Abstract

Mung bean (Vigna Radiata) has been traditionally used in China both as nutritional food and herbal medicine against a number of inflammatory conditions since the 1050s. A nucleosomal protein, HMGB1, has recently been established as a late mediator of lethal systemic inflammation with a relatively wider therapeutic window for pharmacological interventions. Here we explored the HMGB1-inhibiting capacity and therapeutic potential of mung bean coat (MBC) extract in vitro and in vivo. We found that MBC extract dose-dependently attenuated LPS-induced release of HMGB1 and several chemokines in macrophage cultures. Oral administration of MBC extract significantly increased animal survival rates from 29.4% (in saline group, N = 17 mice) to 70% (in experimental MBC extract group, N = 17 mice, P < 0.05). In vitro, MBC extract stimulated HMGB1 protein aggregation and facilitated both the formation of microtubule-associatedprotein-1-light-chain-3-(LC3-)containing cytoplasmic vesicles, and the production of LC3-II in macrophage cultures. Consequently, MBC extract treatment led to reduction of cellular HMGB1 levels in macrophage cultures, which was impaired by coaddition of two autophagy inhibitors (bafilomycin A1 and 3-methyladenine). Conclusion. MBC extract is protective against lethal sepsis possibly by stimulating autophagic HMGB1 degradation.

Highlights

  • Sepsis is an overwhelming systemic inflammatory response to severe infections, and can lead to shock, multiple organ failure, and death if not treated promptly

  • We demonstrated that mung bean coat (MBC) extract remarkably inhibited endotoxin-induced release of HMGB1 and several cytokines/chemokines in macrophage cultures, and rescued mice from lethal sepsis

  • To verify whether mung bean possesses anti-inflammatory properties as historically described in traditional Chinese medicine, we first examined its effects on endotoxininduced HMGB1 release in macrophage cultures

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Summary

Introduction

Sepsis is an overwhelming systemic inflammatory response to severe infections, and can lead to shock, multiple organ failure, and death if not treated promptly. Despite recent advances in therapy, it remains the primary cause of mortality in medical intensive care units. Sepsis afflicts approximately 750,000 Americans each year, and costs the US healthcare system nearly $17 billion annually [1]. Current treatments are predominantly supportive and often ineffective. The only FDA-approved therapy for patients with severe sepsis was activated protein C (APC) [2], which was marginally effective and removed from the market in 2011. The development of effective therapeutic interventions represents significant and yet unmet medical needs in the world

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