Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

A Survey of Plants Used as Wild Vegetables in Four Districts of Botswana

A survey of plants used as wild vegetables was conducted in four districts of Botswana in August and September 2005. The objective was to determine which wild plants were used as vegetables in the study area, and to document their cooking and preservation methods. Fourteen species representing seven families were mentioned as wild vegetables. In addition, six species from four families had other uses in traditional medicine. The implications of the documented processing methods on the retention of nutrients in the vegetables are discussed.     

植物抗体及其应用

20世纪80年代末科学家将抗体基因转入烟草表达,标志着植物抗体的诞生.人类既可以以植物为生物反应器异源表达和生产具有药用及商业价值的蛋白质;也可用抗体在植物体中进行免疫调节,以研究植物生理代谢机制,或增加植物抵抗病虫害的能力.本文旨对植物抗体的优越性、表达生产及其在医药学、植物抗病及代谢等领域的进展进行综述和讨论.     

蓬辣滩水电站泄洪闸门及其监控系统改造

介绍了蓬辣滩水电站泄洪闸门的状况、计算机监控系统改造方案的结构和特点及闸门定轮轴承的改造情况,通过上述改造,提高了泄洪设备运行的自动化水平,同时也为其他闸门工程提供参考。     

Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

Allergic contact dermatitis from grasses

This study attempts to demonstrate the existence of allergic contact dermatitis from grass, and to develop a patch test series to screen patients with grass intolerance. 6 common grass species from lawns and military training areas were collected. Solvent extracts of polar. non-polar and volatile fractions were prepared and used for patch testing in 20 control subjects and 46 patients with a history of grass intolerance. The 20 control had negative responses to patch testing. 5 out of 46 patients had positive patch tests to Axonopus compressus (carpet grass). Ischaenmum muticum (sea-shore centipede grass). Imperata evlindrica (lalang). Panicum maximum (Guinea grass) and Pennisetum purpureum (elephant grass). Reactions to the non-polar fraction for all 5 species were noted. This study demonstrates the existence of allergic contact dermatitis from various common species of grass. In our series, this is seen in 11% of those with a history of grass intolerance.     

Plant cardiac glycosides and digoxin Fab antibody

The potential application of the Digoxin Fab antibody (Wellcome Digibind) in the clinical management of plant poisoning was investigated. The cardiac glycoside contents of various Australian plants were studied using immunoassay techniques. The cross-reactions of the Fab antibody and two digoxin assay antibodies against extracts of these plants were also studied. Results obtained indicated that the Digibind antibody cross-reacted with a wide range of glycosides contained in Australian plants and therefore could be of use in the treatment of life-threatening plant poisoning.     

交感神经亢进引起的心电图改变

植物神经功能失调多见于一些中青年女性 ,临床症状表现为心悸、心前区不适、脉压差小、心电图示 T波异常 ,口服硝酸甘油可缓解 ,体格检查未发现异常     

应用3H-TdR掺入法对SMMC-7721细胞株药敏试验条件的探讨与应用

目的探讨3H-TdR掺入法在进行SMMC-7721系细胞肿瘤药敏试验实验时的最佳实验条件.方法确定出3H-TdR掺入法药敏实验时的最适细胞浓度、最适实验药物浓度、3H-TdR掺入最适时间;在最适条件下采用3H-TdR掺入法测定肝癌SMMC-7721细胞株对临床常用的9种抗癌药物的敏感性.结果应用3H-TdR掺入法检测肝癌SMMC-7721细胞株药敏试验的最适实验细胞浓度为1×104个/孔,最适试验药物浓度为1×PPC,3H-TdR最适掺入时间为收集细胞前8 h;肝癌SMMC-7721细胞株对DDP、ADM、5-FU、CPT高度敏感,对MTX、VP-16、MMC、NVB低度敏感,对PYM不敏感.结论 3H-TdR掺入法可用于肿瘤药物敏感性测定并确定出它的最适实验条件.