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Effects of ginsenoside Re on rat jejunal contractility

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Abstract

Ginsenoside Re (GRe) exerts diverse effects. Based on our observations, the present study was designed to investigate GRe-exerted bidirectional regulation (BR) on the contractility of isolated jejunal segment. Six pairs of different low and high contractile states of rat jejunal segment were established and used in the study. Stimulatory effects on the contractility of jejunal segment were exerted by GRe (10.0 μM) in all 6 low contractile states, and inhibitory effects were exerted in all 6 high contractile states, indicating that GRe exerted BR on the contractility of jejunal segment. The effects of GRe on the phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK) and MLCK mRNA expression in jejunal segment in low and high contractile states were also bidirectional. GRe-exerted BR was abolished in the presence of neurotoxin tetrodotoxin or Ca2+ channel blocker verapamil or c-Kit receptor tyrosine kinase inhibitor imatinib. Atropine blocked the stimulatory effects of GRe on jejunal contractility in low-Ca2+-induced low contractile state; phentolamine, propranolol and l-NG-nitro-arginine blocked the inhibitory effects in high-Ca2+-induced high contractile state, respectively. In summary, GRe-exerted BR depends on jejunal contractile state and requires the presence of enteric nervous system, Ca2+, and interstitial cells of Cajal; the stimulatory effects of GRe on jejunal contractility are related to cholinergic stimulation and inhibitory effects are related to adrenergic activation and nitric oxide relaxing mechanisms.

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References

  1. Pongkitwitoon B, Sakamoto S, Morinaga O, Juengwatanatrakul T, Shoyama Y, Tanaka H, Morimoto S (2011) Single-chain variable fragment antibody against ginsenoside Re as an effective tool for the determination of ginsenosides in various ginsengs. J Nat Med 65:24–30

    Article  CAS  PubMed  Google Scholar 

  2. Peng D, Wang H, Qu C, Xie L, Wicks SM, Xie J (2012) Ginsenoside Re: its chemistry, metabolism and pharmacokinetics. Chin Med 7:2

    Article  PubMed Central  PubMed  Google Scholar 

  3. Ng WY, Yang MS (2008) Effects of ginsenosides Re and Rg3 on intracellular redox state and cell proliferation in C6 glioma cells. Chin Med 3:8

    Article  PubMed Central  PubMed  Google Scholar 

  4. Song X, Chen J, Sakwiwatkul K, Li R, Hu S (2010) Enhancement of immune responses to influenza vaccine (H3N2) by ginsenoside Re. Int Immunopharmacol 10:351–356

    Article  CAS  PubMed  Google Scholar 

  5. Christensen LP, Jensen M (2009) Biomass and content of ginsenosides and polyacetylenes in American ginseng roots can be increased without affecting the profile of bioactive compounds. J Nat Med 63:159–168

    Article  CAS  PubMed  Google Scholar 

  6. Gu XQ, Chen YP, Hu TT, Lu XH, Li XQ, Du XH, Cao X, Wang WH, Xu ZG (2011) Extraction and identification of ginsenoside Re and its effects and mechanism of protecting acute renal ischemia-reperfusion injury in rats. Chem Res Chin Univ 27:84–88

    Google Scholar 

  7. Nakaya Y, Mawatari K, Takahashi A, Harada N, Hata A, Yasui S (2007) The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways. J Med Invest 54:381–384

    Article  PubMed  Google Scholar 

  8. Chen DP, Xiong YJ, Tang ZY, Lv BC, Lin Y (2012) Inhibitory effects of daidzein on intestinal motility in normal and high contractile states. Pharm Biol 50:1561–1566

    Article  CAS  PubMed  Google Scholar 

  9. Xu JR, Luo JY, Shang L, Kong WM (2006) Effect of change in an inhibitory neurotransmitter of the myenteric plexus on the pathogenetic mechanism of irritable bowel syndrome subgroups in rat models. Chin J Dig Dis 7:89–96

    Article  CAS  PubMed  Google Scholar 

  10. Peng LH, Yang YS, Sun G, Wang WF (2004) A new model of constipation-predominant irritable bowel syndrome in rats. World Chin J Digestol 12:112–116

    Google Scholar 

  11. Yamada T, Zimmerman BJ, Specian RD, Grisham MB (1991) Role of neutrophils in acetic acid-induced colitis in rats. Inflammation 15:399–411

    Article  CAS  PubMed  Google Scholar 

  12. Gaut ZN, Baruth H, Randall LO, Ashley C, Paulsrud JR (1975) Stereoisomeric relationships among anti-inflammatory activity, inhibition of platelet aggregation, and inhibition of prostaglandin synthetase. Prostaglandins 10:59–66

    Article  CAS  PubMed  Google Scholar 

  13. Zhu J, Chen L, Xia H, Luo HS (2010) Mechanisms mediating CCK-8S-induced contraction of proximal colon in guinea pigs. World J Gastroenterol 16:1076–1085

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Chen DP, Xiong YJ, Wang L, Lv BC, Lin Y (2012) Characteristics of emodin on modulating the contractility of jejunal smooth muscle. Can J Physiol Pharmacol 90:455–462

    Article  CAS  PubMed  Google Scholar 

  15. Tan W, Zhang H, Luo HS, Xia H (2011) Effects of trimebutine maleate on colonic motility through Ca2+-activated K+ channels and L-type Ca2+ channels. Arch Pharm Res 34:979–985

    Article  CAS  PubMed  Google Scholar 

  16. Dela Peña IC, Yoon SY, Kim SM, Lee GS, Park CS, Kim YC, Cheong JH (2009) Inhibition of intestinal motility by the putative BK(Ca) channel opener LDD175. Arch Pharm Res 32:413–420

    Article  PubMed  Google Scholar 

  17. Frings M, Haschke G, Heinke B, Schäfer KH, Diener M (2000) Spontaneous contractions of intestinal smooth muscle re-aggregates from the new-born rat triggered by thromboxane A2. J Vet Med A Physiol Pathol Clin Med 47:469–475

    Article  CAS  PubMed  Google Scholar 

  18. Kirschstein T, Rehberg M, Bajorat R, Tokay T, Porath K, Köhling R (2009) High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle. Acta Pharmacol Sin 30:1123–1131

    Article  CAS  PubMed  Google Scholar 

  19. Zhi G, Ryder JW, Huang J, Ding P, Chen Y, Zhao Y, Kamm KE, Stull JT (2005) Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction. Proc Natl Acad Sci USA 102:17519–17524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Srinivas SP, Satpathy M, Guo Y, Anandan V (2006) Histamine-induced phosphorylation of the regulatory light chain of myosin II disrupts the barrier integrity of corneal endothelial cells. Invest Ophthalmol Vis Sci 47:4011–4018

    Article  PubMed  Google Scholar 

  21. Hu N, Li Y, Zhao Y, Wang Q, You JC, Zhang XD, Ye LH (2011) A novel positive feedback loop involving FASN/p-ERK1/2/5-LOX/LTB4/FASN sustains high growth of breast cancer cells. Acta Pharmacol Sin 32:921–929

    Article  CAS  PubMed  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  23. Schemann M (2005) Control of gastrointestinal motility by the “gut brain”—the enteric nervous system. J Pediatr Gastroenterol Nutr 41(Suppl 1):S4–S6

    Article  PubMed  Google Scholar 

  24. Booth CC, Alldis D, Read AE (1961) Studies on the site of fat absorption: 2 fat balances after resection of varying amounts of the small intestine in man. Gut 2:168–174

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Ruiz IL, Urbano-Cuadrado M, Gómez-Nieto MÁ (2008) Improving the development of QSAR prediction models with the use of approximate similarity approach. Eng Lett 16:36–43

    Google Scholar 

  26. Webb RC (2003) Smooth muscle contraction and relaxation. Adv Physiol Educ 27:201–206

    PubMed  Google Scholar 

  27. Hwang DF, Noguchi T (2007) Tetrodotoxin poisoning. Adv Food Nutr Res 52:141–236

    Article  CAS  PubMed  Google Scholar 

  28. Daigo Y, Takayama I, Ponder BA, Caldas C, Ward SM, Sanders KM, Fujino MA (2003) Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal. BMC Gastroenterol 3:17

    Article  PubMed Central  PubMed  Google Scholar 

  29. Yamazawa T, Iino M (2002) Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and longitudinal smooth muscle cells during rhythmic activity in mouse ileum. J Physiol 538:823–835

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Cretoiu SM, Simionescu AA, Caravia L, Curici A, Cretoiu D, Popescu LM (2011) Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium. Acta Physiol Hung 98:329–338

    Article  CAS  PubMed  Google Scholar 

  31. Wu TJ, Lee LY, Yeh CN, Wu PY, Chao TC, Hwang TL, Jan YY, Chen MF (2006) Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate. BMC Gastroenterol 6:29

    Article  PubMed Central  PubMed  Google Scholar 

  32. Unno T, Matsuyama H, Izumi Y, Yamada M, Wess J, Komori S (2006) Roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse ileum studied with receptor knockout mice. Br J Pharmacol 149:1022–1030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Obi T, Miyamoto A, Matumoto M, Ishiguro S, Nishio A (1991) Participation of H1-receptors in histamine-induced contraction and relaxation of horse coronary artery in vitro. J Vet Med Sci 53:789–795

    Article  CAS  PubMed  Google Scholar 

  34. Bauer V (1981) Distribution and types of adrenoceptors in the guinea-pig ileum: the action of α- and β-adrenoceptor agonists. Br J Pharmacol 72:201–210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9:1506–1512

    Article  CAS  PubMed  Google Scholar 

  36. Grange RW, Isotani E, Lau KS, Kamm KE, Huang PL, Stull JT (2001) Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles. Physiol Genomics 5:35–44

    CAS  PubMed  Google Scholar 

  37. Ignarro LJ (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560

    Article  CAS  PubMed  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 comments.

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The authors declare that they have no conflict of interest.

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Correspondence to Yuan Lin.

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Supplemental Fig 1. Effects of ginsenoside Re (GRe) on myosin phosphorylation-related mechanisms of jejunal segment isolated from constipation prominent control rats. (A1) The extent of phosphorylation 20-kDa myosin light chain (the ratio of phosphor-myosin light chain to myosin light chain: p-MLC20/MLC20). (B1) The protein content of myosin light chain kinase (MLCK) and (C) the mRNA expression of MLCK in intragastric room-temperature water-treated normal control rats (NC-control) and in intragastric GRe-treated NC-control rats (10, 20, 40 mg/kg). ** P < 0.01 compared with control.

Supplemental Fig 2. Effects of ginsenoside Re (GRe) on myosin phosphorylation-related mechanisms of jejunal segment isolated from diarrhea-prominent control rats. (A1) The extent of phosphorylation 20-kDa myosin light chain (the ratio of phosphor-myosin light chain to myosin light chain: p-MLC20/MLC20). (B1) The protein content of myosin light chain kinase (MLCK) and (C) the mRNA expression of MLCK in intragastric saline-treated normal control control rats (NC-control) and in intragastric GRe-treated NC-control rats (10, 20, 40 mg/kg). ** P < 0.01 compared with control.

Supplementary material 1 (DOCX 13 kb)

11418_2014_831_MOESM2_ESM.tif

Effects of ginsenoside Re (GRe) on myosin phosphorylation-related mechanisms of jejunal segment isolated from constipation prominent control rats. (A1) The extent of phosphorylation 20-kDa myosin light chain (a ratio of phosphor-myosin light chain to myosin light chain (p-MLC20/MLC20) (B1) The protein content of myosin light chain kinase (MLCK) and (C) the mRNA expression of MLCK in intragastric room-temperature water-treated normal control rats (NC-control) and in intragastric GRe-treated NC-control rats (10, 20, 40 mg/kg). **P < 0.01 compared with the control (TIFF 5938 kb)

11418_2014_831_MOESM3_ESM.tif

Effects of ginsenoside Re (GRe) on myosin phosphorylation-related mechanisms of jejunal segment isolated from diarrhea prominent control rats. (A1) The extent of phosphorylation 20-kDa myosin light chain (a ratio of phosphor-myosin light chain to myosin light chain (p-MLC20/MLC20) (B1) The protein content of myosin light chain kinase (MLCK) and (C) the mRNA expression of MLCK in intragastric saline-treated normal control control rats (NC-control) and in intragastric GRe-treated NC-control rats (10, 20, 40 mg/kg). **P < 0.01 compared with the control (TIFF 615 kb)

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Xiong, Y., Chen, D., Lv, B. et al. Effects of ginsenoside Re on rat jejunal contractility. J Nat Med 68, 530–538 (2014). https://doi.org/10.1007/s11418-014-0831-2

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