Skip to main content
SpringerLink
Log in

The characteristics of genistin-induced inhibitory effects on intestinal motility

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Genistin belongs to isoflavones. Based on the facts that genistin exerts inhibitory effects on the contractility of vascular smooth muscle,the present study was designed to characterize the effects of genistin on intestinal contractility and evaluate its potential clinical implication. Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, and in vivo assays were used in the study. The results indicated that genistin (5–80 μmol/L) inhibited the contraction of IJS in a dose-dependent manner and inhibited the increased-contractility of IJS induced by acetylcholine (ACh), histamine, high Ca2+, and erythromycin, respectively. The inhibitory effects of genistin were correlated with the stimulation of alpha adrenergic and beta adrenergic receptors since these inhibitory effects were significantly blocked in the presence of phentolamine and propranolol respectively. No further inhibitory effects of genistin were observed in the presence of verapamil or in Ca2+-free condition, indicating genistin-induced inhibitory effects are Ca2+-dependent. Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg2+-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects. The study suggests the potential clinical implications of genistin in relieving intestinal hypercontractility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ajay, M., A.U. Gilani, and M.R. Mustafa. 2003. Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sciences 74: 603–612.

    Article  PubMed  CAS  Google Scholar 

  • Ammit, A.J., C.L. Armour, and J.L. Black. 2000. Smooth-muscle myosin light-chain kinase content is increased in human sensitized airways. American Journal of Respiratory and Critical Care Medicine 161: 257–263.

    PubMed  CAS  Google Scholar 

  • Boué, S.M., T.E. Wiese, S. Nehls, M.E. Burow, S. Elliott, C.H. Carter-Wientjes, B.Y. Shih, J.A. McLachlan, and T.E. Cleveland. 2003. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. Journal of Agriculture and Food Chemistry 51: 2193–2199.

    Article  Google Scholar 

  • Chen, D.P., Y.J. Xiong, L. Wang, B.C. Lv, and Y. Lin. 2012. Characteristics of emodin on modulating the contractility of jejunal smooth muscle. Canadian Journal of Physiology and Pharmacology 90: 455–462.

    Article  PubMed  CAS  Google Scholar 

  • Chen, H., Z.Y. Tang, J.X. Yang, X.M. Wang, S.F. Dai, and Y. Lin. 2004. Effects of caldesmon, calponin, and tropomyosin on the Mg2+-ATPase activities of smooth muscle myosin. Chinese Medical Sciences Journal 19: 286–289.

    PubMed  CAS  Google Scholar 

  • Conti, M.A., and R.S. Adelstein. 1981. The relationship between calmodulin binding and phosphorylation of smooth muscle myosin kinase by the catalytic subunit of 3’:5’ cAMP-dependent protein kinase. Journal of Biological Chemistry 256: 3178–3181.

    PubMed  CAS  Google Scholar 

  • Deng, J.T., J.E. Van Lierop, C. Sutherland, and M.P. Walsh. 2001. Ca2+-independent smooth muscle contraction. Journal of Biological Chemistry 276: 16365–16373.

    Article  PubMed  CAS  Google Scholar 

  • Deng, M., W. Ding, X. Min, and Y. Xia. 2011. MLCK-independent phosphorylation of MLC20 and its regulation by MAP kinase pathway in human bladder smooth muscle cells. Cytoskeleton (Hoboken) 68: 139–149.

    Article  CAS  Google Scholar 

  • Donovan, S.M., A. Andres, R.A. Mathai, T.B. Kuhlenschmidt, and M.S. Kuhlenschmidt. 2009. Soy formula and isoflavones and the developing intestine. Nutrition Reviews 67: 192–200.

    Article  Google Scholar 

  • Edelman, A.M., W.H. Lin, D.J. Osterhout, M.K. Bennett, M.B. Kennedy, and E.G. Krebs. 1990. Phosphorylation of smooth muscle myosin by type II Ca2+/calmodulin-dependent protein kinase. Molecular and Cellular Biochemistry 97: 87–98.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, A.M., and N. Nagy. 2008. A bird’s eye view of enteric nervous system development: lessons from the avian embryo. Pediatric Research 64: 326–333.

    Article  PubMed  Google Scholar 

  • Ihara, E., L. Moffat, M.A. Borman, J.E. Amon, M.P. Walsh, and J.A. MacDonald. 2009. Ca2+-independent contraction of longitudinal ileal smooth muscle is potentiated by a zipper-interacting protein kinase pseudosubstrate peptide. American Journal of Physiology. Gastrointestinal and Liver Physiology 297: G361–G370.

    Article  PubMed  CAS  Google Scholar 

  • Iwabu, A., K. Smith, F.D. Allen, D.A. Lauffenburger, and A. Wells. 2004. Epidermal growth factor induces fibroblast contractility and motility via a protein kinase C delta-dependent pathway. Journal of Biological Chemistry 279: 14551–14560.

    Article  PubMed  CAS  Google Scholar 

  • Kato, K., S. Takahashi, L. Cui, T. Toda, S. Suzuki, M. Futakuchi, S. Sugiura, and T. Shirai. 2000. Suppressive effects of dietary genistin and daidzin on rat prostate carcinogenesis. Japanese Journal of Cancer Research 91: 786–791.

    Article  PubMed  CAS  Google Scholar 

  • Kühn, H., A. Tewes, M. Gagelmann, K. Güth, A. Arner, and J.C. Rüegg. 1990. Temporal relationship between force, ATPase activity, and myosin phosphorylation during a contraction/relaxation cycle in a skinned smooth muscle. Pflugers Archiv. European Journal of Physiology 416: 512–518.

    Article  PubMed  Google Scholar 

  • Kurita, A., S. Kado, T. Matsumoto, N. Asakawa, N. Kaneda, I. Kato, K. Uchida, M. Onoue, and T. Yokokura. 2011. Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of β-glucuronidase activity in intestinal lumen. Cancer Chemotherapy and Pharmacology 67: 201–213.

    Article  PubMed  CAS  Google Scholar 

  • La, J.H., T.W. Kim, T.S. Sung, J.W. Kang, H.J. Kim, and I.S. Yang. 2003. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World Journal of Gastroenterology 9: 2791–2795.

    PubMed  Google Scholar 

  • Lethaby, A.E., J. Brown, J. Marjoribanks, F. Kronenberg, H. Roberts, and J. Eden. 2007. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database of Systematic Reviews 4: 1–64.

    Google Scholar 

  • Lin, Y., H. Sun, S. Dai, Z. Tang, X. He, and H. Chen. 2000. The bi-directional regulation of filamin on the ATPase activity of smooth muscle myosin. Chinese Medical Sciences Journal 15: 162–164.

    PubMed  CAS  Google Scholar 

  • Megens, A.A., L.L. Canters, F.H. Awouters, and C.J. Niemegeers. 1990. Normalization of small intestinal propulsion with loperamide-like antidiarrheals in rats. European Journal of Pharmacology 178: 357–364.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, R.W., C.Y. Seow, T. Burdyga, R. Maass-Moreno, V.R. Pratusevich, J. Ragozzino, and L.E. Ford. 2001. Relationship between myosin phosphorylation and contractile capability of canine airway smooth muscle. Journal of Applied Physiology 90: 2460–2465.

    PubMed  CAS  Google Scholar 

  • Schemann, M. 2005. Control of gastrointestinal motility by the “gut brain”—the enteric nervous system. Journal of Pediatric Gastroenterology and Nutrition 41: S4–S6.

    Article  PubMed  Google Scholar 

  • Shih, C.H., Y. Chen, M. Wang, I.K. Chu, and C. Lo. 2008. Accumulation of isoflavone genistin in transgenic tomato plants overexpressing a soybean isoflavone synthase gene. Journal of Agriculture and Food Chemistry 56: 5655–5661.

    Article  CAS  Google Scholar 

  • Tan, W., H. Zhang, H.S. Luo, and H. Xia. 2011. Effects of trimebutine maleate on colonic motility through Ca2+-activated K+ channels and L-type Ca2+ channels. Archives of Pharmacal Research 34: 979–985.

    Article  PubMed  CAS  Google Scholar 

  • Tang, K.M., G.R. Wang, P. Lu, R.H. Karas, M. Aronovitz, S.P. Heximer, K.M. Kaltenbronn, K.J. Blumer, D.P. Siderovski, Y. Zhu, and M.E. Mendelsohn. 2003. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nature Medicine 9: 1506–1512.

    Article  PubMed  CAS  Google Scholar 

  • Tang, Z.Y., H. Chen, J.X. Yang, S.F. Dai, and Y. Lin. 2005. The comparison of Ca2+/CaM-independent and Ca2+/CaM-dependent phosphorylation of myosin light chains by MLCK. Physiological Research 54: 671–678.

    PubMed  CAS  Google Scholar 

  • Verin, A.D., L. Gilbert-McClain, C.E. Patterson, and J.G. Garcia. 1998. Biochemical regulation of the nonmuscle myosin light chain kinase isoform in bovine endothelium. American Journal of Respiratory Cell and Molecular Biology 19: 767–776.

    PubMed  CAS  Google Scholar 

  • Webb, R.C. 2003. Smooth muscle contraction and relaxation. Advances in Physiology Education 27: 201–206.

    PubMed  Google Scholar 

  • Weber, L.P., J.E. Van Lierop, and M.P. Walsh. 1999. Ca2+-independent phosphorylation of myosin in rat caudal artery and chicken gizzard myofilaments. Journal of Physiology 516: 805–824.

    Article  PubMed  CAS  Google Scholar 

  • Wirth, A., M. Schroeter, C. Kock-Hauser, E. Manser, J.M. Chalovich, P. De Lanerolle, and G. Pfitzer. 2003. Inhibition of contraction and myosin light chain phosphorylation in guinea-pig smooth muscle by p21-activated kinase 1. Journal of Physiology 549: 489–500.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, J.H., Y. Arao, S.J. Sun, A. Kikuchi, and F. Kayama. 2006. Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat. Life Sciences 78: 812–819.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, J., L. Chen, H. Xia, and H.S. Luo. 2010. Mechanisms mediating CCK-8S-induced contraction of proximal colon in guinea pigs. World Journal of Gastroenterology 16: 1076–1085.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant No. 30772601). The authors wish to thank Zhi Lin and Fan Yuan for their valuable comments.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Dalian Medical University, Dalian, 116044, Liaoning, China

    Yong-jian Xiong, Da-peng Chen, Bo-chao Lv, Fang-fei Liu, Li Wang & Yuan Lin

Authors
  1. Yong-jian Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Da-peng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo-chao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fang-fei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuan Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuan Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiong, Yj., Chen, Dp., Lv, Bc. et al. The characteristics of genistin-induced inhibitory effects on intestinal motility. Arch. Pharm. Res. 36, 345–352 (2013). https://doi.org/10.1007/s12272-013-0053-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-013-0053-2

Keywords

Search

Navigation