Forsythoside E

Forsythoside E (FE, CAS No. 93675-88-8) is a phenolic acid glycoside compound isolated from Forsythia suspensa. Its core therapeutic target is the K311 site of pyruvate kinase M2 (PKM2), and it can also bind to bovine serum albumin (BSA) at a 1:1 stoichiometric ratio (binding constant K = 6.92×10³ M⁻¹), with the complex stabilized mainly through hydrophobic interactions and hydrogen bonds. Its binding affinity (KD) with PKM2 is 277 nM (validated by SPR experiment), and there are no clear IC₅₀ data. The effective in vitro concentration ranges from 12.5 to 50 μM (in RAW264.7 macrophages), and the in vivo therapeutic dose is 20~80 mg/kg/d administered via intraperitoneal injection in mice (divided into low and high doses). Its biological activities are mainly reflected in promoting the formation of PKM2 tetramers, inhibiting macrophage glycolysis, restoring mitochondrial function, while blocking the interaction between PKM2 and STAT3, suppressing STAT3 phosphorylation and downstream NLRP3 transcriptional activation. Furthermore, it drives the polarization of macrophages toward the M2 anti-inflammatory phenotype, effectively alleviating sepsis-induced liver injury. It distributes in serum and liver as the parent compound in vivo without significant multi-organ toxicity. In addition, it can alter the conformation of BSA but does not induce its aggregation.

References:

[1] Wang FN, Ma ZQ, Liu Y, Guo YZ, Gu ZW. New phenylethanoid glycosides from the fruits of forsythia suspense (thunb.) vahl. Molecules. 2009 Mar 25;14(3):1324-31. doi: 10.3390/molecules14031324. PMID: 19325526; PMCID: PMC6253944.

[2] Li Y, Guo Q, Yan Y, Chen T, Du C, Du H. Different effects of Forsythia suspensa metabolites on bovine serum albumin (BSA). Spectrochim Acta A Mol Biomol Spectrosc. 2019 May 5;214:309-319. doi: 10.1016/j.saa.2019.02.076. Epub 2019 Feb 18. PMID: 30798212.

[3] Wu B, Yu X, Li Y, An L, Zhang R, Zhang R, Zhang F, Liu Z, Wang C. Forsythoside E Alleviates Liver Injury by Targeting PKM2 Tetramerization to Promote Macrophage M2 Polarization. Adv Sci (Weinh). 2025 Nov 14:e14514. doi: 10.1002/advs.202514514. Epub ahead of print. PMID: 41236855.