ABSTRACT
This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
Subject(s)
Humans , Rats , Female , Animals , Estrogen Receptor alpha , Oxytocin , Dysmenorrhea/metabolism , Cyclooxygenase 2 , Dinoprostone , RNA, Messenger/metabolism , DinoprostABSTRACT
Objective: To compare the efficacy and metabolic effects of pioglitazone-metformin and basic insulin therapy on type 2 diabetes mellitus (T2DM) patients with overweight or obesity and poor blood glucose control. Methods: A total of 153 T2DM patients with overweight or obesity and poor blood glucose control were enrolled in this study. They received treatment with pioglitazone-metformin (pioglitazone-metformin group, n = 77) or insulin glargine (basal insulin group, n = 76) for 6 months in addition to their previous oral hypoglycemic drugs. At baseline, 3 months and 6 months after treatment, glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 2 h post-prandial blood glucose (2hBG), fasting insulin (FINS), 2 h post-prandial insulin (2hINS), fasting C peptide (FCp), 2 h post-prandial C peptide (2hCp), body mass index (BMI), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), and hepatic fatty degeneration (expressed as controlled attenuation parameter [CAP] value) were observed and recorded. Results: At baseline, there were no significant differences in gender, age, BMI, HbA1c, FBG, 2hBG, FINS, 2hINS, FCp, 2hCp, TC, TG, HDL-C, LDL-C, CAP value, underlying diseases, or concomitant medicine between the two groups (all P>0.05). At 3 and 6 months after treatment, the HbA1c, FBG and 2hBG levels were significantly decreased versus those at the baseline in the two groups (all P0.05). Compared with the basal insulin group, the FINS, BMI and CAP values were significantly decreased in the pioglitazone-metformin group 3 and 6 months after treatment (P<0.05, P<0.01). After 6 months of treatment, there were no significant changes of blood lipid levels in both groups. Conclusion: In T2DM patients with overweight or obesity and poor blood glucose control, adding pioglitazone-metformin and basal insulin to their previous oral hypoglycemic drugs has similar hypoglycemic effect. However, patients receiving pioglitazone-metformin have better metabolic benefts such as lower BMI, lower insulin and improved hepatic fatty degeneration.
ABSTRACT
Objective: To study therapeutic effect of valsartan combined carvedilol on patients with heart failure with preserved ejection fraction (HFPEF) and its influence on heart function and myocardial remodeling. Methods: A total of 92 aged HFPEF patients treated in our hospital were selected. They were randomly and equally divided into routine treatment group and combined treatment group (received valsartan combined carvedilol based on routine treatment), and both groups were treated for six months. Therapeutic effect, heart function, myocardial remodeling indexes and adverse reactions were compared between two groups after six months. Results: Total effective rate of combined treatment group was significantly higher than that of routine treatment group (93. 48％ vs. 78. 26％, P=0. 036). Compared with routine treatment group after treatment, there were significant reductions in blood pressure [(120. 26±9. 17) / (73. 56±5. 86) mmHg vs. (115. 68±10. 31) / (67. 24±4. 92) mmHg], heart rate [(74. 35±8. 53) beats/min vs. (68. 48±7. 17) beats/min]and BNP level [(299. 86±19. 43) pg/ml vs. (231. 71± 20. 15) pg/ml], significant rise in E/A [(1. 02±0. 09) vs. (1. 26±0. 07)] and LVEF [(53. 14±1. 60) ％ vs. (57. 02±1. 51) ％]; and significant reductions in IVRT [(119. 45±14. 23) ms vs. (102. 17±11. 53) ms], LAVI [(35. 82±7. 15) ml/m2 vs. (30. 17±6. 48) ml/m2], LVEDd [(57. 22±7. 24) mm vs. (50. 61±6. 35) mm]and LVESd [(50. 14±5. 06) mm vs. (44. 93±5. 82) mm]in combined treatment group, P＜0. 05 or＜0. 01. During treatment, no obvious adverse reactions occurred in two groups. Conclusion: Valsartan combined carvedilol can significantly increase effective rate, improve heart function and myocardial construction in HFPEF patients. Which is worth extending.