Advances in bacterial Rieske non-heme iron ring-hydroxylating dioxygenases that initiate polycyclic aromatic hydrocarbons degradation / 生物工程学报

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants, which have received widespread attentions due to their carcinogenic and mutagenic toxicity. The microbial degradation of PAHs are usually started from the hydroxylation, followed by dehydrogenation, ring cleavage and step-by-step removal of branched chains, and finally mineralized by the tricarboxylic acid cycle. Rieske type non-heme iron aromatic ring-hydroxylating dioxygenases (RHOs) or cytochrome P450 oxidases are responsible for the conversion of hydrophobic PAHs into hydrophilic derivatives by the ring hydroxylation. The ring hydroxylation is the first step of PAHs degradation and also one of the rate-limiting steps. Here, we review the distribution, substrate specificity, and substrate recognition mechanisms of RHOs, along with some techniques and methods used for the research of RHOs and PAHs.

Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach.

Integrative pharmacology has been used to identify the key active constituents (KACs) of Buchang Naoxintong capsules (BNCs), a traditional Chinese medical preparation; this approach involves the evaluation of the content profiles and drug-like properties of the BNC constituents and development of an ingredient-target network. In this study, we used a sensitive analytical method to simultaneously identify and quantify 16 constituents of BNCs. Metabolism of these constituents by gut microbiota and human oral bioavailability were predicted using an in silico approach, followed by construction of networks to analyze the interactions between BNC constituents, their molecular targets, and proteins known to be the molecular targets for Food and Drug Administration-approved colitis medication. Finally, an animal model of ischemic stroke was used to verify the therapeutic effects of the KACs of BNCs. Amygdalin and paeoniflorin were identified as the KACs because they were the 2 most abundant BNC constituents, having appropriate drug-like properties, and produced therapeutic effects against cerebral ischemia. Amygdalin produced an anti-cerebral ischemia effect, likely by interacting with the glucocorticoid receptor (NR3C1) and serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1). These results form the basis for conducting studies to identify KACs in traditional medicinal preparations; such studies might improve quality control and allow the in vivo evaluation of synergistic interactions between the complex mixtures of compounds.

Characterization and rapid identification of chemical constituents of NaoXinTong capsules by UHPLC-linear ion trap/Orbitrap mass spectrometry.

The BuChang NaoXinTong (BNC) capsule is a well-known, traditional, prescribed Chinese medication for the treatment of cardiovascular and cerebrovascular diseases. Nevertheless, the chemical profile of BNC has not been established. In the present study, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) has been developed for rapid and high-throughput screening of the preliminary chemical profile of BNC in both positive and negative ion modes. Twenty-five compounds were identified as the standard available compounds by comparing the retention time and high-resolution accurate mass. For the standard unavailable compounds, the structures were presumed based on high-accuracy protonated precursors and multi-stage mass spectrometry (MS(n)) using the proposed strategy. In particular, flavones, isoflavones, and tanshinones had the same skeleton. Therefore, the standards were utilized to characterize the fragment pathways and diagnostic fragment ions that could be applied for structural elucidation of their derivatives. Meanwhile, all the constituent groups of the compounds were detected in the individual herbs comprising BNC. Finally, a total of 178 components were identified or tentatively characterized in BNC, including 21 flavones and 6 flavone glycosides, 18 phenanthraquinones, and 22 terpenoids. The identification and structure elucidation of these chemicals provide essential data for further phytochemical studies, quality control, and pharmacological studies of BNC.

Analysis on the relationship between serum alanine aminotransferase and impaired fasting glucose / 中华内分泌代谢杂志

[Summary] To investigate the correlation of serum alanine aminotransferase (ALT) level with impaired fasting glucose (IFG) and evaluate the modification effects of body mass index in Chinese adults.The study samples were from a community-based health examination survey in Xuzhou,Jiangsu province of China.A total of 32 433 subjects with biomarkers available were included in the present study.Serum ALT,triglyceride,total cholesterol,high density lipoprotein-cholesterol,low density lipoprotein-cholesterol,and glucose levels were measured.IFG was defined as from 6.1 mmol/L to 7.0 mmol/L.Results are expressed as x±s.The correlation between serum ALT and impaired fasting glucose was assessed using logistic correlation.The correlation of serum ALT and IFG in the group of fasting blood glucose was segnificantly (r=0.07,P＜0.01),while the correlation with the normal blood glucose group fasting blood glucose is weak (r=0.001,P＞0.05).After adjusted for age,sex,and body mass index,there was a strong correlation between the fasting blood glucose (r =0.04,P＜0.01) in ALT and IFG group.After further adjustment for serum lipids,blood pressure,this correlation still exists (r =0.03,P＜0.01).Body mass index influences correlation of ALT and IFG.The present data indicate that the serum ALT is related to the risk of IFG in Chinese adults,and body mass index level may affect the relationship.

Research progress of inflammation reaction related to endoplasmic reticulum stress in ischemic endoplasmic reticulum stress / 中国药理学通报

Endoplasmic reticulum plays a key role in both basic structure formation and function performance of microenviron-ment. Endoplasmic reticulum homeostasis unbalance caused by endoplasmic reticulum stress has become a hot research topic in recent years. This paper focuses on the role of endoplasmic retic-ulum stress in ischemic stroke. Research progress of related sig-naling pathways were reviewed, especially mechanisms through which endoplasmic reticulum stress trigger the inflammatory reac-tion, so as to provide a new research method for prevention of is-chemic stroke.

Synergistic and protective effects of various combination of major components of YiQiJieDu (YQJD) on focal cerebral ischemia injury based on amino acid metabonomics / 中国药理学通报

Aim To elucidate the therapeutic effect of ginsenosides, berberine and jasminoidin after given a-lone or treatment with combination on the focal cerebral ischemia rats and study the compatibility mechanism. Methods We determined 12 endogenous amino acids in serum of rats after cerebral ischemia over 12 hours with RRLC-QQQ to evaluate the integrated role of YQJD at the dosage of 25 mg·kg-1 and 5 mg·kg-1 . Generally accepted methods were used, including be-havior test, One-Way AVONA, PLS-DA, as well as PCA to evaluate the injury induced by focal cerebral is-chemia. Results The score of neurological deficits and the level of five amino acids, namely Glu, Asp, Met, Hcy, Phe in the combination of ginsenosides, berberine and jasminoidin group in the dosage of 25 mg ·kg-1 and 5 mg·kg-1 significantly decreased (P<0. 05, P<0. 01) compared to those of model group. For another, the largest contribution group in the three principal components of PC1 , PC3 , PC4 at the dosage of 25 mg/kg and the six principal components PC1 ~PC5, PC7 in 5 mg·kg-1 was the combination of gin-senosides, berberine, jasminoidin group. Conclusions The results suggest that the efficacy of the combina-tion of ginsenosides, berberine and jasminoidin is su-perior to the combination of two or any single compo-nent, which can significantly improve the metabolic disorder of the endogenous amino acid after cerebral is-chemia. And it could be speculated that ginsenosides may play a more important role than berberine and jas-minoidin in regulating the level of amino acid metabo-lism.

Analysis on Drug Using Regularity of Rehmanniae Radix in National Standard for Chinese Patent Drugs / 中国中医药信息杂志

Objective To analyze the composition principles of Chinese patent drugs containing Rehmanniae Radix;To provide reference for clinical application and new drug research and development.Methods Based on the software Traditional Chinese Medicine Inheritance Support System (V2.0), the authors built prescription database containing Rehmanniae Radix in National Standard for Chinese Patent Drugs (NSCPD). Then the authors adopted the statistical module by using data mining methods such as association rules and improved mutual information method, with a purpose to analyze the attending disease, combination rules and the core groups in prescriptions containing Rehmanniae Radix.Results In 357 prescriptions containing Rehmanniae Radix, 17 most commonly used drug combinations were mined. Meanwhile, two diseases, namely, insomnia and vertigo were chosen from the 22 diseases that Rehmanniae Radix was most frequently used to make deeper analysis, showing that Rehmanniae Radix can achieve different therapeutic effects through different compatibility.Conclusion Prescriptions containing Rehmanniae Radixin NSCPD mainly concentrate on clear heat and cool blood, and nourish Yin. The composition principles obtained from the research that Rehmanniae Radix used when curing different diseases can fully play the efficacy of RehmanniaeRadix and provide evidence for clinical scientific formulae.

Study on absorption ingredients of yuanhuzhitong pill by everted intestinal sac method / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an everted intestinal sac method for determining absorption ingredients of yuanhuzhitong pill and study absorption characteristics of major chemical constituents of yuanhuzhitong pill.</p><p><b>METHOD</b>The everted intestinal sac model was adopted. Intestinal sac fluid samples at different time points after administration of three concentrations of Yuanhuzhitong pill were collected and determined by HPLC. The accumulative absorbed doses of active constituents were calculated, while the proportion between samples of yuanhuzhitong pill and absorption ingredients was compared.</p><p><b>RESULT</b>Eight ingredients of Yuanhuzhitong pill can be detected in intestinal sac, they are protopine, palmatine, coptisine, imperatorin, berberine, byakangelicin, alpha-allocryptopine and tetrahydropalmatine. The absorption rate constants (Ka) of eight constituents increased in jejunum and ileum with the increase in concentration of Yuanhuzhitong pill extracts (P < 0. 05), indicating a passive absorption.</p><p><b>CONCLUSION</b>As ingredients are selectively absorbed in intestinal sac, the everted intestinal sac method is selected to assess the intestinal absorption characteristics of ingredients of Yuanhuzhitong prescription.</p>