Diterpenoids Derived from <i>Strophioblachia Fimbricalyx</i> Regulate Cardiac Hypertrophy by Blocking Autophagic Flux

Jing YUAN; Xin MA; Hongye ZHANG; Changbo ZHENG

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Jing YUAN, Xin MA, Hongye ZHANG, Changbo ZHENG. Diterpenoids Derived from Strophioblachia Fimbricalyx Regulate Cardiac Hypertrophy by Blocking Autophagic Flux[J]. Journal of Kunming Medical University.

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Jing YUAN, Xin MA, Hongye ZHANG, Changbo ZHENG. Diterpenoids Derived from Strophioblachia Fimbricalyx Regulate Cardiac Hypertrophy by Blocking Autophagic Flux[J]. Journal of Kunming Medical University.

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Diterpenoids Derived from Strophioblachia Fimbricalyx Regulate Cardiac Hypertrophy by Blocking Autophagic Flux

1.
Office of Clinical Pharmacy Management，The Third People’s Hospital of Dali Bai Autonomous Prefecture，Dali Yunnan 672105
2.
School of Pharmacy，Kunming Medical University & Yunnan Key Laboratory of Pharmacology of Natural Medicines，Kunming Yunnan 650500，China

Received Date: 2026-06-26

Abstract

Abstract

Objective To screen the diterpenoid monomer C080914 with anti-myocardial-hypertrophy activity from Strophioblachia fimbricalyx, and to investigate its anti-hypertrophic effect against myocardial hypertrophy as well as the underlying molecular mechanism. Methods Primary cardiomyocytes were isolated from neonatal SD rats. In-vitro myocardial hypertrophy models were induced with phenylephrine （PE, n = 6-10）, angiotensin Ⅱ （AngⅡ, n = 6）, and isoproterenol （ISO, n = 6）, respectively. CCK-8 assay was used to evaluate the cytotoxicity of the compound. Western blot was performed to detect proteins associated with myocardial hypertrophy and autophagy. F-actin immunofluorescence staining was applied to observe the hypertrophic phenotype of cardiomyocytes （n = 10）. mRFP-GFP-LC3 dual-labeled adenovirus was utilized to trace autophagic flux （n = 5）. Network pharmacology combined with molecular docking was adopted to predict and verify candidate targets. Functional intervention experiments were carried out using the autophagy inhibitor 3-MA and autophagy agonist rapamycin （n = 6）. One-way analysis of variance （ANOVA） was used for comparisons among multiple groups, followed by Tukey’ s post-hoc test for pairwise comparisons. P < 0.05 was considered statistically significant. Results C080914 exhibited low cytotoxicity with CC₅₀>50 μM; it significantly suppressed the up-regulation of ANP and MYH7 protein expressions induced by PE, AngⅡ and ISO （P < 0.05 or P < 0.001） and decreased cardiomyocyte surface area （P < 0.001）. C080914 up-regulated LC3B and P62 but down-regulated ATG9A protein expression, leading to autophagic flux blockage. Molecular docking demonstrated strong binding affinity between C080914 and ATG9A , with a Vina score of −7.660 kcal/mol. 3-MA partially reversed the anti-hypertrophic effect of C080914 （P < 0.01）. Rapamycin also produced anti-hypertrophic effects, yet distinct differences existed in their autophagy-modulating modes. Conclusion The diterpenoid C080914 from Strophioblachia fimbricalyx inhibits pathological hypertrophy of primary cardiomyocytes in vitro, This effect is accompanied by ATG9A down-regulation and autophagic flux blockage. C080914 may be used as a candidate lead molecule against myocardial hypertrophy, with ATG9A as a potential therapeutic target.
- Strophioblachia fimbricalyx,
- Diterpenoids,
- Myocardial hypertrophy,
- Autophagy,
- ATG9A,
- Natural medicines

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References(22)

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