Kaempferol-3-rutinoside is a flavonoid glycoside that exists in a variety of plants and is also known as Nicotiflorin[1]. Kaempferol-3-rutinoside has lipid-lowering, anti-glycation, and neuroprotective effects[2-3]. Kaempferol-3-rutinoside can protect cells from oxidative stress-induced damage by increasing the activity of antioxidant enzymes such as superoxide dismutase and catalase[4].
In vitro, After 4 hours of hypoxia and 12 hours of reoxygenation, the endothelial nitric oxide synthase (eNOS) activity, mRNA and protein levels in Kaempferol-3-rutinoside (25, 50, 100μg/ml) treated primary rat brain microvascular endothelial cells were significantly increased compared with untreated hypoxic reoxygenated cells and normally cultured cells[5]. Kaempferol-3-rutinoside (0, 25, 50, 75, 100μg/ml) treatment of human renal epithelial cells (HK-2) significantly reduced hypoxia/reoxygenation-induced cell apoptosis, as evidenced by decreased expression of pro-apoptotic proteins caspase 3 and Bad, and increased expression of anti-apoptotic protein Bcl-2. Moreover, in HK-2 cells treated with Kaempferol-3-rutinoside (75μg/ml) under hypoxia/reoxygenation conditions, cell apoptosis was further inhibited by activating transcription factor 3 (ATF3)[6].
In vivo, Kaempferol-3-rutinoside (2.5, 5, and 10mg/kg) was administered via tail vein injection to treat a male Sprague-Dawley (SD) rat model of permanent focal cerebral ischemia, with administration immediately following ischemia onset. Kaempferol-3-rutinoside significantly reduced the volume of ischemic brain damage in a dose-dependent manner at all three doses and improved behavioral deficits caused by permanent middle cerebral artery occlusion (pMCAO)[7]. Kaempferol-3-rutinoside (10mg/kg) was administered via tail vein injection to treat a male Sprague-Dawley rat model of transient middle cerebral artery occlusion/reperfusion (MCAO/R)-induced cerebral ischemia-reperfusion injury, with administration at the start of reperfusion. Kaempferol-3-rutinoside treatment significantly reduced the volume of ischemic brain damage, decreased the number of apoptotic cells, downregulated the expression of p-JAK2, p-STAT3, caspase-3, and Bax, reduced the immunoreactivity of Bax, and increased the expression and immunoreactivity of Bcl-2 protein[8].
References:
[1] Patel DK. Medicinal Importance, Pharmacological Activities and Analytical Aspects of a Flavonoid Glycoside 'Nicotiflorin' in the Medicine. Drug Metab Bioanal Lett. 2022;15(1):2-11.
[2] Huang JL, Fu ST, Jiang YY, et al. Protective effects of Nicotiflorin on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats. Pharmacol Biochem Behav. 2007 Apr;86(4):741-8.
[3] Papaioannou P, Lazari D, Karioti A, et al. Phenolic compounds with antioxidant activity from Anthemis tinctoria L. (Asteraceae). Z Naturforsch C J Biosci. 2007 May-Jun;62(5-6):326-30.
[4] Yang C, Li F, Zhang X, et al. Phenolic antioxidants from Rosa soulieana flowers. Nat Prod Res. 2013;27(21):2055-8.
[5] Li R, Guo M, Zhang G, et al. Nicotiflorin reduces cerebral ischemic damage and upregulates endothelial nitric oxide synthase in primarily cultured rat cerebral blood vessel endothelial cells. J Ethnopharmacol. 2006 Aug 11;107(1):143-50.
[6] Wang L, Li C, Guan C, et al. Nicotiflorin attenuates cell apoptosis in renal ischemia-reperfusion injury through activating transcription factor 3. Nephrology (Carlton). 2021 Apr;26(4):358-368.
[7] Li R, Guo M, Zhang G, et al. Neuroprotection of nicotiflorin in permanent focal cerebral ischemia and in neuronal cultures. Biol Pharm Bull. 2006 Sep;29(9):1868-72.
[8] Hu GQ, Du X, Li YJ, et al. Inhibition of cerebral ischemia/reperfusion injury-induced apoptosis: nicotiflorin and JAK2/STAT3 pathway.
Kaempferol-3-rutinoside是一种存在于多种植物中的黄酮类糖苷，又称为Nicotiflorin[1]，具有降血脂、抗糖化和神经保护作用[2-3]。Kaempferol-3-rutinoside可以通过增加超氧化物歧化酶和过氧化氢酶等抗氧化酶的活性，保护细胞免受氧化应激诱导的损伤[4]。
在体外，经4小时缺氧和12小时复氧处理后，与未处理的缺氧复氧细胞及正常培养的细胞相比，Kaempferol-3-rutinoside（25、50、100μg/ml）处理的原代大鼠脑微血管内皮细胞中内皮型一氧化氮合酶（eNOS）活性、mRNA和蛋白水平显著提高[5]。Kaempferol-3-rutinoside（0、25、50、75、100μg/ml）处理人肾上皮细胞（HK-2），显著降低了缺氧/复氧诱导的细胞凋亡，表现为降低促凋亡蛋白caspase3和Bad的表达，增加抗凋亡蛋白Bcl-2的表达。此外，Kaempferol-3-rutinoside（75μg/ml）处理的HK-2细胞在缺氧/复氧条件下，通过激活转录因子3（ATF3），进一步抑制了细胞凋亡[6]。
在体内，Kaempferol-3-rutinoside（2.5、5和10mg/kg）通过尾静脉注射给药，用于治疗永久性局灶性脑缺血的雄性Sprague-Dawley（SD）大鼠模型，给药时间为缺血发生后立即进行。Kaempferol-3-rutinoside在所有三个剂量下均能以剂量依赖性方式显著减少缺血性脑损伤的体积，并改善由永久性大脑中动脉闭塞（pMCAO）引起的行为缺陷[7]。Kaempferol-3-rutinoside（10mg/kg）通过尾静脉注射给药，用于治疗短暂性大脑中动脉闭塞/再灌注（MCAO/R）诱导的脑缺血再灌注损伤的雄性Sprague-Dawley大鼠模型，给药时间为再灌注开始时。Kaempferol-3-rutinoside处理显著减少了缺血性脑损伤的体积，降低了细胞凋亡的数量，下调了p-JAK2、p-STAT3、caspase-3和Bax的表达，减少了Bax的免疫反应性，并增加了Bcl-2蛋白的表达和免疫反应性[8]。