Cardiovascular diseases (CVD) are one of the major causes of mortality among individuals. CVD is an umbrella term encompassing disorders of the heart and blood vessels. Coronary heart disease, peripheral arterial disease, rheumatic heart disease, deep vein thrombosis, congenital heart disease and pulmonary embolism are included under the CVD. People with hyperlipidaemia, hyperglycaemia, and hypertension are more prone to developing CVD. Nutraceuticals can be beneficial in the prevention and management of CVD. In this article, we will focus on the role of berberine in the prevention/management of CVD.
Berberine is a plant alkaloid isolated from the species of Berberis. Berberine is reported to have protective effects on cardiac cells. There are reports that berberine can reduce the secretion of inflammatory cytokines associated with CVD and promote collagen synthesis to support heart structure and function. Berberine at a concentration of 10mg/L effectively reduces the secretion of TGF-β1 and IL-1β from cardiac fibroblasts. Moreover, blocking the Notch1 signalling pathway using an γ-secretase inhibitor (DAPT) abolishes the protective effect of berberine1. A similar study reported that berberine has a protective effect on cardiomyocytes. Berberine decreased ROS accumulation and lipid peroxidation and reduced prostaglandin-endoperoxide synthase 2 mRNA levels in cardiomyoblast.
Interestingly, berberine did not show any cardiotoxicity in cardiomyoblast cells2. Another study reported the mechanism behind the cardioprotective effect of berberine. Berberine protected cardiac hypertrophy and senescence via increasing Klotho expression and reduced apoptosis, as evidenced by elevated Bax/Bcl-2 ratio. Additionally, they studied the effect of berberine on the aged heart. Tissue samples obtained from aged mice exhibited random and loose arrangements of cardiomyocytes along with increased size. Treatment with berberine reduced the cell size, intercellular space (Fig. 1 upper panel), and fibrosis (Fig. 1 lower panel).
Heart tissue of aged (old) mice exhibited randomly and loosely arranged cardiomyocytes, which were closely arranged with reduced intercellular space post-berberine treatment (upper panel). Masson trichrome staining revealed reduced fibrosis after low (LB) and high dose (HB) berberine treatment in aged mice (lower panel)3
The markers of cardiac hypertrophy (ANP, α-MHC and β-MHC) were reduced in aged mice post berberine treatment3.
Cyclosporine A is given to individuals undergoing organ transplantation to treat organ rejection post-transplant. A clinical study highlights the effect of berberine in increasing cyclosporine A (Cys A) serum concentration in cardiac transplanted recipients, which can reduce the dose and cost associated with cyclosporine A treatment4. Another clinical trial assesses the safety of berberine in patients with chronic congestive heart failure (CHF). One hundred and fifty patients with CHF were enrolled in this study. All patients were given medicines for CHF, while in the treatment group (n=79), patients were additionally given 1.2-2-gram berberine per day. It was observed that patients receiving berberine in addition to conventional treatment exhibited increased LVEF and decreased VPCs (premature ventricular contractions) frequencies compared to the control group5.
In conclusion, berberine exerts a cardioprotective effect without inducing cardiotoxicity. Berberine could be taken as a supplement to protect the heart from cellular stress and aging-induced cardiac changes.
References
(1) The Protective Effects of Berberine and Hesperidin on Inflammatory Factor-Stimulating Cardiac Fibroblasts.
(2) Yang, K. T.; Chao, T. H.; Wang, I. C.; Luo, Y. P.; Ting, P. C.; Lin, J. H.; Chang, J. C. Berberine Protects Cardiac Cells against Ferroptosis. Tzu Chi Med J 2022, 34 (3), 310–317. https://doi.org/10.4103/tcmj.tcmj_236_21.
(3) Li, C.; Jiang, S.; Wang, H.; Wang, Y.; Han, Y.; Jiang, J. Berberine Exerts Protective Effects on Cardiac Senescence by Regulating the Klotho/SIRT1 Signaling Pathway. Biomedicine and Pharmacotherapy 2022, 151. https://doi.org/10.1016/j.biopha.2022.113097.
(4) Xue-shan Huang; Guo-feng Yang; Yu-chen Pan. Effect of Berberin Hydrochloride on Blood Concentration of Cyclosporine A in Cardiac Transplanted Recipients. Chinese journal of integrated traditional and Western medicine 2008, 28 (8).
(5) Zeng, X.-H.; Zeng, X.-J.; Li, Y.-Y. Efficacy and Safety of Berberine for Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy. Am J Cardiol 2003, 92 (2), 173–176. https://doi.org/https://doi.org/10.1016/S0002-9149(03)00533-2.
