Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on ...nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.
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A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are ...still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy. Therefore, this article discusses the differences in drug development between traditional medicine and Western medicine. Moreover, the article uses the discovery of artemisinin as an example that illustrates the “bedside–bench–bedside” approach to drug discovery to explain that the middle way for drug development is to take advantage of the best features of these two distinct systems and compensate for certain weaknesses in each. This article also summarizes evidence-based traditional medicines and discusses quality control and quality assessment, the crucial steps in botanical drug development. Herbgenomics may provide effective tools to clarify the molecular mechanism of traditional medicines in the botanical drug development. The totality-of-the-evidence approach used by the U.S. Food and Drug Administration for botanical products provides the directions on how to perform quality control from the field throughout the entire production process.
Urine organic acid contains water-soluble metabolites and/or metabolites—derived from sugars, amino acids, lipids, vitamins, and drugs—which can reveal a human’s physiological condition. These urine ...organic acids—hippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acid—were the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography−tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine. Stable-labeled isotope standard (creatinine-d3) and acetonitrile were added to the urine sample. The supernatant was diluted with deionized water and injected into LC-MS/MS. This method was validated with high selectivity for the urine sample, a low limit of quantification (10−40 ng/mL), good linearity (r > 0.995), high accuracy (85.8−109.7%), and high precision (1.4−13.3%). This method simultaneously analyzed creatinine in urine, which calibrates metabolic rate between different individuals. Validation has been completed for this method; as such, it could possibly be applied to the study of gut microbiota clinically.
Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, ...honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs.
•Adjuvants, like vinegar, wine, honey, and brine, are used in TCM processing.•Adjuvants enhance the efficacy and reduce the toxicity of crude drugs.•At certain conditions, adjuvants may change the active or toxic component contents.•We summarize TCM processing methods adopted in the last two decades.•Approaches to identify effects of processing parameters on TCMs are highlighted.
Matrix effects (MEs) continue to be an obstacle in the development of the LC-MS/MS method, with phospholipids being the major cause of MEs. Changing the mobile phase has been a common strategy to ...reduce MEs; however, the underlying mechanism is unclear. "In-source multiple-reaction monitoring" (IS-MRM) for glycerophosphocholines (PCs) has been commonly applied in many bioanalytical methods. "Visualized MEs" is a suitable term to describe the application of IS-MRM to visualize the elution pattern of phospholipids. We selected a real case to discuss the relationship of MEs and phospholipids in different mobile phases by quantitative, qualitative, and visualized MEs in LC-MS/MS bioanalysis. The application of visualized MEs not only predicts the ion-suppression zone but also helps in selecting an appropriate (1) mobile phase, (2) column, (3) needle wash solvent for the residue of analyte and phospholipids, and (4) evaluates the clean-up efficiency of sample preparation. The TRAM-34 LC-MS/MS method, improved by using visualized MEs, was shown to be a precise and accurate analytical method. All data indicated that the use of visualized MEs indeed provided useful information about the LC-MS/MS method development and improvement. In this study, an integrative approach for the qualitative, quantitative, and visualized MEs was used to decipher the complexity of MEs.
Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and ...MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel. Concentrations of HA and o-/m-/p-MHAs were normalized to those of creatinine and used to analyze urine samples of 160 operating room (OR) healthcare personnel, including administrative staff, surgical nurses, nurse anesthetists, and surgeons. The results showed that the five analytes could be accurately separated and exhibited good linearity (r > 0.9992). The rate of recovery was between 86% and 106%, and the relative standard deviation was less than 5%. Urine from administrative staff presented the highest median concentration of hippuric acid (0.25 g/g creatinine); this was significantly higher than that found in the urine of surgeons (0.15 g/g). The concentrations of urinary o-/m-/p-MHAs in surgical nurses were higher than those in administrative staff, nurse anesthetists, and surgeons. Furthermore, the type, sex, and age of healthcare personnel were associated with changes in urine HA and o-/m-/p-MHA concentrations. Healthcare personnel should be aware of the risk of exposure to surgical smoke.
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•LC-MS/MS was used to analyze the contents of HA and o-/m-/p-MHAs in urine.•The administrative staff had the highest concentration of hippuric acid in urine.•The highest concentration of urinary o-/m-/p-MHAs was found in surgical nurses.•Urinary concentrations of HA and o-/m-/p-MHAs were associated with job type, sex, and age.
Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced ...obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of
-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.
The composition and concentration distribution of volatile organic compounds (VOCs) in surgical smoke had seldomly been reported. This study aimed to investigate the profile of VOCs and their ...concentration in surgical smoke from breast surgery during electrocautery in different tissues, electrosurgical units, and electrocautery powers.
Thirty-eight surgical smoke samples from 23 patients performed breast surgery were collected using evacuated stainless steel canisters. The concentrations of 87 VOCs in surgical smoke samples were analyzed by gas chromatography-mass spectrometry. The human tissues, electrosurgical units, and electrocautery power were recorded.
The median level of total VOCs concentrations in surgical smoke samples from mammary glands (total VOCs: 9953.5 ppb; benzene: 222.7 ppb; 1,3-butadiene: 856.2 ppb; vinyl chloride: 3.1 ppb) using conventional electrosurgical knives were significantly higher than that from other tissues (total VOCs: 365.7–4266.8 ppb, P < 0.05; benzene: 26.4–112 ppb, P < 0.05; 1,3-butadiene: 15.6–384 ppb, P < 0.05; vinyl chloride: 0.6–1.8 ppb, P < 0.05) using different electrosurgical units. A high methanol concentration was found in surgical smoke generated during breast surgery (641.4–4452.5 ppb) using different electrosurgical units. An electrocautery power of ≥ 27.5 watts used for skin tissues produced a higher VOCs concentration (2905.8 ppb).
The surgical smoke samples collected from mammary glands using conventional electrosurgical knives had high VOCs concentrations. The carcinogens (including benzene, 1,3-butadiene, and vinyl chloride) and methanol were found in the surgical smoke samples from different electrosurgical units. The type of electrosurgical unit and electrocautery power used affected VOCs concentrations in surgical smoke.
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•Electrocautery conditions include electrosurgical unit and electrocautery power.•The VOCs concentration in surgical smoke was different among human tissues.•Low levels of VOCs were found in surgical smoke from mammary glands using PEAK.•Higher electrocautery power setting increased of VOCs level in surgical smoke.•It is necessary to reduce the exposure risk of surgical smoke in medical personnel.
The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive.
A prospective ...cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3-6 months after therapy and compared with those of sex- and age-matched controls (n = 470).
At baseline, of 415, 168 (40.5%) had insulin resistance (IR). The following were associated: levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), HCV RNA, fibrosis-4 score, and interferon-λ3-rs12979860 genotype with total cholesterol (TC) levels; and TG levels and BMI with HOMA-IR. Over a 3-year follow-up, in SVR patients, BMI and TC levels and TG/HDL-C ratios increased from baseline, while HOMA-IR trended downward by 72 weeks after therapy and then increased. The increased HDL-C levels began to decrease after 72 weeks after therapy. TC and HOMA-IR were negatively associated with each other until 24 weeks after therapy. Earlier increases in BMI and decreases in HOMA-IR were noted in SVR patients with than in those without baseline IR. Compared with controls, in the subgroup without baseline IR, SVR patients had increased BMI and HOMA-IR levels. Metabolic profiles were similar between SVR patients and controls in the subgroup with baseline IR.
In SVR patients treated with DAAs, the recovery of altered lipid and glucose metabolism was not coupled until 72-week post-therapy, when HOMA-IR reached its nadir. SVR patients with baseline IR recovered from HCV-associated metabolic alterations earlier than those without baseline IR.
Hepatic clearance has been widely studied for over 50 yr. Many models have been developed using either theoretical or empirical tests to predict drug metabolism. The well-stirred, parallel-tube, and ...dispersion metabolic models have been extensively discussed. However, to our knowledge, these models cannot fully describe all relevant scenarios in hepatic clearance. We addressed this issue using the isolated perfused rat liver technique with minor modifications. Diazepam was selected to illustrate different levels of drug plasma-protein binding by changing the added concentration of human serum albumin. The free fractions of diazepam at different albumin concentrations were assayed by rapid equilibrium dialysis. The experimental data provide new insights concerning an accepted formula used to describe hepatic clearance. Regarding drug concentrations passing through the liver, the driving force concentration (CH,ss) in terms of Cin (influx in the liver) or Cout (efflux from the liver) needs to be carefully considered when determining drug hepatic and intrinsic clearances. The newly established model, termed the modified well-stirred model, which was derived from the original formula, successfully estimated hepatic drug metabolism. Using the modified well-stirred model, a theoretical driving force concentration of diazepam passing through the liver was evaluated. The model was further used to assess the predictability of in vitro to in vivo extrapolation. This study was not intended to refute the existing models, but rather to augment them using experimental data. The results stress the importance of proper calculation of dose when the drug clearance deviates from the prediction of the well-stirred model.
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•The drug availability is known to deviate from the prediction of hepatic clearance as the level of unbound drug increases.•We derived a new model from the well-stirred model to interpret the actual drug concentration driving drug elimination.•Our modified model explains the reasons for the underestimation of clearance from IVIVE and expands options to the clinic.
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