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Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans.
Sci Rep. 2017 09 12; 7(1):11408.SR

Abstract

Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the Aβ toxicity was significantly reverted by daf-16 RNAi, rather than skn-1 RNAi or hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved Aβ-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases.

Authors+Show Affiliations

Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China. lihy@lzu.edu.cn.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28900141

Citation

Zhi, Dejuan, et al. "Dianxianning Improved Amyloid Β-induced Pathological Characteristics Partially Through DAF-2/DAF-16 Insulin Like Pathway in Transgenic C. Elegans." Scientific Reports, vol. 7, no. 1, 2017, p. 11408.
Zhi D, Wang D, Yang W, et al. Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans. Sci Rep. 2017;7(1):11408.
Zhi, D., Wang, D., Yang, W., Duan, Z., Zhu, S., Dong, J., Wang, N., Wang, N., Fei, D., Zhang, Z., Wang, X., Wang, M., & Li, H. (2017). Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans. Scientific Reports, 7(1), 11408. https://doi.org/10.1038/s41598-017-11628-9
Zhi D, et al. Dianxianning Improved Amyloid Β-induced Pathological Characteristics Partially Through DAF-2/DAF-16 Insulin Like Pathway in Transgenic C. Elegans. Sci Rep. 2017 09 12;7(1):11408. PubMed PMID: 28900141.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans. AU - Zhi,Dejuan, AU - Wang,Dong, AU - Yang,Wenqi, AU - Duan,Ziyun, AU - Zhu,Shuqian, AU - Dong,Juan, AU - Wang,Na, AU - Wang,Ningbo, AU - Fei,Dongqing, AU - Zhang,Zhanxin, AU - Wang,Xin, AU - Wang,Meizhu, AU - Li,Hongyu, Y1 - 2017/09/12/ PY - 2017/01/25/received PY - 2017/08/29/accepted PY - 2017/9/14/entrez PY - 2017/9/14/pubmed PY - 2019/6/22/medline SP - 11408 EP - 11408 JF - Scientific reports JO - Sci Rep VL - 7 IS - 1 N2 - Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the Aβ toxicity was significantly reverted by daf-16 RNAi, rather than skn-1 RNAi or hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved Aβ-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28900141/Dianxianning_improved_amyloid_β_induced_pathological_characteristics_partially_through_DAF_2/DAF_16_insulin_like_pathway_in_transgenic_C__elegans_ L2 - http://dx.doi.org/10.1038/s41598-017-11628-9 DB - PRIME DP - Unbound Medicine ER -