Hyperoside

Hyperoside is a NF-κB inhibitor, found from Hypericum monogynum. Hyperoside shows anti-tumor, antifungal, anti-inflammatory, anti-viral, and anti-oxidative activitie^[1][2].

Hyperoside (0.5, 1, 2mM; 24, 48h) dose-dependently inhibited the phosphorylation of Akt, mTOR, p70S6K and 4E-BP1, but increased the phosphorylation of ERK1/2 in A549 cells^[1]. With increasing concentrations of Hyperoside (25, 50, 100mM) treatment, the phosphorylation levels of IκBα and p65 in MCF-7 and 4T1 cells decreased^[2]. Hyperoside (0-300µM) inhibited cell proliferation in U2OS and MG63 cells in a dose-dependent manner at 72h, with IC₅₀ values of 223.5 and 239.0µM, respectively^[3].

Hyperoside (50mg/kg; ip; every two days for 18 days) inhibited the activation of the NF-κB pathway and reduced translocation of p-p65 in the nucleus by reducing ROS production in 4T1 cells. Inhibition of NF-κB down-regulates the transcription of anti-apoptotic genes, such as Bcl-2 and XIAP, but it also induced the accumulation of Bax, which leads to mitochondrial dysfunction and leads to apoptosis by activating caspase-3^[2]. For ovariectomized (OVX) mice, Hyperoside (20, 40, 80mg/kg) was effective in preventing osteoporosis by increasing bone mineral density, restoring trabecular bone micro-architecture, and enhancing bone strength^[4]. In the bleomycin-induced pulmonary fibrosis model, Hyperoside (50mg/kg; 14 days) treatment can improve the pathological changes of fibrosis and collagen deposition in the lung tissue of mice with bleomycin-induced pulmonary fibrosis. Hyperoside treatment can also reduce the content of MDA, TNF-α and IL-6, and increase the activity of SOD^[5].

References:
[1]. Fu T, Wang L, Jin X, et al. Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro[J]. Acta Pharmacologica Sinica, 2016, 37(4): 505-518.
[2]. Qiu J, Zhang T, Zhu X, et al. Hyperoside induces breast cancer cells apoptosis via ROS-mediated NF-κB signaling pathway[J]. International Journal of Molecular Sciences, 2019, 21(1): 131.
[3].Zhang N, Ying M D, Wu Y P, et al. Hyperoside, a flavonoid compound, inhibits proliferation and stimulates osteogenic differentiation of human osteosarcoma cells[J]. PloS one, 2014, 9(7): e98973.
[4]. Chen Y, Dai F, He Y, et al. Beneficial effects of hyperoside on bone metabolism in ovariectomized mice[J]. Biomedicine & Pharmacotherapy, 2018, 107: 1175-1182.
[5]. Huang J, Tong X, Zhang L, et al. Hyperoside attenuates bleomycin-induced pulmonary fibrosis development in mice[J]. Frontiers in Pharmacology, 2020, 11: 550955.

Hyperoside（金丝桃苷）是一种NF-κB抑制剂，来源于金丝桃。Hyperoside具有抗肿瘤、抗真菌、抗炎、抗病毒和抗氧化活 ^[1][2]。

Hyperoside（0.5、1、2mM；24、48h）剂量依赖性地抑制了A549细胞中Akt、mTOR、p70S6K和4E-BP1的磷酸化，增加了ERK1/2的磷酸化^[1]。MCF-7细胞和4T1细胞中IκBα和p65的磷酸化水平随Hyperoside（25，50，100mM）浓度的增加而降低^[2]。Hyperoside（0-300µM）在72h时以剂量依赖性方式抑制U2OS和MG63细胞中的细胞增殖，IC₅₀值分别为223.5和239.0µM^[3]。

Hyperoside（50mg/kg；ip；每两天一次，共18天）抑制了NF-κB通路的激活，并通过减少4T1细胞中的ROS产生来减少p-p65在细胞核中的易位，NF-κB的抑制会下调抗凋亡基因（如Bcl-2和XIAP）的转录，但也会诱导Bax的积累，从而导致线粒体功能障碍，并通过激活caspase-3导致细胞凋亡^[2]。对于卵巢切除（OVX）小鼠，Hyperoside（20、40、80mg/kg）可通过增加骨矿物质密度、恢复骨小梁微结构和增强骨强度来有效预防骨质疏松症^[4]。在博来霉素（Bleomycin）诱导的肺纤维化模型中, Hyperoside（50mg/kg；14 days）治疗可以改善博来霉素诱导的肺纤维化小鼠肺组织纤维化及胶原沉积的病理改变；Hyperoside治疗还可以降低MDA、TNF-α、IL-6的含量，提高SOD的活性^[5]。