peoniflorin and Autoimmune-Diseases

As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhibit inflammation in the animal models of autoimmune diseases, such as experimental arthritis, psoriatic mice and experimental autoimmune encephalomyelitis, and so on. Pae modulates the functions and activation of immune cells, decreases inflammatory medium production, and restores abnormal signal pathway. Pae could balance the subsets of immune cells through inhibiting abnormal activated cell subsets and restoring regulatory cell subsets. Pae could regulate signaling pathways (GPCR pathway, MAPKs /NF-κB patway, PI3K /Akt /mTOR pathway, JAK2 /STAT3 pathway, TGFβ /Smads, and etc.). TGP is composed of Pae, hydroxyl-paeoniflorin, paeonin, albiflorin and benzoylpaeoniflorin etc. Pae accounts for more than 40% of TGP. Like Pae, TGP has anti-inflammatory and immune regulatory effects. TGP has been widely used to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, allergic contact dermatitis, and etc. in China. Furthermore, TGP has some superior features with immune regulation, gentle effect, many indications and few adverse drug reactions. These findings suggest that TGP may be a promising anti-inflammatory and immune drug with soft regulation and has more superiority in the treatment of AIDs. Currently, TGP is used for the treatment of RA, SLE and other AIDs in more than 1000 hospitals in China, which obtained great social and economic benefits.

Topics: Animals; Anti-Inflammatory Agents; Autoimmune Diseases; Glucosides; Humans; Immunologic Factors; Monoterpenes; Paeonia

It has been widely accepted that macrophages are divided into M1 "pro-inflammatory" macrophages and M2 "anti-inflammatory" macrophages and an uncontrolled macrophage polarization plays an important role in the pathogenesis of different diseases. As the main substance of total glucosides of peony, paeoniflorin (PF), has been widely used to treat autoimmune and autoinflammatory diseases for years. Mechanistically, PF has been found to alter activities of many immune cells, which could further reduce inflammation and tissue damage. However, whether and how PF affects macrophages activities in vitro remains unknown. In current study, using M1 and M2 cells generated from mouse bone marrow precursors, we explored the role of PF in regulating M1/M2 cells activity in vitro. The results showed that PF inhibited LPS-induced M1 activity by reducing iNOS expression and NO production via decreasing LPS/NF-κB signaling pathway; whereas, PF enhanced IL-4-provoked M2 function by up-regulating Arg-1 production and activity via increasing IL-4/STAT6 signaling pathway. Our new finding indicates that PF can suppress M1 cells activity and enhance M2 cells function simultaneously, which could help to ameliorate autoimmune and autoinflammatory diseases in clinical treatment.

Topics: Animals; Arginase; Autoimmune Diseases; Cell Polarity; Cells, Cultured; Glucosides; Immunomodulation; Interleukin-4; Lipopolysaccharides; Macrophage Activation; Macrophages; Male; Mice, Inbred BALB C; Monoterpenes; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Signal Transduction; STAT6 Transcription Factor

B cells are important in the development of autoimmune disorders through mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and targeting which reduces inflammation and tissue damage effectively but often leads to patients suffering from secondary infection. Paeoniflorin (PF) is the main substance of the Total glucosides of peony and has been widely used to treat autoimmune diseases for years. However, whether PF affects B cell activity remains unknown. In this study, using purified murine spleen B cells, we analyzed the effects of PF on B-cell function in vitro. We found that PF inhibited the expression of CD69/CD86 and the proliferation of B cells stimulated by LPS. In addition, PF reduced the B-cell differentiation and immunoglobulin production that was stimulated by LPS. Interestingly, PF did not alter B-cell activation and proliferation provoked by anti-CD40 or IL-4. These results indicated for the first time that PF inhibits B-cell activation, proliferation and differentiation by selectively blocking the LPS/TLR4 signaling pathway. Furthermore, our data suggest that PF selectively inhibits inflammation and tissue damage mediated by LPS-activated B cells but does not alter CD40/CD40L- or IL-4-provoked B-cell function in autoimmune diseases treatment, which might aid in protecting patients from secondary infection.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; B-Lymphocytes; Bipolar Disorder; Cell Differentiation; Cell Proliferation; Cells, Cultured; Female; Glucosides; Immunoglobulins; Lipopolysaccharides; Lymphocyte Activation; Mice, Inbred C57BL; Monoterpenes; Phytotherapy; Signal Transduction; Spleen; Toll-Like Receptor 4

The action mechanisms of Toki-shakuyakusan (TSS), one of Kampo-herbal medicine, on the clearance of immune complexes and macrophage function were investigated. In the in vivo study, oral administration of TSS enhanced the immune complexes clearance from the circulation in MRL Mp-lpr/lpr mice and C3H/He mice, but no effect was observed in the carbon clearance assay. In the in vitro study, TSS increased the binding of immune complexes to macrophages or Kupffer cells, and the digestion of immune complexes by Kupffer cells. By flow cytometric analysis, the expressions of Fc gamma 11/111 receptors and complement receptor 3 (CR3) on macrophages were increased by the treatment with TSS. Besides, it was also reported that the appearance of the activity was owe to the combination of Angelicae Radix and Atractylodis Lanceae Rhizoma, two of six ingredients of TSS. Both outer and inner dialysate of the extract of Angelicae Radix and Atractylodis Lanceae Rhizoma potentiated the binding of immune complexes to macrophages. Low molecular fraction was further fractionated by using colomn chromatography, and the active components were concentrated in fraction 5-C (named LMW5-C). In conclusion, one of the mechanism of enhancement of immune complexes clearance was thought to due to increase the immune complexes binding to macrophage though augment of Fc gamma 11/111 receptors and CR3 expression. And it was revealed that the active components were not only high moleculer substances but low molecular ones.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigen-Antibody Complex; Autoimmune Diseases; Benzoates; Bridged-Ring Compounds; Disease Models, Animal; Drugs, Chinese Herbal; Female; Glucosides; Macrophage-1 Antigen; Mice; Mice, Inbred MRL lpr; Monoterpenes; Receptors, IgG