Suzuki Toshihide, Shimizu Makoto, Yamauchi Yoshio, Sato Ryuichiro
Nutri-Life Science Laboratory Department of Applied Biological Chemistry Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan.
Food Biochemistry Laboratory Department of Applied Biological Chemistry Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan.
Food Sci Nutr. 2022 Mar 24;10(7):2360-2369. doi: 10.1002/fsn3.2844. eCollection 2022 Jul.
Exercise increases the muscular secretion of Interleukin-6 (IL-6), which is partially regulated by β2-adrenergic receptor signaling. Nobiletin is a polymethoxyflavone (PMF) found in citrus fruits that induces the secretion of IL-6 from C2C12 myotubes, but it remains unclear whether nobiletin promotes IL-6 secretion during exercise. The aim of this study was to clarify the effects of nobiletin on IL-6 secretion during exercise. Nobiletin and epinephrine were found to synergistically increase IL-6 secretion from differentiated C2C12 cells, which was suppressed by the inhibition of adenylyl cyclase (AC) or protein kinase A (PKA). Treadmill running for 60 min increased plasma levels of IL-6, epinephrine, and norepinephrine in rats. Nobiletin (5 mg/kg) orally administered 30 min before running increased plasma IL-6 levels further, although it did not increase plasma epinephrine and norepinephrine. In a similar manner to IL-6, nobiletin and epinephrine synergistically increased the secretion of C-X-C motif chemokine ligand 1 (CXCL-1) from C2C12 cells, or the increase in plasma CXCL-1 was enhanced by nobiletin after treadmill running of rats. Our results suggest that nobiletin promotes IL-6 and CXCL-1 secretion from skeletal muscle by synergistic enhancement of the PKA pathway in β2-adrenergic receptor signaling.
运动可增加白细胞介素-6（IL-6）的肌肉分泌，其部分受β2-肾上腺素能受体信号通路调节。川陈皮素是一种在柑橘类水果中发现的多甲氧基黄酮（PMF），可诱导C2C12肌管分泌IL-6，但川陈皮素是否在运动过程中促进IL-6分泌尚不清楚。本研究的目的是阐明川陈皮素在运动过程中对IL-6分泌的影响。研究发现，川陈皮素和肾上腺素可协同增加分化的C2C12细胞分泌IL-6，而这种作用可被腺苷酸环化酶（AC）或蛋白激酶A（PKA）的抑制所抑制。大鼠进行60分钟的跑步机跑步可增加血浆中IL-6、肾上腺素和去甲肾上腺素的水平。跑步前30分钟口服川陈皮素（5毫克/千克）可进一步提高血浆IL-6水平，尽管它不会增加血浆肾上腺素和去甲肾上腺素。与IL-6类似，川陈皮素和肾上腺素可协同增加C2C12细胞分泌C-X-C基序趋化因子配体1（CXCL-1），或者在大鼠跑步机跑步后，川陈皮素可增强血浆CXCL-1的增加。我们的结果表明，川陈皮素通过协同增强β2-肾上腺素能受体信号通路中的PKA途径，促进骨骼肌分泌IL-6和CXCL-1。
