Isosakuranetin, a flavanone found in Citrus species with diverse biological activities, has an IC50 value of 50nM for TRPM3 [1]. Isosakuranetin can inhibit the activity of Sortase A (SrtA) and the transcription and expression of α-Hemolysin (Hla) in Staphylococcus aureus, and regulate the transcription of the upstream operon RNAIII of Hla [2]. Isosakuranetin has been widely used in rat models of peripheral neuropathy to alleviate mechanical, thermal, and cold hypersensitivity[3].
In vitro, Isosakuranetin treatment for 48 hours significantly increased the viability of HL-60 and U937 cells with IC50 values of 115.6µM and 30.4µM, respectively[4]. Treatment of HaCaT cells with 20µM Isosakuranetin for 24 hours significantly inhibited ultraviolet (UV)-B-mediated induction of MMP-1 and inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling pathway components ERK1/2, JNK1/2, and p38 proteins[5]. Treatment with 30µM Isosakuranetin for 48h significantly increased Tyr, TRP1, and TRP2 expression, upregulated MITF expression, and decreased MITF phosphorylation in B16 melanoma cells[6].
In vivo, Isosakuranetin treatment via oral administration at a dose of 5mg/kg daily for 1 week significantly increased the abundance of Parabacteroides in the intestinal tract of mice and affected amino acid metabolism pathways[7]. Intraperitoneal injection of a 2mg/kg dose of Isosakuranetin every other day for 8 weeks, which inhibited the formation of osteoclasts beneath the cartilage in the osteoarthritis (OA) mouse model, improved the degeneration of joint cartilage, and delayed the progression of OA[8].
References:
[1] Straub I, Krügel U, Mohr F, et al. Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo[J]. Molecular pharmacology, 2013, 84(5): 736-750.
[2] Tian L, Wang L, Yang F, et al. Exploring the modulatory impact of isosakuranetin on Staphylococcus aureus: Inhibition of sortase A activity and α-haemolysin expression[J]. Virulence, 2023, 14(1): 2260675.
[3] Jia S, Zhang Y, Yu J. Antinociceptive effects of isosakuranetin in a rat model of peripheral neuropathy[J]. Pharmacology, 2017, 100(3-4): 201-207.
[4] Tseng R H, Lai K M, Chou C M, et al. Isosakuranetin lnduces autophagy and apoptosis through AMPK and PI3K/Akt signaling in human leukemia cells[J]. Anticancer Research, 2025, 45(4): 1481-1500.
[5] Jung H, Lee E H, Lee T H, et al. The methoxyflavonoid isosakuranetin suppresses UV-B-induced matrix metalloproteinase-1 expression and collagen degradation relevant for skin photoaging[J]. International journal of molecular sciences, 2016, 17(9): 1449.
[6] Drira R, Sakamoto K. Isosakuranetin, a 4′-O-methylated flavonoid, stimulates melanogenesis in B16BL6 murine melanoma cells[J]. Life sciences, 2015, 143: 43-49.
[7] Cao X, Guo X, Fang X, et al. Effects of poncirin, a citrus flavonoid and its aglycone, isosakuranetin, on the gut microbial diversity and metabolomics in mice[J]. Molecules, 2022, 27(11): 3641.
[8] Lu S, Fang C. Isosakuranetin inhibits subchondral osteoclastogenesis for attenuating osteoarthritis via suppressing NF-κB/CXCL2 axis[J]. International Immunopharmacology, 2024, 143: 113321.
Isosakuranetin是一种存在于柑橘类植物中的黄烷酮，具有多种生物活性，对TRPM3的IC50值为50nM[1]。Isosakuranetin可抑制金黄色葡萄球菌中Sortase A（SrtA）的活性以及α-溶血素（Hla）的转录和表达，并调控Hla上游操纵子RNAIII的转录[2]。Isosakuranetin已被广泛用于大鼠周围神经病变模型，以缓解机械性、热性和冷性痛觉过敏[3]。
在体外，Isosakuranetin处理48小时显著提高了HL-60和U937细胞的活力，IC50值分别为115.6µM和30.4µM[4]。使用20µM的Isosakuranetin处理HaCaT细胞24小时，显著抑制了紫外线（UV）-B介导的MMP-1诱导，并抑制了UV-B诱导的丝裂原活化蛋白激酶（MAPK）信号通路组分ERK1/2、JNK1/2和p38蛋白的磷酸化[5]。使用30µM的Isosakuranetin处理48小时，显著增加了B16黑色素瘤细胞中Tyr、TRP1和TRP2的表达，上调了MITF的表达，并降低了MITF的磷酸化[6]。
在体内，每日口服给予5mg/kg剂量的Isosakuranetin，连续一周，显著增加了小鼠肠道中副拟杆菌属的丰度，并影响了氨基酸代谢通路[7]。每隔一天腹腔注射2mg/kg剂量的Isosakuranetin，持续八周，抑制了骨关节炎（OA）小鼠模型中软骨下方破骨细胞的形成，改善了关节软骨的退变，并延缓了OA的进展[8]。