Immunomodulation of Rheum tanguticum polysaccharide (RTP) on the immunosuppressive effects of dexamethasone (DEX) on the treatment of colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid.
Dexamethasone (DEX) is still the main choice for colitis, although the immunosuppressive side effects are still the troublesome problems to overcome. In our previous study, Rheum tanguticum polysaccharide (RTP), extracted from traditional Chinese medicine rhubarb, targeted mannose receptor, showed immunoregulatory effect on the balance of Th1 and Th2 polarization in colitis rats. For the present study, we hypothesized that RTP could regulate the immunosuppressive effects of DEX. Taking advantage of the colon delivery ability of the polysaccharide, we prepared the double emulsion of RTP microsphere containing DEX to investigate the potential immunoregulatory effects of RTP on DEX immunosuppression in TNBS-induced colitis in rats. As expected, DEX-RTP microsphere showed not only significant immunomodulatory effects, but also strong anti-inflammation. The microsphere balanced enteric bacteria disorder, decreased TLR4 activation and promoted the balance of Th1 and Th2 polarization, inhibited NF-kappaB activity. Especially, DEX-RTP showed significant colon injury reparation. DEX alone exhibited a strong anti-inflammatory effect by suppressing MPO activity, down-regulate NF-kappaB activity and Th1 cytokines production. However, DEX showed severe immunosuppressive effects. It aggravated the intestinal commensal bacteria disorder, induced thymus atrophy and the further imbalance of Th1/Th1 cytokine polarization. RTP showed significant immunoregulatory effects. A significant protection on the intestinal bacterial balance, TLR4 and NF-kappaB activation decreased, and Th1/Th2 cytokine production balance were showed in RTP. In conclusion, DEX-RTP microsphere delivered DEX directly to the colon avoiding the absorption at the upper intestinal tract and showed synergistic effects on colitis both from the strong anti-inflammatory effects of DEX and from the immunoregulation of RTP.
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
Li
L
Liu
Shifang
S
Yuan
Yin
Y
Long
Zhenjun
Z
Guo
Yang
Y
Sun
Yuhua
Y
Li
Yinbo
Y
Niu
Chen
C
Li
Qibing
Q
Mei
D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000517:prevention & control; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D007166:Immunosuppressive Agents; D016328:NF-kappa B; D053769:Nanocapsules; D011134:Polysaccharides; D051197:Toll-Like Receptor 4; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid