AUTHOR=Liu Yan-Ru , Yang Ning-Juan , Zhao Meng-Li , Tang Zhi-Shu , Duan Jin-Ao , Zhou Rui , Chen Lin , Sun Jing , Song Zhong-Xing , Hu Jin-Hang , Shi Xin-Bo 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.628651

DOI=10.3389/fphar.2021.628651

ISSN=1663-9812

ABSTRACT=<p>Menopause and associated renal complications are linked to systemic redox stress, and the causal factors remain unclear. As the role of <italic>Hypericum perforatum</italic> 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.</p>