The genus Haplopappus: botany, phytochemistry, traditional uses, and pharmacological properties

Abstract

Background:

The genus Haplopappus Cass. [Asteraceae] comprises a large number of species distributed mainly in Chile and with various traditional medicinal uses.

Purpose:

The present review addresses the botany, traditional uses, chemistry, biological and pharmacological activities of the genus, aiming to further potentiate the associated research and applications.

Study design and Methods:

Literature data on the chemistry and bioactivity of the genus Haplopappus were mainly retrieved from digital databases such as SciFinder^®, PubMed^®, and Google Scholar^®, as well as from the scientific journal publishers’ platforms linked with these databases.

Results and discussion:

Although the majority of the botanical taxa of the genus Haplopappus has been understudied, available information is promising regarding its phytochemistry and bioactivity. A total of more than 400 compounds are present in different Haplopappus species, mostly terpenoids and phenolic compounds. Scientific literature supports various health promoting effects of Haplopappus extracts and isolated compounds, principally their effect against human pathogenic bacteria and their high antioxidant capacity. The existing limitations highlighted hereby are mainly associated to the lack of modern investigation regarding a wider number of Haplopappus species and chemical compounds, as well as to the absence of in vivo bioactivity results and clinical trials.

Conclusion:

Scientific literature supports the ethnopharmacological, phytochemical and bioactive potential of the genus Haplopappus, however the aforementioned limitations need to be addressed in order to further promote and broaden both scientific research and future applications and uses.

1 Introduction

Haplopappus Cass. (Asteraceae (Compositae) - Astereae - Machaerantherinae), is a strictly endemic botanical genus of southern South America, distributed in Chile, with some species also present in Argentina (Klingenberg, 2007). The vernacular name ‘bailahuén’ (‘baylahuén’ or ‘vaila-huen’) has been mainly attributed to the species Haplopappus baylahuen Remy, although the other species of the genus are commonly referred to using the same name (Vogel et al., 2007).

The different species of the genus Haplopappus, although used without differentiation in terms of botanical taxa, are of high ethnopharmacological importance and form part of the longstanding traditional medicines of the Andean peoples. In Chile, where the genus is mainly distributed, its species have been widely used in all territory, from the Aymara communities in the north to Mapuche communities in the south, and in big cities by different social groups (Hoffmann et al., 1992). Bailahuén is used at the prevention and/or treatment of various human and animal pathologies, mainly -but not exclusively-associated to gastrointestinal ailments and wound healing (Muñoz et al., 1981; de Mösbach, 1992; Hoffmann et al., 1992). Alongside its traditional use, H. baylahuen is also included in the German Homeopathic Pharmacopeia as a herbal medicine against fatigue and low blood pressure, although its use is considered limited (Arzneibuch, 2006; Vogel et al., 2007).

Regarding its commercialization, it is reported that its production in Chile is exclusively based on the collection of plant material in the wild, which, in most cases, is realized by non-trained individuals (Vogel et al., 2007). Furthermore, in the same study it is highlighted that the 80% of bailahuén commercial samples correspond to Haplopappus multifolius, probably due to the fact that this species is distributed in the Metropolitan Region of Santiago, where the companies that commercialize the plant material at a national and international level are also located. The over-exploitation of H. multifolius, along with inadequate collection practices, have led to the species being recently included in The IUCN Red List of Threatened Species as Near Threatened (Plummer, 2022).

In this context, despite its high botanical diversity and the rich ethnopharmacological background of the genus Haplopappus, both scientific investigation and commercial use is often limited to a few botanical taxa, while in many cases the traditional knowledge associated with the genus is not taken into consideration, thus hindering unravelling the full phytochemical and bioactive potential of the genus.

Thus, the present article aims to present a comprehensive review of the current state of knowledge regarding the botany, traditional uses, chemistry, biological and pharmacological activities of the genus Haplopappus in an attempt to underline its phytochemical uniqueness, elucidate its bioactive potential, and highlight future research opportunities.

2 Methods

Literature data on the chemistry and bioactivity of the genus Haplopappus were mainly retrieved from digital databases such as SciFinder^®, PubMed^®, and Google Scholar^®, as well as from the scientific journal publishers’ platforms linked with these databases. The search strategy included the scientific name of the genus, excluding the species presently classified in other genera, i.e., Ericameria Nutt., Grindelia Willd., Gundlachia A.Gray, Isocoma Nutt., Notopappus L. Klingberg (Klingenberg, 2007; POWO, 2024). All publications in peer-reviewed journals until May 2024 were considered. The chemical compounds present in the raw materials were classified according to their pathway and superclass (Supplementary Table S1; Figures 1–11) using the NPClassifier tool (Kim et al., 2021).

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3 Botany and distribution

The genus Haplopappus Cass. (Asteraceae - Astereae - Machaerantherinae) is a strictly endemic genus of South America and its species are mainly distributed in Chile and, to a lesser extent, Argentina (Klingenberg, 2007; Rodriguez et al., 2018; Zuloaga et al., 2019; García et al., 2024).

According to the latest taxonomic studies of the genus and after the separation of numerous, mainly North American, species that formed the genus Notopappus L. Klingenberg, the genus Haplopappus consists of 70 specific and intraspecific taxa (Table 1) and is subdivided into three subgenera (Haplopappus subgen. Haplopappus, H. subgen. Grindelioidae Klingenberg, and H. subgen. Baylahuen Klingenberg) and five sections: Haplopappus sect. Haplopappus, H. sect. Gymnocoma Nuttall, H. sect. Grindelioidae Klingenberg, H. sect. Chromochaeta Candolle, and H. sect. Leiachaenium Candolle (Klingenberg, 2007; Garcia et al., 2018; García et al., 2024). Haplopappus taxonomy is mainly based on morphological traits, due to the limited phylogenetic data available up to date (García et al., 2024). In general, Haplopappus species are shrubs or subshrubs, with aerial parts that bear glandular trichomes, usually yellow florets, and numerous pappus bristles (Klingenberg, 2007; García et al., 2024).

4 Phytochemistry

Available scientific literature provides relevant information on the phytochemistry of the genus Haplopappus. However, it must be mentioned that this information refers to only 28 species and subspecies of a total of 70 taxa (Table 1), thus highlighting the largely understudied potential of the genus Haplopappus and stressing the need to further investigate its phytochemistry. Moreover, of these 28 taxa for which scientific evidence is available, for the 24 there are less than 35 compounds reported per taxa, whereas the remaining four species are associated to a higher -yet still rather diverse-number of reported compounds, i.e., H. foliosus (n = 146), H. velutinus (n = 59), H. chrysanthemifolius (n = 52), H. bustillosianus (n = 40).

Regarding the type of metabolites reported in Haplopappus species, more than 400 different molecules have been detected in various plant parts of the studied taxa. However, the number of reported compounds per chemical group is highly diverse, to an extent that it raises the question of whether this variability can be solely attributed to differences at a plant metabolic level or it can also be associated with a focus of scientific research towards certain groups of metabolites, e.g., terpenoids and phenolics. Indeed, products of the terpenoid metabolic pathway are by far the most abundant group of molecules reported in the genus Haplopappus, including more than 200 compounds, i.e. 54 monoterpenoids (abbreviated as Mon in compound codification used in the present review), 60 sesquiterpenoids (Sqt), 107 diterpenoids (Dit), five triterpenoids (Tri), one meroterpenoid (Mer) and two steroids (Str). The second most abundant group of reported compounds includes flavonoids (Flv; flavonols, n = 46; flavones, n = 20; flavanones, n = 8; flavanonols, n = 11) and other products of the metabolic pathway of shikimic acid, i.e., coumarins (Cum, n = 16), benzoic (Ben, n = 3) and cinnamic (Cin, n = 12) acid derivatives. Other compounds reported in the genus Haplopappus include alkanes (Ala, n = 29), alkenes (Ale, n = 4), alkynes (Aly, n = 1), alcohols (Alc, n = 5), ethers (Eth, n = 1), aromatic hydrocarbons and derivatives (Arh, n = 10), aldehydes (Ald, n = 8), ketones (Ket, n = 7), esters (Est, n = 8), furanones (Fur, n = 1), lactones (Ltn, n = 2) and lactams (Ltm, n = 1).

The aforementioned compounds as classified per chemical group are detailed in Figures 1–11 and Tables 2–4, and Supplementary Table S1, while their distribution among the studied Haplopappus taxa is presented as follows.

TABLE 2

No.	Compound	R3	R5	R6	R7	R8	R3'	R4'	R5'
Flavonols
Flv1	quercetin	OH	OH	H	OH	H	OH	OH	H
Flv2	quercetin 3-methyl ether	OMe	OH	H	OH	H	OH	OH	H
Flv3	tamarixetin (quercetin 4′-methyl ether)	OH	OH	H	OH	H	OH	OMe	H
Flv4	rhamnazin (quercetin 7,3′-dimethyl ether)	OH	OH	H	OMe	H	OMe	OH	H
Flv5	quercetin 3,3′-dimethyl ether	OMe	OH	H	OH	H	OMe	OH	H
Flv6	quercetin 3,7-dimethyl ether	OMe	OH	H	OMe	H	OH	OH	H
Flv7	ayanin	OMe	OH	H	OMe	H	OH	OMe	H
Flv8	retusin (5-hydroxy-3,7,3′,4′-tetramethoxyflavone)	OMe	OH	H	OMe	H	OMe	OMe	H
Flv9	3-O-acetyl-7-methylquercetin	OAc	OH	H	OMe	H	OH	OH	H
Flv10	isoquercitrin (quercetin-3-β-D-glucoside)	O-Glu	OH	H	OH	H	OH	OH	H
Flv11	hyperoside (quercetin-3-β-D-galactoside)	O-Gal	OH	H	OH	H	OH	OH	H
Flv12	quercetagetin 3-methyl ether	OMe	OH	OH	OH	H	OH	OH	H
Flv13	quercetagetin 3,7-dimethyl ether	OMe	OH	OH	OMe	H	OH	OH	H
Flv14	centaureidin	OMe	OH	OMe	OH	H	OH	OMe	H
Flv15	betuletol (3,5,7-trihydroxy-6,4′-dimethoxyflavone)	OH	OH	OMe	OH	H	H	OMe	H
Flv16	eupatolitin	OH	OH	OMe	OMe	H	OH	OH	H
Flv17	rhamnetin	OH	OH	H	OMe	H	OH	OH	H
Flv18	isorhamnetin	OH	OH	H	OH	H	OMe	OH	H
Flv19	isorhamnetin-3-β-D-glucoside	O-Glu	OH	H	OH	H	OMe	OH	H
Flv20	isorhamnetin-3-β-D-galactoside	O-Gal	OH	H	OH	H	OMe	OH	H
Flv21	kaempferol	OH	OH	H	OH	H	H	OH	H
Flv22	astragalin (kaempferol 3-β-D-glucoside)	O-Glu	OH	H	OH	H	H	OH	H
Flv23	isokaempferide (kaempferol 3-methyl ether)	OMe	OH	H	OH	H	H	OH	H
Flv24	kaempferol 3-methyl ether 7-β-D-glucoside	OMe	OH	H	O-Glu	H	H	OH	H
Flv25	rhamnocitrin (kaempferol 7-methyl ether)	OH	OH	H	OMe	H	H	OH	H
Flv26	ermanin (kaempferol 3,4′-dimethyl ether)	OMe	OH	H	OH	H	H	OMe	H
Flv27	kaempferol 7,4′-dimethyl ether	OH	OH	H	OMe	H	H	OMe	H
Flv28	kumatakenin (kaempferol 3,7-dimethyl ether)	OMe	OH	H	OMe	H	H	OH	H
Flv29	kaempferol 3,7,4′-trimethyl ether	OMe	OH	H	OMe	H	H	OMe	H
Flv30	3-O-acetyl-7,4′-dimethylkaempferol	OAc	OH	H	OMe	H	H	OMe	H
Flv31	haplopappin	OMe	OH	H	OH		H	OMe	H
Flv32	haplopappin A	OH	OH	H	OMe		H	OMe	H
Flv33	myricetin	OH	OH	H	OH	H	OH	OH	OH
Flv34	myricetin 3′,4′-dimethyl ether	OH	OH	H	OH	H	OMe	OMe	OH
Flv35	myricetin 3,3′,4′-trimethyl ether	OMe	OH	H	OH	H	OMe	OMe	OH
Flv36	myricetin 3,7,4′-trimethyl ether	OMe	OH	H	OMe	H	OH	OMe	OH
Flv37	3,8-dimethylherbacetin (5,7,4′-trihydroxy-3,8-dimethoxyflavone)	OMe	OH	H	OH	OMe	H	OH	H
Flv38	3,8,4′-trimethylherbacetin (5,7-dihydroxy-3,8,4′-trimethoxyflavone)	OMe	OH	H	OH	OMe	H	OMe	H
Flv39	5,7,4′-trihydroxy-3,8,3′-trimethoxyflavone	OMe	OH	H	OH	OMe	OMe	OH	H
Flv40	3,5-dihydroxy-3′,4′,6,7-tetramethoxyflavone	OH	OH	OMe	OMe	H	OMe	OMe	H
Flv41	santin	OMe	OH	OMe	OH	H	H	OMe	H
Flv42	eupatorin	H	OH	OMe	OMe	H	OH	OMe	H
Flv43	jaceidin	OMe	OH	OMe	OH	H	OMe	OH	H
Flv44	jaceidin 7-methyl ether	OMe	OH	OMe	OMe	H	OMe	OH	H
Flv45	penduletin	OMe	OH	OMe	OMe	H	H	OH	H
Flv46	pachypodol	OMe	OH	H	OMe	H	OMe	OH	H
Flavones
Flv47	apigenin	H	OH	H	OH	H	H	OH	H
Flv48	3,6-dimethoxyapigenin	OMe	OH	OMe	OH	H	H	OH	H
Flv49	vicenin-2	H	OH	C-Glu	OH	C-Glu	H	OH	H
Flv50	vitexin	H	OH	H	OH	C-Glu	H	OH	H
Flv51	isovitexin	H	OH	C-Glu	OH	H	H	OH	H
Flv52	isoschaftoside	H	OH	C-Ara	OH	C-Glu	H	OH	H
Flv53	luteolin	H	OH	H	OH	H	OH	OH	H
Flv54	luteolin 5-glucoside	H	O-Glu	H	OH	H	OH	OH	H
Flv55	luteolin 7-glucoside	H	OH	H	O-Glu	H	OH	OH	H
Flv56	chrysoeriol	H	OH	H	OH	H	OMe	OH	H
Flv57	velutin (luteolin 7, 3′-dimethyl ether)	H	OH	H	OMe	H	OMe	OH	H
Flv58	diosmetin	H	OH	H	OH	H	OH	OMe	H
Flv59	eupafolin (6-methoxyluteolin)	H	OH	OMe	OH	H	OH	OH	H
Flv60	6-methoxyluteolin 4′-methyl ether	H	OH	OMe	OH	H	OH	OMe	H
Flv61	cirsiliol (6-methoxyluteolin 7-methyl ether)	H	OH	OMe	OMe	H	OH	OH	H
Flv62	hispidulin (scutellarein 6-methyl ether)	H	OH	OMe	OH	H	H	OH	H
Flv63	pectolinaringenin	H	OH	OMe	OH	H	H	OMe	H
Flv64	scutellarein 6-β-D-glucoside	H	OH	O-Glu	OH	H	H	OH	H
Flv65	3′,4′-dihydroxyflavone 5-glucoside	H	O-Glu	H	H	H	OH	OH	H
Flv66	verbenacoside	H	O-Glu	H	H	H	H	OH	H

Substitution pattern of flavonols and flavones reported in species of the genus Haplopappus.

TABLE 4

No.	Compound	R6	R7
Cum1	esculetin	OH	H
Cum2	esculin	Glu	H
Cum3	prenyletin	OH
Cum4	haplopinol	OH
Cum5	6-deoxyhaplopinol	H
Cum6	6-hydroxy-7-(5′-hydroxy-3′,7′-dimethylocta-2′,6′-dien)-oxycoumarin	OH
Cum7	6-hydroxy-7-(7′-hydroxy-3′,7′-dimethylocta-2′,5′-dien)-oxycoumarin	OH
Cum8	6-hydroxy-7-[(E,E)-3′,7′-dimethyl-2′,4′,7′-octatrienyloxy] coumarin	OH
Cum9	scopoletin	OMe	H
Cum10	7-O-prenylscopoletin	OMe
Cum11	7-O-geranylscopoletin	OMe
Cum12	scoparone	OMe	Me
Cum13	hernianin	H	Me
Cum14	umbelliferone	H	H
Cum15	O-prenylumbelliferone	H

Substitution pattern of coumarins reported in species of the genus Haplopappus.

4.1 H. angustifolius (DC.) Reiche

Information on the chemical composition of H. angustifolius is limited to reports of the presence of hentriacontane (Ala22), hexacosanol (Alc1), the diterpenes haplopappic acid (Dit96) and its methylester (Dit97) and the triterpenes friedelin (Tri1) and epi-friedelinol (Tri3) in the aerial parts of the plant (Silva and Sammes, 1973).

4.2 H. anthylloides Meyen & Walp

The ketone 4-hydroxyacetophenone (Ket2) is the only compound identified in the aerial parts of H. antylloides (Zdero et al., 1990).

4.3 H. arbutoides Remy

The majority of the compounds identified in the aerial parts and/or resin of H. arbutoides belong to the diterpenoids group, i.e. 15-oxo-labda-8(17),14E-diene-18-oic acid (Dit32), 15-oxo-labda-8(17),14Z-diene-18-oic acid (Dit33), labda-8(17),13E-dien-15,18-dioic acid 15-methyl ester (Dit34), 15-hydroxylabd-8(17)-en-18-oic acid (Dit35), labd-13(E)-ene-8α,15-diol (Dit62), 13R-labdane-8,15-diol (Dit63), 8α-hydroxy-ent-labd-13(14)Z-en-15-al (Dit64), 8α-hydroxylabdan-15-al (Dit65), epi-manoyl oxide (Dit68), 8,13-epoxy-14-labdeb-3-ol (Dit74), 8,13-epoxy-labdan-15-al (Dit75), 15-oxocleroda-3,13E-dien-18-oic acid (Dit91), and 15-oxocleroda-3,13Z-dien-18-oic acid (Dit92) (Zdero et al., 1991a; Rossomando et al., 1995). Additionally, the aerial parts are reported to contain 4-hydroxyacetophenone (Ket2), the sesquiterpene 1β-hydroxy-β-cyperone (Sqt44) and the flavonols santin (Flv41) and penduletin (Flv45) (Zdero et al., 1991a; Rossomando et al., 1995).

4.4 H. baylahuen Remy

The essential oil of the leaves of H. baylahuen is reported to contain eicosane (Ala11), benzene (Arh1), azulene (Arh2), naphthalene (Arh4), and the sesquiterpenes bergamotol (Sqt8) and α-cadinol (Sqt24) (Becerra et al., 2010). Phenolic compounds detected in this species include quercetin (Flv1), quercetin 3-methyl ether (Flv2), rhamnetin (Flv17), isorhamnetin (Flv18), kaempferol (Flv21), rhamnocitrin (Flv25), velutin (Flv57), sakuranetin (Flv67), persicogenin (Flv69), sternbin (Flv70), 7,4′-dimethylaromadendrin (Flv75), 7-O-methylaromadenrin (Flv76), 7,3′-di-O-methyltaxifolin (Flv81), dihydromyricetin (Flv82), prenyletin (Cum3), and 3,5-dicaffeoylquinic acid (Cin12) (Schwenker et al., 1967; Hörhammer et al., 1973; Nuñez-Alarcon et al., 1993; Vera et al., 2001; Schmeda-Hirschmann et al., 2015).

4.5 H. bezanillanus (Remy) Reiche

The compounds detected in the aerial parts of H. bezanillanus are the diterpenoid labd-13(E)-ene-8α,15-diol (Dit62), the steroid β-sitosterol (Str2) and the flavonol jaceidin 7-methyl ether (Flv44) (Maldonado et al., 1993).

4.6 H. bustillosianus Remy

The aerial parts of H. bustillosianus contain the alkenes C₁₁H₂₄ – C₁₄H₃₀(Ala2 – Ala5), C₁₆H₃₄ – C₃₃H₆₈(Ala7 – Ala24), along with 3-hydroxyacetophenone (Ket1) and the flavonoids santin (Flv41) and 3,6-dimethoxyapigenin (Flv48) (Urzúa et al., 2007a). Their phenolic profile includes α-linalool (Mon4), α-pinene (Mon37), β-pinene (Mon38), α-bisabolol (Sqt4), humulene (Sqt5), α-cadinene (Sqt18), γ-cadinene (Sqt20), δ-cadinene (Sqt21), (−)-isocaryophyllene (Sqt30), α-cubebene (Sqt48), β-cubebene (Sqt49), α-copaene (Sqt58), populifolic acid (Dit89) and its methyl ester (Dit90), and thunbergol (Dit102) (Urzúa et al., 2007a).

4.7 H. chrysanthemifolius (Less.) DC

The phytochemistry of H. chrysanthemifolius has been thoroughly investigated and various chemical groups of compounds have been identified in this species. Among them, in the flower heads there are present the alkanes C₁₀H₂₂ – C₁₉H₄₀(Ala1 – Ala10), C₂₁H₄₄ – C₃₃H₆₈(Ala12 – Ala24), 2-methyldecalin (Ala25), 2,4,6-trimethyloctane (Ala26), 2,6-dimethylundecane (Ala27), 4,6-dimethylundecane (Ala28), and 2,10-dimethylundecane Ala29) (Urzúa et al., 2007a). Furthermore, the terpenoid profile of the species includes β-myrcene (Mon3), limonene (Mon8), α-pinene (Mon37), β-pinene (Mon38), humulene (Sqt5), δ-cadinene (Sqt21), (−)-isocaryophyllene (Sqt30), β-bulgarene (Sqt31), γ-bulgarene (Sqt32), (−)-amorpha-4,11-diene (Sqt33), α-cubebene (Sqt48), β-cubebene (Sqt49), (−)-calarene (Sqt50), 1,3,4,5,6,7-hexahydro-2,5,5-trimethyl-2H-2,4a-ethanonaphthalene (Sqt51), α-copaene (Sqt58), 6α-hydroxy-ent-labd-8(17)-en-15-oic acid (Dit1), 3β-acetoxy-ent-labd-8(17)-en-15-oic acid (Dit2), and 18α-acetoxylabd-8(17)-en-15-oic acid (Dit3) (Faini et al., 1999; Urzua et al., 2007b). Regarding the phenolic compounds of H. chrysanthemifolius, it is reported the presence of quercetin (Flv1), tamarixetin (Flv3), ayanin (Flv7), myricetin 3,7,4′-trimethyl ether (Flv36), luteolin (Flv53), and diosmetin (Flv58) (Faini et al., 1999; Urzua et al., 2007b; Urzúa et al., 2012).

4.8 H. coquimbensis (Hook. & Arn.) Klingenb

The aerial parts of H. coquimbensis (syn. H. hirtellus Phil. (Klingenberg, 2007)) contain the terpenoids 7,13-labdadien-15,18-dioic acid 15-methyl ester (Dit44) and epi-friedelin (Tri2), as well as stigmasterol (Str1) (Maldonado et al., 1993). Regarding its flavonoid profile, the following compounds were detected in its aerial parts: kaempferol 7,4′-dimethyl ether (Flv27), kaempferol 3,7,4′-trimethyl ether (Flv29), pachypodol (Flv46), sakuranetin 4′-methyl ether (Flv68), eriodictyol 7,3′-dimethyl ether (Flv72), 7,4′-dimethylaromadendrin (Flv75), and 7,3′-di-O-methyltaxifolin (Flv81) (Maldonado et al., 1993).

4.9 H. deserticola Phil

In the aerial parts of H. deserticola there were detected the diterpenoids methyl-ent-4-epi-agath-18-oate (Dit17), dimethyl-ent-4-epi-agathoate (Dit18), copaiferolic acid (Dit19), copaiferolic acid 15-methyl ester (Dit20), methyl haplodesertoate (Dit26), 8α-hydroxyanticopalic acid (Dit60), 8α-hydroxyanticopalic acid methyl ester (Dit61), ent-19-hydroxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit98), and 18-acetoxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit99), along with the sesquiterpenoid germacrene D (Sqt7) (Zdero et al., 1990; Urzúa Moll et al., 1997; Tojo et al., 1999).

Regarding its phenolic composition, the aerial parts of this species are reported to contain the flavonoids quercetin (Flv1), quercetin 3-methyl ether (Flv2), isokaempferide (Flv23), 3,8-dimethylherbacetin (Flv37), 3,8,4′-trimethylherbacetin (Flv38), and 5,7,4′-trihydroxy-3,8,3′-trimethoxyflavone (Flv39); the coumarins 7-O-prenylscopoletin (Cum10), 7-O-geranylscopoletin (Cum11), O-prenylumbelliferone (Cum15) and the dimeric umbelliferone 3,3-dimethylallyl ether (Cum16), as well as the cinnamic acid derivatives chlorogenic acid (Cin10), 3,4-dicaffeoylquinic acid (Cin11), and 3,5-dicaffeoylquinic acid (Cin12) (Zdero et al., 1990; Tojo et al., 1999; Schmeda-Hirschmann et al., 2015).

4.10 H. diplopappus Remy

The resinous exudate of H. diplopappus is reported to contain the diterpenoid ent-manool (Dit9) and its 13-O-β-xylopyranoside (Dit8) (Urzua et al., 1995a).

4.11 H. foliosus (Hook. & Arn.) Hook. & Arn

H. foliosus is the species for which the greatest number of compounds has been reported. Among them, there are the alkanes C₁₂H₂₆(Ala3), C₁₄H₃₀(Ala5), C₁₆H₃₄(Ala7), C₁₈H₃₈(Ala9), and C₂₃H₄₈ – C₃₃H₆₈(Ala14 – Ala24) (Silva and Sammes, 1973; Urzúa et al., 2000; Urzúa, 2004). Furthermore, the aerial parts of this species contain 11-tricosene (Ale1), hexacosanol (Alc1), ethylresorcinol (Alc2), diisopropyl ether (Eth1), α-asarone (Arh3), 1,2,3,4,5,6,7,8-octahydro-1-methylphenantrene (Arh5), eugenol (Arh6), styrene (Arh7), safrol (Arh8), elemicin (Arh9), dihydrobenzofuran (Arh10), benzaldehyde (Ald1), 2,3-dichloro-2-methylpropanal (Ald2), trans-2-hexenal (Ald3), nonanal (Ald4), decanal (Ald5), 3-ethylbenzaldehyde (Ald6), 4-vinylbenzaldehyde (Ald7), 3-hydroxyacetophenone (Ket1), 3-ethylacetophenone (Ket3), 4-ethylacetophenone (Ket4), dihydro-α-ionone (Ket6), 4,4-dimethyl-2-allylcyclohexanone (Ket7), (Z)-3-hexenyl acetate (Est8), tetrahydroactinidiolide (Ltn2), 4-phenyl-2-azetidinone (Ltm1), and stigmasterol (Str1) (Silva and Sammes, 1973; Urzúa et al., 2000; 2010; Urzúa, 2004; Villagra et al., 2021).

The terpenoid fraction of H. foliosus has been thoroughly studied and more than 70 compounds have been reported. Among them, there are the monoterpenoids cis-α-ocimene (Mon1), β-ocimene (Mon2), β-myrcene (Mon3), limonene (Mon8), α-terpinene (Mon9), γ-terpinene (Mon10), terpinen-4-ol (Mon11), terpinolene (Mon16), isoterpinolene (Mon17), α-terpineol (Mon18), p-menth-2-en-4-ol (Mon19), trans-p-menth-2-en-1-ol (Mon21), cis-p-menth-2-en-1-ol (Mon22), α-phellandrene (Mon25), m-cymene (Mon27), p-cymene (Mon28), p-cymen-8-ol (Mon29), o-cumenol (Mon30), 3-carene (Mon31), thujane (Mon32), α-thujene (Mon33), cis-(+/−)-4-thujanol (Mon34), 4-thujanol (Mon35), α-thujone (Mon36), α-pinene (Mon37), β-pinene (Mon38), pinocarveol (Mon39), borneol (Mon42), bornyl acetate (Mon43), camphor (Mon44), camphene (Mon45), fenchol (Mon46), 1,5-dimethyl-6-methylenespiro[2.4]heptane (Mon48), sabinene (Mon49), 5-(acetyloxy)-4,6,6-trimethyl-endobiciclo[2.2.1]heptan-2-one (Mon50), ascaridole (Mon52), and tricyclene (Mon54) (Urzúa et al., 2000; 2010; Urzúa, 2004; Villagra et al., 2021). The equally diverse sesquiterpenoid fraction includes germacrene D (Sqt7), (1α,7β,10β)-11-hydroxy-4-guaien-3-one (Sqt9), (1β,7β,10β)-1,11-dihydroxy-4-guaien-3-one (Sqt10), (1α,6α,7β,10β)-6,11-dihydroxy-4-guaien-3-one (Sqt11), α-selinene (Sqt13), γ-selinene (Sqt14), 5-eudesmen-11-ol (Sqt15), γ-eudesmol (Sqt16), cadalene (Sqt17), α-cadinene (Sqt18), β-cadinene (Sqt19), γ-cadinene (Sqt20), δ-cadinene (Sqt21), guaiol (Sqt22), 1(10),11-eremophiladiene (Sqt23), α-cadinol (Sqt24), ionene (Sqt25), 6-(1,1-dimethylethyl)-2,3-dihydro-1,1-dimethyl-3-methylene-1H-indene (Sqt26), δ-ambrinol (Sqt27), decahydro-3a,8-dimethyl-5-(1-methylethenyl)azulene (Sqt28), 1,2,3,4,5,6,7,8-octahydro-1,4-dimethyl-7-(1-methylethylidene)azulene (Sqt29), β-guaiene (Sqt36), (−)-caryophyllene (Sqt38), epi-bicyclosesquiphellandrene (Sqt39), α-muurolene (Sqt40), γ-muurolene (Sqt41), agarospirol (Sqt42), aromadendrene (Sqt47), α-cubebene (Sqt48), β-cubebene (Sqt49), spathulenol (Sqt52), β-bourbonene (Sqt55), α-copaene (Sqt58), β-copaene (Sqt59), and β-ylangene (Sqt60) (Labbé et al., 1998; Urzúa et al., 2000; 2010; Urzúa, 2004; Villagra et al., 2021). Much less diverse are the reported di- and triterpenoid profiles of the species, which include 2α-hydroxy-cis-clero-3,13(Z),8(17)-trien-15-oic acid (Dit87), 2α-acetoxy-cis-clero-3,13(Z),8(17)-trien-15-oic acid (Dit88), haplopappic acid (Dit96), friedelin (Tri1), and epi-friedelinol (Tri3) (Silva and Sammes, 1973; Urzúa et al., 2003).

The flavonoid profile of H. foliosus has also been thoroughly investigated and reported to include quercetin 3-methyl ether (Flv2), rhamnazin (Flv4), isoquercitrin (Flv10), hyperoside (Flv11), beturetol (Flv15), eupatolin (Flv16), isorhamnetin (Flv18), isorhamnetin 3-β-D-glucoside (Flv19), kaempferol (Flv21), astragalin (Flv22), isokaempferide (Flv23), kaempferol 3-methyl ether 7-β-D-glucoside (Flv24), ermanin (Flv26), kumatakenin (Flv28), haplopappin (Flv31), and haplopappin A (Flv32) (Ulubelen et al., 1982; Tschesche et al., 1985; Urzúa, 2004).

Furthermore, the following coumarins were detected in H. foliosus: esculetin (Cum1), prenyletin (Cum3), scopoletin (Cum9), and scoparone (Cum12) (Ulubelen et al., 1982; Urzúa, 2004), along with the benzoic and cinnamic acid derivatives methyl salicylate (Ben3), trans-cinnamic acid (Cin1), cis-cinnamic acid (Cin2), isobutyl-(E)-cinnamate (Cin3), pentyl-(E)-cinnamate (Cin4), benzyl-(E)-cinnamate (Cin5), and 2-phenylethyl-(E)-cinnamate (Cin6) (Urzúa et al., 2000; Urzúa, 2004; Villagra et al., 2021).

4.12 H. glutinosus Cass

The aerial parts of H. glutinosus are reported to contain 4-hydroxyacetophenone (Ket2), β-farnesene (Sqt2), germacrene D (Sqt7), 6,18-dihydroxy-ent-labd-7,13E-dien-15-oic acid (Dit41), 4-hydroxybenzoic acid (Ben1), syringic acid (Ben2), trans-cinnamic acid (Cin1), caffeic acid (Cin9), and chlorogenic acid (Cin10) (Jakupovic et al., 1986; Marambio and Silva, 1996). Furthermore, the flavonoid profile of the species includes isokaempferide (Flv23), ermanin (Flv26), santin (Flv41), jaceidin (Flv43), apigenin (Flv47), 3,6-dimethoxyapigenin (Flv48), luteolin 5- (Flv54) and 7- (Flv55) glucosides, hispidulin (Flv62), pectolinaringenin (Flv63), 3′,4′-dihydroxyflavone 5-glucoside (Flv65), and verbenacoside (Flv66) (Marambio and Silva, 1996; Valant-Vetschera and Wollenweber, 2007).

4.13 H. integerrimus (Hook. & Arn.) H.M. Hall

Scientific literature only contains information on the flavonoid profile of the leaves of H. integerrimus var. punctatus (Willd.) G.K.Br. & W.D.Clark, according to which the following compounds were detected: quercetin (Flv1), quercetin 3-methyl ether (Flv2), rhamnazin (Flv4), quercetin 3,3′-dimethyl ether (Flv5), quercetin 3,7-dimethyl ether (Flv6), isoquercitrin (Flv10), isorhamnetin (Flv18), myricetin 3′,4′dimethyl ether (Flv34), and myricetin 3,3′,4′-trimethyl ether (Flv35) (Ayanoglu et al., 1981).

4.14 H. litoralis Phil

The resin of H. litoralis is reported to contain the diterpenoids 18α-acetoxylabd-8(17)-en-15-oic acid (Dit3),18-hydroxylabd-8(17)-en-15-oic acid (Dit14), (+)-copalic acid (Dit16), and (−)-eperuic acid (Dit21) (Urzúa et al., 2004b). Moreover, the flavonols ayanin (Flv7) and retusin (Flv8) were identified in the resinous exudate of this species (Urzúa et al., 2012).

4.15 H. multifolius Reiche

The terpenoids 2,9-epoxy-p-menth-6-en-8-ol (Mon51), 9-cis-p-coumaroyloxy-α-terpineol (Sqt12), 18-hydroxylabda-7,13(E)-dien-15-oic acid (Dit39), and 18-hydroxylabda-7,13(Z)-dien-15-oic acid (Dit42) are present in the aerial parts of H. multifolius (Maatooq et al., 2002). However, the phenolic composition of this species has been more thoroughly investigated and the following compounds have been identified: quercetin (Flv1), quercetin 3-methyl ether (Flv2), isorhamnetin (Flv18), persicogenin (Flv69), sternbin (Flv70), 3-O-acetylpadmatin (Flv79), blumeatin B (Flv80), esculetin (Cum1), esculin (Cum2), prenyletin (Cum3), haplopinol (Cum4), 6-deoxyhaplopinol (Cum5), 6-hydroxy-7-(5′-hydroxy-3′,7′-dimethylocta-2′,6′-dien)-oxycoumarin (Cum6), 6-hydroxy-7-(7′-hydroxy-3′,7′-dimethylocta-2′,5′-dien)-oxycoumarin (Cum7), 6-hydroxy-7-[(E,E)-3′,7′-dimethyl-2′,4′,7′-octatrienyloxy] coumarin (Cum8), hernianin (Cum13), umbelliferone (Cum14), O-prenylumbelliferone (Cum15), and 3,5-dicaffeoylquinic acid (Cin12) (Chiang et al., 1982; Nuñez-Alarcón and Quiñones, 1995; Urzúa et al., 1995b; Maatooq et al., 2002; Torres et al., 2004; 2006; 2013; Schmeda-Hirschmann et al., 2015).

4.16 H. parvifolius (DC.) Gay

The group of compounds identified in the aerial parts of H. parvifolius includes mainly diterpenoids, as well as the sesquiterpenoids 2,8-dimethyl-2′-vinyl-5-[4-methyl-pent-3-enyl]-chromane (Sqt43) and aphanamol I (Sqt46) (Zdero et al., 1991b). The diterpenoids detected in this species are 13-hydroxylabda-6,8,14-triene (Dit27), 13-hydroxylabda-6,8(17),14-triene (Dit28), 9α,13-epoxy-labda-6,8(17),14-triene (Dit29), 6β-acetoxy-13-hydroxylabda-8,14-dien-7-one (Dit30), 6β-acetoxy-7β,13-dihydroxylabda-8,14-diene (Dit31), 6β-acetoxy-13-hydroxylabda-7,14-diene (Dit47), 13-hydroxy-6α-butyryloxylabda-7,14-diene (Dit48), 13-hydroxylabda-7,14-diene-6-one (Dit49), 9α,13-dihydroxylabda-7,14-dien-6-one (Dit50), 6α,13-dihydroxylabda-7,14-dien-17-al (Dit51), isomanool (Dit52), 6α-hydroxy-9α,13-epoxy-labda-7,14-diene (Dit53), 6α-acetoxy-9α,13-epoxy-labda-7,14-diene (Dit54), 6α-butyryloxy-9α,13-epoxy-labda-7,14-diene (Dit55), 5α-hydroxy-9α,13-epoxy-labda-7,14-diene-6-one (Dit56), 6α-acetoxy-9α,13-epoxy-labda-7,14-dien-17-al (Dit57), 6-oxo-14,15-nor-labda-7-ene (Dit58), 8α,13-dihydroxylabda-6,14-diene (Dit66), 8α,13-dihydroxylabda-5,14-dien-7-one (Dit67), epi-manoyl oxide (Dit68), 6,7-dehydro-13-epi-manoyl oxide (Dit69), 6,7-dehydro-8,13-bis-epi-manoyl oxide (Dit70), 13,17-epoxy-labda-5,7,14-triene (Dit71), 9α,13-epoxy-5α,8α-dihydroxylabda-6,14-diene (Dit72), 5α-hydroxy-7,8-epoxy-7,8-seco-6,7-dehydro-13-epi-manoyl oxide (Dit73), haploparvone (Dit103), 5α-hydroxyhaploparvone (Dit104), haploparviolide (Dit105), 1,1,5,6-tetramethyl-4-[3-hydroxy-3-methyl-pent-(4)-enyl]-tetralin (Dit106), and 1,1,5-trimethyl-6-(3-hydroxy-3-methyl-pent-4-enyl)-tetralin (Dit107) (Zdero et al., 1991b).

4.17 H. poeppigianus (Hook. & Arn.) A. Gray

The aerial parts of H. poeppigianus (syn. H. canescens (Phil.) Reiche (Klingenberg, 2007)) contain the flavonoid compounds centaureidin (Flv14), myricetin (Flv33), chrysoeriol (Flv56), diosmetin (Flv58), hispidulin (Flv62), and scutellarein 6-β-D-glucoside (Flv64) (Oksuz et al., 1981).

4.18 H. paucidentatus Phil

The aerial parts of H. paucidentatus contain 4-hydroxyacetophenone (Ket2) and the terpenoids germacrene D (Sqt7), caryophyllene oxide (Sqt34), 8-oxo-β-cyperone (Sqt45), 18-hydroxy-friedolabd-5-en-15-oic acid (Dit78), 18-hydroxy-cis-cleroda-3-en-15-oic acid (10βH, 16ξ, 19β, 17β, 20α form) (Dit83), 19-hydroxy-cis-cleroda-3-en-15-oic acid (10βH, 16ξ, 19β, 17β, 20α form) (Dit85), 18-hydroxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit93), and 18-acetoxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit99) (Jakupovic et al., 1986).

4.19 H. pulchellus DC

Regarding the compounds identified in the aerial parts of H. pulchellus, those include the diterpenoids 7α-hydroxylabd-8(17)-en-15,18-dioic acid (Dit4), labd-7-en-15,18-dioic acid (Dit36), 18-acetoxy-friedolabd-5-en-15-oic acid (Dit76), 18-acetoxy-friedolabd-5-en-7-one-15-oic acid (Dit77), 18-hydroxy-friedolabd-5-en-15-oic acid (Dit78), 18-hydroxy-7-oxo-friedolabd-5-en-15-oic acid (Dit79), friedolabd-5-en-15,18-dioic acid (Dit80), and 15-hydroxy-friedolabd-5-en-18-oic acid (Dit81) (Zdero et al., 1991a).

4.20 H. remyanus Wedd

The esters benzenepropanoic acid, 2-methyl-6-methylene-2,7-octadienyl ester (Est3), (±)-1-acetoxy-2-(p-tolyl)-2-propanol (Est4), 2-hydroxy-2-(4-methylphenyl)propyl benzenepropanoate (Est5), 2-hydroxy-2-(4-methyl-3-cyclohexen-1-yl)propyl benzenepropanoate (Est6), and 2-hydroxy-2-(4-methyl-3-cyclohexen-1-yl)propyl 3-phenyl-2-propenoate (Est7) have been detected in the aerial parts of H. remyanus (Zdero et al., 1991a). Regarding its terpenoid profile, the species contains uroterpenol (Mon12), 9-benzoyloxy-(1-formyl)-α-terpineol (Mon13), 9-benzoyloxy-α-terpineol (Mon14), 7-hydroxy-9-benzoyloxy-α-terpineol (Mon15), 8-hydroxy-9-acetoxy-β-phellandrene (Mon26), 18-hydroxylabda-7,13(E)-dien-15-oic acid (Dit39), 18-acetoxy-labda-7,13(E)-dien-15-oic acid (Dit40), and 18-dihydrocinnamoyloxy-labda-7,13E-dien-l5-oic acid (Dit46) (Zdero et al., 1991a; Faini et al., 2011). Morever, the following flavonoid compounds are present in H. remyanus: quercetin (Flv1), 3-O-acetyl-7-methylquercetin (Flv9), kaempferol 7,4′-dimethyl ether (Flv27), kaempferol 3,7,4′-trimethyl ether (Flv29), 3-O-acetyl-7,4′-dimethylkaempferol (Flv30), sakuranetin 4′-methyl ether (Flv68), eriodictyol (Flv71), pinostrobin (Flv74), 7,4′-dimethylaromadendrin (Flv75) and alpinone 3-acetate (Flv83) (Zdero et al., 1991a; Faini et al., 2011).

4.21 H. rengifoanus Remy

The aerial parts and/or leaves of H. rengifoanus are reported to contain the sesquiterpenoid liguloxide (Sqt57) and the flavonoids quercetagetin 3-methyl ether (Flv12), quercetagetin 3,7-dimethyl ether (Flv13), isorhamnetin (Flv18), isorhamnetin 3-β-D-glucoside (Flv19), isorhamnetin 3-β-D-galactoside (Flv20), apigenin (Flv47), luteolin (Flv53), and scutellarein 6-β-D-glucoside (Flv64) (Ulubelen et al., 1981; Zdero et al., 1991a).

4.22 H. rigidus Phil

The diterpenoids rigiduside (Dit6), 18-acetoxy-cis-clerode 3,13(Z)-dien-15 oic acid (Dit82), rigidusol (Dit100), and deacetylrigidusol (Dit101) are present in the aerial parts of H. rigidus (Morales et al., 2000a; 2000b; 2003). Furthermore, the flavonoids quercetin 3-methyl ether (Flv2), beturetol (Flv15), kaempferol (Flv21), isokaempferide (Flv23), sakuranetin (Flv67) and sternbin (Flv70) were detected in the aerial parts (Morales et al., 2000a; 2003; 2009; Schmeda-Hirschmann et al., 2015), along with 3,5-dicaffeoylquinic acid (Cin12) (Schmeda-Hirschmann et al., 2015).

4.23 H. schumannii (Kuntze) G.K. Br. & W.D. Clark

The alkanes C₂₃H₄₈ – C₃₁H₆₄(Ala14 – Ala22) and C₃₃H₆₈(Ala14) have been identified in the aerial parts of H. schumannii, along with 1-octadecyne (Aly1), dihydro-α-ionone (Ket6), and the lactone tetrahydroactinidiolide (Ltn2) (Urzúa et al., 2004a). The terpenoid profile of this species includes the sesquiterpenoids β-cadinene (Sqt19), β-bourbonene (Sqt55), and globulol (Sqt56), as well as the diterpenoids manool (Dit7), (−)-eperuic acid (Dit21), epi-manool (Dit25), 8α-hydroxylabdan-15-oic acid (Dit59), and 2-oxoclerod-3-en-15-oic acid (Dit86) (Urzúa et al., 1997; 2004a). Moreover, the flavonoids quercetin (Flv1), isoquercitrin (Flv10), vicenin-2 (Flv49), vitexin (Flv50), and isovitexin (Flv51) are present in the leaves of H. schumannii (Ates et al., 1982).

4.24 H. scrobiculatus (Nees) DC

The presence of the terpenoids α-farnesene (Sqt1), 18-hydroxymanool (Dit15), and 2-oxokolavenic acid (Dit94) has been reported in the case of the aerial parts and resinous exudates of H. scrobicultus (Rossomando et al., 1995; Urzúa et al., 2004b). However, the largest group of compounds in this species is that of phenolics, namely, quercetin (Flv1), isoquercitrin (Flv10), isorhamnetin (Flv18), isorhamnetin 3-β-D-glucoside (Flv19), rhamnocitrin (Flv25), santin (Flv41), eupatorin (Flv42), penduletin (Flv45), vicenin-2 (Flv49), vitexin (Flv50), isovitexin (Flv51), isoschaftoside (Flv52), eupafolin (Flv59), 6-methoxyluteolin 4′-methyl ether (Flv60), cirsiliol (Flv61), and esculetin (Cum1) (Ates et al., 1982; Rossomando et al., 1995; Urzúa et al., 2012).

4.25 H. taeda Reiche

The terpenoid profile of H. taeda includes taedol (Mon41), 18-hydroxylabda-7,13(E)-dien-15-oic acid (Dit39), 7,13-labdadien-15,18-dioic acid (Dit43), cleroda-3,13 (E)-dien-15,18-diol (Dit95), and 18-acetoxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit99) (Marambio and Silva, 1989; Torres et al., 2005; Faini et al., 2007; 2008). However, scientific literature provides more information on the phenolic composition of this species, with the following compounds being reported: quercetin (Flv1), quercetin 3-methyl ether (Flv2), quercetin 3,7-dimethyl ether (Flv6), kaempferol (Flv21), sakuranetin (Flv67), sternbin (Flv70), eriodictyol 7,3′-dimethyl ether (Flv72), eriodictyol 7,3′,4′-trimethyl ether (Flv73), 3-O-acetyl-7-O-aromadendrin (Flv77), padmatin (Flv78), 3-O-acetylpadmatin (Flv79), 9-trans-p-coumaroyloxy-α-terpineol (Cin7), 7-trans-p-coumaroyloxy-taedol (Cin8), chlorogenic acid (Cin10), 3,4-dicaffeoylquinic acid (Cin11), and 3,5-dicaffeoylquinic acid (Cin12) (Marambio and Silva, 1989; Faini et al., 2007; 2008; Schmeda-Hirschmann et al., 2015).

4.26 H. uncinatus Phil

The alkanes C₂₃H₄₈ – C₃₁H₆₄(Ala14 – Ala22) and C₃₃H₆₈(Ala14) have been identified in the resinous exudates and/or aerial parts of H. uncinatus (Urzúa et al., 2000; 2004a; 2006), along with 2,7-dimethyl-5-(1-methylethenyl)-1,8-nonadiene (Ale3) and 3,5-dihydroxy-3′,4′,6,7-tetramethoxyflavone (Flv40) (Urzúa et al., 2004a; 2006). Regarding its terpenoid profile, the species is reported to synthesize 3,3,7,7-tetramethyl-5-(2-methyl-1-propenyl)-tricyclo[4.1.0.0(2,4)]heptane (Mon53), the sesquiterpenoids cadalene (Sqt17), aromadendrene (Sqt47), α-cubebene (Sqt48), β-cubebene (Sqt49), spathulenol (Sqt52), cedryl acetate (Sqt53), β-bourbonene (Sqt55), globulol (Sqt56), α-copaene (Sqt58), as well as the clerodane diterpenoid 18-acetoxy-cis-cleroda-3-en-15-oic acid (10βH, 16ξ, 19β, 17β, 20α form) (Dit84) (Urzúa et al., 2000; 2004a; 2006).

4.27 H. velutinus Remy; H. velutinus Remy subsp. illinitus (Phil.) Klingenb

Several compounds are reported to be present in both H. velutinus and the subspecies H. velutinus subsp. illinitus. These are the alkanes C₂₃H₄₈ – C₃₁H₆₄(Ala14 – Ala22) and C₃₃H₆₈(Ala14), 5,5-dimethyl-2(5H)-furanone (Fur1), β-myrcene (Mon3), limonene (Mon8), α-pinene (Mon37), β-pinene (Mon38), labd-7-en-15,18-dioic acid-18α-methylester (Dit37), β-sitosterol (Str2), and quercetin (Flv1) (Latorre et al., 1990; Marambio and Silva, 1996; Faini et al., 2002; Urzúa et al., 2004a; Echeverría et al., 2019).

In contrast, compounds solely identified in H. velutinus include 3-ethyl-1,4-hexadiene (Ale2), 2-nonyn-1-ol (Alc3), 2-pentadecen-1-ol (Al4), n-dodecenyl-1-ol (Alc5), vanillin (Ald8), picein (Ket5), lavender lactone (Ltn1), linalyl anthranilate (Mon5), davanone (Mon6), davana ether (Mon7), 1,2:8,9-diepoxy-p-menthane (Mon19), cis-p-menth-2-en-1-ol (Mon22), trans-pulegone oxide (Mon23), α-campholenal (Mon24), m-cymene (Mon27), α-thujene (Mon33), pinocarveol (Mon39), trans-2-pinanol (Mon40), cis-verbenol (Mon47), α-sinensal (Sqt3), humulene epoxide II (Sqt6), caryophyllene oxide (Sqt34), α-guaiene (Sqt35), (−)-oplopanone (Sqt37), spathulenol (Sqt52), patchouli alcohol (Sqt54), dehydropinipholic acid 19-methyl ester (Dit11), 4α-hydroxy-18-norlabd-8(17)-en-15-oic acid (Dit12), 4β-hydroxy-19-norlabd-8(17)-en-15-oic acid (Dit13), 18-hydroxylabd-8(17)-en-15-oic acid (Dit14), 7,13-(E)-labdadien-15,18-dioic-acid-18-methyl ester (Dit45), friedelin (Tri1), epi-friedelinol (Tri3), taraxerol (Tri4), erythrodiol (Tri5), stigmasterol (Str1), isoquercitrin (Flv10), isokaempferide (Flv23), kumatakenin (Flv28), luteolin (Flv53), and scopoletin (Cum9) (Urzúa and Mendoza, 1989; Urzúa et al., 1991; Urzúa et al., 1995a; 2004a; Urzua and Mendoza, 1993; Marambio and Silva, 1996; Echeverría et al., 2019).

The group of compounds identified solely in the subspecies H. velutinus subsp. illinitus consists of 3,3,5,5-tetramethylcyclopentene (Ale4), methyl octanoate (Est1), 5-methyl-octanoic acid methyl ester (Est2), β-cadinene (Sqt19), procerin (Mer1), as well as the diterpenoids 7α-hydroxylabd-8(17)-en-15,18-dioic acid-15-methylester (Dit5), pinifolic acid 15-methyl ester (Dit22), pinifolic acid 18-methyl ester (Dit23), pinifolic acid dimethyl ester (Dit24), labd-7-en-15,18-dioic acid (Dit36), labd-7-en-15,18-dioic acid-15-methylester (Dit38), and 7-oxo-labd-8(9)-en-15,18-dioic acid-15-methylester (Dit10), (Faini et al., 2002; Urzúa et al., 2004a).

5 Traditional uses and evidence-based pharmacological activities related to human health

5.1 Traditional uses

The plants of the genus Haplopappus are of high medicinal value and form essential part of the traditional medicines of the Andean region (Chile, Argentina), where the genus presents high endemicity. Haplopappus species and their preparations have traditionally been associated with numerous health benefits, associated with multiple aspects of the human health and also with veterinary applications (Table 5).

The main health benefits traditionally attributed to different preparations of Haplopappus plants are associated with pathologies of the human alimentary tract and metabolism. Various species and preparations have widespread use as digestives, antidiarrheic, remedies against dyspepsia, dysentery and gastrointestinal ailments, in general.

Moreover, there are reported several traditional uses associated with the human genitourinary system, with Haplopappus preparations being considered as aphrodisiacs, emmenagogues, diuretic and as remedies against urinary and renal disorders and colics or even against male and female hormonal disorders.

Other traditional uses are associated with health benefits for the human respiratory (antitussives, expectorants, cold remedies) and nervous (stimulant, antispasmodic) system, as well as with their role as disinfectants.

Finally, it is well-documented in traditional Andean medicines the use of Haplopappus preparations as cicatrizants with veterinary applications, especially to treat horses’ wounds.

It has to be mentioned that H. baylahuen Remy is recognized by the Chilean health authorities as a traditional herbal medicine against liver diseases, abdominal colics, chronic dyspepsia, kidney stones, flus and colds, as well as an aphrodisiac and wound disinfectant (Ministerio de Salud, 2010). Meanwhile, pharmaceutical products that include bailahuén, e.g., the formulations ‘Ulcenat’ and ‘Ubenat’ (Grüne Leben) and ‘Bailahuen extracto fluido’ (Knop Laboratorios S.A.) are commercialized in Chile as treatments against digestive disorders. However, there are no internationally or nationally established norms and/or protocols regarding quality, standardization, safety, and adulteration control of bailahuén preparations and commercial products.

5.2 Evidence-based pharmacological activity related to the human health

Scientific literature provides evidence related to various human health-promoting effects of extracts and isolated compounds of Haplopappus species (Table 6), with their inhibitory effect against human pathogens of bacterial origin being the most thoroughly investigated.

5.2.1 H. anthylloides meyen & walp

Although the bioactivity of the species H. anthylloides has not been extensively studied, it is reported that dichloromethane extracts of its resinous exudates present antibacterial effects, inhibiting the in vitro growth of several human pathogenic bacteria (Urzúa et al., 1995a).

5.2.2 H. baylahuen remy

Haplopappus baylahuen is the species with the highest number of bioactivity studies. Extracts and decoctions of its aerial parts are reported to have antibacterial and bactericide effects against Staphylococcus aureus, Bacillus subtilis, Acremonium falciforme (Lazo, 1990) and Salmonella enteritidis (Elgueta et al., 2021). Moreover, emulsions of its resin have been successfully used to treat the symptoms of dysentery in affected individuals (Fingland, 1903), while extracts of the aerial parts of H. baylahuen have shown anti-inflammatory (Adzet and Gene, 1991), diuretic (Méttola et al., 2018) and hepatoprotective (Nuñez-Alarcon et al., 1993) effects in rat models and hepatoprotective activity in dog models (Martin et al., 1988). The hepatoprotective effect in rats under CCl₄-induced liver injury has also been confirmed in the case of 7-O-methylaromadenrin (Flv76) isolated from the aerial parts of the plant (Nuñez-Alarcon et al., 1993). Moreover, rhamnetin (Flv17) and isorhamnetin (Flv18) isolated from the leaves of H. baylahuen have been found to inhibit in a dose-dependent manner the glucose transporter GLUT1 in human cell lines and in vivo in hamsters (Vera et al., 2001). Finally, extracts of the aerial parts of this species have demonstrated significant antioxidant capacity as measured by various in vitro assays (Vogel et al., 2005a; Speisky et al., 2006; Alarcón et al., 2008; Schmeda-Hirschmann et al., 2015; Méttola et al., 2018; Elgueta et al., 2021), while also inhibiting lipid peroxidation in vitro and in erythrocyte membranes (Vogel et al., 2005a; Méttola et al., 2018).

5.2.3 H. chrysanthemifolius (Less.) DC

In the case of H. chrysanthemifolius, scientific evidence supports the antibacterial effect of the methanolic extracts of its resinous exudates, as this has been demonstrated through the in vitro growth inhibition of several Gram-positive human pathogenic bacterial strains (Urzúa et al., 2004b; 2012).

5.2.4 H. deserticola Phil

The diterpene 18-acetoxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit99) isolated from the resin of H. deserticola presented a bactericidal effect against Streptococcus mutans (Urzúa Moll et al., 1997), while the in vitro antioxidant capacity of the infusion and methanolic extract of the plant’s aerial parts has also been documented (Schmeda-Hirschmann et al., 2015).

5.2.5 H. diplopappus Remy subsp. diplopappus

The resin of H. diplopappus subsp. diplopappus, as well as the isolated diterpenoid 13-O-β-xylopyranosyl-ent-manool (Dit8) present antibacterial effect against various Gram-positive and Gram-negative human pathogenic bacteria (Urzúa et al., 1995a).

5.2.6 H. foliosus (Hook. & Arn.) Hook. & Arn

Scientific evidence supports the antibacterial effect of the resinous exudate of H. foliosus against several Gram-positive and Gram-negative human pathogenic bacteria (Urzúa et al., 1995a; 2003; Urzúa and Mendoza, 2001). Similar bioactivity has been attributed to the diterpenes 2α-hydroxy-cis-clero-3,13(Z),8(17)-trien-15-oic acid (Dit87) and 2α-acetoxy-cis-clero-3,13(Z),8(17)-trien-15-oic acid (Dit88) which were isolated from the resin of H. foliosus (Urzúa et al., 2003).

5.2.7 H. litoralis Phil

In the case of H. litoralis, it has been reported that its resinous exudate inhibits the in vitro growth of Bacillus cereus, B. subtilis, Enterococcus faecalis, Listeria monocytogens, Micrococcus luteus, S. aureus (Urzúa et al., 2004b; 2012).

5.2.8 H. multifolius reiche

Scientific literature provides evidence that support the antibacterial effect of H. multifolius resin and aerial parts extracts against a wide spectrum of Gram-positive and Gram-negative human pathogenic bacteria (Urzúa et al., 1995a; Padilla et al., 2021). Moreover, similar antibacterial activity has been documented for the coumarins esculetin (Cum1), prenyletin (Cum3) and haplopinol (Cum4) isolated from the aerial parts of this species (Chiang et al., 1982). Regarding the in vitro antioxidant capacity of H. multifolius, this has been demonstrated in the case of extracts, aerial parts infusions and resin (Vogel et al., 2005a; Schmeda-Hirschmann et al., 2015), as well as for the isolated compounds quercetin (Flv1), isorhamnetin (Flv18), prenyletin (Cum3), haplopinol (Cum4), 6-hydroxy-7-(5′-hydroxy-3′,7′-dimethylocta-2′,6′-dien)-oxycoumarin (Cum6), 6-hydroxy-7-(7′-hydroxy-3′,7′-dimethylocta-2′,5′-dien)-oxycoumarin (Cum7) and 6-hydroxy-7-[(E,E)-3′,7′-dimethyl-2′,4′,7′-octatrienyloxy] coumarin (Cum8) (Torres et al., 2006). Furthermore, the isolated compounds esculetin (Cum1), esculin (Cum2), prenyletin (Cum3), 6-hydroxy-7-(5′-hydroxy-3′,7′-dimethylocta-2′,6′-dien)-oxycoumarin (Cum6), 6-hydroxy-7-(7′-hydroxy-3′,7′-dimethylocta-2′,5′-dien)-oxycoumarin (Cum7), umbelliferone (Cum14) and O-prenylumbelliferone (Cum15) have demonstrated an anti-inflammatory effect associated to the in vitro inhibition of soybean 15-lipoxygenase (Torres et al., 2013). Finally, methanolic extracts and infusions of H. multifolius leaves inhibited the lipid peroxidation in erythrocyte membranes (Vogel et al., 2005a).

5.2.9 H. remyanus wedd

Infusions, methanolic extracts and resin from the leaves of H. remyanus demonstrated a significant antioxidant capacity in vitro, while also inhibiting lipid peroxidation in erythrocyte membranes (Vogel et al., 2005a). Furthermore, the resinous exudates of the plant exhibited an anti-inflammatory effect in mice (Faini et al., 2011) and a cytotoxic effect against T-lymphoblastic leukemia cell line (CCRF-CEM) (Faini et al., 2011).

5.2.10 H. rigidus Phil

Extracts of the aerial parts of H. rigidus have effectively inhibited the in vitro growth of several Gram-positive bacterial strains (Morales et al., 2003; Ortiz et al., 2019), presented a significant in vitro antioxidant capacity (Schmeda-Hirschmann et al., 2015) and also acted as muscle relaxants in Guinea pig models (Hnatyszyn et al., 2003). The isolated flavanone sternbin (Flv70) presented high in vitro antioxidant capacity, lipid peroxidation inhibitory effects in rat cells and also antitumoral effect against the human breast adenocarcinoma (MCF-7), human lung carcinoma (A-549) and human colon adenocarcinoma (HT–29) cell lines (Morales et al., 2009). The isolated diterpene rigidusol (Dit100) also had a cytotoxic effect on human breast adenocarcinoma cells line (MCF-7) (Morales et al., 2000b).

5.2.11 H. schumannii (Kuntze) G.K. Br. & W.D. Clark

The resinous exudates of H. schumannii inhibited the in vitro growth of several Gram-positive bacterial human pathogens (Urzúa et al., 1995a).

5.2.12 H. scrobiculatus (Nees) DC

Similarly, the only known bioactivity regarding the resin of H. scrobiculatus is that of the in vitro antibacterial effect against several Gram-positive bacteria (Urzúa et al., 1995a; 2004b; 2012).

5.2.13 H. taeda reiche

Ethanolic extracts and infusions of aerial parts of H. taeda successfully inhibited the in vitro growth of several Bacillus and Staphylococcus bacterial strains (Padilla et al., 2021). Regarding the in vitro antioxidant capacity of the species, this has been shown to be significant in the case of aerial parts infusions, extracts and resinous exudates (Vogel et al., 2005a; Schmeda-Hirschmann et al., 2015), as well as for the isolated compounds 9-trans-p-coumaroyloxy-α-terpineol (Cin7) and 7-trans-p-coumaroyloxy-taedol (Cin8) (Faini et al., 2007). Moreover, leaf infusions and methanolic extracts of H. taeda inhibited lipid peroxidation in erythrocyte membranes (Vogel et al., 2005a). Ethanolic extracts, as well as the isolated compounds taedol (Mon41), 18-acetoxy-cis-cleroda-3,13(E)-dien-15-oic acid (Dit99), and sakuranetin (Flv67) exhibited an anti-inflammatory effect against arachidonic acid-induced ear edema in mice (Faini et al., 2008).

5.2.14 H. uncinatus Phil

Extracts of the aerial parts and resinous exudates of H. uncinatus, as well as the isolated diterpenoid 18-acetoxy-cis-cleroda-3-en-15-oic acid (10βH, 16ξ, 19β, 17β, 20α form) (Dit84) have been reported to inhibit in vitro the growth of various Gram-positive human pathogenic bacteria (Urzúa et al., 1995a; 2006; Urzúa and Mendoza, 2001).

5.2.15 H. velutinus remy, H. velutinus Remy subsp. illinitus (Phil.) Klingenb

Dichloromethane extracts of the resinous exudates of H. velutinus and its subspecies H. velutinus subsp. illinitus inhibited in vitro the growth of various Gram-positive and Gram-negative human pathogenic bacteria (Urzúa et al., 1995a).

6 Non-human health related bioactivity and toxicity

Among the pharmacological activities attributed to Haplopappus species and not related to the human health, the most studied is the antimicrobial effect against plant pathogens. The essential oil of the leaves of H. baylahuen inhibited the in vitro growth of the fungi Aspergillus nigra and Fusarium oxysporum (Becerra et al., 2010). Moreover, the diterpenoid 7,13-(E)-labdadien-15,18-dioic acid 18-methyl ester (Dit45) was isolated from the resinous exudate of Haplopappus velutinus and inhibiting in vitro the mycelial growth of Botrytis cinerea (Echeverría et al., 2019). In the case of the phytopathogenic bacterium Clavibacter michiganensis subsp. michiganensis, its in vitro growth was inhibited by the resin (Urzúa and Mendoza, 2001) and the isolated diterpene 18-acetoxy-cis-cleroda-3-en-15-oic acid (10βH, 16ξ, 19β, 17β, 20α form) (Dit84) (Urzúa et al., 2006) from H. uncinatus, as well as by the methanolic extract of the resin of H. foliosus (Urzúa and Mendoza, 2001).

The essential oil of H. foliosus also exhibited insecticide effects against house flies (Musca domestica) (Urzúa et al., 2010), while hydroethanolic and chloroform extracts of H. rigidus presented biotoxic activity against Artemia salina (Morales et al., 2003).

7 Concluding remarks and future perspectives

The available scientific literature on the genus Haplopappus can be said to support, although partially, its widespread and longstanding use as a medicinal plant. However, the results of the present review highlight several limitations that need to be addressed.

Firstly, phytochemical and bioactivity research of the genus Haplopappus is largely concentrated in the 1990s and 2000s, with almost 80% of the investigation having been performed before 2010. Therefore, a revival of scientific interest and the application of modern, more advanced and diverse analytical and biological techniques can further elucidate the composition and bioactivity of Haplopappus plant species, thus broadening the existing knowledge and promoting its potential uses.

Furthermore, phytochemical and pharmacological evidence is available only for the 40% and 23%, respectively, of the botanical taxa of the genus Haplopappus, while for many of the studied taxa, the available information is rather limited. Similarly, terpenoids and phenolics correspond to approximately 70% of the compounds reported in Haplopappus spp., suggesting that scientific investigation up to date has possibly understudied other chemical groups. It is, therefore, suggested to extend the focus of scientific research to more, if not all, Haplopappus species and groups of chemical compounds, thus permitting to fully explore its promising chemical and biological prospects.

Based on the available bioactivity and pharmacological evidence, Haplopappus species can be considered as a valuable plant resource for health-promoting applications. However, the majority of the investigation provides evidence associated to the in vitro antibacterial and antioxidant activity of the genus Haplopappus. In contrast, there is a lack of scientific evidence to support or refute various traditional uses, while, at the same time, the limited number of in vivo studies and/or clinical trials hinders its wider human health-promoting application and secure use.

In this context, the information presented in the present review supports the ethnopharmacological, phytochemical and bioactive potential of the genus Haplopappus, while addressing the aforementioned limitations could further promote and broaden both scientific research and future applications and uses.

References

• 1

  AdzetT. E.GeneR. M. (1991). Estudio de la actividad antiinflamatoria de especies vegetales de origen centro y sudamericano. Dominguezia9, 17–23.

  • Google Scholar

• 2

  AlarcónE.CamposA. M.EdwardsA. M.LissiE.López-AlarcónC. (2008). Antioxidant capacity of herbal infusions and tea extracts: a comparison of ORAC-fluorescein and ORAC-pyrogallol red methodologies. Food Chem.107, 1114–1119. 10.1016/j.foodchem.2007.09.035

  • CrossRef
  • Google Scholar

• 3

  AldunateC.ArmestoJ.CastroV.VillagránC. (1981). Estudio etnobotánico en una comunidad precordillerana de Antofagasta: Toconce. Bol. del Mus. Nac. Hist. Nat.38, 183–223. 10.54830/bmnhn.v38.1981.473

  • CrossRef
  • Google Scholar

• 4

  AlonsoJ. (2005). Monografía: Baylahuén. Bol. Latinoam. del Caribe plantas aromáticas4, 60–62.

  • Google Scholar

• 5

  ArzneibuchH. (2006). Amtliche deutsche Ausgabe. Stuttgart, Germany: Deutscher Apotheker Verlag.

  • Google Scholar

• 6

  AtesN.UlubelenA.ClarkW. D.BrownG. K.MabryT. J.DellamonicaG.et al (1982). Flavonoids of haplopappus scrobiculatus and haplopappus sericeus. J. Nat. Prod.45, 189–190. 10.1021/np50020a014

  • CrossRef
  • Google Scholar

• 7

  AyanogluE.UlubelenA.ClarkW. D.BrownG. K.KerrR. R.MabryT. J. (1981). Myricetin and quercetin methyl ethers from Haplopappus integerrimus var. punctatus. Phytochemistry20, 1715–1717. 10.1016/s0031-9422(00)98561-3

  • CrossRef
  • Google Scholar

• 8

  BecerraJ.BittnerM.HernandezV.BrintrupC.SilvaM. (2010). Activity of essential oils of Canelo, Queule, Bailahuen y Culen against phythopatogenic fungi. Bol. Latinoam. del Caribe Plantas Aromat.9, 212–215.

  • Google Scholar

• 9

  CárdenasU. (1998). Entre el tolar y el pajonal: Percepción ambiental y uso de plantas en la comunidad atacameña de Talabre, II Región, Chile. Estud. Atacameños16, 251–282. 10.22199/s07181043.1998.0016.00010

  • CrossRef
  • Google Scholar

• 10

  ChiangM. T.BittnerM.SilvaM.MondacaA.ZemelmanR.SammesP. G. (1982). A prenylated coumarin with antimicrobial activity from Haplopappus multifolius. Phytochemistry21, 2753–2755. 10.1016/0031-9422(82)83119-1

  • CrossRef
  • Google Scholar

• 11

  Del VittoL. A.PetenattiE. M.PetenattiM. E. (2010). “Ethnomedical plants from Cuyo region, Argentina: uses and conservational status,” in Tradiciones & transformaciones en etnobotánica. Editors PochettinoM. L.LadioA. H.ArenasP. M. (Jujuy, Argentina: CYTED - Programa Iberoamericano Ciencia y Tecnología para el Desarrollo), 223–229.

  • Google Scholar

• 12

  de MösbachE. W. (1992). “Botánica indígena de Chile,”. Chile: Editorial Andrés Bello.

  • Google Scholar

• 13

  EcheverríaJ.González-TeuberM.UrzúaA. (2019). Antifungal activity against Botrytis cinerea of labdane-type diterpenoids isolated from the resinous exudate of Haplopappus velutinus Remy (Asteraceae). Nat. Prod. Res.33, 2408–2412. 10.1080/14786419.2018.1443093

  • CrossRef
  • Google Scholar

• 14

  ElguetaE.MenaJ.OrihuelaP. A. (2021). Hydroethanolic extracts of Haplopappus baylahuen Remy and Aloysia citriodora Palau have bactericide activity and inhibit the ability of Salmonella Enteritidis to form biofilm and adhere to human intestinal cells. Biomed. Res. Int.2021, 3491831. 10.1155/2021/3491831

  • CrossRef
  • Google Scholar

• 15

  EspinozaE. (1897). Plantas medicinales de Chile: Fragmento de la cuarta edición de la Jeografía Descriptiva de la República de Chile. Santiago de Chile: Imprenta i Encuadernación Barcelona.

  • Google Scholar

• 16

  FainiF.LabbéC.DelporteC.BackhouseN.CastroC.TorresR. (2008). Anti-inflammatory and antioxidant activities of Haplopappus taeda extracts. Planta Med.74, PA78. 10.1055/s-0028-1084076

  • CrossRef
  • Google Scholar

• 17

  FainiF.LabbéC.TorresR.Delle MonacheF.Delle MonacheG. (1999). Diterpenes from haplopappus chrysanthemifolius. Phytochemistry52, 1547–1550. 10.1016/s0031-9422(99)00395-7

  • CrossRef
  • Google Scholar

• 18

  FainiF.LabbéC.TorresR.MonacheG. D.MonacheF. D. (2002). Labdane diterpenes from Haplopappus illinitus. Nat. Prod. Lett.16, 223–228. 10.1080/10575630290020460

  • CrossRef
  • Google Scholar

• 19

  FainiF.LabbéC.TorresR.RodillaJ. M.SilvaL.Delle MonacheF. (2007). New phenolic esters from the resinous exudate of Haplopappus taeda. Fitoterapia78, 611–613. 10.1016/j.fitote.2007.06.006

  • CrossRef
  • Google Scholar

• 20

  FainiF.TorresR.RodillaJ. M.LabbéC.DelportedC.JañaaF. (2011). “Chemistry and bioactivity of haplopappus remyanus (“bailahuen”), a chilean medicinal plant,” in J. Braz. Chem. Soc.2344–2349. 10.1590/S0103-50532011001200015

  • CrossRef
  • Google Scholar

• 21

  FinglandW. (1903). The successful treatment of sporadic dysentery by Aplopappus baylahuen. Lancet162, 456–457. 10.1016/s0140-6736(00)67384-1

  • CrossRef
  • Google Scholar

• 22

  GarcíaN.Cádiz-VélizA.VillalobosM.MoralesV. (2024). Taxonomic novelties in haplopappus (Asteraceae, Astereae) from Chile. PhytoKeys237, 201–218. 10.3897/phytokeys.237.114461

  • CrossRef
  • Google Scholar

• 23

  GarciaN.MedinaP.MoralesV. (2018). Haplopappus mieresii sp. nov.(Asteraceae) and the reinstatement of H. reicheanus from central Chile. Phytotaxa376, 103–113. 10.11646/phytotaxa.376.2.4

  • CrossRef
  • Google Scholar

• 24

  GómezD.AhumadaJ.NeculE. (1997). Medicina tracional atacameña. Santiago, Chile: Ministerio de Educación.

  • Google Scholar

• 25

  Gómez-ParraD.Siarez FloresE. (1995). “Alimentación tradicional atacameña,” in Antofagasta, Chile: NORprint.

  • Google Scholar

• 26

  HnatyszynO.MoscatelliV.GarciaJ.RondinaR.CostaM.ArranzC.et al (2003). Argentinian plant extracts with relaxant effect on the smooth muscle of the corpus cavernosum of Guinea pig. Phytomedicine10, 669–674. 10.1078/0944-7113-00261

  • CrossRef
  • Google Scholar

• 27

  HoffmannA.FargaC.LastraJ.VeghaziE. (1992). Plantas medicinales de uso común en Chile. Santiago Fund. Claudio Gayc1992, 2nd.

  • Google Scholar

• 28

  HörhammerL.WagnerH.WilkomirskyM. T.IyengarM. A. (1973). Flavonoide in einigen chilenischen heilpflanzen. Phytochemistry12, 2068–2069. 10.1016/s0031-9422(00)91548-6

  • CrossRef
  • Google Scholar

• 29

  HoughtonP. J.ManbyJ. (1985). Medicinal plants of the Mapuche. J. Ethnopharmacol.13, 89–103. 10.1016/0378-8741(85)90063-7

  • CrossRef
  • Google Scholar

• 30

  JakupovicJ.BaruahR. N.ZderoC.EidF.PathakV. P.Chau-ThiT. V.et al (1986). Further diterpenes from plants of the Compositae, subtribe Solidagininae. Phytochemistry25, 1873–1881. 10.1016/s0031-9422(00)81166-8

  • CrossRef
  • Google Scholar

• 31

  KimH. W.WangM.LeberC. A.NothiasL.-F.ReherR.KangK. B.et al (2021). NPClassifier: a deep neural network-based structural classification tool for natural products. J. Nat. Prod.84, 2795–2807. 10.1021/acs.jnatprod.1c00399

  • CrossRef
  • Google Scholar

• 32

  KlingenbergL. (2007). Monographie der südamerikanischen Gattungen Haplopappus Cass. und Notopappus L. Klingenberg (Asteraceae-Astereae). Stuttgart, Germany: Schweizerbart’sche Verlagsbuchhandlung.

  • Google Scholar

• 33

  LabbéC.FainiF.CollJ.CarbonellP. (1998). Guaiane sesquiterpenoids from Haplopappus foliosus. Phytochemistry49, 793–795. 10.1016/s0031-9422(97)00871-6

  • CrossRef
  • Google Scholar

• 34

  LatorreI.PeñaR. C.ErazoS. (1990). Ensayos farmacognósticos de tres compuestas usadas en medicina popular en Chile Central. An. la Real Acad. Nac. Farm.56, 359–366.

  • Google Scholar

• 35

  LavalE. (1957). Medicina aborigen tradicional atacameña. Rev. del Serv. Nac. Salud2.

  • Google Scholar

• 36

  LazoW. (1990). Acción antimicrobiana de algunas plantas de uso medicinal en Chile: I. Bol. Micol.5, 25–28. 10.22370/bolmicol.1990.5.1-2.1587

  • CrossRef
  • Google Scholar

• 37

  MaatooqG. T.GoharA. A.HoffmannJ. J. (2002). New terpenoids from Haplopappus multifolius. Pharmazie57, 282–285.

  • Google Scholar

• 38

  MadalenoI. M.Delatorre-HerreraJ. (2013). Medicina popular de Iquique, Tarapacá. Idesia (Arica)31, 67–78. 10.4067/s0718-34292013000100009

  • CrossRef
  • Google Scholar

• 39

  MaldonadoZ.HoeneisenM.SilvaM. (1993). Constituents of Haplopappus bezanillanus and H. hirtellus. Bol. la Soc. Chil. Quim.38, 43–48.

  • Google Scholar

• 40

  MarambioO.SilvaM. (1989). New compounds isolated from Haplopappus taeda Reiche. Bol. la Soc. Chil. Quim.34, 105–113.

  • Google Scholar

• 41

  MarambioO.SilvaM. (1996). Compuestos fenólicos y triterpenos aislados desde Haplopappus velutinus Remy y H. glutinosus Cass. Bol. la Soc. Chil. Quím.41, 199–200.

  • Google Scholar

• 42

  MartinR.WittwerF.NúñezJ. (1988). Effect of an infusion of Haploppapus baylahuen in dogs with liver damage. J. Vet. Med. Ser. A Ger. Fr.

  • Google Scholar

• 43

  Mellado CamposV. (1996). Herbolaria médica de Chile: diagnóstico de su estado actual y perspectivas futuras para la medicina oficial chilena. Ministerio: Santiago de Chile.

  • Google Scholar

• 44

  MéttolaR. M.BrodkewicsI. Y.VeraN. R.ReynosoM. A. (2018). Actividad diurética y antioxidante de los extractos etanólicos de especies vegetales usadas en la medicina popular argentina. Rev. Cuba. Plantas Med.23.

  • Google Scholar

• 45

  Ministerio de Salud (2010). MHT. Medicamentos herbarios tradicionales. 103 especies vegetales. Santiago, Chile: Ministerio de Salud.

  • Google Scholar

• 46

  MonterreyN. (1996). Hierbas medicinales andinas de la 2a región. Santiago, Chile: Ministerio de Educación.

  • Google Scholar

• 47

  MontesM.WilkomirskyT. (1987). “Medicina tradicional chilena,” in Editiorial de la Universidad de Concepción.

  • Google Scholar

• 48

  MoralesG.ParedesA.SierraP.LoyolaL. A. (2009). Cytotoxicity, scavenging and lipid peroxidation - inhibiting activities of 5,3´,4´-trihy-droxy - 7 - methoxyflavanone isolated from haplopappus rigidus. J. Chil. Chem. Soc.54, 105–107. 10.4067/S0717-97072009000200001

  • CrossRef
  • Google Scholar

• 49

  MoralesG.SierraP.BorquezJ.LoyolaL. A. (2000a). Rigidúsido, un nuevo glicoditerpenoide de Haplopappus rigidus. Bol. la Soc. Chil. Quím.45, 611–614. 10.4067/s0366-16442000000400014

  • CrossRef
  • Google Scholar

• 50

  MoralesG.SierraP.LoyolaL. A.BorquezJ. (2000b). Diterpenoids from haplopappus rigidus. Phytochemistry55, 863–866. 10.1016/s0031-9422(00)00321-6

  • CrossRef
  • Google Scholar

• 51

  MoralesG.SierraP.MancillaA.ParedesA.LoyolaL. A.GallardoO.et al (2003). Secondary metabolites from four medicinal plants from northern Chile: antimicrobial activity and biotoxicity against Artemia salina. J. Chil. Chem. Soc.48, 13–18. 10.4067/s0717-97072003000200002

  • CrossRef
  • Google Scholar

• 52

  MostnyG.JeldesF.GonzálezR.OberhauserF.GonzàlezR. (1954). “Peine, un pueblo atacameño,” in Instituto de Geografia, Facultad de Filosofia. Santiago, Chile: Universidad de Chile.

  • Google Scholar

• 53

  MunizagaC. (1963). “Un medico herbolario de la actualidad en el norte de Chile,” 26. Santiago, Chile: Rev. Univ. la Univ. Católica Chile.

  • Google Scholar

• 54

  MunizagaC.GunkelH. (1958). “Notas etnobotanicas del pueblo atacameno de Socaire,” in Centro de Estudios Antropológicos. Santiago, Chile: Universidad de Chile.

  • Google Scholar

• 55

  MuñozM.BarreraE.MezaI. (1981). El uso medicinal y alimenticio de plantas nativas y naturalizadas en Chile. Mus. Nac. Hist. Nat.33, 91.

  • Google Scholar

• 56

  MurilloA. (1861). Memoria sobre las plantas medicinales de Chile y el uso medicinal que de ellas se hace en el país. Santiago, Chile: Impr. de Ferrocarril.

  • Google Scholar

• 57

  MurilloA. (1889). Plantes médicinales du Chili. Paris: Exposition Universelle de Paris, Section chilienne.

  • Google Scholar

• 58

  Nuñez-AlarconJ.DolzH.QuiñonesM. H.CarmonaM. T. (1993). Epicuticular flavonoids from Haplopappus baylahuen and the hepatoprotective effect of the isolated 7-methyl aromadendrin. Bol. la Soc. Chil. Quim.38, 15–22.

  • Google Scholar

• 59

  Nuñez-AlarcónJ.QuiñonesM. (1995). Flavonoids and coumarins of Haplopappus multifolius. Biochem. Syst. Ecol.23, 453–454. 10.1016/0305-1978(95)00019-Q

  • CrossRef
  • Google Scholar

• 60

  OksuzS.UlubelenA.ClarkW. D.BrownG. K.BrownT. J. (1981). Flavonoids of haplopappus canescens. Rev. Latinoam. Quim12, 12.

  • Google Scholar

• 61

  OrtizS.Lecsö-BornetM.BonnalC.HouzeS.MichelS.GrougnetR.et al (2019). Bioguided identification of triterpenoids and neolignans as bioactive compounds from anti-infectious medicinal plants of the Taira Atacama’s community (Calama, Chile). J. Ethnopharmacol.231, 217–229. 10.1016/j.jep.2018.10.029

  • CrossRef
  • Google Scholar

• 62

  PadillaC.LobosO.Poblete-TapiaP.Carrasco-SánchezV. (2021). Antimicrobial activity of bioactive compounds of Haplopappus multifolius and Haplopappus taeda against human pathogenic microorganisms. Iran. J. Microbiol.13, 98–103. 10.18502/ijm.v13i1.5498

  • CrossRef
  • Google Scholar

• 63

  PlummerJ. (2022). Haplopappus multifolius. The IUCN Red List of Threatened Species. 2022: e.T184927307A188497867.

  • Google Scholar

• 64

  POWO (2024). Plants of the World online. Kew: Facilitated by the Royal Botanic Gardens. Available at: http://www.plantsoftheworldonline.org/RetrievedDDMonth2021.

  • Google Scholar

• 65

  RateraE.RateraM. (1980). “Plantas de la flora argentina empleadas en medicina popular,”. Buenos Aires, Argentina: Hemisferio Sur.

  • Google Scholar

• 66

  J.,Remington,H.Woods, (1918). The dispensatory of the United States of America. 20th edition (USA: Lippincott).

  • Google Scholar

• 67

  RodriguezR.MarticorenaC.AlarcónD.BaezaC.CavieresL.FinotV. L.et al (2018). Catálogo de las plantas vasculares de Chile. Gayana Bot.75, 1–430. 10.4067/s0717-66432018000100001

  • CrossRef
  • Google Scholar

• 68

  RossomandoP. C.GuerreiroE.GiordanoO. S. (1995). “Diterpenes and other constituents from Argentinean Haplopappus species,” in Anales de la Asociación Química Argentina, 55–58.

  • Google Scholar

• 69

  Schmeda-HirschmannG.QuispeC.GonzálezB. (2015). Phenolic profiling of the South American “baylahuen” tea (Haplopappus spp., Asteraceae) by HPLC-DAD-ESI-MS. Molecules20, 913–928. 10.3390/molecules20010913

  • CrossRef
  • Google Scholar

• 70

  SchrickelS.BittnerM. (2001). “La salud en nuestras manos. Plantas medicinales en Chile, Riqueza Natural y Científica,” in Concepción, Chile. Concepción, Chile: Lamas.

  • Google Scholar

• 71

  SchwenkerG.KlossP.EngelsW. (1967). On the isolation of prenyletin from Haplopappus baylahuen. Pharmazie22, 724–725.

  • Google Scholar

• 72

  SerracinoG.StehbergR.LibermanG. (1974). Informe etnobotánico de Guatin (San Pedro de Atacama). Antropol. Nueva Epoca1, 55–65.

  • Google Scholar

• 73

  SilvaM.SammesP. G. (1973). A new diterpenic acid and other constituents of Haplopappus foliosus and H. angustifolius. Phytochemistry12, 1755–1758. 10.1016/0031-9422(73)80397-8

  • CrossRef
  • Google Scholar

• 74

  SpeiskyH.RoccoC.CarrascoC.LissiE. A.López‐AlarcónC. (2006). Antioxidant screening of medicinal herbal teas. Phyther. Res.20, 462–467. 10.1002/ptr.1878

  • CrossRef
  • Google Scholar

• 75

  SteinmetzE. F. (1954). Materia medica vegetabilis.Amsterdam, The Nethelands.

  • Google Scholar

• 76

  TojoE.RialM. E.UrzúaA.MendozaL. (1999). Clerodane diterpenes from Haplopappus deserticola. Phytochemistry52, 1531–1533. 10.1016/s0031-9422(99)00193-4

  • CrossRef
  • Google Scholar

• 77

  TorresR.FainiF.Delle MonacheF.Delle MonacheG. (2004). Two new O-geranyl coumarins from the resinous exudate of Haplopappus multifolius. Fitoterapia75, 5–8. 10.1016/j.fitote.2003.06.003

  • CrossRef
  • Google Scholar

• 78

  TorresR.FainiF.ModakB.UrbinaF.LabbéC.GuerreroJ. (2006). Antioxidant activity of coumarins and flavonols from the resinous exudate of Haplopappus multifolius. Phytochemistry67, 984–987. 10.1016/j.phytochem.2006.03.016

  • CrossRef
  • Google Scholar

• 79

  TorresR.FainiF.RodillaJ. M. L.SilvaL. A.SanzF. (2005). Crystal structure of taedol, C10H16O2, from Haplopappus taeda. Z. für Krist. Cryst. Struct.220, 537–538. 10.1524/ncrs.2005.220.4.537

  • CrossRef
  • Google Scholar

• 80

  TorresR.MascayanoC.NunezC.ModakB.FainiF. (2013). Coumarins of Haplopappus multifolius and derivative as inhibitors of LOX: evaluation in-vitro and docking studies. J. Chil. Chem. Soc.58, 2027–2030. 10.4067/s0717-97072013000400027

  • CrossRef
  • Google Scholar

• 81

  TschescheR.Sualaheen DelhviM.Sepúlveda‐BozaS.ZillikenF.KirfelA.WillG. (1985). Haplopappin, ein 8‐(α‐Methylbenzyl)flavonoid aus Haplopapus foliosus. Liebigs Ann. Chem.1985, 2465–2471. 10.1002/jlac.198519851215

  • CrossRef
  • Google Scholar

• 82

  UlubelenA.AyanogluE.ClarkW. D.BrownG. K.MabryT. J. (1982). Flavonoids from haplopappus foliosus. J. Nat. Prod.45, 363–364. 10.1021/np50021a021

  • CrossRef
  • Google Scholar

• 83

  UlubelenA.ClarkW. D.BrownG. K.MabryT. J. (1981). Flavonoids of haplopappus rengifoanus Remy in Gay. J. Nat. Prod.44, 294–295. 10.1021/np50015a010

  • CrossRef
  • Google Scholar

• 84

  UrzúaA. (2004). Secondary metabolites in the epicuticle of Haplopappus foliosus DC. (Asteraceae). J. Chil. Chem. Soc.49, 137–141. 10.4067/S0717-97072004000200006

  • CrossRef
  • Google Scholar

• 85

  UrzúaA.AndradeL.JaraF. (2000). Comparative chemical composition of the resinous exudates from Haplopappus foliosus and H. uncinatus. Biochem. Syst. Ecol.28, 491–493. 10.1016/s0305-1978(99)00080-0

  • CrossRef
  • Google Scholar

• 86

  UrzúaA.ContrerasR.JaraP.AvilaF.SuazoM. (2004a). Comparative chemical composition of the trichome secreted exudates and of the waxy coating from Haplopappus velutinus, H. illinitus, H. shumanni and H. uncinatus. Biochem. Syst. Ecol.32 (2), 215–218. 10.1016/S0305-1978(03)00157-1

  • CrossRef
  • Google Scholar

• 87

  UrzúaA.CuadraP.RodriguezR.MendozaL. (1991). Flavonoid aglycones in the resinous exudate of some Chilean plants. Fitoterapia62, 358.

  • Google Scholar

• 88

  UrzúaA.EcheverríaJ.EspinozaJ. (2012). Lipophilicity and antibacterial activity of flavonols: antibacterial activity of resinous exudates of haplopappus litoralis, H. chrysantemifolius and H. scrobiculatus. Bol. Latinoam. del Caribe Plantas Aromat.11, 369–376.

  • Google Scholar

• 89

  UrzúaA.IturraB.SebastiánB.MuñozM. (2007a). Chemical components from the surface of Haplopappus bustillosianus. Biochem. Syst. Ecol.35, 794–796. 10.1016/j.bse.2007.03.020

  • CrossRef
  • Google Scholar

• 90

  UrzúaA.JaraF.TojoE.WilkensM.MendozaL.RezendeM. C. (2006). A new antibacterial clerodane diterpenoid from the resinous exudate of Haplopappus uncinatus. J. Ethnopharmacol.103, 297–301. 10.1016/j.jep.2005.09.042

  • CrossRef
  • Google Scholar

• 91

  UrzúaA.MendozaL. (1989). 19-Metil éster del ácido dehidropinifólico en la resina de Haplopappus velutinus. Bol. la Soc. Chil. Quim.34, 221–223.

  • Google Scholar

• 92

  UrzuaA.MendozaL. (1993). Chemical composition of the resinous exudate of Haplopappus velutinus. Bol. la Soc. Chil. Quim.38, 89–93.

  • Google Scholar

• 93

  UrzúaA.MendozaL. (2001). Antibacterial activity of the resinous exudates from Haplopappus uncinatus and Haplopappus foliosus. Fitoterapia72, 418–420. 10.1016/s0367-326x(00)00332-4

  • CrossRef
  • Google Scholar

• 94

  UrzúaA.MendozaL.AndradeL.MirandaB. (1997). Diterpenoids in the trichome resinous exudate from Haplopappus shumannii. Biochem. Syst. Ecol.25, 683–684. 10.1016/s0305-1978(97)00071-9

  • CrossRef
  • Google Scholar

• 95

  UrzúaA.SantanderR.EcheverriaJ.CabezasN.PalaciosS. M.RossiY. (2010). Insecticide properties of the essential oils from haplopappus foliosus and Bahia Ambrosoides against the house fly, Musca Domestica L. J. Chil. Chem. Soc.55, 392–395. 10.4067/S0717-97072010000300026

  • CrossRef
  • Google Scholar

• 96

  UrzúaA.SantanderR.EcheverríaJ.RezendeM. C. (2007b). Secondary metabolites in the flower heads of Haplopappus berterii (Asteraceae) and its relation with insect-attracting mechanisms. J. Chil. Chem. Soc.52, 1142–1144. 10.4067/s0717-97072007000200005

  • CrossRef
  • Google Scholar

• 97

  UrzuaA.TojoE.SotoJ. (1995a). A diterpene xyloside from the resinous exudate of Haplopappus diplopappus. Phytochemistry38, 555–556. 10.1016/0031-9422(94)00590-p

  • CrossRef
  • Google Scholar

• 98

  UrzúaA.TorresR.MendozaL.Delle MonacheF. (2003). Antibacterial new clerodane diterpenes from the surface of Haplopappus foliosus. Planta Med.69, 675–677. 10.1055/s-2003-41118

  • CrossRef
  • Google Scholar

• 99

  UrzúaA.TorresR.MuñozM.PalaciosY. (1995b). Comparative antimicrobial study of the resinous exudates of some Chilean Haplopappus (Asteraceae). J. Ethnopharmacol.45, 71–74. 10.1016/0378-8741(94)01196-7

  • CrossRef
  • Google Scholar

• 100

  UrzúaA.VinesM.EcheverríaJ.IbacacheA.IturraB.SebastiánB. (2004b). “Actividad antibacteriana y composición química de los extractos superficiales de Haplopappus berteri, H. cuneifolius, H. litoralis, H. scrobiculatus y H. sp. (“Bailahuen”),” in Segundo Simposium Internacional de Plantas Medicinales y Fitoterapia.

  • Google Scholar

• 101

  Urzúa MollA.Caroli RezendeM.BeezerA.MitchellJ. (1997). A calorimetric bioassay of diterpenoids from Chilean medicinal plants against Streptococcus mutans. Bol. la Soc. Chil. Quim.43, 81–85.

  • Google Scholar

• 102

  Valant-VetscheraK. M.WollenweberE. (2007). Chemodiversity of exudate flavonoids in seven tribes of Cichorioideae and Asteroideae (Asteraceae). Z. für Naturforsch. C62, 155–163. 10.1515/znc-2007-3-401

  • CrossRef
  • Google Scholar

• 103

  VeraJ. C.ReyesA. M.VelásquezF. V.RivasC. I.ZhangR. H.StrobelP.et al (2001). Direct inhibition of the hexose transporter GLUT1 by tyrosine kinase inhibitors. Biochemistry40, 777–790. 10.1021/bi001660j

  • CrossRef
  • Google Scholar

• 104

  VillagraC.VeraW.LenitzS.BergmannJ. (2021). Differences in volatile emissions between healthy and gall-induced branches of Haplopappus foliosus (Asteraceae). Biochem. Syst. Ecol.98, 104309. 10.1016/j.bse.2021.104309

  • CrossRef
  • Google Scholar

• 105

  VillagránC.CastroV.SánchezG.RomoM.LatorreC.HinojosaL. F. (1998). La tradición surandina del desierto: Etnobotánica del área del Salar de Atacama (Provincia de El Loa, Región de Antofagasta, Chile). Estud. atacameños, 7–105.

  • Google Scholar

• 106

  VillagránC.RomoM.CastroV. (2003). Etnobotánica del sur de losAndes de la primera región de Chile: Un enlace entre las culturas altiplánicas y las de quebradas altas del Loa Superior. Chungara, Rev. Antropol. Chil.35, 73–124. 10.4067/s0717-73562003000100005

  • CrossRef
  • Google Scholar

• 107

  VogelH.GonzálezB.San MartínJ.RazmilicI.VillalobosP.SchneiderE. (2007). Study of the marketing and sustainability of the forest collection of bailahuén, a Chilean medicinal plant. Med. Plant Conserv.13, 15–21.

  • Google Scholar

• 108

  VogelH.GonzálezM.FainiF.RazmilicI.RodríguezJ.San MartínJ.et al (2005a). Antioxidant properties and TLC characterization of four Chilean Haplopappus-species known as bailahuen. J. Ethnopharmacol.97, 97–100. 10.1016/j.jep.2004.10.027

  • CrossRef
  • Google Scholar

• 109

  VogelH.RazmilicI.San MartínJ.DollU.GonzálezB. (2005b). Plantas medicinales chilenas. Experiencias de domesticación y cultivo de boldo, matico, bailahuén, canelo, peumo y maqui. Talca, Chile. Editor. Univ. Talca.

  • Google Scholar

• 110

  WickensG. E. (1993). Vegetation and ethnobotany of the Atacama Desert and adjacent Andes in northern Chile. Opera Bot.121, 291–307.

  • Google Scholar

• 111

  ZderoC.BohlmannF.NiemeyerH. M. (1990). Diterpenes and umbelliferone derivatives from Haplopappus deserticola. Phytochemistry29, 326–329. 10.1016/0031-9422(90)89064-g

  • CrossRef
  • Google Scholar

• 112

  ZderoC.BohlmannF.NiemeyerH. M. (1991a). Friedolabdanes and other constituents from chilean Haplopappus species. Phytochemistry30, 3669–3677. 10.1016/0031-9422(91)80089-j

  • CrossRef
  • Google Scholar

• 113

  ZderoC.BohlmannF.NiemeyerH. M. (1991b). Seco-nor-normal and rearranged labdanes from Haplopappus parvifolius. Phytochemistry30, 3683–3691. 10.1016/0031-9422(91)80091-e

  • CrossRef
  • Google Scholar

• 114

  ZuloagaF. O.BelgranoM. J.ZanottiC. A. (2019). Actualización del Catálogo de las Plantas Vasculares del Cono Sur. Darwiniana, Nueva Ser.7, 208–278. 10.14522/darwiniana.2019.72.861

  • CrossRef
  • Google Scholar