Serum containing Gengnianchun formula suppresses amyloid β‑induced inflammatory cytokines in BV‑2 microglial cells by inhibiting the NF‑κB and JNK signaling pathways

Chen,Pin‑Li; Wang,Wen‑Jun; Rao,Yan‑Qiu; Li,Jun; Cheng,Ming‑Jun

doi:10.3892/mmr.2018.8524

April-2018 Volume 17 Issue 4

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April-2018 Volume 17 Issue 4

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Serum containing Gengnianchun formula suppresses amyloid β‑induced inflammatory cytokines in BV‑2 microglial cells by inhibiting the NF‑κB and JNK signaling pathways

Authors:
- Pin‑Li Chen
- Wen‑Jun Wang
- Yan‑Qiu Rao
- Jun Li
- Ming‑Jun Cheng
View Affiliations / Copyright

Affiliations: Department of Integrated Traditional Chinese Medicine and Western Medicine, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China

Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 5043-5048
|
Published online on: January 31, 2018

https://doi.org/10.3892/mmr.2018.8524
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Abstract

As the resident macrophages of the brain's innate immune system, microglial cells are key modulators in the neurodegenerative disease Alzheimer's disease (AD). In particular, the activation and accumulation of microglial cells around amyloid plaques is considered to result in chronic neuroinflammation. Although the pathologic mechanism remains to be fully elucidated, inflammation has been shown to be critical in the pathogenesis of AD. The Gengnianchun (GNC) formula has long been used to treat perimenopausal syndrome clinically, and is particularly effective in improving learning ability and memory. Our previous study demonstrated that GNC formula had an anti‑inflammatory effect and offered neuroprotection in animal experiments. In the present study, the anti‑inflammatory properties of GNC and its underlying mechanism of action were examined in BV‑2 microglial cells. Amyloid‑β peptide (Aβ)‑stimulated microglial cells were examined for the production of proinflammatory cytokines and the underlying signaling pathways. Compared with the normal control group, the protein expression levels of IL‑1β and TNF‑α were significantly increased following treatment with Aβ (P<0.01), but medicated rat serum containing GNC formula (MRS) could significantly attenuated the Aβ‑induced secretion of these pro‑inflammatory cytokines. It was identified by CCK‑8 assay that the viability of the BV‑2 cells was not reduced following treatment with various concentrations of MRS. The phosphorylation of factor‑κB (NF‑κB) and c‑Jun N‑terminal kinase (JNK) was markedly increased following treatment with Aβ, compared with the normal control group (P<0.01). However, treatment with MRS resulted in a significant reduction in the phosphorylation of NF‑κB (P<0.05). These results suggested that MRS suppressed the Aβ‑induced inflammatory response of microglial cells by inhibiting the NF‑κB and JNK signaling pathways. These novel findings provide insights into the development of GNC formula as a therapeutic agent for the treatment of neurodegenerative disorders.

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1	Mattson MP: Pathways towards and away from Alzheimer's disease. Nature. 430:631–639. 2004. View Article : Google Scholar : PubMed/NCBI
2	Blennow K, de Leon MJ and Zetterberg H: Alzheimer's disease. Lancet. 368:387–403. 2006. View Article : Google Scholar : PubMed/NCBI
3	Wortmann M: Dementia: A global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 4:402012.PubMed/NCBI
4	Huang Y and Mucke L: Alzheimer mechanisms and therapeutic strategies. Cell. 148:1204–1222. 2012. View Article : Google Scholar : PubMed/NCBI
5	Iqbal K and Grundke-Iqbal I: Alzheimer's disease, a multifactorial disorder seeking multitherapies. Alzheimers Dement. 6:420–424. 2010. View Article : Google Scholar : PubMed/NCBI
6	Rodriguez-Vita J and Lawrence T: The resolution of inflammation and cancer. Cytokine Growth Factor Rev. 21:61–65. 2010. View Article : Google Scholar : PubMed/NCBI
7	Liu L and Chan C: The role of inflammasome in Alzheimer's disease. Ageing Res Rev. 15:6–15. 2014. View Article : Google Scholar : PubMed/NCBI
8	Mandrekar-Colucci S and Landreth GE: Microglia and inflammation in Alzheimer's disease. CNS Neurol Disord Drug Targets. 9:156–167. 2010. View Article : Google Scholar : PubMed/NCBI
9	Solito E and Sastre M: Microglia function in Alzheimer's disease. Front Pharmacol. 3:142012. View Article : Google Scholar : PubMed/NCBI
10	Prokop S, Miller KR and Heppner FL: Microglia actions in Alzheimer's disease. Acta Neuropathol. 126:461–477. 2013. View Article : Google Scholar : PubMed/NCBI
11	Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: Recent advances. Mol Med Today. 6:441–448. 2000. View Article : Google Scholar : PubMed/NCBI
12	Roshak AK, Callahan JF and Blake SM: Small-molecule inhibitors of NF-kappaB for the treatment of inflammatory joint disease. Curr Opin Pharmacol. 2:316–321. 2002. View Article : Google Scholar : PubMed/NCBI
13	Mattson MP: NF-kappaB in the survival and plasticity of neurons. Neurochem Res. 30:883–893. 2005. View Article : Google Scholar : PubMed/NCBI
14	Boissiere F, Hunot S, Faucheux B, Duyckaerts C, Hauw JJ, Agid Y and Hirsch EC: Nuclear translocation of NF-kappaB in cholinergic neurons of patients with Alzheimer's disease. Neuroreport. 8:2849–2852. 1997. View Article : Google Scholar : PubMed/NCBI
15	Mattson MP and Camandola S: NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest. 107:247–254. 2001. View Article : Google Scholar : PubMed/NCBI
16	Harper SJ and Wilkie N: MAPKs: New targets for neurodegeneration. Expert Opin Ther Targets. 7:187–200. 2003. View Article : Google Scholar : PubMed/NCBI
17	Mehan S, Meena H, Sharma D and Sankhla R: JNK: A stress-activated protein kinase therapeutic strategies and involvement in Alzheimer's and various neurodegenerative abnormalities. J Mol Neurosci. 43:376–390. 2011. View Article : Google Scholar : PubMed/NCBI
18	Correa SA and Eales KL: The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. J Signal Transduct. 2012:6490792012. View Article : Google Scholar : PubMed/NCBI
19	Zhao H, Wang SL, Qian L, Jin JL, Li H, Xu Y and Zhu XL: Diammonium glycyrrhizinate attenuates Aβ(1–42)-induced neuroinflammation and regulates MAPK and NF-κB pathways in vitro and in vivo. CNS Neurosci Ther. 19:117–124. 2013. View Article : Google Scholar : PubMed/NCBI
20	Suyu J and Meijuan W: Clinical observation of ‘climacterium capsule’ in improving the memory of climacterium women. Shanghai Zhong Yi Yao Za Zhi. 35:32–33. 2001.(In Chinese).
21	Zhao FG, Wang WJ and Zhou WJ: Effect of Gengnianchun recipe on learning memory function and hippocampal cholinergic system in ovariectmized rats. Zhongguo Zhong Xi Yi Jie He Za Zhi. 28:234–237. 2008.(In Chinese). PubMed/NCBI
22	Li J, Li B, Zhou WJ, Zhao FG, Li DJ and Wang WJ: Medicated rat serum containing Gengnianchun decoction reduces apoptosis of pheochromocytoma cells insulted by amyloid beta protein. Zhong Xi Yi Jie He Xue Bao. 8:472–479. 2010. View Article : Google Scholar : PubMed/NCBI
23	Jun L, Wenjun W, Dajin L and Wenjiang Z: Gengnianchun recipe inhibits apoptosis of pheochromocytoma cells from beta-amyloid 25–35 insult, better than monotherapies and their compounds. Neur Regen Res. 6:2815–2821. 2011.
24	Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW and Hong JT: Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation. 5:372008. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Serum containing Gengnianchun formula suppresses amyloid β‑induced inflammatory cytokines in BV‑2 microglial cells by inhibiting the NF‑κB and JNK signaling pathways

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