[Effect of aqueous extract of Corni Fructus on Aβ_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease]

by Selleckchem | Feb 08 2024

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on β-amyloid protein 25-35(Aβ_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aβ_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of β-amyloid protein 1-42(Aβ_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aβ_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol with β-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aβ_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aβ_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aβ_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aβ_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aβ_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

Comments:

This study seems to have explored the impact of Corni Fructus, a plant extract, on Alzheimer's disease (AD) in mice induced with Aβ_(25-35) protein. Sixty male mice were divided into groups and treated with different doses of Corni Fructus extract, aiming to assess its effect on brain injury and neuroinflammation caused by Aβ_(25-35).

The study conducted various tests and analyses, including behavioral tests, histological examinations (using Hematoxylin-eosin staining), detection of apoptosis levels, measuring levels of specific proteins like Aβ_(1-42), p-Tau, IL-6, TNF-α, Bcl-2, caspase-3, caspase-9, and Bax, as well as using immunofluorescence, Western blot, MTT assays, and molecular docking to analyze interactions with certain proteins (APP, IL-6, and TNF-α).

The findings suggest that the Corni Fructus extract might have several positive effects:

1. **Improvement in cognitive functions:** The extract seemed to enhance learning and memory abilities in mice induced with Aβ_(25-35), possibly by affecting autonomous activity and altering certain behavioral patterns.

2. **Reduction in brain injury and neuroinflammation:** Corni Fructus extract appeared to reduce brain damage caused by Aβ_(25-35) by altering the expression levels of various proteins related to inflammation, apoptosis, and neurodegeneration.

3. **Identification of potential compounds:** Specific compounds within Corni Fructus, such as caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and (+)-lyoniresinol, were suggested to be responsible for its anti-AD effects.

The study's conclusions propose that Corni Fructus extract might ameliorate cognitive dysfunction and brain damage induced by Aβ_(25-35) in mice by reducing apoptosis, inflammation, and regulating protein expression levels. The specific compounds identified within the extract could be crucial in mediating these effects.

This research provides a basis for further investigation into the potential therapeutic benefits of Corni Fructus in Alzheimer's disease treatment, potentially through the development of targeted compounds or medications derived from this extract.