Table 1.

Pharmacological activity of lichen depsides.

Depside	Botanical Origin	Type of Study	Experimental Model	Activities	Results	References
Atranorin	Parmotrema saccatilobum (Taylor) Hale	In vitro	Cyclooxygenase inhibition assay	Analgesic	Inhibition of COX-1 (IC50 45 μM). Inhibition (40%) of COX-2 ranging between 17 μg/mL and 0.17 μg/mL.	[40]
	Cladina kalbi. (Ahti)	In vivo	Male Swiss mice	Analgesic	Acetic acid-induced writhing test—200 and 400 mg/kg (p.o.)—reduction (p < 0.05) abdominal writhing by 52.6 and 61.3%, compared to control. Formalin test—200 and 400 mg/kg (p.o.) inhibition inflammatory processes (second phase) dose dependently.	[42]
	Cladina kalbi. (Ahti)	In vivo	Male Swiss mice	Analgesic Anti-inflammatory	Inhibitory effect in formalin- and capsaicin-induced orofacial pain tests. Anti-inflammatory effects in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced paw edema in rats.	[43]
	-	In vitro In silico	α-Glucosidase assay HEK293 (Human embryonic kidney cell line) Docking studies	Antidiabetic	N-substituted hydrazide derivatives of atranorin, more potent inhibition than the original. Weak or no cytotoxicity toward HEK293 cell line.	[44]
	Parmelia nepalensis (Taylor)	In vitro	Polymorphonuclear leukocytes	Anti-inflammatory	Inhibition of LTB4 biosynthesis via non-redox mechanism.	[41]
Atranorin	Kigelia africana (Lam.) Benth	In vitro	Chloroquine-resistant W-2 and two field isolates (CAM10 and SHF4) of Plasmodium falciparum LLC/MK2 monkey kidney cells	Antimalarial	Good activity against all parasite strains (IC50 < 5 μM). Cytotoxicity at high concentrations.	[36]
	Kigelia africana (Lam.) Benth	In vitro	Multidrug-resistant W2mef strain of Plasmodium falciparum	Antimalarial	Parasite lactate dehydrogenase assay (IC50 1.78 μM). Synergistic effects with artemether.	[37]
	Homalia trichomanoides (Hedw.) B. S. G.	In vitro	Candida albicans	Antimicrobial	Minimum inhibitory doses of 2.0 µg.	[29]
	Parmelia reticulata (Taylor)	In vitro	Sclerotium rolfsii, Rhizoctonia solani, R. bataticola, Fusarium udum, Pythium aphanidermatum and Pythium debaryanum	Antimicrobial	Maximum antifungal activity against Sclerotium rolfsii (ED50: 39.70 µg/mL).	[30]
	Cladonia foliacea (Huds.) Willd	In vitro	Gram-positive bacteria: Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Listeria monocytogenes Gram-negative bacteria: Proteus vulgaris, Aeromonas hydrophila. Fungi: Candida albicans, Candida glabrata	Antimicrobial	Low activity with high MIC values (15.6 µg to 500 µg per disk against 107 cells).	[27]
	Parmotrema dilatatum (Vain.) Hale, Parmotrema tinctorum (Nyl.) Hale	In vitro	Mycobacterium tuberculosis	Antimicrobial	Low-activity compound (MIC value 250 μg/mL).	[31]
Atranorin	-	In vitro	Methicillin-resistant Staphylococcus aureus strains	Antimicrobial	Effective in counteracting adhesion to polystyrene, against biofilm formation and against MRSA.	[28]
	Stereocaulon alpinum Laurer.	In vitro	Mycobacterium aurum strains	Antimicrobial	Low-activity MIC values >/= 125 µg/mL.	[32]
	Usnea laevis Nyl.	In vitro	Mycobacterium tuberculosis Mycobacterial multidrug-resistant (MDR) strains (MDR-A8, MDR-V791, MDR-R, MDR-40)	Antimicrobial	Inactive against mycobacterial strains MIC values ≥ 200 µg/mL.	[33]
	Cladina kalbii Ahti	In vitro	TRAP, TAR, TBARS, hydroxyl radical scavenging activity, nitric oxide scavenging activity, CAT- SOD-like activity. SH-SY5Y neuroblastoma cell line	Antioxidant	TRAP assay: 1–100 μg/mL significant antioxidant effects (dose-dependent). TAR assay: 100 μg/mL significant antioxidant capacity. TBARS: 0.1 to 100 μg/mL AAPH-induced lipoperoxidation. No hydroxyl radical/nitric oxide scavenging activity. Increase (↑) H2O2 formation in vitro ↑ superoxide degradation.	[47]
	Parmotrema austrosinense (Zahlbr.) Hale	In vitro	DPPH assay Anti-linoleic acid peroxidation activity	Antioxidant	IC50: 100 µg/mL. IC50: 116 µg/mL.	[34]
	Hypotrachyna revoluta (Flörke) Hale	In vitro	Hydroxyl radical-scavenging activity	Antioxidant	Metabolite (11.8 mg) same activity as Trolox (1 mg).	[46]
	Parmotrema stuppeum (Taylor) Hale	In vitro	Beta-carotene-linoleate model system	Antioxidant	14% of antioxidant activity at 200 µg/mL.	[48]
Atranorin	-	In vitro	Piroplasm parasites: Babesia. bovis, Babesia bigemina, Babesia divergens, Babesia caballi, and Theileria equi Hosts of piroplasm parasites: human foreskin fibroblasts (HFF), mouse embryonic fibroblast (NIH/3T3) Madin–Darby bovine kidney (MDBK)	Anti-parasitic	Suppression of multiplication: IC 50 (B. bovis): 98.4 µM, IC50 (B. bigemina): 64.5 µM, IC50 (B. divergens): 45.2 µM, IC50 (B. caballi): 46.6 µM, IC50 (T. equi): 71.3 µM. Reduce (↓) Cell viability.	[38]
	-	In vivo	BALB/c mice infected by B. microti	Anti-parasitic	↓ B. microti multiplication in mice by 68.17%.	[38]
	-	In vivo	Normal mammary epithelial NMuMG cells BALB/c mice with T1-induced cancer disease	Antitumoral	↓ Clonogenic ability of carcinoma. ↑ Apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. ↑ Depletion of Bcl-xL protein in 4T1 cells. Longer survival time, reduced tumor size, and higher numbers of apoptotic 4T1 cells. Normal NMuMG cells are less sensitive to ATR.	[57]
	Stereospermum acuminatissimum K. Schum.	In vitro	Urease inhibition assay Chymotrypsin inhibition assay	Antiulcerogenic	Excellent urease inhibition IC50 (18.2 µM). No α-chymotrypsin inhibitory effect.	[45]
	Stereocaulon evolutum Graewe.	In vitro	HCV grown in Huh-7.5.1 human hepatic cell line	Antiviral	Interferes with the lifecycle of hepatitis C virus (HCV), inhibiting only viral entry (IC50: 22.3 µM).	[35]
	Parmotrema rampoddense (Nyl.) Hale	In silico In vitro	Docking studies with breast cancer oncoproteins MDA MB-231 and MCF-7 (breast cancer cell lines)	Cytotoxic	Molecular docking studies interaction: Akt > Bax, Bcl-xL and Bcl-2 > Bcl-w proteins. IC50 (MDA MB-231) = 5.36 μM; IC50 (MCF-7) = 7.55 μM.	[49]
Atranorin	Everniastrum vexans (Zahlbr. ex W.L. Culb. and C.F. Culb.)	In vitro	A549 (human lung cancer cell line)	Cytotoxic	↓ Lung cancer cell motility and tumorigenesis by affecting AP-1, Wnt, and STAT signaling and suppressing RhoGTPase activity.	[50]
	Stereocaulon caespitosum Redinger	In vitro	SKHep1 and Huh-7 (epithelial carcinoma cell line) SNU-182 (primary cancer cell line)	Cytotoxic	↓ Cell growth at 80 µg/mL in all cell lines Cell cycle attenuated. ↑ Cell death through necrosis. ↓ Metastatic potential by suppression of cell migration and invasion.	[51]
	-	In vitro	HTB-140 (melanoma cell line) DU-145 and PC-3 (prostate cancers) normal human skin fibroblasts PNT2 (prostate epithelial cell line)	Cytotoxic	↓ Cancer cell proliferation, migration, and actin cytoskeleton organization.	[52]
	Hypogymnia physodes (L.) Nyl	In vitro	Human lymphocytes- cytochalasin-B blocked micronucleus (CBMN) assay.	Cytotoxic	No significant clastogenic and antiproliferative effects on selected concentrations.	[16]
	-	In vitro	A2780 (human ovarian cancer cell line) HT-29 (human colon cancer cell line)	Cytotoxic	Loss in the mitochondrial membrane potential. ↑ caspase-3 activation (only in HT-29 cells) and phosphatidylserine externalization. ↑ ROS/RNS. ↑ PARP, p53, Bcl-2/Bcl-xL, Bax, p38, pp38.	[56]
Atranorin	-	In vitro	A2780 (human ovarian carcinoma) HCT-116 p53+/+ and HCT-116 p53−/− (human colon carcinoma) HeLa (human cervix adenocarcinoma) SK-BR-3 (human breast adenocarcinoma) HL-60 (human promyelocytic leukemia) HT-29 (human colon adenocarcinoma) Jurkat (human T cells lymphocyte leukemia) MCF-7 (human breast adenocarcinoma)	Cytotoxic	Cytotoxicity against all cell lines except against HeLa (especially effective against HL-60 cells (50 μM). Clonogenic inhibition ability of all tested tumor cells. Accumulation in S-phase at expense of G1/G0-phase. Lower incidence in p53-deficient cells.	[55]
Atranorin SPION	-	In vitro	GCSCs (gastric cancer stem cells)	Cytotoxic	Inhibition proliferation, invasion, angiogenesis, and tumorigenicity of CD44+/CD24+. ↑ Oxidative stress. ↑ Fe2+ accumulation/ferroptosis. Increase mRNA encoding apoptosis factors, COX-2 levels. Inhibition GCSC markers and GPX4, NCOA4.BRF2, CD98. Downregulation mRNA hm5C modification levels.	[54]
	-	In vivo	NOD-scid mice	Cytotoxic Antitumor	Smaller tumors in weight and volume. Inhibition GPX4 and SLC7A11.	[54]
Atranorin	Bacidia stipata I. M. Lamb.	In vitro	A375 (melanoma cancer cell line)	Cytotoxic	Low inhibition (only high concentrations)	[55]
	Parmotrema dilatatum (Vain.) Hale	In vitro	UACC-62 and B16-F10 (melanoma cells) 3T3 (normal cells)	Cytotoxic	IC50: 250 µg/mL. Low cytotoxic effects on all the cell lines.	[59]
	Bacidia stipata I. M. Lamb.	In vitro	Androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cells.	Cytotoxic	Lower activity inhibiting cancer cells only at higher concentrations (25 and 50 μM).	[60]
	Ramalina glaucescens Kremp.	In vitro	P388 murine leukemia cell line	Cytotoxic	Moderate activity against (IC50 of >33 µM).	[53]
	Usnea laevis Nyl.	In vitro	Human acute monocytic leukemia cell line (THP-1)	Cytotoxic	IC50: 286.13 µg/mL. Low cytotoxic effects on macrophages.	[33]
	-	In vitro	Calf thymus DNA	DNA-interacting agents	ATR acts as effective DNA-interacting agent. No inhibitory effect on Topo isomerase I.	[61]
	-	In vitro	Second and third instar larvae of the mosquito Culiseta longiareolata	Larvicidal activity	LC (50) values: 0.52 ppm. LC (90) values: 5.93 ppm.	[39]
	Usnea articulata (L.) Hoffm.	In vitro Ex vivo	Neuro2A (mouse neuroblastoma) cell line Primary neural stem or progenitor cells	Neuroprotective	Neurotrophic activity (131.73 μm at 5 μM). Gene expression of BDNF and NGF modulation.	[62]
	Umbilicaria antarctica Frey and I. M. Lamb.	In vitro	Red cell suspension	Photohemolytic	Significant hemolysis in a red cell suspension after irradiation of atranorin with 366 nm light. Higher in presence of nitrogen.	[64]
	Umbilicaria antarctica Frey and I. M. Lamb.	In vitro	Inhibition of 8-MOP-human serum albumin (HSA) photobinding.	Photoprotective	Atranorin (10 mM) and irradiation (360 nm) inhibited photobinding to HSA by 20.1%.	[63]
Atranorin	Parmotrema austrosinense (Zahlbr.) Hale	In vitro	Bacterial strain Lactobacillus casei	Probiotic bacteria	Moderate growth stimulating activity in terms of increased dry matter of biomass (41.1 mg) of L. casei.	[34]
Baeomycesic acid	Thamnolia subuliformis (Ehrh.) W. Culb.	In vitro	Porcine leucocytes Sheep seminal vesicle microsomes	Cytotoxic	Potent 5-lipoxygenase inhibitor (IC50 = 8.3 µM). Inactive against COX.	[15]
	Thamnolia vermicularis (Sw.) Schaer.	In vitro	Human platelets	Cytotoxic	Weak 12(S)-LOX inhibitor (14.7 +/− 2.76%).	[66]
	Thamnolia vermicularis (Sw.) Schaer.	In vitro	AGS (stomach cancer cell line) Capan-1, Capan-2 and PANC-1 (pancreas cell lines) HL-60, K-562 and JURKAT (blood cancer cell lines) NCI-H1417 (lung cancer cell line) NIH: OVCAR-3 (ovary cancer line) PC-3 (prostate cancer cell line) T47-D (breast cancer line) WiDr (colorectal cancer cell line)	Cytotoxic	Slight anti-proliferative activity. Selective 5-LOX inhibitor.	[65]
Barbatic acid	Cladonia borealis Stenroos	In vitro	Staphylococcus. aureus NEWP0023 Enterococcus. faecalis (NEWP0012) Escherichia. coli (NEWP 0022)	Antimicrobial	MIC values: S. aureus (NEWP0023) = 31.3 µg/mL; S. aureus (clinic) = 31.3 µg/mL; E. faecalis (NEWP0012) = 7.8 µg/mL; E. faecalis (clinic) = 31.3 µg/mL; E. coli = nt.	[68]
	Cladia longissima (Sw.) Nyl.	In vitro	Adult worms of Schistosoma mansoni	Antiparasitic	Schistosomicidal effect (death, tegumentary damages, and changes in mobility).	[18]
	Cladia longissima (Sw.) Nyl.	In vitro	Adult mollusks of Biomphalaria glabrata Cercariae of Schistosoma mansoni	Antiparasitic Antimolluscal	Molluscicidal activity against B. glabrata at 20 and 25 µg/mL. Schistosomicidal effect against the parasite S. mansoni at the second larval stage (1 µg/mL after 60 min of exposure).	[67]
Barbatic acid	Usnea longissima Ach.	In vitro	A549 (lung cancer cell line)	Cytotoxic	Pro-apoptotic effect (G0/G1 accumulation and poly ADP-ribose polymerase cleavage).	[69]
	Usnea longissima Ach	In vitro	Tissue culture	Cytotoxic	Slight inhibitor of tumor promoter-induced Epstein–Barr virus (EBV) activation.	[70]
	Pyrrosia petiolosa (Christ) Ching.	In silico	With-no-lysine 1 (WNK1) kinase	Diuretic	Weak diuretic potential.	[71]
Diffractaic acid	Usnea diffracta Vain.	In vivo	Male ddY mice Lipopolysaccharide (LPS)-induced (hyperthermia model) Acetic acid-induced writhing and tail-pressure method (analgesic model)	Analgesic and antipyretic	Hypothermic effect (dose of 200 mg/kg) on normal body temperature. Analgesic effect (dose of 200 mg/kg).	[14]
	Parmelia nepalensis (Taylor) Parmelia tinctorum Despr. Ex Nyl	In vitro	Polymorphonuclear leukocytes	Anti-inflammatory	Inhibition of LTB4 biosynthesis by specific enzyme interaction.	[41]
	Usnea blepharea Motyka	In vitro	Gram-positive bacteria: Staphylococcus aureus, Gram-negative bacteria: Escherichia coli	Antimicrobial	Antibacterial. Strong inhibition at 750 and 1000 ppm concentration.	[72]
	-	In vitro	Fusarium fujokuroi	Antimicrobial	Antifungal. MIC 16 × 10−3 mg/mL. Similar to amphotericin B, isovuconzole, terbafine, voriconazole.	[73]
	Usnea subcavata (Motyka)	In vitro	Mycobacterium tuberculosis	Antimicrobial	Anti-tubercular activity. High active compound (MIC value 15.6 μg/mL).	[31]
Diffractaic acid	Usnea longissima Ach	In vivo	Albino Wistar rats Indomethacin-induced gastric lesions	Antiulcerogenic	Significant gastroprotective effect. ↑ SOD and GPx activities and GSH levels ↓ lipid peroxidation ↓ myeloperoxidase and inducible NOS (iNOS) activities ↑ constitutive NOS (cNOS) activity.	[74]
	-	In vitro	U87MG (glioblastoma multiforme cell line) PRCC cells (neurons from Sprague Dawley® rats)	Cytotoxic	IC50 value (PRCC) = 122.26 mg/L. IC50 value (U87MG) = 35.67 mg/L. High antioxidant capacity on PRCC cells (10 mg/L).	[75]
	Parmelia nepalensis (Taylor) Parmelia tinctorum Despr. ex Nyl	In vitro	HaCaT (human keratinocyte cell line)	Cytotoxic	Inhibition cell growth (IC50 values of 2.6 mM). No changes on LDH activity, cytostatic effects.	[76]
	Usnea aciculifera Vain.	In vitro	HeLa (human epithelial carcinoma cell line) NCI-H460 (human lung cancer cell line) MCF-7 (human breast cancer cell line)	Cytotoxic	Strong cytotoxic activity against all cell lines (100 μg/mL).	[77]
	Protousnea magellanica (Mont.) Krog	In vitro	MCF-7 (breast adenocarcinoma cell line) HeLa (cervix adenocarcinoma cell line) HCT-116 (colon carcinoma cell line)	Cytotoxic	Cytotoxic effects in a concentration-dependent manner (2.5–100 μM). No increase intracellular ROS level. No prevention of oxidative injury induced by t-butylhydroperoxide in HeLa cells.	[78]
Diffractaic acid	-	In vitro	Mitochondrial TrxR purified from rat lung	Cytotoxic	Moderate inhibitory effect on Thioredoxin reductase (TrxR).	[79]
	Usnea longissima Ach	In vitro	Tissue culture	Cytotoxic	Slight inhibitor of tumor promoter-induced Epstein–Barr virus (EBV) activation.	[14]
	Usnea longissima Ach	In vivo	Titanium-implanted rabbits	Proapoptotic agent	↑ Caspase-2, Csp-8, Csp-9, and Csp-3 activation. ↑ Strong myeloperoxidase and inducible nitric oxide synthase activities. ↓ SOD activity and total glutathione level.	[116]
Divaricatic acid	Evernia mesomorpha Nyl.	In vitro	Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecium, Bacillus subtilis, Micrococcus luteus, Streptococcus epidermidis, Streptococcus mutans Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium, Vibrio vulnificus Fungi: Candida albicans	Antimicrobial	Effective against Gram+ bacteria (MIC values ranging from 7.0 to 64.0 μg/mL) and Candida albicans.	[81]
	-	In vitro	Gram-positive bacteria: Staphylococcus aureus Gram-negative bacteria: Escherichia coli, Mycobacteria: Mycobacterium tuberculosis Protozoan: Plasmodium berghei liver stage (LS) parasites, Plasmodium falciparum blood stage (BS) parasites	Antimicrobial Antiplasmodial	No antibacterial/antimycobacterial activity. Low antiplasmodial activity. Low LS activity (IC50 = 77.3 μM), high BS potential (IC50 = 142.1 μM). Plasmodial FAS-II enzyme (PfFabI and PfFabZ) inhibition.	[86]
Divaricatic acid	-	In vitro	Pseudomonas aeruginosa	Antimicrobial	↓ Pseudomonas aeruginosa virulence factors expression by inhibiting quorum sensing.	[23]
	Ramalina aspera Räsänen	In vitro	Mollusk Biomphalaria glabrata Cercariae of the helminth Schistosoma mansoni	Molluscicidal and cercaricide	High toxicity against: adult snails (5 μg/mL) and embryos (20 μg/mL after 6 h of exposure) cercariae (10 μg/mL after 30 min of exposure).	[82]
	Dirinaria aspera Hasanen	In vitro	UACC-62 and B16-F10 (human and murine melanoma cells) 3T3 normal cells	Cytotoxic	Cytotoxic against both lines (LC50 50.2 μM (UACC-62) LC50 643.7 Μm (B16-F10). More selective against melanoma cells than normal cells.	[59]
	Canoparmelia texana	In vitro	PBMCs (peripheral blood mononuclear cell)	Cytotoxic	No cytotoxicity (IC50 > 200 μM).	[82]
	Cetraria ornata Müll.Arg.	In vitro	Tissue culture	Cytotoxic	Moderate inhibitor of tumor promoter-induced Epstein–Barr virus (EBV) activation.	[70]
Evernic acid	Evernia prunastri (L.) Ach.	In vitro	Gram-positive bacteria: Staphylococcus aureus Gram-negative bacteria: Pseudomonas aeruginosa, Escherichia coli Fungi: Candida albicans	Antimicrobial	Inhibition of the growth of all tested microorganisms (MIC values = from 0.98 to 125 µg/mL).	[84]
	Evernia prunastri (L.) Ach.	In silico	Prediction of toxicity risk based on fragment-based toxicity estimation	Toxicity	No mutagenic, no tumorigenic, no reproductive alterations and no irritant effects.	[84]
	Evernia prunastri (L.) Ach.	In vitro	Candida albicans biofilms	Antimicrobial	Slow maturation and reduction in biofilms with MBIC50 ≤ 12.5 µg/mL.	[85]
	Evernia prunastri (L.) Ach.	In vitro	HeLa (Human epithelial cervical cancer)	Cytotoxic	Strong cytotoxic and antiproliferative effects (25 and 50 µg/mL).	[91]
Evernic acid	Evernia prunastri (L.) Pseudoevernia furfuraceae (L.) Zopf.	In vitro	A549 (human lung cancer cells) HUVEC (umbilical vein endothelial cells)	Cytotoxic	No significant effects in healthy cells. Decrease in proliferation in cancer cells (12.5–100 µg/mL).	[90]
	Evernia prunastri (L.) Ach.	In vitro	Glioblastoma multiforme cell line: A-172 and T98G cell lines.	Cytotoxic	Reduction A-172 cell viability at 10 µM. Mildly cytotoxic on T98G cell line. Anti-IDO1 (32.8 % inhibition). Anti-COX-2 (50.7%) inhibition. Anti-hyaluronidase activity (IC50 600 µg/mL). Weak antioxidant properties (DPPH (750 µg/mL) CUPRAC (250 µg/mL)) (21.2 % SOD and 20 % GPx inhibition). Inhibition of BChE. (85.9 %) No AchE inhibition. BBB Permeability (8.6 × 10−6 (cm/s) at 4 h.	[92]
	Evernia prunastri (L.) Ach.	In vitro	U373-MG (human glioblastoma astrocytoma cell line) SH-SY5Y (human neuroblastoma cell line)	Neuroprotective	↑ Cell viability; GSH/GSSG ratio; antioxidant enzymes expression. ↓ ROS; lipid peroxidation; protein carbonyls; Caspase-3 activity; Nrf2 pathway activation.	[87]
	-	In vitro	Primary neurons	Neuroprotective	Suppression/inhibition MPP+ induced: - Apoptosis (↑ Bcl-2/↓ Bax/Caspase-3) - Mitochondrial Dysfunction - Astrocyte Activation (GFAP expression) - Oxidative stress (↓ ROS production) - NF-κB Signaling Pathway.	[88]
Evernic acid	-	In vivo	MPTP-induced mouse model C57BL/6 mice Rotarod	Neuroprotective	Attenuation of motor dysfunction Reduction in dopaminergic neuronal death and astroglial activation.	[88]
	Evernia prunastri (L.) Ach.	In vitro	MM98 (malignant mesothelioma cell line) A431 (vulvar carcinoma cell line) HaCaT (human keratinocyte cell line)	Wound healing	No wound closure effects.	[89]
Isolecanoric acid	Glarea lozoyensis	In vitro	SH-SY5Y (human dopaminergic neuroblastoma cell line) L-BMAA for amyotrophic lateral sclerosis (ALS) model and rotenone for Parkinson’s disease (PD) model	Neuroprotective	GSK3β and CK1 inhibition. ↓ Oxidative stress, mitochondrial damage, apoptosis, and cell death.	[93]
Lecanoric acid	-	In vitro	α-Glucosidase	Antidiabetic	Active against α-glucosidase (85.9% of inhibition; IC50 value of 350 µM)	[98]
	Umbilicaria ntárctica Frey and I. M. Lamb.	In vitro	PTP1B enzyme activity and kinetic analysis	Antidiabetic Antiobesity	Moderate inhibition PTP1B activity IC50 31 μM.	[99]
	Melanelia subaurifera (Nyl.) Melanelia fuliginosa (Fr. Ex Duby) Ess	In vitro	Gram-positive bacteria: Bacillus cereus, Bacillus subtilis, Staphylococcus aureus. Gram-negative bacteria: Escherichia coli, Proteus mirabilis Fungi: Aspergillus flavus, Candida albicans, Mucor. mucedo, Trichoderma viride, Cladosporium cladosporioides, Fusarium oxysporum	Antimicrobial	Antimicrobial activity against all tested bacteria and fungi with MIC values of 0.5 to 1 mg/mL.	[24]
Lecanoric acid	Parmelia cetrata Ach.	In vitro	Gram-negative bacteria: Aliivibrio fischeri Nematode Caenorhabditis elegans	Antimicrobial Antihelmintic	Antibacterial activity (100% inhibition at 100 µM). Antihelmintic effect (80% mortality at 100 µg/mL).	[4]
	Melanelia subaurifera (Nyl.) Melanelia fuliginosa (Fr. ex Duby) Ess	In vitro	DPPH assay	Antioxidant	Slight DPPH scavenging activity (IC50 value of 424.5 μg/mL) and reducing power (0.0165 at 125 μg/mL).	[24]
	Parmotrema grayanum (Hue) Hale.	In vitro	Superoxide radical (SOR) Nitric oxide radical DPPH assay	Antioxidant	Good antioxidant activity: SOR assay (IC50 value = 91.5 µmol), DPPH (IC50 value = 34 µmol), NOR assay (IC50 value = 53.5 µmol).	[94]
	Parmotrema stuppeum (Nyl.) Hale	In vitro	Beta-carotene-linoleate model system	Antioxidant	Thirty-six percent of antioxidant activity at 500 µg/ml.	[48]
	Hypocenomyce scalaris (Ach. ex. Lilj	In vitro	Colorectal cancer cells (HCT116 and DLD-1) Human keratinocytes HaCaT cell line	Cytotoxic	Moderate cytotoxic effects against colon HCT116 cells. ↓ Slight Axin2 expression in HCT116 cells.	[95]
	Parmotrema tinctorum (Despr. ex Nyl.) Hale.	In vitro	Hep-2 (human larynx carcinoma cells) MCF7 (human breast carcinoma cells) 786-0 (human kidney carcinoma cells) B16-F10 (murine melanoma cells)	Cytotoxic	Slight activity against all tested cancer cell lines (IC50 values > 50 µg/mL).	[97]
	Melanelia subaurifera (Nyl.) Melanelia fuliginosa (Fr. ex Duby) Ess	In vitro	Hela (human epithelial carcinoma cells) A549 (human lung carcinoma cells) LS174 (human colon carcinoma cells)	Cytotoxic	Weak cytotoxic activity against Hela cells (IC50 value of 124 μg/mL) and against A549 and LS174 cells (IC50 value of 200 μg/mL).	[24]
Lecanoric acid	-	In vitro	HCT-116 (human colon cancer cell line)	Cytotoxic	Inhibition cell colony formation already at 0.03 μg/mL. Induction of a G2 cell cycle block. Arrest of cells in the M phase. Upregulated expression of cyclin B1 and pH3. Inactive CDK1. More cell death in cancer cells than in primary human immune and endothelial cells.	[96]
	-	In vitro	Mitochondrial TrxR from rat lung	Cytotoxic	High inhibitory effect on Thioredoxin reductase (TrxR).	[79]
Methyl evernate	Ramalina fastigiata (Pers.) Ach.	In vitro	Gram-positive bacteria: Bacillus cereus, Staphylococcus aureus. Gram-negative bacteria: Escherichia coli, Proteus mirabilis Fungi: Aspergillus flavus, Candida albicans, Mucor mucedo, Trichoderma viride, Cladosporium cladosporioides, Fusarium oxysporum, Alternaria alternata, Penicillium expansum	Antimicrobial	Inhibition against all tested microorganisms. MIC values (from 0.125 to 1 mg/mL).	[24]
	Ramalina fastigiata (Pers.) Ach.	In vitro	DPPH assay Reducing power assay	Antioxidant	Low DPPH radical scavenging activity (IC50 value of 391.57 μg/mL). Isolated components showed higher reducing power than lichen extracts.	[24]
	Ramalina fastigiata (Pers.) Ach.	In vitro	Hela (human epithelial carcinoma cells) A549 (human lung carcinoma cell line) LS174 (human colon carcinoma cells)	Cytotoxic	IC50 values of 46.45 μg/mL (Hela cell line), 76.84 μg/mL (A549 cell line), and 161.37 μg/mL (LS174 cell line).	[24]
Olivetoric acid	Pseudevernia furfuracea var. ceratea (Ach.) D. Hawksw.	In vitro	RATECs (rat adipose tissue endothelial cells)	Anti-angiogenic	↓ Proliferation. Disruption of endothelial tube formation. Depolymerization effects on F-actin stress fibers.	[104]
	Pseudevernia furfuracea var. ceratea (Ach.) D. Hawksw.	In vitro	Gram-positive bacteria: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Streptococcus faecalis, Listeria monocytogenes. Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Pseudomonas vulgaris, Yersinia enterocolitica, Aeromonas hydrophila, Pseudomonas syringae, Klebsiella pneumoniae, Salmonella typhimurium. Fungi: Aspergillus niger, Penicillium notatum, Fusarium solani, Fusarium moniliforme, Fusarium oxysporum, Fusarium. culmorum, Candida albicans, C.glabrata, Alternaria. tenuissima, A. citri, A. alternata, Gaeumannomyces graminis.	Antimicrobial	Active against all bacteria and yeast except K. pneumoniae, P. aeruginosa, and P. syringae. Active against all tested fungi except A. citri, A. tenuissima, A.niger, and G. graminis.	[100]
	Pseudevernia furfuracea (L.) Zopf	In vitro	Cultured human amnion fibroblasts	Antioxidant	↓ Cell viability (IC50 values of 571.27 mg/mL) <50 mg/L no oxidative stress and genotoxicity.	[101]
	Pseudevernia furfuracea (L.) Zopf	In vitro	HLs (cultured human lymphocytes)	Antioxidant	↑ Total antioxidant capacity.	[16]
Olivetoric acid	Pseudevernia furfuracea (L.) Zopf	In vitro	U87MG (glioblastoma multiforme cell line) PRCC cells (neurons from Sprague Dawley® rats)	Cytotoxic	↓ Cell viability (IC50 values of 125.71 mg/mL, for PRCC cells and 17.55 mg/L for U87MG cells). ↑ 8-OH-dG levels. LDH activity and oxidative DNA damage.	[102]
	Pseudevernia furfuracea (L.) Zopf	In vitro	HepG2 (human hepatocellular carcinoma cells)	Cytotoxic	Cytotoxicity with 100–400 mg/L. Upregulation of pro-apoptotic genes (BAK, CASP6, CASP7, CASP8, FADD, FAS, FASLG).	[103]
Perlatolic acid	-	In silico	Microsomal prostaglandin E2 synthase 1	Anti-inflammatory	Potent inhibitor of microsomal prostaglandin E2 synthase-1 (IC50 = 0.43 µM).	[106]
	Cetrelia monachorum (Zahlbr.) W.L. Culb. and C.F. Culb.	In vitro In vivo	Stimulated A549 lung epithelial adenocarcinoma cells Stimulated HEK-293 cells Thioglycollate-induced C57BL/6J male murine peritonitis model	Anti-inflammatory	Microsomal prostaglandin E2 synthase-1 inhibition (IC50 = 0.4 µM), 5-Lipoxygenase inhibition (IC50 = 1.8 µM for cell-based assay and IC50 = 0.4 µM for purified enzyme). Tumor necrosis factor alpha-induced NF-kB (IC50 = 7 µM). Inhibition of leukocyte recruitment.	[107]
	Stereocaulon sp.	In vitro	Methicillin-resistant Staphylococcus aureus strains	Antimicrobial	MIC90 value of 32 µg/mL. Synergic action with gentamicin and antagonism action with levofloxacin.	[105]
	Cladina confusa (Sant.). Folmm and Ahti	In vitro	Cultures of peritoneal macrophage cells from mice	Immune modulating	↑ Hydrogen peroxide release (10.48 nmol). Slight NO release activity.	[108]
	Cladonia portentosa (Dufour) Coem.	In vitro Ex vivo	Neuro2A (mouse neuroblastoma) cell line Primary neural stem or progenitor cells	Neuroprotective	Neurotrophic activity (125.34 μm at 0.5 μM). AChE inhibition activity (IC50 = 6.8 μM). Potent proneurogenic activity. Gene expression of BDNF and NGF modulation. ↑ Acetyl H3 and H4 protein levels.	[63]
Ramalic acid/Obtusatic acid	Ramalina fraxinea (L.) Ach. Ramalina fastigiata (Pers.) Ach.	In vitro	Gram-positive bacteria: Bacillus cereus, Bacillus subtilis, Staphylococcus aureus. Gram-negative bacteria: Escherichia coli, Proteus mirabilis Fungi: Aspergillus flavus, Aspergillus niger, Candida albicans, Mucor mucedo, Trichoderma viride, Cladosporium cladosporioides.	Antimicrobial	Inhibition against all tested microorganisms. MIC values (from 0.125 to 1 mg/mL).	[24]
Ramalic acid/Obtusatic acid	Ramalina fraxinea (L.) Ach. Ramalina fastigiata (Pers.) Ach.	In vitro	DPPH assay Reducing power assay	Antioxidant	Slight to moderate antioxidant activity (DPPH radical scavenging activity with IC50 value of 324.61 μg/mL and reducing power of 0.0142 at 125 µg/mL). Isolated components showed higher reducing power than lichen extracts.	[24]
	-	In vitro	HaCaT (human keratinocyte cell line)	Cytotoxic	No significant inhibitory activity against LTB (4) production via non-mediation by redox reactions. No cytotoxic activity.	[76]
	Ramalina fraxinea (L.) Ach. Ramalina fastigiata (Pers.) Ach.	In vitro	Hela (human epithelial carcinoma cell line) A549 (human lung carcinoma cell line) LS174 (human colon carcinoma cell line)	Cytotoxic	IC50 value (Hela) 43.24 μg/mL; IC50 value (A549) 93.98 μg/mL; IC50 value (LS174) 74.28 μg/mL.	[24]
Sekikaic acid	Dirinaria consimilis (Stirt.) D. D. Awasthi	In vivo	STZ-induced type 2 diabetic albino rat model	Antidiabetic	↑ α-glucosidase and α-amylase inhibition. ↓ Plasma glucose levels (44.17%), low-density. lipoprotein, total cholesterol, and total glycerides.	[111]
	Ramalina roesleri Nyl	In vitro	Gram-positive bacteria: Bacillus subtilis, Staphylococcus aureus, Streptomyces viridochromogenes, Streptococcus mutans. Gram-negative bacteria: Escherichia coli.	Antimicrobial	Maximum antimicrobial activity against E. coli (78% inhibition), moderate against S. mutans, S. aureus, and S. viridochromogenes (60%, 50% and 55% inhibition, respectively), and low against B. subtilis (15% inhibition).	[109]
Sekikaic acid	Ramalina farinacea (L.) Ach	In vitro	Respiratory syncytial virus	Antimicrobial	Potent antiviral action against a recombinant strain rg respiratory syncytial virus (IC50 5.69 µg/mL) and respiratory syncytial virus A2 strain (IC50 7.73 µg/mL).	[110]
	Ramalina roesleri Nyl	In vitro	DPPH assay	Antioxidant	Good antioxidant activity: DPPH radical assay (IC50 value = 11.24 µg/mL).	[109]
	Heterodermia obscurata (Nyl.) Trevisan	In vitro	Superoxide radical (SOR) Nitric oxide radical DPPH assay	Antioxidant	Good antioxidant activity: SOR assay (IC50 value = 82.0 µmol), DPPH (IC50 value = 32.6 µmol). No nitric oxide radical activity.	[94]
	Dirinaria consimilis (Stirt.) D. D. Awasthi	In vitro	Ferric ion reducing power and hydroxyl radical assay.	Antioxidant	Good antioxidant activity: hydroxyl radical assay (IC50 value = 41.5 µg/mL) and ferric ion assay (IC50 value = 42.0 µg/mL).	[33]
	Niebla homalea (Ach.) Rundel and Bowler	In vitro	MCF-7 (human hormone-dependent breast) A2780 (ovarian cancer cell)	Cytotoxic	No antiproliferative activity.	[112]
Squamatic acid	Cladonia uncialis (L.) F. H. Wigg.	In vitro	Gram-positive bacteria: Staphylococcus aureus Gram negative bacteria: Escherichia coli, Fungi: Candida albicans	Antimicrobial	Weak antibacterial activity (MIC = 1250.0 mg/mL against S. aureus).	[113]
	Thamnolia vermicularis (Sw.) Schaer	In vitro	PC-3 (prostate cancer cells)	Cytotoxic	Weak antiproliferative effect.	[114]
Thamnolic acid	Usnea florida (L.) F.H. Wigg	In vitro	Gram-positive bacteria: Bacillus cereus, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Micrococcus luteus. Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimurium, Yersinia enterocolitica. Mycobacteria: Mycobacterium tuberculosis. Fungi: Candida parapsilosis, Candida albicans, Candida globrata, Aspergillus niger, Aspergillus flavus, Fusarium moniliforme, Rhizopus sp., Alternaria brassicola, Sclerotium rolfsii, Fusarium solani	Antimicrobial	Antifungal: Alternaria alternate, Aspergillus fumigatus and Sclerotium rolfsii with MIC values of 400, 400, and 200 µg/mL, respectively. Anti-yeast: Candida krusei with MIC value of 400 µg/mL. Antibacterial: Bacillus cereus, Bacillus subtilis, and Proteus vulgaris with MIC value of 400 µg/mL and Listeria monocytogenes and Micrococcus luteus with MIC value of 200 µg/mL.	[115]
	Thamnolia vermicularis (Sw.) Schaer.	In vitro	PC-3 (prostate cancer cells)	Cytotoxic	Weak antiproliferative effect.	[114]