Analysis of pesticide residues in commercially available chenpi using a modified QuEChERS method and GC-MS/MS determination

To ensure the safety of the commercially available chenpi,a convenient and fast analytical method was developed for the determination of 133 pesticide residues in chenpi using gas chromatography-tandem mass spectrometry(GC-MS/MS).In this study,different extraction solvents,redissolution solvents and adsorbents were tested according to the recovery and purification effect to obtain a modified QuEChERS method.The samples were extracted with acetonitrile.During the clean-up step,octadecyl-modified silica(C18)and graphitized carbon black(GCB)were selected,and aminopropyl(NH2)was used instead of primary secondary amine(PSA)because of its weaker ion exchange capacity which had little effect on the recovery of ditalimfos.Samples were quantified by matrix-matched calibration with internal standards.All pesticides showed good linearity in the respective range,both with values of r2>0.99.The average recoveries of the pesticides spiked samples ranged from 70.0% to 112.2% with the RSDs of 0.2%–14.4%.The modified QuEChERS method was validated and applied to twenty real samples.Five pesticides were found in eight batches,but no pesticide exceeded the maximum residue limits(MRL,MRL reference to European commission).

Toxicological advances of traditional medicine in 2019

There were many researches concerning toxicology of traditional medicine(TM)and active natural products during the past 12 months.This annual toxicology review summarized target organs of TM like liver,kidney and heart.Safety medication of TM has been concerned to different kinds of people,including infants,children,pregnancy and the postnatal period.Besides rodents,zebrafish embryoes have been regarded as common models to evaluate the safety of TM.New technologies in toxicology focus on rapidly screening and identification of toxins in TM.Multispectral optoacoustic tomography imaging the precise location of TM-induced liver injury with 3D information and integrating serum exosomal microRNA and liver microRNA profiles are used to explain the mechanism of TM-induced hepatotoxicity.Taken together,study on the toxicity mechanism of other target organs,drug safety in elders,new models and methods should be paid attention to in the prevention of TM toxicology in the future.

Annual advances of traditional medicine toxicity in 2018

There were many researches concerning toxicology of traditional medicine (TM) and active natural products during the past 12 months. This annual toxicology review summarized different analysis methods of toxicology research, common evaluated models, toxic target organs, toxic mechanisms, and popular research issues and herbs in 2018. The emphasis was on hepatorenal toxicity induced by TM through cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Meanwhile, traditional herbs were listed in this review. Taken together, the herbs mentioned in this paper should be used with caution. Combination of TM, processing drugs, quality control and dose control can be used in the prevention of TM toxicology in the future.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Network Pharmacology Bridges Traditional Application and Modern Development of Traditional Chinese Medicine

Traditional Chinese medicine （TCM） has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This review article briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.

Simultaneous Determination of Saponins in Dripping Pills Made from Astragali Radix and Panax notoginseng by UPLC-ELSD

Objective To develop a simple and fast method for removing polyethylene glycol （PEG） and simultaneous determination of fives saponins, i.e. astragaloside IV, noto- ginsenoside R1, ginsenoside Rgl, ginsenoside Rbl, and ginsenoside Rd in dripping pills made from Astragali Radix and Panax notoginseng. Methods The extraction method was based on a liquid-liquid extraction using water-saturated n-butanol and the quantitative determination was based on ultra-performance liquid chromatography coupled with evaporative light scattering detection （UPLC-ELSD）. The chromatographic analysis was performed on an Acquity UPLC HSS T3 column （100 mm ~ 2.1 mm, 1.8 IJm） with a gradient elution of acetonitrile-0.1% formic acid aqueous solution within a runtime of 15 min. Results Compared to different methods, the proposed method could remove the interference of PEG in formulation. And the calibration curves showed good linearity during the test ranges. The method was validated for limits of detection and quantification, precision, and reproducibility. The recoveries were within the range of 96.87% - 99.97%. In addition, the verified method was firstly applied to determination of the five active ingredients in Qishen Yiqi Dripping Pills （QYDP） simultaneously. Conclusion The contents of five active ingredients are stable and homogeneous in QYDP, which indicates that the method could be readily utilized as a quality evaluation method for this traditional Chinese medicine dripping pills made from AstragaliRadix and Panax notoginseng.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy

Objective:Diabetic retinopathy(DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion.Non-proliferating diabetic retinopathy(NPDR) is the early stage of DR.It eventually occurs to some degree in all patients with diabetes mellitus.In recent years,many clinical trials have shown that Compound Danshen Dripping Pill(CDDP) may be associated with the improvement of NPDR symptoms.The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR.Methods:It was conducted that a systematic literature search of Pub Med,Web of Science,CNKI,VIP and Wanfang Data updated in June 2020 with the following search terms:"diabetic retinopathy° or"retinopathy° or "DR° or "NPDR°,in combination with "Compound Danshen Dripping Pill° or "Salvia miltiorrhiza° or "Danshen°.Risk ratio(RR) and weighted mean difference(WMD) with their 95% confidence interval(CI) was calculated between treatment and control groups.The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared.Subgroup analysis,Metaregression,and publication bias analysis were also conducted.The strength of evidence was evaluated with the Grading of Recommendation,Assessment,Development,and Evaluation(GRADE) method.Results:Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies,extracting the data,and assessing the study quality.The Stata15.0 software was utilized for processing.Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54,95% CI(0.40,0.73);moderate-quality evidence].In addition,the results showed that CDDP was significantly associated with improving retinal hemorrhages[WMD =-0.62,95% CI(-0.78,-0.46);low-quality evidence],the vision [WMD = 0.14,and 95% CI(0.09,0.19),low-quality evidence],fundus fluorescence angiography [RR = 0.37 and 95% CI(0.23,0.60);low-quality evidence],reduction of retinal microaneurysm [WMD =-3.74 and 95% CI(-4.38,-3.11);moderate-quality evidence],hemangioma volume [WMD =-3.15,95%CI(-3.45,-2.85);moderate-quality evidence],macular thickness [WMD =-5.52,95%CI =(-64.27,-48.78);low-quality evidence],mean defect [WMD =-1.65 and 95% CI(-1.95,-1.34);very low-quality evidence],fasting blooding glucose [WMD =-0.95,95% CI(-1.19,-0.70);low-quality evidence),hemoglobin A1c[WMD =-0.62,95% CI(-0.93,-0.30);low-quality evidence],high sensitive C reaction protein[WMD =-5.66,95% CI(-8.01,-3.31);low-quality evidence].Sensitivity,subgroup,and Metaregression analyses were also assessed.Conclusion:The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision.Moreover,it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose,hemoglobin A1c and high sensitive C reaction protein,which was associated with the pathogenesis of NPDR.However,high-quality and large randomized clinical trials will be needed to prove the consequence in future.

Sulfite as the substrate of C-sulfonate metabolism ofα,β-unsaturated carbonyl containing andrographolide:analysis of sulfite in rats'intestinal tract and the reaction kinetics of andrographolide with sulfite

One-sixth of the currently known natural products containα,β-unsaturated carbonyl groups.Our previous studies reported a rare C-sulfonate metabolic pathway.Sulfonate groups were linked to theβ-carbon ofα,β-unsaturated carbonyl-based natural compounds through this pathway.However,the mechanism of this type of metabolism is still not fully understood,especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition.In this work,the enzyme-mediated and non-enzymatic pathways were studied.First,the sulfite content in rat intestine was determined by LC-MS/MS.The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383μg·g^(-1),whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation(20μg·g^(-1)).Second,the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions(pH 6-8)was studied.The half-lives of andrographolide ranged from minutes to hours.This was suggested that the C-sulfonate reaction of andrographolide was very fast.Third,the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite,indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide,which assisted a significant portion of andrographolide metabolism.Finally,the comparison of andrographolide metabolite profiles among liver homogenate(with NADPH),liver S9(with NADPH),small intestine contents homogenate(with no NADPH),and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway.In summary,sulfite can serve as a substrate for C-sulfonate metabolism,and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containingα,β-unsaturated carbonyl moiety.

Phytochemistry,Metabolism, and Metabolomics of Ginseng

Ginseng, as a medicinal plant, has been used for thousands of years in China, Korea, and Japan, and the study on ginseng is a hotspot in the research field as evidenced by about 7000 scientific papers in PUBMED. In recent decades, many ginseng studies focused on the metabolism and metabolomics of ginseng or its active ingredients using modern bioanalytical technologies. To date, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. In the past decades, rapid development of analytical technologies has facilitated the advancement of ginseng research in many ways. In this review, we focus on the advances of ginseng research in chemistry, pharmacology, and metabolomics. We also provide the comments on the significance as well as challenges of metabolomics-based ginseng studies.

Stellate porous silica based surface-enhanced Raman scattering system for traceable gene delivery

Numerous nanocarriers have been currently developed for intracellular delivery.The potential cytotoxicity of these very small inorganic nanocarriers has raised great consideration.Thus,it becomes of utmost importance to conduct the intracellular trace of nanocarriers.Among many analytical techniques,surface enhanced Raman scattering(SERS)method is one of the current state-of-the-art techniques for cell visualization and trace.In this work,a novel stellate porous silica based gene delivery system has been designed for SERS trace purpose.A stellate porous silica nanoparticle modified with many small Au nanoparticles is designed to replace common metallic SERS tags.The results show that the designed system not only could deliver si RNA into cells for therapy,but also could realize SERS trace with high sensitivity and non-invasive features.The constructed delivery system has considerable potential to trace the dynamic gene delivery in living cells.