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. 2023 Aug 4;13(1):12681.
doi: 10.1038/s41598-023-39919-4.

Combination of epigallocatechin 3 gallate and curcumin improves D-galactose and normal-aging associated memory impairment in mice

Md Ashrafur Rahman  1   2 , Arif Anzum Shuvo  3 , Md Mehedi Hasan Apu  3 , Monisha Rani Bhakta  3 , Farzana Islam  3 , Md Atiqur Rahman  3 , Md Rabiul Islam  4   5 , Hasan Mahmud Reza  6
Affiliations

Combination of epigallocatechin 3 gallate and curcumin improves D-galactose and normal-aging associated memory impairment in mice

Md Ashrafur Rahman et al. Sci Rep. .

Abstract

Previously, we observed curcumin improves aging-associated memory impairment in D-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Effect of EGCG + curcumin on RT in D-gal (A) and NA (B) mice group after 24 h of training. The RT was calculated by performing PA tasks among young adult (vehicle, EGCG-Con, Cur-Con), drug induced aging (D-gal, EGCG + D-gal, Cur + D-gal, EGCG + Cur + D-gal, and Ast + D-gal), and nature induced aging (NA, EGCG + NA, Cur + NA, EGCG + Cur + NA, and Ast + NA) groups. RT was expressed in second. Data was presented as mean ± SEM, n = 8 each group; ****p < 0.0001, ns not significant.
Figure 2
Figure 2
Effect of EGCG + Curcumin on the conditioning session (Day 1 of CFC) and context test (Day 2a) of D-gal mice group. The memory was assessed by analyzing the FR. The FR was expressed in percentage (%). Data was presented as mean ± SEM, n = 8 each group; **p < 0.01, ***p < 0.001, ****p < 0.0001, ns not significant.
Figure 3
Figure 3
Effect of EGCG + Curcumin on the conditioning session (Day 1 of CFC) and context test (Day 2a) of NA mice group. The memory was assessed by analyzing the FR. The FR was expressed in percentage (%). Data was presented as mean ± SEM, n = 8 each group; **p < 0.01, ***p < 0.001, ****p < 0.0001, ns not significant.
Figure 4
Figure 4
Effect of EGCG + Curcumin on the context (Day 31a) and cued fear memory (Day 2b and 31b) of D-gal mice group. The memory was assessed by analyzing the FR. The FR was expressed in percentage (%). Data was presented as mean ± SEM, n = 8 each group; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns not significant.
Figure 5
Figure 5
Effect of EGCG + Curcumin on the context (Day 31a) and cued fear memory (Day 2b and 31b) of NA mice group. The memory was assessed by analyzing the FR. The FR was expressed in percentage (%). Data was presented as mean ± SEM, n = 8 each group; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns not significant.
Figure 6
Figure 6
Effect of EGCG + Curcumin on GSH concentration (A,B), SOD (C,D) and CAT (E,F) activity in D-gal and NA mice group. The level of GSH, SOD and CAT activity were detected by using bioassay technique among young adult (vehicle, EGCG-Con, Cur-Con), drug induced aging (D-gal, EGCG + D-gal, Cur + D-gal, EGCG + Cur + D-gal, and Ast + D-gal), and nature induced aging (NA, EGCG + NA, Cur + NA, EGCG + Cur + NA, and Ast + NA) groups. GSH level, SOD and CAT activity were expressed in μmol/mg, U/30 s, and μmol/min/mg, respectively. Data was presented as mean ± SEM, n = 8 each group; *p < 0.05, **p < 0.01 ***p < 0.001, ****p < 0.0001, ns not significant.
Figure 7
Figure 7
Effect of EGCG + Curcumin on AOPP (A,B), NO (C,D), and MDA (E,F) concentration in D-gal and NA mice group. The AOPP, NO, and MDA level were assessed by using bioassay technique among young adult (vehicle, EGCG-Con, Cur-Con), drug induced aging (D-gal, EGCG + D-gal, Cur + D-gal, EGCG + Cur + D-gal, and Ast + D-gal), and nature induced aging (NA, EGCG + NA, Cur + NA, EGCG + Cur + NA, and Ast + NA) groups. AOPP, NO, and MDA level were represented in μmol/ml, mmol/mg, and nmol/ml, respectively. Data was presented as mean ± SEM, n = 8 each group; *p < 0.05, **p < 0.01, ****p < 0.0001, ns not significant.
Figure 8
Figure 8
Schematic presentation of whole experimental procedure: the treatment continued for ten weeks. After that, the behavioral parameters were detected using passive avoidance (PA) and contextual fear conditioning (CFC). The biomarkers were measured after completing the behavioral tasks.
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