Application of an ultra performance liquid chromatography-tandem mass spectrometry method to the pharmacokinetics study of paeoniflorin-6'-O-benzene sulfonate and its active paeoniflorin metabolite in rat plasma

OBJECTIVE To establish a rapid,simple,precise and sensitive ultra performance liquid chromatography(UPLC) method for determination of paeoniflorin-6'-O-benzene sulfonate(acylated derivative of Pae,CP-25) and its primary metabolite(Pae,M1) in rat plasma,and to investigate the effects of gender,food and disease status on the pharmacokinetics after oral administration in rats.METHODS Plasma samples and calibrators were extracted with methanol after addition of the internal standard solution.After evaporation of the methanol layer,the residue was reconstituted in mobile phase,and a 2 μL of the sample was injected into a Waters ACQUITY UPLC BEH C18(2.1 mm × 50 mm,1.7 μm) column for separation at a flow rate of 0.5 mL·min^(-1) at 40℃.The mobile phase was composed of 0.1% formic acid in water and methanol(68∶32,V/V).RESULTS The developed UPLC-MS/MS method was linear in the concentration range of 2-800 mg·L^(-1).Validation of the method proved that the method′s precision,selectivity and stability were all within the acceptable limits.Pharmacokinetics study showed that CP-25 could have more extensive distribution in females than that in males but no differences in M1.Food intake could also increase the extent of absorption and decrease the rate of clearance of CP-25 and M1 after oral administration in rats.The disease status would decrease the absorption of CP-25 in rats.Comparing single-and multiple-dosing in adjuvant arthritis(AA) model,absorption of CP-25 and M1 was improved with increasing dosage.CONCLUSION The developed UPLC-MS/MS method is sensitive,specific and was successfully applied to the pharmacokinetics of CP-25 and M1 in rats.And a significant gender,food intake and disease status differences for CP-25 and M1 were observed in this study.

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension:A randomized,double-blind,placebo-controlled trial

Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional Chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the 216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmHg) and home diastolic blood pressure ([78.47±9.53]vs[71.79±6.82]mm Hg).HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure:[133.75±10.49]vs[132.46±8.84]mmHg and 24-hour diastolic blood pressure:[84.12±8.01]vs[82.11±7.45]mmHg) and an improvement in HOMA-IR ([4.09±1.72]vs[3.98±1.44]),TC ([4.66±1.47]vs[3.75±1.81]mmol/L) and UACR (75.94[5.12,401.12]vs 45.61[4.26,234.26]).Moreover,HQQR demonstrated a decrease in hs-CRP (1.46[0.10,10.53]vs 0.57[0.12,3.99]mg/L) and IL-6 (6.69[2.00,29.74]vs 5.27[2.00,9.73]pg/mL),with no reported side effects (P<0.001).Conclusion:This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure,glycolipid metabolism,and inflammation in patients with hypertension.

Biological, clinical and epidemiological features of COVID-19, SARS and MERS and AutoDock simulation of ACE2

Background:The outbreak of coronavirus disease 2019(COVID-19)has caused a public catastrophe and global concern.The main symptoms of COVID-19 are fever,cough,myalgia,fatigue and lower respiratory tract infection signs.Almost all populations are susceptible to the virus,and thebasic reproduction number(R0)is 2.8-3.9.The fight against COVID-19 should have two aspects:one is the treatment of infected patients,and the other is the mobilization of the society to avoid the spread of the virus.The treatment of patients includes supportive treatment,antiviral treatment,and oxygen therapy.For patients with severe acute respiratory distress syndrome(ARDS),extracorporeal membrane oxygenation(ECMO)and circulatory support are recommended.Plasma therapy and traditional Chinese medicine have also achieved good outcomes.This review is intended to summarize the research on this new coronavirus,to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)and to provide guidance regarding new methods of prevention,diagnosis and clinical treatment based on autodock simulations.Methods:This review compares the multifaceted characteristics of the three coronaviruses including COVID-19,SARS and MERS.Our researchers take the COVID-19,SARS,and MERS as key words and search literatures in the Pubmed database.We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses.Results:We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2,SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S.We also found that the types and severity of clinical symptoms vary,which means that the diagnosis and nursing measures also require differentiation.In addition to the common route of transmission including airborne transmission,these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19.Conclusions:In evolutionary history,these three coronaviruses have some similar biological features as well as some different mutational characteristics.Their receptors and routes of transmission are not all the same,which makes them different in clinical features and treatments.We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2,such as remdesivir,chloroquine,ciclesonide and niclosamide,and may be a potential target in COVID-19.