Repair of Adult Mammalian Heart After Damages by Oral Intake of Gu Ben Pei Yuan San.

Baiping Cui,Jiaqi Zhu,Wei Sheng,Qianqian Liang,Chen Xu,Yufan Zheng,Xinyan Zhou,Guoying Huang,Jiexian Zhuang,Ning Sun,Lina Luan

doi:10.3389/fphys.2019.00607

Abstract

Adult mammalian heart repair after myocardial damage is highly inefficient due to the post-mitotic nature of cardiomyocytes. Interestingly, in traditional Chinese medicine (TCM), there are reported effective treatments of myocardial infarction (MI) and heart failure in adult humans by oral intake of a TCM concoction named Gu Ben Pei Yuan San (GBPYS), which is composed of Panax ginseng, velvet antler, Gekko gecko Linnaeus tail, human placenta, Trogopterus dung, Panax notoginseng, and amber. We fed mice with GBPYS after myocardial damages through everyday self-feeding. We then examined the effect of everyday oral intake of GBPYS on improving cardiac function and myocardial repair in adult mice after apical resection or MI. We found that long-term oral intake of GBPYS significantly improved cardiac function after myocardial damages in adult mice. BrdU, phospho-histone 3, and AuroraB staining indicated increased cell proliferation at the border zone of MI after TCM feeding. GBPYS feeding reduced organ inflammation, induced angiogenesis, and is non-toxic to mice after long-term oral intake. Further, serum derived from TCM-fed MI rats promoted division of both neonatal rat cardiomyocytes and human induced pluripotent stem cell (iPSC)-derived cardiomyocytes in vitro. Oral intake of GBPYS improved heart repair after myocardial damages in adult mice. Our results suggest that there are substances present in GBPYS that help improve adult mammalian heart repair after MI. Also, it could be a good choice of non-invasive alternative therapy for myocardial damages and heart failure after rigorous clinical study in the future.

Highlights

It is well known that hearts of adult zebra fish, amphibians, or fetal mice within 7 days of birth are capable of complete regeneration after myocardial damages (Poss et al, 2002; Kikuchi et al, 2010; Porrello et al, 2011)
To mimic the oral intake process of Gu Ben Pei Yuan San (GBPYS) by human patients as in mice, the seven components of GBPYS (Panax Ginseng, human placenta, G. gecko Linnaeus tails, velvet antler, Trogopterus dung, amber, and P. notoginseng) were all completely powdered and mixed well with the regular mouse feedstuff, with GBPYS taking up 5% or 10% in total weight of the final food (Figure 1A)
We report an interesting phenomenon where oral intake of GBPYS induces repair of the adult mammalian heart after myocardial damages

Summary

Introduction

It is well known that hearts of adult zebra fish, amphibians, or fetal mice within 7 days of birth are capable of complete regeneration after myocardial damages (Poss et al, 2002; Kikuchi et al, 2010; Porrello et al, 2011). It has been reported that, under hypoxia conditions or by manipulating the Hippo–Yap. Repair of Adult Heart by Intake of GBPYS signaling pathway, heart regeneration in adult mice was induced, and cardiac function after myocardial infarction (MI) was improved (Leach et al, 2017; Nakada et al, 2017). Another study reported that agrin, a component of the neonatal heart extracellular matrix, is required for the full regenerative capacity of neonatal mouse hearts and induced cardiac regeneration in adult mice after MI (Bassat et al, 2017). These latest studies suggest that the poor regenerative capacity of the adult mammalian heart can be enhanced by appropriate exogenous inducers

Methods

Results

Conclusion