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. 2022 Dec;60(1):1721-1731.
doi: 10.1080/13880209.2022.2116054.

Modified Taohong Siwu decoction improves cardiac function after myocardial ischaemia and reperfusion in rats by promoting endogenous stem cell mobilization and regulating metabolites

Wan-Ting Meng  1   2 , Zhong-Xin Xiao  2   3 , Han Li  1   2 , Ya-Chao Wang  1   2 , Yue Zhao  1   2 , Yan Zhu  3 , Hai-Dong Guo  1   2
Affiliations

Modified Taohong Siwu decoction improves cardiac function after myocardial ischaemia and reperfusion in rats by promoting endogenous stem cell mobilization and regulating metabolites

Wan-Ting Meng et al. Pharm Biol. 2022 Dec.

Abstract

Context: Taohong Siwu decoction (THSWD) has been shown to promote heart repair in myocardial infarction.

Objective: To determine the effects of modified THSWD (THSWD plus four ingredients) on myocardial ischaemia and reperfusion (I/R) injury.

Materials and methods: Sixty Sprague-Dawley rats were randomly divided into the I/R group and three different modified THSWD dose groups (gavage administration, 1.215, 2.43, and 4.86 g, respectively). 2,3,5-Triphenyltetrazolium chloride and Evans blue staining were used to detect the infarct area at 24 h after treatment. The serum biochemical indexes and cell apoptosis were examined to determine myocardial injury. The number of endogenous stem cells, expression of stromal dell derived factor-1 (SDF-1) and stem cell factor (SCF), and cardiac function were measured at 4 weeks. The serum was collected for metabolomic analysis.

Results: The high-dose modified THSWD group presented a reduced infarction area (decreased by 21.3%), decreased levels of lactate dehydrogenase and creatinine kinase, attenuated cell apoptosis, and enhanced superoxide dismutase activity in early stage I/R compared with other groups. The serum SCF and SDF-1 levels were higher in the high-dose group than in the I/R group. At 4 weeks, the infarct size and collagen content were the lowest, and the ejection fraction and fractional shortening values were the highest in the high-dose group. Moreover, high-dose modified THSWD affected the metabolism of phosphonate and phosphonate, taurine, and hypotaurine.

Conclusions: Endogenous stem cell mobilization and metabolic regulation were related to the cardioprotection of modified THSWD. We provided a new strategy and direction for the treatment of cardiovascular diseases with traditional Chinese medicine.

Keywords: Apoptosis; cardiovascular diseases; heart repair; traditional Chinese medicine.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Effects of modified THSWD on the early myocardial infarction area in I/R rat models. (A) Representative photos of TTC and Evans blue staining. (B) Statistical analysis of the myocardial infarction area. **p < 0.01 compared with I/R group; ##p < 0.01 compared with low-dose modified THSWD group; && p < 0.01 compared with medium-dose modified THSWD group.
Figure 2.
Figure 2.
Effects of modified THSWD on early myocardial injury caused by I/R. (A) Serum CK content. (B) Serum LDH content. (C) Serum SOD activity. *p < 0.05 and **p < 0.01 compared with I/R group; #p < 0.05 and ##p < 0.01 compared with low-dose modified THSWD group; && p < 0.01 compared with medium-dose modified THSWD group.
Figure 3.
Figure 3.
Effects of modified THSWD on early cell apoptosis in infarcted myocardium. (A) TUNEL staining of myocardial tissues (scale bar = 25 μm). (B) Statistical analysis of TUNEL-positive cells. (C–E) The levels of Bcl-2 and Bax were detected by Western blot. *p < 0.05 and **p < 0.01 compared with I/R group; #p < 0.05 and ##p < 0.01 compared with low-dose modified THSWD group; &p < 0.05 and &&p < 0.01 compared with medium-dose modified THSWD group.
Figure 4.
Figure 4.
Effects of high-dose modified THSWD on the recruitment of endogenous stem cells to the infarct sites. (A) c-kit immunofluorescence staining (scale bar = 25 μm). (B) Sca-1 immunofluorescence staining (scale bar = 25 μm). (C) Statistical analysis of the number of c-kit-positive cells. (D) Statistical analysis of Sca-1-positive cells. *p < 0.05 and **p < 0.01 compared with the I/R group.
Figure 5.
Figure 5.
Effects of high-dose modified THSWD on the level of serum chemokines. Levels of serum SCF (A) and SDF-1 (B) were detected by ELISA. *p < 0.05 and **p < 0.01 compared with I/R group.
Figure 6.
Figure 6.
Effects of modified THSWD on the cardiac function of I/R rat models. (A) EF and (B) FS were measured by echocardiography after 4 weeks of intragastric administration of different doses of modified THSWD. **p < 0.01 compared with I/R group; #p < 0.05 compared with low-dose modified THSWD group; &p < 0.05 compared with medium-dose modified THSWD group.
Figure 7.
Figure 7.
Effects of modified THSWD on infarct size and collagen content in late-stage I/R. (A) Masson’s trichrome stainings showed the extent of myocardial infarction in each group. (B) Statistical analysis of infarct size. (C) Masson’s trichrome staining showed collagen content in the infarct area of each group (scale bar = 50 μm). (D) Statistical analysis of collagen content in the infarct area of each group. **p < 0.01 compared with I/R group; ##p < 0.01 compared with low-dose modified THSWD group; &&p < 0.01 compared with medium-dose modified THSWD group.
Figure 8.
Figure 8.
Metabolomics heat map analysis between high-dose modified THSWD and I/R groups.
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Grants and funding

This work was supported by grants from the National Natural Science Foundation of China [82174120], Natural Science Foundation of Shanghai [No. 21ZR1463100] and Shanghai Talent Development Funding Scheme [No. 2019090].

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