Mechanism of puerarin in the treatment of PMOP rats based on JAK2 / STAT3 signaling pathway

  • ZHAO Xinlei ,
  • WANG Jianguo ,
  • LIU Youcai ,
  • ZHOU Jiaxuan ,
  • WANG Beiyu ,
  • LI Chang ,
  • ZHANG Yijun
Expand
  • 1. Baotou Medical College, Baotou 014040, China;
    2. The First Affiliated Hospital of Baotou Medical College

Received date: 2024-04-18

  Online published: 2025-02-24

Abstract

Objective: To investigate the effect and mechanism of puerarin (Pue) in the treatment of postmenopausal osteoporosis (PMOP) in rats. Methods: Female SD rats were divided into sham operation group (SHAM group), model group (PMOP group), low-dose puerarin group (Pue-L group) and high-dose puerarin group (Pue-H group). In the SHAM group, partial fat around the ovary was removed, and bilateral ovaries were removed in the other groups. Bone mineral density (BMD) and hematoxylin-eosin (HE) staining were used to observe the femoral tissue at 4 weeks after operation to determine whether the model was successful. After successful modeling, rats in Pue-L group and Pue-H group were subcutaneously injected with different concentrations of puerarin injection, and rats in SHAM group and PMOP group were injected with the same amount of normal saline. BMD of rats was detected after 8 weeks of administration. The bone structure was observed by micro-CT scanning and the related parameters were calculated. HE staining was used to observe the pathological changes of rat femur. The protein expression level of JAK2/STAT3 signaling pathway was detected by Western Blot (WB). Results: (1) Pue significantly increased BMD in PMOP rats. (2) Micro-CT analysis showed that Pue could improve the bone microstructure of PMOP rats. (3) HE staining showed that after Pue treatment, the bone loss of PMOP rats decreased, the number and density of trabecular bone increased, and the pathological changes were restored. (4) WB results showed that compared with SHAM group, the expression levels of p-JAK2 and p-STAT3 protein in PMOP group were increased (P<0.001). Compared with PMOP group, the expression levels of p-JAK2 and p-STAT3 protein in Pue-L group and Pue-H group were decreased (P<0.001). Conclusion: Puerarin can effectively treat osteoporosis in PMOP rats, which may play an anti-osteoporosis role by inhibiting the activation of JAK2/STAT3 pathway.

Cite this article

ZHAO Xinlei , WANG Jianguo , LIU Youcai , ZHOU Jiaxuan , WANG Beiyu , LI Chang , ZHANG Yijun . Mechanism of puerarin in the treatment of PMOP rats based on JAK2 / STAT3 signaling pathway[J]. Journal of Baotou Medical College, 2025 , 41(1) : 25 -31 . DOI: 10.16833/j.cnki.jbmc.2025.01.005

References

[1] Gopinath V. Osteoporosis[J]. Med Clin North Am, 2023: 107(2): 213-225.
[2] US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening for osteoporosis to prevent fractures: US preventive services task force recommendation statement[J]. JAMA, 2018, 319(24): 2521-2531.
[3] Damani JJ, De Souza MJ, VanEvery HL, et al. The role of prunes in modulating inflammatory pathways to improve bone health in postmenopausal women[J]. Adv Nutr, 2022, 13(5): 1476-1492.
[4] Goyal L, Goyal T, Gupta ND. Osteoporosis and periodontitis in postmenopausal women:a systematic review[J]. J Midlife Health, 2017, 8(4): 151-158.
[5] Fitzpatrick LA. Estrogen therapy for postmenopausal osteoporosis[J]. Arq Bras Endocrinol Metabol, 2006, 50(4): 705-719.
[6] Li B, Wang Y, Gong S, et al. Puerarin improves OVX-induced osteoporosis by regulating phospholipid metabolism and biosynthesis of unsaturated fatty acids based on serum metabolomics[J]. Phytomedicine, 2022, 102: 154198.
[7] Mun JG, Grannan MD, Lachcik PJ, et al. In vivo metabolic tracking of 14C-radiolabelled isoflavones in kudzu (Pueraria lobata) and red clover (Trifolium pratense) extracts[J]. Br J Nutr, 2009, 102(10): 1523-1530.
[8] Wei SY, Chen Y, Xu XY. Progress on the pharmacological research of puerarin: a review[J]. Chin J Nat Med, 2014, 12(6): 407-414.
[9] Jin Y, Kang Y, Wang M, et al. Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis[J]. Signal Transduct Target Ther, 2022, 7(1):52.
[10] Wang G, Zhang L, Yan C, et al. Overexpression of miR125b promotes osteoporosis through miR-125b-TRAF6 pathway in postmenopausal ovariectomized rats[J]. Diabetes Metab Syndr Obes, 2021, 14: 671-682.
[11] Fu Y, Xu Y, Chen S, et al. MiR-151a-3p promotes postmenopausal osteoporosis by targeting SOCS5 and activating JAK2/STAT3 signaling[J]. Rejuvenation Res, 2020, 23(4): 313-323.
[12] Wu W, Fu J, Gu Y, et al. JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells[J]. J Endocrinol, 2020, 245(1): 141-153.
[13] Hong L, Yang C. Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA-211-5p and repressing JAK2/STAT3 pathway[J]. Environ Toxicol, 2024, 39(4): 2218-2228.
[14] Martiniakova M, Babikova M, Omelka R. Pharmacological agents and natural compounds:available treatments for osteoporosis[J]. J Physiol Pharmacol, 2020, 71(3): 10.
[15] Tella SH, Gallagher JC. Bazedoxifene + conjugated estrogens in HT for the prevention of osteoporosis and treatment of vasomotor symptoms associated with the menopause[J]. Expert Opin Pharmacother, 2013, 14(17): 2407-2420.
[16] Boston B, Ipe D, Capitanescu B, et al. Medication-related osteonecrosis of the jaw: a disease of significant importance for older patients[J]. J Am Geriatr Soc, 2023, 71(8): 2640-2652.
[17] Garton M. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates[J]. N Engl J Med, 2020, 383(22): 2189.
[18] Coxam V. Prevention of osteopaenia by phyto-oestrogens: animal studies[J]. Br J Nutr, 2003, 89 Suppl 1: S75-S85.
[19] Malaivijitnond S, Tungmunnithum D, Gittarasanee S, et al. Puerarin exhibits weak estrogenic activity in female rats[J]. Fitoterapia, 2010, 81(6): 569-576.
[20] Xin P, Xu X, Deng C, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases[J]. Int Immunopharmacol, 2020, 80: 106210.
[21] Zhu J, Tang Y, Wu Q, et al. HIF-1α facilitates osteocyte-mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro[J]. J Cell Physiol, 2019, 234(11): 21182-21192.
[22] Wang W, Mao J, Chen Y, et al. Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling[J]. Clin Exp Pharmacol Physiol, 2022, 49(1): 113-121.
Outlines

/