TABLE 1.

Metabolic activation of natural products in their toxicities.

Parents	Class	Herbal source	Reactive metabolites	Involved enzymes	Toxicities	References
Diosbulbin B	Furanoterpenoids	Dioscorea bulbifera	cis-Enedial	CYP3A4	Liver injury	Lin et al. (2014) Lin et al. (2016a)
8-Epidiosbulbin E acetate	Furanoterpenoids	Dioscorea bulbifera	cis-Enedial	CYP3A4	Liver injury	Lin et al. (2015); Lin et al. (2016b)
Diosbulbin B	Furanoterpenoids	Dioscorea bulbifera	cis-Enedial	CYP3A4	DNA Adduction	Lin et al. (2019)
8-Epidiosbulbin E acetate	Furanoterpenoids	Dioscorea bulbifera	cis-Enedial	CYP3A4	DNA Adduction	Lin et al. (2019)
4-Ipomeanol	Furanoterpenoids	Ceratocystis fimbriata Ellis	cis-Enedial	CYP450s monooxygenases	Pulmonary toxin	Buckpitt and Boyd, (1982)
4-Ipomeanol	Furanoterpenoids	Ceratocystis fimbriata Ellis	cis-Enedial	CYP4B	Pulmonary toxin	Parkinson et al. (2012)
4-Ipomeanol	Furanoterpenoids	Ceratocystis fimbriata Ellis	Enedial intermediate	CYP4B1	Pulmonary toxin	Baer et al. (2005); Parkinson et al. (2013); Verschoyle et al. (1993)
Teucrin A	Furanoterpenoids	Teucrium chamaedrys	Enedial	CYP450s	Liver injury	Druckova and Marnett, (2006)
Teuchamaedryn A	Furanoterpenoids	Teuchrium chamaedrys	Enedial	CYP450s	Liver injury	Lekehal et al. (1996)
Pulegone	Furanoterpenoids	Mentha haplocalyx	Menthofuran	CYP450s
Toosendanin	Furanoterpenoids	MeLia toosendan Sieb	Enedial intermediate	CYP 3A4	Liver injury	Yu et al. (2014)
Emodin	Anthraquinones	Polygoni multiflori	Quinone intermediates	CYP 3A	Hepatotoxicity	Jiang et al. (2018)
Aloe-Emodin	Anthraquinones	Polygoni multiflori	Quinone intermediates	Sulfotransferases	Cytotoxicity	Li et al. (2019a)
Physcion	Anthraquinones	Polygoni multiflori	Quinone intermediates	CYP450s	Hepatotoxicity	Qin et al. (2018)
Rhein	Anthraquinones	Polygoni multiflori	Quinone intermediates	CYP 2C9	Hepatotoxicity	Xu et al. (2018)
Chrysophanol	Anthraquinones	Polygoni multiflori	Quinone intermediates	CYP 1A2	Hepatotoxicity	Sun et al. (2018)
Lucidin-3-O-primiveroside	Anthraquinones	Rubia tinctorium Linn	Lucidin		DNA adduct or DNA lesion	Yockey et al. (2017)
Dauricine	Bisbenzylisoquinolines	Menispermum dauricum	Quinone methide intermediate	CYP 3A	Pulmonary toxicity	Jin et al. (2010); Jin et al. (2012)
Berbamine	Bisbenzylisoquinolines	Berberis amurensis	Quinone methide intermediate	CYP 3A4	Pulmonary toxicity	Sun et al. (2017); Sun et al. (2017)
Tetrandrine	Bisbenzylisoquinolines	Stephania tetrandra	Quinone methide intermediate	CYP450s	Pulmonary toxicity	Jin et al. (2011); Tian et al. (2016)
Tetrandrine	Bisbenzylisoquinolines	Stephania tetrandra	Quinone methide intermediate	CYP 3A5	Pulmonary toxicity	Tian et al. (2016)
Neferine	Bisbenzylisoquinolines	Nelumbo nucifera	Quinone methide intermediate	CYP3A4	Pulmonary toxicity	Shen et al. (2014)
3-Methylindole	Bisbenzylisoquinolines		3-Epoxy-3-methylindoline	CYP450s	Pulmonary disease	Skordos et al. (1998)
3-Methylindole	Bisbenzylisoquinolines		Reactive iminium	CYP450s	Pulmonary disease	Yost (1989); Huijzer et al. (1987)
Estragole	Alkenylbenzenes	Tarragon, sweet basil and sweet fennel	1′-Sulfooxyestragole	CYP 1A2, 2A6	Hepatocellular carcinomas	Jeurissen et al. (2007)
Safrole	Alkenylbenzenes	betel oil, sassafras oils, and camphor oil	1′-Sulfooxysafrole	CYP 2C9, 2A6, 2D6,2E1	Hepatocellular carcinomas	Jeurissen et al. (2004)
Methyleugenol	Alkenylbenzenes	Acacia senegal., Cinnamomum verum	1′-Sulfooxymethyleugenol	CYP 1A2, 2C9,2C19	Hepatocellular carcinomas	Jeurissen et al. (2006)
Apiol	Alkenylbenzenes	Parsley	1′-Sulfooxyapiol	CYP450s	DNA RNA adduct	Alajlouni et al. (2016)
Myristicin	Alkenylbenzenes	Myristica fragrans	1′-Hydroxymyristicin	CYP1A1	Cytotoxicity in HepG2	Zhu et al. (2019)
Quercetin	Flavonoids	Quercus Linn	Quinone and quinone methides	Liver extract	Mutagenicity	Vrijsen et al. (1990)
Fisetin	Flavonoids	Genus Citrus	Geraldol	Catechol-O-methyltransferase (COMT)	Cell cycle arrest	Poór et al. (2016)
Quercetin	Flavonoids	Quercus dentata	Isorhamnetin		Cell cycle arrest	Poór et al. (2016)
Fisetin	Flavonoids	Genus Citrus	Geraldol	Catechol-O-methyltransferase (COMT)	Cell cycle arrest	Poór et al. (2016)
Quercetin	Flavonoids	Quercus dentata	Isorhamnetin		Cell cycle arrest	Poór et al. (2016)
Kaempferol	Flavonoids	Kaempferia rotunda		Hepatic S9 microsomal fraction	Cytotoxicity	Soares et al. (2006)
Apigenin	Flavonoids	Apium graveolens	Luteolin	CYP 1A1,B1	Antiproliferative activity in breast cancer cells	Wilsher et al. (2017)
Tangeretin	Flavonoids	Genus Citrus	4′- OH-tangeretin	CYP 1A1,1B1	Antiproliferative activity in breast cancer cells	Surichan et al. (2018a)
Nobiletin	Flavonoids	Genus Citrus	NP1	CYP 1A1,1B1	Antiproliferative activity in breast cancer cells	Surichan et al. (2018b)
Nobiletin	Flavonoids	Genus Citrus	Demethylated nobiletin	CYP 1A1,1B1	Antiproliferative activity in breast cancer cells	Surichan et al. (2012)
Eupatorin	Flavonoids	Eupatorium fortunei	Unidentified metabolites	CYP 1A1,1B1	Antiproliferative activity in breast cancer cells	Androutsopoulos et al. (2008)
Diosmetin	Flavonoids	Spermadictyon suaveolens	Luteolin	CYP1	Antiproliferative activity in breast cancer cells	Androutsopoulos et al. (2009)
Luteolin	Flavonoids		ortho‐Benzoquinone metabolite	CYP450s	Cytotoxicity	Shi et al. (2015)
Arbutin	Iridoids	Arctostaphylos uva-ursi	Hydroquinone	Rat intestinal flora	Cytotoxicity	Kang et al. (2011)
Geniposide	Iridoids	Gardenia jasminoides Ellis	Genipin	Intestinal flora	Cytotoxicity in HepG2 cells	Kang et al. (2012); Li et al. (2019b)
Cycasin	Alkaloids	Cycas revoluta Thunb	Methyl azoxymethanol	Glycosylases	mutagenic	Morgan and Hoffmann, (1983)
Daidzin	Flavonoids	Glycine max	Daidzein, calycosin	Human Faecal suspension	Cytotoxicity in tumour cell lines	Kim et al. (1998)