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1.
Sci Rep ; 14(1): 12430, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816541

ABSTRACT

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.


Subject(s)
Corticosterone , Dinoprostone , Epinephrine , Fibroblast Growth Factors , Glucagon , Linoleic Acids, Conjugated , Mice, Transgenic , Animals , Female , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/genetics , Mice , Linoleic Acids, Conjugated/pharmacology , Linoleic Acids, Conjugated/metabolism , Corticosterone/metabolism , Dinoprostone/metabolism , Glucagon/metabolism , Epinephrine/metabolism , Thermogenesis/drug effects , Thermogenesis/genetics , Male , Lipid Metabolism/drug effects , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/drug effects , Fatty Liver/metabolism , Fatty Liver/genetics , Lipolysis/drug effects , Hypertriglyceridemia/metabolism , Hypertriglyceridemia/genetics , Adiposity/drug effects
2.
Psychoneuroendocrinology ; 165: 107042, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38613945

ABSTRACT

BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.


Subject(s)
Cytokines , Depressive Disorder, Major , Interleukin-2 , Suicidal Ideation , Humans , Male , Female , Depressive Disorder, Major/blood , Depressive Disorder, Major/psychology , Adult , Cross-Sectional Studies , Cytokines/blood , Interleukin-2/blood , Middle Aged , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-10/blood , Interleukin-8/blood , Interleukin-1beta/blood , China , Psychiatric Status Rating Scales , Young Adult
3.
Math Biosci Eng ; 20(10): 18146-18172, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-38052552

ABSTRACT

In conventional message communication systems, the practice of multi-message multi-receiver signcryption communication encounters several challenges, including the vulnerability to Key Generation Center (KGC) attacks, privacy breaches and excessive communication data volume. The KGC necessitates a secure channel to transmit partial private keys, thereby rendering the security of these partial private keys reliant on the integrity of the interaction channel. This dependence introduces concerns regarding the confidentiality of the private keys. Our proposal advocates for the substitution of the KGC in traditional certificateless schemes with blockchain and smart contract technology. Parameters are publicly disclosed on the blockchain, leveraging its tamper-proof property to ensure security. Furthermore, this scheme introduces conventional encryption techniques to achieve user identity privacy in the absence of a secure channel, effectively resolving the issue of user identity disclosure inherent in blockchain-based schemes and enhancing communication privacy. Moreover, users utilize smart contract algorithms to generate a portion of the encrypted private key, thereby minimizing the possibility of third-party attacks. In this paper, the scheme exhibits resilience against various attacks, including KGC leakage attacks, internal privilege attacks, replay attacks, distributed denial of service attacks and Man-in-the-Middle (MITM) attacks. Additionally, it possesses desirable security attributes such as key escrow security and non-repudiation. The proposed scheme has been theoretically and experimentally analyzed under the random oracle model, based on the computational Diffie-Hellman problem and the discrete logarithm problem. It has been proven to possess confidentiality and unforgeability. Compared with similar schemes, our scheme has lower computational cost and shorter ciphertext length. It has obvious advantages in communication and time overhead.

4.
J Nutr Biochem ; 120: 109419, 2023 10.
Article in English | MEDLINE | ID: mdl-37487823

ABSTRACT

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss after oral administration. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to elucidate the enduring influence of t10c12-CLA on overall health. Compared to their wild-type (wt) C57BL/6J littermates, both biallelic Pai/Pai and monoallelic Pai/wt mice exhibited reduced plasma triglycerides levels, and Pai/wt mice exclusively showed increased serum fibroblast growth factor 21. Further analysis of Pai/Pai mice found a decrease in white fat and an increase in brown fat, with more heat release and less physical activity. Analysis of Pai/Pai brown adipose tissues revealed that hyperthermia was associated with the over-expression of carnitine palmitoyltransferase 1B, uncoupling proteins 1 and 2. These findings suggest that the systemic and long-term impact of t10c12-CLA on obesity might be mediated through the pathway of fibroblast growth factor 21 when low doses are administered or through enhanced thermogenesis of brown adipose tissues when high doses are employed.


Subject(s)
Adiposity , Linoleic Acids, Conjugated , Male , Mice , Animals , Mice, Transgenic , Linoleic Acids, Conjugated/pharmacology , Mice, Inbred C57BL , Obesity
5.
Front Psychiatry ; 14: 1144873, 2023.
Article in English | MEDLINE | ID: mdl-37181896

ABSTRACT

Background: Risperidone is a commonly prescribed antipsychotic drug with a potential side effect of weight gain. However, the pathophysiological mechanism is still poorly understood. Here, we sought to identify potential biomarkers of risperidone-induced weight gain by using a targeted metabolomics approach. Methods: We enrolled 30 subjects who received risperidone monotherapy for 8 weeks from a prospective longitudinal cohort study for drug-naïve schizophrenia patients. Plasma metabolites were measured by targeted metabolomics Biocrates MxP® Quant 500 Kit at baseline and 8-week follow-up. Results: After 8 weeks of risperidone treatment, the levels of 48 differential metabolites were upregulated, including lysophosphatidylcholines (2), phosphatidylcholines (PC) (8), cholesteryl esters (CE) (3), and triglycerides (35), while 6 differential metabolites namely PC aa C38:6, methionine (Met), α-aminobutyric acid (AABA), TrpBetaine, CE (22:6), and Taurocholic acid (TCA) were downregulated. Interestingly, the reduction of PC aa C38:6, AABA and CE (22:6) was linearly related with increased BMI. Further multiple regression analysis showed that the changes of PC aa C38:6 and AABA were independent contributors of increased BMI. In addition, baseline levels of PC aa C36:5, CE (20:5) and AABA had positive relationships with the change of BMI. Conclusion: Our findings indicate phosphatidylcholines and amino acids may serve as biomarkers for risperidone-induced weight gain.

6.
J Sci Food Agric ; 103(10): 5126-5137, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37005496

ABSTRACT

BACKGROUND: Fragrant rice is increasingly popular with the public owing to its fresh aroma, and 2-acetyl-1-pyrroline (2-AP) is the main characteristic component of the aroma in fragrant rice. Rice-fish co-culture is an environmentally friendly practice in sustainable agriculture. However, the effect of rice-fish co-culture on 2-AP in grains has received little study. A conventional fragrant rice (Meixiangzhan 2) was used, and a related field experiment during three rice growing seasons was conducted to investigate the effects of rice-fish co-culture on 2-AP, as well as the rice quality, yield, plant nutrients, and precursors and enzyme activities of 2-AP biosynthesis in leaves. This study involved three fish stocking density treatments (i.e. 9000 (D1), 15 000 (D2), and 21 000 (D3) fish fries per hectare) and rice monocropping. RESULTS: Rice-fish co-culture increased the 2-AP content in grains by 2.5-49.4% over that of the monocropping, with significant increases in the early and late rice seasons of 2020. Rice-fish co-culture treatments significantly promoted seed-setting rates by 3.39-7.65%, and improved leaf nutrients and rice quality. Notably, the D2 treatment significantly increased leaf total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents and the head rice rate at maturity stage, while significantly decreased chalkiness degree. There was no significant difference in rice yield. CONCLUSION: Rice-fish co-culture had positive effects on 2-AP synthesis, rice quality, seed-setting rates, and plant nutrient contents. The better stocking density of field fish for rice-fish co-culture in this study was 15 000 fish ha-1 . © 2023 Society of Chemical Industry.


Subject(s)
Oryza , Animals , Oryza/chemistry , Edible Grain , Seeds , Pyrroles
7.
Appl Biochem Biotechnol ; 195(1): 597-609, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36107387

ABSTRACT

Understanding the principle of regulated cell death (RCD) such as ferroptosis and apoptosis provides opportunities to overcome sorafenib resistance of HCC. Complexin II (CPLX2) is involved in calcium-dependent fusion of vesicles and plasma membrane, and recent studies showed CPLX2 is involved in cancer progression. However, the expression and function of CPLX2 are unclear in hepatocellular carcinoma (HCC). qPCR and western blotting assays were used to detect the levels of CPLX2. MTT and colony formation assays were used to detect cell viability. The contents of iron, ROS, MDA, and GSH were used to evaluate the function of CPLX2 on ferroptosis, while the flow cytometry and TUNEL assays were used to evaluate the role of CPLX2 on apoptosis. Our analysis showed CPLX2 is significantly upregulated in HCC, which predicts poor overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and disease-specific survival (DSS) for patients with HCC. Further function enrichment analysis of genes related to CPLX2 showed CPLX2 is involved in the NRF2 pathway. Downregulation of CPLX2 can inhibit NRF2 expression and the transcription of its downstream genes, which confirms that CPLX2 is involved in NRF2 pathway. Cell viability assay showed that ferroptosis and apoptosis inhibitors can reverse the inhibition effect of CPLX2-knockdown on cell survival, respectively. And downregulation of CPLX2 significantly promotes the contents of iron, ROS, and MDA, while inhibiting the GSH level of HCC cell lysate, suggesting CPLX2 involved in ferroptosis. Moreover, downregulation of CPLX2 promotes the apoptosis of HCC cells by flow cytometry and TUNEL assay. And upregulation of NRF2 can partly reverse the inhibitory effect of CPLX2-downregulation on ferroptosis and apoptosis. Finally, we found downregulation of CPLX2 aggravates cell death induced by sorafenib. CPXL2 regulates ferroptosis and apoptosis through NRF2 pathway, and CPLX2 knockdown promotes cell death induced by sorafenib. CPLX2 might be an effective target for therapy patients with HCC.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , NF-E2-Related Factor 2 , Humans , Apoptosis , Carcinoma, Hepatocellular/pathology , Iron/pharmacology , Liver Neoplasms/pathology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Sorafenib/pharmacology , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism
8.
Materials (Basel) ; 15(12)2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35744206

ABSTRACT

The wide Mg alloy sheets produced by hot extrusion usually can easily form an inhomogeneous texture, resulting in anisotropic mechanical properties and poor formability. However, few studies have been carried out on the bulk texture investigation at different areas of as-extruded Mg alloy sheets, especially the Mg alloys with different alloying elements. In this work, the effect of Al on the bulk texture and mechanical properties at different areas for three wide Mg-Al-Zn alloy sheets with different Al contents (Mg-3Al-0.5Zn, Mg-8Al-0.5Zn and Mg-9Al-0.5Zn) are mainly investigated by neutron diffraction. The results showed that a strong and uneven basal texture was formed in the Mg-3Al-0.5Zn sheet. Meanwhile, the intensity of the basal texture was significantly weakened due to the numerous fine precipitates of Mg17Al12 particles, with the Al content increasing, which hinder the grain growth during extrusion, while fine recrystallized grains have a more random orientation. The enhanced tensile properties in Mg-8Al-0.5Zn and Mg-9Al-0.5Zn alloy sheets are ascribed to the cooperation effect of a refined microstructure, precipitates and weakened basal texture. Among the three Mg alloy sheets, the Mg-8Al-0.5Zn alloy sheet has a yield strength of about 270 MPa, an ultimate tensile strength of about 330 MPa and ultimate elongation of about 16% in the extrusion direction, which possesses the most excellent comprehensive mechanical properties.

9.
Br J Clin Pharmacol ; 88(6): 2605-2616, 2022 06.
Article in English | MEDLINE | ID: mdl-35098565

ABSTRACT

AIMS: Unfractionated heparin (UFH) has been the primary anticoagulant of choice on extracorporeal membrane oxygenation (ECMO). However, it is debatable whether bivalirudin (BIV), a direct thrombin inhibitor, may be considered a better alternative anticoagulant option. METHODS: We searched Embase, Pubmed, Cochrane library, Clinicaltrials.gov, CNKI and Wanfang databases up to 15 June 2021. Randomized controlled trials and observational studies were considered eligible for inclusion. Random-effects meta-analyses, including subgroup analyses, were conducted. RESULTS: A total of 9 studies containing 994 patients were enrolled. All articles were retrospective cohort studies. Compared with UFH, BIV was associated with lower risks of major bleeding (risk ratio [RR]: 0.32, 95% confidence interval [CI] 0.22-0.49), ECMO in-circuit thrombosis (RR: 0.57, 95% CI 0.43-0.74), stroke (RR: 0.52, 95% CI 0.29-0.95) and in-hospital mortality (RR: 0.82, 95% CI 0.69-0.99), and higher rates of survival to ECMO decannulation (RR: 1.18, 95% CI 1.03-1.34). Pooled risk estimates did not show a significant association with clinical thrombotic events (RR: 0.69, 95% CI 0.45-1.07). Moreover, BIV was associated with a lower risk of ECMO in-circuit thrombosis and in-hospital mortality in the adult subgroup but not in the paediatric subgroup. However, leave-one-out sensitivity analyses indicated that the results of stroke, survival to ECMO decannulation and in-hospital mortality should be interpreted with caution. CONCLUSION: BIV appears to be a potential alternative to UFH in paediatric and adult patients requiring ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation , Stroke , Thrombosis , Adult , Anticoagulants/adverse effects , Child , Extracorporeal Membrane Oxygenation/adverse effects , Heparin/adverse effects , Hirudins , Humans , Peptide Fragments , Recombinant Proteins/adverse effects , Retrospective Studies , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
10.
Psychiatry Res ; 290: 113026, 2020 08.
Article in English | MEDLINE | ID: mdl-32450414

ABSTRACT

A sequential-recruited clinical trial has been conducted to assess capacity of Patient Health Questionnaire-15 (PHQ-15) in distinguishing bipolar II disorder from major depressive disorder. A total of 73 patients (49 BD-II depression patients) filled sociodemographic characteristics, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 Questionnaire (GAD-7), and PHQ-15. Sum score of PHQ-15 showed statistically significant difference in the two groups (t-test, P = 0.027). The area under the curve was 0.663 (P = 0.025), and the specificity was 0.75 at sum score of 13. Patients with BD-II depression has more somatic symptoms than MDD, and PHQ-15 might be used for identification.


Subject(s)
Bipolar Disorder/diagnosis , Depressive Disorder, Major/diagnosis , Patient Health Questionnaire/standards , Somatoform Disorders/diagnosis , Adult , Bipolar Disorder/psychology , Depressive Disorder, Major/psychology , Female , Humans , Male , Middle Aged , Psychometrics , Sensitivity and Specificity , Somatoform Disorders/psychology , Surveys and Questionnaires
11.
Biosci Biotechnol Biochem ; 84(4): 789-796, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31889476

ABSTRACT

We previously demonstrated the efficient production of trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) in Lactococcus lactis by ectopically expressing a Propionibacterium acnes isomerase (pai) gene and also mentioned that a recombinant strain was unable to accumulate t10c12-CLA product, despite the normal transcription. Here, the molecular analysis indicated that this mutated strain harbors a pai gene with a single-nucleotide mutation converting GC50A to GTA, leading to a corresponding change of Alanine residue into Valine. The expression of the reverse mutation resulted in the recovery for enzyme activity. Site-directed mutagenesis indicated that the codon usage of Val17 was not responsible for the enzyme inactivation in the Ala17Val mutation. Western blot analysis revealed that the recombinant PAI protein was not detectable in the His tag-marked Ala17Val mutant. It is, therefore, reasonable to assume that Ala17 residue is critical for PAI functionality.Abbreviations: pai: propionibacterium acnes isomerase; CLA: conjugated linoleic acid; t10c12-CLA: trans 10, cis 12-CLA; LA: linoleic acid (18:2n-6); FAD: flavin adenine dinucleotide.


Subject(s)
Amino Acid Substitution , Flavin-Adenine Dinucleotide/metabolism , Isomerases/antagonists & inhibitors , Propionibacterium acnes/enzymology , Blotting, Western , Codon , Crystallography, X-Ray , Isomerases/chemistry , Isomerases/genetics , Isomerases/metabolism , Linoleic Acids, Conjugated/metabolism , Loss of Function Mutation , Propionibacterium acnes/genetics , Protein Conformation
12.
Medicine (Baltimore) ; 96(39): e8120, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28953640

ABSTRACT

BACKGROUND: This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. METHODS: A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. RESULTS: For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)]. CONCLUSION: The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.


Subject(s)
Esophagitis, Peptic/drug therapy , Proton Pump Inhibitors/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage , Adult , Comparative Effectiveness Research , Dexlansoprazole/administration & dosage , Esomeprazole/administration & dosage , Esophagitis, Peptic/complications , Female , Heartburn/drug therapy , Heartburn/etiology , Humans , Lansoprazole/administration & dosage , Male , Middle Aged , Network Meta-Analysis , Omeprazole/administration & dosage , Pantoprazole , Rabeprazole/administration & dosage , Treatment Outcome , United States , United States Food and Drug Administration
13.
Acta Pharmacol Sin ; 37(4): 530-44, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26838074

ABSTRACT

AIM: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. METHODS: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. RESULTS: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. CONCLUSION: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Glucosides/pharmacokinetics , Glycosides/pharmacokinetics , Monoterpenes/pharmacokinetics , Paeonia/chemistry , Adult , Animals , Blood Proteins/metabolism , Caco-2 Cells , Cell Membrane Permeability , Female , Glucosides/blood , Glucosides/urine , Glycosides/blood , Glycosides/urine , Humans , Male , Monoterpenes/blood , Monoterpenes/urine , Plant Roots/chemistry , Protein Binding , Rats, Sprague-Dawley , Young Adult
14.
Acta Pharmacol Sin ; 36(5): 627-43, 2015 May.
Article in English | MEDLINE | ID: mdl-25891082

ABSTRACT

AIM: Tanshinol is an important catechol in the antianginal herb Salvia miltiorrhiza roots (Danshen). This study aimed to characterize tanshinol methylation. METHODS: Metabolites of tanshinol were analyzed by liquid chromatography/mass spectrometry. Metabolism was assessed in vitro with rat and human enzymes. The major metabolites were synthesized for studying their interactions with drug metabolizing enzymes and transporters and their vasodilatory properties. Dose-related tanshinol methylation and its influences on tanshinol pharmacokinetics were also studied in rats. RESULTS: Methylation, preferentially in the 3-hydroxyl group, was the major metabolic pathway of tanshinol. In rats, tanshinol also underwent considerable 3-O-sulfation, which appeared to be poor in human liver. These metabolites were mainly eliminated via renal excretion, which involved tubular secretion mainly by organic anion transporter (OAT) 1. The methylated metabolites had no vasodilatory activity. Entacapone-impaired methylation did not considerably increase systemic exposure to tanshinol in rats. The saturation of tanshinol methylation in rat liver could be predicted from the Michaelis constant of tanshinol for catechol-O-methyltransferase (COMT). Tanshinol had low affinity for human COMT and OATs; its methylated metabolites also had low affinity for the transporters. Tanshinol and its major human metabolite (3-O-methyltanshinol) exhibited negligible inhibitory activities against human cytochrome P450 enzymes, organic anion transporting polypeptides 1B1/1B3, multidrug resistance protein 1, multidrug resistance-associated protein 2, and breast cancer resistance protein. CONCLUSION: Tanshinol is mainly metabolized via methylation. Tanshinol and its major human metabolite have low potential for pharmacokinetic interactions with synthetic antianginal agents. This study will help define the risk of hyperhomocysteinemia related to tanshinol methylation.


Subject(s)
Caffeic Acids/pharmacokinetics , Cardiovascular Agents/pharmacokinetics , Drugs, Chinese Herbal/pharmacokinetics , Liver/enzymology , Salvia miltiorrhiza/chemistry , Administration, Oral , Animals , Biotransformation , Caffeic Acids/administration & dosage , Caffeic Acids/isolation & purification , Caffeic Acids/toxicity , Cardiovascular Agents/administration & dosage , Cardiovascular Agents/isolation & purification , Cardiovascular Agents/toxicity , Catechol O-Methyltransferase/metabolism , Chromatography, Liquid , Cytochrome P-450 Enzyme System/metabolism , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/toxicity , Herb-Drug Interactions , Humans , Injections, Intravenous , Kidney Tubules/metabolism , Male , Mass Spectrometry , Membrane Transport Proteins/metabolism , Methylation , Microsomes, Liver/enzymology , Organic Anion Transport Protein 1/metabolism , Phytotherapy , Plant Roots , Plants, Medicinal , Rats, Sprague-Dawley , Renal Elimination , Sulfates/metabolism
15.
Acta Pharmacol Sin ; 34(10): 1337-48, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23974515

ABSTRACT

AIM: Both Borneolum (Chinese name Bingpian; dextrorotatory borneol) and Borneolum syntheticum (synthetic Bingpian; a mixture of optically inactive borneol and isoborneol) have been used for medicinal purposes in Chinese traditional medicine. The aim of this study was to develop a sensitive assay for measuring volatile ingredients borneol, isoborneol, and their metabolite camphor in pharmacokinetic study of Bingpian. METHODS: Rat plasma samples were prepared using liquid-liquid microextraction: 70 µL of plasma sample (containing 125 nmol/L naphthalene as the internal standard) was extracted with 35 µL of n-hexane. The resulting n-hexane extract (20 µL) was introduced into a gas chromatography/mass spectrometry system using programmable temperature vaporizing-based large-volume injection. The assay was validated to demonstrate its reliability for the intended use. Using this assay, pharmacokinetic studies of Bingpian, synthetic Bingpian, and Fufang-Danshen tablets (containing synthetic Bingpian) were conducted in rats. RESULTS: The extraction efficiency for the analytes and the internal standard from plasma was almost constant with decrease in n-hexane-to-plasma volume ratio, thus enabling a small volume of extracting solvent to be used for sample preparation, and enhancing the assay sensitivity. The lower quantification limit for measuring borneol, isoborneol, and camphor in plasma was 0.98 nmol/L, which was 33-330 times more sensitive than those reported earlier for Bingpian and synthetic Bingpian. The applicability of the miniaturized liquid-liquid extraction technique could be extended to measure other volatile and nonvolatile medicinal compounds in biomatrices, which can be predicted according to the analytes' octanol/water distribution coefficient (logD) and acid dissociation constant (pKa). CONCLUSION: This assay is sensitive, accurate and free of matrix effects, and can be applied to pharmacokinetic studies of Bingpian, synthetic Bingpian, and Bingpian-containing herbal products.


Subject(s)
Camphanes/pharmacokinetics , Camphor/pharmacokinetics , Gas Chromatography-Mass Spectrometry/methods , Animals , Drugs, Chinese Herbal/pharmacokinetics , Limit of Detection , Liquid Phase Microextraction , Male , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Solvents/chemistry , Tablets
16.
Environ Manage ; 49(5): 1092-101, 2012 May.
Article in English | MEDLINE | ID: mdl-22434198

ABSTRACT

A large number of soil and water conservation programs have been implemented on the Loess Plateau of China since the 1950s. To comprehensively assess the merits and demerits of the conservation practices is of great importance in further supervising the conservation strategy for the Loess Plateau. This study calculates the impact factors of conservation practices on soil, water, and nutrients during the period 1954-2004 in the Nanxiaohegou Catchment, a representative catchment in the Loess Mesa Ravine Region of the Loess Plateau, China. Brief conclusions could be drawn as follows: (1) Soil erosion and nutrient loss had been greatly mitigated through various conservation practices. About half of the total transported water and 94.8 % of the total transported soil and nutrients, had been locally retained in the selected catchment. The soil retained from small watersheds do not only form large-scale fertile farmland but also safeguard the Yellow River against overflow. (2) Check dam was the most appropriate conservation practice on the Loess Plateau. In the selected catchment, more than 90 % of the retained soil and water were accomplished by the dam farmland, although the dam farmland occupied only 2.3 % of the total area of all conservation measures. Retention abilities of the characteristic conservation practices were in the following order: dam farmland > terrace farmland > forest land and grassland. (3) The conservation practices were more powerful in retaining sediment than in reducing runoff from the Loess Plateau, and the negative effects of the conservation practices on reducing water to the Yellow River were relatively slight.


Subject(s)
Conservation of Natural Resources , Environmental Monitoring/methods , Rivers/chemistry , Soil/analysis , China , Conservation of Natural Resources/methods , Conservation of Natural Resources/statistics & numerical data , Environmental Monitoring/statistics & numerical data , Humic Substances/analysis , Nitrogen/analysis , Phosphorus/analysis , Rain , Soil/standards , Water Movements , Water Quality/standards
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