Recycling of deep eutectic solvent in the extraction of ferulic acid from oil palm empty fruit bunch.

The study explored ferulic acid extraction from palm empty fruit bunch (EFB) fiber using deep eutectic solvent (DES) of chlorine chloride-acetic acid as the extraction medium and the way to recover and recycle the DES thereafter. Antisolvent was added to selectively precipitate the ferulic acid, which was recovered by filtration thereafter. Recycling the DES without further purification led to increased ferulic acid yield with each subsequent extraction, likely due to retained ferulic acid. The retained ferulic acid and other impurities could be removed by precipitation brought upon by the addition of a second antisolvent. 1H nuclear magnetic resonance revealed that there was no excess ferulic acid in the recycled DES-treated with two types of antisolvents (ethanol and water). The yield of ferulic acid increased from 0.1367-0.1856 g/g when treated with only one antisolvent to 0.1368-0.2897 g/g with two antisolvent treatments. Oil droplets were also observed in the DES upon the addition of antisolvent 2, with recovered oil ranging from 0.6% to 3%. The study emphasized the significance of using DES as an extraction medium for ferulic acid from oil palm EFB fiber and the method to recycle the DES for subsequent processes.

Pathophysiological consequences and treatment strategy of obstructive jaundice.

Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

Synergistic action of indole-3-carbinol with membrane-active agents against multidrug-resistant Gram-negative bacteria.

The purpose of this study was to evaluate the antimicrobial activity of indole-3-carbinol (I3C) with membrane-active agents, namely carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and ethylenediaminetetraacetic acid (EDTA) against multidrug-resistant (MDR) Gram-negative bacteria and bacterial persisters. The determination of minimal inhibitory concentration (MIC) showed that I3C was effective against Acinetobacter baumannii (3.13‒6.25 × 10-3 mol l-1), Klebsiella pneumoniae (8 × 10-3 mol l-1), Pseudomonas aeruginosa (6.25‒12.5 × 10-3 mol l-1), and Escherichia coli (6.25‒12.5 × 10-3 mol l-1). Our study demonstrated that EDTA synergistically enhanced the bactericidal activity of I3C against most MDR Gram-negative bacteria isolates and contributed to an 8- to 64-fold MIC reduction compared with that of I3C alone, yet CCCP only displayed synergy with I3C against P. aeruginosa and A. baumannii. The EDTA-I3C combination also significantly reduced the viable number of testing bacteria (P = 7.2E-05), effectively reduced bacterial persisters, and repressed bacterial growth compared with that the use of I3C alone. Our data demonstrate that use of EDTA as adjuvant molecules can effectively improve the antibacterial activity of I3C and may help to reduce the development of antimicrobial resistance.

Perilla, sunflower, and tea seed oils as potential dietary supplements with anti-obesity effects by modulating the gut microbiota composition in mice fed a high-fat diet.

PURPOSE: Obesity has become a serious public health problem with its alarmingly increasing prevalence worldwide, prompting researchers to create and develop several anti-obesity drugs. Here, we aimed to investigate the protective effects of perilla seed oil (PSO), sunflower oil (SFO), and tea seed oil (TSO) against obesity through the modulation of the gut microbiota composition and related metabolic changes in mice fed a high-fat diet (HFD). METHODS: Mice were divided into six equal groups: ND (normal diet); HFD; ORL (HFD supplemented with 20 mg/kg body weight of orlistat); PSO, SFO, and TSO (HFD supplemented with 2 g/kg body weight of PSO, SFO, and TSO, respectively). RESULTS: Our findings showed that PSO, SFO, and TSO supplementation significantly reduced body weight, organ weight, blood glucose, lipopolysaccharides (LPS), insulin resistance, and improved serum lipid levels (TG, TC, LDL-C, and HDL-C). Meanwhile, the three treatments alleviated oxidative stress and hepatic steatosis and reduced liver lipid accumulation. Relative mRNA expression levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and MCP-1) and lipid synthesis-related genes (PPAR-γ, FAS, and SREBP-1) were down-regulated, while ß-oxidation-related genes (PPAR-α, CPT1a, and CPT1b) were up-regulated in the liver tissue of treated mice. Besides, dietary oil supplementation alleviated HFD-induced gut microbiota dysbiosis by promoting gut microbiota richness and diversity, decreasing the Firmicutes-to-Bacteroidetes ratio, and boosting the abundance of some healthy bacteria, like Akkermansia. CONCLUSIONS: PSO, SFO, and TSO supplementation could alleviate inflammation, oxidative stress, and hepatic steatosis, likely by modulating the gut microbiota composition in HFD-fed mice.

Removal of Cd from contaminated farmland soil by washing with residues of traditional Chinese herbal medicine extracts.

Soil washing is one of the effective methods for permanent removal of heavy metals from farmland soil, and selection of washing agents determines heavy metal removal efficiency. However, there is still a lack of cost-efficient and eco-friendly washing agents. In this study, three residues of traditional Chinese herbal medicine (RTCHM) extracts: residues of Prunus mume (Sieb.) Sieb. et Zucc. (RPM), residues of Schisandra chinensis (Turcz.) Baill. (RSC), and residues of Crataegus pinnatifida Bunge (RCP), were tested for their potential of Cd removal. The variations in amounts and compositions of dissolved organic carbon (DOC) and citric acid were responsible for the difference in Cd removal efficiencies of RTCHM extracts. Fourier-transform infrared spectrophotometer (FTIR) analysis showed that hydroxyl, carboxyl, and amine were the main functional groups of RTCHM extracts to chelate with heavy metals. The optimum conditions for RTCHM extracts were 100 g L-1 concentration, solid-liquid ratio 1:10, pH 2.50, and contact time of 1 h, and the highest Cd removal efficiencies of RPM, RSC, and RCP extracts reached 35%, 11%, and 15%, respectively. The ecological risk of Cd decreased significantly due to the decrease of exchangeable and reducible Cd fractions. RTCHM extracts washing alleviated soil alkalinity and had little effect on soil cation exchange capacity. Meanwhile, the concentrations of soil organic matter and nitrogen were enhanced significantly by RPM extracts and the activities of soil catalase and urease were also improved. Overall, among the tested extracts, RPM extracts was a much more feasible and environment-friendly washing agent for the remediation of Cd-contaminated farmland soil.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Reflection on the Changes in the Scope of Ethical Review / 中国医学伦理学

At the end of February 2023, the new Notice on the Issuance of Ethical Review Measures for Life Science and Medical Research Involving Humans was issued by the National Health Commission, the Ministry of Education, the Ministry of Science and Technology, and the State Administration of Traditional Chinese Medicine. It adheres to the basic principles and institutional framework of the Ethical Review Measures for Biomedical Research Involving Humans , and combines with the actual situation of domestic ethical work to optimize and improve the details and procedures of the review. Based on the Ethical Review Measures for Biomedical Research Involving Humans, the Ethical Review Measures for Life Science and Medical Research Involving Humans have expanded the scope of application of ethical review. Different experts in the field have discussed in detail the changes in the scope of review, and proposed review procedures that may need to be corresponding adjustments based on the changes for the readers’ reference.

Analysis of research hotspots and trend of the clinical comprehensive evaluation of Chinese patent medicine in China / 中国药房

OBJECTIVE To analyze the research status， hotspots， and trend of the clinical comprehensive evaluation of Chinese patent medicine in China. METHODS Based on CNKI， VIP and Wanfang database， clinical comprehensive evaluation of Chinese patent medicine was used as the subject of retrieval， and the retrieval time was from the inception to October 30th， 2022. CiteSpace 6.1.R3 and VOSviewer were used to conduct a visualization analysis of the relative literature of clinical comprehensive evaluation of Chinese patent medicine in terms of annual publication quantity， authors， institutions， keywords， etc. RESULTS & CONCLUSIONS A total of 1 460 pieces of literature related to the clinical comprehensive evaluation of Chinese patent medicine were included. The overall annual publication quantity showed a growth trend. There were 714 authors in the included literature. The institutions with a large publication quantity included the Chinese Academy of Traditional Chinese Medicine， Beijing University of Chinese Medicine， Tianjin University of Traditional Chinese Medicine， etc.， and there was little cooperation among the authors and institutions. High-frequency keywords included Chinese patent medicine， safety， adverse drug reactions， rational drug use， etc. Research hotspots focused on the safety and effectiveness evaluation of Chinese patent medicine. It may be a research trend in this field to strengthen the prescription review of Chinese patent medicine， and build a multi-dimensional and multi-criteriaclinical comprehensive evaluation system for the rational use of Chinese patent medicine.

Acupoint catgut embedding versus acupuncture for simple obesity: a systematic review and Meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the clinical effectiveness and safety of acupoint catgut embedding and acupuncture on simple obesity by Meta-analysis. METHODS: Studies on clinical randomized controlled trials of acupoint catgut embedding for simple obesity which were published from January 2015 to November 2020 were searched in Cochrane Central Register of Control Trials (Central), PubMed, China Science and Technology Journal Database, China National Knowledge Infrastructure Database and Wanfang data-bases. And those that met the inclusion criteria were screened. RevMan5.3 was used for Meta-analysis. The "Risk of Bias" tool was used to evaluate the quality of included studies. R studio software was used for the measurement of publication bias. RESULTS: A total of 33 studies were included for Meta-analysis, including 2685 patients with simple obesity. Meta-analysis results showed the comparison of effectiveness rate was relative risk () = 1.12, 95%(1.08, 1.16), body mass index (BMI) was mean difference () = -1.12, 95% (-2.09, -0.14), waist circumference was = -2.14, 95% (-4.22, -0.06), and body mass was = -2.36, 95% (-3.99, -0.73). On the basis of diet and exercise intervention, the effectiveness rate [ = 1.12, 95% (1.05, 1.19)], BMI [ = -0.88, 95% (-1.35, -0.40)], waist circumference [ = -1.10, 95%(-4.27, 2.07)], and body mass [ = -0.68, 95%(-2.90, 1.54)]. The risk of bias of included literatures was low. CONCLUSIONS: Acupoint catgut embedding therapy was slightly better than acupuncture therapy in most of the outcomes. Moreover, the treatment frequency of acupoint catgut embedding is less with larger stimulation intensity, which is more conducive to clinical promotion.

Attention Situation of Chinese Patent Medicine for Constipation in Traditional Chinese Medicine Diagnosis and Treatment Guidelines/Consensus and National Reimbursement Drug List / 中国实验方剂学杂志

ObjectiveTo evaluate the methodological quality of traditional Chinese medicine （TCM） diagnosis and treatment guidelines/consensus of constipation with Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ）tool， and to study the attention situation of the included Chinese patent medicines in China's National Reimbursement Drug List in the guidelines/consensus. MethodThe data of CNKI，VIP，Wanfang Data，SinoMed，PubMed and Cochrane from the inception of the databases to October 2021 were searched to collect the TCM diagnosis and treatment guidelines/consensus of constipation. Then，the diagnosis and treatment standards and recommended Chinese patent medicines were extracted. Two researchers assessed the methodological quality of the guidelines/consensus with AGREE Ⅱ tool independently. The quality of reports was evaluated by Reporting Items for practice Guidelines in HealThcare （RIGHT） Statement. The recommended Chinese patent medicines in the guidelines/consensus were compared with those in the National Reimbursement Drug List. ResultEleven consensus and 2 guidelines were included，involving 794 experts. The scores of AGREE II were clarity of presentation（59.0%），scope and purpose（44.0%），stakeholder involvement（23.1%），rigor of development （12.1%），applicability （11.1%），and editorial independence （8.3%） from high to low. Five articles were recommended at B level（recommended after revision） and 8 articles were at C level （not recommended）. The average scores of RIGHT Statement were as follows：basic information （93.59%），background （57.69%），evidence （18.46%），recommendations （20.88%），review and quality assurance （19.23%），funding，declaration and management of interests （0.00%）， and other information （0.00%）. The included guidelines/consensus recommended a total of 27 Chinese patent medicines，among which 20 were included in the National Reimbursement Drug List，with 4 species of Class A and 16 species of Class B， accounting for 74.1% of all recommended Chinese patent medicines. Ten purgative Chinese patent medicines in the National Reimbursement Drug List were recommended by the guidelines/consensus，accounting for 50% of all purgative drugs， and 8 were not recommended. There were prescriptions for purgation， for promoting digestion and removing food stagnation， for clearing heat and purging fire，and for warming the middle and dissipating cold，Tibetan medicine and Mongolian medicine. ConclusionBy the AGREE Ⅱ assessment，the methodological quality of the TCM diagnosis and treatment guidelines/consensus of constipation included in this study needed to be improved in the future. The report quality evaluated with RIGHT Statement was low. Most drugs included in the National Reimbursement Drug List were paid attention in the TCM diagnosis and treatment guidelines/consensus of constipation. Moreover，the drugs included in the National Reimbursement Drug List could basically fulfill the clinical needs reflexed from the guidelines/consensus recommendations. However， the reasons of some drugs failing to be included in the National Reimbursement Drug List needed to be studied in the future.

Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation.

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (Treg ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p < 0.05), CD8+ (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed Treg cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4+ T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.

Chinese Herbal Medicine for Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis of Randomized, Placebo-Controlled Trials / 中国结合医学杂志

OBJECTIVE@#To provide evidence on the efficacy and safety of Chinese herbal medicine (CHM) as interventions for systemic lupus erythematosus (SLE).@*METHODS@#Seven electronic databases, including the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, Embase, and PubMed, were comprehensively searched, from their inception to August 16, 2020, for all randomized controlled trials (RCTs) that focused on CHM used alone or in combination with conventional medicine for SLE. Outcomes were SLE activity index (SLEDAI), traditional Chinese medicine symptom/syndrome score (TCMSS), dosage of glucocorticoids, main serological testing, and incidence of adverse events. Data were extracted and pooled using Review Manager 5.3 software.@*RESULTS@#A total of 13 RCTs enrolling 856 participants met our inclusion criteria. Meta-analyses showed that, compared to placebo, CHM had statistically significant effect on reducing SLEDAI score (MD=-1.74, 95% CI: -2.29 to -1.18), diminishing TCMSS (SMD=-0.89, 95% CI: -1.16 to -0.62), decreasing dosage of glucocorticoids (MD=-2.41 mg/d, 95% CI: -3.34 to -1.48), lowering erythrocyte sedimentation rate (MD=-4.78 mm/h, 95% CI: -8.86 to -0.71), and increasing serum complement C4 level (MD=0.03 mg/dL, 95% CI: 0.00 to 0.06). No significant difference was found between CHM and placebo on adverse events.@*CONCLUSIONS@#CHM provided significant beneficial effect on controlling disease activity and reducing dose of glucocorticoids used among SLE patients. Future advanced designed RCTs for CHM treating moderate to severe SLE with multicenter and longer follow-up are urgently needed.

Effects of traditional Chinese exercises and general aerobic exercises on older adults with sleep disorders: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs.@*OBJECTIVE@#This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included.@*DATA EXTRACTION AND ANALYSIS@#Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity.@*RESULTS@#A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = -2.14, 95% confidence interval [CI] [-2.82, -1.46], P < 0.001; heterogeneity: P < 0.001, I@*CONCLUSION@#Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

Clinacanthus nutans Mitigates Neuronal Death and Reduces Ischemic Brain Injury: Role of NF-κB-driven IL-1ß Transcription.

Neuroinflammation has been shown to exacerbate ischemic brain injury, and is considered as a prime target for the development of stroke therapies. Clinacanthus nutans Lindau (C. nutans) is widely used in traditional medicine for treating insect bites, viral infection and cancer, due largely to its anti-oxidative and anti-inflammatory properties. Recently, we reported that an ethanol extract from the leaf of C. nutans could protect the brain against ischemia-triggered neuronal death and infarction. In order to further understand the molecular mechanism(s) for its beneficial effects, two experimental paradigms, namely, in vitro primary cortical neurons subjected to oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery (MCA) occlusion, were used to dissect the anti-inflammatory effects of C. nutans extract. Using promoter assays, immunofluorescence staining, and loss-of-function (siRNA) approaches, we demonstrated that transient OGD led to marked induction of IL-1ß, IL-6 and TNFα, while pretreatment with C. nutans suppressed production of inflammatory cytokines in primary neurons. C. nutans inhibited IL-1ß transcription via preventing NF-κB/p65 nuclear translocation, and siRNA knockdown of either p65 or IL-1ß mitigated OGD-mediated neuronal death. Correspondingly, post-ischemic treatment of C. nutans attenuated IκBα degradation and decreased IL-1ß, IL-6 and TNFα production in the ischemic brain. Furthermore, IL-1ß siRNA post-ischemic treatment reduced cerebral infarct, thus mimicking the beneficial effects of C. nutans. In summary, our findings demonstrated the ability for C. nutans to suppress NF-κB nuclear translocation and inhibit IL-1ß transcription in ischemic models. Results further suggest the possibility for using C. nutans to prevent and treat stroke patients.

Epigallocatechin-3-gallate downregulates PDHA1 interfering the metabolic pathways in human herpesvirus 8 harboring primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is an aggressive neoplasm correlated with human herpesvirus 8 (HHV8). Metabolic reprogramming is a hallmark of cancers. The alterations in cellular metabolism are important to the survival of HHV8 latently infected cells. Pyruvate dehydrogenase (PDH) controls the flux of metabolites between glycolysis and the tricarboxylic acid cycle (TCA cycle) and is a key enzyme in cancer metabolic reprogramming. Glutaminolysis is required for the survival of PEL cells. Glutamate dehydrogenase 1 (GDH1) converts glutamate into α-ketoglutarate supplying the TCA cycle with intermediates to support anaplerosis. Previously we have observed that epigallocatechin-3-gallate (EGCG) can induce PEL cell death and N-acetyl cysteine (NAC) attenuates EGCG induced PEL cell death. In this study, results showed that EGCG upregulated the expression of glucose transporter GLUT3, and reduced the expression of pyruvate dehydrogenase E1-alpha (PDHA1), the major regulator of PDH, and GDH1. NAC could partially reverse the effects of EGCG in PEL cells. Overexpression of PDHA1 in PEL cells or supplement of α-ketoglutarate attenuated EGCG induced cell death. EGCG also reduced the levels of oncometabolite D-2-hydroxyglutarate (D2HG). These results suggest that EGCG may modulate the metabolism of PEL cells leading to cell death.

Effects of borneol on the pharmacokinetics of vinpocetine in rats / 药学学报

Vinpocetine (VP) has been widely used to treat cerebrovascular disorders and nerve injury. Borneol (BN), as an important traditional Chinese medicine, is commonly used to promote the absorption and distribution of central nervous system drugs. In this work, a LC-MS/MS method was developed to determine the level of VP in rat plasma and tissues, and to evaluate the effect of co-administration of BN with VP by oral gavage on the absorption and tissue distribution of VP in rats. Rats were divided into VP (10 mg·kg-1), VP (10 mg·kg-1) + BN (75 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for pharmacokinetic study, and divided into VP (10 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for tissue distribution study. The animal experiment was approved by Ethics Committee of Hubei University, and complied with the guideline for caring and using of laboratory animals. Compared to VP group, the AUC0-∞, MRT0-∞ and t1/2z of VP + BN (150 mg·kg-1) group increased significantly, by 1.98-, 1.22- and 1.42-fold respectively, and the exposure in plasma, liver, kidney and brain increased by 2-, 1.5-, 1.5- and 1.3-fold respectively. The pharmacokinetic results suggested that co-administration of BN with VP is beneficial for overcoming the undesirable pharmacokinetic characteristics of VP, such as short residence time, low oral bioavailability and brain exposure in clinical usage.

Preliminary study on response and its mechanism of ginsenoside biosynthesis in Panax ginseng to water regulation / 中国中药杂志

The study is aimed to explore the effect of soil moisture content on ginsenoside biosynthesis and explain its mechanism from the perspectives of antioxidant enzyme system and gene expression of key enzymes in the pathway of ginsenoside synthesis. In the study,two years old Panax ginseng was used as the experimental material and three moisture gradient,40% of saturated water content( W1),60%( W2),80%( W3) were set up. The content of 11 monomeric saponins were determined by HPLC. With GAPDH as a reference gene,six key enzymes( HMGR,SS,β-AS,CYP716 A47,CYP716 A52 v2,CYP716 A53 v2) in ginseng saponin synthesis pathway expression were analyzed by fluorescent quantitative PCR and the activities of superoxide dismutase( SOD),peroxidase( POD),catalase( CAT) activity and MDA content were also determined. With the increase of soil water,the content of ginseng saponin and biomass showed an increasing trend. PPD( Rb1,Rc,Rb2,Rd,Rh2,Rb3,Rg3),PPT( Rg1,Re,Rf) ginsenoside,Ro and total ginsenoside reached the maximum value on August 30,were 9.92,5.48,0.63 mg·g-1,respectively. During the whole regulation period,the antioxidant activity of W3 was greater than that of W1,and the MDA content was less than that of W1. At W3,expression levels of β-AS,CYP716 A47 and CYP716 A53 v2 showed an increasing trend,while HMGR and SS genes showed relatively stable expression levels under various water conditions. According to the correlation analysis,HMGR and SS genes in the W3 treatment group were significantly positively correlated with PPD,PPT ginsenoside and Ro,CYP716 A52 v2 gene was significantly positively correlated with Ro,and CYP716 A47 gene was significantly positively correlated with PPD ginsenoside. There was a significant positive correlation between β-AS gene and PPD ginsenoside in W1 and W2 treatment. Therefore,W3 is the optimum moisture content,ginseng total saponins and monomer saponin content is the highest,the gene closely correlation with content of saponins and more conducive to the accumulation of ginsenosides.

Dangguishaoyao-San attenuates LPS-induced neuroinflammation via the TLRs/NF-κB signaling pathway.

INTRODUCTION: Dangguishaoyao-San (DSS) is composed of six traditional Chinese medicines, including Angelica sinensis, Paeoniae radix, Rhizoma Ligusticum, Poria cocos, Rhizoma Atractylodis Macrocephalae, and Rhizoma Alismatis. DSS has been reported to be effective in alleviating the symptoms of Alzheimer's disease (AD). The aim of this study was to investigate the mechanism of action of DSS in vitro using lipopolysaccharide (LPS)-stimulated BV-2 microglia cells. MATERIALS AND METHODS: BV-2 cells were pretreated with 0.58-1.16 mg/mL of DSS for 2 h and then treated with 1 µg/mL LPS for 24 h. Cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression levels were measured by Western blots. Inflammatory factors were detected by enzyme-linked immunosorbent assays (ELISAs). The mRNA levels of inflammatory factors were analyzed by quantitative real-time PCR (qRT-PCR). RESULTS: DSS treatment at concentrations of 0.58-1.16 mg/mL resulted in no significant cytotoxicity. DSS attenuated the release of pro-inflammatory factors, such as interleukin-1ß (IL-1ß), iNOS and tumor necrosis factor-α (TNF-α) in LPS-induced BV-2 cells. DSS attenuated the mRNA expression of pro-inflammatory cytokines, TLR2, and TLR4 and decreased TLR4 and TLR protein levels as well as the phosphorylation of IκB in LPS-induced BV-2 cells. DSS also down-regulated the nuclear translocation of p65. CONCLUSION: This study demonstrated that DSS has a protective effect on neuroinflammation in LPS-induced BV-2 microglia cells through the TLRs/NF-κB signaling pathway.

Clinacanthus nutans Mitigates Neuronal Apoptosis and Ischemic Brain Damage Through Augmenting the C/EBPß-Driven PPAR-γ Transcription.

Clinacanthus nutans Lindau (C. nutans) is a traditional herbal medicine widely used in Asian countries for treating a number of remedies including snake and insect bites, skin rashes, viral infections, and cancer. However, the underlying molecular mechanisms for its action and whether C. nutans can offer protection on stroke damage in brain remain largely unknown. In the present study, we demonstrated protective effects of C. nutans extract to ameliorate neuronal apoptotic death in the oxygen-glucose deprivation model and to reduce infarction and mitigate functional deficits in the middle cerebral artery occlusion model, either administered before or after hypoxic/ischemic insult. Using pharmacological antagonist and siRNA knockdown approaches, we demonstrated ability for C. nutans extract to protect neurons and ameliorate ischemic injury through promoting the anti-apoptotic activity of peroxisome proliferator-activated receptor-gamma (PPAR-γ), a stress-induced transcription factor. Reporter and chromatin immunoprecipitation promoter analysis further revealed C. nutans extract to selectively increase CCAAT/enhancer binding protein (C/EBP)ß binding to specific C/EBP binding site (-332~-325) on the PPAR-γ promoter to augment its transcription. In summary, we report a novel transcriptional activation involving C/EBPß upregulation of PPAR-γ expression to suppress ischemic neuronal apoptosis and brain infarct. Recognition of C. nutans to enhance the C/EBPߠ→ PPAR-γ neuroprotective signaling pathway paves a new way for future drug development for prevention and treatment of ischemic stroke and other neurodegenerative diseases.

The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil.

There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T1), α-tocotrienol (α-T3), γ-tocotrienol (γ-T3), ß-tocotrioenol (ß-T3) and δ-tocotrienol (δ-T3). These analogs were difficult to separate chromatographically due to their similar structures, physical and chemical properties. This paper reports on the effect of pressure and injection solvent on the separation of the tocol analogs in palm oil. Supercritical CO2 modified with ethanol was used as the mobile phase. Both total elution time and resolution of the tocol analogs decreased with increased pressure. Ethanol as an injection solvent resulted in peak broadening of the analogs within the entire pressure range studied. Solvents with an eluent strength of 3.4 or less were more suitable for use as injecting solvents.