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. 2024 Jan 8;13(1):36.
doi: 10.3390/biology13010036.

Red Ginseng Attenuates the Hepatic Cellular Senescence in Aged Mice

Da-Yeon Lee  1 , Juliana Arndt  1 , Jennifer F O'Connell  2 , Josephine M Egan  2 , Yoo Kim  1
Affiliations

Red Ginseng Attenuates the Hepatic Cellular Senescence in Aged Mice

Da-Yeon Lee et al. Biology (Basel). .

Abstract

Cellular senescence is defined as an irreversible cell cycle arrest accompanied by morphological and physiological alterations during aging. Red ginseng (RG), processed from fresh ginseng (Panax ginseng C.A. Meyer) with a one-time steaming and drying process, is a well-known beneficial herbal medicine showing antioxidant, anti-inflammatory, and anti-aging properties. The current study aimed to investigate the benefits of RG in alleviating hepatic cellular senescence and its adverse effects in 19-month-old aged mice. We applied two different intervention methods and durations to compare RG's effects in a time-dependent manner: (1) oral gavage injection for 4 weeks and (2) ad libitum intervention for 14 weeks. We observed that 4-week RG administration was exerted to maintain insulin homeostasis against developing age-associated insulin insensitivity and suppressed cellular senescence pathway in the liver and primary hepatocytes. Moreover, with remarkable improvement of insulin homeostasis, 14-week RG supplementation downregulated the activation of c-Jun N-terminal kinase (JNK) and its downstream transcriptional factor nuclear factor-κB (NF-κB) in aged mice. Lastly, RG treatment significantly reduced the senescence-associated β-galactosidase (SA-β-gal)-positive cells in primary hepatocytes and ionizing radiation (IR)-exposed mouse embryonic fibroblasts (MEFs). Taken together, we suggest that RG can be a promising candidate for a senolytic substance by preventing hepatic cellular senescence.

Keywords: apoptosis; cellular senescence; inflammation; insulin homeostasis; liver; red ginseng.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Red ginseng supplementation for 4 weeks expresses the possibility of being a senolytic in aged mice. The 19-month-old male C57BL/6 mice were orally administered distilled water (Control, n = 6) or 300 mg/kg of aqueous RG extract (RG, n = 6) for 4 weeks. (A) Body weight (g) and (B) accumulated food intake (g) were monitored every 4 days. (C) 6 h fasted blood glucose levels (mg/dL) on weeks 0 and 4. (D) 16 h fasted blood glucose levels (mg/dL) on week 4. (E) Glucose tolerance test (GTT; 2 g/kg) on week 4 and the calculation of area under the curve (AUC). (F) Insulin tolerance test (ITT; 1 IU/kg) on week 4 and AUC. The GTT and ITT were conducted at three-day intervals. Ordinary two-way ANOVA was used to analyze body weights, food intakes, GTT, and ITT, followed by Student’s t-tests for blood glucose levels and AUC. The results are expressed as mean ± SEM. (** p < 0.01).
Figure 2
Figure 2
Red ginseng administration for 4 weeks suppresses the hepatic cellular senescence pathway in aged mice. Distilled water was orally administered to 9-week-old (Young) and 19-month-old (Old) mice, and 300 mg/kg RG in distilled water was given to 19-month-old (Old + RG) mice (n = 6 per group) for 4 weeks. (A) Total liver tissue lysates were immunoblotted with cellular senescence-related markers: p53, p21, p16, and p15. (B,C) Primary hepatocytes were isolated from Young, Old, and Old + RG mice, followed by immunoblotting with (B) p15 and (C) cleaved caspase-3 and caspase-3. Ordinary two-way ANOVA was used for the quantification of immunoblots followed by Tukey’s multiple comparison tests. The data are expressed as mean ± SEM (* p < 0.05, ** p < 0.01).
Figure 3
Figure 3
Red ginseng intake for 14 weeks maintains insulin homeostasis in aged mice. 19-month-old male C57BL/6 mice were fed ad libitum with a normal chow diet (Control; n = 10) or 0.4% (w/w) RG (RG, n = 10) for 14 weeks. (A) Body weight (g) and (B) accumulated food intake (g) was assessed every two weeks. (C) 6 h fasted blood glucose levels (mg/dL) on weeks 0 and 7. (D) Glucose tolerance test (GTT; 2 g/kg) on week 8 and the calculation of area under the curve (AUC). (E) Insulin tolerance test (ITT; 0.5 IU/kg) on week 7 and the calculation of AUC. Ordinary two-way ANOVA was used to analyze body weights, food intake, GTT, and ITT. Student’s t-test was used to analyze blood glucose levels and AUC. All results are expressed as mean ± SEM. (* p < 0.05, *** p < 0.005, **** p < 0.001).
Figure 4
Figure 4
Red ginseng uptake for 14 weeks downregulates the hepatic JNK/NF-kB signaling pathway in aged mice. Liver tissues were collected from Control and RG-fed mice after 14-week interventions and immunoblotted with inflammation-related antibodies. (A) The immunoblots were quantified by normalizing p-JNK and JNK to β-actin and p-JNK to total JNK. (B) The nuclear and cytoplasmic fractions were fractionated from the mouse liver tissues. The quantification of immunoblots was performed by the normalization of nuclear p65 to HDAC1, and cytoplasmic p65 to β-tubulin. Student’s t-test was used to quantify the immunoblots. The results are presented as mean ± SEM. (* p < 0.05).
Figure 5
Figure 5
Red ginseng delays cellular senescence in primary hepatocytes from aged mice and primary mouse embryonic fibroblasts (MEFs). Representative morphologies of senescence-associated β-galactosidase (SA-β-gal) stained (bluish green) cells. (A) Primary hepatocytes isolated from Control and RG-fed mice after 14 weeks of intervention (left) and SA-β-gal quantification plot (right) (scale bar = 1 mm). (B) Primary mouse embryonic fibroblasts (MEFs) were applied with the acute ionizing radiation of 0 Gy, 20 Gy, or 20 G with 5 μg/mL of aqueous RG. Black arrows point to SA-β-gal stained MEFs (upper). SA-β-gal quantification plots based on staining density (below) (scale bar = 0.1 mm). Student’s t-test was used to analyze the percentage of SA-β-gal-positive cells. Results are expressed as mean ± SEM (**** p < 0.001).
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References

    1. Di Micco R., Krizhanovsky V., Baker D., d’Adda di Fagagna F. Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 2021;22:75–95. doi: 10.1038/s41580-020-00314-w. - DOI - PMC - PubMed
    1. Childs B.G., Durik M., Baker D.J., Van Deursen J.M. Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nat. Med. 2015;21:1424–1435. doi: 10.1038/nm.4000. - DOI - PMC - PubMed
    1. Kumari R., Jat P. Mechanisms of cellular senescence: Cell cycle arrest and senescence associated secretory phenotype. Front. Cell Dev. Biol. 2021;9:485. doi: 10.3389/fcell.2021.645593. - DOI - PMC - PubMed
    1. Mijit M., Caracciolo V., Melillo A., Amicarelli F., Giordano A. Role of p53 in the Regulation of Cellular Senescence. Biomolecules. 2020;10:420. doi: 10.3390/biom10030420. - DOI - PMC - PubMed
    1. Hu S.-J., Jiang S.-S., Zhang J., Luo D., Yu B., Yang L.-Y., Zhong H.-H., Yang M.-W., Liu L.-Y., Hong F.-F., et al. Effects of apoptosis on liver aging. World J. Clin. Cases. 2019;7:691–704. doi: 10.12998/wjcc.v7.i6.691. - DOI - PMC - PubMed
-