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
Diabetes mellitus (DM) is an ever increasing global epidemic and one of the most challenging health problems of 21st century. In 2010, more than 285 million people around the world were afflicted with diabetes, and it was then estimated that the number of people with diabetes will increase to 439 million by 2030. Interestingly, the reports of 2015 show that globally 415 million (215.2 million men and 199.5 million women) had DM with a prevalence of 8.8%. In other words, one in eleven people have DM and global expenditure for treating it in 2015 alone was US$ 673 billion (12% of health expenditure) [
Two main groups of DM are distinguished: (1) autoimmune T1DM or insulin dependent DM or juvenile DM and (2) T2DM or noninsulin dependent DM or Maturity Onset DM. About 90% of people with DM around the world have type 2 DM (T2DM) [
In T1DM,
Recent basic and clinical studies have exposed new understandings into the role of antioxidants to combat diabetic complications [
Lichens are composite organisms consisting of a symbiotic association between a fungal partner (mycobiont) and one or more photosynthetic partners (photobiont) usually either green algae or cyanobacterium or both. Lichens are found in all ecosystems, including the most extreme environments on earth-arctic tundra, hot deserts, icebergs, rocky coast, toxic heaps, and so on. Lichens produce characteristic and unique substances which may help them to survive in these extreme environments [
Adequate literature exists, for certain lichens to be a viable source of antioxidants [
Further confounding the available information, compared to the antioxidant potential, limited information exists on evaluation of the efficacy of lichens as antidiabetic agents. A number of different approaches have been used, including
Importantly, most of the extracts and pure compounds of lichens reported for its antidiabetic potential have been separately studied for their antioxidant potential. Here, we summarize the antidiabetic effect of lichens by referring to recent studies, including those reported by us with the perspective of how their reported radical scavenging activities would influence the relationship (if any) between the antioxidant potential and the antidiabetic activities.
Several studies have discovered the positive potential of exploring lichens as potent antidiabetic agents. Their hypoglycemic action has been assessed in different methods, including through their inhibitory activity of carbohydrate hydrolyzing enzymes (
This review summarizes the reported antidiabetic activity of lichens using
Several lichen extracts have been evaluated for
Up to now, 22 lichen extracts including some in more than one study have been assessed and shown a positive potential in the
Wider interest has been received by plant natural polyphenols for their
The structure activity relationship of polyphenols isolated from other plant sources has shown that
Molecular docking studies have revealed that, overall, the inhibitory activity of phenols depends on two parameters: (i) hydrogen bonding capacity of the OH groups of the phenols with the side chains of amino acids such as Asp197, and Glu233 and (ii) planarity of aromatic rings to form an efficient conjugated
It is important to understand that lichen polyphenols are structurally distinct from other phenols such as flavonoids, catechins, and tannis found in higher plants. Lichen phenolics are mainly monocyclic phenols, depsides, depsidones, dibenzofurans, derived through the acetyl-polymalonly pathway, with mainly orsellinic acid as the basic unit in the biosynthesis. Thus, it would be interesting to estimate the
However, compared to
Monocyclic aromatics, methyl-
Several polyphenols isolated from different sources, especially flavonoids, have been extensively reviewed as inhibitors of
Interestingly, the ubiquitous triterpenoid zeorin found exclusively in almost all lichens, possessed the most significant
The role of triterpenoids in the management of diabetic mellitus and its complications has received as much attention as plant polyphenols. Pentacyclic triterpenoids, belonging to oleanane, ursane, and lupane types, isolated from different plant sources, have been extensively reviewed as
Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a major negative regulator of insulin signaling and therefore has been identified as a possible drug target for the treatment of type 2 diabetes and obesity. Prior to studies by Seo et al., in 2009, no reports existed on PTP1B inhibitory activity of lichens [
The Antarctic lichens which were evaluated against PTP1B inhibitory activity were
Further, over 27 triterpenoids of oleanane, ursane, and lupane types, isolated from different sources, have been reported as PTP1B inhibitors [
Increased glycation and buildup of advanced glycation end products have been implicated in diabetes complications. Thus, there is considerable interest in antiglycation compounds because of their therapeutic potential against diabetes.
Literature on crude lichen extracts for antiglycation was not found; however, antiglycation activity of several secondary metabolites has been described [
Table
Reported lichens and their compounds as antidiabetic agents.
Lichens | Compounds | Activity | Author [Ref.] |
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— |
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Shivanna et al., 2015 [ |
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— |
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Hengameh et al., 2016 [ |
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— |
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Vinayaka et al., 2013 [ |
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— |
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Valadbeigi and Shaddel, 2016 [ |
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— |
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Valadbeigi, 2016 [ |
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Salazinic acid, |
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Sekikaic acid, | Verma et al., 2012 [ | |
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Usnic acid | Antioxidant | |
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Zeorin, |
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Thadhani et al., 2011 [ |
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Gyrophoric acid, |
PTP1B | Seo et al., 2009 [ |
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Lobaric acid, Pseudodepsidones | PTP1B | Seo et al., 2009 [ |
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Zeorin, |
PTP1B | Seo et al., 2011 [ |
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Diterpene furanoids | PTP1B | Cui et al., 2012 [ |
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Atranorin |
Antiglycation | Thadhani 2013 [ |
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Lecanoric acid |
Antiglycation | Choudhary et al., 2011 [ |
Interestingly, ubiquitous compounds, namely, zeorin, methylorsellinate, methyl-
The in vivo antidiabetic studies of three lichen extracts, namely,
Ethanolic extracts of
Lichens appear to be a promising source of unique phenolic compounds, which do not occur in higher plants, and other free living fungi. The antioxidant properties of these phenolic compounds, as well as their crude extracts, have been thoroughly assessed using both in vitro and in vivo studies. Ample data exist to prove lichens as a reliable source of antioxidants. There are already several reviews on antioxidant activities of lichen extracts and their compounds [
The results are summarized in Table
Antioxidant potential of lichens/compounds reported as antidiabetic.
Lichen extracts/compounds | Antioxidant activity [References] | Assayed bioactivity type |
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Stojanović et al., 2010 [ |
DPPH & FRAP assays |
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Ghate et al., 2013 [ |
HORAC, ORAC, DPPH, SOI, & NOS |
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Raj et al., 2014 [ |
DPPH, ABTS, SOI, HORAC |
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Rajan et al., 2016 [ |
DPPH |
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Kumar et al., 2010 [ |
DPPH & FRAP |
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Vivek et al., 2014 [ |
DPPH |
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Kekuda et al., 2011 [ |
DPPH, FRAP & MC |
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Prateeksha et al., 2016 [ |
DPPH |
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Gulluce et al., 2006 [ |
DPPH & ALP |
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Verma et al., 2012 [ |
DPPH, ALP, SOI, NOS & TEAC |
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Verma et al., 2012 [ |
DPPH, ALP, SOI, NOS & TEAC |
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Verma et al., 2012 [ |
DPPH, ALP, SOI, NOS & TEAC |
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Luo et al., 2010 [ |
DPPH, FRAP & ALP |
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Kumar et al., 2009 [ |
DPPH |
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Mastan et al., 2014, [ |
DPPH and HORAC |
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Zambare and Christopher 2012 [ | |
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Luo et al., 2009 [ |
DPPH, SOI, ALP |
Strzalka et al., 2011 [ |
tocopherols, plastoquinone & plastochromanol | |
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Bhattarai et al., 2008 [ |
DPPH |
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Valadbeigi; 2016 [ |
DPPH, FRAP |
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Salazinic acid | Selvaraj et al.; 2015 [ |
DPPH, FRAP, MC, HORAC, ALP, phosphomolybdenum SOI |
Manojlovic et al., 2012 [ |
DPPH, SOI | |
Gyrophoric acid | Kosanic et al., 2014 [ |
DPPH, SOI, FRAP |
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Sekikaic acid, Usnic acid |
Thadhani et al., 2011 [ |
DPPH, SOI, NOS & MC |
DPPH: (1, 1diphenyl-2-picrylhydrazyl) radical scavenging method, FRAP: ferric reducing antioxidant power, MC: metal chelating, SOI: super oxide inhibitory, ALP: anti-linoleic acid peroxidation assay, NOS: nitric oxide-scavenging assay; TEAC: trolox equivalent antioxidant capacity assay; HORAC: hydroxyl radical antioxidant capacity, and ORAC: oxygen radical antioxidant capacity.
Secondary metabolites of lichens reported as both antioxidant and antidiabetic.
Interestingly, most of these lichen extracts and lichen compounds which are reported as antihyperglycemic (Table
It is encouraging to note that out of the 22 lichens extracts which are reported for their antidiabetic potential, 19 have shown antioxidant activity (Table
Similar observations were made in the case of pure compounds. Of the 17 known secondary metabolites which have shown antidiabetic activity, namely, zeorin, methylorsellinate, methyl-
Importantly, methylorsellinate, methyl-
Antioxidant activity of ethyl haematommate, ethyl orsellinate, and brialmontin 1 is not reported, whereas zeorin has not shown potent antioxidant activities in DPPH, SOI, NO, and metal chelating assays [
Diverse antidiabetic benefits of lichen compounds could be summarized as inhibition of starch digestion by inhibition of digestion enzymes (
Further, methylorsellinate, methyl-
Interestingly, most of the above bioactive compounds are ubiquitous compounds and it would be beneficial to develop novel techniques for direct identification of these compounds in a given extract, rather than the laborious and hectic processes of isolation, purification, and structure elucidation. A recent report on “Rapid identification of lichen compounds based on the structure–fragmentation relationship using ESI-MS/MS analysis” [
However, there is a need for more precise investigations to examine the clinical value of both isolated pure compounds and crude extracts and to elucidate their mechanisms of action. Apart from clinical validation and elucidation of their mechanism of action, biosafety studies of the compounds are also important to legitimately use the potential bioactive compounds for the further development of future lead drugs.
Lichen metabolites have demonstrated promising results as a reservoir of biological active compounds. Even though the studies on antioxidant activities of lichens have a comparatively long prior history, the reports on the potential of lichens as antidiabetic agents have evolved in the very recent past. Even from the limited data, the diverse diabetic potential is signified. Several lichens extracts have shown promising effects both in the antioxidant and in the antidiabetic assays. Interestingly and importantly, out of the 22 lichens extracts studied for their antidiabetic potential, 19 have already been established as antioxidants in separate studies. Likewise, of the 17 known secondary metabolites which have proven antidiabetic activity, 13 are recognized as antioxidants in various assays. Thus the study shows that there is a good accordance between antioxidant and antidiabetic activity of lichens.
This review points out the importance of studying lichen specific, polyphenols as
A detailed study of the potential protective role of these agents needs to be carried out to exploit their potential for the effective treatment of DM and associated complications.
Even from the limited number of studies it can be concluded that lichen-derived bioactive compounds hold great promise for biopharmaceutical applications as reported for antidiabetic activity and also antioxidant properties and point out the need to look into gathering the scarce and scattered data on biological activities for effective utilization.
However, unfortunately, lichens have been essentially overlooked to a great extent by the modern pharmaceutical industry, despite all the evidence of biological activity in lichen extracts provided in literature.
The authors declare that there are no competing interests regarding the publication of this paper.