Berberine, a strong polyriboadenylic acid binding plant alkaloid: spectroscopic, viscometric, and thermodynamic study

Yadav, Ram Chandra; Kumar, Gopinatha Suresh; Bhadra, Kakali; Giri, Prabal; Sinha, Rangana; Pal, Sarmistha; Maiti, Motilal

doi:10.1016/j.bmc.2004.09.045

Cited by 89 publications

(77 citation statements)

References 34 publications

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“…BBR exhibits multiple biological and pharmacological effects, including antimicrobial and antitumor activities (16,32), and the cytotoxic effect of BBR has been studied extensively (16,(33)(34)(35). It was reported that BBR could bind DNA to affect DNA replication, transcription, and the cell cycle (36,37). In the present study, we found that intracellular BBR accumulated especially in the nucleus and caused cell cycle arrest of C. albicans, which made us form the hypothesis that cell cycle arrest and DNA damage may contribute to the synergism of FLC and BBR against FLC-resistant C. albicans.…”

Section: Discussionmentioning

confidence: 99%

Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

Zhang

et al. 2013

Antimicrob Agents Chemother

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It was found in our previous study that berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. The aim of the present study was to clarify how BBR and FLC worked synergistically and the underlying mechanism. Antifungal time-kill curves indicated that the synergistic effect of the two drugs was BBR dose dependent rather than FLC dose dependent. In addition, we found that BBR accumulated in C. albicans cells, especially in the nucleus, and resulted in cell cycle arrest and significant change in the transcription of cell cycle-related genes. Besides BBR, other DNA intercalators, including methylene blue, sanguinarine, and acridine orange, were all found to synergize with FLC against FLC-resistant C. albicans. Detection of intracellular BBR accumulation by fluorescence measurement showed that FLC played a role in increasing intracellular BBR concentration, probably due to its effect in disrupting the fungal cell membrane. Similar to the case with FLC, other antifungal agents acting on the cell membrane were able to synergize with BBR. Interestingly, we found that the efflux of intracellular BBR was FLC independent but strongly glucose dependent and associated with the drug efflux pump Cdr2p. These results suggest that BBR plays a major antifungal role in the synergism of FLC and BBR, while FLC plays a role in increasing the intracellular BBR concentration. Candida albicans, one of the most prevalent human fungal pathogens, causes superficial mycoses, invasive mucosal infections, and disseminated systemic disease (1-4). Although the need for effective antifungal therapy is increasing, the available antifungal agents are still limited. Fluconazole (FLC) is most widely used due to its high bioavailability and low toxicity (5, 6). However, with the increasing clinical use of FLC, drug-resistant isolates are emerging rapidly (7-11). The high mortality rate of invasive Candida infections and limited availability of highly effective antifungal agents make it necessary to develop new antifungal therapeutics.The combinations of antimicrobial agents against drug-resistant Candida have been studied (12-15). Members of our group have shown that concomitant use of berberine (BBR; an alkaloid with a long history of medicinal use in traditional Chinese medicine [16]) and FLC is highly efficacious in killing FLC-resistant C. albicans in vitro, and the fractional inhibitory concentration (FIC) index ranges from 0.017 to 0.127 (17, 18). Our comparative proteomic study and further investigations indicated that FLC and BBR treatment affected the expression of proteins functioning in energy metabolism, increased mitochondrial membrane potential, decreased intracellular ATP level, inhibited ATP-synthase activity, and increased generation of endogenous reactive oxygen species (ROS) in FLC-resistant C. albicans strains (19). Nevertheless, the mechanism for how the combination of BBR and FLC augments the efficacy of each agent alone remains unclear.In this study, we fo...

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Section: Discussionmentioning

confidence: 99%

Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

Zhang

et al. 2013

Antimicrob Agents Chemother

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“…Twenty-six 15 ml fractions were collected. A total of 200 ml of each fraction was used directly to measure the fluorescence intensity with a fluorescent microplate reader (Spectra MaxGemini; Molecular Devices, Sunnyvale, CA) at 350 nm excitation and 545 nm emission (23). The rest of the fraction was evaporated under N 2 , and residues in each fraction were dissolved in 250 ml of DMSO.…”

Section: Semipurification Of Goldenseal Alkaloid Componentsmentioning

confidence: 99%

The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms

Abidi

Chen

Kraemer

et al. 2006

Journal of Lipid Research

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Our previous studies have identified berberine (BBR), an alkaloid isolated from the Chinese herb huanglian, as a unique cholesterol-lowering drug that upregulates hepatic low density lipoprotein receptor (LDLR) expression through a mechanism of mRNA stabilization. Here, we demonstrate that the root extract of goldenseal, a BBR-containing medicinal plant, is highly effective in upregulation of liver LDLR expression in HepG2 cells and in reducing plasma cholesterol and low density lipoprotein cholesterol (LDL-c) in hyperlipidemic hamsters, with greater activities than the pure compound BBR. By conducting bioassay-driven semipurifications, we demonstrate that the higher potency of goldenseal is achieved through concerted actions of multiple bioactive compounds in addition to BBR. We identify canadine (CND) and two other constituents of goldenseal as new upregulators of LDLR expression. We further show that the activity of BBR on LDLR expression is attenuated by multiple drug resistance-1 (MDR1)-mediated efflux from liver cells, whereas CND is resistant to MDR1. This finding defines a molecular mechanism for the higher activity of CND than BBR. We also provide substantial evidence to show that goldenseal contains natural MDR1 antagonist(s) that accentuate the upregulatory effect of BBR on LDLR mRNA expression. These new findings identify goldenseal as a natural LDL-c-lowering agent, and our studies provide a molecular basis for the mechanisms of action.-Abidi, P., W. Chen, F. B. Kraemer, H. Li, and J. Liu. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.

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“…38) In addition, YB-1 can act as a poly(A)-binding protein, and stimulates and represses translation at low and high concentrations, respectively. Berberine and palmatine are well known to strongly interact with double-stranded DNA 39) and the poly(A) tails of RNAs, 40,41) whereas coptisine only weakly binds to double-stranded DNA. 42) However, in the cellular context, the aspects of whether berberine and palmatine cause DNA damage are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Selective Regulation of Multidrug Resistance Protein in Vascular Smooth Muscle Cells by the Isoquinoline Alkaloid Coptisine

Suzuki

Tanabe

Mizukami

2010

Biological & Pharmaceutical Bulletin

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When the biological activites of hydrophobic drugs or xenobiotics are studied, it is important to clarify their effects on expression and function of multidrug resistance (MDR) protein. We therefore evaluated the effects of coptisine on MDR in comparison with the structurally related isoquinoline alkaloids berberine and palmatine. To achieve this, we investigated the effects of the three alkaloids on the expression and function of P-glycoprotein/MDR1, MDR1 gene products, in vascular smooth muscle cells (VSMCs). In A10 cells (a rat VSMC line), coptisine upregulated the mRNAs of Mdr1a and Mdr1b, rodent homologues of human MDR1, and these effects were completely abrogated by actinomycin D. Coptisine also induced Mdr1a/1b protein expression and enhanced the efflux of rhodamine 123 from A10 cells. In contrast, berberine and palmatine slightly upregulated the mRNAs of Mdr1a and Mdr1b, but failed to induce Mdr1a/1b protein expression or stimulate rhodamine 123 efflux. To clarify whether these effects occurred in other cells, the effects of the three alkaloids on Mdr1a/1b function were examined in 3Y1, dRLh-84 and B16 cells. Coptisine and berberine enhanced rhodamine 123 efflux in all three cell types, while palmatine inhibited it, based on the finding that palmatine efficiently activated the Mdr1a ATPase activity as a good substrate for Mdr1a. Therefore, the three isoquinoline alkaloids regulated MDR differently in cell type-specific manners. In particular, only coptisine induced Mdr1a/1b in A10 cells and stimulated rhodamine 123 efflux. Taken together, coptisine appears to exert VSMC-selective effects on Mdr1a/1b induction in contrast to berberine and palmatine.

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Berberine, a strong polyriboadenylic acid binding plant alkaloid: spectroscopic, viscometric, and thermodynamic study

Cited by 89 publications

References 34 publications

Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms

Selective Regulation of Multidrug Resistance Protein in Vascular Smooth Muscle Cells by the Isoquinoline Alkaloid Coptisine

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