Possible mechanisms by which silkworm faeces extract ameliorates adenine-induced renal anaemia in rats. (10th February 2021)

• Record Type: Journal Article
• Authors: Mei, Hao; Wu, Niuniu; Huang, Xiao; Cui, Zheng; Xu, Jingya; Yang, Xiawen; Zeng, Fang; Wang, Kaiping
• Is Part Of: Journal of ethnopharmacology. Volume 266(2020)
• Publication Date: 2021-02-10
• Subjects: Silkworm faeces extract -- Chronic kidney disease -- Renal anaemia -- Erythropoietin -- HIF-2α -- Hepcidin; SFE Silkworm faeces Extract -- CKD chronic kidney disease -- EPO erythropoietin -- rhEPO recombinant human erythropoietin -- HIF-2α hypoxia-inducible factor 2α -- PHD2 prolyl hydroxylase 2 -- ESA erythropoiesis-stimulating agent -- TIBC total iron binding capacity -- TS serum transferrin saturation; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113448
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Silkworm faeces are the dry faeces of the insect Bombyx mori ( Linnaeus) and have historically been used in traditional Chinese medicine to treat blood deficiency and rheumatic pain. Silkworm faeces extract (SFE) is derived from silkworm faeces. Aim of the study: Clinical observations of patients in the Department of Nephrology have shown that SFE effectively improves renal anaemia. However, the molecular mechanism remains unclear. This article mainly explores the regulatory effects of SFE on erythropoietin (EPO) and hepcidin to identify the molecular mechanism of SFE. Materials and methods: A rat model of renal anaemia was established by feeding rats food containing 0.75% adenine. SFE was orally administered to the rats, while recombinant human erythropoietin (rhEPO) was used as a positive control drug. Haematological parameters and inflammation levels were compared between rats from each group, and pathological kidney sections from each rat were observed. The serum EPO and hepcidin levels were detected using enzyme-linked immunosorbent assay (ELISA) kits, while Western blot analyses were performed to detect the levels of proteins involved in the EPO-related hypoxia-inducible factor 2α (HIF-2α)/prolyl hydroxylase 2 (PHD2) signalling pathway and hepcidin-related BMP6/SMAD4 and interleukin-6 (IL-6)/STAT3 signalling pathways. Results: SFE significantly ameliorated haematological parameters, renal function, and inflammation levels in the rats. A mechanistic study showed that SFE promoted EPO expression by upregulating HIF-2α expression and inhibiting the expression of NF-κB and GATA2 both in vivo and in vitro . In particular, SFE inhibited PHD2 expression, resulting in a decrease in the enzymatic reaction of HIF-2α to increase EPO expression. Furthermore, SFE inhibited hepcidin expression by blocking the BMP6/SMAD4 and IL-6/STAT3 pathways. Conclusions: SFE regulated iron metabolism by inhibiting hepcidin and simultaneously promoted EPO synthesis to improve renal anaemia in rats. Graphical abstract: Image 1 Highlights: SFE effectively improved renal anaemia by promoting EPO synthesis and regulating iron homeostasis, providing a new experimental basis for the clinical use of SFE in the treatment of renal anaemia. SFE not only inhibited the expression of NF-κB and GATA2 and reversed the inhibition of EPO transcription, but also inhibited PHD2 expression and attenuated HIF-2α degradation, which together promoted EPO transcription and erythrocyte synthesis, confirming that SFE improved renal anaemia by promoting the increase in EPO expression. SFE reduced hepcidin expression by blocking the BMP6/SMAD4, IL-6/STAT3 and TFR2 pathways, which increased Ferroportin1 expression and promoted iron transfer to plasma from the liver and spleen, thereby regulating iron homeostasis and ultimately ameliorating renal anaemia.