Berberine Mediated Positive Inotropic Effects on Rat Hearts via a Ca2+-Dependent Mechanism

Abstract

Previous studies showed that berberine, an alkaloid from Coptis Chinensis Franch, might exert a positive inotropic effect on the heart. However, the underlying mechanisms were unclear. Here, we reported that berberine at 10-20 µM increased the left ventricular (LV) developed pressure and the maximal rate of the pressure rising, and it increased the maximal rate of the pressure descending at 20 µM in Langendorff-perfused isolated rat hearts. These effects diminished with the concentration of berberine increasing to 50 µM. In the concentration range of 50-300 µM, berberine increased the isometric tension of isolated left ventricular muscle (LVM) strips with or without electrical stimulations, and it (30-300 µM) also increased the intracellular Ca 2+ level in the isolated LV myocytes. The removal of extracellular Ca 2+ hindered the berberine-induced increases in the tension of LVM strips and the intracellular Ca 2+ level of LV myocytes. These suggested that berberine might exert its positive inotropic effects via enhancing Ca 2+ influx. The blockade of L-type Ca 2+ channels (LTCCs) with nifedipine significantly attenuated 300 mM berberine-induced tension increase in LVM strips but not the increase in the intracellular Ca 2+ level. Berberine (300 mM) further increased the LVM tension following the treatment with the LTCC opener FPL-64716 (10 mM), indicating an LTCC-independent effect of berberine. Lowering extracellular Na + attenuated the berberine-induced increases in both the tension of LVM strips and the intracellular Ca 2+ level of LV myocytes. In conclusion, berberine might exert a positive inotropic effect on the isolated rat heart by enhancing the Ca 2+ influx in LV myocytes; these were extracellular Na +-dependent.

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels

“…The activated protein kinase phosphorylates the voltage-sensitive calcium channels, opens them and allows more entry of calcium ions into the myocardium. The accumulated calcium then acts on the myofibrils, induces a sliding action, and produces ‘forceful’ contractions of the myocardium [ 16 , 17 ]. The greater increase in the developed tension when the derivatives of the thiazole were combined with Adr suggests that the combination potentiated the myocardial contraction [ 18 ].…”

Non-coding RNAs: targets for Chinese herbal medicine in treating myocardial fibrosis

“…Berberine is a quaternary ammonium alkaloid contained in the rhizome of Coptis chinensis Franch. and has various cardiovascular protective effects, such as anti-heart failure, anti-arrhythmia, and lowering cholesterol effects ( Pagliaro et al, 2015 ; Zhao et al, 2020 ). It was found that berberine relieves hypertension-induced MF by increasing the expression of miR-29b and decreasing its targets Col1a1 and Col3a1 ( Zheng et al, 2020 ).…”

Integrating Evidence of the Traditional Chinese Medicine Collateral Disease Theory in Prevention and Treatment of Cardiovascular Continuum

“…Regarding these overlapped key nodes of the cardiovascular continuum, there are TCM set prescriptions based on collateral disease that could offer intervention targets at various continuum stages ( Figure 1 ). For example, Jinlida granules (JLDG) for metabolic syndrome, Tongxinluo (TXL) for atherosclerotic plaque and myocardial protection, Shensongyangxin (SSYX) capsules for anti-arrhythmias via metabolic reconstruction, and Qiliqiangxin (QLQX) capsules for cardiac remodeling and heart failure have been recognized under the guidance of translational medicine ( Table 1 ) ( Bai et al, 2013 ; Wang et al, 2014 ; Zaki et al, 2014 ; Luan et al, 2015 ; Wang et al, 2015 ; Zhang et al, 2016 ; Fan et al, 2017 ; Shen et al, 2017 ; Zhao et al, 2017 ; Chen H. et al, 2018 ; Chen Y. et al, 2018 ; Gao et al, 2018 ; Wang et al, 2018 ; Zhang et al, 2018 ; Lyu et al, 2019 ; Tung et al, 2019 ; Zhou et al, 2019 ; Cheng W. et al, 2020 ; Li et al, 2020 ; Yang et al, 2020 ; Zhao et al, 2020 ; Jiang et al, 2021 ; Hao et al, 2022 ). These set prescriptions have been approved for by the Chinese National Medical Products Administration (NMPA), and broadly used in clinical practice in the Chinese community.…”

“…Another study showed that SSYX reduces the occurrence of AF after myocardial infarction by inhibiting atrial fibrosis ( Ma et al, 2018 ). At the same time, SSYX has shown to be a multichannel blocker with measurable modulation effects on various ion channels, such as L-type calcium channel and transient outward potassium (Ito), resulting in an overall prolongation of the action potential ( Yang et al, 2020 ; Zhao et al, 2020 ). SSYX could inhibit IK1 and Ito currents by prolonging the duration of action potentials, reversing calcium overload, and inhibiting the occurrence of ventricular arrhythmias after ischemia ( Zhao et al, 2016 ).…”