peoniflorin and Dysmenorrhea

Traditional Chinese medicine (TCM) is used under the guidance of the theory of traditional Chinese medical sciences in clinical application. The Chinese herbal formula, Shaofu Zhuyu decoction (SFZYD), is considered as an effective prescription for treating Cold - Stagnation and Blood - Stasis (CSBS) primary dysmenorrhea. The previous studies showed the SFZYD exhibited significant anti-inflammation and analgesic effect. In this present study the metabolomics of CSBS primary dysmenorrhea diseased rats and the cytokine transcription in PHA stimulated-PBMC were investigated to explore the effects and mechanisms.. Explore a valuable insight into the effects and mechanisms of SFZYD on Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats.. We established CSBS primary dysmenorrhea diseased rats according the clinical symptoms. A targeted tandem mass spectrometry (MS/MS)-based metabolomic platform was used to evaluate the metabolic profiling changes and the intervention effects by SFZYD. The PBMC cell was adopted to explore the mechanisms by analyzing the signaling pathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylation levels.. Estradiol, oxytocin, progesterone, endothelin, β-endorphin and PGF2α were restored back to the normal level after the treatment of SFZYD. Total twenty-five metabolites (10 in plasma and 15 in urine), up-regulated or down-regulated, were identified. These identified biomarkers underpinning the metabolic pathway including pentose and glucuronate interconversions, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in model rats. Among these metabolites, twenty one potential biomarkers were regulated after SFZYD treated. The compound of paeoniflorin, a major bioactive compound in SFZYD, was proved to regulate the MAPK signaling pathway by inhibiting the expression of IL-1β, IL-2, IL-10, IL-12, TNFα, INFγ, c-jun and c-fos in PHA stimulated-PBMC.. These findings indicated that SFZYD improved the metabolic profiling and biochemical indicators on CSBS primary dysmenorrhea rats. And the mechanisms were closely related with the regulation of the MAPK pathway by reduction in phosphorylated forms of the three MAPK (ERK1/2, p38 and JNK) and down regulation of c-jun and c-fos by paeoniflorin. The data could be provided the guidance for further research and new drug discovery.

Topics: Animals; Cells, Cultured; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Female; Glucosides; Humans; Leukocytes, Mononuclear; Metabolomics; Mitogen-Activated Protein Kinases; Monoterpenes; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats, Sprague-Dawley; RNA, Messenger

Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine.. The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics.. GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics.. In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Drug Synergism; Drugs, Chinese Herbal; Dysmenorrhea; Female; Glucosides; Glycyrrhetinic Acid; Meloxicam; Mice; Monoterpenes; Skin Absorption; Thiazines; Thiazoles; Tissue Distribution; Transdermal Patch

We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24-2875 ngmL(-1) for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE).

Topics: Acids, Carbocyclic; Administration, Oral; Animals; Benzoates; Bridged-Ring Compounds; Caffeic Acids; Chromatography, High Pressure Liquid; Coumaric Acids; Drugs, Chinese Herbal; Dysmenorrhea; Female; Glucosides; Monoterpenes; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Vanillic Acid