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Article Open Access

Ganoderma lucidum polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice

  • Authors:
    • Xin Jin
    • Xuan Liu
    • Yun-Juan Wang
    • Zi-Li Lei
    • Yan-Hong Yang
  • View Affiliations / Copyright

    Affiliations: The First Affiliated Hospital (The First School of Clinical Medicine), Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China, Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong 510006, P.R. China
    Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 195
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    Published online on: May 20, 2026
       https://doi.org/10.3892/ijmm.2026.5866
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Abstract

The morbidity of cardiovascular disease in postmenopausal patients increases due to the lack of estrogen protection. One of the most common conditions is hyperlipidemia characterized by abnormally elevated low‑density lipoprotein cholesterol (LDL‑C) and total cholesterol (TC). GLP has multiple effects such as lowering lipid levels, reducing inflammation, and regulating gut microbiota, but its effect on regulating metabolism in menopausal patients is not clear. The present study aimed to study the regulatory effect of Ganoderma lucidum polysaccharides (GLPs) on cholesterol metabolism in the liver. A bilateral ovariectomy mouse model was generated and GLP was given by gavage. Serum biochemistry, hepatic architecture and histopathology were assessed, expression of genes governing glucose and lipid homeostasis and circadian rhythm in the hepatic tissue was detected and the changes of intestinal microbiota of ovariectomized mice was analyzed by 16S rDNA sequencing. The GLPs directly affected the intestinal flora, upregulated the abundance of probiotics and improved the structure of microbiota and might indirectly affect the liver metabolism through the gut‑liver axis. GLP administration markedly lowered circulating TC and LDL‑C, decreased hepatic steatosis and modulated the expression of genes associated with the circadian clock, lipid synthesis and glucose metabolism in hepatic tissue. Collectively, these data position GLP as a promising therapeutic candidate for correcting postmenopausal dysmetabolism and curbing cardiovascular risk in aging female patients.
View Figures

Figure 1

Effects of GLP on body weight, blood
biochemical indexes and liver lipid content. (A) Body weight
curves. ###P<0.005, Sham vs. OVX;
***P<0.005, OVX + LGLP vs. OVX;
$$$P<0.005, OVX + MGLP vs. OVX;
ΔΔΔP<0.005, OVX + HGLP vs. OVX;
▲P<0.05, OVX + Siv vs. OVX. Concentration of (B) E2
and (C) TG, TC, LDL-C, HDL-C, FFA, insulin and FBG in the serum.
(D) Liver injury indexes including ALT and AST. (E) Hematoxylin and
eosin staining and quantitative analysis of liver lipid droplet
area of the liver tissue. Scale bar, 50 μm. (F) TG and TC
content in the liver (n≥6). #P<0.05,
##P<0.01, ###P<0.005 vs. Sham;
*P<0.05, **P<0.01 vs. OVX. GLP,
Ganoderma lucidum polysaccharides; OVX, ovariectomy; LGLP,
low-dose GLP; MGLP, medium-dose GLP; HGLP, high-dose GLP; Siv,
simvastatin; E2, estradiol; LDL-C, low-density lipoprotein
cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total
cholesterol; TG, triglyceride; ALT, alanine aminotransferase; AST,
aspartate transaminase; FFA, free fatty acid; FBG, fasting plasm
glucose.

Figure 2

Effect of GLP on the expression of
cholesterol synthesis-associated genes in the liver tissue. (A)
Relative mRNA expression levels of Srebp2, Hmgcr,
Mvk, Mvd, Fdft1, Idi1, Fdps and
Lss in the liver tissue. Protein levels detected by (B)
western blot and (C) densitometry of HMGCR, LSS, MVK, MVD and IDI1
in the liver (n≥6). #P<0.05, ##P<0.01,
###P<0.005 vs. Sham; *P<0.05,
**P<0.01, ***P<0.005 vs. OVX. GLP,
Ganoderma lucidum polysaccharides; OVX, ovariectomy; LGLP,
low-dose GLP; MGLP, medium-dose GLP; HGLP, high-dose GLP; Siv,
simvastatin; Srebp2, sterol regulatory element-binding protein 2;
Hmgcr, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Mvk,
mevalonate kinase; Mvd, diphosphomevalonate decarboxylase; Fdft1,
farnesyl-diphosphate farnesyltransferase 1; Idi1,
isopentenyl-diphosphate delta isomerase 1; Fdps, farnesyl
diphosphate synthase; Lss, lanosterol synthase.

Figure 3

Effects of GLP on fatty acid
synthesis of liver tissue. (A) mRNA expression of Srebp1-c,
Pparα, Pparγ, Cd36, Scd1, Fasn
and Acc at in the liver. (B) Western blotting and (C)
densitometry of FASN and ACC in the liver (n≥6).
#P<0.05, ##P<0.01 vs. Sham;
*P<0.05, **P<0.01,
***P<0.005 vs. OVX. GLP, Ganoderma lucidum
polysaccharides; OVX, ovariectomy; LGLP, low-dose GLP; MGLP,
medium-dose GLP; HGLP, high-dose GLP; Siv, simvastatin; Srebp1-c,
sterol regulatory element-binding protein 1c; Pparα, peroxisome
proliferator-activated receptor α; Scd1, stearoyl-CoA desaturase 1;
Fasn, fatty acid synthase; Acc, acetyl CoA carboxylase.

Figure 4

Effects of GLP on the expression of
proteins involved in the insulin signaling pathway in the liver.
(A) Expression of (B) p-IRS1, Tyr609, IRS1, p-mTOR, mTOR, p-GS and
GS proteins in the liver (n≥6). *P<0.05,
**P<0.01 vs. OVX. GLP, Ganoderma lucidum
polysaccharides; OVX, ovariectomy; LGLP, low-dose GLP; MGLP,
medium-dose GLP; HGLP, high-dose GLP; Siv, simvastatin; p-,
phosphorylated; IRS1, insulin receptor substrate 1; GS, glycogen
synthase.

Figure 5

GLP improves the abnormal expression
of genes associated with circadian rhythm. (A) mRNA expression
levels of Clock, Bmal1, Per1, Per2,
Cry1, Cry2, Nr1d1 and Bhlhe41 in the
liver. (B) Protein expression levels of (C) CLOCK and BMAL1 in the
liver. #P<0.05, ##P<0.01 vs. Sham;
*P<0.05, **P<0.01,
***P<0.005 vs. OVX. GLP, Ganoderma lucidum
polysaccharides; OVX, ovariectomy; LGLP, low-dose GLP; MGLP,
medium-dose GLP; HGLP, high-dose GLP; Siv, simvastatin; Bmal1,
brain and muscle arnt-like protein 1; Per1, period circadian
regulator 1; Cry1, cryptochrome circadian regulator 1; Nr1d1,
nuclear receptor subfamily 1 group D member 1; Bhlhe41, basic
helix-loop-helix family member e41.

Figure 6

GLP improves intestinal microbiota of
the OVX mice. (A) Shannon diversity index dilution curves. (B) PCo
analysis community structure distribution. (C) Relative abundance
of intestinal microbiota at the species level. Differential
microbial community identification based on LDA effect size
analysis of (D) Sham and (E) OVX + HGLP vs. OVX. (F) Signaling
pathway enrichment analysis of the relative abundance of gut
microbes (n=6). GLP, Ganoderma lucidum polysaccharides; OVX,
ovariectomy; LGLP, low-dose GLP; MGLP, medium-dose GLP; HGLP,
high-dose GLP; Siv, simvastatin; PCo, principal coordinate; LDA,
linear discriminant analysis.

Figure 7

GLP improves liver metabolic disorder
by modulating gut microbiota of OVX mice. GLPs upregulate the
abundance of beneficial bacteria in the intestines of OVX mice, and
then the metabolites produced by the beneficial bacteria and small
molecules degraded from GLPs improve the lipid metabolic disorders
and impaired circadian rhythm in the hepatic tissue of the OVX
mice. GLP, Ganoderma lucidum polysaccharides; LDL-C,
low-density lipoprotein cholesterol; OVX, ovariectomy.
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Copy and paste a formatted citation
Spandidos Publications style
Jin X, Liu X, Wang Y, Lei Z and Yang Y: <em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice. Int J Mol Med 58: 195, 2026.
APA
Jin, X., Liu, X., Wang, Y., Lei, Z., & Yang, Y. (2026). <em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice. International Journal of Molecular Medicine, 58, 195. https://doi.org/10.3892/ijmm.2026.5866
MLA
Jin, X., Liu, X., Wang, Y., Lei, Z., Yang, Y."<em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice". International Journal of Molecular Medicine 58.1 (2026): 195.
Chicago
Jin, X., Liu, X., Wang, Y., Lei, Z., Yang, Y."<em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice". International Journal of Molecular Medicine 58, no. 1 (2026): 195. https://doi.org/10.3892/ijmm.2026.5866
Copy and paste a formatted citation
x
Spandidos Publications style
Jin X, Liu X, Wang Y, Lei Z and Yang Y: <em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice. Int J Mol Med 58: 195, 2026.
APA
Jin, X., Liu, X., Wang, Y., Lei, Z., & Yang, Y. (2026). <em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice. International Journal of Molecular Medicine, 58, 195. https://doi.org/10.3892/ijmm.2026.5866
MLA
Jin, X., Liu, X., Wang, Y., Lei, Z., Yang, Y."<em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice". International Journal of Molecular Medicine 58.1 (2026): 195.
Chicago
Jin, X., Liu, X., Wang, Y., Lei, Z., Yang, Y."<em>Ganoderma lucidum</em> polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice". International Journal of Molecular Medicine 58, no. 1 (2026): 195. https://doi.org/10.3892/ijmm.2026.5866
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