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. 2024 May 11;13(10):1493.
doi: 10.3390/foods13101493.

From Epimedium to Neuroprotection: Exploring the Potential of Wushanicaritin

Donghui Luo  1 , Dingding Shi  2   3 , Lingrong Wen  1   2   3
Affiliations

From Epimedium to Neuroprotection: Exploring the Potential of Wushanicaritin

Donghui Luo et al. Foods. .

Abstract

Epimedium has been used for functional foods with many beneficial functions to human health. Wushanicaritin is one of the most important chemicals int Epimedium. This study investigated the neuroprotective effects of wushanicaritin and potential underlying mechanisms. The results demonstrated that wushanicaritin possessed superior intercellular antioxidant activity compared to icaritin. Wushanicaritin, with an EC50 value of 3.87 μM, showed better neuroprotective effect than quercetin, a promising neuroprotection agent. Wushanicaritin significantly reversed lactate dehydrogenase release, reactive oxygen species generation, cell apoptosis, and mRNA expression related to cell apoptosis and oxidative defense, in glutamate-induced PC-12 cells. Wushanicaritin could also maintain the enzymatic antioxidant defense system and mitochondrial function. The suppression of caspase-3 activation and amelioration of mitochondrial membrane potential loss and nucleus morphology changes were involved in the antiapoptotic effect of wushanicaritin. These findings suggested that wushanicaritin possesses excellent intercellular antioxidant and neuroprotective activities, showing potential promise in functional foods.

Keywords: Epimedium; antiapoptotic effect; intercellular antioxidant activity; neuroprotective activity; oxidative stress.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
The peroxyl radical-induced oxidation of DCFH to DCF in HepG2 cells. The inhibition of DCFH oxidation by quercetin (A,B), incaritin (C,D), and wushanicaritin (E,F) over 1 h, using the protocol involving no PBS wash between antioxidant and ABAP treatments (A,C,E), and the protocol with a PBS wash (B,D,F) to remove antioxidants in the medium after incubation.
Figure 2
Figure 2
Effects of wushanicaritin and quercetin on the cell viability of PC-12 cells. (A) The viability of PC-12 cells incubated with wushanicaritin; (B) the viability of PC-12 cells incubated with quercetin; (C) the viability of PC-12 cells co-treated with glutamate and wushanicaritin; (D) the viability of PC-12 cells co-treated with glutamate and quercetin; (E) effects of wushanicaritin and quercetin on the LDH release. Que refers to quercetin. The bars with no letters in common exhibit significantly different values (p < 0.05).
Figure 3
Figure 3
Effects of wushanicaritin and quercetin on the intracellular antioxidant defense system in glutamate-treated PC-12 cells. (A) Effects of wushanicaritin and quercetin on ROS production and intercellular antioxidant enzyme activities; (B) mRNA expression levels of genes related to oxidative stress. The mRNA expression levels were normalized to the vehicle control by using GAPDH as an endogenous reference. Que refers to quercetin. The values having no letters in common are significantly different (p < 0.05).
Figure 4
Figure 4
Effects of wushanicaritin and quercetin on the morphology of mitochondrial membrane potential (A) and ATP production (B). Control group refers to PC-12 cells with vehicle treatment (0.1% DMSO); Model group refers to PC-12 cells treated with glutamate; wushanicaritin-2 μM, wushanicaritin-5 μM and Que refers to PC-12 cells co-treated with glutamate and wushanicaritin at concentrations of 2, 5 μM, or quercetin (30 μM), respectively. Scale bar = 100 μm. The Bars with no letters in common are significantly different (p < 0.05).
Figure 5
Figure 5
Effects of wushanicaritin and quercetin on cell apoptosis as determined by flow cytometry assay after Annexin V–FITC/PI staining. In the representative dot plots, Q1 indicates necrotic cells, Q2 indicates late apoptotic cells, Q3 indicates viable cells, and Q4 indicates early apoptotic cells. Control group refers to PC-12 cells with vehicle treatment (0.1% DMSO); Model group refers to PC-12 cells treated with glutamate; wushanicaritin-2 μM, wushanicaritin-5 μM and Que refer to PC-12 cells co-treated with glutamate and wushanicaritin at concentrations of 2, 5 μM, or quercetin (30 μM), respectively.
Figure 6
Figure 6
Effects of wushanicaritin and quercetin on the transcriptional levels of apoptotic-related genes (A) and caspase-3 activity (B). The mRNA expression levels were normalized to the vehicle control group by using GAPDH as an endogenous reference. Que refers to quercetin. The bars having no letters in common indicate significantly different values (p < 0.05) (Figure 1).
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Grants and funding

The authors are grateful for the financial support from Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory (No. HJL202202B005).