Objective: To investigate the mechanism of the compatibility of Epimedii Folium and Ligustri Lucidi Fructus decoction and their extract on retinoic acid-induced osteoporosis in rats. Method: Thirty-six male Wistar rats were randomly divided into 6 groups: the normal group

the model group

the combination of Epimedii Folium and Ligustri Lucidi Fructus group (9.5 g·kg-1)

and three extract combination groups (Extract-L 50 mg·kg-1

Extract-M 100 mg·kg-1

and Extract-H 200 mg·kg-1) of 10 rats each. The osteoporosis model was induced in rats by intragastric administration of retinoic acid. The protein expressions of apoptosis factor B-cell lymphoma/Leukemia-2 (Bcl-2) and p53 of bone tissue were detected by immunohistochemical methods. The mRNA expressions of transforming growth factor beta-1 (TGF-β1)

Smad2

Smad3 and Smad7 of bone tissue were detected by using real-time RT-PCR. Result: Compared with the normal group

the protein expression of Bcl-2 decreased significantly

p53 protein increased significantly

mRNA expressions of TGF-β1

Smad2

Smad3 decreased significantly

and Smad7 increased significantly in the model group (P<0.05

P<0.01). Compared with the model group

the expression levels of Bcl-2

TGF-β1

Smad2 and Smad3 increased

the expression levels of p53 and Smad7 decreased in all treatment groups (P<0.05

P<0.01). Conclusion: The mechanism of the compatibility decoction and their extracts against osteoporosis is related to maintaining the balance between apoptosis and anti-apoptotic

inhibiting of apoptosis of bone tissue

regulating and controlling the TGF-β/Smads signal transduction pathways.