Salazinic Acid Research Articles

Lichen-derived caperatic acid and physodic acid inhibit Wnt signaling in colorectal cancer cells

Lichens are a source of secondary metabolites which possess important biological activities, including antioxidant, antibacterial, anti-inflammatory, and cytotoxic effects. The anticancer activity of lichens was shown in many types of tumors, including colorectal cancers (CRC). Several studies revealed that the application of lichen extracts diminished the proliferation of CRC cells and induced apoptosis. Colon carcinogenesis is associated with aberrations in Wnt signaling. Elevated transcriptional activity of β-catenin induces cell survival, proliferation, and migration. Thus, the inhibition of Wnt signaling is a promising therapeutic strategy in colorectal cancer. The aim of this study was the evaluation of the effects of lichen-derived depsides (atranorin, lecanoric acid, squamatic acid) and depsidones (physodic acid, salazinic acid) and a poly-carboxylic fatty acid—caperatic acid, on Wnt signaling in HCT116 and DLD-1 colorectal cancer cell lines. HCT116 cells were more sensitive to the modulatory effects of the compounds. PKF118-310, which was used as a reference β-catenin inhibitor, dose-dependently reduced the expression of the classical β-catenin target gene—Axin2 in both cell lines. Lecanoric acid slightly reduced Axin2 expression in HCT116 cells while caperatic acid tended to reduce Axin2 expression in both cell lines. Physodic acid much more potently decreased Axin2 expression in HCT116 cells than in DLD-1 cells. Physodic acid and caperatic acid also diminished the expression of survivin and MMP7 in a cell line and time-dependent manner. None of the compounds affected the nuclear translocation of β-catenin. This is the first report showing the ability of caperatic acid and physodic acid to modulate β-catenin-dependent transcription.

Chemical Composition of Umbilicaria crustulosa and U. cylindrica

The chemical composition of ether, ethyl acetate and dichloromethane extracts of Umbilicaria crustulosa and U. cylindrica were determined for the first time by HPLC-UV, GC-FID and GC-MS. The HPLC-UV analysis was revealed the presence of methyl orsellinate, lecanoric acid, crustinic acid, gyrophoric acid and atranorin in U. crustulosa extracts while in U. cylindrica extracts were detected following compounds: salazinic acid, norstictic acid, atraric acid, gyrophoric acid and atranorin. GC-FID and GC-MS analysis were enabled the identification of orsellinic acid (40.4%) and orcinol (48.1%) as main components of U. crustulosa extracts and atraric acid (8.5%) and orcinol (10.3%) in U. cylindrica extracts.

Taxonomy of the corticolous, shrubby, esorediate, neotropical species ofUsneaAdans. (Parmeliaceae) with an emphasis on southern Brazil

AbstractSeventeen corticolous shrubby apotheciateUsneaspecies without vegetative propagules are reported from Brazil, including five species that are new to science:Usnea aurantiaca-parvulaA. Gerlach & P. Clerc (characterized by an orange medulla and lageniform spinulose fibrils),U. cirrosaMotyka,U. cladocarpaFée (syn. nov.:U. ramillosaMotyka),U. concinnaStirton (lectotype designated here, syn. nov.U. radiataStirton,U. floridavar.scabrosaZahlbr.),U. cristatulaMotyka,U. erinaceaVain.,U. fleigiaeA. Gerlach & P. Clerc (characterized by large spores and a thin, lax medulla),U. grandisporaA. Gerlach & P. Clerc (characterized by large spores, a black base and protocetraric or salazinic acids in the medulla),U. kalbianaP. Clerc & A. Gerlach (characterized by a vitreous cortex and annular cracks in the basal part),U. lunariaMotyka,U. meridionalisZahlbr. (syn. nov.:U. michauxiiI. I. Tav.),Usneacf.morelianaMotyka,U. parvulaMotyka,U. steineriZahlbr,U. subelegans(Vain.) B. de Lesd. (lectotype designated here),U. subparvulaA. Gerlach & P. Clerc (characterized by spinulose fibrils and protocetraric acid in the medulla) and one as yet unidentified species (namedUsneasp. 1).Usnea cirrosa,U. cristatulaandU. erinaceaare new records for Brazil. A full description with morphological, anatomical (CMA and ascospores) and chemical features (TLC), as well as geographical distribution, is provided for each species along with an identification key to all species reported. Molecular data from the ITS rDNA,RPB1andMcm7markers are present for most taxa, except forU. concinna,U. cristatula,U. kalbiana,U. lunaria,U.cf.morelianaandU. subelegans.

Antigenotoxicity of Depsidones Isolated from Brazilian Lichens

Although phenolic compounds produced by lichens have been widely investigated in antitumor assays, only a small number have been evaluated for mutagenicity and genotoxicity. This study evaluated protocetraric, hypostictic, psoromic, and salazinic acids for their potential genotoxic or antigenotoxic activity against somatic cells of Drosophila melanogaster . These compounds were isolated from the lichens Parmotrema dilatatum, Pseudoparmelia sphaerosphora, Usnea jamaicensis, and Parmotrema cetratum , respectively, collected from the Brazilian Cerrado biome. The compounds were evaluated at 0.75, 1.5, 3.0, and 6.0 mmol L –1 using the SMART test, employing standard and high-bioactivation crosses of Drosophila melanogaster. Doxorubicin (DXR) was the positive control. Psoromic and salazinic acids proved toxic at 6.0 mM. None of the compounds evaluated exhibited mutagenicity, but each of them significantly reduced genetic damage caused by DXR, proving antigenotoxic when tested on somatic cells of D. melanogaster . DOI: http://dx.doi.org/10.17807/orbital.v9i1.897

Potential of Lichen Compounds as Antidiabetic Agents with Antioxidative Properties: A Review.

The advancement in the knowledge of potent antioxidants has uncovered the way for greater insight in the treatment of diabetic complications. Lichens are a rich resource of novel bioactive compounds and their antioxidant potential is well documented. Herein we review the antidiabetic potential of lichens which have received considerable attention, in the recent past. We have correlated the antidiabetic and the antioxidant potential of lichen compounds. The study shows a good accordance between antioxidant and antidiabetic activity of lichens and points out the need to look into gathering the scarce and scattered data on biological activities for effective utilization. The review establishes that the lichen extracts, especially of Parmotrema sp. and Ramalina sp. have shown promising potential in both antidiabetic and antioxidant assays. Ubiquitous compounds, namely, zeorin, methylorsellinate, methyl-β-orcinol carboxylate, methyl haematommate, lecanoric acid, salazinic acid, sekikaic acid, usnic acid, gyrophoric acid, and lobaric acid have shown promising potential in both antidiabetic as well as antioxidant assays highlighting their potential for effective treatment of diabetic mellitus and its associated complications. The available compilation of this data provides the future perspectives and highlight the need for further studies of this potent herbal source to harvest more beneficial therapeutic antidiabetic drugs.

Hemithecium salacinicum, a New Species in the Family Graphidaceae (Lichenized Ascomycota: Ostropales) from Northern Thailand

Abstract: Neuwirth, G., Aptroot, A. & Stocker-Worgotter, E. 2016. Hemithecium salacinicum, a new species in the family Graphidaceae (lichenized Ascomycota: Ostropales) from northern Thailand. — Herzogia 29: 555–560. Hemithecium salacinicum is described as new from the province of Chiang Mai in North Thailand. The distinguishing characters from other species are the thallus, containing the depsidone salazinic acid only, the excipulum with a distinct yellow to orange coloured inner part and the poorly striate labia. The densely muriform, hyaline ascospores with dimensions of 60-110 × 15-22 µm are 25–36/5–7-locular and show conspicious constrictions at transverse septa.

The Impact of Cadmium on Photosynthetic Performance and Secondary Metabolites in the Lichens Parmelia sulcata, Flavoparmelia caperata and Evernia prunastri

Abstract Lichens are one of the most common air quality bioindicators. Airborne heavy metal pollution causes various physiological changes in lichens, but sensitivity to metal pollution is species specific. In this research, three lichen species (Parmelia sulcata, Flavoparmelia caperata and Evernia prunastri) were exposed to cadmium (50 mg L−1) in laboratory conditions. Photosynthetic efficiency of photosystem II and content of secondary metabolites were determined after one, three and eight days of exposure. In all investigated species treatment of lichen thalli with cadmium significantly changed Fv/Fm and RFd only after eight days of exposure. Quantification of metabolites showed a decreased content of the medullary depsidones salazinic acid (in P. sulcata) and protocetraric acid (in F. caperata) but increased content of cortical depside atranorin (in P. sulcata) and dibenzofurane usnic acid (in F. caperata) after cadmium exposure. However, no changes in secondary metabolites were found in E. prunastri. Results show that investigated species are relatively resistant to short-term cadmium-exposure and that secondary metabolites could have an important role in the protection of primary metabolism from negative cadmium impacts, at least in some species.

Antidermatophytic Activity of the Fruticose Lichen Usnea orientalis.

In the present study, the new biological sources in the form of lichen Usnea orientalis Motyka was screened for its antidermatophytic potential. Six species of dermatophytes were chosen on the basis of their prevalence for antidermatophytic assays, and the Clinical Laboratory Standard Institute (CLSI)-recommended broth microdilution procedure was used to detect the efficacy of extract against dermatophytes. Thin layer chromatography of lichen extracts reveals the presence of two secondary metabolites viz. salazinic acid and usnic acid. U. orientalis extract exhibited promising antidermatophytic activity against all tested pathogens. Amongst all tested pathogens, Epidermophyton floccosum exhibited most susceptibility towards extract, whereas Trichophyton mentagrophytes exhibited the least susceptibility. Topical application of U. orientalis extract might be helpful in the cure of dermal infections.

Parmotrema clavuliferum and P. reticulatum are independent species

Parmotrema clavuliferum (<TEX>$R{\ddot{a}}s{\ddot{a}}nen$</TEX>) Streimann and P. reticulatum (Taylor) M. Choisy (Parmeliaceae, lichenized Ascomycotina) have similar morphological characters such as wide lobes with soralia, reticulate-maculate on upper surface of lobes, and marginal cilia. In addition, they both produce salazinic acid and atranorin as major chemical substances. These similar properties found in both species have led to confusion in recognizing them as distinct species; however, P. clavuliferum is distinguished from the latter by capitate soralia on short laciniae which are always mottled white and by the production of fatty acid and gyrophoric acid together with salazinic acid. In addition, the most likely phylogenetic tree of these species shows that they are nested in well-supported monophyletic groups. Therefore, it is reasonable to recognize them as two separate species, P. clavuliferum and P. reticulatum.

Herbicidal and Plant-growth Stimulating Effects of Phenolic Compounds Isolated from Lichens

The depsides atranorin (7) and diffractaic acid (1), the depsidones hypostictic (2) protocetraric (3), salazinic (4) acids, the xanthone secalonic acid (5), and usnic acid (6) were evaluated for their phytotoxic potentials against the target species Allium cepa cv. Baia periforme (onion, Monocotyledoneae). The bioassays, carried out under laboratory conditions, revealed that diffractaic (1) and hypostictic (2) acids stimulated plant growth; secalonic acid (5) stimulated seed germination and radicle growth, while reducing coleoptile length. Usnic acid (6) promoted seed germination and stronger inhibition of radicle and coleoptile growth. Protocetraric (3) and salazinic (4) acids and atranorin (7) exhibited a herbicidal effect, inhibiting seed germination and reducing radicle and coleoptile growth—features that suggest their utility as natural herbicides. These results invite further investigation to elucidate the mode of action of these compounds and to synthesize them for field experiments. DOI: http://dx.doi.org/10.17807/orbital.v7i3.756

Ecological implication of variation in the secondary metabolites in Parmelioid lichens with respect to altitude.

Lichens are known to synthesize a variety of secondary metabolites having multifunctional activity in response to external environmental condition. Two common lichen extrolites, atranorin and salazinic acid, are known to afford antioxidant as well as photoprotectant nature depending on the abiotic/biotic stress. The present investigation aims to study the influence of altitudinal gradient on the quantitative profile of atranorin and salazinic acid in three lichen species, Bulbothrix setschwanensis (Zahlbr.) Hale, Everniastrum cirrhatum (Fr.) Hale and Parmotrema reticulatum (Taylor) Choisy, Parmeliaceae using liquid chromatography-mass spectrometry (LC-MS/MS) technique. Samples were collected from high-altitude area, usually considered as non-polluted sites of Garhwal Himalaya. Characterization and quantification of the lichen substances in samples were carried out comparing with the standards of atranorin and salazinic acid. Results indicated significant variation in the chemical content with the rising altitude. All the three lichen species showed higher quantities of chemical substances with the altitudinal rise, while among the three lichen species, E. cirrhatum showed the highest quantity of total lichen compounds. The higher abundance and frequency of E. cirrhatum with increasing altitude as compared to B. setschwanensis and P. reticulatum may be attributed due to the presence of higher quantity of photoprotecting/antioxidant chemicals especially salazinic acid. Thus, the present study shows the prominent role of secondary metabolite in wider ecological distribution of Parmelioid lichens at higher altitudes.

In Silico Molecular Docking Studies of Lichen Metabolites against Cyclooxygenase-2 Enzyme

Cyclooxygenase-2 (COX-2) is an inducible enzyme that causes inflammation. COX-2 inhibitors are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicities. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular thrombotic events, including myocardial infarction. Therefore, there is still need to develop COX-2 inhibitors with better therapeutic effects and tolerability. The aim of the present study is to explore the anti-inflammatory activity of five lichen metabolites by conducting virtual screenings. In this regard, molecular docking simulations were carried out for the lichen metabolites namely atranorin, diffractic acid, lecanoric acid, salazinic acid and usnic acid with human COX-2 enzyme and the docked results were compared with the standard reference ligands (Celecoxib and Rofecoxib). Among all the docked ligands, the lecanoric acid demonstrated best binding affinity -9.83 kcal/mol followed by atranorin (-8.7 kcal/mol) and diffractic acid (-8.6 kcal/mol) which are comparable to the reference ligands celecoxib (-12.3 kcal/mol) and rofecoxib (-11.2 kcal/mol). The salazinic acid and usnic acid has shown binding affinity of -7.9 kcal/mol and -4.7 kcal/mol, respectively. Moreover, all the ligands except atranorin and diffractic acid satisfied Lipinski’s rule of 5. From the docking results it was revealed that the lichen metabolites might have inhibitory activity against COX-2 enzyme, and are expected to be useful in conducting in vivo anti-inflammatory screenings on animal model which may lead to the development of more effective and potent new chemical entities with anti-inflammatory properties.Bangladesh Pharmaceutical Journal 18(2): 90-96, 2015

IN VITRO ANTIOXIDANT ACTIVITIES OF SALAZINIC ACID AND ITS DERIVATIVE HEXAACETYL SALAZINIC ACID

The stress generated upon oxidation can lead to the production of free radicals which may cause many degenerative diseases. In order to eliminate the free radicals antioxidants have been used. The present study was to estimate the antioxidant activity of salazinic acid and its derivative hexaacetyl salazinic acid. The antioxidant property were studied under the categories DPPH, FRAP, Metal chelating activity, Hydroxyl scavenging activity, Lipid peroxidation activity, Phosphomolybdenum activity, Superoxide dismutase activity. We have isolated salazinic acid from the lichen Parmotrema reticulatum collected from Kodaikanal hills. The Derivative hexaacetyl salazinic acid was also prepared. Both the compounds were subjected to determine the in vitro antioxidant activity and their IC50 value are also calculated. The Lichen metabolite and its derivative have shown better antioxidant efficiency.

New species and new records of thelotremoid Graphidaceae (Ascomycota: Ostropales) from Thailand

Six new species of thelotremoid Graphidaceae are described from Thailand. Leucodecton confusum Papong, Mangold &amp; Lücking has a densely corticate thallus and small, lepadinoid ascomata with double margin producing small, hyaline, submuriform ascospores. Ocellularia cerebriformis Papong, Lücking &amp; Lumbsch is characterized by a brain-like, folded thallus surface, in combination with small, (sub-)muriform ascospores and protocetraric acid chemistry. Ocellularia kohphangangensis Papong, Mangold &amp; Lücking features an unusual combination of small, brown, submuriform ascospores and the cinchonarum unknown chemistry. Ocellularia pseudopapillata Papong, Mangold &amp; Lücking differs from O. papillata in the uneven-verrucose thallus, the thin, indistinctly fissured proper margin of the ascomata, and the carbonized columella. Ocellularia salazinica Papong, Mangold &amp; Lücking is characterized by the presence of salazinic acid (a rare substance in Graphidaceae), in combination with ascomata resembling those of Rhabdodiscus, and comparatively large, muriform ascospores. A further species of Ocellularia, O. subdolichotata Papong, Mangold &amp; Lumbsch, has a smooth, white thallus, prominent, columellate and carbonized ascomata, large, transversely septate ascospores (smaller than in O. dolichotata), and lacks secondary substances. The following 11 species are new records for Thailand: Chapsa discoides (Stirt.) Lücking, Glaucotrema glaucophaenum (Kremp.) Rivas Plata &amp; Lumbsch, Leucodecton anamalaiense (Patw. &amp; C. R. Kulk.) Rivas Plata &amp; Lücking, Ocellularia fumosa (Ach.) Müll. Arg., O. granulifera (Kremp.) Müll. Arg., O. violacea Räsänen, O. viridipallens Müll. Arg., Rhabdodiscus subcavatus (Nyl.) Rivas Plata &amp; Lumbsch, Stegobolus berkeleyanus Mont., Thelotrema defossum (Müll. Arg.) Mangold, and T. subadjectum Mangold.

Antimicrobial Activity of &lt;i&gt;Ramalina conduplicans&lt;/i&gt; Vain. (Ramalinaceae)

The members of the genus Ramalina (Ramalinaceae) are fruticose lichens growing on various types of substrata. The present study was conducted with an aim of determining antimicrobial activity of Ramalina conduplicans Vain. The powdered lichen material was extracted sequentially using petroleum ether, ethyl acetate and ethanol. The solvent extracts were screened for antibacterial activity by Agar well diffusion assay against 15 bacteria which included reference strains and isolates from burn, dental caries and urinary tract infections. Poisoned food technique was performed to determine antifungal effect of solvent extracts against fungal isolates from anthracnose of chilli, foot rot of finger millet and mouldy grains of sorghum. Usnic acid, Salazinic acid and Sekikaic acid were detected in the lichen. The solvent extracts were shown to exhibit dose dependent inhibitory activity against test bacteria. Ethyl acetate extract inhibited reference bacterial strains to higher extent. Among solvent extracts, only ethanol extract inhibited all urinary tract bacteria. S. aureus isolates from burn were inhibited to higher extent when compared to S. mutans isolates from dental caries. The solvent extracts exhibited varied inhibitory activity against test fungi. Ethyl acetate extract inhibited Alternaria sp., Aspergillus flavus and Sclerotium rolfsii to higher extent while Colletotrichum capsici and Helminthosporium sp. were inhibited to higher extent by petroleum ether and ethanol extract respectively. The observed inhibitory potential of solvent extracts of R. conduplicans could be ascribed to the presence of secondary metabolites. The lichen can be used in the treatment of bacterial infections and to manage plant pathogenic fungi.Keywords: i Antimicrobial Agar well diffusion Poisoned food technique

Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials.

Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.

Bulbothrix asiaticasp. nov., and other new records of Parmeliaceae with bulbate cilia from Cambodia

Bulbothrix asiatica Y. Y. Zhang & Li S. Wang sp. nov. is proposed to accommodate specimens with a black lower surface, an emaculate and cracked upper surface and salazinic acid in the medulla. The species is currently known only from Cambodia and southwestern China. Other Parmeliaceae with bulbate cilia here newly reported from Cambodia are: Bulbothrix lyngei, B. subscortea, Relicina abstrusa and R. circumnodata. Phylogenetic trees for Bulbothrix are established to assess the affinities of the new species and test for a differentiation of saxicolous and epiphytic populations of B. subscortea. A key to these species is presented.

Overview of Xanthoparmelia taxa from South Korea including the description of two new species (Parmeliaceae, Ascomycota)

In the genus Xanthoparmelia, species boundaries are based on morphological and chemical features such as the presence and/or absence of secondary metabolites, diagnostic reproductive structures, isidia morphology, and color of lower surface. Two new species of Xanthoparmelia are described from South Korea, X. kolriana with cylindrical isidia containing atranorin and salazinic acid as major components in the medulla together with cortical usnic acid, while X. volcanicola is characterised by a red coloured medulla, and subglobose isidia. The characteristics of Xanthoparmelia species and their distribution in South Korea are outlined and an identification key given. Additionally, we used ITS ribosomal DNA sequences to assess the monophyly of Xanthoparmelia species from South Korea. Our results reveal that traditionally circumscribed species were not recovered as monophyletic clades. Further, we here show that ITS is insufficient to estimate a well-supported phylogenetic hypothesis, but suggests that traditional taxonomy may not reflect natural groups. This communication provides an important framework for future studies assessing species boundaries in Xanthoparmelia species in South Korea.

Parmotrema marcellii, a new species of Parmeliaceae (lichenized Ascomycota) from Brazil

Parmotrema marcellii is described as a new saxicolous species on granitic rocks in the rocky shores of Santa Catarina State, southern Brazil. The rocky shores generally are extensions of rocky mountains, near the coast, reaching the sea floor. They are included among the less studied environments in Brazil and despite showing a remarkable lichenized fungi diversity, just over 10 % of the species on Brazilian rocky shores are supposed to be known. From southern Brazil, a total of 33 species representing the parmelioid lichens and distributed in nine genera are so far known. The Parmotrema species form the largest and most important portion of the lichenized micobiota of this habitat, with over half the number of known species producing medullary salazinic acid. Belonging to this group, the new species presented here is characterized by reticulate maculate upper cortex, bacilliform conidia and marginal to mainly submarginal pustules that usually form dense agglomerations forming no soredia. Herein, we describe this new species and compare it with other morphologically similar species.

New species of Pertusaria from China

Seven new species, Pertusaria neotropica (with lichexanthone, hypothamnolic and salazinic acids), P. parasommerfeltii (with 4,5-dichlorolichexanthone and 2'-O-methylperlatolic acid), P. qinbaensis (norstictic acid and stictic acids), P. qiujiabaensis (with norstictic acid and 4,5-dichlorolichexanthone), P. sejilaensis (with protocetraric acid), P. subviolacea (with hypothamnolic and cryptothamnolic acids) and P. taibaiensis (with norstictic acid), are reported from China.