate of ethanol metabolism. Blood glucose levels were enhanced in these conditions, but were unaffected in rats treated with epinephrine plus alprenolol. These results suggest that chronic epinephrine treatment induces an increased oxidative capacity in the liver characterized by enhanced rates of oxygen uptake and ethanol metabolism, which is not related to its beta-adrenergic actions.     

Comparative effects of acute ethanol dosage on liver and muscle protein metabolism

Experiments were performed to address some outstanding issues and investigate possible mechanisms relating to the acute comparative effects of ethanol on liver and skeletal muscle protein metabolism. Ethanol (EtOH)-treated rats were injected (i.p.) with a bolus of EtOH (75 mmol/kg body weight) and sacrificed at 20 min, 1-, 2.5-, 6-, and 24-hr time points. Control rats were injected with saline (Con-Sal; 0.15 mmol/L NaCl). All 24-hr ethanol-treated animals were compared with saline-injected rats subjected to controlled feeding (i.e. pair-fed controls for 24 hr EtOH). At 24 hr, there was no measurable alcohol in the plasma, whereas high levels were seen from 20 min to 6 hr (up to 448 mg/dL). Plasma levels of albumin were reduced at initial time points, and activities of aspartate aminotransferase increased, but there was no histological evidence of overt tissue damage either in muscle or liver. Hepatic protein and RNA contents and indices of tissue (C_s and k_s) and whole-body (V_s) protein synthesis were significantly increased in ethanol-dosed rats relative to saline-injected pair-fed controls at 24 hr. In the liver, four of the seven cytoplasmic proteases investigated (alanyl-, arginyl-, and pyroglutamyl-aminopeptidases and proline-endopeptidase) showed significant increases in activity at 24 hr relative to pair-fed controls; four of the six lysosomal proteases showed significant decreases in activity (dipeptidyl-aminopeptidase II and cathepsins B, L, and H). In skeletal muscle, k_s fell progressively between 1 and 24 hr (−25 to −69%; P < 0.001), but no significant changes in skeletal muscle protease activities were seen at 24 hr. At 24 hr after ethanol dosage in vivo, there were no significant increases in protein carbonyl content in liver or skeletal muscle compared to pair-fed controls (muscle levels actually decreased slightly). However, using either rat or human tissue, both liver and muscle carbonyl increased in vitro in response to superoxide and hydroxyl radicals: muscle was more susceptible to carbonyl formation than liver and both tissues were more sensitive to hydroxyl compared to superoxide radicals. These results show divergent effects of acute ethanol treatment on liver and skeletal muscle protein metabolism, which may not be linked to in vivo free radical-mediated protein damage (as indicated by carbonyl formation), at least in the short term.     

Quality assessment of trace Cd and Pb contaminants in Thai herbal medicines using ultrasound-assisted digestion prior to flame atomic absorption spectrometry

A simple, efficient, and reliable ultrasound-assisted digestion (UAD) procedure was used for sample preparation prior to quantitative determination of trace Cd and Pb contaminants in herbal medicines using flame atomic absorption spectrometry. The parameters influencing UAD such as the solvent system, sample mass, presonication time, sonication time, and digestion temperature were evaluated. The efficiency of the proposed UAD procedure was evaluated by comparing with conventional acid digestion (CAD) procedure. Under the optimum conditions, linear calibration graphs in a range of 2–250 μg/L for Cd, and 50–1000 μg/L for Pb were obtained with detection limits of 0.56 μg/L and 10.7 μg/L for Cd and Pb, respectively. The limit of quantification for Cd and Pb were 1.87 μg/L and 40.3 μg/L, respectively. The repeatability for analysis of 10 μg/L for Cd and 100 μg/L for Pb was 2.3% and 2.6%, respectively. The accuracy of the proposed method was evaluated by rice flour certified reference materials. The proposed method was successfully applied for analysis of trace Cd and Pb in samples of various types of medicinal plant and traditional medicine consumed in Thailand. Most herbal medicine samples were not contaminated with Cd or Pb. The contaminant levels for both metals were still lower than the maximum permissible levels of elements in medicinal plant materials and finished herbal products sets by the Ministry of Public Health of Thailand. The exception was the high level of Cd contamination found in two samples of processed medicinal plants.     

欧盟草药临床安全性和有效性评估指导原则介绍

欧盟（European Union,EU）于2016年7月发布了《在欧盟草药专论编写中评估公认的和传统的草药产品临床安全性和有效性的指导原则（第一次修订版）》。其中最值得注意的是,草药产品申请注册时可用文献资料替代试验资料,并且可根据文献资料科学性不同,获准不同的适应证。介绍该指导原则的主要内容,期望对我国的中药和植物药研究及其监管有所帮助。     

Effect of chronic ethanol treatment on metabolism of drugs in vitro and in vivo.

A daily intake of ethanol ranging from 10 to 12 g/kg for 1 month in either high-fat adequate protein (HFAP) or low-fat high protein (LFHP) liquid diets resulted in significant increases in liver weight, microsomal protein and microsomal metabolism of aminopyrine, zoxazolamine, aniline and meprobamatc, when related to 100 g body weight. Morphine metabolism was increased only after the HFAP diet; pentobarbital metabolism was studied only after HFAP diet, and was increased. The increase in vitro was highest with aminopyrine and lowest with pentobarbital. The analysis of variance showed highly significant differences among the various drugs. There were significant interaction effects of drugs × ethanol and drugs × fat content, but no significant interaction between ethanol × fat or drugs × ethanol × fat except in the case of morphine. The marked between-drug variability in induction of metabolism in vitro by ethanol is also reflected in vivo among the various drugs examined. The increase in vivo was greatest with meprobamate, intermediate with aniline and zoxazolamine, low with aminopyrine and absent with pentobarbital. Moreover, there was variability in inductive effect of ethanol in vivo as compared to in vitro. It is, therefore, concluded that chronic ethanol administration does increase the metabolism of drugs in vitro and in vivo, but the diversity of effects on different drugs cannot be explained by a single mechanism based on an increase in the amount of cytochrome P-450 or other component of the mixed function oxidase system.     

Problems in the use of herbal and natural substances,with a specific example concerning the cardiovascular system

1. There has been increasing awareness and use of natural preparations for health purposes by consumers. 2. However, recent studies have repeatedly shown that many natural products marketed as nutraceuticals or health food do not deliver the health benefit as claimed and are inconsistent from batch to batch. 3. The present paper describes the scientific rationale of such inconsistency and uses an antihypertensive preparation as an example to demonstrate the significant value of natural products if developed scientifically and properly.     

间歇性高糖对NRK-52E细胞抗氧化能力作用研究

目的探讨间歇性高糖抑制大鼠肾小管导管上皮细胞株NRK-52E抗氧化能力。方法实验开始72 h后,Western blot检测空白组、正常葡萄糖组(5 mmol/L葡萄糖)、高糖干预组(25 nmol/L葡萄糖)、间歇性高糖干预组(5 mmol/L葡萄糖与25 mmol/L葡萄糖交替)中氧化物歧化酶-1(SOD-1)、还原型辅酶Ⅱ(NADPH)在NRK-52E细胞表达。一氧化氮合酶(eNOS)试剂盒应用液闪仪测定3[H]的放射强度,活性氧(ROS)含量应用CM2H2DCFDA试剂盒检测。结果高浓度葡萄糖及间歇性高糖均下调SOD-1及NADPH表达,而提高ROS含量,间歇性高糖作用更显著。间歇性高糖eNOS含量低于持续性高糖组。结论间歇性高糖抑制肾小管导管上皮细胞抗氧化能力显著。     

复方中药"津精元"对大鼠组织超氧化物歧化酶活性和丙二醛含量的影响

目的：探讨复方中药“津精元”治病机制。方法：用掺有“津精元”的饲料饲喂大鼠,2个月后处死,取肾、心、肝和脾组织用NBT光还原法测定超氧化物歧化酶活性（SOD）及TBA法测定丙二醛（MDA）含量。结果：复方中药“津精元”能显著提高大鼠脏器SOD活性及MDA含量,从而增强其抗氧化能力。结论：复方中药“津精元”能抑制脂质过氧化反应,提高机体抗氧化能力,有较好的延缓脑老化作用。