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.
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 β-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.
Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX.
Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug substances with a theoretical possibility of NA impurity, 141 of which had not been reported previously. In addition, the DMA moiety was significantly dominant among the eight NA substructures. The results were validated using data from the literature, and a high detection sensitivity of 0.944 was demonstrated. Furthermore, our approach has the advantage of scalability, owing to which 31 additional drugs with suspected NA-contaminated substructures were identified using the substructures of 1-methyl-4-piperazine in rifampin and 1-cyclopentyl-4-piperazine in rifapentine. In conclusion, the reported substructure-based approach provides an effective and scalable method for the screening and investigation of NA impurities in various pharmaceuticals and might be used as an ancillary technique in the field of pharmaceutical quality control for risk assessments of potential NA impurities.
1 February 2021 in Ecotoxicology and Environmental Safety
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.