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Plumbagin ameliorates memory dysfunction in streptozotocin induced Alzheimer's disease via activation of Nrf2/ARE pathway and inhibition of β-secretase
Nakhate KT, Bharne AP, Verma VS, Aru DN, Kokare DM.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018-03-22
Topic: Brain proteins, microglia and lab models
Although plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) protects against cerebral ischemia and spinal cord injury-induced oxidative stress and inflammation by activating the nuclear factor-erythroid 2-related factor-2 /antioxidant response element (Nrf2/ARE) pathway, its role in the amelioration of neurodegenerative diseases remains unexplored. In the present study, we investigated the effect of plumbagin on Alzheimer's disease (AD)-like condition in mice. The animals were treated intracerebroventricularly with streptozotocin (STZ; 3 mg/kg) twice, on day 1 and 3, to induce AD-like condition, and the symptoms were evaluated after 14 days. While the loss of learning and memory performance was evident in the mice subjected to Morris water maze (MWM), there was a striking increase in the population of astrocytes labelled with glial fibrillary acidic protein (GFAP) in the hippocampus. Daily intraperitoneal (i.p.) treatment with plumbagin (0.5 and 1 mg/kg), starting from 1 h prior to first dose of STZ, significantly prevented the cognitive deficits in MWM. On the other hand, administration of Nrf2/ARE pathway inhibitor, trigonelline (10 and 15 mg/kg, i.p.) enhanced the effects of STZ. Pre-treatment with subeffective dose of trigonelline (5 mg/kg) significantly attenuated the effects of plumbagin in MWM. While plumbagin prevented the STZ induced GFAP expression, this effect of plumbagin was attenuated by trigonelline. Moreover, the in silico docking study revealed potent inhibitory effect of plumbagin on β-secretase enzyme. The results of the present study suggest that plumbagin improves cognitive function in STZ induced mouse model of AD possibly via Nrf2/ARE mediated suppression of astrogliosis and inhibition of β-secretase enzyme.
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APA 7th
Nakhate, K. T., Bharne, A. P., Verma, V. S., Aru, D. N., & Kokare, D. M. (2018). Plumbagin ameliorates memory dysfunction in streptozotocin induced Alzheimer's disease via activation of Nrf2/ARE pathway and inhibition of β-secretase. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. https://doi.org/10.1016/j.biopha.2018.02.052
Vancouver
Nakhate KT, Bharne AP, Verma VS, Aru DN, Kokare DM. Plumbagin ameliorates memory dysfunction in streptozotocin induced Alzheimer's disease via activation of Nrf2/ARE pathway and inhibition of β-secretase. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018. doi:10.1016/j.biopha.2018.02.052. PMID: 29501041.
BibTeX
@article{nakhate2018-29501041,
author = {Nakhate, K. T. and Bharne, A. P. and Verma, V. S. and Aru, D. N. and Kokare, D. M.},
title = {{Plumbagin ameliorates memory dysfunction in streptozotocin induced Alzheimer's disease via activation of Nrf2/ARE pathway and inhibition of β-secretase}},
journal = {Biomedicine \& pharmacotherapy = Biomedecine \& pharmacotherapie},
year = {2018},
doi = {10.1016/j.biopha.2018.02.052},
pmid = {29501041},
url = {https://doi.org/10.1016/j.biopha.2018.02.052}
}
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Key findings
- Daily intraperitoneal (i.p.) treatment with plumbagin (0.5 and 1 mg/kg), starting from 1 h prior to first dose of STZ, significantly prevented the cognitive deficits in MWM.
- Pre-treatment with subeffective dose of trigonelline (5 mg/kg) significantly attenuated the effects of plumbagin in MWM.
- Moreover, the in silico docking study revealed potent inhibitory effect of plumbagin on β-secretase enzyme.
- The results of the present study suggest that plumbagin improves cognitive function in STZ induced mouse model of AD possibly via Nrf2/ARE mediated suppression of astrogliosis and inhibition of β-secretase enzyme.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29501041) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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