Cardiovascular Actions of Berberine

Lau, Chi-Wai; Yao, Xiaoqiang; Chen, Zhenyu; Ko, Wing‐Hung; Huang, Yü

doi:10.1111/j.1527-3466.2001.tb00068.x

Cited by 238 publications

(131 citation statements)

References 29 publications

(56 reference statements)

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“…We pharmacologically upregulated Fbxo32 using Berberine, which is derived from the plant Hydrastis canadensis L. 26,27 Application of Berberine to Ad-shPak1-phenylephrine-NRCMs upregulated Fbxo32 expression to similar levels when compared with Ad-shC2-phenylephrine-NRCMs; this resulted in PP2B downregulation ( Figure 6A). These results indicate that Berberine does not act through Pak1.…”

Section: Treatment Potential Of Fbxo32 Induction In Ameliorating Pak1mentioning

confidence: 99%

Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32

Tsui

Wang

et al. 2015

Hypertension

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Pathological cardiac hypertrophy is regarded as a critical intermediate step toward the development of heart failure. Many signal transduction cascades are demonstrated to dictate the induction and progression of pathological hypertrophy; however, our understanding in regulatory mechanisms responsible for the suppression of hypertrophy remains limited. In this study, we showed that exacerbated hypertrophy induced by pressure overload in cardiac-deleted Pak1 mice was attributable to a failure to upregulate the antihypertrophic E3 ligase, Fbxo32, responsible for targeting proteins for the ubiquitin-degradation pathway. Under pressure overload, cardiac overexpression of constitutively active Pak1 mice manifested strong resilience against pathological hypertrophic remodeling. Mechanistic studies demonstrated that subsequent to Pak1 activation, the binding of Smad3 on a critical singular AGAC -286 -binding site on the FBXO32 promoter was crucial for its transcriptional regulation. Pharmacological upregulation of Fbxo32 by Berberine ameliorated hypertrophic remodeling and improved cardiac performance in cardiac-deficient Pak1 mice under pressure overload. Our findings discover Smad3 and Fbxo32 as novel downstream components of the Pak1-dependent signaling pathway for the suppression of hypertrophy. This discovery opens a new venue for opportunities to identify novel targets for the management of cardiac hypertrophy.

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Section: Treatment Potential Of Fbxo32 Induction In Ameliorating Pak1mentioning

confidence: 99%

Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32

Tsui

Wang

et al. 2015

Hypertension

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Qiu

Zhu²,

Kang³

et al. 2008

Drug Metab Dispos

117

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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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“…Berberine (BBR) is a naturally occurring structurally characterized compound present in many herbs and has a variety of pharmacological properties including glucose lowering (9,15,41) and antimicrobial activities (17). We and others (9,19,38) have reported that BBR reduces body weight, causes a significant improvement in glucose tolerance, and improves insulin action in obese and/or diabetic subjects by activating AMPK.…”

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confidence: 99%

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

Kim

Lee

Hun

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

208

146

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AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, it has been demonstrated that berberine (BBR) exerts antiobesity and antidiabetic effects in obese and diabetic rodent models through the activation of AMPK in peripheral tissues. Here we show that BBR improves lipid dysregulation and fatty liver in obese mice through central and peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, intracerebroventricular administration of BBR decreased the level of malonyl-CoA and stimulated the expression of fatty acid oxidation genes in skeletal muscle. Together, these data suggest that BBR would improve fatty liver in obese subjects, which is probably mediated not only by peripheral AMPK activation but also by neural signaling from the central nervous system.

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Cardiovascular Actions of Berberine

Cited by 238 publications

References 29 publications

Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32

Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32

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

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

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