Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

Application value of enhanced recovery after surgery in patients with colorectal cancer / 中国基层医药

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in colorectal cancer patients.Methods:From January 2017 to December 2018, 60 patients with colorectal cancer who admitted to the Second People′s Hospital of Lianyungang were selected and divided into ERAS group and control group according to the random digital table method, with 30 patients in each group.The inflammation, nutritional indicators, immune indicators and clinical manifestations before and after surgery in the two groups were compared.Results:At 1 d and 3 d after surgery, the C-reactive protein (CRP) levels in the ERAS group were (70.2±10.3)mg/L, (82.5±8.2)mg/L, respectively, which were lower than those in the control group [(81.5±9.9)mg/L, (110.2±12.9)mg/L] ( t=4.324, 9.911, all P<0.05). On the third day after operation, the levels of albumin and prealbumin in the ERAS group were (31.6±4.8)g/L, (196.8±40.6)g/L, respectively, which were higher than those in the control group [(28.0±5.8)g/L, (172.1±38.8)g/L]( t=2.621, 2.409, all P<0.05). The immune parameters(IgA, IgM, IgG, CD 4+, CD 4+ /CD 8+) in the ERAS group were higher than those in the control group( t=2.132, 2.223, 6.063, 4.253, 2.828, all P<0.05). The number of cases with thirsty and hunger on the day of surgery in the ERAS group was 3 cases and 7 cases, respectively, which were less than 21 cases and 25 cases of the control group(χ 2=22.500, 21.696, all P<0.05). The first exhaust time, defecation time and hospital stay time in the ERAS group were (36.2±12.1)h, (63.4±13.4)h and (9.5±3.2)d, respectively, which were shorter than those in the control group [(54.7±13.8)h, (96.5±18.8)h and (12.1±4.0)d] ( t=5.513, 7.845, 2.761, all P<0.05). The incidence of complications between the two groups had no statistically significant difference ( P>0.05). Conclusion:ERAS can significantly reduce the physical and psychological traumatic stress of patients with colorectal cancer, achieve rapid recovery, improve the treatment effect, shorten the length of hospital stay, reduce social and family burden, and provide a basis for the choice of clinical treatment program.

Comparison of the effects of laparoscope and open complete mesocolic excision in the treatment of right colon cancer / 中国基层医药

Objective@#To compare the effects of laparoscope and open complete mesocolic excision (CME) in the treatment of right colon cancer.@*Methods@#The retrospective case-control study was adopted.The clinical data of 139 patients with right colon cancer who underwent CME at the Second People's Hospital of Lianyungang from January 2014 to November 2017 were collected.The patients were divided into laparoscopy group(55 cases) and open group(84 cases). The postoperative recovery and oncology efficacy were compared.@*Results@#The operation time in the laparoscopy group[(172.8±25.9)min]was longer than that in the open group[(142.3±20.6)min](t=7.387, P<0.05), but the blood loss of the laparoscopy group[(111.6±36.7)mL] was less than that in the open group[(150.1±61.1)mL](t=4.017, P<0.05). There was no statistically significant difference in numbers of lymph nodes harvested.Compared with open group, there were advantages in the laparoscopy group such as less anal exhaust time, less postoperative eating liquid diet time and shorter hospitalization time, the differences were statistically significant (t=4.695, 5.517, 4.642, all P<0.05). There was no statistically significant difference in postoperative complication rate (P>0.05). There were no statistically significant differences in the cumulative recurrence rate, cumulative survival rate and cumulative survival rate between the two groups after 3 years (all P>0.05).@*Conclusion@#Laparoscopic CME is minimally invasive and quick recovery, and laparoscopic CME has the same oncologic clearance effects, and is worthy of clinical application.

Effect of preoperative administration of immunomodulating enteral nutrition for gastric cancer / 中国基层医药

Objective@#To explore the application effect of preoperative administration of immunomodulating enteral nutrition for gastric cancer.@*Methods@#From January 2016 to December 2017, 90 cases with gastric cancer in the Second People′s Hospital of Lianyungang were selected and randomly divided into observation group, control group A and control group B, with 30 cases in each group.The observation group was given enteral nutrition emulsion(TPFT, Ruineng) before and after operation, the control group A was given Ruineng before operation and the enteral nutrition emulsion(TP, Ruisu) after operation, the control group B was given Ruisu before operation and Ruineng after operation.The recovery, serum markers of nutritional status and immune function were evaluated and compared, and the postoperative situations were observed.@*Results@#There were no statistically significant differences in the total protein, albumin, prealbumin and transferrin among the three groups during admission, 1 day before operation and 5 days after operation(all P>0.05). There was no statistically significant difference in immune indicators among the three groups during admission and 1 day before operation(all P>0.05). At 5 days after operation, IgA, IgM, IgG, CD4+ and CD4/CD8 in the observation group were (2.9±0.6)g/L, (1.4±0.4)g/L, (12.4±0.9)g/L, (37.4±5.1)%, (2.2±0.7), respectively, which were significantly higher than those in the control group A[(2.3±0.8)g/L, (1.1±0.6)g/L, (10.8±0.8)g/L, (34.2±4.8)%, (1.7±0.8), respectively, t=3.324, 2.250, 7.100, 2.506, 2.660, all P<0.05], the IgA and CD4/CD8 in the observation group were higher than those in the control group B[(2.6±0.8)g/L, (1.9±0.7), t=2.021, 2.127, all P<0.05]. The postoperative exhaust time of the observation group, control group A and control group B were (56.4±7.8)h, (78.6±10.4)h, (60.7±10.6)h, respectively, and the postoperative exhaust time of the observation group was significantly shorter than that of the control group A(t=9.323, P<0.05). There was no statistically significant difference in the gastrointestinal symptoms and postoperative complications among the three groups (P>0.05).@*Conclusion@#In perioperative period, immunomodulating enteral nutrition has little effect on the nutritional indicators of patients with gastric cancer and the incidence of postoperative complications, but it can improve the immune function.

L-carnitine sensitizes human glioblastoma cells to TRAIL-induced apoptosis / 中国药理学通报

Aim To investigate the enhancing effect of L-carnitine as a sensitizer on tumor necrosis factor-re-lated apoptosis inducing ligand ( TRAIL)-induced ap-optosis in glioma cells. Methods Glioma cell U87 was used as model cell line. Cell viability was determined by CCK-8 , and apoptosis was assessed by Annexin V-FITC/PI staining, caspase-3 activity and expres-sion. The expression and transcription of nuclear factor kappa B ( NF-κB ) and FLICE inhibiting protein ( c-FLIP) were measured by RT-PCR and Western blot. In addition, NF-κB was knockdown to analyze its regu-lating effect on c-FLIP expression. Results The com-bination treatment with TRAIL and L-carnitine signifi-cantly inhibited cell proliferation and induced apopto-sis. Compared with control, combinational treatment significantly suppressed the transcription and expres-sion of c-FLIP as well as translocation of NF-κB. Through silencing NF-κB, NF-κB was found to act as upstream signaling to regulate c-FLIP. Conclusion L-carnitine sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent c-FLIP expres-sion.

Investigation on Active Components inTong-MaiGranules Reflecting Its Effect of Activating Blood Circulation Based on Serum Pharmacochemistry/Serum Pharmacology / 世界科学技术-中医药现代化

Tong-Mai(TM) granules were composed ofRadix Salviae Miltiorrhizae(Danshen),Rhizoma Chuanxiong(Chuanxiong) andRadix Puerariae(Gegen). It had the effect of activating blood circulation. It had been used to treat ischemic cardio-cerebrovascular diseases in the clinical practice. This research combined serum pharmacochemistry and serum pharmaocology to study the material basis of active components in TM granules. After single or multiple intragastric administrations of TM granules, serum blood samples of rats were collected at different time points. LC-MS/MS method was developed to analyze chemical components of TM in blood serum samples. The cardiomyocyte hypoxia / reoxygenation (H/R) model was used in the evaluation of cardiomyocyte protection by TM. The correlation analysis was also conducted between serum concentration of TM and cardiomyocyte activity. The results showed that 8 components of pueraria flavonoid, 5 components of salvianolic acids and 2 components fromGegen were promptly absorbed and reached their highest concentrations at 5 or 30 min after administration. After 3 times of medication, the serum concentration was obviously higher compared to single medication. The drug-serum of TM showed significant protective effect on the cardiomyocyte H/R injury with dose-effect relationship. Daidzein, lithospermic acid, salvianolic acid A, salvianic acid A and rosmarinic acid presented as the most correlated components linked to the effect of activating blood circulation by TM. The serum pharmacochemistry / serum pharmacology related studies provided references for the verification of material basis of active components in compound Chinese medicine.

Constituents from the leaves of Aquilaria sinensis / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the leaves of Aquilaria sinensis.</p><p><b>METHOD</b>The compounds were isolated and purified by the methods of solvent extraction and chromatographic technique, and their structures were identified on the basis of the analyses of spectral data.</p><p><b>RESULT</b>Thirty-three compounds were obtained. Among them, twelve compounds were identified as 5-hydroxyl-7,4'-dimethoxyflavone (1), acacetin (2), luteolin (3), genkwanin (4), yuankanin (genkwanin-5-O-beta-D-primeveroside, 5), adenosine (6), genkwanin-5-O-beta-D-glucopyranoside (7), hypolaetin-7-O-beta-D-glucopyranoside (8), hypoxanthine (9), uracil (10), 8-C-beta-D-galactopyranosylisovitexin (11), and 4-(1,2,3-trihydroxypropyl) -2,6-dimethoxyphenyl-1-O-beta-D-glucopyranoside (12), respectively.</p><p><b>CONCLUSION</b>All compounds except for 1, 3 and 4 were isolated from the leaves of A. sinensis for the first time.</p>

A new natural product from root of Angelica dahurica cv. Qibaizhi / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the root of Angelica dahurica cv. Qibaizhi.</p><p><b>METHOD</b>The compounds were isolated and purified by the methods of solvent extraction and chromatographic technique, and their structures were identified on the basis of the analyses of spectral data.</p><p><b>RESULT</b>Twenty-seven compounds were obtained and identified as isoimperatorin (1), alloisoimperatorin (2), oxypeucedanin hydrate (3), byakangelicin (4), alloimperatorin (5), beta-sitosterol (6), dibutylphthalate (7), 6-(3,3-dimethylallyloxy) -7-hydroxycoumarin {7-hydroxy-6-[ (3-methyl-2-butenyl) oxy] -coumarin, 8}, xanthotoxol (9), 5-hydroxy-8-methoxypsoralen ( 5-hydroxyxanthotoxin, 10), smyrindiol (11), umbelliferone (12), bergapten (13), imperatorin (14), phellopterin (15), isoimpinellin (16), 6-acyl-7-methoxycoumarin (17), psoralen (18), isoscopletin (19), scoparone (20), xanthotoxin (21), angelol A (22), oxypeucedanin ethanolate (oxypeucedanin hydrate-3"-ethyl ether, 23), dehydrogeijerin (pablohopin, 24) , ulopterol (25), heraclenol (26), and pabulenol (27), respectively.</p><p><b>CONCLUSION</b>Compound 8 was a new natural product and the above-mentioned all the compounds except for compounds 1, 3 and 14 were isolated from the root of A. dahurica cv. Qibaizhi for the first time.</p>

Establishment of model and standard operation procedure for biotransformation of chemical constituents of traditional Chinese medicine by human intestinal bacteria / 中国中药杂志

<p><b>OBJECTIVE</b>To establish human intestinal bacteria biotransformation model and the standard operation procedure for studying and assessing intestinal biotransformation of chemical constituents of traditional Chinese medicine (TCM).</p><p><b>METHOD</b>The chemical constituent of TCM was incubated together with human intestinal flora or isolated strain, or their secretory enzymes at anaerobic environment and 37 degrees C. The biotransformation products were extracted by solvent extraction methods, separated by column chromatographic methods, and identified by spectroscopic analysis. The biotransformation mechanisms would be deduced by comparison of structural characteristics of the biotransformation products and the parent drug and/or compound, as well as the enzyme(s)-catalysed bioreactions.</p><p><b>RESULT</b>The established biotransformation model of human intestinal bacteria is facile for operation and has the capability of converting the chemical constituent of traditional Chinese medicine. The growing cells transformation method, the resting cells transformation method or enzyme(s)-catalysed transformation method can all be selected as the transformation approach.</p><p><b>CONCLUSION</b>The established human intestinal bacteria biotransformation model can be used to study the intestinal biotransformation of orally administrated chemical constituents of TCM and their biotransformation mechanism.</p>

Liposolubility constituents from leaves of Aquilaria sinensis / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the leaves of Aquilaria sinensis.</p><p><b>METHOD</b>The compounds were isolated and purified by the methods of solvent extraction and chromatographic technique, and their structures were identified on the basis of the analyses of spectral data.</p><p><b>RESULT</b>Eleven compounds were obtained and identified as beta-sitosterol (1), hexacosanic acid (2), cryptotanshinone (3), 2alpha-hydroxyursane (4), dihydrotanshinone I (5), tanshinone I (6), tanshinone II(A) (7), 2alpha-hydroxyursolic acid (8), p-hydroxybenzoic acid (9), hydroquinone (10), and daucosterol (11), respectively.</p><p><b>CONCLUSION</b>All compounds except for compound 9 were isolated from the leaves of A. sinensis for the first time.</p>

Chemical constitutents from pre-formulation of lonicerae japonicae flos in shuanghuanglian lyophilized powder for injection / 中国中药杂志

<p><b>OBJECTIVE</b>To research the chemical constitutents for the pre-formulation of Lonicerae Japonicae Flos (the dried buds of Lonicera japonica) in Shuanghuanglian lyophilized powder for injection and provide substance foundation for the adverse reaction of Shuanghuanglian lyophilized powder for injection.</p><p><b>METHOD</b>The chemical constituents were isolated by column chromatography and preparative HPLC. All structures were characterized by the spectroscopic methods including ESI-MS, 1H-NMR, 13C-NMR, and compared with data in the literature.</p><p><b>RESULT</b>Twenty compounds were isolated and identified as sophoraricoside(1), luteolin-7-O-beta-D-glucopyranoside(2), rutin(3), quercetin(4), 3,5-O-dicaffeoyl quinic acid methyl ester(5), 4,5-O-dicaffeoyl quinic acid methyl ester(6), 3,4-O-dicaffeoyl quinic acid methyl ester(7), 4,5-dicaffeoyl quinic acid(8), 3,4-dicaffeoyl quinic acid(9), chlorogenic acid(10), epi-vogeloside (11), sweroside(12), vogeloside(13), secoxyloganin(14), macranthoidin A(15), macranthoidin B(16), loniceroside A(17), loniceroside B(18), loniceroside C(19), dipsacoside B(20).</p><p><b>CONCLUSION</b>Compound 1 was identified in genus Lonicera for the first time and compounds 1-20 were isolated from the pre-formulation for the first time.</p>

GC-MS analysis of essential oil from root of Angelica dahurica cv. Qibaizhi / 中国中药杂志

<p><b>OBJECTIVE</b>Essential oil from root of Angelica dahurica cv. Qibaizhi were studied.</p><p><b>METHOD</b>Essential oil was extracted by water-steam distillation and analyzed by GC-MS.</p><p><b>RESULT</b>Two hundreds and ninety chromatographic peaks were detected, among which 111 compounds have been identified. The contents of them made up 90.61% of the total essential oil.</p><p><b>CONCLUSION</b>The main compounds in the essential oil were 3-carene (12.70%), beta-elemene (6.20%), beta-terpinene (3.53%), beta-myrcene (1.97%), gamma-elemene (1.82%), beta-phellandrene (1.65%), and beta-maaliene (1.61%), et al. In addition, suberosin (0.16%), a coumarins compound, was also determined.</p>

Assay of andrographolide bulk drug by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a method for the determination of andrographolide bulk drug by HPLC.</p><p><b>METHOD</b>The condition of HPLC was Diamonsil C18 (2) column (4.6 mm x 250 mm, 5 microm) with methanol-water (60:40) as a mobile phase. The flow rate was 1.0 mL x min(-1) and the detection wavelength was 235 nm.</p><p><b>RESULT</b>The standard curve was linear in the range of 0.5-5.0 microg and the correlation coefficient was 1.000. The average recoveries of the low, middle and high concentrations were 99.1%, 99.5% and 100.8%, respectively.</p><p><b>CONCLUSION</b>The method is simple, precise and accurate, and it can be used for the quality control of andrographolide bulk drug.</p>

Absorption and transportation characteristic of alkaloids from herba ephedra in model of Caco-2 cells monolayer / 中国中药杂志

<p><b>OBJECTIVE</b>To study the absorption and transportation characteristic of 1-ephedrine (LEP), d-pseudoephedrine (DPEP), d-norpseudoephedrine (DNPE) isolated from Herba Ephedrae, which were classified the alkaloids, in human intestinal epithelium.</p><p><b>METHOD</b>Caco-2 (the human colon adeno carcinoma cell lines) cells monolayer was used as an intestinal epithelial cell model. The permeability of the three alkaloids from apical side (AP side) to basolateral side (BL side) or from BL side to AP side was evaluated. The concentration of the three alkaloids was measured by HPLC coupled with UV detector. Transportation parameters and apparent permeability coefficients (P(app)) were then calculated, and P(app) values were compared with the reported values for model compounds, propranolol and atenolol.</p><p><b>RESULT</b>The P(app) values of the three alkaloids in the bi-directional transportation were quantitative degree of 1.0 x 10(-5) cm x s(-1), which was comparable with the P(app), value of propranolol, which is a transcellular transportation marker and a well-transported compound with a P(app) > or = 1.0 x 10(-5) cm x s(-1). The absorption and transportation of the three alkaloids were positive correlation to the concentration of 10-200 mol x L(-1).</p><p><b>CONCLUSION</b>LEP, DPEP and DNPE can be absorbed across intestinal epithelial cells by passive diffusion mechanism, and are well absorbed compounds.</p>

Chemical constituents of roots of Saposhnikovia divaricata / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents in the dried roots of Saposhnikovia divaricata.</p><p><b>METHOD</b>The chemical constituents were isolated by various column chromatographic methods and structurally elucidated by IR, UV, MS and NMR evidences.</p><p><b>RESULT</b>Eighteen compounds were obtained and identified as 3'-O-angeloylhamaudol (1), isobergapten (2), imperatorin (3), pentacosane acid (4), anomalin (5), decursin (6), 5-methoxy-7-(3,3-dimethylallyl- oxy)coumarin (7), decursinol angelate (8), xanthotoxin (9), bergapten (10), tectochrysin (11), scopoletin (12), hamaudol (13), ledebouriellol (14), cimifugin (15), sec-O-glucosylhamaudol (16), 4'-O-beta-D-glucosyl-5-O-methylvisamminol (17), and prim-O-glucosylcimifugin (18).</p><p><b>CONCLUSION</b>Compounds 2, 6-8, and 11 were isolated from the roots of S. divaricata for the first time. Compounds 1 and 13-18 were chromones, 2, 3, 5-10 and 12 were coumarins, 4 was fatty acid, and 11 was flavonoid.</p>

O-methylnotopterol, a new natural product from the roots and rhizomes of Notopterygium incisum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of ethyl acetate-soluble fraction from methanolic extract of the roots and rhizomes of Notopterygium incisum .</p><p><b>METHOD</b>The chemical constituents were isolated and purified by various chromatographic methods, and their structures were identified by NMR and MS data analysis.</p><p><b>RESULT</b>Five compounds were obtained and identified as falcarindiol (1), 8-hydroxy-l-methoxy-( Z) -9-heptadecene-4, 6-diyn-3-one (2) angenomalin (3), scopoletin (4), O-methylnotopterol (5).</p><p><b>CONCLUSION</b>Compound 5 was a new natural product and compounds 2-4 were isolated from the roots and rhizomes of N. incisum for the first time.</p>

Sapodivarin, a new coumarin from roots of Saposhnikovia divaricata / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents in the dried roots of Saposhnikovia divaricata (Turcz.) Schischk.</p><p><b>METHOD</b>The chemical constituents were isolated by various column chromatographic methods and structurally elucidated by IR, UV, MS and NMR evidences.</p><p><b>RESULT</b>Two compounds were obtained and identified as nodakenetin (1) and 8-[4-(beta-D-glucopyrano-sy-loxy)-3-methyl-2-buten-1-yl]oxy-5-methoxy-6,7-furanocoumarin (2), respectively.</p><p><b>CONCLUSION</b>Compound 2 is a new compound and named sapodivarin.</p>

Fingerprints of Tongmai Keli by HPLC-DAD-MS / 药学学报

In order to clarify the chemical composition of Tongmai Keli, a HPLC fingerprint was established, and the 22 peaks were characterized by LC-DAD-MS. The herbal sources of these peaks were assigned. The results implied that genistin 8-C-glucoside, puerarin, daidzein 8-C-apiosyl (1, 6)-O-glucoside, daidzin, and salvianolic acid B were the main constituents of in Tongmai Keli. Ten batches of Tongmai Keli produced by different pharmaceutical companies were analyzed. Although different batches contained similar compounds, the contents of major compounds were significantly different. The method established in this study could be used for the quality control of Tongmai Keli.

New dibenzofuran and anthraquinone from Usnea longissima / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of Usnea longissima.</p><p><b>METHOD</b>The compounds were isolated and purified by the methods of solvent extraction and chromatographic technique, and their structures were identified on the basis of the analyses of spectral data.</p><p><b>RESULT</b>Two compounds were obtained and identified as 3, 6-diacetyl-2, 7, 9-trihydroxy-8, 9b-dimethyl-1 [9bH]-dibenzofuranone(1) and 1, 3, 8-trihydroxy4, 6-dimethyl-9, l0-anthracenedione(2), respectively.</p><p><b>CONCLUSION</b>Compounds 1 and 2 were new compounds and were named as longiusnine and longissimausnone, respectively.</p>

GC-MS analysis of essential oil of honeyed red ginseng / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the constituents of essential oil of honeyed red ginseng, and provide scientific basis for its quality evaluation.</p><p><b>METHOD</b>The essential oil was extracted by hydrodistillation and separated by capillary GC. The chemical constituents were determined by normalization and were identified by MS.</p><p><b>RESULT</b>One-hundred ninety-five chromatographic peaks were detected and among them 76 compounds were identified, which were 78.27% of the total essential oil.</p><p><b>CONCLUSION</b>The main constituents of the essential oil were sesquiterpenoids. Among identified compounds, 24 monoterpenoids and sesquiterpenoids were isolated from the essential oil of red ginseng for the first time.</p>