Palmatine attenuates isoproterenol-induced pathological hypertrophy via selectively inhibiting HDAC2 in rats

Abstract

This study aimed to exploit the potential therapeutic value of palmatine in treatment of cardiac hypertrophy and the underlying molecular mechanism. Rat hypertrophy model was established by intraperitoneal isoproterenol (ISO) injection. The hypertrophy was evaluated with cardiac hypertrophic parameters, hemodynamic parameters, lipid profile, and non-specific cardiac markers. The animals were intraperitoneally administrated with either palmatine or vehicle. The relative expressions of ANP, BNP, HDAC2, HDAC5, KLF4, and INPP5F transcripts were determined by real-time polymerase chain reaction (PCR). The relative protein levels of HDAC2, HDAC5, KLF4, and INPP5F were analyzed by immunoblotting. Palmatine treatment significantly attenuated ISO-induced hypertrophy in rats and elicited remarkable repressions in ANP, BNP, and HDAC2 transcriptions but not HDAC5. The downstream effector genes KLF4 and INPP5F were greatly restored in a dose-dependent manner in response to palmatine treatment. Our data demonstrated that palmatine possessed promising therapeutic potential against hypertrophy, which was mediated by modulation of HDAC2-KLF4/INPP5F pathway.

Histone Deacetylase Inhibition has Cardiac and Vascular Protective Effects in Rats With Pressure Overload Cardiac Hypertrophy

“…VPA (Iyer et al 2010, Kee et al 2013 and CG200475 (Lee et al 2016) suppress cardiac hypertrophy and fibrosis in DOCA-salt hypertensive rats. Palmatine (Yuan et al 2017) and tubacin (Tao et al 2016) attenuate isoprenaline-induced cardiac hypertrophic rats.…”

“…The roles of the HDAC inhibitors in cardiac hypertrophy are being widely studied. For example, the expression of HDAC2 is increased by palmatine in isoprenaline-induced hypertrophic rat model (Yuan et al 2017). In DOCA-salt induced hypertrophic heart rat model, the enzyme activity of HDAC6 and HDAC8 was up-regulated, and their activities were inhibited by VPA (Kee et al 2013).…”

Palmatine: A review of pharmacological properties and pharmacokinetics

“…PLT is also a promising therapeutic agent in the treatment of heart hypertrophy. In rats with hypertrophy induced by isoproterenol, administration of PLT at doses of 25–50 mg/kg showed significant impairment of symptoms through modulation of the HDAC2‐KLF4/INPP5F pathway and repression of ANP and BNP transcription (Yuan et al, ).…”

“…The plants containing PLT have been used in traditional Chinese, Korean, and Indian medicines for centuries as a remedy against various ailments such as jaundice, liver‐related diseases, hypertension, inflammation, and dysentery (Kuete, ). In the Chinese pharmacopoeia, it is registered as an anti‐inflammatory drug and has been used clinically in the treatment of gynecological inflammation, respiratory tract infections, bacterial dysentery caused by gastrointestinal infections, and surgical infections associated with the urinary tract (Yuan, Peng, Liu, & Xu, ; Zhang et al, ).…”

Rhodium-Catalyzed Ortho-Vinylation of 2-Arylpyridines and Its Application in the Total Synthesis of Palmatine

“…Palmatine, an isoquinoline alkaloid isolated from Fibraurea recisa Pierre (Chinese name: Huangteng), has a wide range of pharmacological and biological activities, such as antibacterial, antifungal, and antiviral effects. 10,11 Clinically, palmatine has been used for the treatment of surgical infections, respira-tory and urinary tract infections, conjunctivitis, and gynecological inflammation. 12 Due to the wide range of applications and exact efficacy in clinic, the demand for palmatine in the pharmaceutical market is growing.…”