Metabolomic and transcriptomic analyses of the anti-rheumatoid arthritis potential of xylopic acid in a bioinspired lipoprotein nanoformulation.

Autor: Alolga RN; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China., Opoku-Damoah Y; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Qld, 4072, Australia., Alagpulinsa DA; Massachusetts General Hospital Vaccine & Immunotherapy Center, Harvard Medical School, Boston, MA, 02129, USA., Huang FQ; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China., Ma G; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China., Chavez Leon MASC; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China., Kudzai C; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China., Yin X; State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing, 211198, China. Electronic address: ajian.517@163.com., Ding Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: dydszyzf@163.com.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2021 Jan; Vol. 268, pp. 120482. Date of Electronic Publication: 2020 Nov 27.
DOI: 10.1016/j.biomaterials.2020.120482
Abstrakt: Xylopic acid (XA), a diterpene kaurene and the major active ingredient of the African spice Xylopia aethiopica (Annonaceae), is reported to possess anti-inflammatory and analgesic properties. Here, we investigated the therapeutic potential of XA for rheumatoid arthritis (RA), a debilitating autoimmune inflammatory disease characterized by joint damage, in the complete Freund's adjuvant (CFA)-induced arthritis model in rats. We synthesized bioinspired reconstituted high-density lipoprotein (rHDL) nanoparticles loaded with purified XA crystals (rHDL/XA) that passively accumulate in inflamed joints of CFA-induced arthritic rats. Treatment with rHDL/XA minimized mononuclear cell infiltration of CFA-induced arthritic sites and ameliorated disease burden. Metabolomic and transcriptomic analyses revealed that the major molecular pathways perturbed following CFA-induced arthritis correlated with amino acid and lipid metabolism, which were restored to normal states by rHDL/XA treatment. This work demonstrates the anti-RA potential of XA in a nanoformulation and uncovers its underlying therapeutic mechanisms at the transcript and metabolite levels.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: