Qingre Lidan Jiedu Recipe improves high copper load-induced cognitive dysfunction in rats by regulating mitophagy

doi:10.12122/j.issn.1673-4254.2025.11.16

Abstract

Abstract:

Objective To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. Methods Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. Results Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. Conclusion QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.

Key words: Qingre Lidan Jiedu Recipe, Wilson's disease, cognitive impairment, NIX, FUNDC1

Yulan WANG, Xiang FANG, Zeming CHEN, Bingkun RUAN, Xinli HAN, Yujie TANG, Luyao ZHU. Qingre Lidan Jiedu Recipe improves high copper load-induced cognitive dysfunction in rats by regulating mitophagy[J]. Journal of Southern Medical University, 2025, 45(11): 2437-2443.

Figures/Tables 8

References 29

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Group	1 day	2 days	3 days	4 days
NG	203.12±26.11	157.55±30.61	79.14±17.49	50.01±15.38
MG	230.58±21.85¹⁾	204.83±38.17²⁾	142.24±15.02²⁾	134.99±32.44²⁾
TCM	215.44±16.70	190.55±29.41	124.26±28.70²⁾	117.23±14.60²⁾
PCA	212.14±16.81	187.89±25.33	125.87±30.75²⁾	120.49±15.22²⁾
TCM+PCA	209.21±10.49	186.68±19.86	117.89±26.67¹⁾	106.59±12.45²⁾³⁾

Group	1 day	2 days	3 days	4 days
NG	203.12±26.11	157.55±30.61	79.14±17.49	50.01±15.38
MG	230.58±21.85¹⁾	204.83±38.17²⁾	142.24±15.02²⁾	134.99±32.44²⁾
TCM	215.44±16.70	190.55±29.41	124.26±28.70²⁾	117.23±14.60²⁾
PCA	212.14±16.81	187.89±25.33	125.87±30.75²⁾	120.49±15.22²⁾
TCM+PCA	209.21±10.49	186.68±19.86	117.89±26.67¹⁾	106.59±12.45²⁾³⁾

Group	5 days (Short-term memory)	12 days (Long-term memory)
NG	16.02±5.54	17.88±10.21
MG	49.08±13.54²⁾	50.32±23.64²⁾
TCM	32.99±10.91¹⁾³⁾	31.26±19.93⁴⁾
PCA	35.51±11.99²⁾	33.11±20.10¹⁾⁴⁾
TCM+PCA	29.21±10.25⁴⁾	28.55±18.92⁴⁾

Group	5 days (Short-term memory)	12 days (Long-term memory)
NG	16.02±5.54	17.88±10.21
MG	49.08±13.54²⁾	50.32±23.64²⁾
TCM	32.99±10.91¹⁾³⁾	31.26±19.93⁴⁾
PCA	35.51±11.99²⁾	33.11±20.10¹⁾⁴⁾
TCM+PCA	29.21±10.25⁴⁾	28.55±18.92⁴⁾

Group	Latency (s)	Error count
NG	189.02±58.94	1.75±1.40
MG	64.07±40.38²⁾	7.75±1.04²⁾
TCM	155.22±40.82⁴⁾	4.75±1.28²⁾⁴⁾⁶⁾
PCA	152.01±48.44⁴⁾	5.00±1.69²⁾⁴⁾⁶⁾
TCM+PCA	179.73±38.11⁴⁾	2.13±1.96⁴⁾