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Steroid-Enriched Fraction of Achyranthes bidentata Protects Amyloid β Peptide 1–40-Induced Cognitive Dysfunction and Neuroinflammation in Rats

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Abstract

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aβ 1–40-induced Alzheimer’s disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aβ 1–40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aβ 1–40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aβ 1–40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aβ 1–40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aβ 1–40-induced AD rat model.

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Abbreviations

Aβ:

amyloid β peptide

AB:

Achyranthes bidentata

ABS:

steroid-enriched fraction of Achyranthes bidentata

AChE:

acetylcholinesterase

AD:

Alzheimer’s disease

DTNB:

5,5′-dithiobis(2-nitrobenzoic acid)

ERK:

extracellular signal–regulated kinase

GADPH:

glyceraldehyde 3-phosphate dehydrogenase

GFAP:

glial fibrillary acidic protein

GPx:

glutathione peroxidase

GR:

glutathione reductase

GSH:

glutathione

HPLC:

high-performance liquid chromatography

IBA-1:

ionized calcium binding adaptor molecule 1

IL-1β:

interleukin-1β

IL-6:

interleukin-6

JNK:

c-Jun N-terminal kinase

MAPKs:

mitogen-activated protein kinases

MDA:

malondialdehyde

MWM:

Morris water maze

NADPH:

nicotinamide adenine dinucleotide phosphate

NF-κB:

nuclear factor kappa-light-chain-enhancer of activated B cells

NFT:

neurofibrillary tangle

p-ERK:

phospho-ERK

PD:

Parkinson’s disease

p-JNK:

phospho-JNK

p-p38:

phospho-p38

p-p65:

phospho-p65

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TBA:

thiobarbituric acid

TBARS:

thiobarbituric acid reactive substances

TNF-α:

tumor necrosis factor alpha.

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Funding

Financial support is from the Ministry of Science and Technology, Taiwan (NSC 100-2320-B-214 -001, MOST104-2320-B-039-027-MY2, and MOST105-2622-B-039-003-CC2) and ISU-103-01-E-02.

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Author notes

  1. Li-Wei Lin and Fan-Hsuan Tsai contributed equally to this work.

Authors and Affiliations

  1. School of Chinese Medicines for Post-Baccalaureate, I-Shou University, Kaohsiung, 82445, Taiwan

    Li-Wei Lin & Fan-Hsuan Tsai

  2. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 40402, Taiwan

    Wan-Cheng Lan & Chi-Rei Wu

  3. Department of Pharmacy, China Medical University Hospital, Taichung, 40402, Taiwan

    Yih-Dih Cheng

  4. Pintung Branch, Kaohsiung Veterans General Hospital, Pitung, 91245, Taiwan

    Sheng-Chi Lee

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  1. Li-Wei Lin
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Correspondence to Sheng-Chi Lee or Chi-Rei Wu.

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The Institutional Animal Care and Use Committee of I-Shou University approved the experimental protocol (IACUC-ISU-9905), and the animals were cared according to the Guiding Principles for the Care and Use of Laboratory Animals.

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Lin, LW., Tsai, FH., Lan, WC. et al. Steroid-Enriched Fraction of Achyranthes bidentata Protects Amyloid β Peptide 1–40-Induced Cognitive Dysfunction and Neuroinflammation in Rats. Mol Neurobiol 56, 5671–5688 (2019). https://doi.org/10.1007/s12035-018-1436-7

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