Polysaccharide from Angelica Sinensis Suppresses Inflammation and Reverses Anemia in Complete Freund’s Adjuvant-induced Rats

Abstract

The anti-inflammatory and antianemic activities of Angelica sinensis polysaccharide (ASP) isolated from roots of Angelica sinensis (AS) was investigated in a complete Freund’s adjuvant (CFA)-induced arthritic rat model. It was observed that serum iron (SI) and total iron binding capacity (TIBC) levels were elevated after 4-week oral administration of ASP. Red blood cell (RBC) count and hemoglobin (Hb) concentrations were ameliorated as well. Moreover, inflammatory cytokines IL-6 and TNF-a were decreased strikingly in CFA-induced arthritic rats after treatment of ASP. Evidence also showed that ASP strongly inhibited hepcidin expression through the Janus kinase/signal transducers and activators of transcription (JAK2/STAT3) pathway. Furthermore, ASP exhibited reduced primary and secondary lesions in adjuvant arthritis, attenuating synovitis and inflammatory joint damage. Data presented in this article collectively indicated that ASP significantly decreased proinflammatory cytokines (TNF-a, IL-6), which might play a crucial role in the CFA-induced arthritic rats, and had a therapeutic effect on adjuvant arthritis in rats. Results of Western blot analysis indicated that ASP inhibited the activation of IL-6/JAK2/STAT3 signaling pathway in the CFA-induced arthritic rats.

Keywords

polysaccharide / Angelica sinensis / arthritis / inflammation / anemia

References

[1] NikiphorouE, de LusignanS, MallenC, et al.. Haematological abnormalities in new-onset rheumatoid arthritis and risk of common infections: a population-based study. Rheumatology (Oxford), 2019[Epub ahead of print]

[2] GangatN, WolanskyjAP. Anemia of chronic disease. Semin Hematol, 2013, 50(3): 232-238

[3] KimEY, MoudgilKD. Immunomodulation of autoimm-une arthritis by pro-inflammatory cytokines. Cytokine, 2017, 98: 87-96

[4] ChoyE. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford), 2012, 51(Suppl5): v3-v11

[5] De DomenicoI, ZhangTY, KoeningCL, et al.. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest, 2010, 120(7): 2395-2405

[6] WeiWL, ZengR, GuCM, et al.. Angelica sinensis in China-A review of botanical profile, ethnopharmacology, phytochemistry and chemical analysis. J Ethnoph-armacol, 2016, 190: 116-141

[7] ChenXP, LiW, XiaoXF, et al.. Phytochemical and pharmacological studies on Radix Angelica sinensis. Chin J Nat Med, 2013, 11(6): 577-587

[8] XiaoH, XiongL, SongX, et al.. Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil. Int J Mol Sci, 2017, 1811: E2265

[9] ZhaoL, WangY, ShenHL, et al.. Structural characterization and radioprotection of bone marrow hematopoiesis of two novel polysaccharides from the root of Angelica sinensis (Oliv.) Diels. Fitoterapia, 2012, 83(8): 1712-1720

[10] TianS, HaoC, XuG, et al.. Optimization conditions for extracting polysaccharide from Angelica sinensis and its antioxidant activities. J Food Drug Anal, 2017, 25(4): 766-775

[11] ZhuangC, XuNW, GaoGM, et al.. Polysaccharide from Angelica sinensis protects chondrocytes from H2O2-induced apoptosis through its antioxidant effects in vitro.. Int J Biol Macromol, 2016, 87: 322-328

[12] ChengY, ZhouJ, LiQ, et al.. The effects of polysaccharides from the root of Angelica sinensis on tumor growth and iron metabolism in H22-bearing mice. Food Funct, 2016, 7(2): 1033-1039

[13] LeeJG, HsiehWT, ChenSU, et al.. Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells. J Ethnopharmacol, 2012, 139(3): 739-745

[14] LiY, HetetG, MaurerAM, et al.. Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM-CSF. Br J Haematol, 1994, 87(3): 471-476

[15] ZhangY, ChengY, WangN, et al.. The action of JAK, SMAD and ERK signal pathways on hepcidin suppression by polysaccharides from Angelica sinensis in rats with iron deficiency anemia. Food Funct, 2014, 5(7): 1381-1388

[16] ZhangY, LiMM, ZengF, et al.. Study to establish the role of JAK2 and SMAD1/5/8 pathways in the inhibition of hepcidin by polysaccharides from Angelica sinensis. J Ethnopharmacol, 2012, 144(2): 433-440

[17] WangK, WuJ, ChengF, et al.. Acidic Polysaccharide from Angelica sinensis Reverses Anemia of Chronic Disease Involving the Suppression of Inflammatory Hepcidin and NF-kappaB Activation. Oxid Med Cell Longev, 2017, 2017: 7601592

[18] ZhangY, ZhouT, WangH, et al.. Structural characterization and in vitro antitumor activity of an acidic polysaccharide from Angelica sinensis (Oliv.) Diels. Carbohydr Polym, 2016, 147: 401-408

[19] DallalioG, FleuryT, MeansRT. Serum hepcidin in clinical specimens. Br J Haematol, 2003, 122(6): 996-1000

[20] CuiX, WangR, BianP, et al.. Evaluation of antiarthritic activity of nimbolide against Freund’s adjuvant induced arthritis in rats. Artif Cells Nanomed Biotechnol, 2019, 47(1): 3391-3398

[21] GuidaC, AltamuraS, KleinFA, et al.. A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia. Blood, 2015, 125(14): 2265-2275

[22] AkchurinO, SureshbabuA, DotySB, et al.. Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease. Am J Physiol Renal Physiol, 2016, 311(5): F877-F889

[23] Am J Occup Ther, 2017, 71(1):

[24] CavallaroF, DucaL, PisaniLF, et al.. Anti-TNF-Mediated Modulation of Prohepcidin Improves Iron Availability in Inflammatory Bowel Disease, in an IL-6-Mediated Fashion. Can J Gastroenterol Hepatol, 2017, 2017: 6843976

[25] ReinP, MuellerRB. Treatment with Biologicals in Rheumatoid Arthritis: An Overview. Rheumatol Ther, 2017, 4(2): 247-261

[26] FraenkelPG. Anemia of Inflammation: A Review. Med Clin North Am, 2017, 101(2): 285-296

[27] GarbersC, Aparicio-SiegmundS, Rose-JohnS. The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol, 2015, 34: 75-82

[28] TianL, GoldsteinA, WangH, et al.. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature, 2017, 544(7649): 250-254