Amelioration of Experimental Autoimmune Encephalomyelitis by Isogarcinol Extracted from Garcinia mangostana L. Mangosteen

Abstract

Isogarcinol is a new natural immunosuppressant that was extracted from Garcinia mangostana L. in our laboratory. Knowledge of its effects on treatable diseases and its mechanism of action is still very limited. In this study, we explored the therapeutic effect of isogarcinol in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Treatment with oral 100 mg/kg isogarcinol markedly ameliorated clinical scores, alleviated inflammation and demyelination of the spinal cord, and reduced intracranial lesions in EAE mice. The percentages of Th cells and macrophages were also strongly reduced. Isogarcinol appeared to act by inhibiting T helper (Th) 1 and Th17 cell differentiation via the janus kinase/signal transducers and activators of transcription pathway and by impairing macrophage function. Our data suggest that isogarcinol has the potential to be an effective therapeutic agent of low toxicity for treating MS and other autoimmune diseases.

Xanthones from the Pericarp of Garcinia mangostana

“…In Southeast Asia, mangosteen fruit shell is a traditional folk medicine used for the treatment of diarrhea, sprains, typhoid, ulcers, skin infections, and is used as an anti-inflammatory and for sterilization. In the previous extensive investigations on the phytochemical constituents of G. mangostana [ 2 ], G. hanburyi [ 3 ], G. bracteata [ 4 ], G. cowa [ 5 ], etc., Garcinia species are known to be rich in a variety of benzophenones and xanthones, some of which showed a wide range of biological and pharmacological activities including cytotoxic, anti-inflammatory, antimicrobial, and antifungal activity, as well as immune regulation and the amelioration of experimental autoimmune encephalomyelitis [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. A dietary α-mangostin isolated from genus Garcinia had anticancer and antiproliferative properties in leukemia as well as prostate, breast, colorectal, and brain cancers [ 14 ], and another caged polyprenylated xanthone—gambogic acid—was exhibited to have anti-proliferative and pro-apoptotic effects on hepatocarcinoma, gastric carcinoma, lung carcinoma, breast cancer, and glioma in vivo and in vitro [ 15 ].…”

A polypeptide inhibitor of calcineurin blocks the calcineurin-NFAT signalling pathway in vivo and in vitro

“…In our previous studies, we focussed on screening small molecule inhibitors of CN. We used CN as a target enzyme to screen its inhibitors and identified some small molecule compounds, such as quercetin 21 , kaempferol 22 , and isogarcinol 23 , 24 . For example, isogarcinol inhibits the activity of CN in vitro and has an immunosuppressive effect on experimental autoimmune encephalomyelitis.…”

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

“…Experimental autoimmune encephalomyelitis (EAE) is a preclinical murine model for the investigation of multiple sclerosis (MS). EAE mice treated with isogarcinol (100 mg/kg/day, orally) showed lower degrees of intracranial lesions and demyelination of the spinal cord due to drug interference with the JAK/STAT signaling pathway . Thus, isogarcinol can be a little toxic alternative to currently applied drugs for the treatment of MS. Intrathecal injections of garcinol in rats (L 5 spinal nerve ligation/SNL model) prolonged thermal withdrawal latency (TWL) and, thus, reduced neuropathic pain likely via suppression of acetyl‐p65 .…”

“…Suppression of osteoclastogenesis in vitro and in vivo [79] Suppression of PI3 K/Akt, MAPK and NF-κB signaling [79] Multiple sclerosis, experimental autoimmune encephalomyelitis Reduced intracranial lesions and demyelination of the spinal cord in vivo [80] Targeting of JAK/STAT signaling pathway [80] Neuropathic pain Prolonged thermal withdrawal latency [81] Suppression of acetyl-p65 [81]…”