Immune Regulation and Anti-inflammatory Effects of Isogarcinol Extracted from Garcinia mangostana L. against Collagen-Induced Arthritis

Abstract

Isogarcinol is a natural compound that we extracted from Garcinia mangostana L., and we were the first to report that it is a new immunosuppressant. In the present study, we investigated the immune regulation and anti-inflammatory effects of isogarcinol on collagen-induced arthritis (CIA) and explored its potential mechanism in the treatment of rheumatoid arthritis. The oral administration of isogarcinol significantly reduced clinical scores, alleviated cartilage and bone erosion, and reduced the levels of serum inflammatory cytokines in CIA mice. Isogarcinol inhibited xylene-induced mouse ear edema in vivo. In vitro, isogarcinol decreased iNOS and COX-2 mRNA expression and NO content by inhibiting NF-κB expression. Furthermore, isogarcinol decreased the activity of NFAT and inhibited IL-2 expression. The mechanism of action of isogarcinol is associated with down-regulation of both autoimmune and inflammatory reactions.

Isogarcinol Extracted from Garcinia mangostana L. Ameliorates Systemic Lupus Erythematosus-like Disease in a Murine Model

“…19,20 The inflammatory cytokines TNF-α, IL-1β, and IL-6 produced by macrophages play an essential role in responding to infection and inflammation. Moreover, the kidney mRNA levels of TNF-α and IL-1β as well as protein levels in lupus-prone MRL/lpr mice have been found to increase.…”

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

“…Suppression of CIA and ear edema, reduced bone and cartilage damage and low concentrations of inflammatory cytokines in vivo …”

“…Reduced bone and cartilage damage as well as low concentrations of inflammatory cytokines were observed upon isogarcinol treatment of CIA mice. Suppression of the expression of NF‐ κ B, iNOS, COX‐2, NFAT and IL‐2 was observed after treatment with isogarcinol from in vitro experiments . The same group investigated the activity of isogarcinol against systemic lupus erythematosus (SLE).…”

“…Suppression of CIA and ear edema, reduced bone and cartilage damage and low concentrations of inflammatory cytokines in vivo [68] Suppression of NF-κB, iNOS, COX-2, NFAT and IL-2 [68] Systemic lupus erythematosus (SLE) disease Protection of kidneys in vivo, reduced renal histopathology and proteinuria, normalized serum biochemical indicator [69] -Psoriasis Amendment of skin lesions induced by imiquimod, less toxic to liver and kidneys than cyclosporine A in vivo [70] Suppression of IL-23/Th17 axis genes [70] Macrophages Beneficial effects on macrophages and peritoneal macrophages, reduced excretion of lysosomal enzymes in vivo [71] Suppression of collagenase, elastase and hyaluronidase excretion [71] Liver inflammation and acute liver failure Prolonged survival of mice with acute liver failure [73] Suppression of histone acetylation [73] Endometriosis Suppression of fibrosis in Klf11 À /À animals [74] Restoration of transcription factor KLF11 function, suppression of scar-tissue collagen (COL1 A1/ Col1a1) [74] Obesity-related inflammation Inhibition of high fat diet (HFD)-induced obesity in vivo [75] Increased levels of intestinal commensal bacteria Akkermansia, suppression of glutamate pyruvate transaminase, cholesterol and triacylglycerol [75] Diabetes Normalization of diabetic parameters in vivo [77]…”

“…Suppression of the expression of NF-κB, iNOS, COX-2, NFAT and IL-2 was observed after treatment with isogarcinol from in vitro experiments. [68] The same group investigated the activity of isogarcinol against systemic lupus erythematosus (SLE). Mice with chronic graft-versus-host disease (cGVHD, an SLE in vivo model) were treated with isogarcinol (60 mg/kg) leading to reduced renal histopathology and proteinuria as well as normalized serum biochemical indicator.…”