Open Access

Scutellarein suppresses Aβ‑induced memory impairment via inhibition of the NF‑κB pathway in vivo and in vitro

  • Authors:
    • Xiao‑Wei Huang
    • Yan Xu
    • Xin Sui
    • He Lin
    • Jia‑Ming Xu
    • Dong Han
    • Dou‑Dan Ye
    • Guang‑Fu Lv
    • Yue‑Xin Liu
    • Xiao‑Bo Qu
    • Ming‑Hua Duan
  • View Affiliations

  • Published online on: April 18, 2019     https://doi.org/10.3892/ol.2019.10274
  • Pages: 5581-5589
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid β (Aβ)‑induced AD‑like pathology were investigated. An in vitro model of inflammation and an aged rat model were used to confirm the effects of Scue. In vitro MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aβ deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro‑inflammatory factors and nuclear factor‑κB (NF‑κB) activation in hippocampal tissues in vivo were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells in vitro, inhibited Aβ‑induced cognitive impairment, suppressed hippocampal neuro‑inflammation and suppressed activation of NF‑κB in vivo. Therefore, Scue may be a useful agent for the treatment of Aβ‑associated pathology in the central nervous system through inhibition of the protein kinase B/NF‑κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.

References

1 

Duits FH, Teunissen CE, Bouwman FH, Visser PJ, Mattsson N, Zetterberg H, Blennow K, Hansson O, Minthon L, Andreasen N, et al: The cerebrospinal fluid ‘Alzheimer profile’: Easily said, but what does it mean? Alzheimers Dement. 10:713–723.e2. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Wortmann M: Dementia: A global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 4:402012.PubMed/NCBI

3 

Blennow K, de Leon MJ and Zetterberg H: Alzheimer's disease. Lancet. 368:387–403. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Bagheri M, Joghataei MT, Mohseni S and Roghani M: Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer's disease. Neurobiol Learn Mem. 95:270–276. 2011. View Article : Google Scholar : PubMed/NCBIPubMed/NCBI

5 

He FQ, Qiu BY, Zhang XH, Li TK, Xie Q, Cui DJ, Huang XL and Gan HT: Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-β(1–42). Brain Res. 1384:89–96. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Zhou J, Zhou L, Hou D, Tang J, Sun J and Bondy SC: Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer's disease. Brain Res. 1388:141–147. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Song JX, Lin X, Wong RN, Sze SC, Tong Y, Shaw PC and Zhang YB: Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells. Phytother Res. 25:435–443. 2011.PubMed/NCBI

8 

Dargahi L, Nasiraei-Moghadam S, Abdi A, Khalaj L, Moradi F and Ahmadiani A: Cyclooxygenase (COX)-1 activity precedes the COX-2 induction in Aβ-induced neuroinflammation. J Mol Neurosci. 45:10–21. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Zeng YQ, Cui YB, Gu JH, Liang C and Zhou XF: Scutellarin mitigates Aβ-induced neurotoxicity and improves behavior impairments in AD mice. Molecules. 23:E8692018. View Article : Google Scholar : PubMed/NCBI

10 

Baluchnejadmojarad T, Zeinali H and Roghani M: Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat: Insights into underlying mechanisms. Int Immunopharmacol. 54:311–319. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Chledzik S, Strawa J, Matuszek K and Nazaruk J: Pharmacological effects of scutellarin, an active component of genus scutellaria and erigeron: A systematic review. Am J Chin Med. 46:319–337. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Sun CY, Zhu Y, Li XF, Wang XQ, Tang LP, Su ZQ, Li CY, Zheng GJ and Feng B: Scutellarin increases cisplatin-induced apoptosis and autophagy to overcome cisplatin resistance in non-small cell lung cancer via ERK/p53 and c-met/AKT signaling pathways. Front Pharmacol. 9:922018. View Article : Google Scholar : PubMed/NCBI

13 

Yan WJ and Zhang SQ: Inhibition Mechanism of Baicalein on the Liver Metastasis of Breast Cancer cell in Vivo. Pract J Cancer. 33:1915–1919. 2018.

14 

Liu W, Liu ZY, Qi HW, et al: Enhancement role of baicalein used as adjuvant on the immuno-response of -Tcells in vivo of mice with melanoma. Prac J Med Pharm. 35:1114–1118. 2018.

15 

Li Q, Chen Y, Zhang X, Zuo S, Ge H, Chen Y, Liu X, Zhang JH, Ruan H and Feng H: Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats. J Clin Neurosci. 34:264–270. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Mo J, Yang R, Li F, Zhang X, He B, Zhang Y, Chen P and Shen Z: Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation. Phytomedicine. 42:66–74. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Huang H, Geng Q, Yao H, Shen Z, Wu Z, Miao X and Shi P: Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats. Iran J Basic Med Sci. 21:267–276. 2018.PubMed/NCBI

18 

Yang N, Zhao Y, Wang Z, Liu Y and Zhang Y: Scutellarin suppresses growth and causes apoptosis of human colorectal cancer cells by regulating the p53 pathway. Mol Med Rep. 15:929–935. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Yang H, Du Y, Wan S, Trahan GD, Jin Y and Zhang W: Mesoporous 2D covalent organic frameworks based on shape-persistent arylene-ethynylene macrocycles. Chem Sci. 6:4049–4053. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Erbele ID, Lin FR, Agrawal Y, Francis HW, Carey JP and Chien WW: Racial differences of pigmentation in the human vestibular organs. Otolaryngol Head Neck Surg. 155:479–484. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Hou L, Chen L and Fang L: Scutellarin inhibits proliferation, invasion, and tumorigenicity in human breast cancer cells by regulating HIPPO-YAP signaling pathway. Med Sci Monit. 23:5130–5138. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Tang H, Tang Y, Li NG, Lin H, Li W, Shi Q, Zhang W, Zhang P, Dong Z, Shen M, et al: Comparative metabolomic analysis of the neuroprotective effects of scutellarin and scutellarein against ischemic insult. PLoS One. 10:e01315692015. View Article : Google Scholar : PubMed/NCBI

23 

Thirusangu P, Vigneshwaran V, Vijay Avin BR, Rakesh H, Vikas HM and Prabhakar BT: Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation. Biochem Biophys Res Commun. 484:85–92. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Mamadalieva NZ, Herrmann F, El-Readi MZ, Tahrani A, Hamoud R, Egamberdieva DR, Azimova SS and Wink M: Flavonoids in Scutellaria immaculata and S. ramosissima (Lamiaceae) and their biological activity. J Pharm Pharmacol. 63:1346–1357. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Ni G, Tang Y, Li M, He Y and Rao G: Synthesis of scutellarein derivatives with a long aliphatic chain and their biological evaluation against human cancer cells. Molecules. 23:E3102018. View Article : Google Scholar : PubMed/NCBI

26 

Estevez-Garcia IO, Gallegos-Nava S, Vera-Pérez E, Silveira LH, Ventura-Ríos L, Vancini G, Hernández-Díaz C, Sánchez-Muñoz F, Ballinas-Verdugo MA, Gutierrez M, et al: Levels of cytokines and microRNAs in individuals with asymptomatic hyperuricemia and ultrasonographic findings of gout: A bench-to-bedside approach. Arthritis Care Res (Hoboken). 70:1814–1821. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Devkota K, Wang YH, Liu MY, Li Y and Zhang YW: Case report: III° atrioventricular block due to fulminant myocarditis managed with non-invasive transcutaneous pacing. Version 2. F1000Res. 7:2392018. View Article : Google Scholar : PubMed/NCBI

28 

van der Stelt M, Mazzola C, Esposito G, Matias I, Petrosino S, De Filippis D, Micale V, Steardo L, Drago F, Iuvone T and Di Marzo V: Endocannabinoids and beta-amyloid-induced neurotoxicity in vivo: Effect of pharmacological elevation of endocannabinoid levels. Cell Mol Life Sci. 63:1410–1424. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Yamaguchi Y, Higashi M, Matsuno T and Kawashima S: Ameliorative effects of azaindolizinone derivative ZSET845 on scopolamine-induced deficits in passive avoidance and radial-arm maze learning in the rat. Jpn J Pharmacol. 87:240–244. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Ma Y, Wang Q, Liu F, Ma X, Wu L, Guo F, Zhao S, Huang F and Qin G: KLF5 promotes the tumorigenesis and metastatic potential of thyroid cancer cells through the NF-κB signaling pathway. Oncol Rep. 40:2608–2618. 2018.PubMed/NCBI

31 

Liao J and Dong W: Effects of donepezil and verapamilon on learning and memory function in Alzheimer's disease rat model. China Academica Journal Electronic Publishing House. 34:58–60. 2012.

32 

Hu D, Li C, Han N, Miao L, Wang D, Liu Z, Wang H and Yin J: Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Aβ142-induced memory impairment in mice. Planta Med. 78:1332–1336. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Kim SR, Lee MK, Koo KA, Kim SH, Sung SH, Lee NG, Markelonis GJ, Oh TH, Yang JH and Kim YC: Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity. J Neurosci Res. 76:397–405. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Yan T, Shang L, Wang M, Zhang C, Zhao X, Bi K and Jia Y: Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats. Metab Brain Dis. 31:653–661. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Tang YY and Tang XQ: Research progress in the neurobiological effects of hydrogen sulfide. Sheng Li Ke Xue Jin Zhan. 48:42–51. 2017.(In Chinese). PubMed/NCBI

36 

Hu BL and Guo CY: Advances achievements about neuroprotective mechanisms of paeoniflorin. Acta Neuropharmacologica. 5:51–56. 2015.

37 

Jang JH and Surh YJ: Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death. Free Radic Biol Med. 34:1100–1110. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Qu HM, Liu SJ and Zhang CY: Antitumor and antiangiogenic activity of Schisandra chinensis polysaccharide in a renal cell carcinoma model. Int J Biol Macromol. 66:52–56. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Moosavi M, Khales GY, Abbasi L, Zarifkar A and Rastegar K: Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation. Neuropharmacology. 62:2018–2023. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Shi J, Liu Q, Wang Y and Luo G: Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats. Pharmacol Biochem Behav. 96:449–453. 2010.

41 

Dong Y, Xu Z, Zhang Y, McAuliffe S, Wang H, Shen X, Yue Y and Xie Z: RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation. Med Gas Res. 1:52011. View Article : Google Scholar : PubMed/NCBI

42 

Zhang J, Dong Y, Xu Z, Zhang Y, Pan C, McAuliffe S, Ichinose F, Yue Y, Liang W and Xie Z: 2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells. Anesth Analg. 113:1468–1475. 2011. View Article : Google Scholar : PubMed/NCBI

43 

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M and Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 39:44–84. 2007. View Article : Google Scholar : PubMed/NCBI

44 

Moreira FTC, Sale MGF and Di Lorenzo M: Towards timely Alzheimer diagnosis: A self-powered amperometric biosensor for the neurotransmitter acetylcholine. Biosens Bioelectron. 87:607–614. 2017. View Article : Google Scholar : PubMed/NCBI

45 

Engblom M, Alexanderson K, Englund L, Norrmén G and Rudebeck CE: When physicians get stuck in sick-listing consultations: A qualitative study of categories of sick-listing dilemmas. Work. 35:137–142. 2010.PubMed/NCBI

46 

Knezovic A, Osmanovic-Barilar J, Curlin M, Hof PR, Simic G, Riederer P and Salkovic-Petrisic M: Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. J Neural Transm (Vienna). 122:577–592. 2015. View Article : Google Scholar : PubMed/NCBI

47 

Heo K, Cho YJ, Cho KJ, Kim HW, Kim HJ, Shin HY, Lee BI and Kim GW: Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice. Neurosci Lett. 398:195–200. 2006. View Article : Google Scholar : PubMed/NCBI

48 

Bu P, Keshavarzian A, Stone DD, Liu J, Le PT, Fisher S and Qiao L: Apoptosis: One of the mechanisms that maintains unresponsiveness of the intestinal mucosal immune system. J Immunol. 166:6399–6403. 2001. View Article : Google Scholar : PubMed/NCBI

49 

Steinberg I, McCoy HI and Dotter CT: Angiocardiographic findings in pulmonary tuberculosis. Dis Chest. 19:510–520. 1951. View Article : Google Scholar : PubMed/NCBI

50 

Gilmore TD and Wolenski FS: NF-κB: Where did it come from and why? Immunol Rev. 246:14–35. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Yang LP, Zhu XA and Tso MO: Role of NF-kappaB and MAPKs in light-induced photoreceptor apoptosis. Invest Ophthalmol Vis Sci. 48:4766–4776. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Huang, X., Xu, Y., Sui, X., Lin, H., Xu, J., Han, D. ... Duan, M. (2019). Scutellarein suppresses Aβ‑induced memory impairment via inhibition of the NF‑κB pathway in vivo and in vitro. Oncology Letters, 17, 5581-5589. https://doi.org/10.3892/ol.2019.10274
MLA
Huang, X., Xu, Y., Sui, X., Lin, H., Xu, J., Han, D., Ye, D., Lv, G., Liu, Y., Qu, X., Duan, M."Scutellarein suppresses Aβ‑induced memory impairment via inhibition of the NF‑κB pathway in vivo and in vitro". Oncology Letters 17.6 (2019): 5581-5589.
Chicago
Huang, X., Xu, Y., Sui, X., Lin, H., Xu, J., Han, D., Ye, D., Lv, G., Liu, Y., Qu, X., Duan, M."Scutellarein suppresses Aβ‑induced memory impairment via inhibition of the NF‑κB pathway in vivo and in vitro". Oncology Letters 17, no. 6 (2019): 5581-5589. https://doi.org/10.3892/ol.2019.10274