ArticleChinese medicine2026
Homo- and hetero-dimeric sesquiterpenoids with unprecedented skeletons and their co-occurring monomers from Vernonia solanifolia with anti-liver steatotic potential.
Article in Chinese medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSesquiterpenoids show potential as therapeutics against metabolic dysfunction-associated steatotic liver disease (MASLD). Vernonia solanifolia Benth. has been traditionally used to treat abdominal pain and enteritis. However, the anti-steatotic effect of V. solanifolia and its chemical principles have not been illustrated.
methodsThe structures of new compounds were determined through extensive spectroscopic analysis including 1D/2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry, ultraviolet and infrared. Especially, the structure of compound 6 was further verified by single crystal X-ray diffraction, and the relative and absolute configurations of compounds 1-5 and 7-9 were resolved with the help from density-functional theory-NMR and time-dependent density-functional theory-electronic circular dichroism calculation. The lipid-lowering activity was evaluated on palmitic acid/oleic acid (P/O)-treated AML12 hepatocytes. The biological evaluation was performed using Nile Red staining, flow cytometry, commercial kits, and Western blotting.
resultsNine new sesquiterpenoid dimers and their co-occurring monomers (1-9) were identified from the leaves of V. solanifolia. A unique 10/5/6/5/7 pentacyclic ring system is exemplified in compounds 1 and 2. These compounds were constructed from a germacranolide and a 4,5-seco-guaianolide monomer through an unprecedented spiro cyclohexene ring. The first examples of germacrane-guaiane and guaiane-xanthane heterogeneous dimers are shown in compounds 3 and 4, respectively, which also possess a spiro cyclohexene ring linkage. A guaianolide dimer featuring a rare C-13/C-13' linkage is exhibited in compound 5. The plausible biosynthetic pathways for compounds 1 and 5 were proposed. The isolates were tested for their lipid-lowering effect on P/O-treated AML12 hepatocytes, and the results showed that compound 3 significantly reduced lipid content in hepatocytes by triggering the AMP-activated protein kinase/acetyl-CoA carboxylase/peroxisome proliferator-activated receptor γ coactivator-1α signaling pathway.
conclusionFive homo- and hetero-dimeric sesquiterpenoids with unprecedented skeletons were characterized from V. solanifolia, together with four new co-occurring monomers. It's the first time to report the lipid-lowering activity of sesquiterpenoids from this genus, which might be developed as lead compounds against MASLD.
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