Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Abstract

Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.

Isoquinoline Alkaloids from Coptis chinensis Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells

“…Berberine ( 13 ) and coptisine ( 11 ) share the same molecular skeleton divided into four rings, A, B, C, D with a methylenedioxyl group at C2 and C3 on the A ring and small differences in substituent patterns in the D ring [ 52 ]. In the berberine ( 13 ) structure, C9 and C10 of the D ring are each attached to a methoxyl group, whereas the D ring of 11 forms a methylenedioxyl group [ 53 ]. From the view of the structure—activity relationship, it has been shown that a methylenedioxy group of 13 and 11 compared to dimethoxyl group of 12 at the 2,3-positions on the ring A is important among others for anticancer activity [ 54 ], and markedly improves the inhibitory effect of 13 and 11 on cancer cell proliferation [ 55 , 56 ].…”

WNT/β-Catenin-Mediated Resistance to Glucose Deprivation in Glioblastoma Stem-like Cells

“…In vitro drug screening identified LGK974 and berberine (WNT inhibitor used for hypercholesterinemia, diabetes, and hypertension [32]) as drugs that sensitize cells to starvation-induced cell death. In addition to that, we characterized the metabolic profile under glucose starvation, WNT inhibition, and a combination of WNT inhibition and glucose starvation, by utilizing GC-MS. We observed significant changes in various metabolites under WNT inhibition alone and in combination with glucose depletion.…”

Can Isoquinoline Alkaloids Affect Platelet Aggregation in Whole Human Blood?

“…The first major issue are the potential side effects; in particular, the risk of hepatotoxicity and cytotoxic effects [ 1 , 3 ]. Secondly, berberine is a quaternary ammonium salt with a very low oral bioavailability [ 4 ]; hence, the tens of μM plasma concentrations that would be required to observe this activity are not achievable with an oral administration. Importantly, our study showed that much higher concentrations were required for the effective inhibition of platelet aggregation in whole blood.…”

“…An example is berberine, which is especially known in traditional Chinese medicine; it could potentially be used as an antidiabetic and hypolipidemic drug. Berberine can, however, also cause gastrointestinal hemorrhage [ 2 , 3 , 4 ], which is not very surprising given its known antiplatelet effects. Other isoquinoline alkaloids have also previously been shown to block platelet aggregation; on the other hand, there are no clear data on whether these effects have a clinical significance.…”