Paeoniflorin

Paeoniflorin is a herbal constituent extracted from the root of Paeonia albiflora Pall. Target: Others Paeoniflorin (PF) is the principal bioactive component of Radix Paeo- niae alba, which is widely used in Traditional Chinese Medicine for the treatment of neurodegenerative disorders such as Parkinson's disease(PD) [1]. Paeoniflorin, a compound found in white peony that inhibited the production of testosterone and promoted the activity of aromatase, which converts testosterone into estrogen [2]. Treatment of cells with paeoniflorin but not glycyrrhizin resulted in enhanced phosphorylation and acquisition of the deoxyribonucleic acid-binding ability of heat shock transcription factor 1 (HSF1), as well as the formation of characteristic HSF1 granules in the nucleus, suggesting that the induction of HSPs by paeoniflorin is mediated by the activation of HSF1. Also, thermotolerance was induced by treatment with paeoniflorin but not glycyrrhizin. Paeoniflorin had no toxic effect at concentrations as high as 80 microg/ mL (166.4 microM). To our knowledge, this is the first report on the induction of HSPs by herbal medicines [3].

References:
[1]. Cao, B.Y., et al., Paeoniflorin, a potent natural compound, protects PC12 cells from MPP+ and acidic damage via autophagic pathway. J Ethnopharmacol, 2010. 131(1): p. 122-9. [2]. Takeuchi, T., et al., Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production. Am J Chin Med, 1991. 19(1): p. 73-8. [3]. Yan, D., et al., Paeoniflorin, a novel heat shock protein-inducing compound. Cell Stress Chaperones, 2004. 9(4): p. 378-89.

Antihyperglycemic effects of paeoniflorin and 8-debenzoylpaeoniflorin, glucosides from the root of Paeonia lactiflora.[Pubmed:9270377]

Planta Med. 1997 Aug;63(4):323-5.

Paeoniflorin and 8-debenzoylPaeoniflorin were isolated from the dried root of Paeonia lactiflora Pall. (Ranunculaceae). They produced a significant blood sugar lowering effect in streptozotocin-treated rats and had a maximum effect at 25 min after treatment. This hypoglycemic action was also observed in normoglycemic rats only at 1 mg/kg. The antihyperglycemic activity of 8-debenzoylPaeoniflorin seems lower than that of Paeoniflorin. Plasma insulin was not changed in Paeoniflorin-treated normoglycemic rats indicating an insulin-independent action. Also, this glucoside reduced the elevation of blood sugar in glucose challenged rats. Increase of glucose utilization by Paeoniflorin can thus be considered. There are no previous data showing the hypoglycemic activity of Paeoniflorin and/or 8-debenzoylPaeoniflorin in rats.

Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis.[Pubmed:17386414]

Int Immunopharmacol. 2007 May;7(5):662-73.

Paeoniflorin (Pae), a monoterpene glucoside, is one of the main bioactive components of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora. TGP has anti-inflammatory and immunoregulatory effects. In this study, we investigated the effects of Pae on inflammatory and immune responses to the mesenteric lymph node (MLN) lymphocytes and the mechanisms by which Pae regulates beta 2-adrenergic receptor (beta 2-AR) signal transduction in adjuvant arthritis (AA) rats. The onset of secondary arthritis in rats appeared around day 14 after injection of Freund's complete adjuvant (FCA). Remarkable secondary inflammatory response and lymphocytes proliferation were observed in AA rats, along with the decrease of anti-inflammatory cytokines interleukin (IL)-4 and transforming growth factor-beta 1 (TGF-beta 1) of MLN lymphocytes, and the increase of pro-inflammatory cytokine IL-2. The administration of Pae (50, 100 mg kg(-1), days 17-24) significantly diminished the secondary hind paw swelling and arthritis scores, reversed the changes of cytokines as discussed above, and further decreased the lowered proliferation of MLN lymphocytes in AA rats. In vitro, Pae restored the previously increased level of cAMP of MLN lymphocytes at the concentrations of 12.5, 62.5 and 312.5 mg l(-1). Meanwhile, Pae increased protein expressions of beta 2-AR and GRK2, and decreased that of beta-arrestin 1, 2 of MLN lymphocytes in AA rats. These results suggested that Pae might induce the Th1 cells immune tolerance, which then shift to Th2, Th3 cells mediated activities to take effect the anti-inflammatory and immunoregulatory effects. The mechanisms of Pae on beta 2-AR desensitization and beta 2-AR-AC-cAMP transmembrane signal transduction of MLN lymphocytes play crucial roles in pathogenesis of this disease.

Inhibitory effect of paeoniflorin on methylglyoxal-mediated oxidative stress in osteoblastic MC3T3-E1 cells.[Pubmed:24916708]

Phytomedicine. 2014 Sep 15;21(10):1170-7.

PURPOSE: Methylglyoxal (MG) has been suggested to be one major source of intracellular reactive carbonyl compounds. In the present study, the effect of Paeoniflorin on MG-induced cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. METHODS: Osteoblastic MC3T3-E1 cells were pre-incubated with Paeoniflorin before treatment with MG, and markers of oxidative damage and mitochondrial function were examined. RESULTS: Pretreatment of MC3T3-E1 cells with Paeoniflorin prevented the MG-induced cell death and formation of intracellular reactive oxygen species, cardiolipin peroxidation, and protein adduct in osteoblastic MC3T3-E1 cells. In addition, Paeoniflorin increased glutathione level and restored the activity of glyoxalase I to almost the control level. These findings suggest that Paeoniflorin provide a protective action against MG-induced cell damage by reducing oxidative stress and by increasing MG detoxification system. Pretreatment with Paeoniflorin prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate loss. Additionally, the nitric oxide and nuclear respiratory factor 1 levels were significantly increased by Paeoniflorin, suggesting that Paeoniflorin may induce mitochondrial biogenesis. Paeoniflorin treatment decreased the levels of proinflammatory cytokines such as TNF-alpha and IL-6. CONCLUSIONS: These findings indicate that Paeoniflorin might exert its therapeutic effects via upregulation of glyoxalase system and mitochondrial function. Taken together, Paeoniflorin may prove to be an effective treatment for diabeteic osteopathy.

[Role of PI3K/Akt pathway in effect of paeoniflorin against Abeta25-35-induced PC12 cell injury].[Pubmed:25751960]

Zhongguo Zhong Yao Za Zhi. 2014 Oct;39(20):4045-9.

OBJECTIVE: To study the role of PI3K/Akt pathway in the neuroprotective effect of Paeoniflorin on PC12 cells. METHOD: The Paeoniflorin group (5, 10, 20 mumol . L(-1)) was pretreated for 30 min, and then added with Abeta25-35 (20 mumol . L(-1)) for interaction for 24 h. Inhibitor LY294002 (10 mumol . L(-1)) was pretreated for 30 min before the action of Paeoniflorin (10 mumol . L(-1)). The MTT colorimetric method was used to detect the cell viability. The apoptosis rate was tested by the FITC-Annexin V/PI staining. The protein expression of p-AKT, Bax, Bcl-2 and cleaved caspase-3 protein were detected by Western blot analysis. RESULT: Paeoniflorin could significantly inhibit the Abeta25-35-induced PC12 cell toxicity and apoptosis. Its protection effect may be achieved by up- regulating AKT phosphorylation level, increasing Bcl-2 protein expression, reducing Bax protein expression, inhibiting the activation of caspase-3. Inhibitor LY294002 could weaken the above protective effects of Paeoniflorin. CONCLUSION: Paeoniflorin could activate PI3K/Akt signaling pathway to protect the PC12 cell injury induced by Abeta25-35.

Antiallergic effect of the root of Paeonia lactiflora and its constituents paeoniflorin and paeonol.[Pubmed:18449501]

Arch Pharm Res. 2008 Apr;31(4):445-50.

The root of Paeonia lactiflora PALL (PL, Family Paeoniaceae) has been used frequently as an antipyretic and anti-inflammatory agent in traditional medicines of Korea, China and Japan. To evaluate antiallergic effect of PL, we isolated its main constituents, Paeoniflorin and paeonol, and evaluated in vivo their inhibitory effects against passive cutaenous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors induced by compound 48/80. PL, Paeoniflorin and paeonol potently inhibited PCA reaction and scratching behaviors in mice. Paeoniflorin exhibited the most potent inhibition against scratching behaviors and the acetic acid-induced writhing syndrome in mice. Paeonol most potently inhibited PCA reaction and mast cells degranulation. These findings suggest that PL can improve IgE-induced anaphylaxis and scratching behaviors, and may be due to the effect of its constituents, Paeoniflorin and paeonol.