Flos puerariae ameliorates the intestinal inflammation of Drosophila via modulating the Nrf2/Keap1, JAK-STAT and Wnt signaling

Abstract

Gut homeostasis is important for human health, and its disruption can lead to inflammatory bowel disease (IBD). Flos Puerariae is a herb with a wide variety of pharmacological activities including antioxidant, antidiabetic, antialcoholismic and anti-inflammatory properties. However, the role of Flos Puerariae on treating IBD remains obscure. Here, we employed Drosophila melanogaster as a model organism to investigate the protective effect of Flos Puerariae extract (FPE) against sodium dodecyl sulfate (SDS)-induced intestinal injury. Our data showed that FPE had no toxic effect in flies, and significantly extended lifespan in SDS-inflamed flies, reduced stem cell proliferation in the midgut, and maintained intestinal morphological integrity. Furthermore, FPE remarkably recused the altered expression level of genes and proteins in Nrf2/Keap1 signaling, JAK-STAT signaling and Wnt signaling pathways in gut of inflammation flies. Thus, FPE has a protective effect against intestinal injury possibly via increasing the Nrf2/keap1 pathway and suppressing the JAK-STAT and Wnt signaling pathways, which would have tremendous potential for treating IBD.

Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease

“…Survival assays in flies are used to determine the role of potential drugs on lifespan, stress resistance and developmental defects ( Dai et al, 2020 ). Simple feeding assays are used to investigate the therapeutic effect of drug candidates ( Yang et al, 2022 ). In addition, survival assays, development and reproduction assays in flies are used to evaluate the toxicity of drug candidates and determine the optimal drug concentrations.…”

“…The activator of Nrf2, 5-aminosalicylic acid, has been used clinically in the treatment of IBD ( Kang et al, 2017 ; El-Baz et al, 2020 ). Meanwhile, various plant-derived natural compounds have been demonstrated to alleviate IBD by affecting the Keap1-Nrf2-ARE pathway in animal model systems of IBD, such as luteoline ( Li et al, 2016 ), curcumin ( Lin et al, 2019 ) and Flos puerariae extract ( Yang et al, 2022 ) Therefore, the Nrf2 activator is considered as a potential drug for the treatment of IBD.…”

“…The Notch gene is first named in flies in the 1910s ( Stubbs et al, 1990 ). Most essential components of the Notch signaling pathway are conserved between flies and humans ( Yang et al, 2022 ) . Notch pathway participates in regulating the self-renewal and differentiation of ISCs.…”

“…Disruption of intestinal homeostasis is closely related to the occurrence and development of IBD. Many signaling pathways related with IBD such as JAK/STAT, Wnt/Wg, Nrf2/Keap1, TLR4/NF-κB, Notch pathways were identified in flies, and are conserved in humans ( Hu et al, 2021 ; Yang et al, 2022 ). Various natural products have shown that various natural molecules or herbal extractions are widely applied in the prevention and treatment of IBD in various animal models ( Yang et al, 2022 ).…”

“…Many signaling pathways related with IBD such as JAK/STAT, Wnt/Wg, Nrf2/Keap1, TLR4/NF-κB, Notch pathways were identified in flies, and are conserved in humans ( Hu et al, 2021 ; Yang et al, 2022 ). Various natural products have shown that various natural molecules or herbal extractions are widely applied in the prevention and treatment of IBD in various animal models ( Yang et al, 2022 ). Consistently, the similar function of natural products treating intestinal inflammatory diseases are found in flies and mammals ( Pereira et al, 2017 ).…”