Abstract
Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4 T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4 T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NFB signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases.
References
- Molecular mechanisms of the action of vitamin A in Th17/Treg axis in multiple sclerosis. J. Mol. Neurosci. 57: 605–613, 2015. Crossref, Medline, ISI, Google Scholar .
- Multiple sclerosis: Mechanisms and immunotherapy. Neuron 97: 742–768, 2018. Crossref, Medline, ISI, Google Scholar .
- Combining the anticancer and immunomodulatory effects of Astragalus and Shiitake as an integrated therapeutic approach. Nutrients 13: 2564, 2021. Crossref, Medline, ISI, Google Scholar .
- Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine. J. Ethnopharmacol. 258: 112895, 2020. Crossref, Medline, ISI, Google Scholar .
- Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules 22: 134, 2017. Crossref, Medline, ISI, Google Scholar .
- T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 162: 1–11, 2010. Crossref, Medline, ISI, Google Scholar .
- Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother. Res. 28: 1275–1283, 2014. Crossref, Medline, ISI, Google Scholar .
- Experimental autoimmune encephalomyelitis (EAE) as animal models of multiple sclerosis (MS). Cold Spring Harb. Perspect. Med. 8: a028977, 2018. Crossref, Medline, ISI, Google Scholar
- Evaluation of the pharmaceutical properties and value of Astragali Radix. Medicines (Basel) 5: 46, 2018. Crossref, Medline, Google Scholar .
- Artemisia annua water extract attenuates DNCB-induced atopic dermatitis by restraining Th2 cell mediated inflammatory responses in BALB/c mice. J. Ethnopharmacol. 291: 115160, 2022. Crossref, Medline, ISI, Google Scholar .
- Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways. J. Neuroimmunol. 324: 26–34, 2018. Crossref, Medline, ISI, Google Scholar .
- FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration. Cell Mol. Immunol. 2: 439–448, 2005. Medline, ISI, Google Scholar .
- Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: Beneficial effects in experimental autoimmune encephalomyelitis. BMC Complement. Altern. Med. 13: 149, 2013. Crossref, Medline, ISI, Google Scholar .
- Connection between JAK/STAT and PPAR signaling during the progression of multiple sclerosis: Insights into the modulation of T-cells and immune responses in the brain. Curr. Mol. Pharmacol. 14: 823–837, 2021. Crossref, Medline, ISI, Google Scholar .
- The balance of Th17 versus Treg cells in autoimmunity. Int. J. Mol. Sci. 19: 730, 2018. Crossref, Medline, ISI, Google Scholar
- RGS10 deficiency ameliorates the severity of disease in experimental autoimmune encephalomyelitis. J. Neuroinflamm. 13: 24, 2016. Crossref, Medline, ISI, Google Scholar .
-
N. Multiple sclerosis and T lymphocytes : An entangled story. J. Neuroimmune. Pharmacol. 10: 528–546, 2015. Crossref, Medline, ISI, Google Scholar and Arbour, - Dexmedetomidine directs T helper cells toward Th1 cell differentiation via the STAT1-T-bet pathway. Biomed. Res. Int. 2021: 3725316, 2021. Crossref, Medline, ISI, Google Scholar .
- Microglia polarization from M1 toward M2 phenotype is promoted by Astragalus polysaccharides mediated through inhibition of miR-155 in experimental autoimmune encephalomyelitis. Oxid. Med. Cell Longev. 2021: 5753452, 2021. Crossref, Medline, ISI, Google Scholar .
- Multiple sclerosis: A complicated picture of autoimmunity. Nat. Immunol. 8: 913–919, 2007. Crossref, Medline, ISI, Google Scholar
- NF-B: Roles and regulation in different CD4 T-cell subsets. Immunol. Rev. 252: 41–51, 2013. Crossref, Medline, ISI, Google Scholar .
- C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Int. Immunopharmacol. 11: 29–38, 2011. Crossref, Medline, ISI, Google Scholar .
- Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice. Neuroscience 290: 279–287, 2015. Crossref, Medline, ISI, Google Scholar .
- Antioxidant and antibacterial insights into the leaves, leaf tea and medicinal roots from Astragalus membranaceus (Fisch.) Bge. Sci. Rep. 11: 19625, 2021. Crossref, Medline, ISI, Google Scholar .
- Inflammation in CNS neurodegenerative diseases. Immunology 154: 204–219, 2018. Crossref, Medline, ISI, Google Scholar .
- The PD-1/PD-Ls pathway is up-regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides. J. Neuroimmunol. 332: 78–90, 2019. Crossref, Medline, ISI, Google Scholar .
- CD226 attenuates Treg proliferation via Akt and Erk signaling in an EAE model. Front. Immunol. 11: 1883, 2020. Crossref, Medline, ISI, Google Scholar .
- CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells. Brain Behav. Immun. 71: 158–168, 2018. Crossref, Medline, ISI, Google Scholar .
- NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis. CNS Neurol. Disord.-Dr. 7: 536–557, 2008. Crossref, Medline, ISI, Google Scholar
- Total flavonoids of astragalus attenuates experimental autoimmune encephalomyelitis by suppressing the activation and inflammatory responses of microglia via JNK/AKT/NFB signaling pathway. Phytomedicine 80: 153385, 2021. Crossref, Medline, ISI, Google Scholar .
- Early astragaloside IV administration attenuates experimental autoimmune encephalomyelitis in mice by suppressing the maturation and function of dendritic cells. Life Sci. 249: 117448, 2020a. Crossref, Medline, ISI, Google Scholar .
- Astragaloside IV regulates differentiation and induces apoptosis of activated CD4 T cells in the pathogenesis of experimental autoimmune encephalomyelitis. Toxicol. Appl. Pharmacol. 362: 105–115, 2019. Crossref, Medline, ISI, Google Scholar .
- Eriodictyol suppresses Th17 differentiation and the pathogenesis of experimental autoimmune encephalomyelitis. Food Funct. 11: 6875–6888, 2020b. Crossref, Medline, ISI, Google Scholar .
- He Disulfiram and diphenhydramine hydrochloride upregulate miR-30a to suppress IL-17-associated autoimmune inflammation. J. Neurosci. 36: 9253–9266, 2016. Crossref, Medline, ISI, Google Scholar and C.
- TGF-beta-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORgammat function. Nature 453: 236–240, 2008. Crossref, Medline, ISI, Google Scholar .
- Th17 cell development: From the cradle to the grave. Immunol. Rev. 252: 78–88, 2013. Crossref, Medline, ISI, Google Scholar .
Remember to check out the Most Cited Articles! |
---|
Check out our Chinese Medicine Titles today. |