Protective effect of Astragaloside IV to inhibit thiram-induced tibial dyschondroplasia

  • Khalid Mehmood
  • Hui Zhang
  • Wangyuan Yao
  • Xiong Jiang
  • Muhammad Waqas
  • Aoyun Li
  • Yaping Wang
  • Li Lei
  • Lihong Zhang
  • Hammad Qamar
  • Jiakui LiEmail author
Research Article


Tibial dyschondroplasia (TD) is most the common tibiotarsal bone disease in rapidly growing birds throughout the world. There is accumulating evidence that COX-2 abnormal expression in tibia plays an important role in TD progression. So, the regulation of COX-2 is an ever more appealing target for therapeutic intervention in TD. Astragaloside IV has an indispensable role in maintaining COX-2 expression in many diseases. So, we designed this study to use Astragaloside IV (AST-IV) against TD-affected chickens. A total of 180 Arbor Acres chickens were randomly divided in the control group, TD group, and Astr (AST-IV-treated chickens) group. During the experiment, mortality, feed conversion ratio, physiological changes, biochemical criterion, liver antioxidant enzymes, and gene expression of COX-2 were examined in all the chicken groups at various days. The results showed that AST-IV administration restored the growth performance and tibia lesions and decreased the mortality as compared with TD chickens. The biochemical criterion (ALP, AST, and ALT) of serum and liver antioxidant enzymes (SOD, GSH-Px, MDA, and T-AOC) improved after the administration of AST-IV. The COX-2 gene was upregulated significantly (P < 0.05) in TD chickens. Whereas, AST-IV treatment downregulated both gene and protein expression of COX-2 significantly (P < 0.05) in TD-affected chickens. AST-IV recovered tibial dyschondroplasia chickens by increasing the growth performance, ameliorating tibial cartilage damage, and decreasing COX-2 expression. In conclusion, AST-IV can be used to prevent thiram-induced TD in chickens.


Tibial dyschondroplasia (TD) Thiram Astragaloside IV COX-2 Chickens 


Funding information

The study was supported by the National Key R&D Program of China (Project no. 2017YFD0502200).

Compliance with ethical standards

Animals experiment was conducted under the Institutional Animal Care and Use committees of Huazhong Agricultural University approval (31272517), China.

Conflict of interest

The authors declare that they have no competing interest.


  1. Ashok V, Dash C, Rohan TE, Sprafka JM, Terry PD (2011) Selective cyclooxygenase-2 (cox-2) inhibitors and breast cancer risk. Breast 20(1):66–70CrossRefGoogle Scholar
  2. Bian Q, Huang JH, Liang QQ, Shu B, Hou W, Xu H et al (2011) The osteogenetic effect of astragaloside iv with centrifugating pressure on the oct-1 cells. Die Pharmazie- An International Journal of Pharmaceutical Sciences 66:63–68Google Scholar
  3. Bradley EW, Carpio LR, van Wijnen AJ, Mcgee-Lawrence ME, Westendorf JJ (2015) Histone deacetylases in bone development and skeletal disorders. Physiol Rev 95(4):1359–1381CrossRefGoogle Scholar
  4. Chen T, Wang R, Jiang W, Wang H, Xu A, Lu G, Ren Y, Xu Y, Song Y, Yong S, Ji H, Ma Z (2016) Protective effect of astragaloside IV against paraquat-induced lung injury in mice by suppressing Rho signaling. Inflammation. 39(1):483–492CrossRefGoogle Scholar
  5. Chen, C. J., Daoud, S., Kierszenbaum, A., Levy, R., Rogers, J., & Vinkler, A. (2014). Endochondral ossificationGoogle Scholar
  6. Daumer KM, Tufan AC, Tuan RS (2004) Long-term in vitro analysis of limb cartilage development: involvement of wnt signaling. J Cell Biochem 93(3):526–541CrossRefGoogle Scholar
  7. Fan DD, Lin S, Song YP, Wang ZY, Liu B, Gao SN, Fan YH, Zhu S, Li S, Jiang L (2016) Astragaloside iv protects rat gastric mucosa against aspirin-induced damage. Int Immunopharmacol 41:47–55CrossRefGoogle Scholar
  8. Foitzik T, Hotz HG, Hotz B, Wittig F, Buhr HJ (2003) Selective inhibition of cyclooxygenase-2 (cox-2) reduces prostaglandin e2 production and attenuates systemic disease sequelae in experimental pancreatitis. Hepato-Gastroenterol 50(52):1159–1162Google Scholar
  9. Iqbal M, Hui Z, Mehmood K, Li A, Jiang X, Wang Y, Zhang J, Iqbal MK, Rehman MU, Yao W, Yang S, Li J (2018a) Icariin: a potential compound for the recovery of tibial dyschondroplasia affected chicken via up-regulating bmp-2 expression. Biol Proced Online 20:15CrossRefGoogle Scholar
  10. Iqbal MK, Nabi F, Mehmood K, Rehman MU, Huang S, Zhang H, Zhang L, Ahmad HI, Iqbal M, Li J, Shen Y (2018b) Healing of growth plate cartilage by hypoxia inducible factor-1α inhibitor apigenin on thiram induced tibial dyschondroplasia. Pak Vet J 38(2):143–148Google Scholar
  11. Kamei G, Adachi N, Deie M, Eguchi A, Ochi M (2016) Tissue-engineered cartilage implantation for the chondral lesion in a patient with multiple epiphyseal dysplasia. J Orthop Sci 21(1):91–96CrossRefGoogle Scholar
  12. Lescot T, Karvellas C, Beaussier M, Magder S (2012) Acquired liver injury in the intensive care unit. Anesthesiology 117(4):898–904CrossRefGoogle Scholar
  13. Luo H, Li K, Weng S, Bai Y, Zhang H, Mehmood K, Shahzad M, Wang J (2018) Assessment of serum trace elements in thiram induced tibial dyschondroplasia chickens. Pak Vet J 38:101–104Google Scholar
  14. Mehmood K, Zhang H, Iqbal MK, Rehman MU, Li K, Huang S, Shahzad M, Nabi F, Iqbal M, Li J (2018a) Tetramethylpyrazine mitigates toxicity and liver oxidative stress in tibial dyschondroplasia chickens. Pak Vet J 38:76–80CrossRefGoogle Scholar
  15. Mehmood K, Zhang H, Iqbal MK, Rehman MU, Shahzad M, Li K, Huang S, Nabi F, Zhang L, Li J (2017) In vitro effect of apigenin and danshen in tibial dyschondroplasia through inhibition of Hsp90 and VEGF expressions in avian growth plate cells. Avian Dis 61(3):372–377CrossRefGoogle Scholar
  16. Mehmood K, Zhang H, Jiang X, Yao W, Tong X, Iqbal MK, Rehman MU, Iqbal M, Waqas M, Qamar H, Zhang J, Li J (2019) Ligustrazine recovers thiram-induced tibial dyschondroplasia in chickens: involvement of new molecules modulating integrin beta 3. Ecotoxicol Environ Saf 168:205–211CrossRefGoogle Scholar
  17. Mehmood K, Zhang H, Li K, Wang L, Rehman MU, Nabi F, Iqbal MK, Luo H, Shahzad M, Li J (2018b) Effect of tetramethylpyrazine on tibial dyschondroplasia incidence, tibial angiogenesis, performance and characteristics via HIF-1α/VEGF signaling pathway in chickens. Sci Rep 8:2495CrossRefGoogle Scholar
  18. Nabi F, Li K, Shahzad M et al (2016a) Gambogic acid inhibits Hsp90 expressions in thiram-induced tibial dyschondroplasia. Pak Vet J 36:224–226Google Scholar
  19. Nabi F, Shahzad M, Liu J, Li K, Han Z, Zhang D, Iqbal MK, Li J (2016b) Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibial dyschondroplasia. Avian Pathol 45:187–193CrossRefGoogle Scholar
  20. Nabi F, Zhang H, Iqbal MK, Rehman MU, Shahzad M, Mehmood K, Li JK (2018) Salvia miltiorrhiza reinstates growth plate width, reduces liver oxidative stress and toxicity in avian tibial dyschondroplasia. Pak J Zool 50(4):1553–1556CrossRefGoogle Scholar
  21. Rasaputra KS, Liyanage R, Lay JJ, Lay JO Jr, Slavik MF, Rath NC (2013) Effect of thiram on avian growth plate chondrocytes in culture. J ToxicolSci 38:93–101Google Scholar
  22. Rath NC, Huff WE, Balog JM, Huff GR (2004) Comparative efficacy of different dithiocarbamates to induce tibial dyschondroplasia in poultry. Poult Sci 83:266–274CrossRefGoogle Scholar
  23. Ren L, Jiang H, Ye T, Zhao W, Wu X (2016) Astragaloside iv protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes. J Surg Res 200(1):315–323CrossRefGoogle Scholar
  24. Shahzad M, Liu JY, Gao JF, Wang Z, Zhang D, Nabi F, Li JK (2014) Hsp-90 inhibitor geldanamycin attenuates liver oxidative stress and toxicity in thiram-induced tibialdyschondroplasia. Pak Vet J 34:545–547Google Scholar
  25. Szpalski C, Barr J, Wetterau M, Saadeh PB, Warren SM (2010) Cranial bone defects: current and future strategies. Neurosurg Focus 29(6):E8CrossRefGoogle Scholar
  26. Tian WX, Li J, Qin P, Wang R, Ning GB, Qiao JG, Li HQ, Bi DR, Pan SY, Guo DZ (2013) Screening of differentially expressed genes in the growth plate of broiler chickens with tibial dyschondroplasia by microarray analysis. BMC Genomics 14:276CrossRefGoogle Scholar
  27. Xu H, Wang CY, Zhang HN, Lv CY, Wang YZ (2016) Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collagen-induced arthritic rats. Mol Med Rep 13(4):3289–3296CrossRefGoogle Scholar
  28. Yao W, Zhang H, Jiang X, Mehmood K, Iqbal M, Li A, Zhang J, Wang Y, Waqas M, Shen Y, Li J (2018) Effect of Total flavonoids of Rhizoma drynariae on tibial dyschondroplasia by regulating BMP-2 and Runx2 expression in chickens. Front Pharmacol 9:1251CrossRefGoogle Scholar
  29. Yu WN, Sun LF, Yang H (2016) Inhibitory effects of Astragaloside IV on bleomycin-induced pulmonary fibrosis in rats via attenuation of oxidative stress and inflammation. Inflammation. 39(5):1835–1841CrossRefGoogle Scholar
  30. Zhang H, Mehmood K, Jiang X, Yao W, Iqbal M, Li K, Tong X, Wang L, Wang M, Zhang L, Nabi F, Rehman MU, Li J (2018b) Effect of icariin on tibial dyschondroplasia incidence and tibial characteristics by regulating P2RX7 in chickens. Biomed Res Int 2018(6796271):11Google Scholar
  31. Zhang H, Mehmood K, Li K, Rehman MU, Jiang X, Huang S, Wang L, Zhang L, Tong X, Nabi F, Yao W, Iqbal MK, Shahzad M, Li J (2018a) Icariin ameliorate thiram-induced tibial dyschondroplasia via regulation of WNT4 and VEGF expression in broiler chickens. Front Pharmacol 9:123CrossRefGoogle Scholar
  32. Zhang H, Mehmood K, Jiang X, Yao W, Iqbal M, Waqas M, Rehman MU, Li A, Shen Y, Li J (2018c) Effect of tetramethyl thiuram disulfide (thiram) in relation to tibial dyschondroplasia in chickens. Environ Sci Pollut Res 25:28264–28274CrossRefGoogle Scholar
  33. Zhang H, Mehmood K, Jiang X, Li Z, Yao W, Zhang J, Tong X, Wang Y, Li A, Waqas M, Iqbal M, Li J (2019) Identification of differentially expressed MiRNAs profile in a thiram-induced tibial dyschondroplasia. Ecotoxicol Environ Saf 175:83–89Google Scholar
  34. Zhao Y, Li Q, Zhao W, Li J, Sun Y, Liu K, Liu B, Zhang N (2015) Astragaloside iv and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated txnip/nlrp3 inflammasome activation in the endothelium. J Ethnopharmacol 169(20):210–218CrossRefGoogle Scholar
  35. Zhou W, Chen Y, Zhang X (2017) Astragaloside IV alleviates lipopolysaccharide-induced acute kidney injury through down-regulating cytokines, CCR5 and p-ERK, and elevating anti-oxidative ability. Med Sci Monit 23:1413–1420CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineHuazhong Agricultural UniversityWuhanPeople’s Republic of China
  2. 2.College of Animals Husbandry and Veterinary MedicineTibet Agricultural and Animal Husbandry UniversityLinzhiPeople’s Republic of China
  3. 3.University College of Veterinary & Animal SciencesIslamia University of BahawalpurBahawalpurPakistan

Personalised recommendations