Zerumbone prevents pressure overload-induced left ventricular systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis

Sari, Nurmila; Sugiyama, Yuga; Sunagawa, Yoichi; Miyazaki, Yusuke; Funamoto, Masafumi; Shimizu, Satoshi; Shimizu, Kana; Murakami, Akira; Mori, Kiyoshi; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

doi:10.1016/j.phymed.2021.153744

Cited by 8 publications

(11 citation statements)

References 29 publications

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“…Strophioblachin J (10) 2), it could be concluded that compound 10 has one less terminal double bond and one less methyl group and two more methoxy groups as well as one more ester group than compound 7. The location of the two methoxy groups was determined from the HMBC correlations (Figure 4) from δ H 4.01 (OMe-12) to C-12 (δ C 162.5) and from δ H 3.93 (OMe-15) to C-15 (δ C 165.3).…”

Section: Journal Ofmentioning

confidence: 99%

Strophioblachins A–K, Structurally Intriguing Diterpenoids fromStrophioblachia fimbricalyxwith Potential Anticardiac Hypertrophic Inhibitory Activity

et al. 2023

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Three new rearranged diterpenoids, strophioblachins A–C (1–3), eight new diterpenoids, strophioblachins D–K (4–11), and seven previously described diterpenoids (12–18) were purified from the aerial parts of Strophioblachia fimbricalyx. Compounds 1 and 2 contain a rare 6/6/5/6 ring system, while 3 has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1–11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11 and 9. The absolute configurations of compounds 1, 3, and 10 were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10 and 15 dose-dependently lowered the mRNA expression of Nppa and Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10 and 15 lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10 and 15 were only very weakly active in the range.

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Section: Journal Ofmentioning

confidence: 99%

Strophioblachins A–K, Structurally Intriguing Diterpenoids fromStrophioblachia fimbricalyxwith Potential Anticardiac Hypertrophic Inhibitory Activity

et al. 2023

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“…Histological analysis was performed as described previously 23 . Heart tissues were harvested and sliced across the papillary muscles, then xed with 10% formalin and embedded in para n. Five-µm-thick sections were de-para nized and rehydrated.…”

Section: Histological Analysismentioning

confidence: 99%

“…Cardiomyocyte cross-sectional area (CSA) analysis CSA analysis was performed as described previously 23 . Heart sections were stained with Alexa Fluor 488 conjugated-WGA (Thermo Fisher, Tokyo, Japan, Cat #C10607).…”

Section: Histological Analysismentioning

confidence: 99%

“…Transverse aortic constriction (TAC) models TAC surgery was performed as previously described 23 . Brie y, 8-to 10-week-old mice were anesthetized with 2% iso urane, and their limbs were xed.…”

Section: Micementioning

confidence: 99%

“…Preparation of primary cultured cardiac broblasts was performed as previously described with some modi cation 23 . Brie y, hearts from 1-to 3-day-old SD rats were removed, minced, and incubated with collagenase (Worthington Industries, Worthington, OH, USA) / pancreatin (Sigma-Aldrich) in Hank's Balanced Salt Solution (HBSS, Nacalai Tesque) at 37°C.…”

Section: Forward Primermentioning

confidence: 99%

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Fibroblast-specific PRMT5 deficiency suppresses pressure overload-induced cardiac fibrosis and left ventricular dysfunction

Yabe

Murata

Sobukawa

et al. 2022

Preprint

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Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduced pressure overload-induced cardiac fibrosis and improved cardiac dysfunction. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppressed the expression of α-smooth muscle actin (α-SMA) induced by transforming growth factor-β (TGF-β) in cultured cardiac fibroblasts. TGF-β stimulation promoted the recruitment of the PRMT5/Smad3 complex to the promoter site of α-SMA. It also increased PRMT5-mediated H3R2 symmetric dimethylation, and this increase was inhibited by knockdown of Smad3. TGF-β stimulation also increased H3K4 tri-methylation mediated by the WDR5/MLL1 lysine methylase complex, which recognizes H3R2 symmetric dimethylation. Finally, treatment with EPZ015666 significantly improved pressure overload-induced cardiac fibrosis and dysfunction. These findings reveal that PRMT5 regulates TGF-β/Smad3-dependent fibrotic gene transcription through histone methylation crosstalk and plays a critical role in cardiac fibrosis and dysfunction.

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Development and characterization of pH-sensitive zerumbone-encapsulated liposomes for lung fibrosis via inhalation route

Elsayed,

How,

Foo

2025

European Journal of Pharmaceutics and Biopharmaceutics

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Zerumbone prevents pressure overload-induced left ventricular systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis

Cited by 8 publications

References 29 publications

Strophioblachins A–K, Structurally Intriguing Diterpenoids fromStrophioblachia fimbricalyxwith Potential Anticardiac Hypertrophic Inhibitory Activity

Strophioblachins A–K, Structurally Intriguing Diterpenoids fromStrophioblachia fimbricalyxwith Potential Anticardiac Hypertrophic Inhibitory Activity

Fibroblast-specific PRMT5 deficiency suppresses pressure overload-induced cardiac fibrosis and left ventricular dysfunction

Development and characterization of pH-sensitive zerumbone-encapsulated liposomes for lung fibrosis via inhalation route

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