Phytochemical review of the lichen genus Stereocaulon (Fam. Stereocaulaceae) and related pharmacological activities highlighted by a focus on nine species
- 106 Downloads
The Stereocaulon genus is one of the fruticose lichen groups distributed worldwide from tropical zones to polar zones. However, the scientific study of this tricky genus is still limited, making it a challenge to study the group further. Detailed morphological studies are essential to discriminate closely shaped species which is illustrated through personal data focused on phyllocladia, apothecia and spores of nine species. Secondary metabolites isolated from Stereocaulon species are mostly some depsides, depsidones, diphenylethers and dibenzofurans which can have a taxonomic value. The use of Stereocaulon lichens as a traditional medicine in several regions of the world and pharmacological studies of extracts and isolated compounds have been compiled. Biological activities as cytotoxic, anti-inflammatory, antibacterial, antifungal or antioxidant are reported.
KeywordsBiogenetic Bioactivities Folk medicines Lichens Secondary metabolites Stereocaulon
Anyone who has attempted to determine material of Stereocaulon or has studied the material in our herbaria must have realized the confusion which exists in regard to the distinctive of the species characters of the species. This confusion arises in part from the great variability and their tendency to intergrade.
Fortunately, thanks to his work and many other works of famous lichenologists as Nylander in his Synopsis Lichenum (Nylander 1860), Magnusson (Magnusson 1926), Dodge (Dodge 1929), Johnson (Johnson 1938), Duvigneaud (Duvigneaud 1942, 1944, 1955) and more recently to Lamb compendium (Lamb 1951, 1977, 1978), complemented by Boehkout (1982) for the Columbian Stereocaulon species and McCarthy (2012) for the Australasian lichens, the lack of monographies and papers has disappeared and keys of classification for the Stereocaulon species are now available. Nevertheless, although there have been numerous taxonomic studies of Stereocaulon, it remains a tricky genus for lichenologists and the systematic arrangement of the species within the genus is not an easy task. The extreme polymorphic, the high plasticity and adaptability of some Stereocaulon species (sometimes not supported by any variation in chemistry) is a source of confusion and as a result many superfluous names were established. 34 taxa corresponding to the common name “snow lichen” are recognized in the plants database of US while 813 species and varieties are listed in Index Fungorum website (Index Fungorum 2018; Natural Resources Conservation Service 2018). As usual in lichenology, chemotaxonomy is often addressed and useful but their determination has to be based on both morphological and chemical data. New trends are the use of barcoding based on ITS molecular analysis resulting in revised classifications (Högnabba 2006; Hognabba et al. 2014).
Proper identification of the material to be phytochemically studied is required as a first step before isolation and biological valorization of its metabolites. Stereocaulon lichens are a source of a number of lichen compounds, some being very common such as the depside atranorin encountered in many lichens but others are unusual such as diphenylethers. For all these compounds but also for crude extracts, few biological studies have been conducted. We propose to report in this paper the chemical composition described for Stereocaulon species along with their traditional use and the reported pharmacological activities.
Morphology and classification of genus Stereocaulon
Among the several lichenologists who described Stereocaulon species, Lamb remains the most famous. In 1951, he proposed a classification based on morphological form and anatomy, thus dividing Stereocaulon genus into three subgenera namely Enteropodium, Pilophoris and Holostelidium including also sections and subsections (Lamb 1951). However, the identification process does not depend solely on Stereocaulon morphology. The main compounds observed with microchemistry or Thin Layer Chromatography (TLC) in Stereocaulon also play an important role in the lichen identification, as used by Duvigneaud (1955) and Lamb (1977, 1978) in The Conspectus about The Lichen Genus Stereocaulon. Another way to confirm the identity of the species is the use of molecular biology analysis. Three recent papers are based on molecular data: Myllys studied the phylogenetic relationships of all members of the Stereocaulaceae (Myllys et al. 2005), Högnabba (2006) and Hognabba et al. (2014) attempted to clarify phylogenetic relationships of several taxa within this genus. Through ITS1-5.8S-ITS2 and partial β-tubulin analysis, 49 different Stereocaulon species were organized by Högnabba in 2006 and compared to the classification by Lamb (Lamb 1977).
Biogenetic pathways of lichen compounds and secondary metabolites of the genus Stereocaulon
The number of secondary metabolites isolated from lichens was around 800 compounds in 1996 (Huneck and Yoshimura 1996) and has now increased beyond 1050 compounds (Stocker-Wörgötter 2008; Elix 2014). However, the phytochemical studies of the Stereocaulon genus are still limited and most of the compounds were only major ones and were usually detected by TLC. As an example, the major compounds were easily TLC-visualized from the nine previous species collected in several places in the world, The composition of their methanolic extracts revealed until 17 spots using HPTLC-UV (Fig. S1, SD M2); S. halei was the less rich extract (4 spots) compared to S. dactylophyllum, S. montagneanum, S. graminosum, S. vulcani exhibiting 7 spots. Among these compounds, only the major compounds revealed in all Stereocaulon extracts with (Rf = 0.80; λmax = 280,310 nm), (Rf = 0.64; λmax = 220,250,280 nm), (Rf = 0.51; λmax = 280,310 nm), (Rf = 0.33; λmax = 280,310,340 nm) were unambiguously identified as atranorin, methyl orcinol carboxylate, lobaric acid and stictic acid (Fig. S2). These preliminary data were in agreement with the compounds reported by Lamb (1977) from 123 species in its Conspectus about Stereocaulon genus (Fig. S2).
Phytochemical studies were thoroughly only performed on 40 species and subspecies and structural diversity from Stereocaulon genus was restricted to depsides, depsidones, diphenylethers, dibenzofuranes, monoaromatic phenols, terpenoids and steroids and polyols.
Depsides, depsidones, monoaromatic phenols, diphenylethers, dibenzofurans and anthraquinones are derivatives synthetised from acetate-polymalonate pathways. The biosynthesis of depsides and depsidones begin with the condensation of monoaromatic compounds such as orsellinate and orcinol. These latter may also be regarded as the precursor of depside biogenesis (Seshadri 1944; Yamazaki et al. 1965; Stocker-Wörgötter 2008) or from the decomposition or degradation of a depside (Hylands and Ingolfsdottir 1985; Huneck et al. 1989) Diphenylethers are a combination of two phenolics with ether bonds. This group of compounds is formed from the opening of the ester bond from the depsidone ring by hydrolysis reaction followed by nucleophilic attack and prototropic regulation, but without decarboxylation or O-methylation as described for the biosynthesis of loxodin and norlobaridone respectively (Foo and Galloway 1979; Chooi 2008) (Fig. S3). Others suggested that some diphenylethers have been formed during extraction (Gonzalez et al. 1995; Millot et al. 2008) or by treatment of depsidones using hot alkali as described for lobariol carboxylic acid or lobarin from lobaric acid (Asahina and Nonomura 1935; Han et al. 2012). One of the most common and widely known depside is atranorin, and almost all species of Stereocaulon genus contain it (Fig. S2). Furthermore, several other depsides have been also discovered. Among depsides without aliphatic chain (such as atranorin), lecanoric acid was isolated from S. curtatum and S. corticulatum (Huneck and Follman 1965; Hamada and Ueno 1990), while from S. evolutum were reported for the first time methyl-3-methyllecanorate and cladonioidesin, along with a new depside (Vu et al. 2015).
Meanwhile, three depsidones of prenyl-type have been recorded. The first one is lobaric acid which represents the most third common compound in Stereocaulon genus. Methanolic extracts of S. evolutum, S. grande, S. halei contained lobaric acid as major compound (Ismed 2012). Other close structural compounds are colensoic acid which was isolated from S. colensoi (Fox et al. 1970) and norlobaric acid from S. paschale (Carpentier et al. 2017) (Fig. 9).
Folk medicine and pharmacological studies
The utilization of Stereocaulon genus in traditional medicine is quite rare. However, some ethnopharmacological reports mention Stereocaulon to be used in treatments of ailments. Lavergne reported that S.vulcani with its called name “fleur de roche” was used by Reunion Islanders as a treatment against syphilis, ulcers and wound healers (Lavergne 1989). The people of Indo-Tibetan Himalayas call S. himalayense under the name “chanchal” which they use for the treatment of urinary infection (Sharma 1997). S. paschale is used as symptomatic treatment for type 2 diabetes in Cree community in Quebec, Canada (Fraser et al. 2007).
Some usual cytotoxic, antioxidant or antimicrobial assays have been carried out on extracts from this genus. For instance, a methanolic extract of S. paschale showed a weak free radical scavenging activity IC50 0.88 mg/mL, a MIC (Minimum Inhibitory Concentration) ranging from 0.625 to 10 mg/mL against the growth of Bacillus subtilis and B.cereus and a very moderate cytotoxic effect against FemX (human melanoma) and LS174 (human colon carcinoma) cell line with IC50 46.67 and 71.71 μg/mL respectively (Rankovic et al. 2014).
The crude acetone extract of four lichen species collected in the Philippines was reported active against the growth of S. aureus and B. subtilis. One of them, S. massartianum, was the most powerful against both bacteria with a diameter of inhibition > 19 mm. (Santiago et al. 2010). An ethanolic extract from S. foliolosum inhibits the growth of M. tuberculosis H37Rv with MIC 500 μg/mL which is compared to rifampicin and isoniazid (MIC value 0.25 and 0.1 μg/mL, respectively) (Gupta et al. 2007). The n-hexane extract of S. himalayense is highly active against the soil pathogenic fungi Rhizoctonia bataticola with an ED50 value 51.36 μg/mL (Goel et al. 2011). Unfortunately, no further phytochemical studies led to isolation of the compounds involved in the antimicrobial activities.
Moreover, some isolated lichen substances from the Stereocaulon genus are reported to be pharmacologically active. Lobaric acid has been tested as an anti-inflammatory, cytotoxic and antimicrobial agent. Suggesting a possible anti-inflammatory activity, lobaric acid inhibits selectively four times higher the 5-lipoxygenase enzyme (IC50 7.3 μM) than cyclooxygenase (Ingolfsdottir et al. 1996). Moreover, it inhibits the growth of S. aureus-1199B, a type of multidrug resistant bacteria to certain fluoroquinolones, with a MIC value of 17.52 μM compared to norfloxacin (MIC 100 μM) (Kokubun et al. 2007). This compound was not very cytotoxic as a moderate cytotoxic activity was shown on three malignant cell lines (T-47D and ZR-75-1 from breast carcinomas and K-562 from erythro-leukemia), with ED50 31.76, 97.92 and 53.67 µM, respectively (Ogmundsdóttir et al. 1998).
Furthermore, lobaric acid and its derivatives, two pseudodepsidones, isolated from S. alpinum but also diphenylethers isolated from S. evolutum (Vu 2014) potentially inhibit protein tyrosine phosphatase1B (PTP1B), a negative regulator of insulin considered to be a promising target for treatment of type 2 diabetes mellitus and breast cancer. The IC50 values for lobaric acid (0.87 µM), methyl sakisacaulon (2.48 µM) and methyl lobarin (6.86 µM) were better than those of the positive control, ursolic acid (3.08 µM) (Seo et al. 2009). Another pseudodepsidone from this species, lobastin, was evaluated as antibacterial against gram-positive bacteria (B. subtilis and S. aureus) with MIC values 44 and 35.2 μM compared to ampicillin 2.7 μM (Bhattarai et al. 2013). Lobastin has also been reported active as anti-inflammatory in atherosclerotic conditions inhibiting protein expression of VCAM 1 (Vascular Cell Adhesion Molecules 1) inducted by TNF-α at concentrations of 0.22–21.9 μM (Lee et al. 2016).
Recently, atranorin and its derivatives were reported as antiviral agents against hepatitis C virus with IC50 10–70 μM (Vu et al. 2015). Atranorin was found to inhibit virus penetration in cells like the positive control erlotinib while two hemisynthetic compounds inhibits the viral replication like telaprevir (Vu et al. 2015). Among monoaromatic phenols, methyl β-orsellinate from S. alpinum was reported 5–40 times more active as preservative (MIC 0.16–2.74 mM) than p-hydroxybenzoate (MIC 2.92–14.58 mM) and chlorocresol (MIC 0.70–2.80 mM) against Pseudomonas aeruginosa (Ingolfsdottir et al. 1985). Methyl haematommate was active as an antifungal (Hickey et al. 1990), 9-cis-octadecenamide from the group of alkamides as anti-inflammatory agent with IC50 64.3 μM (Ingólfsdóttir et al. 1997).
Stereocaulon is a tricky genus to be identified but largely distributed and quite easy to collect as sometimes covering large parts of lands or rocks, particularly in volcanic places. Although partially investigated for phytochemistry, a variety of compounds have been isolated. Some compounds are frequently found and abundant in many species of this genus like atranorin, stictic acid or lobaric acid. Some of them have shown interesting activities but uses in traditional medicines are not fully supported as bioassays are only carried with in vitro tests However, abundance of Stereocaulon species in some places combined with high amount of specific compounds offers a unique opportunity to go further in finding and optimizing new drug candidates.
The collaboration has been initiated in the frame of a Bioasia program (LICHENASIA 2009–2010) and further supported by the French Embassy in Indonesia. The authors also acknowledge A. Burel, V. Gouesbert and M.T. Lavault (Mric TEM. Univ. Rennes, BIOSIT—UMS 3480) for technical contribution in preparing lichens sections for light microscopy. J. Le Lannic is acknowledged for SEM images performed at CMEBA (ScanMAT, UMS 2001 CNRS—University of Rennes 1). A great acknowledgement is due to A. Chambet who provided some unvaluable documents and specimens from the Des Abbayes lichen Herbarium Collection and to JM Sussey for providing some sample of S. grande. Dr H Sipman (Berlin Museum) was also of great support with expertise in tropical lichen identification.
- Aghoramurthy K, Sarma K, Seshadri T (1961) Chemical investigation of Indian lichens: part XXV—chemical components of some rare Himalayan lichens. J Sci Ind Res 20B:166–168Google Scholar
- Boekhout T (1982) Studies on Colombia cryptogams XVIII. the genus Stereocaulon (SCHREBER)HOFFMAN (Lichenes). J Hattori Bot Lab 53:483–511Google Scholar
- Cai Z, Song M, Zhang L et al (2009) Phenolic constituents of Stereocaulon paschale Hoffm. Sanxia Daxue Xuebao Ziran Kexueban 31:94–109Google Scholar
- Chooi Y (2008) Genetic potential of lichen-forming fungi in polyketide biosynthesis. RMIT University, MelbourneGoogle Scholar
- Dodge C (1929) A synopsis of Stereocaulon with notes on some exotic species. Ann Cryptog Exot 2:93–153Google Scholar
- Duvigneaud P (1942) Contribution à l’étude systématique et chimique du genre Stereocaulon. Biol Jaarb “Dodonaea” 25:80–98Google Scholar
- Duvigneaud P (1955) Les Stereocaulons des hautes montagnes du Kivu. Rev Bot 14:1–141Google Scholar
- Elix J (1996) Biochemistry and secondary metabolites. In: Nash T (ed) Lichen biology. Cambridge University Press, Cambridge, pp 154–180Google Scholar
- Elix J (2014) A Catalogue of standardized chromatographic data and biosynthetic relationships for lichen substances, 3rd edn. CanberraGoogle Scholar
- Gonzalez A, Rodriguez E, Bermejo J (1995) Depsidone chemical transformations in an extract of the lichen Stereocaulon azoreum. An Quim 5:461–466Google Scholar
- Han YJ, Chan K I, Kyu KD et al (2012) Lobarin for treating diabetes and obesity. Republic of Korea: KIPRIS. 1020100097678Google Scholar
- Hickey B, Lumsden A, Cole A, Walker J (1990) Antibiotic compounds from New Zealand plants: methyl haematommate, an anti-fungal agent from Stereocaulon ramulosum. NZ Nat Sci 17:49–53Google Scholar
- Huneck S, Follman G (1965) Über die inhaltstoffe von Nephroma gyelnikii (RAES) LAMB, Byssocaulon niveum MONT. und Stereocaulon corticulatum NYL. var.procerum LAMB. Z Naturforsch C Bio Sci 20b:1012–1013Google Scholar
- Index Fungorum (2018) Stereocaulon. http://www.indexfungorum.org/names/Names.asp. Accessed 23 Apr 2018
- Ismed F (2012) Phytochimie de lichens du genre Stereocaulon: étude particulière de S. halei Lamb et S. montagneanum Lamb, deux lichens recoltés en Indonésie. Universite de Rennes 1Google Scholar
- Kirk P, Cannon P, David J, Stalpers J (2001) Ainsworth and Bisby’s dictionary of the fungi, 9th edn. CABI Publishing, WallingfordGoogle Scholar
- Lamb M (1976) Structurally unusual types of cephalodia in the lichen Stereocaulon (subgen. Holostelidium). J Jpn Bot 51:1–7Google Scholar
- Lamb M (1977) A conspectus of the lichen genus Stereocaulon (SCHREB.) HOFFM. J Hattori Bot Lab 43:191–355Google Scholar
- Lamb M (1978) Keys to the species of the lichen genus Stereocaulon (SCHREB.) HOFFM. J Hattori Bot Lab 44:209–250Google Scholar
- Lavergne R (1989) Plantes medicinales indigenes tisanerie et tisaneurs de la Reunion. Universite des Sciences et Techniques du Languedoc, FranceGoogle Scholar
- Li B, Lin Z, Sun H (1991) The chemical constituents of four lichens from China. Yunnan Zhiwu Yanjiu 13:81–84Google Scholar
- Magnusson A (1926) Studies on boreal Stereocaula. K Vet O Vitterh Samh Handl 30:1–89Google Scholar
- Malik S, Pardeshi N, Seshadri T (1972) Chemical investigation of Indian lichens. Part XXX. Indian J Chem 10:1040Google Scholar
- McCarthy P (2012) Checklist of the lichens of Australia and its island territories. In: Aust Biol Resour Study. http://www.anbg.gov.au/abrs/lichenlist/introduction.html. Accessed 10 Jan 2018
- Natural Resources Conservation Service (2018) Classification for kingdom plantae down to genus Stereocaulon Hoffm. In: USDA. https://plants.usda.gov/java/ClassificationServlet?source=profile&symbol=STERE2&display=31. Accessed 23 Apr 2018
- Nylander W (1860) Synopsis methodica lichenum. Martinet, ParisGoogle Scholar
- Ogmundsdóttir HM, Zoëga GM, Gissurarson SR, Ingólfsdóttir K (1998) Anti-proliferative effects of lichen-derived inhibitors of 5-lipoxygenase on malignant cell-lines and mitogen-stimulated lymphocytes. J Pharm Pharmacol 50:107–115. https://doi.org/10.1111/j.2042-7158.1998.tb03312.x CrossRefPubMedGoogle Scholar
- Purvis O, Coppins B, Hawksworth D et al (1992) The lichen flora of Great Britain and Ireland. The British Lichen Society, LondonGoogle Scholar
- Rankovic B, Kosanic M, Stanojkovic T (2014) Stereocaulon paschale lichen as antioxidant, antimicrobial and anticancer agent. Farmacia 62:306–317Google Scholar
- Santiago K, Borricano J, Canal J et al (2010) Antibacterial activities of fructicose lichens collected from selected sites in Luzon Island, Philippines. Philipp Sci Lett 3:18–29Google Scholar
- Seshadri T (1944) A theory of biogenesis of lichen depsides and depsidones. In: Proceedings of the Indian Academy of Sciences—section A. Springer, India, pp 1–14Google Scholar
- Sharma G (1997) Ethnomedicinal flora: ayurvedic system of medicine in a remote part of the Indo-Tibetan Himalayas. J Tenn Acad Sci 72:53–54Google Scholar
- Solberg Y (1987) Chemical constituents of the lichens Cetraria delisei, Lobaria pulmonaria, Stereocaulon tomentosum and Usnea hirta. J Hattori Bot Lab 63:357–366Google Scholar
- Vila J, Mollinedo P, Flores Y, Sterner O (2008) 1,3,7-trimethylguanine from the lichen Stereocaulon ramulosum. Rev Bol Quim 25:1–3Google Scholar
- Vu TH (2014) Etude des acides gras du genre Stereocaulon etude phytochimique du lichen S. evolutum Graewe. Université de Rennes1Google Scholar