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Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway

  • Authors:
    • Pei Li
    • Xinyu Wan
    • Wenjie Li
    • Ding Cheng
    • Ying Yang
    • Yuhan Wang
    • Ruyuan Zhu
    • Yanjing Chen
    • Haixia Liu
    • Zhiguo Zhang
  • View Affiliations / Copyright

    Affiliations: Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 83
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    Published online on: January 12, 2026
       https://doi.org/10.3892/mmr.2026.13793
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Abstract

With the aging of the population, the incidence of postmenopausal osteoporosis (PMOP) is increasing. Extracts from Artemisiae Scopariae Herba, also known as Yinchen (YC), promote osteogenic differentiation and bone formation; however, the specific mechanism is unclear. The present study aimed to investigate the effects and mechanism of YC on PMOP. Ultra‑performance liquid chromatography‑tandem mass spectrometry was used to determine the potential predominant components of YC, and an ovariectomized (OVX) mouse model was established to evaluate the effects of YC on PMOP and its potential mechanisms. Initially, the therapeutic effect of YC on PMOP was assessed by micro‑CT bone analysis, pathological observation and ELISA detection. Combined with serum ELISA, reverse transcription‑quantitative PCR and immunohistochemical staining, the potential key anti‑PMOP pathway of YC was explored. A total of 2,072 compounds were identified in YC. The main active components of YC included chlorogenic acid, ferulic acid and caffeic acid. Experimental studies provided evidence that YC may improve bone loss and bone microstructure deterioration caused by ovariectomy. YC treatment also upregulated serum estrogen levels, and the expression of osteoprotegerin, runt‑related transcription factor 2 and glutathione peroxidase 4 (Gpx4) in bone tissue. Ovariectomy led to abnormal iron metabolism and increase the accumulation of lipid peroxides. YC reduced liver iron deposition, restored glutathione levels, and downregulated serum tartrate‑resistant acid phosphatase, osteocalcin, ferritin and hepcidin levels in mice. In addition, YC reversed the decreased expression of nuclear factor erythroid 2‑related factor 2 (Nrf2), solute carrier family 7 member 11 (Slc7a11) and Gpx4 in the bone tissues of OVX mice. In conclusion, the present study suggested the effectiveness of YC in potentially reducing ovariectomy‑induced osteoporosis in mice. YC promoted bone formation and improved bone microstructure, potentially by inhibiting ferroptosis via activation of the Nrf2/Slc7a11/Gpx4 pathway in OVX mice.

View Figures

Figure 1

Ring diagram of the composition of
the metabolite categories of YC.

Figure 2

Effect of YC on body weight, E2
levels and uterine coefficient in OVX mice. (A) Changes in body
weight. (B) Uterine coefficient of mice. (C) E2 levels in mice.
Data are presented as mean ± SD; n=8. #P<0.05 vs.
SHAM group; *P<0.05 vs. OVX group. YC, Yinchen; OVX,
ovariectomized; EV, estradiol valerate; YCL, YC low dose; YCH, YC
high dose; E2, estradiol.

Figure 3

Effect of YC on femoral bone
microstructure in OVX mice. (A) Micro-CT scanning images of bone
microstructure. Changes in (B) BMD, (C) Tb.N, (D) Tb.Sp, (E) BV/TV
and (F) SMI. Data are presented as the mean ± SD; n=8.
#P<0.05 vs. SHAM group; *P<0.05 vs. OVX group.
OVX, ovariectomized; EV, estradiol valerate; YC, Yinchen; YCL, YC
low dose; YCH, YC high dose; BMD, bone mineral density; Tb.N,
trabecular number; Tb.Sp, trabecular separation; BV/TV, bone
volume/total volume; SMI, structure model index.

Figure 4

Effect of YC on the pathological
morphology of femurs in OVX mice. Image analysis (×200
magnification) of (A) Hematoxylin and eosin staining and (B)
Masson's trichrome staining. OVX, ovariectomized; EV, estradiol
valerate; YC, Yinchen; YCL, YC low dose; YCH, YC high dose.

Figure 5

Effect of YC on bone metabolism in
OVX mice. Results of (A) TRAP and (B) OCN ELISA. Relative protein
expression levels of (C) OPG and (D) RUNX2. Immunohistochemical
staining of (E) OPG and (F) RUNX2 protein expression (×200
magnification). (G) Double immunofluorescence staining images of
OCN and GPX4 (×400 magnification). (H) OCN-GPX4 double positive
area. Data are presented as the mean ± SD; n=8.
#P<0.05 vs. SHAM group; *P<0.05 vs. OVX group.
OVX, ovariectomized; EV, estradiol valerate; YC, Yinchen; YCL, YC
low dose; YCH, YC high dose; TRAP, tartrate-resistant acid
phosphatase; OCN, osteocalcin; OPG, osteoprotegerin; RUNX2,
runt-related transcription factor 2; GPX4, glutathione peroxidase
4.

Figure 6

Effect of YC on iron metabolism in
OVX mice. (A) Prussian blue staining image of mouse livers (×200
magnification). (B) Hepc and (C) ferritin Levels. Relative mRNA
expression levels of (D) Ncoa4 and (E) Fth. Data are presented as
the mean ± SD; n=8. #P<0.05 vs. SHAM group;
*P<0.05 vs. OVX group. OVX, ovariectomized; EV, estradiol
valerate; YC, Yinchen; YCL, YC low dose; YCH, YC high dose; Hepc,
hepcidin; Ncoa4, nuclear receptor coactivator 4; Fth, ferritin
heavy chain.

Figure 7

Effect of YC on lipid peroxidation in
OVX mice. Tibia and serum levels of (A) MDA, (B) 4-HNE and (C) GSH.
Data are presented as the mean ± SD; n=8. #P<0.05 vs.
SHAM group; *P<0.05 vs. OVX group. OVX, ovariectomized; EV,
estradiol valerate; YC, Yinchen; YCL, YC low dose; YCH, YC high
dose; MDA, malondialdehyde; 4-HNE, 4-hydroxynonenal; GSH,
glutathione.

Figure 8

Effect of YC on the Nrf2/Slc7a11/Gpx4
pathway. (A) Relative mRNA and protein expression levels of Nrf2.
(B) Immunohistochemical images of Nrf2 in mouse femurs (×200
magnification). (C) Relative mRNA and protein expression levels of
Slc7a11. (D) Immunohistochemical images of Slc7a11 in mouse femurs
(×200 magnification). (E) Relative mRNA and protein expression
levels of Gpx4. (F) Immunohistochemical images of Gpx4 in mouse
femurs (×200 magnification). Data are presented as the mean ± SD;
n=8. #P<0.05 vs. SHAM group; *P<0.05 vs. OVX
group. OVX, ovariectomized; EV, estradiol valerate; YC, Yinchen;
YCL, YC low dose; YCH, YC high dose; Nrf2, nuclear factor erythroid
2-related factor 2; Slc7a11, solute carrier family 7 member 11;
Gpx4, glutathione peroxidase 4.
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Copy and paste a formatted citation
Spandidos Publications style
Li P, Wan X, Li W, Cheng D, Yang Y, Wang Y, Zhu R, Chen Y, Liu H, Zhang Z, Zhang Z, et al: <p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>. Mol Med Rep 33: 83, 2026.
APA
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y. ... Zhang, Z. (2026). <p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>. Molecular Medicine Reports, 33, 83. https://doi.org/10.3892/mmr.2026.13793
MLA
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y., Zhu, R., Chen, Y., Liu, H., Zhang, Z."<p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>". Molecular Medicine Reports 33.3 (2026): 83.
Chicago
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y., Zhu, R., Chen, Y., Liu, H., Zhang, Z."<p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>". Molecular Medicine Reports 33, no. 3 (2026): 83. https://doi.org/10.3892/mmr.2026.13793
Copy and paste a formatted citation
x
Spandidos Publications style
Li P, Wan X, Li W, Cheng D, Yang Y, Wang Y, Zhu R, Chen Y, Liu H, Zhang Z, Zhang Z, et al: <p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>. Mol Med Rep 33: 83, 2026.
APA
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y. ... Zhang, Z. (2026). <p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>. Molecular Medicine Reports, 33, 83. https://doi.org/10.3892/mmr.2026.13793
MLA
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y., Zhu, R., Chen, Y., Liu, H., Zhang, Z."<p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>". Molecular Medicine Reports 33.3 (2026): 83.
Chicago
Li, P., Wan, X., Li, W., Cheng, D., Yang, Y., Wang, Y., Zhu, R., Chen, Y., Liu, H., Zhang, Z."<p>Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway</p>". Molecular Medicine Reports 33, no. 3 (2026): 83. https://doi.org/10.3892/mmr.2026.13793
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