Lycium barbarum polysaccharides alleviates cisplatin-induced granulosa cell injury by downregulating miR-23a

doi:10.12122/j.issn.1673-4254.2025.11.06

Abstract

Abstract:

Objective To evaluate the protective effect of Lycium barbarum polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. Methods Human granulosa-like tumor cell line (KGN) were treated with 2.5 µg/mL cisplatin for 24 h, followed by treatment with 100, 500, and 1000 mg/L LBP, and the changes in cell viability, apoptosis, level of anti-Müllerian hormone (AMH), and cell ultrastructure were detected with CCK-8 assay, flow cytometry, ELISA and transmission electron microscopy. The cellular expressions of Bax, caspase-3, Bcl-2, and the PI3K/AKT pathway proteins were analyzed using Western blotting, and the expression of miR-23a was detected with RT-qPCR. KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP. Results Cisplatin treatment significantly inhibited cell viability, induced apoptosis, decreased AMH level, caused ultrastructural abnormalities, increased Bax and caspase-3 expression, and lowered Bcl-2 expression in KGN cells. Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells. LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells, and in particular, LBP treatment at the medium dose for 24 h significantly improved KGN cell viability, reduced apoptosis, enhanced their endocrine function, and ameliorated ultrastructural abnormalities. Mechanistically, medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells, subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2. Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP. Conclusion LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway, suggesting a potential therapeutic strategy for ovarian function preservation.

Key words: Lycium barbarum polysaccharides, miR-23a, KGN cells, cell apoptosis, PI3K/AKT signaling pathway

Liuqing LIU, Kun WANG, Xueqing WANG, Bingxin DU. Lycium barbarum polysaccharides alleviates cisplatin-induced granulosa cell injury by downregulating miR-23a[J]. Journal of Southern Medical University, 2025, 45(11): 2340-2349.

Figures/Tables 22

References 32

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Group	CDDP exposure duration(h)
Group	0	12	24	48
NC	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
CDDP 1.25	0.97±0.15	0.87±0.10	0.65±0.07^a	0.61±0.07^a
CDDP 2.5	0.98±0.14	0.77±0.09^b	0.50±0.03^a	0.41±0.04^a
CDDP 5	0.94±0.12	0.65±0.08^a	0.42±0.03^a	0.28±0.04^a
CDDP 10	0.97±0.10	0.55±0.10^a	0.32±0.03^a	0.25±0.06^a

Group	CDDP exposure duration(h)
Group	0	12	24	48
NC	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
CDDP 1.25	0.97±0.15	0.87±0.10	0.65±0.07^a	0.61±0.07^a
CDDP 2.5	0.98±0.14	0.77±0.09^b	0.50±0.03^a	0.41±0.04^a
CDDP 5	0.94±0.12	0.65±0.08^a	0.42±0.03^a	0.28±0.04^a
CDDP 10	0.97±0.10	0.55±0.10^a	0.32±0.03^a	0.25±0.06^a

Group	LBP exposure duration (h)
Group	12	24	48
NC	1.00±0.00	1.00±0.00	1.00±0.00
MC	0.71±0.04^a	0.59±0.06^a	0.52±0.07^a
LBP-L	0.72±0.04	0.74±0.03^c	0.58±0.07^e
LBP-M	0.80±0.09	0.85±0.06^c	0.74±0.04^c
LBP-H	0.76±0.11	0.70±0.06^f	0.65±0.04^df

Group	LBP exposure duration (h)
Group	12	24	48
NC	1.00±0.00	1.00±0.00	1.00±0.00
MC	0.71±0.04^a	0.59±0.06^a	0.52±0.07^a
LBP-L	0.72±0.04	0.74±0.03^c	0.58±0.07^e
LBP-M	0.80±0.09	0.85±0.06^c	0.74±0.04^c
LBP-H	0.76±0.11	0.70±0.06^f	0.65±0.04^df

Group	Apoptosis rate (%)
NC	5.27±0.22
MC	45.70±1.14^a
LBP-L	29.29±0.52^ce
LBP-M	16.55±0.02^c
LBP-H	27.82±0.28^ce