ReferenceID 4324

Aurantii Fructus Immaturus enhances natural killer cytolytic activity and anticancer efficacy in vitro and in vivo

Front Med (Lausanne)

Aurantii Fructus Immaturus (AFI), extensively used in traditional herbal medicine, is known to have diverse physiological effects against various diseases, including obesity, diabetes, and cardiovascular disease. However

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Reference Id
4324
Evidence Id
20914
Core Evidence Id
20914
Source Reference Id
1921
Herb2 Reference Id
HBREF002718
Subject Paper Key
HERB007034_36059847
Pubmed Id
36059847
Doi
10.3389/fmed.2022.973681
Paper Title
Aurantii Fructus Immaturus enhances natural killer cytolytic activity and anticancer efficacy in vitro and in vivo
Paper Abstract
Aurantii Fructus Immaturus (AFI), extensively used in traditional herbal medicine, is known to have diverse physiological effects against various diseases, including obesity, diabetes, and cardiovascular disease. However, the effects of AFI on the immune system, especially natural killer (NK) cells, remain largely unknown. We aimed to investigate the effect of AFI on NK cell activity in vitro and in vivo and to elucidate the underlying mechanisms. Further, we verified the anticancer efficacy of AFI in a mouse lung metastasis model, underscoring the therapeutic potential of AFI in cancer therapy. Our results revealed that AFI significantly enhanced the cytolytic activity of NK cells in a dose-dependent manner, accompanied by an increase in the expression of NK cell-activating receptors, especially NKp30 and NKp46. AFI treatment also increased the expression of cytolytic granules, including granzyme B and perforin. Furthermore, the expression of CD107a, a degranulation marker, was increased upon treatment with AFI. A signaling study using western blot analysis demonstrated that the phosphorylation of extracellular signal-regulated kinase (ERK) was involved in increasing the NK cell activity following AFI treatment. In the in vivo study performed in mice, oral administration of AFI markedly enhanced the cytotoxic activity of spleen mononuclear cells against YAC-1 cells, which was accompanied by NKp46 upregulation. In addition, we confirmed that cancer metastasis was inhibited in a mouse cancer metastasis model, established using the mouse melanoma B16F10 cell line, by the administration of AFI in vivo. Collectively, these results indicate that AFI enhances NK cell-mediated cytotoxicity in vitro and in vivo via activation of the ERK signaling pathway and suggest that AFI could be a potential supplement for cancer immunotherapy.
Journal
Front Med (Lausanne)
Publish Year
2022
Experiment Subject
mouse; mouse melanoma b16f10 cell line; yac-1 cells
Experiment Type
Animal Experiment
Phenotype Related
Obesity; Melanoma; Cancer; Diabetes; Cardiovascular Disease
Paper Title Cn
Paper Title En
Aurantii Fructus Immaturus enhances natural killer cytolytic activity and anticancer efficacy in vitro and in vivo
Bilingual Status
semi_complete