Nutr Res Pract.  2023 Apr;17(2):371-385. 10.4162/nrp.2023.17.2.371.

Role of soy lecithin combined with soy isoflavone on cerebral blood flow in rats of cognitive impairment and the primary screening of its optimum combination

• Li H
• Wang X
• Li X
• Zhou X
• Wang X
• Li T
• Xiao R
• Xi Y

• KMID: 2541372
• DOI: http://doi.org/10.4162/nrp.2023.17.2.371

Abstract

BACKGROUND/OBJECTIVES
Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells.
MATERIALS/METHODS
In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylineosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2′-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 μM of Gen were used, while the 25, 50, or 100 μM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells.
RESULTS
In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective antioxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity.
CONCLUSIONS
SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

Keyword

Cerebral blood flow; cognitive impairment; lecithin; isoflavone; beta-amyloid peptide

Figure

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  Fig. 1 Effect of SIF and Aβ1-42 on weight (mean ± SD, n = 6/group).SIF, soy isoflavone; SL, soy lecithin; Aβ, β-amyloid.

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  Fig. 2 Neuroprotective effect of SIF combined with SL on (A) swimming trace and (B) target crossing of learning and memory impairment rats induced by Aβ1-40. The control group was the rats treated with 0.5% CMC-Na and injected with normal saline; the Aβ1-40 group was rats treated with 0.5% CMC-Na and injected with Aβ1-40; the SIF50 + SL40 + Aβ1-40 group was the rats treated with SIF (25 mg/kg·d) + SL (40 mg/kg·d) and injected with Aβ1-40; the SIF50 + SL80 + Aβ1-40 group and the SIF50 + SL160 + Aβ1-40 group were the same as that shown above (n = 6 per group). All the data are reported as mean ± SD.SIF, soy isoflavone; SL, soy lecithin; Aβ, β-amyloid.*P < 0.05 compared with the control group; †P < 0.05 compared with the Aβ1-40 group.

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  Fig. 3 Neuroprotective effect of SIF combined with SL on the CBF (%) of learning and memory impairment rats induced by Aβ1-40. The 3 pictures of every group are detected position image, CBF perfusion color image, and blood flow time window (TOI is 60 seconds detection time). Position 1 is the target of CBF detection. → showed marked bregma of rats. The control group was the rats treated with 0.5% CMC-Na and injected with normal saline; the Aβ1-40 group was the rats treated with 0.5% CMC-Na and injected with Aβ1-40; the SIF50 + SL40 + Aβ1-40 group was the rats treated with SIF (50 mg/kg·d) + SL (40 mg/kg·d) and injected with Aβ1-40; SIF50 + SL80 + Aβ1-40 group and the SIF50 + SL160 + Aβ1-40 group were the same as that shown above (n = 5 per group). All the data are reported as mean ± SD.SIF, soy isoflavone; SL, soy lecithin; CBF, cerebral blood flow; Aβ, β-amyloid; TOI, time of interest.*P < 0.05 compared with control group; †P < 0.05 compared with Aβ1-40 group.

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  Fig. 4 Neuroprotective effect of SIF combined with SL on brain tissue and cerebrovascular learning and memory impairment rats induced by Aβ1-40. The control group was the rats treated with 0.5% CMC-Na and injected with normal saline; the Aβ1-40 group was the rats treated with 0.5% CMC-Na and injected with Aβ1-40; the SIF50 + SL40 + Aβ1-40 group was the rats treated with SIF (50 mg/kg·d) + SL (40 mg/kg·d) and injected with Aβ1-40; SIF50 + SL80 + Aβ1-40 and SIF50 + SL160 + Aβ1-40 group were the same as that shown above (n = 3 per group). The staff gauge showed 50 μm at the right side of the bottom of every picture.SIF, soy isoflavone; SL, soy lecithin; Aβ, β-amyloid.

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  Fig. 5 Neuroprotective effect of SIF combined with SL on RNA oxidative damage maker 8-OHdG (A), GSSG (B), SOD (C), and GSH (D) levels in the plasma of learning and memory impairment rats induced by Aβ1-40. The Control group was the rats treated with 0.5% CMC-Na and injected with normal saline; the Aβ1-40 group was the rats treated with 0.5% CMC-Na and injected with Aβ1-40; the SIF50 + SL40 + Aβ1-40 group was the rats treated with SIF (50 mg/kg·d) + SL (40 mg/kg·d) and injected with Aβ1-40; the SIF50 + SL80 + Aβ1-40 group and SIF50 + SL160 + Aβ1-40 group were the same as that shown above (n = 5 per group). All the data are reported as mean ± SD.SIF, soy isoflavone; SL, soy lecithin; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; GSSG, oxidized glutathione; SOD, superoxide dismutase; GSH, glutathione; Aβ, β-amyloid.*P < 0.05 compared with control group; †P < 0.05 compared with Aβ1-40 group.

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  Fig. 6 Cell viability of bEND.3 cells in different pretreatment doses of SL or Gen at different times. (A) Cell viability of bEND.3 cells from untreated cells (control group), cells exposed to 25 μM Aβ25-35 (Aβ25 group), and cells exposed to 10/100/1,000/2,000 μM SL 2/6/12/24 hours before 25 μM Aβ25-35 was added (SL10/100/1,000/2,000 μM + Aβ groups). (B) Cell viability of bEND.3 cells from untreated cells (control group), cells exposed to 25 μM Aβ25-35 (Aβ25 group), and cells exposed to 10/25/50/100/200/400 μM SL 2/6 hours before 25 μM Aβ25-35 was added (SL10/25/50/100/200/400 μM + Aβ groups). All data are reported as the mean ± SD.SL, soy lecithin; Gen, genistein; Aβ, β-amyloid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.*P < 0.05 compared to the control group; †P < 0.05 compared to the Aβ25 group.

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  Fig. 7 Neuroprotective effect of SIF combined with SL on RNA oxidative damage maker 8-OHdG (A), GSSG (B), SOD (C), and GSH (D) levels in bEND.3 cell. The control group was untreated cells; the Aβ25 group was the cells exposed to 25 μM Aβ25-35; the Gen50 + SL25 + Aβ group was the cell exposed to 25 μM Aβ25-35 and treated with Gen (50 μM) + SL (25 μM); the Gen50 + SL50 + Aβ group and Gen50 + SL100 + Aβ group were the same as that shown above. All data were shown as mean ± SD.SIF, soy isoflavone; SL, soy lecithin; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; GSSG, oxidized glutathione; SOD, superoxide dismutase; GSH, glutathione; Aβ, β-amyloid.*P < 0.05 compared with control group; †P < 0.05 compared with Aβ1-40 group.

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