Abstract
Aim
The plant species reported here are traditionally used in Northern Peru for a wide range of illnesses. Most remedies are prepared as ethanol or aqueous extracts and then ingested. The aim of this study was to evaluate the potential toxicity of these extracts.
Materials and methods
The toxicity of ethanolic and water extracts of 341 plant species was determined using a Brine-Shrimp assay.
Results
Overall 24% of the species in water extract and 76% of the species in alcoholic extract showed elevated toxicity levels to brine-shrimp. Although in most cases multiple extracts of the same species showed very similar toxicity values, in some cases the toxicity of different extracts of the same species varied from non-toxic to highly toxic.
Conclusions
Traditional preparation methods take different toxicity levels in aqueous and ethanol extracts into account when choosing the appropriate solvent for the preparation of a remedy.
Keywords: Medicinal Plants, Ethnobotany, Brine Shrimp, Artemia salina, Toxicity, Northern Peru
1. Introduction
In many developing countries, Traditional Medicine (TM) is commonly used as it is an accessible and affordable treatment (WHO, 1999a,b; 2002), while Complementary Alternative Medicine (CAM) is popular in developed countries (WHO, 1998; UNCCD 2000).
Peru is a prime example for a developing country rich in biodiversity, with a millennia old tradition of curers using the rich flora. Many of same plants are still being used nowadays. Northern Peru is believed to be the center of the Central Andean Health Axis (Camino, 1992), and TM practices in the whole Andean region are part of everyday life (Bussmann and Sharon, 2006; De Feo, 1992; Joralemon and Sharon, 1993; Polia, 1988; Revene et al., 2008). Peru's Social Security System recently implemented a National Program in Complementary Medicine in clinics and hospitals (EsSalud, 2000). The efficacy and potential toxicity of remedies employed in folk medicine do however have to be scientifically evaluated (Baker et al., 1995; Cox and Balick, 1994; Elisabetsky and Castilhos, 1990; Farnsworth et al., 1985; Muñoz and Sauvain, 2002).
A wide variety of studies have reported that some are bioactive (e.g. Perumal Samy and Ignacimuthu, 2000), but potentially active compounds have been isolated only from a few of the plants tested (D'Agostino et al., 1995a,b; Okuyama et al., 1994; Rodriguez et al. 1994; Umana and Castro, 1990). In contrast, crude medicinal activities have been investigated for a wide variety of plants (e.g. Bussmann et al., 2008, 2009a,b, 2010; Hammond et al., 1998, Lee at al., 1999; Neto et al., 2002; Villegas et al., 1997). But while toxicity assays are available for many countries (e.g. Argentina (Bustos et al., 1996; Hernández et al., 2000), Bahrain (Taha and Alsayed, 2000), Bangladesh (Costa-Lotufo et al., 2005), Brazil (Hammer and Johns, 1993; Alves et al., 2000; Holetz et al., 2002; Santos Piemanta et al., 2003; Quignard et al., 2004; Ferreira de Lima et al., 2006; Suffredini et al., 2006; dos Santos et al., 2007), Canada (McCuthcheon, 1992), Chile (Cuadra et al., 2005), China (Duffy and Power, 2001), Cuba (Martinez et al., 1996; Logarto Parra et al., 2001), Ecuador (Guerrero et al., 2003), Guatemala (Cáceres et al., 1993a, b, 1998; Michel et al., 2007), Honduras (Lenz et al., 1998), India (Padmaja et al., 2002), Kenya (Kirira et al. 2006; Wanyoike et al., 2004), Mexico (Sánchez-Medina et al., 2001), Nicaragua (Coe et al. 2010), Nigeria (Ajaiyeoba et al., 2006), Panama (Sánchez et al., 1993), Papua New Guinea (Nick et al., 1995), Philippines (Horgen et al., 2001), Uruguay (González et al., 1993), USA (Turker and Camper, 2002; Badisa et al., 2007; Van Slambrouck et al., 2007), no data exists on the potential toxicity of Peruvian medicinal species.
In this communication we report on brine-shrimp toxicity assays for 341 plant species ingested for a wide range of traditional uses. The brine shrimp, Artemia sp., Artemiidae, are small invertebrates occurring in sea-water and other saline ecosystems. Artemia is frequently used as agent in laboratory assays to determine toxicity values by estimating LC50 values (median lethal concentration) (Meyer et al., 1982; McLaughlin et al., 1991; Cepleanu et al., 1994, Coe et al., 2010).
2. Materials and Methods
2.1. Plant Material
Plants for the presented assays were collected in Northern Peru (Fig. 1) in the field, in markets, and at the homes of traditional healers (curanderos) during March–April and June–August 2009, and January–February 2010. The specimens are registered under the collection series “JP”, “ACR,” “KMM,” and AKT”. Vouchers of all specimens were deposited at the Herbarium Truxillense (HUT, Universidad Nacional de Trujillo), and Herbario Antenor Orrego (HAO, Universidad Privada Antenor Orrego, Trujillo). In recognition of Peru's rights under the Convention on Biological Diversity, most notably with regard to the conservation of genetic resources in the framework of a study treating medicinal plants, the identification of the plant material was conducted entirely in Peru. No plant material was exported in any form whatsoever.
2.2. Nomenclature
The nomenclature of plant families, genera, and species follows the Catalogue of the Flowering Plants and Gymnosperms of Peru (Brako and Zarucchi, 1993) and the Catalogue of the Vascular Plants of Ecuador (Jørgensen and León-Yanez, 1999). The nomenclature was compared to the TROPICOS database (Tropicos, 2010). Species were identified using the available volumes of the Flora of Peru (McBride, 1936–1981), as well as Jørgensen and Ulloa Ulloa (1994), Pestalozzi (1998) and Ulloa Ulloa and Jørgensen (1993), and the available volumes of the Flora of Ecuador (Sparre and Harling, 1978–2010), and reference material in the herbaria HUT and HAO.
2.3. Preparation of Extracts
For each species tested, above ground material (in case of trees leaves and) was collected, and the entire material used for extract preparation. This corroborates with the traditional preparation (Bussmann and Sharon 2006). Plant material was dried at 35 °C for three days. After drying, the material was ground with an industrial grinder, and 2 samples of 5 g. of plant material each were weighted out. One sample was submerged in 100 ml of 96 % ethanol and left to macerate for 7 days, while another sample was submerged in 100 ml of boiling distilled water and left to macerate for 24 h. After maceration the plant material was filtered and 100 ml 96 % ethanol was added to the water extracts to allow faster solvent removal. The solvent was then evaporated to complete dryness using a standard Buchi rotary-evaporator. The resulting dry extracts were re-suspended in 5 ml distilled water. In order to determine the real concentration of each extract, 1ml of previous homogenization of the respective extracts was removed and again completely oven-dried and then weighed to determine amount of extract per ml of final solution. The remaining extract was used for MIC assays.
2.4. Brine shrimp hatching
Eggs of brine shrimp (Artemia sp., Artemiidae) were purchased from Carolina Biological Supply (Burlington, NC, USA) and were incubated for 48 h in a culture vessel (15 × 15 × 15 cm) containing saltwater (1% NaCl) prepared from nitrate, phosphate, and silicate-free sea-salt and distilled water (35 g/l) at 25°C under constant illumination. The saltwater solution was aerated continuously during incubation with an aquarium air pump). After 48 h the Nauplius-larvae were collected from the culture vessel.
2.5. Brine shrimp lethality assay
The brine shrimp lethality assay (BSLA) was used to determine if the plant extracts of medicinal species were cytotoxic (Meyer et al., 1982; McLaughlin et al., 1991; Cepleanu et al., 1994, Coe et al., 2010). Plant extracts were diluted to concentrations of 1000; 500; 250; 125; 62.5; 31.25; 0 (μg/ml). Ten brine shrimp larvae were placed in each vial using a plastic pipette with a 2 mm diameter tip. The larvae were released under the surface of the solution to avoid killing them by trapping air under their carapaces. Survivors were counted under the stereomicroscope after 24 h, and the percent death at each dose and control was determined. All assays were run in triplicate. Vials with brine-shrimp in salt-water, and vials treated with 96 % Ethanol were used as controls.
2.6. Data analysis
The mean results of brine shrimp mortality were plotted against the logarithms of concentrations using the Probit Analysis tool of the NCSS statistical software package from which the median lethal concentration (LC50) at 95% confidence intervals (CI) were calculated according to the method of Finney (1971). Biological activity using the brine shrimp assay was recorded as the concentration when 50% of the larvae were killed within 24h of contact with the extract. LC50 values below 249 μg/ml were considered as highly toxic, 250–499 μg/ml as median toxicity and 500–1000 μg/ml as light toxicity. Values above 1000 μg/ml were regarded as non-toxic.
3. Results and Discussion
The Brine shrimp lethality activity of 501 aqueous and ethanolic extracts of 341 plant species belonging to 218 genera of 91 families used in Peruvian traditional medicine was tested. The results are shown in Tab. 1. The aqueous extracts of 55 species showed high toxicity values (LC50 below 249 μg/ml), 18 species showed median toxicity (LC50 250–499 μg/ml) and 18 low toxicity (LC50 500–1000 μg/ml). The alcoholic extracts proved to be much more toxic: 220 species showed high toxicity values (LC50 below 249 μg/ml, with 37 species having toxicity levels of >1μg/ml), 43 species showed median toxicity (LC50 250–499 μg/ml) and 23 species low toxicity (LC50 500–1000 μg/ml). Over 24% of the aqueous extracts and 76% of the alcoholic extracts showed elevated toxicity levels to brine-shrimp. Traditional preparation methods are taking this into account – most remedies are prepared as simple water extracts, thus avoiding potential toxic effects. Excellent examples where the water extracts are non-toxic, while the ethanolic extracts show high toxicity are Ocimum basilicum L., Salvia sp., or Laccopetalum giganteum (Wedd.) Ulbrich,. In contrast, Cinchona officinalis L. ethanolic extracts were nontoxic, and are traditionally used, while the highly toxic water extract has no traditional use.
Table 1.
Col# | NCSS code | Common name | Family | Scientific name | LC50 μg/ml Aqueous | 5–95% CI μg/ml | LC50 μg/ml Ethanol | 5–95% CI μg/ml | Traditional use (O=oral, T=topical; Traditional preparation (A=aqueous, E=ethanolic) |
---|---|---|---|---|---|---|---|---|---|
ACR91 | c166 | Culantrillo | Adiantaceae | Adiantum concinnum Willd. | 1131 | 64–>10000 | 4 | 0.01–1344 | OA |
AKT1226 | c303 | Cochayuyo | Algae | Gigartina sp. | >10000 | >10000 | >10000 | >10000 | OA |
ACR149, KMM395 | c93 | Moradilla Blanca | Amaranthaceae | Alternanthera porrigens (Jacquin) Kuntze | >10000 | >10000 | 130 | 21–780 | OA/TA |
KMM468 | c195 | Sanguinara | Amaranthaceae | Alternanthera sp. | >10000 | 2–>10000 | 42 | 0.4–4034 | OA/TA |
ACR103 | c533 | Hierba de Oso | Amaranthaceae | Alternanthera villosa Kunth | >10000 | >10000 | OA/TA | ||
ACR191 | c40 | Siempre viva (corta) | Amaranthaceae | Gomphrena globosa L. | >10000 | >10000 | 6.7 | 0.001–3539 | OA |
ACR162 | c242 | Color | Amaranthaceae | Iresine herbstii Hook. | >10000 | >10000 | 0.2 | >10000 | OA |
ACR119, ACR138 | c298 | Para Para | Amaryllidaceae | Eustephia coccinea Cav. | 611 | 34–>10000 | 530 | 118–5417 | OA/TA |
ACR77 | c654 | Chacur | Anacardiaceae | Mauria heterophylla Kunth | 35 | >10000 | OA/TA | ||
KMM404 | c285 | Molle | Anacardiaceae | Schinus molle L. | >10000 | >10000 | >10000 | >10000 | OA/OE |
ACR81 | c268 | Guanabana | Annonaceae | Annona muricata L. | >10000 | >10000 | >10000 | >10000 | OA |
KMM566 | c49 | Bisnaga | Apiaceae | Ammi visnaga (L.) Lam. cf. | 8467 | 31–>10000 | 131 | 18–942 | TA |
KMM439, ACR22 | c80 | Apio del campo | Apiaceae | Apium graveolens L. | 171 | 28–1024 | 25 | 2–248 | OA/TA |
KMM466 | c702 | Ricacha de zorro | Apiaceae | Arracacia xanthorrhiza Bancr. | 0.05 | 0.01–333 | TA | ||
KMM548 | c208 | Cilantro | Apiaceae | Coriandrum sativum L. | 22 | 0.1–>10000 | 0.015 | >10000 | TA |
KMM409 | c217 | Hinojo | Apiaceae | Foeniculum vulgare Mill. | >10000 | >10000 | 2.75 | 0.1–16904 | OA |
ACR82 | c272 | Hinojo | Apiaceae | Foeniculum vulgare Mill. | >10000 | >10000 | >10000 | >10000 | OA |
KMM467 | c91 | Sombrero | Apiaceae | Hydrocotyle globiflora Ruiz. & Pav. | >10000 | 857–>10000 | 185 | >10000 | TA |
AKT1196 | c541 | Hornamo Toro | Apiaceae | Niphogeton dissecta J.F. Macbr. | 606 | >10000 | OA/TA | ||
AKT1217 | c663 | Bejuco colambo | Apocynaceae | Mandevilla antennacea K. Schum. | >10000 | >10000 | TA | ||
AKT1221 | c235 | Bejuco negro | Apocynaceae | Mandevilla cf. trianae Woodson | >10000 | >10000 | TA | ||
ACR34 | c28 | Venenosa/Laurel | Apocynaceae | Nerium oleander L. | 831 | 86–7988 | 71 | 62–2602 | TA |
KMM416 | c341 | Maichil | Apocynaceae | Thevetia peruviana K. Schum. | >10000 | >10000 | >10000 | >10000 | OA/OE |
ACR192 | c76 | Cuncuno | Apocynaceae | Vallesa glabra (Cav.) Link. | 3486 | 144–>10000 | 1000 | 4–>10000 | OA |
KMM513, AKT1179 | c39 | Guayusa | Aquifoliaceae | Ilex guayusa Loes. | >10000 | >10000 | 300 | 55–1624 | OA |
KMM486 | c265 | Patecina negra | Aracaceae | Anthurium sp. | >10000 | >10000 | >10000 | >10000 | OA |
KMM445, ACR59 | c343 | Maqui Maqui | Araliaceae | Oreopanax eriocephalus Harms | >10000 | >10000 | 0.00001 | >10000 | OA/TA |
KMM563 | c230 | Bejuco del Aire | Aristolochiaceae | Aristolochia cf. ruiziana Duch. | >10000 | >10000 | 8680 | 0.07–>10000 | OA |
AKT1127 | c148 | Juan Alonzo/ Espina de Perro | Asteraceae | Acanthoxanthium spinosum (L.) Fourr. | 263 | 32–2134 | 290 | 51–1640 | OA |
AKT1188 | c123, c193 | Milenrama | Asteraceae | Achillea millefolium L. | 34 | 3–308 | 487 | 16–14543 | OA/TA |
ACR139 | c474 | Milenrama | Asteraceae | Achillea millefolium L. | 34 | 3–311 | OA/TA | ||
AKT1199, ACR2 | c240 | Hierba (o Flor) de Ishpingo | Asteraceae | Achyrocline alata (Kunth) DC | >10000 | >10000 | >10000 | >10000 | TA |
KMM547 | c65 | Espino de Hoja | Asteraceae | Achyrocline sp. | 40154 | >10000 | 79 | 23–384 | TA |
ACR11 | c543 | Marco o Altamisa | Asteraceae | Ambrosia peruviana Willd. | 14320 | >10000 | TA | ||
AKT1099, KMM432 | c146 | Ajenco | Asteraceae | Artemisia absinhitum L. | 93 | 15–557 | >10000 | >10000 | OA/TA |
AKT1144, KMM421, ACR78 | c257 | Carqueja | Asteraceae | Baccharis genistelloides (Lam.) Pers. | 1261 | >10000 | 1 | >10000 | OA |
KMM556 | c94 | Pega Pega | Asteraceae | Baccharis glutinosa Pers. | 4395 | 113–>10000 | 62 | 10–367 | OA |
AKT1126 | c241 | Cedron | Asteraceae | Baccharis salicifolia (Ruiz. & Pav.) Pers | >10000 | >10000 | 1742 | 0.07–>10000 | TA |
KMM562 | c26 | Chilca chica | Asteraceae | Baccharis sp | >10000 | 1432–>10000 | 155 | 32–735 | OA |
KMM498 | c204 | Chilca | Asteraceae | Baccharis sp. | >10000 | 341–>10000 | 0.4 | >10000 | OA |
KMM427, KMM469, ACR177, ACR58, KMM552 | c143 | Amor seco | Asteraceae | Bidens pilosa L. | >10000 | >10000 | 157 | 24–995 | OA/TA |
KMM446 | c160 | Arquitecta | Asteraceae | Chersodoma deltoidea M.O. Dillon & Sagast. | >10000 | >10000 | 113 | 22–576 | OA |
ACR46 | c317 | Arquitecta | Asteraceae | Chersodoma deltoidea M.O. Dillon & Sagast. | 0.1 | 0.1–100 | >10000 | >10000 | OA |
ACR113, KMM555 | c350 | Asma Chilca | Asteraceae | Chromolaena sp. | 4017 | 49–>10000 | 16 | 5–1824 | OA |
KMM434 | c300 | Huaman pinta | Asteraceae | Chuquiraga spinosa D. Don. ssp. humanpita C. Ezcurra | >10000 | >10000 | 1.1 | 0.1–>10000 | OA |
ACR85, KMM551 | c128 | Amaro/ Padre amaro | Asteraceae | Chuquiraga weberbaueri Tovar | >10000 | >10000 | 0.25 | 61–2804 | OA |
KMM414 | c286 | Alcachofa | Asteraceae | Cynara cardunclus L. | >10000 | >10000 | 21 | >10000 | OA |
ACR124, ACR153, KMM478, AKT1145, AKT1192 | c42 | Gato Simuro | Asteraceae | Diplostephium sagasteguii Cuatrec. | >10000 | >10000 | 0.004 | 0.001–>10000 | OA/TA |
KMM412 | c329 | Mata gusanos | Asteraceae | Flaveria bidentis (L.) Kuntze | >10000 | >10000 | OA | ||
KMM393, ACR41 | c188 | Lechugilla | Asteraceae | Gnaphalium americanum Mill. | >10000 | >10000 | 1311 | >10000 | OA |
AKT1174, ACR63 | c104 | Palmilla | Asteraceae | Loricaria cf. ferruginea Wedd. | >10000 | >10000 | 15 | 0.8–276 | TA |
KMM473 | c304 | Palma | Asteraceae | Loricaria pauciflora Cuatrec. | >10000 | >10000 | 20 | 0.03–11551 | TA |
ACR182 | c135 | Palma Bendita | Asteraceae | Loricaria sp. | 141 | 27–734 | 271 | 35–2054 | TA |
AKT1175 | c226 | Lavanda (la banda) | Asteraceae | Matricaria frigidum (Kunth) Kunth. | >10000 | >10000 | 262 | 45–1505 | OA/TA |
ACR6 | c68 | Manzanilla | Asteraceae | Matricaria recutita L. | 2970 | 24–>10000 | 35 | 2–437 | OA/TA |
KMM519 | c58 | Caniahuanga | Asteraceae | Munnozia lyrata (A. Gray) Rob. & Brett. | 2286 | 47–>10000 | 163 | 24–1091 | OA/TA |
ACR148 | c348 | Salvia blanca | Asteraceae | Munnozia sp. | >10000 | >10000 | >10000 | >10000 | OA/TA |
ACR150 | c293 | Hierba Aguila | Asteraceae | Onoseris odorata (D. Don.) Hooker & Amott | >10000 | >10000 | 1258 | >10000 | OA |
KMM535, AKT1153, ACR54 | c313 | Escorcionera | Asteraceae | Perezia multiflora Less. | >10000 | >10000 | 4575 | >10000 | OA |
ACR29, KMM436, KMM540, ACR39 | c158 | Chicorial Hachecoria | Asteraceae | Picrosia cf. longifolia D. Don. | 2215 | 21–>10000 | 52 | 5–502 | OA |
KMM515, ACR49 | c61 | Hierba de Gallinazo | Asteraceae | Porophyllum ruderale Less. | >10000 | >10000 | 239 | 42–1337 | TA |
AKT1168 | c54 | Hiedra/ San Juan | Asteraceae | Pseudogynoxys cordifolia (Cass.) Cabrera | >10000 | >10000 | 200 | 31–1279 | TA |
ACR17, KMM536 | c97 | Encanchallacha | Asteraceae | Schkuhria pinnata (Lam.) Kuntze | >10000 | 243–>10000 | 93 | 16–512 | OA |
ACR44, ACR28, AKT1156, AKT1098 | c60 | Vida Vida/ Vira Vira | Asteraceae | Senecio canescens (Humb. & Bonpl.) Cuatrec. | 1614 | 71–>10000 | 365 | 0.5–>10000 | OA/TA |
KMM449 | c684 | Huamanripa | Asteraceae | Senecio sp. | 0.4 | >10000 | OA | ||
KMM442 | c17 | Huamanripa (macho) | Asteraceae | Senecio sp. | >10000 | >10000 | 252 | 46–1377 | OA |
KMM523 | c575 | Ornama blanco | Asteraceae | Senecio sp. | 0.018 | >10000 | OA | ||
KMM480 | c19 | Ornamo | Asteraceae | Senecio sp. | 1989 | 66–>10000 | 255 | 39–1650 | OA |
AKT1158 | c274 | Ornamo tigre | Asteraceae | Senecio sp. | >10000 | >10000 | 20 | 0.3–1311 | OA |
ACR40, ACR197 | c344 | Yacon | Asteraceae | Smallanthus sonchifolius (Poepp. & Endl.) H. Rob. | >10000 | >10000 | >10000 | >10000 | OA |
ACR35, KMM438 | c179 | Cerraja | Asteraceae | Sonchus oleraceus L. | >10000 | >10000 | 262 | 41–1677 | OA |
KMM413, AKT1104 | c70 | Flor de Muerto | Asteraceae | Tagetes erecta L. | >10000 | 1419–>10000 | 12 | 0.1–1268 | OA/TA |
KMM524, AKT1167 | c44 | Anis | Asteraceae | Tagetes filifolia Lag. | 961 | 26–>10000 | >10000 | >10000 | OA |
ACR14 | c316 | Manzanilla de campo | Asteraceae | Tanacetum parthenium (L.) Sch.Bip. | 508 | >10000 | 900 | >10000 | OA |
KMM465 | c294 | Pajaro bobo | Asteraceae | Tessaria integrifolia Ruiz. & Pav. | >10000 | >10000 | 5 | 0.08–302 | OA |
KMM497 | c164, c201 | Anasquero | Asteraceae | Trixis cf. cacalioides D. Don. | 2248 | 58–>10000 | 271 | 51–1440 | TA |
KMM521 | c138 | Ornamo | Asteraceae | Werneria nubigena Kunth | 384 | 45–3290 | 26 | 3–193 | TA |
ACR151 | c647 | Chilca Dulce | Asteraceae | unidentified | 2873 | >10000 | OA | ||
KMM405 | c107 | Chunguis | Asteraceae | unidentified | >10000 | >10000 | 69 | 12–386 | OA |
KMM522 | c147 | Hierba de Amor | Asteraceae | unidentified | >10000 | 248–>10000 | 341 | 65–1787 | OA |
KMM490 | c183 | Miscichilca | Asteraceae | unidentified | >10000 | >10000 | 0.1 | >10000 | OA |
KMM538 | c134 | Olivo | Asteraceae | unidentified | 3001 | 88–>10000 | 448 | 71–2793 | OA |
KMM565 | c99 | Sigueme Sigueme | Asteraceae | unidentified | >10000 | 315–>10000 | 218 | 16–1314 | OA |
KMM497 | c201 | Asteraceae | unidentified | >10000 | >10000 | OA | |||
KMM474, ACR130, AKT1169 | c119 | Huanarpo | Balanophoraceae | Corynaea crassa Hook. f. | >10000 | >10000 | 116 | 11–1152 | OA |
KMM573 | c145 | Palo Amarillo | Berberidaceae | Berberis buceronis J.F. Macbr. | >10000 | >10000 | >10000 | >10000 | OA |
ACR75, KMM418 | c111 | Avedul | Betulaceae | Alnus acuminata Kunth | 64 | 10–384 | 90 | 15–519 | OE/TA |
ACR24 | c176 | Turuma | Bignoniaceae | Crescentia cujete L. | 15 | 0.1–>10000 | 0.74 | 0.01–7711 | TA |
KMM429 | c66 | Achiote | Bixaceae | Bixa orellana L. | >10000 | >10000 | 8 | 0.03–2008 | OA |
ACR9 | c71 | Borraja | Boraginaceae | Borago officinalis L. | >10000 | 169–>10000 | 1.4 | 0.02–81 | OA |
KMM489 | c328 | Ajo Sacha | Boraginaceae | Cordia alliodora (Ruiz. & Pav.) Oken. | 4721 | >10000 | 352 | 0.5–217030 | OA/TA |
AKT1114 | c170 | Overo | Boraginaceae | Cordia lutea Lam. | 462 | 15–>10000 | 108 | 17–668 | OA |
ACR57 | c297 | Alegran | Boraginaceae | Heliotropium curassavicum L. | >10000 | >10000 | 1 | >10000 | TA |
KMM406 | c184 | Flor de arena | Boraginaceae | Tiquilia paronychioides (Phil.) A. Richardson | >10000 | >10000 | >10000 | >10000 | OA |
KMM451 | c248 | Bolsa pastor | Brassicaceae | Capsella bursa-pastoris (L.) Medik. | 223 | 1–>10000 | 82 | 14–472 | OA |
AKT1163, ACR94 | c86 | Berros | Brassicaceae | Rorippa nasturtium-aquaticum (L.) Hayek | 286 | 44–1859 | 49 | 8–287 | OA |
KMM520 | c122 | Hierba del carnero | Bromeliaceae | Puya hamata L.B. Sm | >10000 | >10000 | 1.4 | 0.1–>10000 | OA/TA |
KMM520 | c473 | Bromeliaceae | Puya sp. | 2 | 0.03–128 | TA | |||
ACR183 | c32 | Siempre viva | Bromeliaceae | Tillandsia cf. cacticola L.B. Sm. | >10000 | >10000 | 1461 | 51–>10000 | OA/TA |
ACR132 | c106 | Palo Santo | Burseraceae | Bursera graveolens Triana & Planch. | >10000 | >10000 | 139 | 4–>10000 | OA/TA |
ACR95, ACR207 | c175 | San Pedro | Cactaceae | Echinopsis pachanoi (Britton & Rose) H. Friedrich & G.D. Rowley | >10000 | >10000 | 543 | 23–5149 | OA/TA |
AKT1220 | c228 | Tuna | Cactaceae | Opuntia ficus-indica (L.) Mill. | >10000 | >10000 | 465 | >10000 | OA/TA |
AKT1195 | c202 | Canillahuanga | Calceolariaceae | Calceolaria percaespitosa Wooden | >10000 | >10000 | 924 | 91–9334 | OA |
ACR147 | c57 | Canchulaly | Campanulaceae | Centropogon sp. | >10000 | >10000 | 40 | 5–304 | TA |
KMM545 | c77 | Trinoso | Campanulaceae | Centropogon sp. | 181 | 26–1235 | 26 | 0.002–>10000 | OA |
KMM443 | c130 | Contolla | Campanulaceae | Lobelia decurrens Cav. | >10000 | >10000 | 324 | 54–1922 | OA |
ACR194 | c50 | Alcaparilla | Capparidaceae | Capparis crotonoides Kunth | 83 | 11–593 | 314 | 30–3213 | OA/TA |
KMM586 | c221 | Simura | Capparidaceae | Capparis crotonoides Kunth | 1338 | 1–>10000 | 27 | >10000 | OA/TA |
KMM554 | c79 | Zapote | Capparidaceae | Capparis scabrida Kunth | 4805 | 80–>10000 | 76 | 9–601 | OA |
KMM390 | c115 | Madre de Selva | Caprifoliaceae | Lonicera cf. japonica Thunb. | 455 | 48–4238 | 24 | 2–288 | OA |
KMM539 | c23 | Flor de Novia | Caprifoliaceae | Sambucus peruviana Kunth | >10000 | 74–>10000 | 124 | 19–778 | OA/TA |
KMM455, ACR66, AKT1103 | c117 | Sauco | Caprifoliaceae | Sambucus peruviana Kunth | 168 | 15–5758 | 26 | 2–307 | OA/TA |
AKT1125 | c243 | Claveles | Caryophyllaceae | Dianthus caryophyllus L. | 1000 | >10000 | 71 | >10000 | OA/TA |
ACR31 | c46 | Paico | Chenopodiaceae | Chenopodium ambrosioides L. | >1000 | 357–>10000 | 159 | 32–789 | OA |
KMM505 | c108 | Asancito | Chloranthaceae | Hedyosmum racemosum (Ruiz. & Pav.) G. Don. | 148 | 20–1081 | 221 | 33–1477 | OE/TA |
KMM549 | c198 | Hierba del olvido | Clethraceae | Clethra castaneifolia Meiss. | 980 | 49–>10000 | 1.4 | 0.1–>10000 | TA |
ACR109 | c338 | Olvido | Clethraceae | Clethra castaneifolia Meiss. | >10000 | >10000 | >10000 | >10000 | TA |
KMM533, AKT1172 | c41 | Pachuli/Chinchango | Clusiaceae | Hypericum laricifolium Juss. | >10000 | >10000 | 637 | 62–6491 | TA |
AKT1154, ACR152, KMM387 | c152 | Cintaura | Clusiaceae | Hypericum silenoides Juss. | 545 | >10000 | 45 | 7–271 | OA |
KMM568 | c131 | Mamey | Clusiaceae | Mammea americana L. | >10000 | >10000 | 197 | 20–1869 | OA |
KMM579 | c299 | Mirra | Commiphoraceae | Commiphora sp. | 750 | >10000 | 23336 | 39–>10000 | TA |
ACR98 | c258 | Pelo de duende | Convolvulaceae | Cuscuta foetida Kunth | 13 | >10000 | OA/TA | ||
ACR169, AKT1165, KMM537, AKT1113 | c340 | Pin Pin | Crassulaceae | Echeveria peruviana Meyen | >10000 | >10000 | 424 | >10000 | OA/TA |
ACR96 | c262 | Sicana | Cucurbitaceae | Sicana odorifera Naudin | >10000 | >10000 | 488 | 73–3241 | OA |
AKT1181, KMM506 | c156 | Cipres | Cupressaceae | Cupressus sempervirens L. | 467 | 51–4245 | 284 | 51–1576 | OA/TA |
KMM493, ACR126 | c102 | Hierba del Carpintero | Cyperaceae | Oreobolus goeppingeri Suess. | 597 | 18–>10000 | 55 | 7–422 | TA |
AKT1184 | c98 | Pica flor | Cyperaceae | Oreobolus goeppingeri Suess. | >10000 | 357–>10000 | 290 | 33–2545 | TA |
KMM462 | c289 | Papa de las Buenas Tardes | Dioscoreaceae | Dioscorea sp. | >10000 | >10000 | >10000 | >10000 | OA |
KMM583 | c668 | Papa cimentona | Dioscoreaceae | Dioscorea tambillensis Kunth | 74 | 0.05–>10000 | OA | ||
KMM503 | c124 | Papa madre | Dioscoreaceae | Dioscorea trifida L.f. | 492 | 43–5590 | 0.018 | >10000 | OA/TA |
KMM503 | c475 | Dioscoreaceae | Dioscorea trifida L.f. | 361 | 39–3318 | OA/TA | |||
ACR158, KMM512 | c126 | Ambarina | Dipsaceae | Scabiosa atropurpurea L. | >10000 | 4–>10000 | 1.1 | 0.1–>10000 | OA |
ACR158, KMM512 | c477 | Dipsaceae | Scabiosa atropurpurea L. | 192 | 21–1753 | OA | |||
KMM511, AKT1159, AKT1222 | c29 | Diego Lopez | Ephedraceae | Ephedra americana Endl. | 689 | 67–7056 | 8 | 0.4–197 | OA/TA |
ACR1 | c3, c140 | Cola de caballo | Equisetaceae | Equisetum bogotense Kunth | >10000 | >10000 | 782 | 95–6415 | OA/TA |
ACR1 | c140 | Equisetaceae | Equisetum bogotense Kunth | >10000 | 3130–>10000 | OA/TA | |||
AKT1109, KMM527 | c255 | Purunrosa | Ericaceae | Bejaria aestuans L. | 17 | 1–>10000 | 3.5 | 0.004–>10000 | OA |
KMM472 | c690 | Mullaca | Ericaceae | Gaultheria erecta Vent | 162 | >10000 | OA | ||
AKT1203 | c269 | Maique | Ericaceae | Gaultheria reticulata Kunth | >10000 | >10000 | 628 | >10000 | OA/TA |
ACR151 | c200 | Chilca Dulce | Euphorbiaceae | Acalypha mandonii Müll.Arg. | >10000 | >10000 | OA | ||
KMM546 | c30 | Sangre de grado | Euphorbiaceae | Croton lechleri Muell.-Arg. | >10000 | 74–>10000 | 152 | 13–1673 | OA/TA |
KMM487, ACR122 | c87 | Pinones | Euphorbiaceae | Jatropha macrantha L. | 410 | 39–4209 | 93 | 11–732 | OA |
AKT1230 | c278, c327 | Pinones | Euphorbiaceae | Jatropha macrantha L. | 2872 | 1–>10000 | 34 | >10000 | OA |
KMM517, AKT1151 | c144 | Chanca Piedra | Euphorbiaceae | Phyllanthus niuriri L. | >10000 | >10000 | 119 | 20–679 | OA |
KMM581 | c191 | Pai pai | Fabaceae | Caesalpinia paipai R. & P. | 106 | 16–701 | 0.15 | 0.01–>10000 | TA |
ACR111 | c82 | Taya or Tara | Fabaceae | Caesalpinia spinosa (Molina) Kuntze | 168 | 29–956 | 0.1 | 0.1–>10000 | OA/TA |
ACR10 | c280 | Chibato | Fabaceae | Cajanus cajan (L.) Millesp. | >10000 | >10000 | >10000 | >10000 | TA |
ACR88 | c261 | Cana fistula | Fabaceae | Cassia fistula L. | 24155 | 1–>10000 | 243 | 33–1750 | OA |
AKT1162, KMM392, ACR201 | c151 | Pata de Pero, Marrayupa | Fabaceae | Desmodiuc colliculum (Kunth.) DC | 360 | 7–>10000 | 15088 | 195–>10000 | OA/TA |
ACR102 | c210 | Chochos | Fabaceae | Lupinus mutabilis Sweet | 4.74 | 0.1–>10000 | 1878 | >10000 | OA |
KMM463, ACR51 | c311 | Trebol de agua | Fabaceae | Medicago sativa L. | >10000 | >10000 | 965 | 26–34747 | OA |
KMM459 | c277 | Fenogreco | Fabaceae | Melilotus albus Medik. | >10000 | >10000 | 487 | 16–14543 | OA |
ACR79 | c127 | Tapa Tapa | Fabaceae | Mimosa albida Humb. & Bonpl. | >10000 | >10000 | 965 | 26–34747 | OA |
KMM560, AKT1118, ACR190, ACR79 | c266 | Tutapure | Fabaceae | Mimosa albida Humb. & Bonpl. | >10000 | >10000 | 5385 | >10000 | OA |
ACR196 | c306 | Quina | Fabaceae | Myroxylon balsamum (L.) Harms | >10000 | >10000 | 8 | 0.1–>10000 | OE/TE |
AKT1223 | c602 | Quina Quina | Fabaceae | Myroxylon balsamum (L.) Harms | 927 | 2–>10000 | OE/TE | ||
ACR164 | c700 | Quina Quina | Fabaceae | Myroxylon balsamum (L.) Harms | 0.001 | >10000 | OE/TE | ||
ACR203 | c342 | Algarrobina | Fabaceae | Prosopis pallida (Humb. & Bonpl. ex Willd) Kunth | >10000 | >10000 | >10000 | >10000 | OA/TA |
KMM470 | c260 | Sen | Fabaceae | Senna monilifera H.S. Irwin & Barnaby | >10000 | >10000 | 69 | >10000 | OA |
KMM407 | c129 | Retama | Fabaceae | Spartium junceum L. | 616 | 70–5357 | 164 | 23–1155 | OA/TA |
ACR108, KMM407 | c237 | Retamia | Fabaceae | Spartium junceum L. | >10000 | >10000 | 144 | 64–>10000 | OA/TA |
AKT1194, KMM577 | c264 | Trebol | Fabaceae | Trifolium repens L. | >10000 | >10000 | OA | ||
KMM526, ACR30, AKT1207, AKT1147, ACR156 | c22 | Corpusway, Amargon | Gentianaceae | Gentianella bicolor (Wedd.) J.S. Pringle | 472 | 55–4015 | 42 | 46–1292 | OA |
KMM403 | c711 | Angamacha | Gentianaceae | Gentianella bruneotricha (Gilg.) J.S. Pringle | 0.2 | >10000 | OA | ||
ACR20, KMM422 | c173 | Genciana | Gentianaceae | Gentianella crassicaulis J.S. Pringle | 143 | 19–1069 | 419 | 57–3048 | OA |
KMM576, ACR155 | c308 | Genciana | Gentianaceae | Gentianella dianthoides (Kunth) Fabris ex J.S. Pringle | >10000 | >10000 | 0.08 | 0.0009–8 | OA |
AKT1164, KMM529, ACR55 | c310 | Sumaran | Gentianaceae | Gentianella graminea (Kunth) Fabris | 2915 | 35–>10000 | 1066 | 0.4–>10000 | OA |
ACR92 | c691 | Horma de amarilla | Gentianaceae | Gentianella sp. | 6 | >10000 | OA | ||
AKT1171, ACR142 | c139 | Anijilla | Geraniaceae | Erodium cicutarium (L.) L'Her. | 1075 | 5–>10000 | 127 | 26–623 | OA |
KMM578 | c227 | Cachujillo | Geraniaceae | Erodium cicutarium (L.) L'Her. | 4.8 | 1–>10000 | 0.06 | >10000 | OA |
KMM400 | c220 | Pasuchaca | Geraniaceae | Geranium sessiliflorum Cavanilles | 1472 | 95–>10000 | 55 | 8–679 | OA |
AKT1208 | c281 | Anis estrella | Iliciaceae | Ilicium verum Hook. f. | 3.6 | >10000 | 323 | 61–1697 | OA |
AKT1100, ACR45 | c252 | Hierba de la justicia | Iridaceae | Hesperoxiphion niveum (Rav.) Rav. | >10000 | >10000 | 91 | >10000 | OA |
AKT1111, KMM435, ACR71 | c159 | Nogal | Juglandaceae | Juglans neotropica Diels | 4734 | 152–>10000 | 213 | 35–1266 | OA/TA |
ACR48 | c549, c606 | Ratania | Krameriaceae | Krameria lappacea (Dombey) H.M. Burdet & B.B. Simpson | 1507 | >10000 | OA | ||
ACR97 | c141 | Panizara | Lamiaceae | Clinopodium pulchellum (Kunth) Govaerts | 7745 | 5–>10000 | 211 | 39–1137 | OA |
ACR18 | c142 | Albaca serrana | Lamiaceae | Hyptis sidifolia (L'Her.) Briq. | 3574 | 23–>10000 | 151 | 28–816 | OA |
ACR69 | c199 | Pedorera | Lamiaceae | Hyptis sidifolia (L'Her.) Briq. | >10000 | 357–>10000 | >10000 | >10000 | OA |
KMM452, ACR33 | c292 | Cordon de Muerto | Lamiaceae | Marrubium vulgare L. | >10000 | >10000 | 536 | >10000 | TA |
ACR4 | c229 | Toronjil | Lamiaceae | Melissa officinalis L. | >10000 | >10000 | 1.7 | 0.001–>10000 | OA/TA |
ACR68 | c5 | Poleo | Lamiaceae | Mentha piperita Stokes | 1439 | 20–>10000 | 322 | 18–5536 | OA |
KMM453, AKT1101, AKT1166 | c64 | Menta | Lamiaceae | Mentha spicata L. | >10000 | >10000 | 345 | 49–2382 | OA/TA |
AKT1142, KMM417, KMM456, ACR7 | c12 | Chancas de muerto | Lamiaceae | Minthostachys mollis Grieseb. | >10000 | 586–>10000 | 142 | 28–723 | OA |
KMM437, KMM428, ACR32 | c16 | Albaca | Lamiaceae | Ocimum basilicum L. | 8483 | 67–>10000 | 274 | 51–1465 | OA/TE |
ACR24, KMM471 | c307 | Mejorana | Lamiaceae | Origanuc cajorana L. | >10000 | >10000 | 1000 | >10000 | OA |
KMM509 | c216 | Oregano | Lamiaceae | Origanum vulgare L. | 309 | 33–2863 | 0.14 | 0.1–24811 | OA |
KMM419, AKT1134 | c133 | Culen | Lamiaceae | Otholobium glandulosum (L.) Grimes | >10000 | 172–>10000 | 271 | 35–2054 | OA |
ACR67 | c101 | Culén | Lamiaceae | Otholobiuc cexicanum (L.f.) Grimes | >10000 | 278–>10000 | 743 | 77–7163 | OA |
ACR16, AKT1129 | c116 | Romero | Lamiaceae | Rosmarinus officinalis L. | 5357 | 104–>10000 | 36 | 3–364 | OA/TA |
ACR184 | c10 | Alamo Silvestre | Lamiaceae | Salvia sp. | >10000 | 42–>10000 | >10000 | >10000 | OA |
KMM572 | c291 | Hierba de los sieta vientos | Lamiaceae | Salvia sp. | >10000 | >10000 | 0.006 | >10000 | OA |
AKT1160 | c215 | Hierba del Aire | Lamiaceae | Salvia sp. | >10000 | >10000 | 4 | 0.06–273 | OA/TE |
KMM567 | c336 | Paja Amargoza | Lamiaceae | Salvia sp. | >10000 | >10000 | 7122 | 132–>10000 | OA |
ACR115 | c239 | Paja del Aire | Lamiaceae | Salvia sp. | 1000 | >10000 | 153 | 16–1428 | OA |
KMM550 | c335 | Unquia Real | Lamiaceae | Salvia sp. | >10000 | >10000 | 0.58 | 0.1–860 | OA |
KMM543 | c59 | Panizara | Lamiaceae | Satureja pulchella (Kunth.) Briq. | >10000 | 287–>10000 | 144 | 30–693 | OA |
KMM397 | c171 | Romerillo | Lamiaceae | Satureja sericea (C. Presl. & Benth.) Briq. | 59 | 4–794 | 382 | 54–2692 | OA |
ACR100 | c55 | Romerillo | Lamiaceae | Satureja sericea (C. Presl. & Benth.) Briq. | >10000 | >10000 | 80 | 13–461 | OA |
ACR178 | c657 | Poleo Gentil | Lamiaceae | Scutellaria cf. scutellarioides (Kunth) Harley | >10000 | >10000 | TA | ||
KMM575 | c218 | Canela | Lauraceae | Cinnamomum verum J. Presl. | 194 | 1–>10000 | 132 | 13–2773 | OA/TA |
AKT1120, KMM444 | c155 | Palta | Lauraceae | Persea americana Mill. | >10000 | >10000 | 121 | 24–618 | OA |
ACR87 | c322 | Pelo de Pierda | Lichen | Siphula sp. | >10000 | >10000 | 12 | 0.9–158 | OA |
AKT1107 | c319 | Aloe | Liliaceae | Aloe vera | >10000 | >10000 | >10000 | >10000 | OE |
ACR157 | c189 | Contolla | Lobeliaceae | Lobelia decurrens Cav. | >10000 | 247–>10000 | 351 | 0.01–>10000 | OA |
AKT1131 | c238 | Flor Blanca | Loganiaceae | Buddleja utilis Kraenzl. | >10000 | >10000 | OA | ||
AKT1170 | c69 | Condor | Lycopodiaceae | Huperzia sp. | >10000 | >10000 | 11 | 0.01–7493 | TA |
KMM541 | c24 | Condor | Lycopodiaceae | Huperzia sp. | 422 | 18–9770 | 201 | 34–1190 | TA |
KMM477 | c219 | Condor crespo | Lycopodiaceae | Huperzia sp. | >10000 | >10000 | >10000 | >10000 | TA |
KMM479 | c35 | Condor Misha | Lycopodiaceae | Huperzia sp. | 4524 | >10000 | 157 | 17–1429 | TA |
KMM482, AKT1212 | c231 | Condor Purga | Lycopodiaceae | Huperzia sp. | 4979 | 71–>10000 | 1.3 | >10000 | TA |
KMM391 | c165 | Corontilla | Lycopodiaceae | Huperzia sp. | 543 | 13–>10000 | 278 | 46–1650 | TA |
AKT1183, AKT1197 | c320 | Enredadera | Lycopodiaceae | Huperzia sp. | >10000 | >10000 | 85 | 0.5–>10000 | TA |
KMM483 | c196 | Trencilla blanca | Lycopodiaceae | Huperzia sp. | >10000 | >10000 | 0.04 | 0.04–>10000 | TA |
AKT1206 | c85 | Guamingo | Lycopodiaceae | Lycopdium sp. | >10000 | >10000 | 49 | 8–287 | TA |
AKT1198, AKT1191 | c302 | Trencilla verde | Lycopodiaceae | Lycopdium thuyoides Humb. & Bonpl. ex Willd. | >10000 | >10000 | 0.01 | 0.01–4.5 | TA |
KMM448 | c72 | Hierba del Toro | Lythraceae | Cuphea sp. | 1464 | 82–>10000 | 15 | 0.2–1246 | OA/TA |
AKT1102 | c100 | Hierba del Toro | Lythraceae | Cuphea strigulosa Kunth | >10000 | >10000 | 14 | 0.1–1997 | OA/TA |
ACR135 | c84 | Ayahuasca | Malpighiaceae | Banisteriopsis caapi (Spruce ex Grieseb.) Morton | 1099 | 70–>10000 | >10000 | >10000 | OA |
ACR26 | c225 | Malva de Olor | Malvaceae | Malva sp. | >10000 | >10000 | 0.0002 | >10000 | OA/TA |
AKT1201 | c282 | Malva Real | Malvaceae | Malva sp. | >10000 | >10000 | 118 | 15–7331 | OA/TA |
AKT1200 | c337 | Malva rosa | Malvaceae | Malva sp. | 1.8 | 1–>10000 | 0.4 | >10000 | OA/TA |
ACR8 | c56 | Malva Blanca Alta | Malvaceae | Malva sylvestris L. | >10000 | >10000 | 6 | 0.2–157 | OA/TA |
ACR185 | c683 | Buenas Horas | Malvaceae | Urena cf. lobata L. | 11 | >10000 | OA | ||
ACR140, AKT1189 | c137 | Zarcilleja | Melastomataceae | Brachyotum naudinii Triana | 0.59 | 0.1–2136 | 202 | 26–1109 | OA |
AKT1204 | c62 | Mococho | Melastomataceae | Miconia salicifolia (Bonp. ex Naud.) Naud. | 188 | 31–1148 | 53 | 2–1443 | OA |
KMM544 | c251 | Porontillo | Melastomataceae | Miconia salicifolia (Bonp. ex Naud.) Naud. | 1 | 1–>10000 | 2309 | >10000 | OA |
ACR136 | c249 | Abuta | Menispermaceae | Abuta grandifolia (Mart.) Sandwith. | >10000 | >10000 | 317 | 35–2850 | OA |
ACR37, ACR99, AKT1132 | c177 | Boldo (Chilean) | Monimiaceae | Peumus boldus Molina | 34163 | 0.5–>10000 | 43 | >10000 | OA |
KMM570 | c31 | Palo Sangre | Moraceae | Brosimum rubescens Taub. | 2605 | 119–>10000 | 537 | 63–4532 | OA |
ACR73, AKT1128 | c287 | Higo | Moraceae | Ficus carica L. | >10000 | >10000 | 1233 | 0.1–>10000 | OE |
KMM454 | c197 | Ciotrodora | Myrtaceae | Eucalyptus citriodora Hook. | >10000 | >10000 | 1114 | >10000 | OA |
KMM408, AKT1110, ACR74 | c136 | Eucalypto | Myrtaceae | Eucalyptus globulus Labill | 29 | 1–701 | 240 | 30–1895 | OA/TA |
ACR19 | c73 | Arrayn | Myrtaceae | Eugenia obtusifolia Cambess. | 3755 | 2–>10000 | 47 | 4–503 | OA |
ACR180 | c267 | Limoncillo | Myrtaceae | Eugenia obtusifolia Cambess. | 1000 | >10000 | >10000 | >10000 | OA |
ACR76 | c43 | Rumilanche | Myrtaceae | Eugenia obtusifolia Cambess. | 174 | 19–1542 | 189 | 34–1032 | OA |
AKT1143 | c162 | Rumilanche | Myrtaceae | Eugenia obtusifolia Cambess. | 78 | 6–896 | 164 | 23–1153 | OA |
KMM399 | c14 | Guanabana | Myrtaceae | Psidium guajava L. | 1578 | 66–>10000 | 195 | 16–2302 | OA |
ACR207 | c271 | Pial | Myrtaceae | Scutia spicata (Humb. & Bonpl. ex Willd.) Weberb. | >10000 | >10000 | >10000 | >10000 | TA |
ACR188 | c37 | Clavo de olor | Myrtaceae | Syzygium aromaticum (L.) Merr. & L.M. Perry | 254 | 44–1471 | 0.08 | 0.0009–8 | OA/TA |
ACR174 | c290 | Poma Rosa | Myrtaceae | Syzygium jambos (L.) Alston | 12913 | >10000 | OA | ||
KMM507 | c109 | Chchuhuasi | Olacaceae | Heisteria acuminata (Humb. & Bonpl.) Engl. | 4479 | 151–132688 | 261 | 41–1661 | OA/TA |
AKT1211 | c247 | Jasmin | Oleacaceae | Jasminum sp. | 1000 | >10000 | 0.88 | 0.006–130 | OA |
AKT1187 | c13 | Anasquero | Onagraceae | Fuchsia sp. | >10000 | >10000 | 123 | 21–697 | TA |
ACR144, AKT1185 | c276, c349 | Hierba esperanza | Orchidaceae | Aa paleacea (Kunth) Rchb.f. | >10000 | >10000 | >10000 | >10000 | OA |
KMM530 | c323 | Hierba sola | Orchidaceae | Aa paleacea (Kunth) Rchb.f. | >10000 | >10000 | 0.001 | >10000 | OA |
ACR165 | c550 | Espadilla | Orchidaceae | Epidendrum sp. | 35 | >10000 | OA | ||
AKT1177 | c305 | Hierba de la Espada | Orchidaceae | Epidendrum sp. | 3.5 | 0.1–>10000 | OA | ||
KMM484 | c190 | Lancilla | Orchidaceae | Epidendrum sp. | 3874 | 46–332446 | 164 | 29–919 | OA |
KMM492 | c206 | Hierba del Olor | Orchidaceae | Stelis sp. | >10000 | >10000 | TA | ||
KMM433, AKT1135, ACR61 | c168 | Cardo Santo | Paparvaceae | Argemone mexicana L. | 101 | 6–1549 | 698 | 93–5250 | OA |
KMM420, AKT1112 | c169 | Hoja de granadilla | Passifloraceae | Passiflora ligularis A. Juss. | 697 | 2–185545 | 299 | 42–2116 | OA |
KMM510 | c88 | Norgo | Passifloraceae | Passiflora punctata L. | 22832 | 210–>10000 | 112 | 18–691 | OA |
AKT1122 | c149 | Hierba del Partero | Passifloriaceae | Passiflora sp. | 601 | 72–5015 | 152 | 27–834 | OA |
ACR52 | c125 | Mocura | Phytolaccaceae | Petiveria alliacea L. | 126 | 24–642 | 0.67 | >10000 | TA |
KMM447, AKT1115 | c132 | Mocura | Phytolaccaceae | Petiveria alliacea L. | 685 | 73–6430 | 1126 | 34–36468 | TA |
ACR52 | c476 | Phytolaccaceae | Petiveria alliacea L. | 159 | 19–1324 | TA | |||
KMM457, AKT1180 | c18 | Ailambo | Phytolaccaceae | Phytolacca bogotensis Kunth | >10000 | >10000 | 53 | 7–382 | TA |
AKT1148, KMM534 | c121 | Congona | Piperaceae | Peperomia inaequalifolia Ruiz. & Pav. | >10000 | 605–>10000 | 1076 | 92–12469 | OA/TA |
AKT1148, KMM534 | c579 | Congona | Piperaceae | Peperomia inaequalifolia Ruiz. & Pav. | 0.25 | >10000 | OA/TA | ||
KMM532 | c727 | Piri Piri | Piperaceae | Peperomia quadrifolia Miq. | 301 | 8–11047 | TA | ||
AKT1190 | c621 | Congonilla | Piperaceae | Peperomia sp. | 12 | >10000 | OA | ||
ACR21 | c658 | Lancetillo | Piperaceae | Peperomia sp. | 242 | 15–3797 | OA | ||
AKT1148, KMM534 | c472 | Piperaceae | Peperomia sp. | 39 | 4–395 | OA | |||
ACR15 | c120 | Matico (sierra) | Piperaceae | Piper acutifolium Ruiz. & Pav. | >10000 | >10000 | 32 | 2–411 | OA |
ACR12, AKT1150 | c67 | Matico | Piperaceae | Piper aduncum L. | 16070 | 114–>10000 | 164 | 17–799 | OA/TA |
KMM411 | c332 | Llanten | Plantaginaceae | Plantago major L. | >10000 | >10000 | 2.75 | 0.1–16904 | OA/TA |
KMM411 | c565 | Plantaginaceae | Plantago major L. | 537 | 55–5194 | OA/TA | |||
AKT1182 | c223 | Paja blanca | Plantaginaceae | Plantago sericea Ruiz. & Pav. | 500 | >10000 | 9 | >10000 | OA |
KMM389 | c114 | Carrizo | Poaceae | Arundo donax L. | >10000 | >10000 | 39 | 5–269 | TA |
ACR5 | c48 | Hierba Luisa | Poaceae | Cymbopogon citratus (DC.) Stapf | 73976 | 235–>10000 | 58 | 2–1778 | OA |
KMM450, ACR62 | c110 | Gramadulce | Poaceae | Cynodon dactylon (L.) Pers. | 84 | 9–740 | 81 | 13–476 | OA |
AKT1096 | c318 | Gramadulce | Poaceae | Distichlis spicata (L.) Greene | 56 | 1–>10000 | 51 | 4–560 | OA |
ACR47 | c346 | Carrizo | Poaceae | Gynerium sagittatum (Aubl.) P. Beauv. | 2474 | 1–>10000 | >10000 | >10000 | OA |
KMM502, AKT1261 | c596 | Cuña Cuña | Poaceae | Saccharum officinarum L. | 9 | 0.3–247 | OA/TA | ||
KMM415 | c233 | Barra de oro | Poaceae | unidentified | >10000 | >10000 | 12967 | 138–>10000 | OA |
ACR86 | c649 | Cantuta o Cando | Polemoniaceae | Cantua buxifolia Juss. ex Lam. | 1.5 | 0.1–50755 | TA | ||
AKT1161, KMM495 | c172 | Adormidora | Polemoniaceae | Cantua quercifolia Juss. | 374 | 9–15319 | 147 | 25–857 | OA/TA |
ACR80 | c279 | Pica Pica | Polygonaceae | Polygonum hydropiperoides Michaux | >10000 | >10000 | 2.35 | >10000 | OA |
KMM496 | c224 | Mala Hierba | Polygonaceae | Rumex crispus L. | >10000 | >10000 | 45 | >10000 | OA/TA |
AKT1137 | c11 | Calaguala | Polypodiaceae | Polypodium crassifolium L. | 5255 | 106–>10000 | 129 | 20–839 | OA |
ACR176, KMM514, AKT1173 | c232 | Chucharilla | Proteaceae | Oreocallis grandiflora (Lam.) R. Br. | >10000 | >10000 | OA/TA | ||
KMM460 | c187 | Doradillo | Pteridaceae | Argyrochosma nivea (Poir.) Windham | 131 | 0.1–>10000 | 208 | 37–1171 | OA |
ACR145 | c7 | Cuti Blanco | Pteridaceae | Cheilanthes pruinata Kaulf. | >1000 | 349–>10000 | 383 | 59–2470 | OA |
KMM461 | c245 | Cuty Cuty | Pteridaceae | Cheilanthes pruinata Kaulf. | 7064 | 1–>10000 | 1 | 0.1–39676 | OA |
AKT1108 | c81 | Cuty Cuty | Pteridaceae | Cheilanthes pruinata Kaulf. | >10000 | >10000 | 566 | 69–4610 | OA |
ACR112, AKT1215 | c45, c47 | Baston del Inca | Pteridaceae | Jamesonia alstonii A.F. Tryon | >10000 | >10000 | 41 | 0.01–112079 | TA |
KMM458 | c321 | Doradilla | Pteridaceae | Notholaena sulphurea (Cav.) L. Sm. | 2564 | >10000 | 12 | >10000 | OA |
KMM464 | c203, c214 | Contra Hierba | Pteridaceae | unidentified | >10000 | >10000 | 0.003 | >10000 | OA |
AKT1119, KMM410 | c51 | Pacra/ Flor de huamanripa | Ranunculaceae | Laccopetalum giganteum (Wedd.) Ulbrich | >10000 | >10000 | 51 | 5–484 | OA/TE |
ACR56 | c4 | Membrillo | Rosaceae | Cydonia oblonga Miller | >10000 | >10000 | 42 | 5–332 | OA |
ACR146 | c284 | China Linda | Rosaceae | Margyricarpu spinnatus (Lam.) Kuntze | >10000 | >10000 | 407 | 0.01–>10000 | OA |
ACR3 | c164 | Quinal | Rosaceae | Polylepis racemosa Ruiz. & Pav. | 127 | >10000 | 112 | 20–605 | OA/TA |
ACR172 | c9 | Capuli | Rosaceae | Prunus serotina Ehrh. | 731 | 21–5289 | 81 | 14–465 | TE |
ACR70, AKT1155 | c181 | Zarzamora | Rosaceae | Rubus robustus C. Presl. | >10000 | 387–>10000 | 2 | 0.001–>10000 | OA/TA |
ACR23 | c296 | Pimpinela | Rosaceae | Sanguisorba minor Scop. | >10000 | >10000 | 11 | 0.01–>10000 | OA/TA |
AKT1214 | c650 | Ornamo Leon | Rosaceae | unidentified | 241 | 0.01–>10000 | OA | ||
ACR123, KMM525 | c211 | Cascarilla | Rubiaceae | Cinchona officinalis L. | 0.5 | 0.1–250 | 950 | >10000 | OE |
ACR160 | c8 | Noni | Rubiaceae | Morinda citrifolia L. | 142 | 24–842 | 156 | 30–809 | OA |
AKT1218, ACR198 | c295 | Uña de Gato | Rubiaceae | Uncaria tomentosa (Willd. ex Roem & Schult.) DC. | >10000 | >10000 | 644 | 4–>10000 | OA/TA |
KMM425 | c63 | Lima | Rutaceae | Citrus limetta Risso | >10000 | 224–>10000 | 198 | 22–1776 | OA/TA |
KMM424 | c15 | Limon | Rutaceae | Citrus limon (L.) Burm. f. | 4111 | 131–>10000 | 483 | 63–3675 | OA/TA |
AKT1097, AKT1105, KMM430 | c157 | Ruda Seca | Rutaceae | Ruta graveolens L. | >10000 | >10000 | 73 | 12–447 | OA/TA |
ACR42, AKT1106 | c212 | Sauce | Salicaeae | Salix chilensis Molina | >10000 | 332–>10000 | 1 | >10000 | OA/TA |
KMM574 | c27 | Te de Judio | Scrophulariaceae | Capraria peruviana Bentham | >10000 | 1075–>10000 | 7012 | 127–>10000 | OA |
ACR64 | c678 | Macacha | Scrophulariaceae | Galvezia fruticosa J. Gmelin | 9848 | 142–>10000 | OA/TE | ||
KMM440 | c207 | Chiciricoma | Scrophulariaceae | unidentified | >10000 | >10000 | 1.3 | >10000 | OA |
KMM516 | c185 | Palo china | Smilacaceae | Smilax kunthii Killip & Morton | >10000 | >10000 | 31 | 0.1–>10000 | OA |
KMM564 | c312 | Misha Blanca | Solanaceae | Brugmansia candida Pers. | 3187 | 141–>10000 | 1.8 | >10000 | OA/TA |
KMM528 | c288 | Misha | Solanaceae | Brugmansia sanguinea (Ruiz. & Pav.) D. Don | >10000 | >10000 | 0.2 | 0.01–>10000 | OA/TA |
ACR90 | c36 | Misha | Solanaceae | Brugmansia sp. | >10000 | >10000 | 67 | 9–476 | OA/TA |
AKT1116 | c671 | Floripondio (Flori pondio) | Solanaceae | Brugmansia suaveolens (Willd.) Bercht. & Presl | 106 | >10000 | OA/TA | ||
ACR36 | c103 | Hierba Santa (Sierra) | Solanaceae | Cestrum auriculatum L'Her. | 1006 | 8–>10000 | 24 | 0.6–978 | OA/TA |
ACR83 | c681 | Hierba Santa | Solanaceae | Cestrum humboldtii Francey | 28 | >10000 | OA/TA | ||
AKT1121 | c75 | Agrosejo/ Cuncuno | Solanaceae | Cestrum sp. | >10000 | 210–>10000 | 80 | 5–1192 | OA/TA |
KMM426 | c33 | Hierba Santa | Solanaceae | Cestrum sp. | >10000 | 372–>10000 | 1.4 | 0.0045–435 | OA/TA |
KMM441, KMM582 | c192 | Floripondio | Solanaceae | Datura ferox L. | 8677 | 59–>10000 | 234 | 15–8363 | OA |
KMM557 | c209 | Chilca Macho | Solanaceae | Nicotiana tabacum L. | 7.5 | 0.1–>10000 | >10000 | >10000 | OA/TA |
KMM388, ACR53 | c118 | Tabaco | Solanaceae | Nicotiana tabacum L. | 178 | 31–1005 | 39 | 4–337 | OA/TA |
AKT1124 | c331 | Hierba de Senorita | Solanaceae | Nolana cf. humifusa (Gouan) I.M. Johnston | >10000 | >10000 | >10000 | >10000 | OA |
ACR99, ACR37 | c333 | Hierba Moro | Solanaceae | Solanum americanum Mill. | 0.3 | 0.3–>10000 | 310 | 16–5788 | OA/TA |
AKT1138 | c640 | Torito | Solanaceae | Solanuc cammosum L. | >10000 | >10000 | OA/TA | ||
KMM561 | c25 | Palo Huaco | Ulmaceae | Celtis loxensis C.C. Berg | 5388 | 58–>10000 | 508 | 70–3647 | OA |
KMM402, ACR72 | c92 | Ortiga | Urticaceae | Urtica magellanica Juss. ex Poir. | >10000 | >10000 | 2281 | 15–>10000 | OA/TA |
ACR199 | c234 | Chin Chin | Urticaceae | Urtica urens L. | >10000 | >10000 | 2494 | 0.2–>10000 | OA/TA |
KMM491 | c398 | Boton de oro | Valerianaceae | Belonanthus cf. | >10000 | >10000 | OA/TA | ||
KMM481, AKT1205 | c186 | Estrella | Valerianaceae | Phyllactis rigida (Humb. & Bonpl.) Pers. | 201 | 0.1–>10000 | 3 | 0.1–>10000 | OA/TA |
AKT1117 | c250 | Valeriana estrella | Valerianaceae | Phyllactis rigida (Humb. & Bonpl.) Pers. | 1 | 1–>10000 | 1265 | >10000 | OA/TA |
ACR181 | c34 | Fortuna | Valerianaceae | Valeriana cf. bonplandiana Wedd. | 109 | 12–969 | 112 | 17–703 | TA |
AKT1140, ACR120 | c324 | Hornamo del Caballo | Valerianaceae | Valeriana plantaginea Kunth cf. | >10000 | >10000 | 168 | 25–1122 | OA/TA |
AKT1141 | c666 | Ornamo | Valerianaceae | Valeriana sp. | 64 | >10000 | OA/TA | ||
AKT1213 | c253 | Valeriana | Valerianaceae | Valeriana sp. | >10000 | >10000 | 54 | 0.2–10591 | OA/TA |
KMM394 | c244 | Valeriana Delgada | Valerianaceae | Valeriana sp. | >10000 | >10000 | 40 | 3–408 | OA/TA |
KMM396 | c194 | Valeriana gruesa | Valerianaceae | Valeriana sp. | >10000 | 260–>10000 | 0.8 | >10000 | OA/TA |
ACR43 | c113 | Santa Maria | Verbenaceae | Aloysia scorodonioides (Kunth) Chamisso | >10000 | >10000 | 0.6 | 0.006–59 | OA/TA |
ACR159 | c178 | Cedron | Verbenaceae | Aloysia triphylla Royle | 390 | 54–2818 | 1897 | >10000 | OA/TA |
KMM398 | c283 | Cedron | Verbenaceae | Aloysia triphylla Royle | >10000 | >10000 | 0.01 | >10000 | OA/TA |
ACR50, AKT1123 | c112 | Pacha Rosa | Verbenaceae | Lantana scabiosaeflora Kunth | >10000 | >10000 | 92 | 13–650 | OA |
AKT1202 | c205 | Hierba del Hombre | Verbenaceae | Lantana sp. | >10000 | >10000 | >10000 | >10000 | OA |
ACR25 | c167 | Salvia Real | Verbenaceae | Lantana sp. | 290 | 36–2293 | 23 | 2–256 | OA |
ACR13 | c3 | Verbena | Verbenaceae | Verbena littoralis Kunth | >10000 | >10000 | 120 | 21–678 | OA/TA |
ACR154 | c78 | Sabadilla | Verbenaceae | Verbesina sp. | 2750 | 87–>10000 | 34 | 2–390 | OA |
AKT1210 | c153 | Hierba de Susto | Verbenaceae | >10000 | >10000 | 22 | 2–208 | OA | |
KMM423 | c345 | Violeta | Violaceae | Viola sp. | >10000 | >10000 | 410 | 69–2440 | OA |
ACR195, AKT1203 | c174 | Cinta de Novia | Violaceae | Viola tricolor L. | >10000 | >10000 | >10000 | >10000 | OA |
ACR27 | c330 | Pensamiento | Violaceae | Viola tricolor L. | >10000 | >10000 | 728 | 19–>10000 | OA |
ACR189 | c325 | Suelda con suelda | Viscaceae | Phoradendron sp. | >10000 | >10000 | 11 | >10000 | OA |
KMM485 | c20 | Chimipampana Blanca | Zingiberaceae | unidentified | >10000 | 0.62–>10000 | 234 | 32–1679 | OA |
KMM518 | c105 | Ajo Caspi | unidentified | unidentified | 6919 | >10000 | 74 | 7–926 | OA |
KMM403 | c334 | Anga macha | unidentified | unidentified | >10000 | >10000 | OA | ||
ACR101 | c38 | Anguarate | unidentified | unidentified | >10000 | 235–>10000 | >10000 | 114–>10000 | OA |
AKT1219 | c150 | Anti ajo | unidentified | unidentified | >10000 | >10000 | 1621 | 100–>10000 | OA |
ACR193 | c314 | Arnica (Solo la corteza) | unidentified | unidentified | >10000 | >10000 | 164 | 23–1155 | OA |
ACR206 | c83 | Balsa blanca | unidentified | unidentified | >10000 | >10000 | 178 | 20–4171 | OA |
ACR173 | c275 | Bejuco de montaña | unidentified | unidentified | >10000 | >10000 | >10000 | >10000 | OA |
KMM501 | c53 | Beldaco | unidentified | unidentified | 42 | 2–696 | 13 | 0.2–818 | OA |
ACR143 | c273 | Canchalagua Morada | unidentified | unidentified | >10000 | >10000 | 395 | >10000 | OA |
KMM508 | c21 | Cardo Bendito | unidentified | unidentified | >10000 | >10000 | 780 | 55–11043 | OA |
AKT1139 | c259 | Chimipanpana | unidentified | unidentified | >10000 | >10000 | 716 | >10000 | OA |
KMM569 | c301 | Chivato | unidentified | unidentified | >10000 | >10000 | 17 | 0.7–406 | OA |
ACR84 | c675 | Choloque | unidentified | unidentified | >10000 | >10000 | OA | ||
ACR106 | c52 | Contra hechizo | unidentified | unidentified | >10000 | 102–>10000 | >10000 | >10000 | OA |
ACR141 | c339 | Estiagra | unidentified | unidentified | >10000 | >10000 | OA | ||
ACR200 | c326 | Hercampuri | unidentified | unidentified | >10000 | >10000 | 1.8 | >10000 | OA |
ACR65 | c89 | Huamanrripa | unidentified | unidentified | 5893 | 5–>10000 | 3693 | 12–>10000 | OA |
AKT1209 | c154 | Huarate | unidentified | unidentified | 1329 | 122–14481 | 3873 | 146–>10000 | OA |
AKT1231 | c270 | Llanten Blanco | unidentified | unidentified | >10000 | >10000 | 1219 | >10000 | OA |
AKT1130 | c254 | Milagroso | unidentified | unidentified | >10000 | >10000 | 1205 | 3–>10000 | OA |
ACR93 | c315 | Orillo de Brujo | unidentified | unidentified | >10000 | 233–>10000 | 30948 | 2–>10000 | OA |
ACR104 | c309 | Paja del susto | unidentified | unidentified | >10000 | >10000 | >10000 | >10000 | OA |
ACR60 | c256 | Pegajosa | unidentified | unidentified | >10000 | >10000 | 0.43 | >10000 | OA |
ACR202 | c161 | Tutapure blanco | unidentified | unidentified | 322 | 0.1–>10000 | 252 | 48–1308 | OA |
ACR110 | c351 | Yetama | unidentified | unidentified | 672 | 84–5335 | 216 | 35–1314 | OA |
AKT1136 | c222 | Zarzaparrilla | unidentified | unidentified | 750 | >10000 | 1 | 0.1–>10000 | OA |
ACR182 | c486 | unidentified | unidentified | 141 | 27–733 | OA |
Species which showed higher levels of toxicity were Bejaria aestuans L., Erodium cicutarium (L.) L'Her., Brachyotum naudinii Triana, Miconia salicifolia (Bonp. ex Naud.) Naud., Cuscuta foetida Kunth, Caesalpinia spinosa (Molina) Kuntze, and Phyllactis rigida (Humb. and Bonpl.) Pers.. Achillea millefolium L., Artemisia absinhitum L., and Eucalyptus globulus Labill all frequently used as medicinal teas also fall in this group, as do Lupinus mutabilis Sweet, and Ilicium verum Hook. f.. Solanaceae (e.g. Nicotiana tabacum L. and Solanum americanum Mill.) proved highly toxic, while other species, known to be highly toxic when ingested (e.g. Datura sp. and Brugmansia spp.) did not show toxicity in Brine Shrimp.
Multiple extracts from different collections of the same species showed in most cases very similar toxicity values. However, in some cases the toxicity of extracts from different collections of the same species varied from non-toxic to highly toxic. Examples for such variation in toxicity were found for Chersodoma deltoidea M.O. Dillon and Sagast., Satureja sericea (C. Presl. and Benth.) Briq., Eugenia obtusifolia Cambess., Epidendrum sp., Capparis crotonoides Kunth, Sambucus peruviana Kunth, and Malva sp. In case of these frequently used species, harvest time, collection locality or use of specific plant parts might be important for a reduction of toxicity.
4. Conclusions
Brine-shrimp bioassays offer a quick, simple and cost-efficient way of testing the toxicity of plant extracts, and allow a high throughput. This is of particular importance in developing countries where a large percentage of the population relies on the use of crude medicinal plant extracts to meet their health care needs, and where large numbers of different species are used, often prepared in complex mixtures (WHO, 1998). The test does not necessarily constitute a direct link to toxicological effects in mammals (Sanchez et al., 1993), and should ideally be subjected to additional laboratory validation. However, it does give a good initial indication for the toxicity of the material tested.
Toxicity values with LC50 values below 1000 μg/ml are considered to be bioactive and might provide leads for further screening (Meyer et al., 1982). Over 75% of the species in the present study might have some cytotoxic potential. The toxicity values reported fall in the range reported by other authors (e.g. Coe et al., 2010).
Acknowledgments
The presented study was financed through MHIRT (Minority Health Disparity International Research and Training, Fund: 54112B MHIRT Program, Grant: G0000613), coordinated by San Diego State University (SDSU) in cooperation with the San Diego Museum of Man (SDMM), the P.A. Hearst Museum of Anthropology at the University of California Berkeley (PAHMAUCB), the Missouri Botanical Garden, USA, and the Universidad Privada Antenor Orrego (UPAO, Herbarium HAO), the Universidad Nacional de Trujillo (UNT, Herbarium HUT and Instituto de Medicina Tropical) and the Clínica Anticona Trujillo (CAT) in Peru.
None of the work would have been possible without the invaluable collaboration of our Peruvian colleagues, curanderas Julia Calderón, Isabel Chinguel, and Olinda Pintado, curandero Germán Santisteban, and herbalists Manuel Bejarano, Elmer Cruz, and Iván Cruz. With regard to ritual and therapeutic practices we especially want to thank the above curanderas, as well as curandero Leoncio Carrión.
Thanks also go to Eric Rodriguez (Herbarium Truxillense, HUT) and Abundio Sagastegui, Segundo Leiva, and Mario Zapata (Herbario Antenor Orrego, HAO) for the use of their facilities and their assistance in plant identification.
Most of all, we want to express our sincere gratitude to the people of Northern Peru for sharing their ethnobotanical knowledge.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Declaration of interest This study was supported by grants from the National Institutes of Health.
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