Abstract

The traditional Chinese medicine Astragalus polysaccharide (APS) has been widely used to improve glucose homeostasis and immunoregulator properties. In recent years, it has also been shown to extend the lifespan of Caenorhabditis elegans; however, the underlying molecular mechanisms are not fully understood. Here, our study shows that APS could significantly extend adult stage, mean, and maximum lifespan of the silkworm, Bombyx mori and increase body weight without affecting food intake and fecundity. Meanwhile, the activities of glutathione S-transferase and superoxide dismutase are significantly enhanced, and the reaction oxygen species content is reduced concomitantly. Moreover, the activity of lysozyme is increased dramatically. In addition, APS rescues the shortened lifespan by Bacillus thuringiensis infection in silkworm. Furthermore, the transcription of the crucial genes involved in endoplasmic reticulum stress is upregulated upon the endoplasmic reticulum stress stimulation. APS also significantly ameliorates endoplasmic reticulum stress in silkworm cell line and in vivo. Together, the results of this study indicate that APS can prolong the silkworm lifespan by mitigating endoplasmic reticulum stress. This study improves our understanding of the molecular mechanism of APS-induced lifespan extension and highlights the importance of the silkworm as an experimental animal for evaluating the effects and revealing the mechanisms in lifespan extension of traditional Chinese medicine.

Highlights

  • The traditional Chinese medicine Astragalus polysaccharide (APS) has been widely used to improve glucose homeostasis and immunoregulator properties

  • The results showed that 2% APS significantly shortened the mean lifespan of the female silkworm with no obvious effect on the male silkworm

  • The results showed that the daily food intake of 5th instar larvae with 0.1% APS treatment was similar to that in the control female and male silkworms (Fig. 3A, B), indicating that daily food intake did not play a role in the observed lifespan extension

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Summary

Introduction

The traditional Chinese medicine Astragalus polysaccharide (APS) has been widely used to improve glucose homeostasis and immunoregulator properties. APS is the polysaccharide component and major active component of Astragalus and a commonly used nutraceutical with lifespan-extending capabilities [1] It improves wholebody glucose homeostasis by activating AMPK [13] and attenuating endoplasmic reticulum stress (ERS) and affecting insulin/insulin-like growth factor-1 signaling (IIS) pathways, which are associated with longevity [14]. The ERS response consists of three signaling pathways [17], which are mediated upstream by ATF6, protein kinase R-like ER kinase (PERK), and inositol-requiring enzyme 1 (IRE1), three ER-resident transmembrane proteins. The ERSsensing proteins IRE-1 and X-box binding protein 1 are involved in longevity of insulin/insulin growth factor-1 pathway mutants [25] These studies revealed that the UPR signaling pathway is directly related to lifespan. As a typical representative of Lepidopteran insects, the silkworm Bombyx mori has numerous advantages and convenience as an experimental animal model for evaluating the effects of TCMs [26,27,28,29,30]

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