Isorhamnetin

Isorhamnetin is a flavonoid compound extracted from the traditional Chinese medicine Hippophae rhamnoides L., possessing various biological activities including antioxidant, anti-inflammatory, anticancer, and neuroprotective effects^{[1, 2]}. Isorhamnetin exerts its effects by regulating multiple cellular signaling pathways (such as NF-κB and PI3K/AKT), and is beneficial for cardiovascular health, diabetes, and potentially neurodegenerative diseases^[3].

In vitro, treatment of A549 cells with Isorhamnetin (31.6, 63.2µM) for 24h resulted in the accumulation of A549 cells in the G0/G1 phase, a decrease in the number of cells in the S phase, and induced apoptosis. Isorhamnetin upregulated the expression of apoptotic genes Bax, caspase-3, and p53, and downregulated the expression of Bcl-2, cyclin D1, and PCNA proteins^[4]. Treatment of HepG2 cells with Isorhamnetin (10-100µM) enhanced the nuclear translocation of NF-E2-related factor 2 (Nrf2) in a dose- and time-dependent manner, increased antioxidant response element (ARE) reporter gene activity, and elevated the protein levels of heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCL), and increased intracellular glutathione (GSH) levels^[5].

In vivo, Isorhamnetin (5mg/kg) administered via intraperitoneal injection for 7 days to rats with a chronic cardiotoxicity model significantly reduced myocardial damage, decreased serum cardiac enzyme release, and reduced myocardial vacuolization^[6]. Isorhamnetin (5mg/kg) administered via intraperitoneal injection to mice with experimental stroke significantly reduced cerebral edema, improved blood-brain barrier function and neurological function, and upregulated the gene expression of tight junction proteins (including occludin, ZO-1, and claudin-5)^[7].

References:
[1] Khaled R. Biological activities of isorhamnetin: A review[J]. Plantae Scientia, 2020, 3(5): 78-81.
[2] Teng B, Lu Y H, Wang Z T, et al. In vitro anti-tumor activity of isorhamnetin isolated from Hippophae rhamnoides L. against BEL-7402 cells[J]. Pharmacological research, 2006, 54(3): 186-194.
[3] Mao Y, Zha Y, Zang Y, et al. Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway[J]. Biomedicine & Pharmacotherapy, 2024, 177: 116987.
[4] Li Q, Ren F Q, Yang C L, et al. Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in vivo[J]. Asian Pacific Journal of Cancer Prevention, 2015, 16(7): 3035-3042.
[5] Yang J H, Shin B Y, Han J Y, et al. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes[J]. Toxicology and applied pharmacology, 2014, 274(2): 293-301.
[6] Sun J, Sun G, Meng X, et al. Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro[J]. PloS one, 2013, 8(5): e64526.
[7] Zhao J J, Song J Q, Pan S Y, et al. Treatment with isorhamnetin protects the brain against ischemic injury in mice[J]. Neurochemical Research, 2016, 41(8): 1939-1948.

Isorhamnetin是一种从中草药Hippophae rhamnoides L.中提取的类黄酮化合物，具有抗氧化、抗炎、抗癌和神经保护等多种生物活性^{[1, 2]}。Isorhamnetin通过调节多种细胞信号通路（如NF-κB、PI3K/AKT）来发挥作用，对心血管健康、糖尿病及潜在的神经退行性疾病有益^[3]。

在体外，Isorhamnetin（31.6, 63.2µM）处理A549细胞24h，导致A549细胞在G0/G1期积累，同时S期细胞数量减少，诱导了细胞凋亡，上调了凋亡基因Bax、caspase-3和p53的表达，下调了Bcl-2、cyclinD1和PCNA蛋白的表达^[4]。Isorhamnetin（10-100µM）处理HepG2细胞，以剂量和时间依赖性方式增强了 NF-E2相关因子2（Nrf2）的核内易位，升高了抗氧化反应元素（ARE）报告基因活性以及血氧加氧酶（HO-1）和谷氨酸半氨酸连接酶（GCL）蛋白水平，升高了细胞内谷胱甘肽（GSH）水平^[5]。

在体内，Isorhamnetin（5mg/kg）通过腹腔注射治疗慢性心脏毒性模型大鼠7天，显著减轻了大鼠的心肌损伤，降低了血清心肌酶释放，减轻了心肌空泡化^[6]。Isorhamnetin（5mg/kg）通过腹腔注射治疗实验性卒中小鼠，显著减轻了小鼠的脑水肿，改善了血脑屏障功能和神经功能，上调了紧密连接蛋白（包括occludin、ZO-1和claudin-5）的基因表达^[7]。