BOLETÍN LATINOAMERICANO Y DEL CARIBE DE PLANTAS MEDICINALES Y AROMÁTICAS 18 (3): 223 - 238 (2019) © / ISSN 0717 7917 / www.blacpma.usach.cl Revisión | Review Phytochemistry and Biological Activities of Werneria and Xenophyllum species [Fitoquímica y actividades biológicas de especies de Werneria y Xenophyllum] Olga Lock1 & Rosario Rojas2 1Departamento de Química, Pontificia Universidad Católica del Perú, Lima, Perú 2Unidad de Investigación en Productos Naturales, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú Contactos | Contacts: Olga LOCK - E-mail address: [email protected] Contactos | Contacts: Rosario ROJAS - E-mail address: [email protected] Abstract: Plants of the genera Werneria (Asteraceae) and Xenophyllum (genus extracted from Werneria) are used in traditional medicine of Latin America for the treatment of mountain sickness, hypertension and gastrointestinal disorders. Only a small number of species of these genera have been studied, leading to the isolation of compounds belonging to the classes of benzofurans, chromenes, acetophenones, coumarates, diterpenes and pyrrolizidine alkaloids. Some of the plant extracts and/or compounds have shown antimicrobial, anti-HIV, hypotensive and photoprotective activities. Keywords: Werneria; Xenophyllum; Medicicinal plants; Mountain sickness; Hypertension. Resumen: Las plantas de los géneros Werneria (Asteraceae) y Xenophyllum (género extraido de Werneria) son usadas en la medicina tradicional de América Latina para el tratamiento del mal de montaña, hipertensión y desórdenes gastrointestinales. Solo un pequeño número de especies de estos géneros ha sido investigado, lográndose aislar compuestos que pertenecen a las clases de benzofuranos, cromenos, acetofenonas, cumaratos, diterpenos y alcaloides pirrolizidínicos. Algunos de los extractos y/o compuestos de dichas plantas han mostrado actividades antimicrobianas, anti-HIV, hipotensoras y fotoprotectoras. Palabras clave: Werneria; Xenophyllum; Plantas medicinales; Mal de montaña; Hipertensión. Recibido | Received: March 6, 2019 Aceptado | Accepted: April 6, 2019 Aceptado en versión corregida | Accepted in revised form: April 16, 2019. Publicado en línea | Published online: May 30, 2019 Este artículo puede ser citado como / This article must be cited as: O Lock, R Rojas. 2019 Phytochemistry and biological activities of Werneria and Xenophyllum species. Bol Latinoam Caribe Plant Med Aromat 18 (3): 223 – 238. 223 Lock et al. Werneria and Xenophyllum – A review INTRODUCTION The genus Werneria was established by Carl S. Kunth Hooker & Arnott (1). In the case of the genus and dedicated to the German geologist Abraham G. Xenophyllum, only two species have been investigated: Werner. The morphological characteristics of this X. poposum (Phillipi) V.A. Funk (7 publications) and genus show the variability of the species and support X. incisum (Phillipi) V.A. Funk (1). It has to be noted that it is not a monophyletic genus, for this reason, that W. poposa is now known as X. poposum. Of the almost half of the species were transferred to the new 28 publications found in the scientific literature for genera Xenophyllum, Misbrookea and Anticona (Funk Werneria and Xenophyllum species, 16 refer to 1997a; Funk, 1997b; Linares-Perea et al., 2014; samples collected in Peru, 7 in Argentina, 3 in Chile, 1 Beltrán, 2017). Currently, the Werneria genus could in Bolivia and 1 in Ecuador. be composed of 25-30 species, distributed in the South Phytochemical studies on the genus Werneria American Andes (2.800 m.a.s.l) from Venezuela, have reported a variety of chemical constituents that Colombia, Ecuador, Perú, Bolivia to northern include pyrrolizidine-type alkaloids, phenolics (such Argentina and Chile, with an isolated population of W. as benzofurans, benzopyrans, p-coumarates, nubigena in Mexico and northern Guatemala. The coumarins, flavonoids, p-hydroxyacetyphenones, Peruvian territory hosts the greatest wealth of caffeoylquinic acids), as well as volatile terpenes, Werneria genus with 22 species, of which 5 are diterpenes (mainly kauran and manoyl derivatives), endemic (Beltrán, 2017). Recently, Werneria triterpenes and steroids; all these compounds will be microphylla was described as new species from the presented in the following sections. Some of them high Andes of Peru (Beltrán & Leiva, 2018), it is have been reported in a previous review (Lock Sing, likely that there are more Werneria species to be 2006). discovered. The genus Xenophyllum consists of 22 species CHEMICAL CONSTITUENTS extracted from Werneria, 14 of them have been Alkaloids reported in Peru (Beltrán, 2016). “Xeno” means A total of 6 pyrrozilidine alkaloids (PAs) have been “strange” or “foreign”, while “phyllum" means isolated from 2 Werneria species. Alkaloids N- “leaves”. Members of this genus grow at high oxoretronecine (1) and N-oxoretrorsine (4) have been elevations (3,000-5,200 m) in the Andes from isolated from W. decora (Lock de Ugaz et al., 1990), Colombia to northern Argentina and Chile (Funk, while alkaloids retrorsine (2), senecionine (3), 4, 1997a). integerrimine (5) and N-oxorosmarinine (6) were Misbrookea is a new genus extracted from reported for W. nubigena (Roeder et al., 1992; Werneria, named after its collector Winifred M.A. Piacente et al., 1997). Brooke. For this genus, only one species The presence of PAs is important from the (Misbrookea strigosissima (A. Gray) V.A. Funk) has chemotaxonomic point of view of Werneria, as it is been reported; it grows at the grasslands of the generally regarded as a member of the tribe highlands of southern Peru and Bolivia (Funk 1997b; Senecioneae which is known to contain PAs. Linares-Perea et al., 2014). More recently, Linares- Pyrrolizidine alkaloids contain an azabicyclo [3,3,0] Perea et al. collected Werneria glareophila described octane as a basic structure; they generally are found as by Cuatrecasas and found that its characters deviate esters with rare mono- or di-basic acids, the necic from the genera Werneria, Misbrookea, and acids, producing a 12-membered macrocycle (2-6). It Xenophyllum. They described the new genus Anticona is also worth noting that, in general, the PAs comprised by only one species, named as accumulate in the plant as polar N-oxides (1,4,6). Anticona glareophila (Cuatrec.) E. Linares, J. Campos & A. Galán (Linares-Perea et al., 2014). Benzofurans So far, the phytochemical study and/or Benzofurans are commonly found in Asteraceae biological activities of 9 Werneria species have been family. Benzofurans dihydroeuparin or 6- reported: W. ciliolate A. Gray (5 publications), W. hydroxytremetone (7) (Lock de Ugaz et al., 1984; poposa Philippi (4), W. nubigena H.B.K. (3), W. Palacios et al., 2018), 2,5-diacetyl-6-hydroxy- dactylophylla Schultz-Bip (3), W. stuebelli Hieron (1), benzofurane (8) (Lock de Ugaz & Peralta, 1988), toxol W. decora cf. Blake (1), W. staffordiae Sandwith (1), (9) (Piacente et al., 1992), toxolacetate (10) (Córdova W. digitata Wedell (1) and W. pigmeae Gillies ex et al., 1998; de Marchese et al., 2007), toxolangelate Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/224 Lock et al. Werneria and Xenophyllum – A review (11) (de Marchese et al., 2007) and lactone 2,3- hydroxyethyl)-6-hydroxybenzofurane (13) (Castro et dihydro-2-oxo-5-formyl-6-methoxy-7-(3’-methyl-3’- al., 2000) has another substituent. These benzofurans butenyl)-benzo-furane (12) (Castro et al., 2000) have a were found in W. ciliolata, W. poposa, W. nubigena methylcetone group in para position to the oxygen of and X. poposum. the heterocycle ring, while 2-acetyl-5-(2’- Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/225 Lock et al. Werneria and Xenophyllum – A review Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/226 Lock et al. Werneria and Xenophyllum – A review Benzopyran derivatives (Chromenes) Sometimes this substituent is different like in 9-E- The basic structure of chromenes, which are werneria chromene (17), 9-Z-werneria chromene (18), benzopyrans derivatives, is a joined benzene and 8-[3’,3’-dimethylallyl]-werneria chromene (19) and 8- pyrane rings with two dimethyl group in position 2 and [3’,3’-dimethyl-3’-hydroxyallyl]-werneria chromene the methyl cetone group in para position to the oxygen (20). of the heterocycle ring, as observed in 2,2-dimethyl-6 Compounds 14 and 15 were found in W. acetyl-8-(3’-hydroxy-3’-methyl-trans-but-1’-enyl)- nubigena (Piacente et al., 1997); 16 in X. incisum (de chroman-4-one (14), 2,2-dimethyl-6-acetyl-8-(3’- Marchese et al., 2007) and 17-20 in W. stuebelli hydroxy-3’-methyl-trans-but-1’-enyl)-chrom-3-ene (Bohlmann et al., 1984). Benzopyran 14 was reported (15) and 2,2-dimethyl-6-acetyl-3-chromene (16). as a new structure by Piacente et al. (1997). Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/227 Lock et al. Werneria and Xenophyllum – A review p-Coumarates and derivatives 3’-en-1’-yl]-p-coumarate (24), Plicatin A (25) and p-coumaric acid is formed through the deamination of Plicatin B (26) contain substituents in C-3 of the L-tyrosine, one simple derivative is the compound aromatic ring. Compounds 22-24 were reported for W. methyl p-coumarate (21). Other p-coumarates like stuebelli (Bohlmann et al., 1984), while Plicatin A and methyl 3-[3’, 3’-dimethyl-3’-hydroxyallyl]-p- B were isolated from W. dactylopylla (Bravo et al., coumarate-O-methyl ether (22), ethyl-3-senecioyl-p- 2009). coumarate (23), methyl-3-[3’-methyl-1’-hydroxy-but- Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/228 Lock et al. Werneria and Xenophyllum – A review Coumarins (30) and 7-hydroxy-8-methoxycoumarin (31). These Coumarins are phenolic compounds that are much coumarins were found in W. ciliolata, W. extended in the plant kingdom; however, only five dactylophylla, W. poposa and W. staffordiae (Bonilla coumarins were reported so far for Werneria species: et al., 1991; Ponce & Gros, 1991; Piacente et al., aesculetin (27), aesculetin-7-O-β-D-glucopyranoside 1994; Chavez & Lock de Ugaz, 1997; Córdova et al., (28), scopoletin (29), 6-hydroxy-7-methoxycoumarin 1998).