Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

Abstract

A flavonoid Astragalin (kaempferol-3-O-β-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O-β-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

Phyllanthus niruri (Meniran) Sebagai Imunomodulator: Mekanisme aksi dan senyawa bioaktif

“…Astragalin dapat menurunkan respon inflamasi yang diinduksi lipopolisakarida (LPS) dengan menekan jalur persinyalan NF-кB (Riaz et al, 2018;Shukla et al, 2019). Senyawa astragalin galaktosidase dilaporkan lebih aktif daripada astragalin dalam proses maturasi sel dendritik untuk meningkatkan respon imun yang dimediasi oleh sel helper TH1 (Jeon et al, 2018). (5) Niruriflavon, merupakan flavonon yang memiliki aktivitas farmakologi sebagai hepatoprotektor dengan mekanisme menangkal radikal bebas yang berperan dalam proses hepatotoksik (Bagalkotkar et al, 2006;Kaur et al, 2017).…”

Osteogenic Effects of the Diospyros lotus L. Leaf Extract on MC3T3-E1 Pre-Osteoblasts and Ovariectomized Mice via BMP2/4 and TGF β Pathways

“…Both BMP2/4 and TGFβ are upregulated by DLE and are molecules related to the immune system. Myricetin, quercetin, and kaempferol exert anti-inflammatory and modulatory effects on various types of immune cells [ 24 , 25 ]. Bone marrow has various immune cells, and T cells are a source of BMP2/4 and TGFβ.…”

Revealing the Mechanism of Astragali Radix against Cancer-Related Fatigue by Network Pharmacology and Molecular Docking

“…Many previous studies have proved that kaempferol has good anti-inflammatory, immune regulation, antioxidation, antitumor, and other pharmacological properties [ 20 ]. It has been shown that kaempferol can induce Th1-mediated immune responses through dendritic cells [ 24 ]. Kaempferol can also exhibit antioxidant activities by increasing the expression of related antioxidant enzymes and reducing oxidative stress [ 25 ].…”