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Updated: Aug 29, 2026
Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
Cyclopeptide heterophyllin from Pseudostellaria heterophylla alleviates neuroinflammation: a study integrating
Bo Li1,2, Xueying Shi1,2, Erhua Chen1,2
1Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022 China.
Abstract:
This study evaluated the ameliorative effects of Heterophyllin J, a cyclic peptide derived from Pseudostellaria heterophylla, on lipopolysaccharide (LPS)-induced neuroinflammation in mice. Biochemical, and molecular analyses revealed that Heterophyllin J dose-dependently reduced hippocampal pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, TNF-α), suppressed oxidative stress (restoring glutathione and lowering malondialdehyde), and alleviated iron accumulation. Western blotting demonstrated Heterophyllin J downregulated NLRP3, Caspase1, and TLR4/NF-κB pathway proteins (COX-2, iNOS, Myd88) while enhancing antioxidant markers (Nrf2, HO-1, NQO1) via Keap1/Nrf2 activation. Heterophyllin J also modulated JAK/STAT signaling, restoring JAK1/2 phosphorylation and reducing STAT1/3 activation, thereby attenuating apoptosis (lower Bax, cleaved caspase-3; higher Bcl-2) and ferroptosis (upregulating GPX4, PCBP1, SLC40A1). These findings highlight Heterophyllin J's multimodal mechanism: regulating TLR4-driven inflammation, rebalancing iron metabolism, and activating antioxidant pathways to counteract neuroinflammation. The results position Heterophyllin J as a promising therapeutic candidate for neurodegenerative diseases linked to neuroinflammatory and oxidative stress pathways.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10068-026-02223-8.
