1.Physicochemical Analysis and Pharmacokinetics of Vanillin from Vanilla planifolia
Meng-Die CHEN ; Ya-Nan WU ; Ming GUO ; Jie CHENG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(11):1596-1607
The medicinal value of vanilla planifolia is of great interest.We analyzed the common princi-pal components of VOCs in different parts of vanilla planifolia,and the human serum albumin (HSA),β-lactoglobulin (β-La) andα-lactalbumin (α-La) were used as template proteins to establish a chain a-nalysis approach with the 'solid phase microextraction gas chromatography-mass spectrometry-multispec-troscopy-physical modelling-pharmacokinetics' (S-M-P-P ) .The mechanisms of the transport and phar-macodynamics for the common principal components of vanilla planifolia were analyzed.The results showed that the common primary VOCs in different parts of vanilla planifolia was vanillin (Van),which attenuated the endogenous fluorescence of HSA/β-La/α-La by static bursting,and formed hydrogen bonds and Van der Waals forces with HSA,and noncovalent complexes with β-La/α-La through hydro-phobic forces.Their interaction facilitates the transport of Van in vivo to intestinal and hepatic tissues and its metabolism by CYP1A2 and CYP2C9 enzymes to exert its pharmacological effects.This study provides a comprehensive and in-depth investigation of the transport mechanisms and pharmacological effects of VOCs from vanilla planifolia,which provides an important reference for understanding the medicinal po-tential of plant derived VOCs.
2.Association between body health score and the risk of hypertension among health examination population aged 40-65 years
Dashan WANG ; Li ZHENG ; Jing ZHOU ; Jin HU ; Yue MENG ; You LI ; Die WANG ; Junhua WANG ; Ziyun WANG
Chinese Journal of Health Management 2024;18(8):581-586
Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.
3.Effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in a rat model of cardiac hypertrophy
Hao ZHANG ; Xiao-Yun DING ; Hu WANG ; Ting-Ting LI ; Yu-Mei QIU ; Meng-Die XIE ; Wei DONG ; Yi-Xin SHEN ; Xi-Lan TANG
Chinese Traditional Patent Medicine 2024;46(11):3594-3602
AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P<0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P<0.05);and increased levels of serum TC,TG and LDL-C(P<0.05);and decreased HDL-C level(P<0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P<0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P<0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.
4.Factors influencing survival after treatment for dilated cardiomyopathy with decreased LVEF
Hongmei WANG ; Die MENG ; Fen WANG ; Xiuming GU
China Modern Doctor 2024;62(31):8-12,17
Objective To investigate the factors affecting survival of dilated cardiomyopathy(DCM)after treatment with decreased left ventricular ejection fraction(LVEF).Methods A total of 158 DCM patients with decreased LVEF treated in Huzhou First People's Hospital from June 2020 to June 2023 were selected and divided into death group(n=40)and survival group(n=1 18)according to their survival status.The clinical data of two groups were analyzed by Cox proportional risk regression model to analyze the factors affecting the survival of DCM with decreased LVEF after treatment.Results The age of patients in death group was significantly higher than that in survival group,and the combination of hypertension,New York Heart Association(NYHA)cardiac function grade Ⅳ,ventricular arrhythmia and left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),and brain natriuretic peptide(BNP)were significantly higher than those in survival group,global longitudinal strain(GLS),standard deviation of RR interval(SDNN),standard deviation of the average RR interval(SDANN),the average standard deviation of RR interval(SDNNindex),root mean square of RR interval difference(rMSSD),the percentage of total number of adjacent RR intervals>50ms to total heart rate(pNN50),end diastolic interventricular septal thickness(IVSd),left ventricular posterior wall diastolic thickness(LVPWD),stroke volume(SV),and cardiac output(CO)were significantly lower than those in survival group(P<0.05).Cox regression analysis showed that age,combined hypertension,NYHA cardiac function grade,ventricular arrhythmia,GLS,SDNN,SDANN,SDNNindex,rMSSD,pNN50,LVEDD,LVESD and BNP were risk factors affecting the survival rate of DCM patients with decreased LVEF after treatment,IVSd and LVPWD were protective factors(P<0.05).Conclusion DCM patients with decreased LVEF had a higher mortality rate,which was affected by multiple factors such as age,hypertension,NYHA cardiac function grade,ventricular arrhythmia,GLS,heart rate variability,LVEDD,LVESD,BNP,IVSd,LVPWD,etc.Targeted intervention should be given early to improve the survival rate of patients after treatment.
5.Self-screening for arteriosclerosis in middle-aged and elderly residents and the construction of a primary care initial screening tool
Yue MENG ; Li ZHENG ; Jing ZHOU ; Dashan WANG ; Jin HU ; Die WANG ; You LI ; Junhua WANG ; Ziyun WANG
The Journal of Practical Medicine 2024;40(14):1947-1951
Objective To establish a simple model for arteriosclerosis(AS)screening to provide a viable tool for the timely identification of AS risk among residents aged 40~65 years.Methods Data were obtained from the Sleep and Chronic Diseases Program in Fuquan City.The original dataset was divided into a training subset and a validation subset(80%:20%).LASSO and logistic regression models were used to screen variables,perform multivariate regression analyses.Internal validation was performed using the Bootstrap method.Nomogram Plot was constructed,and risk score thresholds were determined based on ROC curves to classify high-risk populations.Results RS Model was established to include age,gender,napping,sleep efficiency,sleep disorders,hyperten-sion and diabetes,with AUC=74.80%and a model risk score threshold=84.20.PHC Model was established to include age,gender,napping,sleep efficiency,systolic blood pressure,fasting blood glucose,and pulse variables,with AUC=82.80%and a risk score threshold of 78.00.Decision curves showed that both models performed well in terms of calibration and actual benefits for health management.Conclusion The two AS screening models exhibit acceptable accuracy and differentiation.Therefore,it can be applied in residents'self-health management and in primary care organizations'screening work in a large scale.
6.Experimental study on anti-fatigue effect of Polysaccharides of Panax notoginseng
Pan-Pan WEI ; Zi-Jun YAN ; Meng-Yue DENG ; Die XIA ; Yu-Zhen DING ; Lei ZHANG ; Tong CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(1):87-91
Objective To explore the effect of Polysaccharides of Panax notoginseng(PPN)on anti-exercise fatigue in mice.Methods One hundred male KM mice were randomly divided into negative control group,positive control group and experimental-L,-M,-H groups,with 20 cases per group.Experimental-L,-M,-H groups was given 100,200,400 mg·kg-1 PPN,respectively;positive control group was given 200 mg·kg-1 vitamin C;negative control group was given 0.1 mL·10 g-1 0.9%NaCl.Five groups were gavaged once a day for 28 days.After the last administration,the loaded swimming time was measured;after 90 minutes of the unloaded swimming test,the mice were allowed to rest for 30 minutes,the levels of lactic acid(LD),blood urea nitrogen(BUN),glycogen,and malondialdehyde(MDA)were measured,the safety of PPN with organ indices and histopathology.Results LD levels in negative control group,positive control group and experimental-L,-M,-Hgroupswere(4.76±0.84),(2.86±0.34),(3.00±0.69),(2.35±0.65)and(1.39±0.48)mg·kg-1;BUN contents were(13.65±1.25),(12.55±0.91),(12.12±1.24),(11.06±1.30)and(9.85±1.05)mmol·L-1;liver glycogen contents were(3.24±0.56),(11.11±2.16),(5.61±1.41),(6.60±1.49)and(12.05±2.25)mg·g-1;MDA levels were(2.36±0.21),(1.23±0.41),(1.93±0.23),(1.73±0.21)and(1.04±0.18)mg prot·mL-1.Compared with negative control group,the differences of above indexes in the positive control group and experimental-L,-M,-H groups were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion PPN can increase exercise endurance in mice and has an anti-fatigue effect.This study provides a theoretical basis for the application of PPN in the field of anti-fatigue research.
7.Antioxidant activity and organ protection of Panax notoginseng polysaccharide on oxidative damage and aging model mice
Meng-Yue DENG ; Pan-Pan WEI ; Ming LI ; Zi-Jun YAN ; Die XIA ; Yu-Zhen DING ; Lei ZHANG ; Tong CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(6):889-893
Objective To study the antioxidant activity and organ protection of different components of Panax notoginseng polysaccharide(PNPS)in D-galactose-induced oxidative damage aging model mice.Methods KM mice were randomly divided into normal group,model group,vitamin C(VC)group(given 200 mg·kg-1 VC),crude polysaccharide from Panax notoginseng(CPPN)group,neutral polysaccharide from Panax notoginseng(NPPN)group and acidic polysaccharide from Panax notoginseng(APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ)group(given 400 mg·kg-1 CPPN,NPPN,APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ,respectively).Except for the normal group,oxidative injury aging mouse models were established by intraperitoneal injection of 1 g·kg-1 D-galactose.The mice were sacrificed after continuous administration for 42 days,and serum and liver homogenate were prepared.Malondialdehyde(MDA)was determined by thiobarbituric acid method;superoxide dismutase(SOD)was determined by tetrazole salt method;glutathione peroxidase(GSH-Px)was determined by double antibody sandwich method.Results Serum SOD in the normal group,model group,VC group,CPPN group,NPPN group and APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ groups were(15.07±0.69),(12.79±1.51),(15.56±1.01),(13.69±0.96),(14.27±0.64),(14.31±0.99),(14.18±0.79)and(15.85±0.89)U·mL-1;serum GSH-Px were(105.35±4.97),(90.36±4.31),(111.51±7.00),(113.03±8.06),(118.77±5.19),(123.60±8.08),(131.65±3.60)and(149.22±13.32)ng·L-1;serum MDA were(1.72±0.26),(4.16±0.92),(2.26±0.59),(2.82±0.47),(2.46±0.50),(1.98±0.41),(2.39±0.39)and(2.07±0.24)nmol·mL-1;the liver SOD were(234.22±3.84),(205.04±7.28),(234.63±6.37),(214.99±17.66),(234.13±3.63),(234.63±3.44),(233.87±5.63)and(235.42±2.33)U·mgprot-1;liver GSH-Px were(274.27±23.72),(207.00±15.22),(257.68±16.39),(249.79±18.78),(252.62±10.92),(256.25±21.83),(261.20±17.52)and(263.16±17.98)ng·L-1;liver MDA were(35.70±3.52),(49.65±6.32),(36.15±2.48),(39.17±4.29),(37.40±6.19),(35.34±4.06)and(35.90±5.36),(33.31±7.64)nmol·mgprot-1.Compared with the normal group,SOD,GSH-Px in serum and liver of mice in the model group were significantly reduced,and the content of MDA was significantly increased(all P<0.01).After treatment with different components of Panax notoginseng polysaccharide,the oxidative indicators in mice were significantly improved,among which APPN-Ⅲ have the best antioxidant activity,which could significantly increase the activities of SOD,GSH-Px in serum and liver,and reduce the content of MDA(all P<0.01).Conclusion Different components of Panax notoginseng polysaccharide have antioxidant activity and organ protection in vivo,among which APPN-Ⅲ has the best antioxidant activity and has a good organ protection effect.
8.Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System.
Rong-Rong HU ; Meng-Die YANG ; Xiao-Yan DING ; Ning WU ; Jin LI ; Rui SONG
Neuroscience Bulletin 2023;39(11):1655-1668
Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats
;
Mice
;
Animals
;
Analgesics, Opioid
;
Dopamine
;
Heroin/pharmacology*
;
Dopamine Antagonists/pharmacology*
;
Receptors, Dopamine D3/metabolism*
;
Morphine/pharmacology*
;
Behavior, Addictive/drug therapy*
;
Self Administration
9.Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft.
Qiong ZOU ; Xiao Ping WU ; Jin Ji WANG ; Die XIA ; Meng Yue DENG ; Yu Zhen DING ; Yu Ling DAI ; Song Yue ZHAO ; Tong CHEN
Journal of Southern Medical University 2022;42(4):538-545
OBJECTIVE:
To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.
METHODS:
We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.
RESULTS:
Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).
CONCLUSION
PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.
Animals
;
Carcinoma, Hepatocellular/pathology*
;
Cyclophosphamide/therapeutic use*
;
Hemolysin Proteins
;
Heterografts
;
Humans
;
Interleukin-2
;
Liver Neoplasms/pathology*
;
Mice
;
Panax notoginseng
;
Saponins/therapeutic use*
;
Tumor Necrosis Factor-alpha
10.Tetrahedral DNA Nanostructure-modified Gold Nanorod-based Anticancer Nanomaterials for Combined Photothermal Therapy and Chemotherapy
Hao WU ; Shan Jiang XU ; Hong Yan LI ; Han Xing WU ; Wei HU ; Die Meng LIU ; Qiang SUN ; Bin GUO
Biomedical and Environmental Sciences 2022;35(12):1115-1125
Objective To develop an effective treatment strategy to simultaneously avoid fatal adverse effects in the treatment of oral cancer, combination therapy has been explored because of its multiple functions. This work aims to develop a novel type of gold-nanorod-based nanomaterials decorated with tetrahedral DNA nanostructures (TDN) carrying antitumor drugs, namely, GNR@TDN-DOX nanocomposites. Methods In the designed structure, TDN, with a three-dimensional geometry composed of DNA strands, can provide GC base pairs for binding with the anticancer drug doxorubicin (DOX). The photothermal heating properties, biocompatibility properties, and antitumor performance of obtained GNR@TDN-DOX nanocomposites were investigated to assess their application potential in tumor treatment. Results Systematic studies have shown that the obtained GNR@TDN-DOX nanocomposites have high photothermal conversion under the illumination of an 808-nm infrared laser, leading to effective antitumor applications. In addition, the cell viability study shows that GNR@TDN-DOX nanocomposites have good biocompatibility. In vitro studies based on A375 cells show that the GNR@TDN-DOX nanocomposites can effectively eliminate cancer cells because of the combination of photothermal therapy induced by GNRS and chemotherapy induced by TDN-carrying DOX. The result shows that the obtained GNR@TDN-DOX nanocomposites have efficient cellular uptake and lysosome escape ability, together with their nuclear uptake behavior, which results in a significant antitumor effect. Conclusion This work has demonstrated a potential nanoplatform for anticancer applications.

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