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Patients with chronic aortic dissections are at high risk of catheter-induced complications. We report a Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for th...
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... did not present signs of heart failure, and cardiac, pulmonary, and vascular examinations were normal. The electrocardiogram (ECG) showed sinus bradycardia with a heart rate of 45 bpm, first-degree atrioventricular block (PR interval of 280 ms), and a competitive junctional rhythm at 55 bpm (Figure 1). Both blood analysis and echocardiography did not show any justification for the marked bradycardia. ...
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Citations
... In addition, intravenous administration of BBR can cause allergic reactions (190). Additionally, arrhythmia has been reported in hypervagotonic individuals after the administration of BBR (191). Other side effects, including nausea, cramping, diarrhea, flatulence, vomiting, rash, fever, constipation, and stomachache, have also been reported (192)(193)(194). ...
Colorectal cancer (CRC) is one of the most commonly diagnosed and deadly malignancies worldwide. The incidence of CRC has been increasing, especially in young people. Although great advances have been made in managing CRC, the prognosis is unfavorable. Numerous studies have shown that berberine (BBR) is a safe and effective agent presenting significant antitumor effects. Nevertheless, the detailed underlying mechanism in treating CRC remains indistinct. In this review, we herein offer beneficial evidence for the utilization of BBR in the management and treatment of CRC, and describe the underlying mechanism(s). The review emphasizes several therapeutic effects of BBR and confirms that BBR could suppress CRC by modulating gene expression, the cell cycle, the inflammatory response, oxidative stress, and several signaling pathways. In addition, BBR also displays antitumor effects in CRC by regulating the gut microbiota and mucosal barrier function. This review emphasizes BBR as a potentially effective and safe drug for CRC therapy.
... In addition to the pharmacological efficacy, safety and toxicity data of berberine should also be reviewed carefully. Though uncommon, a case report showed electrocardiogram sinus bradycardia, first-degree atrioventricular block and competitive junctional rhythm in a sportsman taking berberine for hypercholesterolemia indicating that berberine might have side effect in hypervagotonic persons (Cannillo et al., 2013). Additionally, berberine might increase risk for kernicterus in jaundiced newborn infants because administration of berberine resulted in a significant decrease in bilirubin serum protein binding due to displacement of bilirubin from albumin by berberine in an experimental study (Chan, 1993). ...
The exacerbation of oxidative and inflammatory reactions has been involved in atherosclerotic cardiovascular diseases leading to morbidity and mortality worldwide. Discovering the underlying mechanisms and finding optimized curative approaches to control the global prevalence of cardiovascular diseases is needed. Growing evidence has demonstrated that gut microbiota is associated with the development of atherosclerosis, while berberine, a natural product exhibits antiatherogenic effects in clinical and pre-clinical studies, which implies a potential link between berberine and gut microbiota. In light of these novel discoveries, evidence of the role of berberine in modulating atherosclerosis with a specific focus on its interaction with gut microbiota is collected. This review synthesizes and summarizes antioxidant and anti-inflammatory effects of berberine on combating atherosclerosis experimentally and clinically, explores the interaction between berberine and intestinal microbiota comprehensively, and provides novel insights of berberine in managing atherosclerotic cardiovascular diseases via targeting the gut-heart axis mechanistically. The phenomenon of how berberine overcomes its weakness of poor bioavailability to conduct its antiatherogenic properties is also discussed and interpreted in this article. An in-depth understanding of this emerging area may contribute to identifying therapeutic potentials of medicinal plant and natural product derived pharmaceuticals for the prevention and treatment of atherosclerotic cardiovascular diseases in the future.
... To justify, according to a clinical case, a 53-year-old man admitted to the emergency department for fatigue, dyspnoea upon exertion and bradycardia, six days after starting a berberine-containing product to treat hypercholesterolaemia, was reported. Therefore, this case study suggests that berberine's use should be carefully weighed in hypervagotonic people due to the drug's bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks ( Cannillo et al., 2013 ). Because of its ability to inhibit the hERG (human ether-a-go-go-related gene) potassium channel, a target of numerous antiarrhythmic drugs, berberine can also induce cardiotoxicity ( Xu et al., 2017 ). ...
Berberine is a quaternary ammonium salt and naturally occurring benzylisoquinoline alkaloid, present in numerous medicinal herbs' roots and stem bark as an active constituent, especially in the genus Berberis. It contains many pharmacological properties such as antioxidant, antiviral, antidiabetic, antidepressant, antidiarrheal, an-tibacterial any many more. Since nature is the best healer, it has been traditionally used in Ayurvedic and Chinese medicine to mitigate several disease conditions. Besides the beneficial effects of berberine, some drawbacks such as its poor aqueous solubility and low oral bioavailability hinder its applications. Although it has been used for dietary supplements, despite its vast potential to evolve as a drug candidate, there are no approved pure berberine formulations available in market for any particular disease. Therefore, this review provides an overview to the reader by incorporating recent studies on berberine's sources, extraction techniques, chemistry, different Nano carriers and bioavailability enhancers for enhancing bioavailability, versatile applications, toxicological aspects and recent patents along with future perspectives. The accumulated evidence may broaden the horizon of drug designers, scientists, academicians, and researchers on berberine and help design and develop effective berberine formulations on a large scale for treating several diseases.
... However, several data in vivo and in vitro, as well as clinical studies, demonstrated that BRB modulates the cardiovascular functionality with great effectiveness, acting through multiple mechanisms that impact on the electrical and contractile properties of the heart 5 . Generally, BRB is considered beneficial at cardiovascular level 5,17,50 although data obtained in some experimental models 51 and in a hypervagotonic patient 52 indicate that BRB actions on cardiac functionality remain in part controversial. Our results, showing bradycardic effects and the reduction www.nature.com/scientificreports/ ...
The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation.
... However, minimal information on the adverse drug reactions of berberine and evodiamine supplementation is available. Some studies have demonstrated that the maternal toxicity lowest observed adverse effect levels of berberine were 531 mg/kg/day and 841 mg/kg/day in rats and mice [32], and berberine could present certain side effects in hypervagotonic people [33]. The incidence of toxic adverse effect is connected with the doses of berberine, which showed that the dose of berberine increase lead to the rising risk of toxic side effect [34]. ...
Background
Hyperlipidemia characterized of elevated serum lipid levels is a prevalent disease frequently resulting in cardiovascular disease (CVD). Berberine and evodiamine are herbal products of traditional Chinese herb Coptis chinensis and Evodia rutaecarpa, which are indicated to exert regulation of lipid metabolism. Therefore, the objective of this study was to investigate the lipid-lowering effect of berberine and evodiamine combination in hyperlipidemic rats. Method
The rat model of hyperlipidemia was established by providing high-fat-diet (HFD) for 4 weeks. Berberine (BB), evodiamine (EV), and their combination (BB + EV) were orally administered to HFD induced rats for 4 weeks. Body weight, food utilization, histopathology of liver tissues, lipid profiles of serum and liver were measured. Gas chromatography (GC) analysis was applied to examine the level of plasma total cholesterol and ß- Sitosterol (BS) to estimate cholesterol absorption activity. Furthermore, intestinal NPC1L1, ACAT2, and ApoB48 protein expressions were evaluated by immunohistochemical assay. ResultAccording to the results, decreased levels of serum cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), as well as hepatic TC were showed in hyperlipidemic rats treated by combination of berberine and evodiamine. GC analysis indicated that the elevated plasma BS was significantly ameliorated by BB, EV, and BB + EV. In addition, immunohistochemical analysis revealed that BB + EV treatment down-regulated the expressions of intestinal NPC1L1 and ACAT2, and ApoB48 in HFD induced rats. Conclusion
Based on the above results, combination of berberine and evodiamine exerted a promising preventive effect on hyperlipidemia, partially through inhibiting intestinal absorption of cholesterol.
... Previous biochemical fractionation studies showed berberine and palmatine as some of the major active components associated with the biological activity of Nx [26]. Here we tested, if berberine or some of its derivatives could recapitulate the Nx-induced combinatorial growth inhibitory effects [27][28][29][30][31][32]. Chemical structures of Ber and its derivatives are shown in Fig. S2. ...
There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model. Nx is an extract derived from the bark of Phellodendron amurense and has been utilized in traditional Chinese medicine as antidiarrheal, astringent, and anti-inflammatory agent for centuries. We hypothesized that "Nx-mediated inhibition of survival molecules like STAT3 and NF-κB in pancreatic cancer cells will improve the efficacy of the conventional chemotherapeutic agent, gemcitabine (GEM)". Therefore, we explored the utility of Nx, one of its active constituents berberine and its derivatives, to enhance the effects of GEM. Using multiple human pancreatic cancer cells we found that combination treatment with Nx and GEM resulted in significant alterations of proteins in the STAT3/NF-κB signaling axis culminating in growth inhibition in a synergistic manner. Furthermore, GEM resistant cells were more sensitive to Nx treatment than their parental GEM-sensitive cells. Interestingly, although berberine, the Nx active component used, and its derivatives were biologically active in GEM sensitive cells they did not potentiate GEM activity when used in combination. Taken together, these results suggest that the natural extract, Nx, but not its active component, berberine, has the potential to improve GEM sensitivity, perhaps by down regulating STAT3/NF-κB signaling. This article is protected by copyright. All rights reserved.
... In a randomized controlled trial, Li et al. reported that Tongxinluo Capsules, a TCM used to treat coronary disease and angina pectoris, caused an adverse reaction in the form of stomachaches in the treatment group (70). Berberine, an active compound extracted from the herb Berberis, may induce the onset of competitive junctional rhythm, causing a loss of atrioventricular synchronization, and reduce chronotropic competence with the onset of symptoms upon exertion (71). In fact, the present evidence of adverse reactions and toxicity is insufficient. ...
Traditional Chinese medicine (TCM), as a type of complementary and alternative medicine (CAM), is a sophisticated and time-honored form of healthcare in China. Many TCMs are widely used to treat hepatitis B and hepatitis C in countries like China, Japan, and South Korea. Since conventional clinical preparations like interferon-α cause obvious dose-dependent adverse reactions and drug resistance, TCMs and related bioactive compounds have garnered increasing attention from physicians and medical researchers. Thus far, a number of TCMs and compounds have been used to inhibit the hepatitis B virus (HBV) or hepatitis C virus (HCV) in vitro, in vivo, and even in clinical trials. The current review summarizes TCMs and related compounds that have been used to inhibit HBV or HCV. Most of these medicines are derived from herbs. HepG2.2.15 cells have been used to study HBV in vitro and Huh7.5 cells have been similarly used to study HCV. Ducks have been used to study the anti-HBV effect of new medication in vivo, but there are few animal models for anti-HCV research at the present time. Thus far, a number of preclinical studies have been conducted but few clinical trials have been conducted. In addition, a few chemically modified compounds have displayed greater efficacy than natural products. However, advances in TCM research are hampered by mechanisms of action of many bioactive compounds that have yet to be identified. In short, TCMs and related active compounds are a CAM that could be used to treat HBV and HCV infections.
... Zhao GL et al Acta Pharmacologica Sinica npg and animal studies have demonstrated the beneficial effects of BBR on cardiovascular performance [6][7][8][9][10] . BBR has been found to prevent ischemia-induced ventricular tachyarrhythmias, enhance the force of cardiac contractions, and decrease peripheral vascular resistance and blood pressure [11][12][13][14] . Recently, we have also demonstrated that Notch1 signaling plays a key role in BBR's cardioprotective action [15] . ...
Aim:
Endoplasmic reticulum (ER) stress plays a pivotal role in mediating cellular apoptosis during myocardial ischemia/reperfusion (MI/R) injury. Berberine (BBR) exerts potential cardioprotective effects. However, whether BBR can modulate the myocardial ER stress level during MI/R injury and the underlying mechanisms for its effects are still unknown. This study was performed to determine whether BBR protects against MI/R injury by attenuating the ER stress-induced apoptosis and to define the role of JAK2/STAT3 signaling in this process.
Methods:
Male Sprague-Dawley rats were treated with BBR (200 mg·kg(-1)·d(-1), ig, 2 weeks) and then subjected to MI/R surgery. An in vitro study was performed on cultured H9C2 cells exposed to simulated ischemia/reperfusion (SIR) injury.
Results:
In vivo MI/R injury significantly impaired cardiac function and increased myocardial apoptosis, oxidative damage and the ER stress level. BBR treatment effectively reduced the myocardial apoptosis, infarct size, oxidative damage and ER stress induced by PERK/eIF2α/ATF4 signaling, thus improving myocardial function. Furthermore, BBR significantly activated JAK2/STAT3 signaling, and inhibition with AG490 (the inhibitor of JAK2/STAT3 signaling) blocked BBR's protective effects. BBR also markedly reduced the cardiac apoptosis, oxidative stress and ER stress induced by SIR treatment in H9C2 cells. Consistent with the other results, these effects were abolished by JAK2 siRNA administration.
Conclusion:
We demonstrate that BBR ameliorates MI/R injury by attenuating endoplasmic reticulum stress-induced apoptosis via the JAK2/STAT3 signaling pathway.
... Furthermore, in vitro the dose of Ber used to prolong RR interval and ERP can led to extreme bradycardia and cardiac arrest during ACh infusion. Although we do not completely understand the reasons for these differences, the higher concentration of ACh and Ber together may adversely affect the cardiac conduction system and heart function [25]. Additional work must be performed to understand the mechanism of the differences mentioned above. ...
The purpose of this study was to test the efficacy of Berberine (Ber) on atrial fibrillation (AF) induced by acetylcholine (ACh) and explore its underlying mechanisms of action. In vivo electrophysiology experiments were performed in adult anesthetized rabbits. Single atrial myocytes were isolated from rabbit hearts and action potentials recorded using patch clamp techniques. AF was induced by rapid atrial burst pacing during intravenous (IV) ACh infusion alone or with IV Ber. Compared to the Baseline, IV Ber (2 mg/kg) prolonged the RR interval and effective refractory period (195 ± 10 vs. 215 ± 11 msec; 80 ± 4 vs. 85 ± 5 msec, respectively; both P<0.05). The induced rate of sustained 1 min AF was lower during ACh infusion with Ber than during ACh infusion alone (4/10 vs. 30/35, P<0.01). The termination rate of ACh-induced AF was higher with IV Ber (1 mg/kg) than with IV saline (sustained 1 min AF: 6/8 vs. 6/20, sustained 10 min AF: 8/10 vs. 1/6, both P<0.05). ACh perfusion significantly shortened the action potential duration (APD) of isolated atrial myocytes (APD50: 152 ± 13 vs. 81 ± 10 msec; APD90: 256 ± 19 vs. 132 ± 13 msec, both P<0.01). Application of Ber reversed the APD shortening induced by ACh (APD50: 81 ± 10 vs. 134 ± 15 msec; APD90: 132 ± 13 vs: 213 ± 17 msec, both P<0.01). We conclude that Ber suppresses ACh-induced AF in the rabbit by increasing atrial effective refractory period and prolonging the APD of atrial myocytes.
... In human clinical trials, only a small percentage of patients reported nausea, vomiting, diarrhea, or constipation with BBR treatment, and no severe side effects were observed with standard doses (Sabir and Bhide 1971;Zhang et al. 2010). High doses of BBR resulted in rare adverse effects including headache, skin irritation, and bradycardia (Cannillo et al. 2013). BBR is excreted mainly through the hepatobiliary system, and no adverse effect has been observed in hepatic function. ...
The incidence of type 2 diabetes is increasing rapidly worldwide, and the development of novel anti-diabetic drugs is emerging. However, most anti-diabetic drugs cannot be used in patients with hepatic dysfunction, renal disease, and heart disease, which makes pharmacological therapy of type 2 diabetes complicated. Despite continued introduction of novel agents, the search for an ideal drug that is useful as both a hypoglycemic agent and to reduce diabetes-related complications remains elusive. Berberine is an isoquinoline alkaloid extract that has shown promise as a hypoglycemic agent in the management of diabetes in animal and human studies. Mechanistic studies have revealed beneficial effects of berberine on diabetes-related complications. Although there have been few clinical reports of the anti-diabetic effects of berberine, little documentation of adverse effects in humans positions it as a potential candidate drug to treat type 2 diabetes. In the present review, the anti-diabetic mechanism of berberine, its effect on diabetes-related complications, and its recent use in human clinical studies is highlighted. In addition, we summarize the different treatments for type 2 diabetes in adults and children.
