In Vitro Cytotoxicity of Nonpolar Constituents from Different Parts of Kava Plant (<i>Piper methysticum</i>)

Jhoo, Jin‐Woo; Freeman, Jeremiah P.; Heinze, Thomas M.; Moody, Joanna D.; Schnackenberg, Laura K.; Beger, Richard D.; Dragull, Klaus; Tang, Chung-Shih; Ang, C. Y. W.

doi:10.1021/jf051853j

Cited by 62 publications

(57 citation statements)

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“…Jhoo et al (62) investigated in vitro cytotoxicity of kavalactones-containing fractions from different parts of kava plant (Piper methysticum) to HepG2. It was found that the hexane fraction of the root exhibited stronger cytotoxic effects than the fractions of root extracted by other solvents or extracts from the leaves and stem peelings of kava.…”

Section: Short-term Testsmentioning

confidence: 99%

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Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity. KeywordsKava; anti-anxiety herbal beverage; top-selling botanical; hepatotoxicity; metabolism; mechanism Kava, prepared from the rhizome of the kava tropical shrub plant, Piper methysticum Forst F., is a traditional beverage used for many centuries, especially at ceremonial activities in the South Pacific (1-6). During recent years, kava has been used in Europe for treatment of anxiety and nervous disorders such as stress and restlessness, and in the United States as a natural alternative to anti-anxiety drugs and sleeping pills (6). Kava sales totaled more than $ 100 million in 1998, being the fifth leading seller of the North American botanicals (7).The association between the use of kava products and hepatotoxicity has prompted many countries, including Germany, Switzerland, France, Canada, and the United Kingdom, to take regulatory actions, ranging from warning consumers to removing kava-containing products from the marketplace. On March 25, 2002, the Center for Food Safety and Applied Nutrition (CFSAN), U.S. Food and Drug Administration (FDA) issued a Consumer Advisory entitled "Kava-containing dietary supplements may be associated with severe liver injury" to the public (8, 9). Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it Address correspondence to Peter P. Fu, National Center for Toxicological Research, Jefferson, AR 72079. peter.fu@fda.hhs.gov; chanp@niehs.nih.gov. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript was banned in Germany, France, Switzerland, Australia, and Canada (10). In this review, human exposure and metabolism of kava are briefly addressed, recent findings on the toxicity of kava are reported, and possible mechanisms by which kava induces toxicity are described. CHEMICAL COMPOSITIONThe kava plant, belonging to the Piperacae family, is widely cultivated in the South Pacific.Kava is cultivated for its rootstock. Depending upon the amount of kavalactones contained in the resin, the rootstock shows different color, varying from white to dark yellow (2,5,6). Fresh kava rootstock contains about 80% water. Dried rootstock consists of about 43% starch, 20% fibers, 12% water, 3-4% proteins, 3% sugars, 3% minerals, ...

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Section: Short-term Testsmentioning

confidence: 99%

“…Jhoo et al (62) reported that kava enhanced the hypnotic effect of alcohol in mice. Liu et al (85) determined that alteration of cytochrome P450 expression level can affect the preneoplastic changes in the early stage of hepatocarcinogenesis in Sprague-Dawley rats.…”

Section: Alteration Of Cytochrome P450 Metabolizing Isozymes-it Has Bmentioning

confidence: 99%

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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“…Com relação a citotoxicidade, Jhoo et al (2006) encontraram nas frações aquosas da raiz de 79,6 a 102% de viabilidade celular, sendo o composto responsável pela citotoxicidade identificado, a flavokavaina B. Esses resultados estão de acordo com os resultados encontrados neste trabalho. Em todas as repetições, T1 e T2 apresentaram menor quantidade de conídios viáveis em comparação com o controle.…”

Section: Resultado E Discussãounclassified

“…Estes casos de hepatotoxicidade podem ser causados pelas kavalactonas por meio de três mecanismos: inibição do citocromo P450, redução da glutationa no rim, ou inibição da atividade da enzima ciclooxigenase (Clouatre, 2004). Muitos dos casos de hepatotoxicidade são relacionados ao consumo de produtos contendo extratos de kava preparados por métodos de extração com solventes (Jhoo et al, 2006). Assim, este trabalho mostrou a relevância do estudo das propriedades mutagênicas das plantas medicinais que, por serem consideradas "naturais" pela cultura popular, muitas vezes são utilizadas indiscriminadamente.…”

Section: Resultado E Discussãounclassified

Avaliação da mutagenicidade de Piper methysticum L. f. no sistema methG1 em Aspergillus nidulans

Palioto

Rocha

2013

Rev. bras. plantas med.

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Recebido para publicação em 05/11/2010 Aceito para publicação em 12/11/2012 RESUMO: O extrato seco da raiz de Piper methysticum L. f. Forster (PIPERACEAE), a kava-kava, é usado no tratamento de diversos problemas envolvendo ansiedade como um dos sintomas. Por não causar dependência, sedação e ter ação ansiolítica, muitas pessoas têm recorrido a kava-kava para auxiliá-las no emagrecimento. Isto pode levar ao consumo indiscriminado da planta e acarretar riscos, pois todo medicamento fitoterápico deve respeitar limites de doses. Um risco na utilização de plantas medicinais é a toxicidade e, dentro deste, a mutagenicidade. Como a mutagenicidade está relacionada com a carcinogenicidade tornase importante testar este potencial na kava-kava. Assim, o objetivo deste trabalho foi avaliar o potencial mutagênico do extrato seco da raiz de P. methysticum no sistema methG1 em Aspergillus nidulans. A linhagem utilizada foi a biA1methG1, auxotrófica para biotina e metionina. Conídios dormentes de colônias crescidas por cinco dias foram tratados com soluções da kavakava nas concentrações de 0,35 mg mL -1 e 3,5 mg mL -1 , e depois de 24h, semeados em meio seletivo contendo metionina, para análise dos sobreviventes, e sem metionina, para a análise dos mutantes. Os números de sobreviventes e mutantes dos tratamentos foram comparados aos do controle. Os resultados indicaram que o extrato da raiz da kava-kava é mutagênica, pois a freqüência de mutação dos tratamentos foi maior que da mutação espontânea, porém não ocorrendo diferença significativa entre as doses. Palavras-chave:Piper methysticum L. f., kava-kava, mutagenicidade, sistema methG1, Aspergillus nidulans ABSTRACT: Mutagenic evaluation of Piper methysticum L. f. in Aspergillus nidulans methG1 system. The dry root extract of Piper methysticum L. f. Forster (Piperaceae), kavakava, is used as to treat several health problems involving anxiety symptoms. As it causes no addiction, it can be applied as a sedative and anxiolytic. Many people have been relying on kava-kava as an auxiliary treatment. This can lead to an indiscriminate plant consumption and lead to risks, because all phytotherapic medications must observe dosage limits. One risk in the folk medicinal plant use is toxicity, and within it, mutagenicity. As mutagenicity is closely related to carcinogenicity, it is important to test the kava-kava mutagenicity potential. Thus, the purpose of this work was to test the mutagenicity of the dry root extract of P. methysticum in the methG1 system of Aspergillus nidulans. The bia1methG1 lineage, which is auxotrophic for biotine and methione, was used. Conidia from five-day-old colonies were collected and treated with kava-kava solutions at 0.35 mg mL -1 and 3.5 mg mL -1 concentrations and, after 24h, they were planted in selective growth medium with and without methione, in order to analyze the survivors and mutants, respectively. The number of survivors and mutants analyzed under effect of the treatments was compared with the control. The results indicated that the kava-kava d...

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“…Root and aereal parts of plants may exert different cytotoxic effects due to the active component contents and its distribution (Jhoo et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effects ofEryngium kotschyiandEryngium maritimumon Hep2, HepG2, Vero and U138 MG cell lines

Yurdakok¹,

Baydan²

2013

Pharmaceutical Biology

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Context: Eryngium maritimum L. and the endemic Eryngium kotschyi Boiss. of the Apiaceae family are used for antiinflammatory, antivenom, antinociceptive and diuretic purposes in folk medicine in Turkey.Objective: This study investigated the cytotoxic effects of the plant extracts belonging to Eryngium L. genus on various cell lines. Materials and methods: Cytotoxic activites of the lyophilized aqueous aereal and root parts of the plant extracts on human hepatocellular carcinoma (HepG2), human laryngeal epidermoid carcinoma (Hep2), human glioma (U138-MG) and African green monkey kidney epithelial (Vero) cell lines at 8.33-266.62 mg/ml concentrations were analyzed by lactate dehydrogenase (LDH) leakage and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) cell viability assays. Results: Inhibitory concentration 50 (IC 50 ) values were found 5100 mg/ml in most cases varying around 16.33-125.66 mg/ml. IC 50 values for E. kostchyi and E. maritimum root parts on Hep2 cells (32.86 and 30.25 mg/ml, respectively), E. kotschyi aereal, E. maritimum aereal and root parts on HepG2 cells (31.75, 32.42 and 35.01 mg/ml, respectively) by MTT assay were found to be close to the US National Cancer Institute (NCI) recommendations (IC 50 530 mg/ml) to define the antivity aganist cancer cells. The lowest IC 50 values according to the LDH method were observed in Hep2 cells and the highest in U138-MG cells. Root parts were found to be more toxic than aereal parts for both plants in both methods in general. Discussion and conclusion: Both plant extracts exerted cytotoxic activity aganist Hep2 and HepG2 cells, with low IC 50 values defining their promising anticancer property according to NCI; however, further analysis are needed to confirm their activity.

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In Vitro Cytotoxicity of Nonpolar Constituents from Different Parts of Kava Plant (Piper methysticum)

Cited by 62 publications

References 10 publications

Toxicity of Kava Kava

Toxicity of Kava Kava

Avaliação da mutagenicidade de Piper methysticum L. f. no sistema methG1 em Aspergillus nidulans

Cytotoxic effects ofEryngium kotschyiandEryngium maritimumon Hep2, HepG2, Vero and U138 MG cell lines

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