Irisflorentin Modifies Properties of Mouse Bone Marrow-Derived Dendritic Cells and Reduces the Allergic Contact Hypersensitivity Responses

Abstract

Irisflorentin is an isoflavone component derived from the roots of Belamcanda chinensis (L.) DC. In traditional Chinese medicine, this herb has pharmacological properties to treat inflammatory disorders. Dendritic cells (DCs) are crucial modulators for the development of optimal T-cell immunity and maintenance of tolerance. Aberrant activation of DCs can induce harmful immune responses, and so agents that effectively improve DC properties have great clinical value. We herein investigated the effects of irisflorentin on lipopolysaccharide (LPS)-stimulated maturation of mouse bone marrow-derived DCs in vitro and in the contact hypersensitivity response (CHSR) in vivo. Our results demonstrated that treatment with up to 40 mM irisflorentin does not cause cellular toxicity. Irisflorentin significantly lessened the proinflammatory cytokine production (tumor necrosis factor-a, interleukin-6, and interleukin-12p70) by LPS-stimulated DCs. Irisflorentin also inhibited the expression of LPS-induced major histocompatibility complex class II and costimulatory molecules (CD40 and CD86) on LPS-stimulated DCs. In addition, irisflorentin diminished LPS-stimulated DC-elicited allogeneic T-cell proliferation. Furthermore, irisflorentin significantly interfered with LPS-induced activation of IkB kinase, c-Jun N-terminal kinase, and p38, as well as the nuclear translocation of NF-kB p65. Subsequently, treatment with irisflorentin obviously weakened 2,4-dinitro-1-fluorobenzene-induced delayed-type hypersensitivity. These findings suggest new insights into the role of irisflorentin as an immunotherapeutic adjuvant through its capability to modulate the properties of DCs.

Irisflorentin promotes bacterial phagocytosis and inhibits inflammatory responses in macrophages during bacterial infection

“…While the therapeutic mechanisms of TCM remain largely undefined, it represents a treasure of medicines and deserves to be explored in depth for novel drug discovery. As a natural product that serves as an important gradient in anti-infective and anti-inflammatory TCM, IFL has been reported to suppress the secretion of LPS-induced inflammatory mediators in Raw264.7 and dendritic cells, but the underlying mechanism has not been characterized [ 16 , 17 ]. In the present study, we demonstrated that IFL could remarkably inhibit bacterial mimics, Pam3CSK4 or PGN -stimulated production of proinflammatory cytokines, such as IL-6, TNF-α, IL-12p70, IL-10 and IL-1β, not only in Raw264.7 cells but also in mouse primary macrophages (BMDMs or peritoneal macrophages) and dendritic cells through suppressing the activation of ERK and p38 MAPK pathways.…”

Glycine-Alanine Dipeptide Repeat Protein from C9-ALS Interacts with Sulfide Quinone Oxidoreductase (SQOR) to Induce the Activity of the NLRP3 Inflammasome in HMC3 Microglia: Irisflorentin Reverses This Interaction

“…IFT has also been shown to ameliorate 6-OHDA-induced dopaminergic neuronal degeneration and α-synuclein accumulation in Parkinson's disease models [72]. Moreover, IFT can inhibit allergic contact hypersensitivity by modifying the properties of mouse bone marrow dendritic cells [73] and can improve the LPS-induced inflammatory response of RAW 264.7 macrophages [74]. Therefore, in addition to diminishing the activity of the NLRP3 inflammasome induced by GA 50 , IFT may also have neuroprotective activities in regulating cellular anti-oxidation, anti-inflammation, and clearing amyloid in C9-ALS patients.…”

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo

“… 7 , 36 Moreover, the anti-inflammatory activity of irisflorentin may be attributed to the inhibition of NO, TNF-α, IL-1β, and IL-6 mediated by the inactivation of ERK1/2- and p38-mediated activator protein-1 pathways. 37 , 38 Lim et al 25 reported that tectorigenin exerts anti-inflammatory effects through downregulation of the inflammatory mediators iNOS, COX-2, TNF-α, and IL-6 by suppressing NF-kB/ERK/JNK-related signaling pathways. Recent experiments by Kim and co-workers (2021) showed that triterpenoids, such as isoiridogermanal and iridobelamal A, isolated from B. chinensis exert anti-inflammatory effects through the NF-κB pathway.…”