Effects of Saikosaponin D on Apoptosis, Autophagy, and Morphological Structure of Intestinal Cells of Cajal with Functional Dyspepsia

  • Authors: Zeng Y.1, Zhou L.2, Wan Y.3, Fu T.4, Xu P.5, Zhang H.6, Guan Y.7
  • Affiliations:
    1. Department of Hospital Infection Management Office,, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine
    2. Department of Rehabilitation, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,
    3. Department of Gastroenterology, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,
    4. Department of Traditional Chinese Medicine, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine
    5. College of Acupuncture and Orthopedics,, Hubei University of Chinese Medicine
    6. , Jianghan University
    7. Department of Hospital Infection Management Office, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,
  • Issue: Vol 27, No 10 (2024)
  • Pages: 1513-1522
  • Section: Chemistry
  • URL: https://vietnamjournal.ru/1386-2073/article/view/643831
  • DOI: https://doi.org/10.2174/0113862073262404231004053116
  • ID: 643831

Cite item

Full Text

Abstract

Objective:Functional dyspepsia (FD) is one of the most common gastrointestinal diseases, with a global prevalence of 10%-30%. However, the specific pathogenesis of FD has not yet been determined. As such, the aim of this study was to investigate the effects of saikosaponin D (SSD) administration on the apoptosis, autophagy, and morphological structure of the intestinal cells of Cajal (ICCs) in FD.

Methods:A rat model of FD was constructed by stimulating the rat tail with a sponge clamp at one-third of the distal tail length. An autophagy model was constructed for ICCs using glutamate. The apoptosis rate in each group of cells was determined using flow cytometry. The expressions of ghrelin and substance P (SP) were detected using ELISA.

Results:The body weight and food intake of male and female rats in the SSD group were consistently higher than those in the model group. The SSD group showed substantial improvement compared with the model group, with no inflammatory cell infiltration and normal gastric mucosal structures. After intervention with SSD, the ultrastructure of the ICCs considerably improved and was clear. Compared with the model group, the expressions of LC3 I/II, ghrelin, and SP proteins in the SSD group were significantly upregulated, and the apoptosis rate was significantly reduced.

Conclusion:The administration of SSD improved ICC morphology and structure, inhibited excessive autophagy, and improved FD, a gastrointestinal motility disorder, by regulating ghrelin and SP levels.

About the authors

Yi Zeng

Department of Hospital Infection Management Office,, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine

Email: info@benthamscience.net

Li Zhou

Department of Rehabilitation, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,

Email: info@benthamscience.net

Ying Wan

Department of Gastroenterology, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,

Email: info@benthamscience.net

Ting Fu

Department of Traditional Chinese Medicine, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine

Email: info@benthamscience.net

Paidi Xu

College of Acupuncture and Orthopedics,, Hubei University of Chinese Medicine

Email: info@benthamscience.net

Hongxing Zhang

, Jianghan University

Author for correspondence.
Email: info@benthamscience.net

Ying Guan

Department of Hospital Infection Management Office, Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,

Author for correspondence.
Email: info@benthamscience.net

References

  1. Ford, A.C.; Mahadeva, S.; Carbone, M.F.; Lacy, B.E.; Talley, N.J. Functional dyspepsia. Lancet, 2020, 396(10263), 1689-1702. doi: 10.1016/S0140-6736(20)30469-4 PMID: 33049222
  2. Sayuk, G.S.; Gyawali, C.P. Functional dyspepsia: Diagnostic and therapeutic approaches. Drugs, 2020, 80(13), 1319-1336. doi: 10.1007/s40265-020-01362-4 PMID: 32691294
  3. Voiosu, T.A.; Giurcan, R.; Voiosu, A.M.; Voiosu, M.R. Functional dyspepsia today. Maedica, 2013, 8(1), 68-74. PMID: 24023602
  4. Wauters, L.; Talley, N.J.; Walker, M.M.; Tack, J.; Vanuytsel, T. Novel concepts in the pathophysiology and treatment of functional dyspepsia. Gut, 2020, 69(3), 591-600. doi: 10.1136/gutjnl-2019-318536 PMID: 31784469
  5. Ohno, T.; Mochiki, E.; Kuwano, H. The roles of motilin and ghrelin in gastrointestinal motility. Int. J. Pept., 2010, 2010, 820794. doi: 10.1155/2010/820794
  6. Yagi, T.; Asakawa, A.; Ueda, H.; Miyawaki, S.; Inui, A. The role of ghrelin in patients with functional dyspepsia and its potential clinical relevance (Review). Int. J. Mol. Med., 2013, 32(3), 523-531. doi: 10.3892/ijmm.2013.1418 PMID: 23778458
  7. Zagari, R.M.; Law, G.R.; Fuccio, L.; Cennamo, V.; Gilthorpe, M.S.; Forman, D.; Bazzoli, F. Epidemiology of functional dyspepsia and subgroups in the Italian general population: an endoscopic study. Gastroenterology, 2010, 138(4), 1302-1311. doi: 10.1053/j.gastro.2009.12.057 PMID: 20074574
  8. Futagami, S.; Itoh, T.; Sakamoto, C. Systematic review with meta-analysis: Post-infectious functional dyspepsia. Aliment. Pharmacol. Ther., 2015, 41(2), 177-188. doi: 10.1111/apt.13006 PMID: 25348873
  9. Okumura, T.; Tanno, S.; Ohhira, M.; Tanno, S. Prevalence of functional dyspepsia in an outpatient clinic with primary care physicians in Japan. J. Gastroenterol., 2010, 45(2), 187-194. doi: 10.1007/s00535-009-0168-x PMID: 19997854
  10. Du, L.; Chen, B.; Kim, J.J.; Chen, X.; Dai, N. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis. Neurogastroenterol. Motil., 2018, 30(4), e13304. doi: 10.1111/nmo.13304 PMID: 29392796
  11. Otaka, M.; Jin, M.; Odashima, M.; Matsuhashi, T.; Wada, I.; Horikawa, Y.; Komatsu, K.; Ohba, R.; Oyake, J.; Hatakeyama, N.; Watanabe, S. New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment. Pharmacol. Ther., 2005, 21(S2), 42-46. doi: 10.1111/j.1365-2036.2005.02473.x PMID: 15943846
  12. Kelber, O.; Bauer, R.; Kubelka, W. Phytotherapy in functional gastrointestinal disorders. Dig. Dis., 2017, 35(S1), 36-42. doi: 10.1159/000485489 PMID: 29421793
  13. Huizinga, J.D.; Lammers, W.J.E.P. Gut peristalsis is governed by a multitude of cooperating mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(1), G1-G8. doi: 10.1152/ajpgi.90380.2008 PMID: 18988693
  14. Ueshima, S.; Nishida, T.; Koike, M.; Matsuda, H.; Sawa, Y.; Uchiyama, Y. Nitric oxide-mediated injury of interstitial cells of Cajal and intestinal dysmotility under endotoxemia of mice. Biomed. Res., 2014, 35(4), 251-262. doi: 10.2220/biomedres.35.251 PMID: 25152034
  15. Thein, W.; Po, W.W.; Choi, W.S.; Sohn, U.D. Autophagy and digestive disorders: Advances in understanding and therapeutic approaches. Biomol. Ther., 2021, 29(4), 353-364. doi: 10.4062/biomolther.2021.086 PMID: 34127572
  16. Li, X.; Li, X.; Huang, N.; Liu, R.; Sun, R. A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins. Phytomedicine, 2018, 50, 73-87. doi: 10.1016/j.phymed.2018.09.174 PMID: 30466994
  17. Lu, C.N.; Yuan, Z.G.; Zhang, X.L.; Yan, R.; Zhao, Y.Q.; Liao, M.; Chen, J.X. Saikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of NF-κB signaling pathway. Int. Immunopharmacol., 2012, 14(1), 121-126. doi: 10.1016/j.intimp.2012.06.010 PMID: 22728095
  18. Wong, V.K.W.; Zhou, H.; Cheung, S.S.F.; Li, T.; Liu, L. Mechanistic study of saikosaponin-d (Ssd) on suppression of murine T lymphocyte activation. J. Cell. Biochem., 2009, 107(2), 303-315. doi: 10.1002/jcb.22126 PMID: 19301261
  19. Zhang, G.; Xie, S.; Hu, W.; Liu, Y.; Liu, M.; Liu, M.; Chang, X. Effects of electroacupuncture on interstitial cells of cajal (ICC) ultrastructure and connexin 43 protein expression in the gastrointestinal tract of functional dyspepsia (FD) rats. Med. Sci. Monit., 2016, 22, 2021-2027. doi: 10.12659/MSM.899023 PMID: 27297942
  20. Liu, A.; Tanaka, N.; Sun, L.; Guo, B.; Kim, J.H.; Krausz, K.W.; Fang, Z.; Jiang, C.; Yang, J.; Gonzalez, F.J. Saikosaponin d protects against acetaminophen-induced hepatotoxicity by inhibiting NF-κB and STAT3 signaling. Chem. Biol. Interact., 2014, 223, 80-86. doi: 10.1016/j.cbi.2014.09.012 PMID: 25265579
  21. Tan, R.Q.; Zhang, Z.; Ju, J.; Ling, J.H. Effect of chaihu shugan powder-contained serum on glutamate-induced autophagy of interstitial cells of cajal in the rat gastric antrum. Evid. Based Complement. Alternat. Med., 2019, 2019, 7318616. doi: 10.1155/2019/7318616
  22. Tan, R.Q.; Zhang, Z.; Ning, H.E.; Zhang, L.M.; Wang, Y.; Ling, J.H. Establishment of autophagy model of rat gastric interstitial cells of Cajal induced by glutamic acid. Chin. J. Physiol., 2018, 34, 1532-1536.
  23. Adad, S.J.; Silva, G.B.; Jammal, A.A. The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM. Virchows Archiv: Int. J. Pathology., 2012, 461(4), 385-392.
  24. Mönkemüller, K.; Malfertheiner, P. Drug treatment of functional dyspepsia. World J. Gastroenterol., 2006, 12(17), 2694-2700. doi: 10.3748/wjg.v12.i17.2694 PMID: 16718755
  25. Park, I.K.; Kim, J.H.; Park, C.G.; Kim, M.Y.; Parajuli, S.P.; Hong, C.S.; Choi, S.; Jun, J.Y. Effects of ATP on pacemaker activity of interstitial cells of cajal from the mouse small intestine. Chonnam Med. J., 2018, 54(1), 63-71. doi: 10.4068/cmj.2018.54.1.63 PMID: 29399568
  26. Foong, D.; Zhou, J.; Zarrouk, A.; Ho, V.; O’Connor, M.D. Understanding the biology of human interstitial cells of cajal in gastrointestinal motility. Int. J. Mol. Sci., 2020, 21(12), 4540. doi: 10.3390/ijms21124540 PMID: 32630607
  27. Corsello, A.; Pugliese, D.; Gasbarrini, A.; Armuzzi, A. Diet and nutrients in gastrointestinal chronic Diseases. Nutrients, 2020, 12(9), 2693. doi: 10.3390/nu12092693 PMID: 32899273
  28. Duncanson, K.; Burns, G.; Pryor, J.; Keely, S.; Talley, N.J. Mechanisms of food-induced symptom induction and dietary management in functional dyspepsia. Nutrients, 2021, 13(4), 1109. doi: 10.3390/nu13041109 PMID: 33800668
  29. Hajishafiee, M.; Bitarafan, V.; Feinle-Bisset, C. Gastrointestinal sensing of meal-related signals in humans, and dysregulations in eating-related disorders. Nutrients, 2019, 11(6), 1298. doi: 10.3390/nu11061298 PMID: 31181734
  30. Bento, C.F.; Renna, M.; Ghislat, G.; Puri, C.; Ashkenazi, A.; Vicinanza, M.; Menzies, F.M.; Rubinsztein, D.C. Mammalian autophagy: How does it work? Annu. Rev. Biochem., 2016, 85(1), 685-713. doi: 10.1146/annurev-biochem-060815-014556 PMID: 26865532
  31. Rubinsztein, D.C. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature, 2006, 443(7113), 780-786. doi: 10.1038/nature05291 PMID: 17051204
  32. Runwal, G.; Stamatakou, E.; Siddiqi, F.H.; Puri, C.; Zhu, Y.; Rubinsztein, D.C. LC3-positive structures are prominent in autophagy-deficient cells. Sci. Rep., 2019, 9(1), 10147. doi: 10.1038/s41598-019-46657-z PMID: 31300716
  33. Zhang, L.; Zeng, L.; Deng, J.; Zhang, Y.; Wang, Y.; Xie, T.; Ling, J. Investigation of autophagy and differentiation of myenteric interstitial cells of Cajal in the pathogenesis of gastric motility disorders in rats with functional dyspepsia. Biotechnol. Appl. Biochem., 2018, 65(4), 533-539. doi: 10.1002/bab.1635 PMID: 29274173
  34. Battaglia, E.; Bassotti, G.; Bellone, G.; Dughera, L.; Serra, A.M.; Chiusa, L.; Repici, A.; Mioli, P.; Emanuelli, G. Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis. World J. Gastroenterol., 2006, 12(38), 6172-6177. doi: 10.3748/wjg.v12.i38.6172 PMID: 17036390
  35. Farrugia, G. Interstitial cells of Cajal in health and disease. Neurogastroenterol. Motil., 2008, 20(S1), 54-63. doi: 10.1111/j.1365-2982.2008.01109.x PMID: 18402642
  36. Ohlsson, B.; Veress, B.; Lindgren, S.; Sundkvist, G. Enteric ganglioneuritis and abnormal interstitial cells of Cajal. Inflamm. Bowel Dis., 2007, 13(6), 721-726. doi: 10.1002/ibd.20095 PMID: 17230538
  37. Huizinga, J.D. Neural injury, repair, and adaptation in the GI tract. IV. Pathophysiology of GI motility related to interstitial cells of Cajal. Am. J. Physiol., 1998, 275(3), G381-G386. PMID: 9724247
  38. Kazemi, M.H.; Eshraghian, A.; Hamidpour, L.; Taghavi, S.A. Changes in serum ghrelin level in relation to meal‐time in patients with functional dyspepsia. United European Gastroenterol. J., 2015, 3(1), 11-16. doi: 10.1177/2050640614563373 PMID: 25653854
  39. Ariyasu, H.; Takaya, K.; Tagami, T.; Ogawa, Y.; Hosoda, K.; Akamizu, T.; Suda, M.; Koh, T.; Natsui, K.; Toyooka, S.; Shirakami, G.; Usui, T.; Shimatsu, A.; Doi, K.; Hosoda, H.; Kojima, M.; Kangawa, K.; Nakao, K. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab., 2001, 86(10), 4753-4758. doi: 10.1210/jcem.86.10.7885 PMID: 11600536
  40. Kršek, M.; Rosická, M.; Haluzík, M.; Svobodová, J.; Kotrlíková, E.; Justová, V.; Lacinová, Z.; Jarkovská, Z. Plasma ghrelin levels in patients with short bowel syndrome. Endocr. Res., 2002, 28(1-2), 27-33. doi: 10.1081/ERC-120004535 PMID: 12108787
  41. Kim, S.K.; Joung, J.Y.; Ahn, Y.C.; Jung, I.C.; Son, C.G. Beneficial potential of Banha-Sasim-Tang for stress-sensitive functional dyspepsia via modulation of ghrelin: A randomized controlled trial. Front. Pharmacol., 2021, 12, 636752. doi: 10.3389/fphar.2021.636752 PMID: 33959008
  42. Hwang, S.J.; Wang, J.H.; Lee, J.S.; Lee, H.D.; Choi, T.J.; Choi, S.H.; Son, C.G. Yeokwisan, a standardized herbal formula, enhances gastric emptying via modulation of the ghrelin pathway in a loperamide-induced functional dyspepsia mouse model. Front. Pharmacol., 2021, 12, 753153. doi: 10.3389/fphar.2021.753153 PMID: 34630123
  43. Mönnikes, H.; van der Voort, I.R.; Wollenberg, B.; Heymann-Mönnikes, I.; Tebbe, J.J.; Alt, W.; Arnold, R.; Klapp, B.F.; Wiedenmann, B.; McGregor, G.P. Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia. Digestion, 2005, 71(2), 111-123. doi: 10.1159/000084625 PMID: 15785037

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers