Neohesperidin suppresses IgE‐mediated anaphylactic reactions and mast cell activation via Lyn‐PLC‐Ca²⁺ pathway

Abstract

Mast cells play an essential role in IgE-FcεR1-mediated allergic diseases. Citrus aurantium is a prolific source of flavonoids with various biological activities, including anti-inflammatory, antioxidant, and anti-tumor efficacies. Neohesperidin is a novel flavonoid isolated from the leaves of C. aurantium. In this study, the anti-allergic and antiinflammatory potentials of neohesperidin were investigated along with its molecular mechanism. The anti-anaphylactic activity of neohesperidin was evaluated through hind paw extravasation study in mice. Calcium imaging was used to assess intracellular Ca 2+ mobilization. The levels of cytokines and chemokines were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Neohesperidin suppressed IgE-induced mast cell activations, including degranulation and secretion of cytokines and eicosanoids through inhibiting phosphorylation of Lyn kinase. Neohesperidin inhibited the release of histamine and other proinflammatory cytokines through a mast cell-dependent passive cutaneous anaphylaxis animal model. Histological studies demonstrated that neohesperidin substantially inhibited IgE-induced cellular infiltration and attenuated mast cell activation in skin tissue. In conclusion, our study revealed that neohesperidin could inhibit allergic responses in vivo and in vitro, and the molecule may be regarded as a novel agent for preventing mast cell-immediate and delayed allergic diseases.

Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high‐fat diet‐fed mice

“…Due to its multiple biological effects and low intrinsic toxicity, it has recently attracted attention as a health-promoting compound. [26][27][28] The pharmacologic potential of Neo includes but not limited to anti-tumor, anti-oxidation, and anti-inflammatory effects. [29][30][31][32][33] In vitro, Neo has been shown to increase the consumption of glucose by HepG2 cells.…”

“…Neohesperidin (Neo), a plant polyphenol, is found abundantly in citrus fruits. Due to its multiple biological effects and low intrinsic toxicity, it has recently attracted attention as a health‐promoting compound 26‐28 . The pharmacologic potential of Neo includes but not limited to anti‐tumor, anti‐oxidation, and anti‐inflammatory effects 29‐33 .…”

Metabolic Variations of Flavonoids in Leaves of T. media and T. mairei Obtained by UPLC-ESI-MS/MS

“…According to the results of peak area calculations, prunin and apigenin displayed higher accumulations in T. media than in T. mairei , indicating a strong reactive oxygen species (ROS) scavenging activity, and a medicinal potential against UV-induced skin tumorigenesis in T. media leaves [28,29]. The high level of neohesperidin in T. mairei leaves implied specific antioxidant, anti-inflammatory, and anti-allergic activities for preventing mast cell-immediate and delayed allergic diseases [30]. Quercetin is one of the most abundant dietary flavonoids [31].…”

Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies

“…This flavanone has a wide range of biological activities, including neuroprotective activity [ 117 ] and anti-proliferative effects [ 118 ]. Recently, neohesperidin was found to inhibit common allergic responses in vivo and in vitro [ 119 ], exhibit protective effects in progressive pulmonary fibrosis [ 120 ], and show anti-osteoclastic properties, presenting it as a potential anti-catabolic biomolecule for the treatment of osteoporosis [ 121 ].…”