Elsevier

Journal of Functional Foods

Volume 36, September 2017, Pages 362-374
Journal of Functional Foods

The aerial parts of Salvia miltiorrhiza Bge. strengthen intestinal barrier and modulate gut microbiota imbalance in streptozocin-induced diabetic mice

https://doi.org/10.1016/j.jff.2017.06.010Get rights and content

Highlights

  • DJ showed an effect on strengthening the intestinal barrier in diabetic mice.

  • DJ could modulate the diversity and balance of gut microbiota in diabetic mice.

  • Our manuscript is the first attempt to investigate DJ as a novel food on DM mice.

  • Our manuscript might provide the basis for DJ on curing intestinal symptoms.

Abstract

Salvia miltiorrhiza Bge., a Traditional Chinese medicine for promoting blood circulation and removing blood stasis, has been used as a health-care food recently. The aerial parts of S. miltiorrhiza Bge. (DJ) are rich in phenolic acids similar to the rhizome. However, the functional and health-care effects of DJ are not clear. We aimed to investigate the impact of DJ on the intestinal barrier and gut microbiota dysfunction in diabetic mice. DJ could reverse the decreased VIP level and the increased AGEs level in diabetic mice. Importantly, DJ strengthened the intestinal barrier of diabetic mice by up-regulating the tight junction proteins expressions (ZO-1, Occludin and Claudin-5) in ileum and colon but not in duodenum. DJ could modulate the diabetes-induced gut microbiota imbalance. Additionally, DJ was proved to have no enterotoxicity on normal mice, which suggested that DJ might serve as a novel functional food for preventing diabetes-induced intestinal symptoms.

Introduction

Salvia species were used as food and celebrated traditional Chinese materia medica all around the world for its antimicrobial, toxicity, antioxidant, and enzyme inhibitory activity (Bahadori et al., 2017). The rhizome of S. miltiorrhiza Bge. has recently been listed as a health-care food which can soothe the nerves. Traditionally, it was widely used for cardiovascular diseases, diabetes, and its complications around the world (Lei and Chiou, 1986, Ren et al., 2016, Xie and Du, 2011). Total salvianolic acids, the abundant bioactive components of S. miltiorrhiza, has received a considerable attention in studies on DM by lowing the blood glucose, triglyceride levels, and increasing insulin sensitivity (Huang et al., 2012). As our study clearly demonstrated that the content of total salvianolic acids in the aerial parts is about the same as that in roots. The aerial parts of S. miltiorrhiza Bge. (DJ) have been developed as a “Danshen Tea” (Sichuan Tongxing natural plant Pharmaceutical Co. Ltd., Sichuan, China) for treatment and prevention of coronary artery disease and dilation of blood vessels, often used for daily health care about regulating blood lipids and hypoxia tolerance. Blood-activating and stasis-dissolving drugs could ameliorate intestinal epithelial barrier damage induced by high glucose through regulating syndecan-1 and heparanase expression (Qiang et al., 2014, Raoufi et al., 2015). Moreover, salvianolic acid B and rosmarinic acid, the two main phenolic acids of DJ, could attenuate vascular dysfunction of aorta induced by diabetes and modulate intestinal SGLT1 levels by working on blood glucose (Qing et al., 2015). According to the literature, salvianolic acid B possesses a certain protective effect on blood glycemic, insulin resistance and glycogen synthesis in diabetes (Mackie, Rigby, Harvey, & Bajka, 2016).

Diabetes mellitus (DM) is a chronic and progressive disease that without medical curable method (Qing et al., 2015, Sanyal, 2013). It requires lifelong medical treatment and has with a rapidly rising incidence worldwide. Besides, cardiovascular diseases, cancers, and infectious diseases, and gastrointestinal complications also frequently come along with the diabetes (de Ferranti et al., 2014, Qu and Jiang, 2014, Sharma et al., 2014). Gastrointestinal complications, known as gastroparesis and diabetic enteropathy (DE), significantly reduce the quality of individuals with DM. Indeed, intestinal symptoms have up to 80% of individuals with Type 1 diabetes (T1D) (Fiorina et al., 2001). Previous studies on DE mainly concentrated on the dysfunction of gastrointestinal motility especially the changes in intestinal smooth muscle cells and the enteric nervous system. It has been demonstrated that colon morphological and biomechanical remodeling could be induced in experimental diabetes (Zhao, Nakaguchi, & Gregersen, 2009). Simultaneously, in diabetic rodents, intestinal mucosa morphology was deranged significantly, suggesting that intestinal homeostasis may be altered in T1D (Domènech et al., 2011). In recent years, the associations between common chronic human disorders and gut microbiome composition dysfunction have been reported (Aguirre & Venema, 2015). Accumulating studies have indicated that an abnormal gut microbiota is responsible for human obesity and DM by influencing energy extraction, inflammation, and neuroendocrine secretions (Musso et al., 2011, Qin et al., 2012).

However, the functional and health-care effects of the aerial parts of S. miltiorrhiza and their potential use as functional food resources have not been explored clearly. The current study was conducted to investigate the protective effect of DJ on DE mice, especially emphasizing the impact on ameliorating the intestinal epithelial barrier and gut microbiota dysfunction induced by diabetes.

Section snippets

Herbal extraction and component analysis

The aerial parts of S. miltiorrhiza (DJ) were collected from the medicine court of Nanjing University of Chinese Medicine. All DJ were crushed into powder after having been dried until the water content was 9.01%. For extraction of DJ, 1 kg chopped herbs were weighed and then extracted with 10 L 60% ethanol for 2 h each time. A reflux extraction device was used to extract twice. LABCONCO Freezone1 lyophilizer (Kansas City, MO) was used to lyophilize the extraction. The dry powder was then stored

Component analysis of DJ

Eleven components were identified in DJ, containing danshensu, protocatechualdehyden, caffeic acid, rutin, isoquercitrin, astragalin, rosmarinic acid, lithospermic acid, salvianolic acid B, salvianolic acid A, and salvianolic acid C (Fig. 1). The content of total salvianolic acids was probably 5.28% while that of flavonoids was 0.37%.

DJ improves the general histological changes of intestine in STZ-induced diabetic mice

The layer and mucosa thickness in the diabetic duodenum did not differ from the normal group (Fig. 2A). Whereas, the intestinal mucosa was altered in the ileum and

Discussion

Salvia miltiorrhiza Bge. has been widely used to cure many diseases for a long time. It is a celebrated traditional Chinese herbal medicine, having been recorded in many classics like Sheng Nong's herbal classic, Compendium of Materia Medica, etc. And now it is also used as a kind of health-care food (Chen, Shu, Chuang, & Wang, 2016). The wild Salvia sources in China have almost been exhausted with the increasing demands of rhizomes of Salvia miltiorrhiza. It is notable that the contents of

Conclusion

In conclusion, the present study is the first attempt to investigate the protective effects of the aerial parts of S. miltiorrhiza, a novel and valuable food or medical supplement, on the intestinal symptoms of DM mice. We obtained evidence showing an obvious effect of DJ on strengthening the intestinal barrier and modulating gut microbiota in streptozotocin-induced diabetic mice. In addition, DJ had no enterotoxicity on normal mice. Thus, it is reasonable to take the aerial parts of S.

Conflict of interest

The authors have declared that there is no conflict of interest.

Author contribution

Jun-fei Gu, analysis and interpretation of data, conception and design; Shu-lan Su, acquisition of data and writing of the manuscript; Jian-Ming Guo, acquisition of data, analysis and interpretation of data; Yue Zhu, experimental design; Jin-Ao Duan, conception and design, study supervision, revision of the manuscript.

Acknowledgements

The authors gratefully acknowledge the financial support of the Key Project from National Natural Science Foundation of China (81673533) and the Key Project of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-2-5).

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