Modern Researches of White Peony Root,Red Peony Root.Paeoniflorin and Peony Root Extract.

  seminal trace...White Peony Root Extract.10:1.Radix Paeoniae Alba.Peony Root Extract, White.Paeoniflorin 10%.20%.90%.C23H28O11,CAS RN:23180-57-6.Chinese Peony Root Extract.Paeonia lactiflora,Paeonia officinalis,Bai Shao Yao,Paeonol,C9H10O3,Benzoylpaeoniflorin,C30H32O12...

   Phytochemical info of Paeoniflorin and Peony Root Extract:

 Product Name:
 Synonym:
 Definition: Peony Root Extract.are majorly composed of Paeoniflorin.
 Chemical information disclosed as following table:


   Modern Researches of White Peony Root,Red Peony Root.Paeoniflorin and Peony Root Extract.:

  Modern Researches of White Peony Root.:
 The most important ingredient medicinally in the white peony root is paeoniflorin, which has been shown to have a strong antispasmodic effect on mammalian intestines, inhibiting the smooth muscle of the stomach, intestines and uterus in the rat; and also has certain effects of analgesia, sedation, anti-convulsion; it also reduces blood pressure, reduces body temperature caused by fever and protects against stress ulcers.
 Decoction of white peony root has bacteriostatic action on staphylococus, pseudomonas aeruginosa, herpes virus and some fungi, and especially on Shigella Shigae.
 White peony root is taken internally in the treatment of menstrual disorders, injuries, high blood pressure, pre-menstrual tension and liver disorders.
 A tea made from the dried crushed petals of various peony species has been used as a cough remedy, and as a treatment for heamorrhoids and varicose (abnormally swollen or dilated) veins.
 Modern uses: An infusion of the powdered root - 1 oz (28 g) to 1 pt (568 ml) of boiling water - is taken in doses Of 2 fl OZ (56 ml) three or four times as an anti-spasmodic remedy for spasms, convulsions and epilepsy. It is an effective liver tonic.
 Chinese herbalists favour the White Paeony (Paeonia lactiflora) which they use in prescriptions for arthritis. It is used to promote blood circulation and to relieve muscle spasms.
 


  Experimental pharmacology of White Peony Root.:
 The primary pharmacological effects of Radix Paeoniae are antispasmodic, anti- inflammatory, and analgesic. A decoction of the drug had antispasmodic effects on the ileum and uterus when administered orally to mice, rabbits, and guinea-pigs. Similar effects were observed with a methanol extract in rat uterus, but an ethanol extract had uterine stimulant activity in rabbits. Radix Paeoniae extracts tested in vitro relaxed smooth muscles in both rat stomach and uterine assays.
 Intragastric administration of a hot-water extract of Radix Paeoniae to rats inhibited inflammation in adjuvant-induced arthritis and carrageenin- induced paw oedema. The major active constituent of the drug, paeoniflorin, a monoterpenoid glycoside, has sedative, analgesic, antipyretic, anti-inflammatory and vasodilatory effects in vivo. Hexobarbital-induced hypnosis was potentiated and acetic acid-induced writhing was inhibited in mice after intragastric administration of paeoniflorin.
 Intragastric administration of hot-water or ethanol extracts of Radix Paeoniae to rats inhibited ADP-, arachidonic acid- and collagen-induced platelet aggregation, as well as endotoxin-induced disseminated intravascular coagulation. Similar effects were observed in rabbits and mice after intraperitoneal administration of the drug. When tested by the standard fibrin plate method, ethanol and hot-water extracts of the drug had antifibrinolytic activity in vitro. Paeoniflorin had anticoagulant activity both in vitro, and in vivo (in mice).
 Intragastric administration of extracts of Radix Paeoniae protected the liver against carbon tetrachloride-induced hepatotoxicity in mice and rats.
 Oral administration of water extracts of Radix Paeoniae or its major constituent, paeoniflorin, attenuated the scopolamine-induced impairment of radial maze performance in rats. Paeoniflorin prevented the scopolamine- induced decrease in acetylcholine content in the striatum, but not in the hippocampus or cortex. Oral administration of paeoniflorin further attenuated learning impairment of aged rats in operant brightness discrimination tasks. The results of this study suggest that further research to explore the therapeutic potential of paeoniflorin in cognitive disorders such as senile dementia may be promising.


  The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.:

 J Ethnopharmacol. 2006; 103(3):425-32 (ISSN: 0378-8741).Chan K; Liu ZQ; Jiang ZH; Zhou H; Wong YF; Xu HX; Liu L.School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, PR China.
 Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

  Mechanisms responsible for poor oral bioavailability of paeoniflorin: Role of intestinal disposition and interactions with sinomenine.:

 Pharm Res. 2006; 23(12):2768-80 (ISSN: 0724-8741).Liu ZQ; Jiang ZH; Liu L; Hu M.Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77030, USA.
 PURPOSE: To determine the intestinal disposition mechanisms of paeoniflorin, a bioactive glucoside, and to investigate the mechanisms by which sinomenine increases paeoniflorin bioavailability. MATERIALS AND METHODS: A single-pass "four-site" rat intestinal perfusion model and a cultured Caco-2 cell model were employed. RESULTS: In both model systems, paeoniflorin permeability was poor. In the perfusion model, maximal absorption and metabolism of paeoniflorin occurred in duodenum and jejunum, which were significantly decreased by a glucosidase inhibitor gluconolactone (20 mM). On the other hand, paeoniflorin absorption in terminal ileum increased significantly but its metabolism did not in the presence of sinomenine and cyclosporine A. In the Caco-2 cell model, paeoniflorin was transported 48-fold slower than its aglycone (paeoniflorigenin). Absorptive transport of paeoniflorin was significantly (p < 0.05) increased by sinomenine (38%), verapamil (27%), and cyclosporine A (41%), whereas its secretory transport was significantly (p < 0.01) decreased by sinomenine (50%), verapamil (35%) and cyclosporine A (37%). In contrast, MRP inhibitors MK-571 and leukotriene C4 did not affect transport of paeoniflorin. Lastly, sinomenine was also shown to significantly increase the absorptive transport of digoxin (a prototypical p-glycoprotein substrate) and to significantly decrease its secretory transport. CONCLUSIONS: Poor permeation, p-gp-mediated efflux, and hydrolysis via a glucosidase contributed to the poor bioavailability of paeoniflorin. Sinomenine (an inhibitor of the p-gp-mediated digoxin efflux) increased paeoniflorin's bioavailability via the inhibition of p-gp-mediated paeoniflorin efflux in the intestine.

  Protective effect of paeoniflorin on immunological liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide: modulation of tumour necrosis factor-alpha and interleukin-6 MRNA.:

 Clin Exp Pharmacol Physiol. 2006; 33(4):332-9 (ISSN: 0305-1870).Liu DF; Wei W; Song LH.Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Research and Development of Chinese Medicine in Anhui Province, Anhui, PR China.
 1. Paeoniflorin is one of the main effective components of the total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora which has been used for gynaecological problems and for cramp, pain and giddiness for over 1,500 years in Chinese medicine. Anti-inflammatory, antioxidative, antihepatic injury and immunoregulatory activities of TGP have been extensively proved in our laboratory for many years. Our present study investigates the effects and mechanisms of paeoniflorin on immunological liver injury in mice. 2. A model of immunological liver injury was induced by tail vein injection of bacillus Calmette-Gu??rin (BCG) and lipopolysaccharide (LPS) in mice. Activities of serum alanine aminotransferase (ALT) were measured by biochemical methods. Hepatic tissue sections were stained with haematoxylin and eosin and examined under a light microscope. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, lipopolysaccharide binding protein (LBP) and CD14 mRNA (messenger ribonucleic acid) expression in mouse liver were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. 3. Immunological liver injury induced by BCG plus LPS was successfully duplicated. Serum ALT activities were significantly decreased by paeoniflorin. (25, 50, 100 mg/kg). Histological examination demonstrated that paeoniflorin could attenuate the area and extent of necrosis and reduce the immigration of inflammatory cells. The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection. 4. Paeoniflorin could significantly protect against immunological liver injury in mice. TNF-alpha, IL-6, LBP and CD14 mRNA expression in mouse liver may be involved in BCG plus LPS induced liver injury. The protective mechanism of paeoniflorin might be partially related to modulation of TNF-alpha, IL-6, LBP and CD14 mRNA expressions in mouse liver.

  Studies of the pharmacokinetics of paeoniflorin in two Jing-Zhi-Guan-Xin formulations after oral administration to beagle dogs.:

 J Pharm Biomed Anal. 2006; 41(1):320-4 (ISSN: 0731-7085).Yang XG; Peng B; Zhang GH; Wei LL; Nie SF; Pan WS.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
 Paeoniflorin is the principal bioactive component of Paeoniae Radix. The traditional chinese medicine compound recipe (TCMCR) tablets of Jing-Zhi-Guan-Xin (JZGX), which is composed of Radix Salviae Miltiorrhizae, Radix Paeoniae Rubrae, Rhizoma Chuan-xiong, Flos Carthami and Lignum Dalbergiae Odorafera, have been widely used in China. The plasma concentrations of paeoniflorin in beagle dogs after oral administration of two Jing-Zhi-Guan-Xin formulations (the dose used in the two formulations were both 200 mg paeoniflorin) were measured using a simple and rapid HPLC method. The mean terminal half-lives (t1/2) of JZGX tablet and JZGX elementary osmotic pump tablet (EOPT) formulations of paeoniflorin were 147.52 +/- 28.98 and 276.60 +/- 24.24 min, the maximum plasma concentrations (Cmax) of paeoniflorin were 210.49 +/- 23.89 and 94.36 +/- 14.01 ng/ml, times to reach maximum concentrations (tmax) were 130.00 +/- 30.98 and 280.00 +/- 48.99 min, the area under the plasma concentration-time curves (AUC0-infinity) were 43066.50 +/- 10119.51 and 42266.87 +/- 2654.90 ng min/ml, the mean residence times (MRT) were 212.87 +/- 41.82 and 399.14 +/- 34.98 min, respectively, and the relative bioavailability (Fr) of JZGX EOPT compared with JZGX tablet was 101.8 +/- 18.8%. These results, compared with the pharmacokinetic parameters of paeoniflorin after oral administration of Paeoniae Radix extract alone, indicated that the absorption of paeoniflorin after oral administration of the two JZGX formulations was significantly greater than that after oral administration of Paeoniae Radix extract alone.

  Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia-reperfusion rats after intravenous administration of Paeoniae Radix extract.:

 Biomed Chromatogr. 2006; 20(12):1283-8 (ISSN: 0269-3879).Cao C; He X; Wang W; Zhang L; Lin H; Du L.Laboratory of Pharmaceutical Sciences, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
 The time course of paeoniflorin in the cortex of normal and cerebral ischemia-reperfusion rats, following intravenous administration of Paeoniae Radix extract at a dose of 60 mg/kg of paeoniflorin, was determined using high-performance liquid chromatographic (HPLC) assay. The results showed that paeoniflorin could penetrate through the blood-brain barrier to reach the cortex, and that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin in the cortex after intravenous administration of Paeoniae Radix extract. The cortex concentrations of paeoniflorin in cerebral ischemia-reperfusion rats were lower 5 min after dosing and declined more slowly than that in normal control.


  Determination of paeoniflorin in rat plasma by a liquid chromatography-tandem mass spectrometry method coupled with solid-phase extraction.:

 Biomed Chromatogr. 2006; 20(2):173-9 (ISSN: 0269-3879).Wang Q; Yang H; Liu W; Feng X; Zhang L; Li Y; Bi K; Guo D.The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, People's Republic of China.
 A rapid, sensitive and selective liquid chromatography-tandem spectrometry method was developed and validated for determination of paeoniflorin in rat plasma using geniposide as the internal standard. The samples were pretreated with solid-phase extraction using Extract-Clean cartridges. Separation of paeoniflorin and IS was achieved on a reversed-phase C18 column (50x4.6 mm i.d.) with a mobile phase made up of acetonitrile and 0.05% formic acid (25:75, v/v) at a flow rate of 0.5 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer by multiple-reaction monitoring and an electrospray ionization source was employed as the ionization source. The lower limit of quantification obtained was 4 ng/mL (n=6) using 200 microL plasma with an accuracy of -3.67% (relative error) and a precision of 4.13% (relative standard deviation). A good linearity was found in the range of 4-1000 ng/mL. The intra- and inter-day relative standard deviations in the measurement of quality control samples 10, 150 and 800 ng/mL ranged from 3.73 to 4.94% and from 4.31 to 6.56%, respectively. The accuracy was from -3.93 to -1.11% in terms of relative error. The analyte and IS were stable in the battery of stability studies. This method was successfully applied to a pharmacokinetic study of paeoniflorin after a single oral administration of 53.36 mg/kg paeoniflorin to rats.

  Effects of paeoniflorin on cerebral energy metabolism, nitric oxide and nitric oxide synthase after cerebral ischemia in mongoliagerbils.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(10):832-5 (ISSN: 1001-5302).Sun R; Lv LL; Liu GQ.Department of pharmacology, China Pharmaceutical University, Nanjing 210009, China.
 OBJECTIVE: To explore the effects of paeoniflorin on antagonising the delayed neuronal death (DND) induced by cerebral ischemia,and the relation between DND, cerebral tissue energy metabolism, nitric oxide (NO) and nitric oxide synthase (NOS). METHOD: Incomplete cerebral ischemia induced was induced by ligating bilateral arteries carotis communis for 20 min followed by reperfusion 48 h in rats. The indexes including Na(+)-K(+)-ATPase activity, lactic acid content, Ca(2+)-ATPase, Mg(2+)-ATPase activity, NO content and NOS activity were determined in fore brain cortex at 48 h after reperfusion. RESULT: Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activity were lowered (P < 0.01), NO level was decreased (P < 0.01), NOS activity dropped (P < 0.01) in cerebral tissue at 48h after reperfusion, but lactic acid level had no change. Paeoniflorin could prevent reduction of Na(+)-K(+)-ATPase activity (P < 0.05, P < 0.01), increase NO level (P < 0.01), enhance NOS activity (P < 0.01) at 48h after reperfusion. CONCLUSION: DND induced by ischemia may be concerned with energy metabolism disorder and decrease of NO formation. Paeoniflorin may play the role of antagonising cerebral ischemia by adjusting cerebral energy metabolism and nitric oxide formation.

  RP-HPLC detection of a sulphiting-induced artefact from paeoniflorin in dried roots of Paeonia lactiflora.:

 Phytochem Anal. 2006; 17(4):251-4 (ISSN: 0958-0344).Hayes PY; Lehmann R; Penman K; Bone KM; Kitching W; De Voss JJ.SMMS, Chemistry Department, The University of Queensland. Brisbane Qld 4072, Australia.
 Paeoniflorin is one of the bioactive ingredients of the roots of Paeonia lactiflora (Paeoniaceae). A comparative study of processed and non-processed commercial samples of dried roots of P. lactiflora indicated a very low level of paeoniflorin in the processed sample and the formation of a new more polar component, sodium paeoniflorin sulphonate, during treatment of the roots with sulphiting agents.

  Determination of salvianolic acid B and paeoniflorin in Shuangdan granules by HPLC.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(13):1062-4 (ISSN: 1001-5302).Ge ZW; He Q; Shui WB; Cheng YY.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
 OBJECTIVE: To develop a method for the determination of salvianolic acid B and paeoniflorin in Shuangdan granules. METHOD: The chromatographic separation was performed on a Zorbax SB C18 column with a linear gradient elution of phosphoric acid-water (0.05:100) and phosphoric acid-acetonitrile-methanol (0.05:4:96) was used. The flow rate was 1 mL x min(-1) and column temperature was set at 25 degrees C. The UV detection wavelength was set at 230 nm. RESULT: The linear ranger was of 0.710-22.7 microg for salvianolic acid B and 0.103-3.30 microg for paeoniflorin. Three batches of Shuangdan granules were analyzed, and the content of salvianolic acid B ranged from 6.46-11.6 mg x g(-1) and paeoniflorin ranged from 1.44-1.78 mg x g(-1). CONCLUSION: The method was accurate, reproducible, reliable, and could be used for quantitative control of Shuangdan granules.

  Construction and expression of a single chain Fv fragment against pharmacologically active paeoniflorin in Escherichia coli, and its potential use in an enzyme-linked immunosorbent assay.:

 A recombinant single chain variable-fragment (scFv) antibody against paeoniflorin (PF) was produced using the hybridoma cell line C31B9. Variable regions of heavy (V (H)) and light (V (L)) chain antibody genes were directly cloned from cDNA resources of hybridoma C31B9 and assembled using splicing by overlap extension (SOE)-PCR using a (Gly (4)Ser) (3) linker DNA. The constructed scFv genes were cloned into pET28a vectors for the generation of recombinant proteins in Escherichia coli. Most of the recombinant proteins were expressed in inclusion bodies. The yield of refolded and purified scFv was 1.89 mg per 100 mL of cell culture. The recombinant scFv displayed cross-reactivity as its mother monoclonal antibody (MAb) C31B9. Therefore, the newly expressed scFv protein was applied to quantitative ELISA to determine the total paeoniflorin (PF) and albiflorin (Alb) concentrations in peony root samples. Using PF as a standard compound, the full linear range of the assay was extended from 0.78 to 25 microg/mL. The results obtained by ELISA employing both the recombinant scFv and the original MAbC31B9 showed a reasonably good agreement with each other.


  Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.:

 Br J Pharmacol. 2006; 148(3):314-25 (ISSN: 0007-1188).Liu HQ; Zhang WY; Luo XT; Ye Y; Zhu XZ.Department of Pharmacology II, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China.
 1. This study examined whether Paeoniflorin (PF), the major active components of Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). 2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four-dose injection of MPTP (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1)) also significantly attenuated the dopaminergic neurodegeneration in a dose-dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated MPTP-induced proinflammatory gene upregulation and microglial and astrocytic activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF. 5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.

  Determination of paeonol and paeoniflorin in Chinese medicine Cortex Moutan and 'Shuangdan' granule by micellar electrokinetic capillary chromatography.:

 J Pharm Biomed Anal. 2006; 40(5):1257-62 (ISSN: 0731-7085).Yu K; Wang YW; Cheng YY.Department of Chinese Medicine Science and Engineering, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310027, China.
 An easy, simple and rapid micellar electrokinetic capillary chromatography (MEKC) method was developed for the separation of two active components paeonol (PN) and paeoniflorin (PF) within 7 min. Capillary electrophoresis (CE) was performed using a 50.0 cm (42.0 cm to the detector window) x 75 microm i.d. fused-silica capillary. The optimal running buffer containing 10mM borate and 25 mM SDS at pH 9.54 was employed. The applied voltage 15 kV and the temperature 25 degrees C was used in CE separation. The linearities between peak areas and the concentrations of the analytes were investigated, and they exhibited excellent linear behavior over the investigated concentration ranges (R(2): 0.9945 for PN and 0.9992 for PF). The method was successfully applied to the determination of these two components contained in Cortex Moutan and 'Shuangdan' granule. The average recoveries ranged between 97.6 and 105.3% for PN and 95.3 and 106.1% for PF, respectively.

  Involvement of multitargets in paeoniflorin-induced preconditioning.:

 J Pharmacol Exp Ther. 2006; 319(1):165-80 (ISSN: 0022-3565).Chen DM; Xiao L; Cai X; Zeng R; Zhu XZ.Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Pudong Shanghai 201203, China.
 Paeoniflorin (PF) is the principal component of Paeoniae radix prescribed in traditional Chinese medicine. The delayed neuroprotection induced by PF preconditioning and its underlying mechanisms were investigated in rat middle cerebral artery occlusion (MCAO) and reperfusion model. At a dosage of 20 or 40 mg/kg, PF preconditioning 48 h before MCAO followed by 24-h reperfusion significantly reduced the mortality and infarct volume and reversed the neurological deficits caused by ischemia. Likewise, the ameliorative effects on mortality, infarct size, and neurological impairment induced by MCAO emerged as well when PF was administered 24 h, 48 h, or 5 days before MCAO at the dose of 20 mg/kg. Furthermore, comparative proteomics analysis was adopted to identify the differentially expressed proteins induced by PF preconditioning itself. The relative levels of 42 proteins were altered after PF preconditioning, among which 20 were elevated and 22 reduced. In summary, A(1) receptor-regulator of G protein signaling-K(ATP) signaling, arachidonic acid cascade, nitric oxide system, markers of neuronal damage, mitochondrial damage-related molecules, and the mitogen-activated protein kinase and nuclear factor-kappaB pathway are associated with the mechanisms of PF preconditioning.

  Potentiation of adenosine A1 receptor agonist CPA-induced antinociception by paeoniflorin in mice.:

 Biol Pharm Bull. 2006; 29(8):1630-3 (ISSN: 0918-6158).Liu DZ; Zhao FL; Liu J; Ji XQ; Ye Y; Zhu XZ.Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
 The effect of paeoniflorin (PF), a major constituent isolated from Paeony radix, on N6-Cyclopentyladenosine (CPA), a selective adenosine A1 receptor (A1 receptor) agonist, induced antinociception was examined in mice. In the tail-pressure test, CPA (0.05, 0.1, 0.2 mg/kg, s.c.) could induce antinociception in a dose-dependent manner. PF (5, 10, 20 mg/kg, s.c.) alone failed to exhibit any antinociceptive effect in mice; however, pretreatment of PF (20 mg/kg, s.c.) could significantly enhance CPA-induced antinociception. Additionally, pretreatment of 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.25 mg/kg, s.c.), a selective A1 receptor antagonist, could antagonize the antinociceptive effect of combining CPA with PF. Furthermore, in the competitive binding experiments, PF did not displace the binding of [3H]-8-Cyclopentyl-1,3-dipropylxanthine ([3H]-DPCPX) but displaced that of [3H]-2-Chloro-N6-cyclopentyladenosine ([3H]-CCPA, a selective A1 receptor agonist) to the membrane preparation of rat cerebral cortex. These results suggested that PF might selectively increase the binding and antinociceptive effect of CPA by binding with A1 receptor.

  Design and synthesis of a biotin-tagged photoaffinity probe of paeoniflorin.:

 Bioorg Med Chem Lett. 2006; 16(12):3306-9 (ISSN: 0960-894X).Qiu WW; Xu J; Liu DZ; Li JY; Ye Y; Zhu XZ; Li J; Nan FJ.Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, 189 Guo-Shou-Jing Road, Shanghai 201203, China.
 A trifunctional probe (binding element-photoreactive group-affinity tag) of natural product paeoniflorin was designed and synthesized based on the previous primary structure-activity relationship. This new probe is a potential tool for labeling, purification, and identification of the target proteins.


  Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rats.:

 Brain Res. 2006; 1089(1):162-70 (ISSN: 0006-8993).Liu J; Jin DZ; Xiao L; Zhu XZ.Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
 Chronic cerebral hypoperfusion, a mild ischemic condition, is associated with the cognitive deficits of AD. Paeoniflorin (PF), a major constituent of peony root, was proved to be neuroprotective in middle cerebral artery occlusion model. In this study, we investigated whether PF could attenuate chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rat. Seven weeks after permanent bilateral occlusion of the common carotid arteries, the rats were tested in the Morris water maze. Subsequently, the animals were sacrificed and neurons, astrocytes and microglias were labeled with immunocytochemistry in hippocampus. PF at the dose of 2.5 mg/kg ameliorated cerebral hypoperfusion-related learning dysfunction and prevented CA1 neuron damage. Chronic cerebral hypoperfusion increased the immunoreactivity of astrocytes and microglias in hippocampus. The increase was prevented by PF at the dose of 2.5 mg/kg. Cerebral hypoperfusion also increased expression of nuclear factor-kappaB (NF-kappaB), mostly in astrocytes, but not in neurons. With the treatment of PF (2.5 mg/kg), NF-kappaB immunostaining was diminished in hippocampus. Our results demonstrated that PF could attenuate cognitive deficit and brain damage induced by chronic cerebral hypoperfusion and that suppression of neuroinflammatory reaction in brain might be involved in PF-induced neuroprotection.

  Study on influence of processing methods on chemical constituents in Radix Paeoniae Alba.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(17):1418-21 (ISSN: 1001-5302).Wang Q; Liu RX; Guo HZ; Zhu ZN; Bi KS; Guo DA.Modern Research Center for Traditional Chinese Medicine, Peking University, Beijing 100083, China.
 OBJECTIVE: The influence of processing methods on chemical constituents in Radix Paeoniae Alba was observed. METHOD: A HPLC method was used for analyzing the changes of eight major constituents, namely gallic acid, paeoniflorin sulfonate, catechin, paeoniflorin sulfonate, albiflorin, paeoniflorin, benzoic acid, pentagalloylglucose and benzoylpaeoniflorin, with the three processing procedures of decorticating, boiling and fumigating by burning of sulphur. Analysis was performed using a Zorbax SB-C18 column (4.6 mm x 250 mm, 5 microm) with the mixture of acetonitrile (A) and 0.015% phosphoric acid solution as mobile phase in gradient mode. The detection wavelength was set at 230 nm and the column temperature was at 30 degrees C. RESULT: Except for gallic acid and pentagalloylglucose, the other constituents decreased during procedure of decorticating and boiling. Fumigating by burning of sulphur would produce a new compound, paeoniflorin sulfonate, which was a byproduct from the reaction of paeoniflorin with SO2. CONCLSION: The significant changes were produced in chemical constituents of Radix Paeoniae Alba during three processing procedures. Therefore, the processing of Radix Paeoniae Alba should be strictly controlled and standardized.

  Effects of active components extracted from Qixue Bingzhi Recipe on proliferation of vascular smooth muscle cells and expressions of platelet-derived growth factor and its receptor genes.:

 Zhong Xi Yi Jie He Xue Bao. 2006; 4(1):30-4 (ISSN: 1672-1977).Ji B; Geng P; Liu JG; Shi DZ; Wang YY.Department of Cardiology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Science, Beijing 100091, China.
 OBJECTIVE: To observe the effects of paeoniflorin and total flavones extracted from Qixue Bingzhi Recipe on proliferation of vascular smooth muscle cells (VSMCs) cultured in endothelial cell conditioned medium (EC-CM) induced by oxidized low-density lipoprotein (ox-LDL) and the expressions of platelet-derived growth factor and its receptor genes. METHODS: The VSMCs were cultured in normal culture medium, EC-CM, simvastatin-medicated EC-CM, paeoniflorin and total flavones (low, medium and high dose) -medicated EC-CM respectively. The growth activity of VSMCs was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. The expressions of platelet-derived growth factor (PDGF)-BB and platelet-derived growth factor receptor-alpha (PDGFR-alpha) mRNAs were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The growth activity of VSMCs cultured in the EC-CM induced by ox-LDL was significantly higher than that in the normal culture medium (P<0.01), and the expressions of PDGF-BB and PDGFR-alpha mRNAs were obviously increased as compared with those in the normal culture medium. The growth activity of VSMCs cultured in each paeoniflorin and total flavones-medicated EC-CM was significantly lower than that in the EC-CM (P<0.01), and the expressions of PDGF-BB and PDGFR-alpha mRNAs were obviously decreased as compared with those in the EC-CM. CONCLUSION: The paeoniflorin and total flavones extracted from Qixue Bingzhi Recipe may be beneficial to the prevention and treatment of arteriosclerosis, and this efficacy may be correlated with down-regulating the expressions of PDGF-BB and PDGFR-alpha mRNAs which are related to the proliferation of VSMCs cultured in EC-CM induced by ox-LDL.

  Experimental study on processing of Paeonia lactiflora.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(11):882-3, 891 (ISSN: 1001-5302).He Y; Zhao HD; He BX; Tang LY; Zhang QW; Wang ZJ.Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
 OBJECTIVE: To provide experimental data for the quality control of processed Paeonia lactiflora, a Chinese herbal medicine. METHOD: Traditional processing of P. lactiflora was simulated, content of paeoniflorin and water extracts among different preparations were assayed by HPLC; The quantitative correlations among different processing conditions were analyzed, the effects of processing parameters on the contents of paeoniflorin and water extracts were assayed and analysed. RESULT AND CONCLUSION: The controlled processing parameters were correlated with covariables which showed that processing procedures was controllable, and the heating temperature was a factor impacting the content of paeoniflorin.

  Experimental study on processing of Paeonia lactiflora.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(11):889-91 (ISSN: 1001-5302).He Y; Zhao HD; He BX; Tang LY; Zhang QW; Wang ZJ.Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
 OBJECTIVE: To provide experimental data for the quality control of processed Paeonia lactiflora, a Chinese herbal medicine. METHOD: Traditional processing of P. lactiflora was simulated, content of paeoniflorin and water extracts among different preparations were assayed by HPLC; The quantitative correlations among different processing conditions were analyzed, the effects of processing parameters on the contents of paeoniflorin and water extracts were assayed a nanalysed. RESULT AND CONCLUSION: The controlled processing parameters were correlated with covariables which showed that processing procedures was controllable, and the heating temperature was a factor impacting the content of paeoniflorin.


  Study on quality control of Paeonia lactiflora.:

 Zhongguo Zhong Yao Za Zhi. 2006; 31(13):1070-1 (ISSN: 1001-5302).He Y; Zhao HD; Tang LY; Wang ZJ; Zhang QW.Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing.
 OBJECTIVE: To provide the experimental data for the quality control of Paeonia lactiflora a prepared Chinese medicinal herb. METHOD: The contents paeoniflorin among different growing areas and different processing methods methods were assayed by HPLC. RESULT: The quantitative differences of paeoniflorin content among different growing areas and different processing methods wereanalyzed quantitatively. CONCLUSION: The quantitative differences among different growing areas were not significant and the quantitative differences among different processing methods within 10%.

  Vasorelaxant effect of the rootbark extract of Paeonia moutan on isolated rat thoracic aorta.:

 Planta Med. 2006; 72(14):1338-41 (ISSN: 0032-0943).Yoo MY; Lee BH; Choi YH; Lee JW; Seo JH; Oh KS; Koo HN; Seo HW; Yon GH; Kwon DY; Kim YS; Ryu SY.Korea Research Institute of Chemical Technology, Daejeon, Korea.
 The vascular relaxant effect of the rootbark extract of Paeonia moutan was evaluated in isolated rat thoracic aorta. The methanolic extract of the rootbark showed a vasorelaxant activity in rat aortic preparations precontracted with 0.3 microM phenylephrine (IC50 value: 16.8 microg/mL). The activity-guided fractionation of the extract led to the isolation of five active principles such as paeoniflorin (1), paeonidanin (2), methylpaeoniflorin (4), tetragalloylglucose (5) and pentagalloylglucose (6), and these active ingredients potently relaxed phenylephrine-induced contraction of rat aortic preparations in a concentration-dependent manner (IC50 values: 19.4, 7.9, 10.1, 5.1 and 3.6 microM, respectively). These results suggest that pinane glycosides and galloylglucoses might be the components responsible for the vasorelaxant properties of the rootbark extract of P. moutan, and their vasorelaxant effects may be mediated through increases in the release of nitric oxide from endothelial cells.

  Effects of four Si-Wu-Tang's constituents and their combination on irradiated mice.:

 Biol Pharm Bull. 2006; 29(7):1378-82 (ISSN: 0918-6158).Liang QD; Gao Y; Tan HL; Guo P; Li YF; Zhou Z; Tan W; Ma ZC; Ma BP; Wang SQ.Beijing Institution of Radiation Medicine, China.
 Effects of four Si-Wu-Tang (SWT)'s constituents, fructose (Fru), paeoniflorin (Pae), ferulic acid (FA), tetramethyl pyrazine (TP), and their combination on irradiated mice as model of anaemia were investigated, with the purpose of further understanding the relationship between SWT's constituents and activities. Similarly to SWT, oral administration of Fru, Pae, FA, TP and their combination, to some extent, all showed effects of increasing the number of peripheral leukocyte and increasing four types of progenitor cells in bone marrow, including colony-forming unit-granulocyte-macrophage (CFU-GM), colony-forming unit-mature erythroid (CFU-E), colony-forming unit-immature erythroid (BFU-E) and colony-forming unit-multipotential (CFU-mix). Pae and FA showed significant body weight reducing effect, which were largely abolished when they were combined with Fru and TP. The SWT, Fru and combination significantly increased the thymus index while Pae significantly decreased it. Both SWT and TP significantly increased the spleen index but the combination did not. The results suggested that multiple constituents contribute to the promoting effect of SWT on hematopoiesis. Although being a very common compound in plants, the Fru has a special contribution to SWT's effect, which cannot be neglected. It may be an important active constituent that is responsible for SWT's promoting effect on hematopoiesis and immunity. Another suggestion is that when being combined, some effect of one constituent, sometimes is unexpected side effect, may be abolished by other. This may reflect the advantage of multiple constituent characteristics possessed by most TCMs.

  Determination of glycosides and sugars in Moutan Cortex by capillary electrophoresis with electrochemical detection.:

 J Pharm Biomed Anal. 2006; 41(1):129-34 (ISSN: 0731-7085).Chen G; Zhang L; Zhu Y.Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. gangchen@fudan.edu.cn
 A method based on capillary electrophoresis with electrochemical detection has been developed for the separation and determination of paeoniflorin, sucrose, paeonoside, glucose, and fructose in Moutan Cortex for the first time. Effects of several important factors such as the concentration of NaOH, separation voltage, injection time, and detection potential were investigated to acquire the optimum conditions. The detection electrode was a 300 microm diameter copper disc electrode at a working potential of +0.60 V (versus saturated calomel electrode (SCE)). The five analytes can be well-separated within 12 min in a 40 cm length fused silica capillary at a separation voltage of 12 kV in a 75 mM NaOH aqueous solution. The relation between peak current and analyte concentration was linear over about 3 orders of magnitude with detection limits (S/N = 3) ranging from 0.9 to 1.3 microM for all analytes. The proposed method has been successfully applied to monitor glycoside and sugar contents in the real plant samples with satisfactory assay results.

  Quality evaluation of cortex moutan by high performance liquid chromatography coupled with diode array detector and electrospary ionization tandem mass spectrometry.:

 Chem Pharm Bull (Tokyo). 2006; 54(9):1271-5 (ISSN: 0009-2363).He Q; Ge ZW; Song Y; Cheng YY.Department of Chinese Medicine Science & Engineering, Zhejiang University, 148 Tianmushan Road, Hangzhou 310027, People's Republic of China.
 An high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) and electrospray ionization tandem mass spectrometry (ESI/MS(n)) method was developed for quality evaluation of Cortex Moutan through identification of common constituents based on chromatographic fingerprints and determination of key pharmacological compounds. The representative chromatographic fingerprints of Cortex Moutan were obtained by analyzing 10 batches of samples under the optimized HPLC conditions and the results showed that the chromatographic profiles of the analyzed samples were very similar. Total of nineteen common peaks were detected and seventeen of them were identified rapidly by their characteristic UV profile and the information of molecular structure provided by ESI/MS(n) experiments. Simultaneously, five key pharmacological compounds, namely gallic acid, oxypaeoniflorin, paeoniflorin, benzoylpaeoniflorin and paeonol, were determined by the validated HPLC-DAD method. The linear calibration curves were acquired with correlation coefficients higher than 0.999. The precisions of intra-day and inter-day were not exceeding 3.1%, and the recoveries of five analytes were from 92.86 to 99.35%. This developed method that combined the chromatographic fingerprints and quantification assay ensured the phytoequivalence and pharmacological effects of Cortex Moutan and was successfully applied to the quality control of Cortex Moutan.


  Protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model.:

 Exp Neurol. 1997; 146(2):518-25 (ISSN: 0014-4886)
 Protective effects of peony root extract and its components on neuron damage in the CA1 area of the hippocampus induced by the cobalt focus epilepsy model were examined. Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were completely prevented when peony root extract was continuously administered orally at 1 g/kg/day for 30 days prior to cobalt application. Component crude gallotannin fraction showed marked but incomplete protective action. A combination of crude gallotannin fraction and paeoniflorin showed complete protective action in the same way as peony root extract against neuron damage although use of paeoniflorin alone had no effect. These findings together with our previous reports indicate that peony root extract and its component, gallotannin, have excellent protective effects on neuron damage in addition to anticonvulsant action by prior oral administration.

  Studies on immunoregulating effect of monkshood root and peony root used singly and in combination.:

 Zhongguo Zhong Yao Za Zhi. 2002; 27(7):541-4 (ISSN: 1001-5302).Qin L; Zhang SH; Li XL.Shandong University of TCM, Jinan 250014, Shandong, China.
 OBJECTIVE: To investigate the abirritation and antiinflammation effects of Monkshood Root and Peony Root used singly and in combination, and to find the enhanced effects of the two drugs used in combination; To observe the effect of Monkshood Root and Peony Root used singly and in combination by studing the immunoregulation function in experimental animals. METHOD: The response of delayed type hypersensitivity in mice, the phagocytosis of abdominal macrophages in mice, and the production of special antibodies in mice were observed. RESULT: The two drugs used in combination could increase phagocytosic function of mononuclear macrophagocyte in hypoimmuitic model mice, and inhibit the responses of delayed type hypersensitivity in the hyperimmunitic model mice and the nonimmunosuppressive treated mice, with nosignificant effect on the production of special antibodies in mice. CONCLUSION: In accordance with the mechanism of the disorder between the anti-inflammation effect and the induce-inflammation effect on arthritis in the immune system, these data show the bidirectional effect of the two drugs used in combination on the immune responses, which may be one of the main mechanisms of treating arthralgia due to wind-dampness.

  Paeoniflorin, a major constituent of peony root, reverses muscarinic M1-receptor antagonist-induced suppression of long-term potentiation in the rat hippocampal slice.:

 We previously reported that paeoniflorin but not albiflorin, components of peony root, produced ameliorative effects on scopolamine-induced spatial cognitive impairment in rats. In this study, we examined the effects of paeoniflorin and muscarinic receptor antagonists on long-term potentiation (LTP) of population spike recorded from the CA1 region of rat hippocampal slices. Bath applications of an M1- and M2-receptor antagonist scopolamine and a selective M1-receptor antagonist pirenzepine, at a concentration of 10 microM, significantly suppressed LTP, whereas AF-DX116, a selective M2-receptor antagonist, failed to affect it. Paeoniflorin (0.1-1 microM), which alone was ineffective on LTP induction, significantly reversed the suppressive effects of scopolamine and pirenzepine (10 microM). In contrast, albiflorin (0.1- 1 microM) had no effect on the scopolamine-induced LTP suppression. These results suggest that paeoniflorin reversal of the muscarinic M1-receptor-mediated inhibition of LTP may be implicated in the ameliorative effect of paeoniflorin on spatial cognitive impairment caused by cholinergic dysfunction.

  Ameliorative effects of paeoniflorin, a major constituent of peony root, on adenosine A1 receptor-mediated impairment of passive avoidance performance and long-term potentiation in the hippocampus.:

 Biol Pharm Bull. 2001; 24(5):496-500 (ISSN: 0918-6158)
 We examined the effects of paeoniflorin on adenosine A1 receptor-mediated memory disturbance in the mouse passive avoidance test and inhibition of long-term potentiation (LTP) in the rat hippocampal CA1 region. The pretraining administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) significantly impaired the retention performance determined 24 h after the training test. The intraperitoneal injections of paeoniflorin and the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) significantly attenuated the deficit in retention performance caused by CPA. The in vitro studies revealed that adenosine (1 and 10 microM) dose dependently reduced both the population spike (PS) amplitudes and the tetanic stimulation-induced LTP in the hippocampus. DPCPX, at the concentration (0.1 microM) that had no effect on PS amplitudes or LTP induction, significantly reversed the suppressive effects of adenosine on both indices. Paeoniflorin also dose dependently reversed 10 microM adenosine-induced suppression of LTP but had no effect on PS reduced by adenosine. These results suggest that paeoniflorin ameliorates memory disruption mediated by adenosine A1 receptor and that modulation of adenosine-mediated inhibition of LTP in the hippocampus is implicated in its beneficial effect on learning and memory impairment in rodents.

  Restorative effect of repetitive administration of Shaoyao-Gancao-tang on bioavailability of paeoniflorin reduced by antibacterial synthetic drugs treatment in rats.:

 Biol Pharm Bull. 2003; 26(11):1585-90 (ISSN: 0918-6158)
 Paeoniflorin (PF) is an active glucoside in Shaoyao (peony root), and is transformed into an antispasmodic metabolite, paeonimetabolin-I (PM-I), by intestinal bacteria in the gut after oral administration of Shaoyao or Shaoyao-Gancao-tang (SGT). SGT is a pain-relieving traditional Chinese formulation and is often used together with antibacterial synthetic drugs, such as amoxicillin and metronidazole (AMPC-MET), in peptic ulcer therapy. Since the bioavailability of PF in SGT has been reported to be significantly reduced by co-administered antibacterial drugs, we investigated how to minimize this reducing effect of antibacterial treatment in the present study. We found that repetitive administration of SGT starting 24 h after AMPC-MET treatment rapidly restored the plasma PM-I concentration from SGT reduced by AMPC-MET, due to its restorative effect on the decreased PF-metabolizing activity of intestinal bacteria in rat feces. The present findings suggest that it may be clinically useful to administer SGT repetitively, starting 1 or 2 d after treatment with a mixture of AMPC-MET during their combination therapy, to accelerate the recovery of the reduced bioavailability of PF in SGT. Similar administration regimens may also be useful in other combination therapies involving traditional Chinese formulations and antibacterial synthetic drugs to ensure the efficacy of the bioactive glycosides in the formulations.


  Scientific References:

  1.Paeoniflorin and Peony Root Extract.White.Red.
  2.Modern Researches of White Peony Root,Red Peony Root.Paeoniflorin and Peony Root Extract.