Bisbenzylisoquinoline Alkaloids

Schiff, Paul L.

doi:10.1021/np9700174

Cited by 41 publications

(22 citation statements)

References 55 publications

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“…[5][6][7] Radix Stephaniae tetrandrae is a key ingredient of traditional Chinese medicine that has been broadly used for thousands of years in China to treat patients with arthritis, hypertension, inflammation and even silicosis. Studies have demonstrated that tetrandrine could block Ca 2þ channels 7,8 and possessed immunosuppressive property, 9 free radical scavenging effects 10 and even antiproliferative feature. 11 In addition, tetrandrine could regulate astrocyte activation through inhibiting IKKs-IkB-NF-kB signaling pathway.…”

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confidence: 99%

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Liu¹,

Gong²,

Mao³

et al. 2011

Intl Journal of Cancer

130

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Tetrandrine, a bisbenzylisoquinoline alkaloid component of broadly used traditional Chinese medicine, has antitumor effects against some cancers. In our study, we investigated the effects of tetrandrine on the human hepatocellular carcinoma (HCC) in vitro and in vivo. The results showed that tetrandrine effectively induced apoptosis of liver cancer cell in a dose-and time-dependent manner accompanied by alteration of cell morphology, chromatin fragmentation and caspase activation. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS), and ROS scavengers (LNAC and GSH) completely blocked the effects of tetrandrine-induced apoptosis, suggesting that the generation of ROS plays an important role in tetrandrine-induced apoptosis. Although the activities of JNK and ERK were inhibited significantly by tetrandrine treatment, JNK and ERK are not involved in the tetrandrine-induced apoptosis. In contrast, Akt activity was found to be closely related to tetrandrine-induced apoptosis. The data demonstrated that Akt activity inhibitor LY294002 synergistically promoted tetrandrine-induced apoptosis of HCC, whereas ectopic expression of Akt contrastly abrogated partial of the tetrandrine-induced apoptosis. These data suggest that Akt signal is the downstream event of ROS generation in the tetrandrine-induced HCC cell apoptosis. Moreover, the results of xenograft in nude mice were consistent with that of the in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of HCC as a regulator of ROS/Akt pathway.

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confidence: 99%

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Liu¹,

Gong²,

Mao³

et al. 2011

Intl Journal of Cancer

130

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“…To minimize free radical-induced damages and to repair damages occurred, many radical-related enzymes and antioxidants are developed. Several dimeric phenol families such as bisbenzylisoquinoline alkaloids (Curare alkaloids) [55], resveratrol dimers, depsides [56], and biflavonoids [6] are important antioxidants among natural products, but here we discuss only some dimeric natural products outside these scopes.…”

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confidence: 99%

Naturally Occurring Dimers from Chemical Perspective

Lian

2010

Chemistry & Biodiversity

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“…The majority of naturally occurring BBIQ alkaloids are mainly identified from families Menispermaceae, Ranunculaceae, Annonnaceae, and Moniaceae (Guha et al, 1979;Schiff, 1983Schiff, , 1987Schiff, , 1991. Bisbenzylisoquinoline alkaloids have been reported to show a variety of pharmacological activities (Schiff, 1991). Many herbs containing alkaloids have been used as traditional medicines in cultures in China, India, Japan, Chile, and other nations (Chang and Wu, 2005;Martínez et al, 1997;Koh et al, 2006;Amresh et al, 2008).…”

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Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice

Jin¹,

Dai²,

Chen³

et al. 2009

J Pharmacol Exp Ther

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Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. and has shown promising pharmacological activities with a great potential for clinic use. However, the adverse effects and toxicity of the alkaloid are unfortunately ignored. The objective of the current study was to evaluate the toxicity of dauricine in vitro and in vivo. Mice (CD-1) were treated intraperitoneally with dauricine at various doses, and sera and lung lavage fluids were collected after 24 h of treatment. No changes in serum aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were noticed, whereas a dose-dependent increase in lactate dehydrogenase activity was observed in lung lavage fluids. Ethidium-based staining studies showed that remarkable cells lost membrane integrity in the lungs of the animals treated with dauricine at 150 mg/kg. Histopathological evaluation of lungs of mice showed that dauricine at the same dose caused significant alveolar edema and hemorrhage. Exposure to dauricine at 40 M for 24 h resulted in up to 60% cell death in human lung cell lines BEAS-2B, WI-38, and A549. Ketoconazole showed protective effect on the pulmonary injury in mice given dauricine. A quinone methide metabolite of dauricine was identified in mouse lung microsomal incubations, and the presence of ketoconazole in the microsomal incubations suppressed the formation of the quinone methide metabolite. In conclusion, dauricine produced pulmonary injury in CD-1 mice. The pulmonary toxicity appears to depend on the metabolism of dauricine mediated by CYP3A. The electrophilic quinone methide metabolite probably plays an important role in the pulmonary toxicity induced by dauricine.

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Bisbenzylisoquinoline Alkaloids

Cited by 41 publications

References 55 publications

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Naturally Occurring Dimers from Chemical Perspective

Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice

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