Skip to main content

Effects of Sanoshashinto on left ventricular hypertrophy and gut microbiota in spontaneously hypertensive rats


In our previous study, we found that the methanolic extract of Sanoshashinto (三黄瀉心湯) (SHXXTM) exhibited significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine were the main antihypertensive constituents in SHXXTM. We also speculated that the baicalin–berberine (BB) combination produced vasorelaxant effects by activating the NO/cGMP pathway, and the BKCa channel and the DAG/PKC/CPI-17 pathway were involved. In this study, we examined the vasorelaxant effects using helical strips of rat aorta pretreated with different activators or inhibitors. The results suggested that the KATP channel and the voltage-dependent Ca2+ channel (VDCC) were also involved in the vasorelaxant effects. Furthermore, we found that SHXXTM and the BB combination reduced left ventricular hypertrophy and altered gut microbiota. Together, the results indicated that Sanoshashinto might have comprehensive effects on ameliorating hypertension.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. Motoo Y, Seki T, Tsutani K (2011) Traditional Japanese medicine, Kampo: its history and current status. Chin J Integr Med 17:85–87

    Article  Google Scholar 

  2. Wu JB, Nakashima S, Shigyo M, Yamasaki M, Ikuno S, Morikawa A, Takegami S, Nakamura S, Konishi A, Kitade T, Matsuda H (2020) Antihypertensive constituents in. Sanoshashinto. J Nat Med.

    Article  PubMed  Google Scholar 

  3. Lin YL, Dai ZK, Lin RJ, Chu KS, Chen IJ, Wu JR, Wu BN (2010) Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca2+-activated K+ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery. Phytomedicine 17:760–770

    Article  CAS  Google Scholar 

  4. Ko WH, Yao XQ, Lau CW, Law WI, Chen ZY, Ho WKK, Huang Y (2000) Vasorelaxant and antiproliferative effects of berberine. Eur J Pharmacol 399:187–196

    Article  CAS  Google Scholar 

  5. Antza C, Stabouli S, Kotsis V (2018) Gut microbiota in kidney disease and hypertension. Pharmacol Res 130:198–203

    Article  CAS  Google Scholar 

  6. Sircana A, De Michieli F, Parente R, Framarin L, Leone N, Berrutti M, Paschetta E, Bongiovanni D, Musso G (2018) Gut microbiota, hypertension and chronic kidney disease: recent advances. Pharmacol Res 144:390–408

    Article  Google Scholar 

  7. Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong MH, Qi YF, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, Mohamadzadeh M (2015) Gut dysbiosis is linked to hypertension. Hypertension 65:1331–1340

    Article  CAS  Google Scholar 

  8. Sui HX (2009) Study on the safety evaluation of apigenin and its effect on decreasing blood pressure as well as its possible mechanisms. Accessed 20 Dec 2019

  9. Liang QY (2008) Studies on the anti-hypetension, anti-hyperlipidemia and anti-hyperglycaemia, and the action mechanisms of cactus pear fruit polysaccharide. Accessed 20 Dec 2019

  10. Brozovich FV, Nicholson CJ, Degen CV, Gao YZ, Aggarwal M, Morgan KG (2016) Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders. Pharmacol Rev 68:476–532

    Article  CAS  Google Scholar 

  11. Yan WH, Liu K, Zheng Y, Cao JJ, Zhang A, Wei GH (2018) Antihypertensive effect of a Chinese herbal formula (Salvia miltiorrhiza compound recipe) in hypertensive rats induced by high-fructose, high-salt, and high-fat diet. ScienceAsia 44:187–196

    Article  CAS  Google Scholar 

  12. Pevsner-Ficher M, Blacher E, Tatirovsky E, Ben-Dov IZ, Elinav E (2016) The gut microbiome and hypertension. Curr Opin Nephrol Hypertens 26:1–8

    Article  CAS  Google Scholar 

  13. Hsu CN, Hou CY, Lee CT, Chan JYH, Tain YL (2019) The interplay between maternal and post-weaning high-fat diet and gut microbiota in the developmental programming of hypertension. Nutrients 11:1982–1996

    Article  Google Scholar 

  14. Kanbay M, Onal EM, Afsar B, Dagel T, Yerlikaya A, Covic A, Vaziri ND (2018) The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus. Int Urol Nephrol 50:1453–1466

    Article  Google Scholar 

  15. Xie D, Zhang MS, Wang BL, Lin H, Wu EQ, Zhao HH, Li SC (2019) Differential analysis of hypertension-associated intestinal microbiota. Int J Med Sci 16:872–881

    Article  Google Scholar 

  16. Suchodolski JS, Markel ME, Mazcorro JFG, Unterer S, Heilmann RM, Dowd SE, Kachroo P, Ivanov I, Minamoto Y, Dillman EM, Steiner JM, Cook AK, Toresson L (2012) The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. PLoS ONE 7:e51907

    Article  CAS  Google Scholar 

  17. Shariff M, Aditi BK (2018) Corynebacterium striatum: an emerging respiratory pathogen. J Infect Dev Ctries 12:581–586

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Hisashi Matsuda.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1283 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, J., Nakashima, S., Nakamura, S. et al. Effects of Sanoshashinto on left ventricular hypertrophy and gut microbiota in spontaneously hypertensive rats. J Nat Med 74, 482–486 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Sanoshashinto
  • Baicalin
  • Berberine
  • KATP
  • VDCC
  • Gut microbiota