Objective

2

To investigate the effects and mechanisms of Psoralea corylifolia extract on chemokine ligand 4 （CCL4）， inflammatory response， and bone metabolism in osteoporosis model rats.

Methods

2

A total of 55 SPF-grade female SD rats were selected， with 10 rats assigned to the blank group. The remaining 45 rats were used to establish an osteoporosis model. Forty successfully modeled rats were divided into the model group and low， medium， and high dose groups of

P. corylifolia

extract， with 10 rats in each group. On the 9th week of modeling， the low， medium， and high dose groups were administered

P. corylifolia

extract at doses of 50， 100， and 200 mg/（kg•d） by gavage， respectively. The blank and model groups were given physiological saline at 10 mL/（kg·d）. The intervention lasted for 8 weeks. After 8 weeks of intervention， the rats were euthanized， and femur tissue was collected. Histopathological changes in the femur were observed under a light microscope after hematoxylin-eosin （HE） staining. CCL4 and inflammatory cytokines ［tumor necrosis factor-alpha（TNF-α），interleukin-6（IL-6）］were detected by enzyme-linked immunosorbent assay（ELISA）.Bone metabolism markers［osteocalcin（OC），type I collagen N-terminal propeptide （P1NP）］were detected by electrochemiluminescence. Western blotting was used to detect the expression of transforming growth factor-beta 1（TGF-β1）/Smad4 signaling pathway-related proteins in the femur tissue.

Results

2

The bone marrow cavity area was smallest in the blank group and largest in the model group. The bone marrow cavity area in the low， medium， and high-do

se

P. corylifolia

extract groups gradually decreased， but remained larger than that in the blank group. Compared to the model group， the CCL4 level in the low， medium， and high-dose groups was significantly lower （

P

<

0.05）， and the level of CCL4 decreased in a dose-dependent manner （

P

<

0.05）. The levels of OC and P1NP were lower in the model than in the blank group （

P

<

0.05）. The OC and P1NP levels in the low， medium， and high-dose

P. corylifolia

extract groups were higher than that in the model group （

P

<

0.05）， with a dose-dependent increase observed （

P

<

0.05）. The levels of TNF-α and IL-6 were higher in the model group than in the blank group （

P

<

0.05）. The levels of TNF-α and IL-6 in the low， medium， and high-dose groups were significantly lower than those in the model group （

P

<

0.05）， with a dose-dependent decrease （

P

<

0.05）. The relative protein expression levels of TGF-β1 and Smad4 in the model group were lower than those in the blank group （

P

<

0.05）. In contrast， the relative protein expression levels of TGF-β1 and Smad4 in the low， medium， and high-dose

P. corylifolia

extract groups were significantly higher than those in the model group （

P

<

0.05）， with a dose-dependent increase （

P

<

0.05）.

Conclusion

2

P. corylifolia

extract can reduce the CCL4 level in osteoporotic rats， suppress inflammatory response， and improve bone metabolism. The underlying mechanism may be related to the inhibition of the TGF-β1/Smad4 signaling pathway.