Despite abietane diterpenoids exhibit various biological activities, their anti-fibrotic activity has rarely been investigated. In the study, 19 diterpenoids (twelve abietanes and seven other types) were isolated from
E. helioscopia
, comprising five undescribed
ent
-abietane type diterpenoids (
1a
,
1b
, and
2−4
). Among them, (+)-euphonane A (
1a
) and (−)-euphonane A (
1b
) represent previously unreported
ent
-abietane enantiomers. The structures of unreported diterpenes were mainly assigned through comprehensive nuclear magnetic resonance (NMR) data analysis, in combination with computational techniques involving NMR and electronic circular dichroism (ECD) calculations. In addition, single crystal diffraction analysis precisely defined the absolute stereochemistry of euphonane C (
3
). The effect of these 19 diterpenoids to inhibit fibronectin (FN) expression was evaluated in transforming growth factor-β (TGF-β1)-stimulated human hepatic stellate cell line (LX-2 cells), and three compounds (
1a
,
1b
, and
3
) showed significant inhibitory activity at micromolar level, being stronger than the positive control silymarin. A dose-dependent suppression of fibrotic marker expression, particularly that of FN, collagen I, and α-smooth muscle actin (α-SMA), was observed upon the treatment with compounds
1a
and
1b
. Mechanistic investigations, including transcriptomics analysis and western blotting, revealed that the anti-fibrotic action of
1b
in hepatic cells is probably mediated through the TGF-β/Smad signaling cascade. The above results both extend our knowledge regarding the bioactivities of diterpenes isolated from
E. helioscopia
, and position abietane-type diterpenoids as prospective molecular structures for the innovation of new therapeutics against liver fibrosis.
Li Jiang, Qian Wang, Jun-Yan Ran et al.· Arabian Journal of Chemistry· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Persicaria capitata, a vital Miao medicine, is traditionally employed to "clear heat and promote diuresis" and "detoxify". In traditional theory, alcoholic liver injury (ALI) is categorized as a "Damp-Heat accumulation" syndrome, often manifesting as damp-heat jaundice. The traditional application of P. capitata in treating jaundice and inflammatory conditions provides a rationale for its hepatoprotective use.
AIM OF THE STUDY
To provide a scientific basis for the traditional use of P. capitata by systematically investigating the protective effects of its water extract (WP) on ALI and exploring the associated molecular mechanisms.
MATERIALS AND METHODS
An ALI mouse model was established by alcohol feeding for 28 days. Mice were orally administered with WP (175, 350, 700 mg/kg/day). Liver and intestinal functions were assessed by biochemical assays, histology, transcriptomics, 16S rRNA sequencing, and Western blotting.
RESULTS
WP significantly reduced serum ALT, AST, and hepatic lipid levels while alleviating oxidative stress. Mechanistically, WP regulated the gut-liver axis by maintaining intestinal barrier integrity (increased ZO-1 and Occludin expression) and enriching beneficial Akkermansia bacteria. This restoration of the intestinal barrier subsequently suppressed hepatic inflammatory responses and hepatocyte apoptosis by blocking the LPS-TLR4/NF-κB signaling cascade while simultaneously promoting the PI3K-Akt survival pathway.
CONCLUSIONS
By modulating the gut-liver axis-specifically through the restoration of intestinal barrier integrity and the regulation of TLR4/NF-κB and PI3K-Akt signaling-P. capitata effectively mitigates ALI. This study provides a mechanistic rationale for its traditional use and supports its development as a promising intervention for alcoholic liver-related pathologies.
Lu Hu, Jin Li, Ya-Xin Yang et al.· Journal of Ethnopharmacology· 0 citations
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