Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.     

Apigenin对黄嘌呤氧化酶活性抑制的实验研究

目的:通过体外酶学试验研究Apigenin对黄嘌呤氧化酶活性的影响及抑制机制。方法:运用紫外分光光度计测定尿酸生成导致的吸光度变化值,测定波长为292 nm,以黄嘌呤为底物根据测定结果绘制Lineweaver-Burk和Dixon图。结果:Apigenin对黄嘌呤氧化酶具有较强的抑制作用,其Ki值为0.151 3μg/ml,抑制类型为混合型;而别嘌呤醇作为参照,其Ki值为0.62μg/ml,抑制类型为竞争性抑制。结论:Apigenin可明显抑制黄嘌呤氧化酶活性。     

芹菜素对链脲佐菌素诱导糖尿病大鼠肝损伤的影响

目的：探讨芹菜素对糖尿病大鼠肝脏的保护作用。方法将大鼠按随机数字表法分为正常对照组,模型组,芹菜素5、10、20和40 mg/kg治疗组。除正常对照组外,其余各组大鼠采用腹腔注射链脲佐菌素（STZ）的方法建立大鼠糖尿病模型。造模成功后,芹菜素5、10、20和40 mg/kg治疗组大鼠腹腔注射相应浓度的芹菜素溶液,正常对照组和模型组腹腔注射等体积生理盐水,1 d/次。连续给药4周后,测定各组大鼠体质量、肝脏/体质量比;采用 HE 染色方法观察各组大鼠肝组织病理学改变;测定血清谷氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）水平;检测肝组织超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）活性及丙二醛（MDA）水平。结果与模型组比较,芹菜素10、20和40 mg/kg治疗组体质量[(261.3±15.8)g、(274.2±18.4)g、(265.9±19.0)g比(250.8±21.4)g]显著增高（P＜0.05或P＜0.01）,肝脏/体质量比[(27.7±5.69)、(26.2±4.91)、(27.3±4.58)比(32.9±5.85)]显著降低（P＜0.05或 P＜0.01）,肝组织病理学改变明显改善;芹菜素5、10、20和40 mg/kg治疗组血清ALT水平[(1039.3±453.9)U/L、(917.6±445.2)U/L、(828.4±309.5)U/L、(721.7±318.3)U/L比(1205.2±484.1)U/L]、AST水平[(97.8±23.8)U/L、(90.1±19.6)U/L、(81.7±15.7)U/L、(86.4±19.2)U/L比(105.3±25.7)U/L]、LDH水平[(983.7±192.6)U/L、(918.3±212.9)U/L、(830.4±174.2)U/L、(871.8±183.1)U/L比(1102.8±211.6)U/L]均较模型组显著降低(P＜0.05或P＜0.01);芹菜素10、20和40 mg/kg治疗组肝组织中SOD[(10.5±1.9)U/mg、(11.6±2.1)U/mg、(10.5±2.0)U/mg 比(9.1±1.8)U/mg]、GSH-Px[(14.2±2.7)U/mg、(15.3±2.9)U/mg、(14.6±2.6)U/mg 比(12.9±2.3)U/mg],CAT[(3.15±0.90)U/mg、(3.58±0.88)U/mg、(3.31±1.09)U/mg比(2.58±0.79)U/mg]活性较模型组升高(P＜0.05或 P＜0.01),MDA 水平[(5.03±1.70)nmol/mg、(4.66±1.51)nmol/mg、(4.73±1.65)nmol/mg 比(5.98±1.62)nmol/mg]较模型组降低(P＜0.05或 P＜0.01)。结论芹菜素具有抗氧化酶活性,可降低自由基损伤,保护糖尿病大鼠肝组织。     

4′,5,7-三羟基黄酮,芹菜配基对人乳腺癌细胞生长和侵袭潜力的影响

目的探讨透明质酸酶（Hyaluronidase，Hyase）抑制剂4′，5，7-三羟基黄酮，芹菜配基（Apigenin）对人乳腺癌细胞生长、增殖及侵袭潜力的影响。方法通过体外侵袭模型观察Apigenin对人乳腺癌细胞穿透Matrigel（人工基底膜）能力的影响；MTT法和流式细胞仪检测Apigenin对人乳腺癌细胞株生长和增殖的影响。结果8株人乳腺癌细胞的侵袭潜力存在明显差异。加用Apigenin后其侵袭潜力均明显降低（P〈0．05），并与Apigenin存在量效关系；Apigenin对MDA-MB-435S和T47D细胞株的生长抑制作用均呈浓度依赖性；流式细胞仪显示Apigenin阻滞人乳腺癌细胞株MDA-MB-231和ZR-75-30生长于G2／M期（P〈0．05）。结论Apigenin可抑制人乳腺癌细胞的增殖和Hyase的表达，并可降低人乳腺癌细胞株的侵袭潜能。     

芹菜素对人CIK细胞杀伤结肠癌SW1116细胞的影响

目的观察芹菜素对人结肠癌细胞SW1116及CIK细胞的作用,探讨芹菜素对人CIK细胞杀伤结肠癌SW1116细胞的影响。方法不同浓度的芹菜素分别诱导人CIK细胞和结肠癌细胞SW1116细胞24、48、72 h,四甲基偶唑蓝(MTT)法检测上述两种细胞的生长。乳酸脱氢酶释放法检测CIK细胞对结肠癌SW1116细胞杀伤活性。结果体外培养10 d后,CIK细胞比例由3.12%增加到17.55%。与对照组比较,浓度1.17～4.7μmol/L芹菜素作用后的CIK细胞的增殖率显著提高(P<0.05),浓度37.5～600μmol/L的芹菜素对SW1116细胞生长抑制率显著提高(P<0.05),三个时间段比较均无明显差异。浓度2.35～9.4μmol/L的芹菜素作用48 h后,CIK细胞对结肠癌SW1116细胞的杀伤活性显著高于对照组(P<0.05)。结论芹菜素在一定浓度范围内可促进CIK细胞的生长,明显提高CIK细胞对SW1116细胞的杀伤作用,且抑制结肠癌SW1116细胞的生长。     

芹菜素在体外对宫颈癌HeLa细胞生长的影响

目的探讨芹菜素在体外对宫颈癌HeLa细胞生长的影响。方法通过四甲基偶氮唑蓝法及平板克隆形成实验研究芹菜素在体外对宫颈癌HeLa细胞生长的影响。结果不同浓度的芹菜素(5、10、20 mg/L)对HeLa细胞的生长均有显著的抑制作用,随着芹菜素浓度的增加,抑制作用显著增强;平板克隆实验结果表明,芹菜素能使HeLa细胞的平板克隆形成能力减弱,不论从克隆的大小还是克隆的数目上,实验组均较对照组明显下降,芹菜素浓度越大,平板克隆形成能力越弱。结论芹菜素在体外对宫颈癌HeLa细胞的生长有显著的抑制作用。     

紫外分光光度法测定大蝎子草药材中总黄酮的含量

目的:建立大蝎子草总黄酮含量测定方法。方法:采用紫外分光光度法,以芹菜素为标准品,检测波长为268nm。结果:芹菜素检测浓度在1.984～11.904μg·mL-1范围内与吸光度呈良好的线性关系(r=0.9999);平均加样回收率为96.15%,RSD=1.98%(n=6)。结论:本方法稳定、准确、可靠,可用于大蝎子草总黄酮的含量测定。     

芹菜素对雄性小鼠肝脏SOD、GSH-Px、CAT活力影响

目的观察不同剂量、不同作用时间,芹菜素（AP）对雄性小鼠肝脏氧化还原酶活力的影响。方法将200只雄性小鼠按体重随机分为对照组（生理盐水）、低剂量组（AP252mg/kgbw）、中剂量组（AP504mg/kgbw）和高剂量组（AP1008mg/kgbw）4组,各组动物又随机分成5个时间组即：7d组、14d组、21d组、28d组、35d组。小鼠给予0.01ml/gbw生理盐水和不同浓度的芹菜素灌胃,1次/d。分批处死小鼠,制备肝匀浆。测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）及过氧化氢酶（CAT）活力。结果 SOD活力28d高剂量组明显低于其他组（P〈0.05）,35d中剂量组SOD活力低于对照组及低剂量组（P〈0.05）;GSH-Px活力28d高剂量组较对照组及低剂量组低（P〈0.05）;CAT活力变化不明显。结论 AP对雄性小鼠肝脏SOD、GSH-Px活力具有一定抑制作用。     

Anti-oxidant and anti-inflammatory effects of apigenin in a rat model of sepsis: an immunological,biochemical, and histopathological study

Objective: We hypothesize that apigenin may inhibit some cellular process of sepsis-induced spleen injury and simultaneously improve inflammation and oxidative stress. Therefore, the aim of this study was to investigate the potential protective effects of apigenin in a polymicrobial sepsis rat model of by cecal ligation and puncture.

Materials and methods: 64 female Wistar albino rats were divided into 8 groups. The pro-inflammatory (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta) and anti-inflammatory (tumor growth factor-beta and interleukin-10) cytokine levels were measured by enzyme-linked immunosorbent assay. CD3, CD68, and nuclear factor kappa B (NF-κB) positivity rates were detected by immunohistochemical methods. Oxidative stress parameters were measured by tissue biochemistry.

Results: Sepsis caused a significant increase in TNF-alpha, IL-1-beta, IL-6, and TGF-beta levels whereas it reduced IL-10 level. Additionally, it led to an increase in CD3, CD68, and NF-κB positivity rates as well as oxidative stress parameters levels. However, apigenin inhibited the inflammation process, increased the IL-10 level and normalized the oxidative stress parameters.

Discussion and conclusion: Pretreatment with apigenin results in a significant reduction in the amount of inflammatory cells. The beneficial effect of apigenin on spleen injury also involved inhibition of NF-κB pathway, suppression of proinflammatory cytokines, and induction of anti-inflammatory cytokine production. Additionally, it led to a decrease in oxidative stress in spleen tissue. Taking everything into account, apigenin may be an alternative therapeutic option for prevention of sepsis-induced organ.     

Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage

Apigenin (API) is a naturally occurring plant flavone that exhibits powerful antioxidant and antiapoptosis. Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The potential anti-oxidative and anti-apoptosis effects of API on EBI following SAH, however, have not been elucidated. The aim of this study was to assess whether API alleviates EBI after SAH via its anti-oxidative and anti-apoptotic effects. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 24 h after SAH. Our data demonstrated that administration of API could significantly alleviate EBI (including neurological deficiency, brain edema, blood–brain barrier permeability, and cortical cell apoptosis) after SAH in rats. Meanwhile, API treatment reduced the reactive oxygen species (ROS) level and the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO), elevated the ratio of glutathione (GSH) and oxidized glutathione (GSSG), and increased the amount of super-oxide dismutase (SOD) and hydrogen peroxide in brain cortex at 24 h following SAH. Moreover, API treatment inhibited SAH-induced the expression of Bax and caspase-3, significantly reduced neuronal apoptosis. Collectively, API exerts its neuroprotective effect likely through the dual activities of anti-oxidation and anti-apoptosis, at least partly. These data provide a basic platform to consider API may be safely used as a potential drug for treatment of SAH.