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Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats.
J Ethnopharmacol. 2017 Apr 06; 201:91-99.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Combined Herba Epimedii and Fructus Ligustri Lucidi, based on traditional Chinese formula Er-Zhi pills, were frequently used in TCM formulas that were prescribed for kidney tonifying and bone strengthening. However, it is unclear whether the combination of the two herbs may have a protective influence on glucocorticoid-induced osteoporosis (GIOP). The objective of this study was to evaluate the therapeutic effects and the underlying molecular mechanism of the decoction and the active fractions of the combined herbs in GIOP rats.

MATERIALS AND METHODS

Male Sprague-Dawley rats were divided into seven groups, including the normal control (NC), GIOP model (MO), active fractions low (100mg/kg, LAF), active fractions high (200mg/kg, HAF), decoction low (3.5g/kg, LD), decoction high (7g/kg, HD) and Calcium with Vitamin D3 (0.2773g/kg, CaD)-treated group. The GIOP model was established by intramuscular injection of dexamethasone (1mg/kg) twice a week for 8 weeks. Different kinds of indicators were measured, including bone mineral density (BMD), bone biomechanical properties, serum bone alkaline phosphatase (b-ALP), serum bone γ-carboxyglutamic acid-containing protein (BGP), serum bone morphogenetic protein-2 (BMP-2), serum tartrate-resistant acid phosphatase (TRACP) and serum carboxy terminal cross linked telopeptide of typeⅠcollagen (ICTP), bone mineral content (BMC) and bone structured histomorphometry. The protein and mRNA expression of TGF-β1, Smad2, Smad3, Smad4 and Smad7 were detected by Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR), respectively.

RESULTS

Administration of combined Herba Epimedii and Fructus Ligustri Lucidi decoction and combined active fractions could significantly prevent GC-induced bone loss by increasing the contents of serum b-ALP, BGP and BMP-2 as the markers of bone formation, reducing the serum TRACP and ICTP contents to inhibit bone resorption and enhancing BMC. They could also attenuate biomechanical properties and BMD reduction, deterioration of trabecular architecture in MO rats. The mRNA and protein expressions of TGF-β1, smad2, smad3 and smad4 were up-regulated, and the mRNA and protein expression of Smad7 was down-regulated following combined Herba Epimedii and Fructus Ligustri Lucidi treatment.

CONCLUSION

Combination of Herba Epimedii and Fructus Ligustri Lucidi exhibited protective effects on promoting bone formation and precluding bone resorption. The underlying mechanism may be attributed to its regulations on TGF-β1/Smads pathway. The substance bases of the combined herbs on anti-osteoporosis were total flavonoids of Herba Epimedii, total iridoids and flavonoids of Fructus Ligustri Lucidi.

Authors+Show Affiliations

Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No.10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No.10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No.10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No.10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China. Electronic address: wxj0517@sina.com.Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No.10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China. Electronic address: gzblrh45@ccmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28254481

Citation

Yang, Yan, et al. "Effects of the Combined Herba Epimedii and Fructus Ligustri Lucidi On Bone Turnover and TGF-β1/Smads Pathway in GIOP Rats." Journal of Ethnopharmacology, vol. 201, 2017, pp. 91-99.
Yang Y, Nian H, Tang X, et al. Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats. J Ethnopharmacol. 2017;201:91-99.
Yang, Y., Nian, H., Tang, X., Wang, X., & Liu, R. (2017). Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats. Journal of Ethnopharmacology, 201, 91-99. https://doi.org/10.1016/j.jep.2017.02.033
Yang Y, et al. Effects of the Combined Herba Epimedii and Fructus Ligustri Lucidi On Bone Turnover and TGF-β1/Smads Pathway in GIOP Rats. J Ethnopharmacol. 2017 Apr 6;201:91-99. PubMed PMID: 28254481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats. AU - Yang,Yan, AU - Nian,Honglei, AU - Tang,Xiufeng, AU - Wang,Xiujuan, AU - Liu,Renhui, Y1 - 2017/02/27/ PY - 2016/10/17/received PY - 2017/02/06/revised PY - 2017/02/13/accepted PY - 2017/3/4/pubmed PY - 2017/6/7/medline PY - 2017/3/4/entrez KW - Active fractions KW - Bone formation KW - Bone resorption KW - Glucocorticoid-induced osteoporosis KW - Herba Epimedii/Fructus Ligustri Lucidi KW - Icariin (PubChem CID: 5318997) KW - Oleanolic Acid (PubChem CID: 10494) KW - Rutin (PubChem CID: 5280805) KW - TGF-β1/Smads SP - 91 EP - 99 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 201 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Combined Herba Epimedii and Fructus Ligustri Lucidi, based on traditional Chinese formula Er-Zhi pills, were frequently used in TCM formulas that were prescribed for kidney tonifying and bone strengthening. However, it is unclear whether the combination of the two herbs may have a protective influence on glucocorticoid-induced osteoporosis (GIOP). The objective of this study was to evaluate the therapeutic effects and the underlying molecular mechanism of the decoction and the active fractions of the combined herbs in GIOP rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into seven groups, including the normal control (NC), GIOP model (MO), active fractions low (100mg/kg, LAF), active fractions high (200mg/kg, HAF), decoction low (3.5g/kg, LD), decoction high (7g/kg, HD) and Calcium with Vitamin D3 (0.2773g/kg, CaD)-treated group. The GIOP model was established by intramuscular injection of dexamethasone (1mg/kg) twice a week for 8 weeks. Different kinds of indicators were measured, including bone mineral density (BMD), bone biomechanical properties, serum bone alkaline phosphatase (b-ALP), serum bone γ-carboxyglutamic acid-containing protein (BGP), serum bone morphogenetic protein-2 (BMP-2), serum tartrate-resistant acid phosphatase (TRACP) and serum carboxy terminal cross linked telopeptide of typeⅠcollagen (ICTP), bone mineral content (BMC) and bone structured histomorphometry. The protein and mRNA expression of TGF-β1, Smad2, Smad3, Smad4 and Smad7 were detected by Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Administration of combined Herba Epimedii and Fructus Ligustri Lucidi decoction and combined active fractions could significantly prevent GC-induced bone loss by increasing the contents of serum b-ALP, BGP and BMP-2 as the markers of bone formation, reducing the serum TRACP and ICTP contents to inhibit bone resorption and enhancing BMC. They could also attenuate biomechanical properties and BMD reduction, deterioration of trabecular architecture in MO rats. The mRNA and protein expressions of TGF-β1, smad2, smad3 and smad4 were up-regulated, and the mRNA and protein expression of Smad7 was down-regulated following combined Herba Epimedii and Fructus Ligustri Lucidi treatment. CONCLUSION: Combination of Herba Epimedii and Fructus Ligustri Lucidi exhibited protective effects on promoting bone formation and precluding bone resorption. The underlying mechanism may be attributed to its regulations on TGF-β1/Smads pathway. The substance bases of the combined herbs on anti-osteoporosis were total flavonoids of Herba Epimedii, total iridoids and flavonoids of Fructus Ligustri Lucidi. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/28254481/Effects_of_the_combined_Herba_Epimedii_and_Fructus_Ligustri_Lucidi_on_bone_turnover_and_TGF_β1/Smads_pathway_in_GIOP_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)31349-6 DB - PRIME DP - Unbound Medicine ER -