The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides

Zhi, Duo; Feng, Pan-Feng; Sun, Jialiang; Guo, Feng-Feng; Zhang, Rui; Zhao, Xin; Li, Baoxin

doi:10.1016/j.ejps.2015.05.009

Cited by 34 publications

(19 citation statements)

References 37 publications

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“…Treatment with BBR has been reported to act on numerous targets and signaling pathways underlying pathophysiological process, including proliferation, apoptosis, angiogenesis, migration and invasion in a variety of cancer cells (35)(36)(37). In our previous study, BBR was observed to exert a strong inhibitory effect on hERG potassium channels (22,38,39), which are often aberrantly expressed in carcinoma. Therefore, the present study proposed that BBR may inhibit ovarian cancer by targeting hERG1.…”

Section: Discussionmentioning

confidence: 88%

“…However, to the best of our knowledge, few investigations into the function of hERG1 in human ovarian cancer have been conducted (17,18) hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells and the underlying mechanisms regulating hERG1 expression in ovarian cancer progression remain unknown. Previous studies have revealed that numerous traditional Chinese herbal medicines (19)(20)(21), including berberine (BBR), a clinically important natural isoquinoline alkaloid that was the subject of our previous study (22), exhibit significant antitumor activities and reverse the drug resistance of cancer cells. BBR has been reported to exert antitumor activity against various types of cancer, including gastric, oral, prostate and ovarian cancer (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

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hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells

Zhi

Zhou

et al. 2019

Oncol Lett

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The human ether-ago go related potassium channel 1 (hERG1) is a functional component of the voltage-gated Kv11.1 potassium channel, which is commonly described as a crucial factor in the tumorigenesis of a variety of tumors. Ovarian cancer is one of the most severe types of cancer, with an extremely poor prognosis. Advances have been made in recent years; however, drug resistance and tumor recurrence remain critical issues underlying satisfactory treatment outcomes. Therefore, more effective antitumor agents with low levels of drug resistance for ovarian cancer treatment are urgently required in clinical practice. In the present study, hERG1 mRNA expression in ovarian tumor tissues and cell lines were measured by reverse transcription-quantitative polymerase chain reaction. Immunohistochemistry and western blotting were used to assess the expression levels of hERG1 protein. Cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 assay and Transwell assay. A tumor xenograft assay was used to determine the growth of tumors in vivo. It was demonstrated that the expression levels of hERG1 were significantly elevated in ovarian cancer tissues and expressed in ovarian cancer cell lines, particularly in SKOV3 cells. Abnormal hERG1 expression was significantly associated with the proliferation, migration and invasion abilities of ovarian cancer. In addition, berberine (BBR) may be used as a potential drug in the treatment of ovarian cancer, possibly due to its inhibitory effects on the hERG1 channels. In conclusion, the present study demonstrated that hERG1 may be a potential therapeutic target in the treatment of ovarian cancer and provided novel insights into the mechanism underlying the antitumor effects of BBR in ovarian cancer.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells

Zhi

Zhou

et al. 2019

Oncol Lett

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“…combination therapy is widely used in the treatment of acS and other diseases due to its advantages, such as improving therapeutic effects and reducing adverse reactions (21,22). at present, patients with cardiovascular diseases are likely to take an anti-platelet agent concomitantly with a statin (23,24). cYP3a4, which is one of the most important drug-metabolizing P450 isoforms, plays an important role in the biotransformation of many clinical drugs (25,26).…”

Section: Effects Of Ticagrelor or Prasugrel On The Protein Expressionmentioning

confidence: 99%

Evaluation of cytochrome P450 3A4‑mediated drug‑drug interaction potential between P2Y12 inhibitors and statins

et al. 2019

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Ticagrelor and prasugrel are widely used in the treatment of acute coronary syndrome. The co-administration of ticagrelor or prasugrel with statins in the clinic has already drawn a great deal of attention. The aims of the present study were to evaluate the safety and effectiveness, and guide the rational clinical use of, co-administration of ticagrelor or prasugrel with statins by exploring potential drug interactions. The activity of cytochrome P450 family 3 subfamily a member 4 (cYP3a4) was detected, and its protein and mrna expression levels were measured in a rat model and liver microsomes to evaluate the effect of the drug combinations on cYP3a4. High performance liquid chromatography, western blotting and reverse transcription-quantitative Pcr were used to perform these investigations. The in vitro experiments suggested that ticagrelor inhibited cYP3a4 activity, with ic 50 and inhibitor constant (K i) values of 68.74 and 26.47 µM, respectively; prasugrel also inhibited cYP3a4, activity with ic 50 and K i values of 16.24 and 10.84 µM, respectively. When different dosages of the antagonists were combined with simvastatin or atorvastatin, the metabolic rate was reduced more effectively at higher dosages when compared with lower dosages. an in vivo pharmacokinetic study demonstrated that the co-administration of ticagrelor or prasugrel with simvastatin caused an increase in the principal pharmacokinetic parameters of the probe drug dapsone [area under the concentration/time curve (auc) 0-t , auc 0-∞ and t 1/2 ] and a decrease in clearance compared with ticagrelor, prasugrel or simvastatin alone. Additional studies confirmed that the two investigated P2Y12 inhibitors were able to decrease the protein level of cYP3a4 by promoting protein degradation through the proteasomal pathway, and combination with statins such as simvastatin had a synergistic inhibitory effect on cYP3a4 activity. These results demonstrated that the co-administration of P2Y12 inhibitors with simvastatin could markedly inhibit the activity of CYP3A4, and these findings will further influence the assessment of the clinical effectiveness (reduced or enhanced efficacy) and safety (bleeding and rhabdomyolysis) in the clinic.

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“…Meanwhile, both inhibition and induction of CYP enzymes by BER were reported in recent years. Some reports pointed out that BER showed a powerful inhibitory effect on CYP3A activity (Zhi et al, ), and could inhibit the activities of CYP2E1 and CYP2D6 in a concentration‐dependent manner (Chen, Zhang, Dong, Gong, & Cui, ). Decreased activities of CYPs2D6, 2C9, and 3A4 were reported in humans after repeated treatment with BER (Guo et al, ).…”

Section: Introductionmentioning

confidence: 99%

Metabolism‐based herb–drug interaction of Corydalis Bungeanae Herba with berberine in vitro and in vivo in rats

Mao

Zhao

Wang

et al. 2019

Biomedical Chromatography

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Corynoline (CRL) and berberine (BER) are the major bioactive components found in traditional Chinese medicines Corydalis Bungeanae Herba (Corydalis bungeanae) and Coptidis Rhizoma, respectively. The two herbs serve as anti‐inflammatory agents and are generally applied to many prescriptions. The aims of the study were to evaluate herb–drug interaction of C. bungeanae with BER and to investigate the mechanisms of the interaction action. Pre‐treatment of BER caused reduction of plasma CRL in rats with increased formation of its three oxidative metabolites (M1–M3). Compared with the vehicle‐treated group, the peak concentration and area under the concentration–time curve of CRL decreased by ~60% (given CRL) and ~50% (given extracts) in rats pre‐treated with BER, respectively, along with 130 and 100% increases in apparent clearance. More M1–M3 were formed in liver microsomes of rats pretreated with BER (7 days) than in those pretreated with vehicle. Additionally, elevated activities of rCYPs2D2 and 1A2 (CYPs2D6 and 1A2) were observed in the BER‐induced group. Up‐regulated expression of hepatic rCYP2D2 (CYP2D6) was found in animals after 7 days of treatment of BER. The study illustrated that C. Bungeanae and BER produced metabolic herb–drug interaction and provided important information that combination of C. bungeanae with BER‐containing herbal medicines may encounter the risk of decreased efficacy of CRL.

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The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides

Cited by 34 publications

References 37 publications

hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells

hERG1 is involved in the pathophysiological process and inhibited by berberine in SKOV3 cells

Evaluation of cytochrome P450 3A4‑mediated drug‑drug interaction potential between P2Y12 inhibitors and statins

Metabolism‐based herb–drug interaction of Corydalis Bungeanae Herba with berberine in vitro and in vivo in rats

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