Piceatannol-3ʹ-O-β-d-glucopyranoside alleviates nephropathy via regulation of High mobility group B-1 (HMGB1)/Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) signalling pathway

Abstract Objectives Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3ʹ-O-β-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. Methods In vitro, the podocyte protection of PG was assesse...

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Published in:Journal of pharmacy and pharmacology 2023-04, Vol.75 (5), p.693-702
Main Authors: Du, Shi-Hao, Yang, Ming-Yan, Gan, Hai-Lin, Song, Ze-Yu, Wang, Meng-Ying, Li, Zhen-Yuan, Liu, Ke, Qi, Dong, Fan, Hua-Ying
Format: Article
Language:English
Subjects:
Animals
Cytokines
Doxorubicin
HMGB1 Protein
NF-kappa B - metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
Toll-Like Receptor 4 - metabolism
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Summary:Abstract Objectives Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3ʹ-O-β-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. Methods In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. Key findings The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKβ and yet up-regulated IκBα expression by western blot analysis. Conclusions Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS. Graphical Abstract Graphical Abstract
ISSN:0022-3573
2042-7158
DOI:10.1093/jpp/rgad021