Lichens as promising resources of enzyme inhibitors: A review
Inhibition of some enzymes seems to be one of the therapeutic strategies for the management of certain diseases or conditions such as diabetes, Alzheimer’s disease, cancer and obesity. In this review, an updated information on the enzyme inhibitory activity of lichen extracts and lichen compounds by an intensive literature survey is presented. Crude solvent extracts and isolated compounds from lichens were shown to be effective in causing inhibition of several enzymes such as amylase, lipase, lipoxygenase, aromatase, cyclooxygenase, trypsin, β-glucoronidase, prolyl endopeptidase, monoamine oxidase, urease, tyrosinase, xanthine oxidase, Thioredoxin reductase, glucosidase, topoisomerase, pancreatic elastase, phosphodiesterase, telomerase and acetylcholinesterase. Lichen metabolites such as usnic acid and its derivatives, lobaric acid, physodic acid, ramalin, protolichestrinic acid, salazinic acid, atranorin, evernic acid, zeorin, diffractic acid, psoromic acid, methyl β-orcinolcarboxylate, methylorsellinate, and anziaic acid were shown to be inhibitors of some enzymes. In conclusion, lichens can be employed as promising therapeutic agents in terms of their potential to inhibit the activity of certain enzymes that are involved in some diseases or disorders. In vitro culturing of lichen symbionts in optimized media can be carried out to isolate enzyme inhibitors in larger scale and to develop effective therapeutic agents.
Keywords: Lichens, lichen substances, enzyme inhibitors, enzyme inhibitory activity
2. Molnár K, Farkas E. Current results on biological activities of lichen secondary metabolites: a review. Z Naturforsch C, 2010; 65(3-4):157-173.
3. Boustie J, Tomasi S, Grube M. Bioactive lichen metabolites: alpine habitats as an untapped source. Phytochem Rev 2011; 10:287-307.
4. Jagtap V, Tripathi M, Joshi Y. First report on the occurrence of plasticolous lichens from Uttarakhand, India. J Appl Nat Sci 2013; 5(2):342-344.
5. Rogers RD. Medicinal lichens. Fungi 2014; 7(2-3):56-58.
6. Kusmoro J, Noer IS, Jatnika MF, Permatasari RE, Partasasmita R. Lichen diversity in geothermal area of Kamojang, Bandung, West Java, Indonesia and its potential for medicines and dyes. Biodiversitas 2018; 19(6):2335-2343.
7. Soundararajan S, Shanmugam P, Nagarajan N, Palanisamy D, Ponnusamy P. In vitro study on screening antimicrobial and anti-oxidant potential of Ramalina fastigiata. J Drug Delivery Ther 2019; 9(1):216-219.
8. Upreti DK, Divakar PK, Nayaka S. Commercial and ethnic use of lichens in India. Econ Bot 2005; 59(3): 269-273.
9. Shukla P, Upreti DK, Nayaka S, Tiwari P. Natural dyes from Himalayan lichens. Indian J Tradit Know 2014; 13(1):195-201.
10. Singh S, Upreti DK, Lehri A, Paliwal AK. Quantification of lichens commercially used in traditional perfumery industries of Uttar Pradesh, India. Indian J Plant Sci 2015; 4(1):29-33.
11. Weissbuch BK. Medicinal lichens: the final frontier. Journal of the American Herbalists Guild 2016; 12(2):23-28.
12. Londoño-Castañeda PA, Buril MLL, Rego-Cunha IP, Silva NH, Honda NK, Pereira EC, Andrade LHC. Lichens used in the traditional medicine by the Pankararu Indigenous Community, Pernambuco-Brazil. Global Journal of Science Frontier Research: C Biological Science 2017; 17(4): 15-22.
13. Ogmundsdóttir HM, Zoëga GM, Gissurarson SR, Ingólfsdóttir K. Anti-proliferative effects of lichen-derived inhibitors of 5-lipoxygenase on malignant cell-lines and mitogen-stimulated lymphocytes. J Pharm Pharmacol 1998; 50(1):107-115.
14. Romagni JG, Meazza G, Nanayakkara DNP, Dayan FE. The phytotoxic lichen metabolite, usnic acid, is a potent inhibitor of plant p-hydroxyphenylpyruvate dioxygenase. FEBS Lett 2000; 480: 301-305.
15. Karunaratne V, Bombuwela K, Kathirgamanathar S, Thadhani VM. Lichens: A chemically important biota. J Natn Sci Foundation Sri Lanka 2005; 33(3):169-186.
16. Turk H, Yılmaz M, Tay T, Turk AO, Kıvanc M. antimicrobial activity of extracts and chemical races of the lichen Pseudevernia furfuracea and their physodic acid, chloroatranorin, atranorin, and olivetoric acid constituents. Z Naturforsch 2006; 61c: 499-507.
17. Choudhary IM, Ali M, Atia-tul-Wahab, Khan A, Rasheed S, Shyaula SL, Attar-ur-Rahman. New antiglycation and enzyme inhibitors from Parmotrema cooperi. Sci China Chem 2011; 54(12): 1926-1931.
18. Mitrovic T, Stamenkovic S, Cvetkovic V, Radulovic N, Mladenovic M, Stankovic M, Topuzovic M, Radojevic I, Stefanovic O, Vasic S, Comic L. Platismatia glauca and Pseudevernia furfuracea lichens as sources of antioxidant, antimicrobial and antibiofilm agents. EXCLI Journal 2014; 13:938-953.
19. Varol M. Natural small-molecules obtained from lichens as a novel source of anti-angiogenic agents. J Appl Pharm 2015; 8: 1.
20. Thorsteinsdottir UA, Thorsteinsdottir M, Lambert IH. Protolichesterinic acid, isolated from the lichen Cetraria islandica, reduces LRRC8A expression and volume-sensitive release of organic osmolytes in human lung epithelial cancer cells. Phytother Res 2016; 30(1):97-104.
21. Prateeksha, Paliya BS, Bajpai R, Jadaun V, Kumar J, Kumar S, Upreti DK, Singh BR, Nayaka S, Joshi Y, Singh BN. The genus Usnea: a potent phytomedicine with multifarious ethnobotany, phytochemistry and pharmacology. RSC Adv 2016; 6:21672.
22. Tomović J, Kosanić M, Ristić S, Ranković B, Stanojković T, Manojlović N. Chemical composition and bioactive properties of the lichen, Pleurosticta acetabulum. Trop J Pharm Res 2017; 16(12):2977-2984.
23. Castro ON, Benites J, Rodilla J, Santiago JC, Simirgiotis M, Sepulveda B, Areche C. Metabolomic analysis of the lichen Everniopsis trulla using Ultra High Performance Liquid Chromatography-Quadrupole-Orbitrap Mass Spectrometry (UHPLC-Q-OT-MS). Chromatographia 2017; 80:967–973.
24. Cardile V, Graziano ACE, Avola R, Piovano M, Russo A. Potential anticancer activity of lichen secondary metabolite physodic acid. Chem Biol Interact 2017; 263:36-45.
25. Kekuda PTR, Vinayaka KS, Sachin MB. Chemistry, ethnobotanical uses and biological activities of the lichen genus Heterodermia Trevis. (Physciaceae; Lecanorales; Ascomycota): A comprehensive review. J Appl Pharm Sci 2018; 8(5):148-155.
26. Steckelings UM, Artuc M, Wollschlager T, Wiehstutz S, Henz BM. Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions. Acta Derm Venereol 2001; 81:321-325.
27. Balbaa M, El Ashry ESH. Enzyme inhibitors as therapeutic tools. Biochem Physiol 2012; 1(2):1000103.
28. Kumar AHS, Kekuda PTR, Vinayaka KS, Swathi D, Venugopal TM. Anti-obesity (pancreatic lipase inhibitory) activity of Everniastrum cirrhatum (Fr.) Hale (Parmeliaceae). Phcog J 2011; 3(19):65-68.
29. Lunagariya NA, Patel NK, Jagtap SC, Bhutani KK. Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI Journal 2014; 13:897-921.
30. Awllia JAJ, Sara A, Atia-tul-Wahab, AL-Ghamdi M, Rasheed S, Huwait E, Choudhary IM. Discovery of new inhibitors of urease enzyme: A study using STD-NMR Spectroscopy. Lett Drug Des Discovery 2015; 12: 819-827.
31. Satish BNVS, Kumar P, Avanti SM, Singh S. Salivary amylase as potential biochemical marker in diabetes mellitus. International Journal of Recent Surgical and Medical Sciences 2016; 2(1): 19-22.
32. Buitrago E, Hardre R, Haudecoeur R, Jamet H, Belle C, Boumendjel A, Bubacco L, Reglier M. Are human tyrosinase and related proteins suitable targets for melanoma therapy?. Curr Top Med Chem 2016; 16: 3033-3047.
33. Ramsay RR, Tipton KF. Assessment of enzyme inhibition: a review with examples from the development of monoamine oxidase and cholinesterase inhibitory drugs. Molecules 2017; 22: 1192.
34. Shivaraj B, Pattabiraman TN. Natural plant enzyme inhibitors. Characterization of an unusual alpha-amylase/trypsin inhibitor from ragi (Eleusine coracana Geartn.). Biochem J 1981; 193(1):29-36.
35. Schneider I, Bucar F. Lipoxygenase inhibitors from natural plant sources. Part 1: Medicinal plants with inhibitory activity on arachidonate 5-lipoxygenase and 5-lipoxygenase[sol]cyclooxygenase. Phytother Res 2005; 19(2):81-102.
36. Subramanian R, Asmawi ZM, Sadikun A. In vitro α-glucosidase and α-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide. Acta Biochim Pol 2008; 55(2):391-398.
37. Jiang C, Liang L, Guo Y. Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades. Acta Pharmacol Sin 2012; 33:1217-1245.
38. Behera BC, Mahadik N, Morey M. Antioxidative and cardiovascular-protective activities of metabolite usnic acid and psoromic acid produced by lichen species Usnea complanata under submerged fermentation. Pharm Biol 2012; 50(8):968-979.
39. Kumar S, Kumar V, Rana M, Kumar D. Enzyme inhibitors from plats: An alternate approach to treat diabetes. Pharmacogn Commun 2012; 2(2):18-33.
40. Cheng B, Cao S, Vasquez V, Annamalai T, Tamayo-Castillo G, Clady J, Tse-Dinh Y. Identification of Anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor. PLoS ONE 2013; 8(4): e60770.
41. Revathy T, Jayasri MA, Suthindhiran K. Anti-oxidant and enzyme-inhibitory potential of marine Streptomyces. Am J Biochem Biotechnol 2013; 9(3):282-290.
42. Ramanjooloo A, Cresteil T, Lebrasse C, Beedessee G, Oogarah P, van Soest RWM, Marie DEP. α-Glucosidase inhibitory activity of marine sponges collected in Mauritius waters. Nat Prod Res 2015; 29(4):383-387.
43. Jayaraj S, Suresh S, Kadeppagari R. Amylase inhibitors and their biomedical applications. Starch 2013; 65(7-8):535-542.
44. van de Laar FA. Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 2008; 4(6):1189-95.
45. Taylor SD, Hill B. Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs 2004; 13(3):199-1214.
46. Verma N, Behera BC, Sonone A, Makhija U. Lipid peroxidation and tyrosinase inhibition by lichen symbionts grown in vitro. Afr J Biochem Res 2008; 2(12):225-231.
47. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006; 58(1):87-114.
48. Follmer C. Ureases as a target for the treatment of gastric and urinary infections. J Clin Pathol 2010; 63(5): 424-430.
49. Steinhilber D, Hofmann B. Recent advances in the search for novel 5-Lipoxygenase inhibitors. Basic Clin Pharmacol Toxicol 2014; 114:70–77.
50. Harris RC, Breyer MD. Update on cyclooxygenase-2 inhibitors. Clin J Am Soc Nephrol 2006; 1: 236-245.
51. Psarra A, Nikolaou A, Kokotou MG, Limnios D, Kokotos G. Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review. Expert Opin Ther Pat 2017; 27(9):1047-1059.
52. Dastidar SG, Rajagopal D, Ray A. Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr Opin Investig Drugs 2007; 8(5):364-372.
53. Kelland LR. Overcoming the immortality of tumour cells by telomere and telomerase based cancer therapeutics--current status and future prospects. Eur J Cancer 2005; 41(7):971-979.
54. Zhang JS, Lei JP, Wei GQ, Chen H, Ma CY, Jiang HZ. Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review. Pharm Biol 2016; 54(9):1919-1925.
55. Dexheimer TS, Antony S, Marchand C, Pommier Y. Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy. Anticancer Agents Med Chem 2008; 8(4):381-389.
56. Berdis AJ. DNA polymerases as therapeutic targets. Biochemistry 2008; 47(32):8253-8260.
57. Liu X. Targeting Polo-like kinases: A promising therapeutic approach for cancer treatment. Transl Oncol 2015; 8(3): 185-195.
58. Sinha BK. Topoisomerase inhibitors. A review of their therapeutic potential in cancer. Drugs 1995; 49(1): 11-19.
59. Sane KM, Mynderse M, Lalonde DT, Dean IS, Wojtkowiak JW, Fouad F, Borch RF, Reiners JJ, Gibbs RA, Mattingly RR. A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells. J Pharmacol Exp Ther 2010; 333(1): 23-33.
60. Lampe JW, Li SS, Potter JD, King IB. Serum β-glucuronidase activity is inversely associated with plant-food intakes in humans. J Nutr 2002; 132(6): 1341-1344.
61. Fabian CJ. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract 2007; 61(12): 2051-2063.
62. Shah R, Singh J, Singh D, Jaggi AS, Singh N. Sulfatase inhibitors for recidivist breast cancer treatment: A chemical review. Eur J Med Chem 2016; 114: 170-190.
63. Grossberg GT. Cholinesterase inhibitors for the treatment of Alzheimer's disease: getting on and staying on. Curr Ther Res Clin Exp 2003; 64(4): 216-235.
64. Männisto PT, Venäläinen J, Jalkanen A, García-Horsman JA. Prolyl oligopeptidase: a potential target for the treatment of cognitive disorders. Drug News Perspect 2007; 20(5): 293-305.
65. Rosenson RS, Hurt-Camejo E. Phospholipase A2 enzymes and the risk of atherosclerosis. Eur Heart J 2012; 33(23): 2899-2909.
66. Schemmel KE, Padiyara RS, D'Souza JJ. Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review. J Diabetes Complications 2010; 24(5): 354-360.
67. White WB. Angiotensin-converting enzyme inhibitors in the treatment of hypertension: an update. J Clin Hypertens (Greenwich) 2007; 9(11): 876-882.
68. Pazzucconi F, Dorigotti F, Gianfranceschi G, Campagnoli G, Sirtori M, Franceschini G, Sirtori CR. Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity. Atherosclerosis 1995; 117(2): 189-198.
69. Entzeroth M, Ratty AK. Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle. Open Journal of Depression 2017; 6: 31-68.
70. Castro HC, Loureiro NI, Pujol-Luz M, Souza AM, Albuquerque MG, Santos DO, Cabral LM, Frugulhetti IC, Rodrigues CR. HIV-1 reverse transcriptase: a therapeutical target in the spotlight. Curr Med Chem 2006; 13(3): 313-324.
71. Brandl T, Simic O, Skaanderup PR, Namoto K, Berst F, Ehrhardt C, Schiering N, Mueller I, Woelcke J. Trypsin inhibitors for the treatment of pancreatitis. Bioorg Med Chem Lett 2016; 26(17): 4340-4304.
72. Westwood IM, Bhakta S, Russell AJ, Fullam E, Anderton MC, Kawamura A, Mulvaney AW, Vickers RJ, Bhowruth V, Besra GS, Lalvani A, Davies SG, Sim E. Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars. Protein Cell 2010; 1(1): 82-95.
73. Soltero-Higgin M1, Carlson EE, Phillips JH, Kiessling LL. Identification of inhibitors for UDP-galactopyranose mutase. J Am Chem Soc 2004; 126(34): 10532-10533.
74. Saccoccia F, Angelucci F, Boumis G, Carotti D, Desiato G, Miele AE, Bellelli A. Thioredoxin reductase and its inhibitors. Curr Protein Pept Sci 2014; 15: 621-646.
75. Williams DE, Loganzo F, Whitney L, Togias J, Harrison R, Singh MP, McDonald LA, Kathirgamanathar S, Karunaratne V, Andersen RJ. Depsides isolated from the Sri Lankan lichen Parmotrema sp. exhibit selective Plk1 inhibitory activity. Pharm Biol 2011; 49(3): 296–301.
76. Cui Y, Yim JH, Lee DS, Kim YC, Oh H. New diterpene furanoids from the Antarctic lichen Huea sp. Bioorg Med Chem Lett 2012; 22(24): 7393-7396.
77. Lauinger IL, Vivas L, Perozzo R, Stairiker C, Tarun A, Zloh M, Zhang X, Xu H, Tonge PJ, Franzblau SG, Pham DH, Esguerra CV, Crawford AD, Maes L, Tasdemir D. Potential of lichen secondary metabolites against Plasmodium liver stage parasites with FAS-II as the potential target. J Nat Prod 2013; 76(6): 1064-1070.
78. Karunaratne V, Thadhani VM, Khan SN, Choudhary IM. Potent α-glucosidase inhibitors from the lichen Cladonia species from Sri Lanka. J Natn Sci Foundation Sri Lanka 2014; 42(1): 95-98.
79. Thadhani VM, Naaz Q, Choudhary IM, Mesaik AM, Karunaratne V. Enzyme inhibitory and immunomodulatory activities of the depsidone lobaric acid extracted from the lichen Heterodermia sp. J Natn Sci Foundation Sri Lanka 2014; 42(2): 193-196.
80. Yusof H, Azahar H, Din LB, Ibrahim N. Chemical constituents of the lichens Cladonia multiformis and Cryptothecia sp. Malaysian J Anal Sci 2015; 19(5): 930-934.
81. Honda NK, Lopes TIB, Costa RCS, Coelho RG, Yoshida NC, Rivarola CRV, Marcelli MP, Spielmann AA. Radical-scavenging potential of phenolic compounds from Brazilian lichen. Orbital: Electronic J Chem 2015; 7(2): 99-107.
82. Studzińska-Sroka E, Dubino A. Lichens as a source of chemical compounds with antiinflammatory activity. Herba Pol 2018; 64(1): 56-64.
83. Valadbeigi T. Chemical composition and enzymes inhibitory, brine shrimp larvae toxicity, antimicrobial and antioxidant activities of Caloplaca biatorina. Zahedan J Res Med Sci 2016; 18(11): e4267.
84. Hengameh P, Rashmi S, Rajkumar HG. In vitro inhibitory activity of some lichen extracts against α-amylase enzyme. European Journal of Biomedical and Pharmaceutical Sciences 2016; 3(5): 315-318.
85. Tekale SS. The Α-amylase inhibitory and dye degradation potential of the lichen (parmelia perlata). International Journal of Basic and Applied Research 2018; 8(8): 256-260.
86. Shivanna R, Parizadeh H, Garampalli RH. Screening of lichen extracts for in vitro antidiabetic activity using alpha amylase inhibitory assay. International Journal of Biological and Pharmaceutical Research 2015; 6(5): 364-367.
87. Raj PS, Prathapan A, Sebastian J, Antony AK, Riya MP, Rani MR, Biju H, Priya S, Raghu KG. Parmotrema tinctorum exhibits antioxidant, antiglycation and inhibitory activities against aldose reductase and carbohydrate digestive enzymes: an in vitro study. Nat Prod Res 2014; 28(18): 1480-1484.
88. Vinayaka KS, Karthik S, Nandini KC, Kekuda PTR. Amylase inhibitory activity of some macrolichens of Western Ghats, Karnataka, India. Indian Journal of Novel Drug Delivery 2013; 5(4): 225-228.
89. Valadbeigi T, Shaddel M. Amylase inhibitory activity of some macrolichens in Mazandaran province, Iran. Physiol Pharmacol 2016; 20: 215-219.
90. Karthik S, Nandini KC, Kekuda PTR, Vinayaka KS, Mukunda S. Total phenol content, insecticidal and amylase inhibitory efficacy of Heterodermia leucomela (L). Ann Biol Res 2011; 2(4): 38-43.
91. Parizadeh H, Garampalli RH. Evaluation of some lichen extracts for β-glucosidase inhibitory as a possible source of herbal anti-diabetic drugs. Am J Biochem 2016; 6(2): 46-50.
92. Verma N, Behera BC, Sharma BO. Glucosidase inhibitory and radical scavenging properties of lichen metabolites salazinic acid, sekikaic acid and usnic acid. Hacettepe J Biol Chem 2012; 40(1): 7-21.
93. Lee KA, Kim MS. Glucosidase inhibitor from Umbilicaria esculenta. Can J Microbiol 2000; 46(11): 1077-1081.
94. Seo C, Sohn JH, Park SM, Yim JH, Lee HK, Oh H. Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum. J Nat Prod 2008; 71(4): 710-712.
95. Seo C, Choi YH, Ahn JS, Yim JH, Lee HK, Oh H. PTP1B inhibitory effects of tridepside and related metabolites isolated from the Antarctic lichen Umbilicaria antarctica. J Enzyme Inhib Med Chem 2009; 24(5): 1133-1137.
96. Seo C, Sohn JH, Ahn JS, Yim JH, Lee HK, Oh H. Protein tyrosine phosphatase 1B inhibitory effects of depsidone and pseudodepsidone metabolites from the Antarctic lichen Stereocaulon alpinum. Bioorg Med Chem Lett 2009; 19(10): 2801-2803.
97. Seo C, Yim JH, Lee HK, Oh H. PTP1B inhibitory secondary metabolites from the Antarctic lichen Lecidella carpathica. Mycology 2011; 2(1): 18-23.
98. Higuchi M, Miura Y, Boohene J, Kinoshita Y, Yamamoto Y, Yoshimura I, Yamada Y. Inhibition of tyrosine activity by cultured lichen tissues and bionts. Planta Med 1993; 59(3): 253-255.
99. Behera BC, Adawadkar B, Makhija U. Capacity of some Graphidaceous lichens to scavenge superoxide and inhibition of tyrosinase and xanthine oxidase activities. Curr Sci 2004; 87(1): 83-87.
100. Behera BC, Adawadkar B, Makhija U. Tyrosinase-inhibitory activity in some species of the lichen family Graphidaceae. J Herb Pharmacother 2006; 6(1): 55-69.
101. Behera BC, Adawadkar B, Makhija U. Tissue-culture of selected species of the Graphis lichen and their biological activities. Fitoterapia 2006; 77(3): 208-215.
102. Paudel B, Bhattarai HD, Koh HY, Lee SG, Han SJ, Lee HK, Oh H, Shin HW, Yim JH. Ramalin, a novel nontoxic antioxidant compound from the Antarctic lichen Ramalina terebrata. Phytomedicine 2011; 18(14): 1285-1290.
103. Chang Y, Ryu J, Lee S, Park SG, Bhattarai HD, Yim JH, Jin MH. Inhibition of melanogenesis by Ramalin from the Antarctic lichen Ramalina terebrata. J Soc Cosmet Scientists Korea 2012; 38(3): 247-254.
104. Lopes TIB, Coelho RG, Honda NK. Inhibition of mushroom tyrosinase activity by orsellinates. Chem Pharm Bull (Tokyo) 2018; 66(1): 61-64.
105. Behera BC, Makhija U. Inhibition of tyrosinase and xanthine oxidase by lichen species Bulbothrix setschwanensis. Curr Sci 2002; 82(1): 61-66.
106. Honda NK, Goncalves K, Brandao LFG, Coelho RG, Micheletti AC, Spielmann AA, Canez LS. Screening of lichen extracts using tyrosinase inhibition and toxicity against Artemia salina. Orbital: Electronic J Chem 2016; 8(3): 181-188.
107. Kim MS, Cho HB. Melanogenesis inhibitory effects of methanolic extracts of Umbilicaria esculenta and Usnea longissima. J Microbiol 2007; 45(6): 578-582.
108. Matsubara H, Kinoshita K, Koyama K, Ye Y, Takahashi K, Yoshimura I, Yamamoto Y, Miura Y, Kinoshita Y. Anti-tyrosinase activity of lichen metabolites and their synthetic analogues. J Hattori Bot Lab 1997; 83: 179-185.
109. Behera BC, Adawadkar B, Makhija U. Inhibitory activity of xanthine oxidase and superoxide-scavenging activity in some taxa of the lichen family Graphidaceae. Phytomedicine 2003; 10(6-7): 536-543.
110. Xu HB, Yang TH, Xie P, Liu SJ, Liang YN, Zhang Y, Song ZX, Tang ZS. Pheophytin analogues from the medicinal lichen Usnea diffracta. Nat Prod Res 2018; 32(9): 1088-1094.
111. Bessadóttir M, Skúladóttir EÁ, Gowan S, Eccles S, Ögmundsdóttir S, Ogmundsdóttir HM. Effects of anti-proliferative lichen metabolite, protolichesterinic acid on fatty acid synthase, cell signalling and drug response in breast cancer cells. Phytomedicine 2014; 21(12): 1717-1724.
112. Pejin B, Tommonaro G, Iodice C, Tesevic V, Vajs V. Acetylcholinesterase inhibition activity of acetylated depsidones from Lobaria pulmonaria. Nat Prod Res 2012; 26(17): 1634-1637.
113. Reddy RG, Veeraval L, Maitra S, Chollet-Krugler M, Tomasi S, Dévéhat FL, Boustie J, Chakravarty S. Lichen-derived compounds show potential for central nervous system therapeutics. Phytomedicine 2016; 23(12): 1527-1534.
114. Pejin B, Tommonaro G, Iodice C, Tesevic V, Vajs V, De Rosa S. A new depsidone of Lobaria pulmonaria with acetylcholinesterase inhibition activity. J Enzyme Inhib Med Chem 2013; 28(4): 876-878.
115. Heng L, Li C, Kim JC, Liu Y, Jung JS, Koh YJ, Hur J. Biruloquinone, an acetylcholinesterase inhibitor produced by lichen-forming fungus Cladonia macilenta. J Microbiol Biotechnol 2013; 23(2): 161-166.
116. Ingolfsdottir K, Breu W, Huneck S, Gudjonsdottir GA, Müller-Jakic B, Wagner H. In vitro inhibition of 5-lipoxygenase by protolichesterinic acid from Cetraria islandica. Phytomedicine 1994; 1: 187–191.
117. Ingolfsdottir K, Gissurarson SR, Müller-Jakic B, Breu W, Wagner H. Inhibitory effects of the lichen metabolite lobaric acid on arachidonate metabolism in vitro. Phytomedicine 1996; 2: 243–246.
118. Ingólfsdóttir K, Wiedemann B, Birgisdóttir M, Nenninger A, Jónsdóttir S, Wagner H. Inhibitory effects of baeomycesic acid from the lichen Thamnolia subuliformis on 5-lipoxygenase in vitro. Phytomedicine 1997; 4(2): 125-128.
119. Ingólfsdóttir K, Gissurarson SR, Nenninger A, Neszmelyi A, Wiedemann B, Wagner H. Biologically active alkamide from the lichen Stereocaulon alpinum. Phytomedicine 1997; 4(4): 331-334.
120. Oettl SK, Gerstmeier J, Khan SY, Wiechmann K, Bauer J, Atanasov AG, Malainer C, Awad EM, Uhrin P, Heiss EH, Waltenberger B, Remias D, Breuss JM, Boustie J, Dirsch VM, Stuppner H, Werz O, Rollinger JM. Imbricaric acid and perlatolic acid: Multi-targeting anti-inflammatory depsides from Cetrelia monachorum. PLoS ONE 2013; 8(10): e76929.
121. Ingolfsdottir K, Gudmundsdottir GF, Ogmundsdottir HM, Paulus K, Haraldsdottir S, Kristinsson H, Bauer R. Effects of tenuiorin and methyl orsellinate from the lichen Peltigera leucophlebia on 5-/15-lipoxygenases and proliferation of malignant cell lines in vitro. Phytomedicine 2002; 9(7): 654-658.
122. Haraldsdóttir S, Guolaugsdóttir E, Ingólfsdóttir K, Ogmundsdóttir HM. Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro. Planta Med 2004; 70(11): 1098-1100.
123. Bucar F, Schneider I, Ogmundsdóttir H, Ingólfsdóttir K. Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets. Phytomedicine 2004; 11(7-8): 602-606.
124. Behera BC, Morey MV, Gaikwad SB. Anti-lipoxygenase, radical scavenging and antimicrobial activities of lichen species of genus Heterodermia (Physciaceae). Botanica Pacifica 2016; 5(1): 79-85.
125. Bugni TS, Andjelic CD, Pole AR, Rai P, Ireland CM, Barrows LR. Biologically active components of a Papua New Guinea analgesic and anti-inflammatory lichen preparation. Fitoterapia 2009; 80(5): 270-273.
126. Jager AK, Weber DJ, van Staden J. Screening of South African lichens for prostaglandin-synthesis inhibitors. S Afr J Bot 1997; 63(5): 300-302.
127. Khan MF, Nabila SA, Rashid RB, Rahman MS, Chowdhury AA, Rashid MA. In silico molecular docking studies of lichen metabolites against cyclooxygenase-2 enzyme. Bangladesh Pharm J 2015; 18(2): 90-96.
128. Engel K, Schmidt U, Reuter J, Weckesser S, Simon-Haarhaus B, Schempp CM. Usnea barbata extract prevents ultraviolet-B induced prostaglandin E2 synthesis and COX-2 expression in HaCaT keratinocytes. J Photochem Photobiol B. 2007; 89(1): 9-14.
129. Savale SA, Pol CS, Khare R, Verma N, Gaikwad S, Mandal B, Behera BC. Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum. Pharm Biol 2016; 54(4): 692-700.
130. Kim J, Song K, Yoo I, Chang H, Yu S, Bae K, Min T. Two phenolic compounds isolated from Umbilicaria esculenta as Phospholipase A2 inhibitors. Korean J Mycol 1996; 24(3): 237-242.
131. Bauer J, Waltenberger B, Noha SM, Schuster D, Rollinger JM, Boustie J, Chollet M, Stuppner H, Werz O. Discovery of depsides and depsidones from lichen as potent inhibitors of microsomal Prostaglandin E2 synthase-1 using pharmacophore models. ChemMedChem 2012; 7(12): 2077-2081.
132. Le DH, Takenaka Y, Hamada N, Mizushina Y, Tanahashi T. Polyketides from the cultured lichen mycobiont of a Vietnamese Pyrenula sp. J Nat Prod 2014; 77(6): 1404-1412.
133. Shivanna R, Parizadeh H, Garampalli RH. In vitro anti-obesity effect of macrolichens Heterodermia leucomelos and Ramalina celastri by pancreatic lipase inhibitory assay. Int J Pharm Pharm Sci 2017; 9(5): 137-140.
134. Lage TCA, Maciel TMS, Mota YCC, Sisto F, Sabino JR, Santos JCC, Figueiredo IM, Masia C, Fatima A, Fernandes SA, Modolo LV. In vitro inhibition of Helicobacter pylori and interaction studies of lichen natural products with jack bean urease. New J Chem 2018; 42: 5356-5366.
135. Aydin S, Kinalioglu K, Sokmen BB. Antioxidant, anti-urease and anti-elastase activities of Usnea longissima Ach. Bangladesh J Bot 2018; 47(3): 429-435.
136. Proksa B, Adamcová J, Sturdíková M, Fuska J. Metabolites of Pseudevernia furfuracea (L.) Zopf. and their inhibition potential of proteolytic enzymes. Pharmazie 1994; 49(4): 282-283.
137. Ozgencli I, Budak H, Ciftci M, Anar M. Lichen acids may be used as a potential drug for cancer therapy; by inhibiting mitochondrial thioredoxin reductase purified from rat lung. Anticancer Agents Med Chem 2018; 18(11): 1599.
138. Mahadik ND, Morey MV, Behera BC, Makhija UV, Naik DG. Cardiovascular-protective, antioxidative, and antimicrobial properties of natural thallus of lichen Usnea complanata. Lat Am J Pharm 2011; 30(2): 220-228.
139. Zakharenko A, Luzina O, Koval O, Nilov D, Gushchina I, Dyrkheeva N, Švedas V, Salakhutdinov N, Lavrik O. Tyrosyl-DNA Phosphodiesterase 1 inhibitors: Usnic acid enamines enhance the cytotoxic effect of camptothecin. J Nat Prod 2016; 79(11): 2961-2967.
140. Zakharova O, Luzina O, Zakharenko A, Sokolov D, Filimonov A, Dyrkheeva N, Chepanova A, Ilina E, Ilyina A, Klabenkova K, Chelobanov B, Stetsenko D, Zafar A, Eurtivong C, Reynisson J, Volcho K, Salakhutdinov N, Lavrik O. Synthesis and evaluation of aryliden- and hetarylidenfuranone derivatives of usnic acid as highly potent Tdp1 inhibitors. Bioorg Med Chem 2018; 26(15): 4470-4480.
141. Dyrkheeva N, Luzina O, Filimonov A, Zakharova O, Ilina E, Zakharenko A, Kuprushkin M, Nilov D, Gushchina I, Švedas V, Salakhutdinov N, Lavrik O. Inhibitory effect of new semisynthetic usnic acid derivatives on human Tyrosyl-DNA Phosphodiesterase 1. Planta Med 2019; 85(2): 103-111.
142. Ingólfsdóttir K, Lee SK, Bhat KPL, Lee K, Chai H, Kristinsson H, Song LL, Gills J, Gudmundsdottir JT, Mata-Greenwood E, Jang M, Pezzuto JM. Evaluation of selected lichens from Iceland for cancer chemopreventive and cytotoxic activity. Pharm Biol 2000; 38(4): 313-317.
143. Xu B, Li C, Sung C. Telomerase inhibitory effects of medicinal mushrooms and lichens, and their anticancer activity. Int J Med Mushrooms 2014; 16(1): 17-28.
144. Deraeve C, Guo Z, Bon RS, Blankenfeldt W, DiLucrezia R, Wolf A, Menninger S, Stigter AE, Wetzel S, Choidas A, Alexandrov K, Waldmann H, Goody RS, Wu Y. Psoromic acid is a selective and covalent rab-prenylation inhibitor targeting autoinhibited RabGGTase. J Am Chem Soc 2012; 134(17):7384-7391.
145. Hassan STS, Sudomova M, Berchova-Bimova K, Gowrishankar S, Rengasamy KRR. Antimycobacterial, enzyme inhibition, and molecular interaction studies of psoromic acid in Mycobacterium tuberculosis: Efficacy and safety investigations. J Clin Med 2018; 7:226.
146. Pengsuparp T, Cai L, Constant H, Fong HHS, Lin L, Kinghorn DA, Pezzuto JM, Cordell GA. Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse transcriptase. J Nat Prod 1995; 58(7):1024-1031.
147. Okuyama E, Hossain CF, Yamazaki M. Monoamine oxidase inhibitors from a lichen, Solorina crocea (1.) ACH. Jpn J Pharmacogn 1991; 45(2):159-162.
148. Kinoshita K, Saito D, Koyama K, Takahashi K, Sato Y, Okuyama E, Fujimoto H, Yamazaki M. Monoamine oxidase inhibitory effects of some lichen compounds and their synthetic analogues. J Hattori Bot Lab 2002; 92:277-284.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).