Table 2. Overview on natural compounds tested for hERG channel inhibition (alphabetically listed) a .
| Name | No. | Natural source* species (family) | hERG channel inhibition |
Ref. | ||
| Category | IC50 [μM]* | Assay type | ||||
| Alkaloids | ||||||
| Aconitine | 37 | Aconitum sp. (Ranunculaceae) | + | B | 80 and 106 | |
| ++ | 1.8 | C | 107 | |||
| ++ | 13.5 | D | 108 | |||
| Aconosine | 38 | Aconitum anthora L. (Ranunculaceae) | B | 80 and 106 | ||
| Acotoxicine | 39 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| Acotoxinine | 40 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Acovulparine | 41 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Ajacine | 42 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Ajmaline | 43 | ++ | 1.0 | A | 109 | |
| + | 42.3 | C | 109 | |||
| Allocryptopine | 44 | Corydalis decumbens (Thunb.) pers. (Papaveraceae) | + | 49.7 | A | 110 |
| Arecoline | 45 | ++ | 9.6 | A | 111 | |
| (–)-Argemonine | 46 | – | C | 112 | ||
| (–)-Asimilobine | 14 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | – | C | 48 | |
| Azaspiracid 1 | 47 | Azadinium sp. (Dinophyceae) | ++ | 0.8 | A | 113 |
| Azaspiracid 2 | 48 | Azadinium sp. (Dinophyceae) | ++ | 0.6 | A | 113 |
| Azaspiracid 3 | 49 | Azadinium sp. (Dinophyceae) | ++ | 0.8 | A | 113 |
| 14-Benzoylaconine 8-O-palmitate | 50 | Aconitum anthora L. (Ranunculaceae) | + | B | 80 | |
| Benzoylecgonine | 16 | Metabolite of cocaine | – | A | 114 | |
| Benzyltetrahydropalmatine | 51 | Corydalis ambigua Cham. & Schltdl. (Papaveraceae) | + | 22.4 | A | 110 |
| Berberine | 10 | Berberis sp. & Coptis sp. (Berberidaceae; Ranunculaceae) | ++ | 3.1 | A | 115 |
| ++ | 6.5 | A | 72 | |||
| + | 80 | C | 115 | |||
| + | ∼75 | C | 67 and 116 | |||
| Bisindolylmaleimide I | 52 | ++ | 0.8 | A | 117 | |
| (+)-Boldine | 53 | ++ | 19.3 | C | 112 | |
| (+)-Bulbocapnine | 54 | ++ | 7.4 | C | 112 | |
| Caffeine | 28 | – | A | 118 | ||
| (–)-Californidine | 55 | – | C | 112 | ||
| Capsaicin | 56 | Capsicum sp. (Solanaceae) | ++ | 17.5 | C | 119 |
| Cephaeline | 57 | Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae) | ++ | 5.3 | A | 49 |
| Changrolin | 58 | Dichroa febrifuga Lour (Hydrangeaceae) | + | 18.2 | A | 120 |
| Chelerythrine | 59 | ++ | 0.1 (EC50) | A | 117 | |
| Chelidonine | 60 | Chelidonium majus L. (Papaveraceae) | ++ | 1.0 | A | 72 |
| ++ | 11.5 | C | 112 | |||
| Cocaethylene | 17 | Metabolite of cocaine | ++ | 1.2 | A | 114 |
| Cocaine | 61 | ++ | 7.2 | A | 121 | |
| ++ | 4.4 | A | 114 | |||
| ++ | 8.7–14.4 | A | 122 | |||
| ++ | ∼4 | D | 123 | |||
| ++ | 5.6 | D | 124 | |||
| Codeine | 26 | – | >300 | A | 91 | |
| – | 97 | B | 92 | |||
| Coptisine | 12 | Chelidonium majus L., Coptis chinensis Franch., (Papaveraceae; Ranunculaceae) | + | 90.1 | A | 72 |
| – | C | 67 | ||||
| (+)-Corynoline | 62 | ++ | 7.1 | C | 112 | |
| Cyclovirobuxine D | 63 | Buxus microphylla Siebold & Zucc. (Buxaceae) | + | 19.7 | A | 125 |
| Dauricine | 64 | Menispermum dauricum DC. (Menispermaceae) | ++ | 3.5 | A | 126 |
| + | 16–33 | D | 127 | |||
| Daurisoline | 65 | Menispermum dauricum DC. (Menispermaceae) | ++ | 9.1/9.6 | A | 128 |
| Delcosine | 66 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Delectinine | 67 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| 14-Desacetyl-18-demethylpubescenine | 68 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| Dehydroevodiamine | 6 | Evodia rutaecarpa (Juss.) Hook. f. et Thoms. (Rutaceae) | ++ | C | 68 | |
| Dihydroberberine | 4 | Coptis chinensis Franch. (Ranunculaceae) | + | C | 66 and 67 | |
| Dihydrosanguinarine | 69 | – | C | 112 | ||
| Dolaconine | 70 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| Ecgonine methylester | 71 | Metabolite of cocaine | – | A | 114 | |
| Emetine | 72 | Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae) | + | 21.4 | A | 49 |
| – | C | 112 | ||||
| Ephedrine | 73 | – | A | 129 | ||
| – | C | 112 | ||||
| Epiberberine | 74 | Coptis chinensis Franch. (Ranunculaceae) | – | C | 67 | |
| (–)-Eschscholtzine | 75 | – | C | 112 | ||
| Flavopereirine | 76 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Galanthamine | 77 | – | 760 | A | 130 | |
| – | C | 112 | ||||
| – | D | 130 | ||||
| (–)-Galanthine | 78 | – | C | 112 | ||
| Gigactonine | 79 | Aconitum anthora L. (Ranunculaceae) | + | B | 80 | |
| Guan-fu base A | 80 | Aconitum coreanum (H.Lév.) Rapaics (Ranunculaceae) | – | 1640 | A | 131 |
| Guan-fu base G | 81 | Aconitum coreanum (H.Lév.) Rapaics (Ranunculaceae) | + | 17.9 | A | 131 |
| (+)-Haemanthamine | 82 | – | C | 112 | ||
| Harmine | 83 | + | C | 112 | ||
| Hetisinone | 84 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| (+)-Hippeastidine | 85 | + | C | 112 | ||
| Hortiamine | 7 | Evodia rutaecarpa (Juss.) Hook. f. et Thoms. (Rutaceae) | ++ | C | 68 | |
| 10-Hydroxy-8-O-methyltalatizamine | 86 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Ibogaine | 87 | Tabernanthe iboga Baill. (Apocynaceae) | ++ | 3.53 | A | 132 |
| Indirubin | 88 | – | C | 112 | ||
| Isotalatizidine | 89 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Jatrorrhizine | 90 | Coptis chinensis Franch. (Ranunculaceae) | – | C | 67 | |
| Karacoline | 91 | Aconitum napellus subsp. Firmum (Rchb.) Gáyer (Ranunculaceae) | – | A | 106 | |
| Liensinine | 92 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | – | A | 48 and 133 | |
| Lobeline | 93 | Lobelia inflata L. (Campanulaceae) | ++ | 0.3 | A | 134 |
| Lochneram | 94 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Lycoctonine | 95 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Matrine | 20 | Sophora flavescens Aiton (Fabaceae) | – | A | 89 | |
| – | 411 | B | 135 | |||
| 18-Methoxycoronaridine | 96 | Semisynthetic | + | >50 | A | 132 |
| 10-Methoxypanarine | 97 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Methylecgonidine | 98 | Metabolite of cocaine | – | 171.7 | A | 114 |
| N-Methylemetine | 99 | Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae) | – | A | 49 | |
| (+)-N-Methyllaurotetanine | 100 | ++ | 3.4 | C | 112 | |
| N 12-Methylnukuhivensium | 101 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | ++ | 0.4 | B | 81 |
| O-Methylpsychotrine | 102 | Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae) | + | 12.5 | A | 49 |
| Morphine | 25 | – | >1000 | A | 91 | |
| Napelline | 103 | Aconitum napellus subsp. Firmum (Rchb.) Gáyer (Ranunculaceae) | – | A | 106 | |
| Neferine | 104 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | ++ | 7.4 | A | 133 and 136 |
| (–)-Neocaryachine | 105 | – | C | 112 | ||
| Neoline | 106 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| Neolinine | 107 | Aconitum anthora L. (Ranunculaceae) | + | B | 80 and 106 | |
| Nicotine | 108 | ++ | 16.8 | C | 137 | |
| ++ | D | 138 | ||||
| ++ | 1.3 | D | 139 | |||
| Noribogaine | 109 | Metabolite of ibogaine | ++ | 2.9 | A | 132 |
| N-Nornuciferine | 110 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | ++ | 9.8 | A | 48 |
| O-Nornuciferine | 15 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | ++ | 7.9 | A | 48 |
| Norsandwicine | 111 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Nortueiaoine | 112 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Noscapine | 113 | – | C | 112 | ||
| Nuciferine | 114 | Nelumbo nucifera Gaertn. (Nelumbonaceae) | ++ | 2.9 | A | 48 |
| Nukuhivensium | 115 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | ++ | 4 | B | 81 |
| 8-Oxoberberine | 11 | – | C | 112 | ||
| 8-Oxocoptisine | 13 | – | C | 112 | ||
| Oxymatrine | 21 | Sophora flavescens Aiton (Fabaceae) | – | 665 | A | 90 |
| – | B | 89 | ||||
| Palmatine | 116 | Coptis chinensis Franch. (Ranunculaceae) | + | C | 67 | |
| Papaverine | 117 | Papaver somniferum L. (Papaveraceae) | ++ | 7.3 | A | 129 |
| ++ | 0.6 | A | 140 | |||
| + | 71.0 | C | 141 | |||
| + | 30.0 | C | 140 | |||
| Piperine | 5 | Piper nigrum L. (Piperaceae) | – | >300 | C | 66 |
| Protopine | 118 | Eschscholzia californica Cham. (Papaveraceae) | ++ | 4.1 | C | 112 |
| Psychotrine | 119 | Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae) | – | C | 49 | |
| Pyroaconitine | 120 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Quinidine | 9 | ++ | 0.4 | A | 142 | |
| ++ | 3.2 | B | 143 | |||
| ++ | 4.6 | C | 85 | |||
| ++ | 0.7 | D | 108 | |||
| Quinine | 8 | + | 57.0 | C | 85 | |
| (–)-Remerine | 121 | + | C | 112 | ||
| Reserpine | 122 | ++ | 1.9 | B | 144 | |
| ++ | 7.6 | C | 112 | |||
| ++ | 4.9 | D | 144 | |||
| (+)-Reticuline | 123 | + | C | 112 | ||
| Rhynchophylline | 124 | Uncaria rhynchophylla (Miq.) Miq. ex Havil. (Rubiaceae) | – | 773 | C | 145 |
| (+)-Salutaridine | 27 | – | C | 112 | ||
| Sandwicine | 125 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Sanguinarine | 126 | Chelidonium majus L. (Papaveraceae) | ++ | 0.9 | A | 72 |
| Senbusine A | 127 | Aconitum napellus subsp. Firmum (Rchb.) Gáyer (Ranunculaceae) | – | A | 106 | |
| Senbusine C | 128 | Aconitum napellus subsp. Firmum (Rchb.) Gáyer (Ranunculaceae) | – | A | 106 | |
| Septentriodine | 129 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Songoramine | 130 | Aconitum anthora L. (Ranunculaceae) | + | B | 80 | |
| Songorine | 131 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 and 106 | |
| Sophocarpine | 18 | Sophora flavescens Aiton (Fabaceae) | – | 100–300 | A | 88 |
| Sophoridine | 19 | Sophora flavescens Aiton (Fabaceae) | – | >300 | A | 87 |
| (–)-Sparteine | 132 | – | C | 112 | ||
| Spegatrine | 133 | Rauwolfia nukuhivensis (Fosberg & Sachet) Lorence & Butaud (Apocynaceae) | + | B | 81 | |
| Swatinine | 134 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| Takaosamine | 135 | Aconitum anthora L. (Ranunculaceae) | – | B | 80 | |
| (+)-Tazettine | 136 | – | C | 112 | ||
| Tetrahydroberberine | 137 | Coptis chinensis Franch. (Ranunculaceae) | – | C | 67 | |
| Theobromine | 30 | – | B | 92 | ||
| Theophylline | 29 | – | C | 141 | ||
| Tryptanthrin | 24 | – | C | 112 | ||
| Vasicine | 22 | – | C | 112 | ||
| Vasicinone | 23 | – | C | 112 | ||
| Voacangine | 138 | Metabolite of ibogaine | ++ | 0.3/2.3 | A | 19 and 132 |
| Yohimbine | 139 | + | 67.1 | C | 112 | |
| Non-alkaloids | ||||||
| Acacetin | 140 | Saussurea laniceps Hand.-Mazz. (Asteraceae) | + | 32.4 | A | 146 |
| Allitridin | 141 | Allium sativum L. (Amaryllidaceae) | + | 19.6 | A | 147 and 148 |
| Apigenin | 142 | – | C | 93 | ||
| Bergapten | 143 | – | C | 93 | ||
| (+)-Catechin | 144 | – | C | 66 | ||
| Celastrol | 145 | ++ | A | 149 | ||
| Chrysin | 146 | – | C | 93 | ||
| Coumarin | 147 | – | C | 93 | ||
| Curcumin | 34 | ++ | 5.6/4.9 | A | 99–101 | |
| + | 22 | B | 144 | |||
| Digitoxin | 148 | – | A | 150 | ||
| Digoxigenin | 149 | – | A | 150 | ||
| Digoxin | 150 | – | A | 150 | ||
| Dihydroartemisinin | 151 | ++ | 9.6 | A | 151 | |
| 5,7-Dihydroxy-6-methoxyflavone | 152 | Galenia africana L. (Aizoaceae) | – | C | 69 | |
| (2R)-6,7-Dimethoxyflavanone | 153 | Galenia africana L. (Aizoaceae) | – | C | 69 | |
| 6,7-Dimethoxyflavone | 154 | Galenia africana L. (Aizoaceae) | – | C | 69 | |
| 7,8-Dimethoxyflavone | 155 | Galenia africana L. (Aizoaceae) | – | C | 69 | |
| EGCG | 33 | Camellia sinensis (L.) Kuntze (Theaceae) | ++ | 6.0 | A | 97 |
| – | B | 98 | ||||
| ++ | 20.5 | C | 97 | |||
| Ellagic acid | 156 | – | C | 66 | ||
| 7-Ethoxycoumarin | 157 | – | C | 93 | ||
| (4′Z)-Excoecariatoxin | 3 | Gnidia polycephala Gilg ex Engl. (Thymelaeaceae) | ++ | C | 70 | |
| Fisetin | 158 | – | C | 93 | ||
| Flavone | 159 | – | C | 93 | ||
| Galangin | 160 | – | C | 93 | ||
| Gallic acid | 161 | – | C | 66 | ||
| Ginsenoside Rb1 | 162 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Rc | 163 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Re | 164 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Rf | 165 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Rg1 | 166 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Rg3 | 35 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Ginsenoside Rh2 | 167 | Panax ginseng C.A.Mey. (Araliaceae) | – | C | 103 | |
| Glycyrrhetinic acid | 168 | – | C | 152 | ||
| Hesperetin | 169 | Citrus sp. (Rutaceae) | – | 288.8 | C | 93 |
| – | 267.4 | C | 153 | |||
| Hesperidin | 170 | – | C | 93 | ||
| Hirsutenone | 171 | Alnus japonica (Thunb.) Steud. (Betulaceae) | + | 14.9 | B | 154 |
| Mallotoxin | 36 | Mallotus philippensis (Lam.) Müll.Arg. (Euphorbiaceae) | – | B | 105 | |
| Methoxsalen | 172 | – | C | 93 | ||
| 7,8-(Methylenedioxy) flavone | 173 | Galenia africana L. (Aizoaceae) | – | C | 69 | |
| Morin | 174 | – | 111.4 | C | 93 | |
| Myricetin | 175 | – | C | 93 | ||
| Naringenin | 31 | Citrus sp. (Rutaceae) | + | 36.5 | A | 93 |
| – | 102.6 | C | 94 | |||
| – | 102.3 | C | 93 | |||
| – | 173.3 | C | 95 | |||
| Naringin | 32 | – | C | 93 | ||
| Neohesperidin | 176 | – | C | 93 | ||
| Novel daphnane-type diterpenoid orthoester | 2 | Gnidia polycephala Gilg ex Engl. (Thymelaeaceae) | + | C | 70 | |
| Ouabain | 177 | – | D | 108 | ||
| Oxypeucedanin | 178 | Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (Apiaceae) | – | A | 155 | |
| Paeoniflorin | 179 | Paeonia lactiflora Pall. (Paeoniaceae) | – | A | 156 | |
| Phorbol 12-myristate 13-acetate | 180 | – | C, D | 157 | ||
| Psoralen | 181 | – | C | 93 | ||
| Quercetin | 182 | – | C | 93 | ||
| Resveratrol | 183 | Fresh grape skin and red wine | – | A | 129 | |
| – | D | 158 | ||||
| Rutin | 184 | – | C | 93 | ||
| Scopoletin | 185 | – | C | 93 | ||
| Tanshinone IIA | 186 | Salvia miltiorrhiza Bunge (Lamiaceae) | – | A | 159 | |
| Taxifolin 3-O-β-d-glucopyranoside | 187 | Rhododendron mucronulatum Turcz. (Ericaceae) | ++ | 9.6 (EC50) | B | 160 |
| 5,7,4′-Trimethylapigenin | 188 | + | 18.4–31.9 | A | 161 | |
| Umbelliferone | 189 | – | C | 93 | ||
| Yuanhuacine | 1 | Gnidia polycephala Gilg ex Engl. (Thymelaeaceae) | ++ | C | 70 | |
a* if provided in original study; ++ strong hERG block; + moderate hERG block; – no hERG block; A = whole-cell patch-clamp assay using HEK293 cells; B = whole-cell patch-clamp assay using CHO cells; C = two-microelectrode voltage-clamp assay using Xenopus oocytes; D = ex vivo (e.g. guinea pigs' hearts) or others.