Hypericum perforatum L. Regulates Glutathione Redox Stress and Normalizes Ggt1/Anpep Signaling to Alleviate OVX-Induced Kidney Dysfunction

Abstract

Menopause and associated renal complications are linked to systemic redox stress, and the causal factors remain unclear. As the role of Hypericum perforatum L. (HPL) in menopause-induced kidney disease therapy is still ambiguous, we aim to explore the effects of HPL on systemic redox stress under ovariectomy (OVX)-induced kidney dysfunction conditions. Here, using combined proteomic and metabolomic approaches, we constructed a multi-scaled “HPL-disease-gene-metabolite” network to generate a therapeutic “big picture” that indicated an important link between glutathione redox stress and kidney impairment. HPL exhibited the potential to maintain cellular redox homeostasis by inhibiting gamma-glutamyltransferase 1 (Ggt1) overexpression, along with promoting the efflux of accumulated toxic amino acids and their metabolites. Moreover, HPL restored alanyl-aminopeptidase (Anpep) expression and metabolite shifts, promoting antioxidative metabolite processing, and recovery. These findings provide a comprehensive description of OVX-induced glutathione redox stress at multiple levels and support HPL therapy as an effective modulator in renal tissues to locally influence the glutathione metabolism pathway and subsequent redox homeostasis.

Anthocyanin improves kidney function in diabetic kidney disease by regulating amino acid metabolism

“…As a result, Fmo5 and Ggt1 immunostaining was present in normal renal tubular (CT group) in a perinuclear pattern and was localized mainly to tubular epithelial cells (Additional file 1: Fig. S4A and C), which is consistent with previous studies that Fmo5 are primarily localized to the distal tubules of the cortex, proximal tubules and the collecting ducts of the medulla [20], and Ggt1 is expressed at high levels in renal proximal tubules [21]. Then, we found that immunostaining for Fmo5 and Ggt1 confirmed the proteomics data (Fig.…”

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

“…These endotoxins can activate TLR4-mediated reactions, including initiation of the NF-κB signaling pathway ( Tang et al, 2021 ). NF-κB is a major transcription factor involved in inflammatory diseases, which can respond to heat-stress stimuli and activate the NF-κB signaling pathway in broilers ( Xu et al, 2023 ), thereby inducing tissue damage ( Liu W. C. et al, 2021 ; Liu Y. R. et al, 2021 ). NF-κB acts downstream of TLR4 and other immune receptors, increasing the excessive production of IL-6, IL-1β, and TNF-α leads to the occurrence of inflammatory responses in response to heat stress ( Vallabhapurapu and Karin, 2009 ).…”