Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Zeng, Xiang; Zeng, Xianjun; Li, Yunyun

doi:10.1016/s0002-9149(03)00533-2

Cited by 180 publications

(104 citation statements)

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“…However, the therapeutic use of DOX has been limited by its serious dose-related cardiotoxicity (25). BER has been reported to be safe and beneficial in the treatment of patients with chronic congestive heart failure (16). Therefore, combining DOX with BER is a novel strategy for the treatment of cancer and reduction of the cardiotoxicity induced by DOX.…”

Section: Discussionmentioning

confidence: 99%

“…For the cardioprotective property, BER is known to modulate Cdk9 and cyclin T1 protein expression. BER possesses muscarinic agonist-like properties which may contribute to a reduction in myocardial damage (15)(16)(17). BER also suppresses tumor growth through the induction of apoptosis and cell cycle arrest in cancer cells (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro

et al. 2012

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Abstract. The clinical use of doxorubicin (DOX), a potent antineoplastic agent, is limited by its serious side-effects, which include acute and chronic cumulative dose-related cardiotoxicity. Berberine (BER), a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay was used to detect the cell viability of A549, HeLa and HepG2 cells after each cell line was treated with DOX, BER or a combination of DOX and BER for 24 h. Apoptosis was evaluated by acridine orange staining. The results showed that BER and DOX exhibited dose-dependent inhibitory effects on A549 and HeLa cells which were likely mediated by inducing apoptosis. The same result was found in the combination group. Isobologram illustration and combination index (CI) analyses revealed that the combination of DOX and BER generates synergistic effects in A549 (CI=0.61) and HeLa (CI= 0.73) cells. These findings indicate that BER sensitizes cells to the anticancer effects of DOX. IntroductionDoxorubicin (DOX), an anthracycline antibiotic and antineoplastic agent, was first isolated from Streptomyces peucetius (1). DOX is a potent chemotherapeutic agent that is used in the treatment of solid tumors and malignant hematological diseases (2). DOX exerts its antitumor activity by inserting into DNA, leading to double-stranded DNA breaks (DSB), and intercepting DNA topoisomerase II activity (3,4). However, the clinical use of DOX has been largely restricted due to its cardiotoxicity, which may lead to the development of cardiomyopathy and ultimately congestive heart failure (5). The molecular mechanisms underlying DOX-induced cardiotoxicity include the formation of free radicals, activation of transcription factor NF-κB, increased lipid peroxidation and Ca 2+ overloading (6-8). The use of cardioprotective drugs is an alternative approach to reduce the cardiotoxicity of DOX. Pharmacological and clinical attempts to reduce the cardiotoxicity of DOX have had little success thus far. Consequently, it is important to develop a therapy to reduce DOX-induced cardiotoxicity and increase the antitumor effect of DOX.Berberine (BER), a botanical alkaloid, is purified from the roots and bark of the Berberis species (9). BER reportedly possesses multiple biological and pharmacological properties, including anti-diarrheal, anti-fungal, anti-diabetic (10-12), hepatoprotective and cardioprotective effects. The possible mechanism of the hepatoprotective effect is that BER inhibits the activity of CYP 2E1 and CYP 1A2, reduces the production of nitric oxide and lowers the AST and ALT levels in serum (13,14). For the cardioprotective property, BER is known to modulate Cdk9 and cyclin T1 protein expression. BER possesses muscarinic agonist-like properties which may contribute to a reduction in myocardial damage (15-17). BER also suppresses tumor growth through the induction of apoptosis and cell cycle arrest in cancer cells (18)(19)(20)(21). Notably, it has been reported tha...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro

et al. 2012

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“…15,16 Numerous pollsters have reported salutary prospective of berberine as compassionate in the management of hypertension, atherosclerosis, and heart disease, together with left ventricular remodeling. [17][18][19] It is demonstrated that berberine concealed expression of transforming growth factor-b (TGF-b) in renal tissue to alleviate renal dysfunction and decelerate the development of diabetic nephropathy in rats. 20 Berberine exerts its renoprotective effect via modulating G proteins-AC-cAMP signaling pathway in diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation

2015

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Ischemic acute renal failure is a condition that extends subsequent to sudden and momentary fall in overall or regional blood flow to the kidney. The present investigation was deliberated to scrutinize the renoprotective potential of berberine in animal model of renal ischemia reperfusion (RIR) induced dent via assessment of various biochemical and molecular biomarkers. Male Wistar rats were anesthetized and the right kidney was removed through a small flank incision. Renal ischemia reperfusion was persuaded in uni-nephrectomized rats by occlusion of left renal artery for 45 min and reperfusion for 4 weeks. After 4 weeks of treatment of berberine (10, 20, and 40 mg/kg, p.o.), hemodynamic and left ventricular function were evaluated. Induction of ischemia reperfusion resulted callous mutilation in kidney which was confirmed by alterations in oxidative stress (SOD, GSH, and MDA), membrane bound enzymes, kidney function markers (serum creatinine and BUN), and mitochondrial dysfunction. Moreover, RIR injury exhibited incredible alterations in mRNA expression of KIM-1, NGAL, Caspase-3, Bax, Bcl-2, and TNF-a levels. Conversely treatment of berberine (20 and 40 mg/kg) significantly (p50.01 and p50.001) restored ischemia reperfusion induced marring via intonation of biochemical and molecular biomarkers. To sum up, berberine demonstrated compelling renoprotective effect in RIR injury via caspase-mitochondria-dependent pathway.

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“…Its chloride salt has been used for several decades in clinical situations to treat gastroenteritis and secretory diarrhea in China. In recent years, berberine has also shown significant effects in treatment of diabetes mellitus (Ni, 1988), hyperlipemia (Kong et al, 2004), arrhythmia, and heart failure (Zeng and Zeng, 1999;Lau et al, 2001;Zeng et al, 2003). However, pharmacokinetic studies have indicated that berberine has poor oral bioavailability (Shen et al, 1993;Yu et al, 2000;Zuo et al, 2006), and a few of the metabolites have been identified in rats (Zuo et al, 2006) and in humans (Pan et al, 2002).…”

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confidence: 99%

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

Qiu

Zhu²,

Kang³

et al. 2008

Drug Metab Dispos

118

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ABSTRACT:The urinary metabolites of berberine, an isoquinoline alkaloid isolated from several Chinese herbal medicines, were investigated in rats and humans. Using macroporous adsorption resin chromatography, open octadecyl silane column chromatography and preparative high-performance liquid chromatography, we isolated seven metabolites (HM1-HM7) from human urine and five metabolites (RM1-RM5) from rat urine after oral administration. Berberine is an isoquinoline alkaloid isolated from several Chinese herbal medicines such as rhizoma coptidis, cortex phellodendri, and caulis mahoniae. Its chemical structure is 5,8-dihydro-9,10-dimethoxy-6H-benzo(g)-1,3-benzodioxolo(5,6-a)quinolizine. Berberine exhibits a wide variety of bioactivities such as antidiarrheic (Sack and Froehlich, 1982;Taylor and Greenough, 1989), antimicrobial (Yan et al., 2008), hypolipidemic (Kong et al., 2004;Doggrell, 2005;Brusq et al., 2006;Cicero et al., 2007), hypoglycemic (Yin et al., 2002;Pan et al., 2003;Zhou et al., 2007;Turner et al., 2008;Yin et al., 2008), antiarrhythmic (Wang et al., 1994;Lau et al., 2001), anticancer (Inoue et al., 2005;Lanvers-Kaminsky et al., 2006;Lin et al., 2006Lin et al., , 2007Piyanuch et al., 2007;Serafim et al., 2008;Yu et al., 2007), anti-inflammatory (Kuo et al., 2004Lee et al., 2007), antiviral (Hayashi et al., 2007), antidepressant (Kulkarni and Dhir, 2007), and hepatoprotective (Zhang et al., 2008) effects. Its chloride salt has been used for several decades in clinical situations to treat gastroenteritis and secretory diarrhea in China. In recent years, berberine has also shown significant effects in treatment of diabetes mellitus (Ni, 1988), hyperlipemia (Kong et al., 2004), arrhythmia, and heart failure (Zeng and Zeng, 1999;Lau et al., 2001;Zeng et al., 2003). However, pharmacokinetic studies have indicated that berberine has poor oral bioavailability (Shen et al., 1993;Yu et al., 2000;Zuo et al., 2006), and a few of the metabolites have been identified in rats (Zuo et al., 2006) and in humans (Pan et al., 2002). To obtain more information about its metabolism to improve its clinical applications, we examined the biotransformation of berberine in rats and humans. In the present article we describe the isolation and identification of urinary metabolites of berberine in these two species. Materials and Methods Materials.Berberine chloride (purity Ͼ 99.5%) was supplied by the Northeast General Pharmaceutical Factory (Shenyang, China). Methanol was HPLC grade and water was double-distilled in our laboratory. All other reagents were of analytical grade and were purchased from Shenyang Chemical Company (Shenyang, China). Normal-phase and reverse-phase preparatory thin-layer chromatography was performed using products from Merck (Darmstadt, Germany). Macroporous resin D101 was purchased from the Chemical Plant of Nankai University (Tianjin, China) and Diaion ion exchange resin HP20 from Mitsubishi Chemical Corporation (Tokyo, Japan). Sephadex LH-20 and ODS were obtained from Pfizer (Freiburg, Germany). Spot...

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Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Cited by 180 publications

References 12 publications

Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro

Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro

Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

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