An integrative review of the biology and chemistry of lichens and their ecological, ethnopharmacological, pharmaceutical and therapeutic potential

This purpose of this paper is to review and evaluate published literature on the biology and chemistry of lichens and their ecological, ethnopharmacological, pharmaceutical and therapeutic potential. A systematic method was used to gather literature on “the biology and chemistry of lichens and their ecological, ethnopharmacological, pharmaceutical and therapeutic potential.” A total of fifty-five research papers published between the years 1963 to 2022 were selected and utilized for this review. Tables were used to present the results. The subtopics were then chosen using a subjective method: lichens and their benefits/ importance. In this paper, eight (8) ecological functions and fourteen (14) pharmaceutical properties and therapeutic potentials were evaluated and presented. Lichen biology and chemistry and their roles in ethnopharmacological are also discussed. Additionally, lichens as pioneer and keystone species and their role as bioindicators to assess ecosystem health, sustainability and productivity was also addressed in this research. The published papers established that lichens have many benefits and importance, they are capable of synthesizing a range of chemicals that are beneficial to us and they are used in both traditional and pharmaceutical preparation of different treatments to combat many different diseases that affect human beings. More studies to investigate the uses of lichens should be done, especially in neotropics as there is a paucity of data and in this biodiversity rich region.


Lichens
Lichens are slow-growing organisms that can endure extreme climatic changes for hundreds of years [19], [99]. Theophrastus, the Father of Botany, popularized the term "lichen" for a class of plants in the scientific community around 300 BC [19], [120], [121]. There are between fifteen to twenty thousand (15,000-20,000) species of lichens in the world. According to Peterson and Ikeda (2017), Grimm et al. (2017) and Bhagarathi et al. 2022, many of them are specialized to particular habitats and seldom across the landscapes.
Over time, lichens have been variously categorized as a single organism, gradually mistaken for bryophytes (mosses), or for seaweeds due to previous descriptions based on their outward appearance. The complex anatomy of lichens was only discovered and documented by scientists after the invention and use of microscopes in the early 1800s [19], [62], [116], [186], [187].
Lichens are thought to be complex living organisms that are created through symbiotic relationships between a fungus and an alga or cyanobacteria [19], [118], [175], [176], [204]. The mycobiont is a heterotrophic fungus that forms the main body of the lichen and is thought to be the dominant partner that gives the lichen its distinctive features, including the shape of its thallus and the type of fruiting body. The photobiont, which is typically found between the upper and lower fungal cortex, is an autotrophic algae or cyanobacterium [19], [62], [97], [116], [175], [186], [187], [191], [204].
Lichens are sometimes referred to be pioneer species since they invade many settings. The majority of terrestrial habitats, including hot deserts, rocky beaches, and tropical rainforests in the tropics as well as frigid polar regions like the arctic tundra and even high-altitude environments, contain them. Other extreme habitats, such as toxic slag heaps, are also home to lichen species [19], [80], [116]. Ascomycetes make up more than half (50%) of the known species of lichenized fungus, which have an estimated range of thirteen thousand five hundred to twenty thousand (13,,000) species globally [19], [77].

Lichen Morphology
The mycobiont is heavily influenced by the morphology of lichens. In a lichenized partnership, the mycobiont creates around 80% of the lichen thalli and the photobiont creates the remaining 20%, but there are exceptions to the thallus development pattern [144]. The phylum Ascomycota, where about forty percent (40%) of species maintain symbiotic interactions, is where the majority of lichenized fungi are found. Approximately 98% (98%) of lichens also associate with an Ascomycota mycobiont [120], [121], [158], [181].
The phylum Deuteromycota contains the second-highest proportion of lichenized fungi in the fungi kingdom. When fungal sexual reproduction has never been seen, they are sometimes referred to as fungi imperfecti [181]. Additionally, roughly twenty (20) of the total species are from the phylum Basidiomycota and are lichenized [181]. Examples include species of agarics like species of Lichenomphalia, corticioid fungus like species of Dictyonema, and clavarioid fungi like species of Multiclavula. Lichens adopt the scientific names of their mycobiont in accordance with the International Code of Botanical Nomenclature (ICN) norm for algae, fungi, and plants [118], [121], [158].
Lichens can be distinguished from other organisms by the variety of thallus shapes and morphologies. The fruticose lichens ( Figure 2) have a multi-branched, leafless, or mini-shrub growth pattern similar to Usnea species. They often stand upright or hang down, and the limbs on their three-dimensional plants either have a circular cross-section or are flattened. The foliose lichens (Figure 2), including Lobaria pulmonaria (L.) Hoffm, thrive best in a two-dimensional environment. Like Pertusaria scaberula, the crustose lichens ( Figure 2) stick firmly to the substrate and tend to resemble a thick layer of paint. Squamulose lichens, such as Phyllopsora santensis, have thin scales that resemble leaves and are crustose at their tips and bottoms. As opposed to Chrysothrix xanthine, which has a distinct fungal and algal layer, the majority of leprose lichens are powdery, composed of granular particles, and lack an organized thallus [86], [120], [121], [158], [204]. Other lichenized forms are referred to as micro-lichens, whereas members of the foliose and fruticose lichens are categorized as macro-lichens [61].
The degree of necessary synergy for the partners involved gradually changes. Twenty percent (20%) of all lichens contain the green alga Trebouxia, which is infrequently encountered as a free-living organism. Some phytobiont genera, such as Gleocapsa, Nostoc, Scytonema, and Trentepohlia, can, on the other hand, frequently be found in both their lichenized and their free-living states [105]. In some instances, the lichenized symbionts (Collema and Peltula) and the free-living populations (Nostoc and Scytonema) coexist in the same habitat, such as desert soils.
Additionally, because only a few lichen algae have been identified as species and because the systematics of the majority of cyanobacteria and unicellular green algae have not been thoroughly researched and assessed, it is difficult to describe how a single phytobiont species can exist in both a free-living and a lichenized state at the same time [13]. Last but not least, it has been observed that the majority of lichens are very specific with the photobiont selected [14], [146], [158].
Due to competition with other fungi and/or nutrient intake by other living species, the growth of the mycobionts is often quite slow, and they are unlikely to survive well in a free-living form [117]. Later, various thalli of lichens belonging to the same lichen species have also yielded multiple photobiont species, such as Trebouxia [47], [70], [158].

Lichen Thallus Structure
The lichen thallus, which is an alliance of fungus and alga, was originally shown to have a dual nature by Swiss botanist Schwendener in 1867. Fungal hyphae make up the thallus, which is the vegetative tissue that makes up the lichen's body. A mesh, which may be loose or dense, is produced by the filaments branching outward. Normally, the photobiotic cells are surrounded by the fungus's mesh, which keeps them enclosed within its intricate tissues. Studies have shown that the cortex, a layer of fungus hyphae that protects the thallus, can exist or not ( Figure 3) [12], [67], [103], [118]. Only one cortical layer, which wraps around the branches, is present in fruticose lichens ( Figure 4). Foliose lichens, on the other hand, have a distinct lower cortex present on the bottom side of their structure and an upper cortex present on the top side ( Figure 4). Only the upper cortex is found in the lichens that are crustose and squamulose ( Figure 4). The lichen is in intimate contact with the substrate from the interior of its body. There is no cortex in the other lichen body groups of gelatinous, filamentous, leprous, byssoid, etc. This form of lichen is referred to as ecorticate (absence of cortex) [12], [67], [103], [118].
Additionally, the photobiotic layer, which is located underneath the cortex, is less densely packed and contains the photobiotic partner that is embedded inside the fungal filaments ( Figure 3). The less dense packing subsequently makes it possible for air to move about during the photosynthesis process. The medulla is located beneath the photobiotic layer ( Figure 3). In comparison to the layers above it, the medulla is less densely packed with hyphae. Most crustose and squamulose lichens maintain touch with the lichen substrate through the medulla layer [12], [67], [103], [118].

Lichen Reproduction
Lichens have the ability to reproduce either sexually or asexually, depending on the fungus partner. The majority of the time, the projecting lichen thallus structures found on the surface are crucial for sexual reproduction. Only the fungal partner reproduces sexually in this lichenized connection. Before a functioning lichen symbiosis may develop, fungal spores must be dispersed and come into contact with a suitable photobiont [2], [67], [118], [172].

Figure 5
Reproduction strategies utilized by lichens (Beigel, 2023) Basidiomycete-symbiotic lichens produce mushroom-like reproductive structures that are similar to those of their nonlichenized ancestors. The majority of lichens develop spores in organs referred to as ascomata and are connected with an ascomycete symbiont. The most prevalent varieties of ascomata are apothecia, which are cup-or plate-shaped structures ( Figure 5), perithecia, which are immersed structures in the thallus, and pycnidia, which are structured like perithecia but lack asci. The apothecia feature a layer of exposed asci, which are the cells that produce spores. Apothecia typically have a hue that differs from vegetative tissues. Many species of lichen appear to reproduce primarily by their sexual spores, and many are capable of creating large numbers of sexual structures [67], [118], [172].
Lichens that are unable to reproduce sexually do so by using vegetative reproduction, which can either be accomplished by breaking off a portion of their thallus and letting it grow on its own or by dispersing diaspores, which are little spheres of algal cells that are covered by fungal cells. The fruticose lichens are easily broken apart, and the broken pieces can produce new lichens. During dry seasons, a lot of lichens break apart, and the pieces are carried away by the wind. Later, when moisture returns during the wet seasons, they start growing again. Small clusters of algae cells known as soredia ( Figure 5) are encircled by fungus hyphae. The soredia are created in the soralia, and the wind also scatters them like shards. According to Hoegger (1993), Sillett et al. (2000), and Kirika (2012), isidia ( Figure 5) are branched, spiny, elongated outgrowth structures from the thallus that separate for mechanical dissemination.

Nutritional Aspects of Lichens
Lichens are easily found in boreal woodlands and provide a large amount of non-structural carbohydrates. They are also poor in easily digestible fibers. This characteristic also offers adequate energy, and small mammals in the wild frequently consume them. In the winter, herbivorous animals such reindeer, caribou, squirrels, marmots, musk oxen, lemmings, and Eurasian deer devour various portions of the lichen condition. The lichen Aspilicia esculenta is also consumed by Libyan sheep that graze in the desert, and saxicolous lichens are occasionally eaten by various mollusc and insect species [34].
Therefore, the majority of lichens contain nutritional components. For instance, Cladonia stellaris has 2% water-soluble carbohydrates, 3.1% crude protein, 78.4% hemicellulose, and the remaining 1.7% cellulose [74]. The therapeutic and frequently consumed edible lichen Bryoria fremontii is found in North America and is used by many different populations to prevent famine. The three main types of structures produced by lichens are α-glucans, β-glucans, and galactomannans [4], [127]. Lichens also include necessary polysaccharides. It is proposed that the lichen polysaccharides of the β-glucan and galactomannan types have chemotaxonomic significance. It was discovered that the photobiont produced a wide range of polysaccharides, while the mycobiont in the lichenized relationship produced polysaccharides that are identical to the parent lichen [182].
Furthermore, nitrogen may be constrictive and affect lichen development and spread, and as a result, little is known about the sources of nitrogen that are readily available and the rates at which lichens acquire nitrogen in their natural environments. Furthermore, the problem of how various lichens differ in their capacity to absorb various N compounds has been poorly addressed [35], [85]. Along with chlorophylls and phycobilins, which are known to act as light energy receptors and aid to stop chlorophyll from being degraded by molecular oxygen, lichen contains a number of carotenoids that range from 23.25 to 123.5 g/g of dry weight [139].
The products lichens synthesize can protect them from different nutrient deficiencies e.g., dibenzofuran Usnic acid. This acts as an extensive secondary cortical metabolite produced by lichen forming fungi that promotes intracellular absorption of cupric ions (Cu2+) in epiphytic lichens. As a result, lichen generates divaric acid depside and usnic acid hence, indicating that this depside facilitates the absorption of Cu2+ in order to survive in habitats where nutrients are low [65].

Lichen Substrate Preference
Lichens are well known for thriving in practically every type of terrestrial habitat, including aquatic habitats [37], [132], 148]. Lichens are widely known for their capacity to colonize a wide range of man-made and organic substrates. Peat mosses, tree bark, rocks, wood, soil, and even other lichens, the backs of sloths, some insects, and broad evergreen leaves are examples of natural lichen substrates. Plastic, glass, metal, concrete, and cloth are examples of artificial substrates where lichens can be discovered [26], [148].
Lichens can grow on practically any firm surface, and some stray or tumbleweed lichens float over parched soils while others grow unattached. Epiphytic lichens include those that develop on wood, bark, or even organic fence materials [37], [132], [148]. Lichenologists classified lichens based on the type of substrate they grew on, such as foliicolous lichens that grew on vascular plants' leaves or corticolous lichens that grew on living plants' bark [26], [148], [163]. The saxicolous lichens live on rocks and can be divided into two (2) separate groups: siliceous lichens, which live on acidic rocks, and calcareous lichens, which live on basic calcium-rich rocks like limestone, cement, and even pavements. According to Davis (1999 Biocrusts, also known as biological soil crusts or simply biocrusts, are essential soil enhancers and even function as stabilizers in many desert habitats [37], [132], [148]. Terricolous lichens that grow alongside moss and free-living cyanobacteria help to generate biocrusts. Lücking coined the word "plasticolous" in 1988 to describe the lichens that develop on plastics.

Lichens and Host Plant Specificity
Lichens often display preferences for particular tree species when choosing where to live. This can be affected by the bark's characteristics, as well as its microclimate and chemical circumstances [191]. Understanding host specificity is crucial when examining the ecology and distribution of lichens, and having a solid understanding of the degree of specificity can be helpful for calculating and tracking lichen diversity and conservation. For instance, depending on areas, forest types, and different species of phorophyte (host), the substrate factors can affect the lichen distributions [191].
According to Rosabal et al. (2013), the texture, water interactions, and chemical composition of plant bark, including pH, are crucial substrate characteristics that control the dispersion of lichens like corticolous lichens. In 2003, Gradstein et al. reported that the bark's roughness has a significant role in the development of lichenized symbionts. When investigating substrate ecology, the diameter of the trunk is considered as relates to the age of the tree. Another element that affects the distribution of lichen is bark moisture, however even on the same tree, this parameter can change frequently because microhabitats and microclimates differ depending on tree height [152], [191]. As a result, due to the chemistry of the bark, certain inorganic and organic chemicals, ash content, and pH may have an impact on where lichens are distributed. Although phorophytes are significant, there is no evidence that lichen-phorophyte specialization exists in some tropical forests [152]. Despite this, there are still a number of factors that can alter the spread of lichens.

Lichen Distribution and Habitats
Numerous abiotic elements, such as the availability of moisture, light, wind velocity, and temperature, can have an impact on lichen formation. Lichens have a variety of habitats and can thrive in various environments [18], [19], [51].
There are resilient lichen species that can endure in frigid tundra and scorching deserts. Their ability to survive drying and their complex chemistry are the two (2) primary traits that are claimed to have had a substantial role in their formation [19], [79], [117], [158].
Globally, lichens are found in a variety of environments, including the freezing Antarctic continent's most southerly rocks, tropical rain forests, and even deserts with no predictable annual precipitation. Rock shorelines, freshwater lakes, and mountain streams are examples of semi-aquatic locations in marine tidal zones where certain lichen species can be found. Formerly known as the western populations of Peltigera hydrothyria (or Hydrothyria venosa), the Peltigera gowardii is a species of lichen that even thrives permanently submerged in places like spring-fed mountain streams [19], [37], [132].
Many lichens and mosses, which are prevalent in many terrestrial ecosystems, tend to create a gradient, with mosses predominating regions that remain the wettest throughout the year (though some lichens are present) and even lichens predominating areas that remain the driest. In the lichens themselves, several slopes are frequently visible. The Pacific Northwest and the mountains and conifer forests of northern California are among the regions where the chlorolichen species can be found. They have common mossy zone that are close to the ground; as they mature and long fruticose lichens known as alectorioid lichens (generally Alectoria and Bryoria) colonize the mid-canopy of trees; then as the oldgrowth conditions develop, cyanolichens will start to colonize a specific zone in the lower canopy of the tree, just above a mossy understory [19].
Some lichens have evolved to inhabit more compact microhabitats. Around a tree trunk, gradients may be present. Mosses may predominate in the areas that receive the most moisture from the canopy drip, followed by larger fruticose and foliose lichens. Researchers may locate a variety of powdered crustose leprarioid lichens and tiny pin-lichens with tiny stalked fruiting bodies when they move to protected locations without direct liquid water. The best development of these protected microhabitats occurs in very old-growth forests. A single enormous rock's face is another location where extremely similar gradients are frequently encountered [19], [82], [131].
There is extremely little vegetation and a harsh environment in the icy Antarctica. The most prevalent types of creatures in this area are lichens, of which roughly 350 species have been identified in the Antarctic region [19], [79], [151]. The prominent fruticose lichen of the Usnea and Umbilicaria genera, which can grow to a height of about twenty centimeters (20 cm), is thought to be the largest primary producer in these Antarctic biomes. The shape and size of some crustose lichen thalli on the sandstone varies greatly [19], [48]. According to Kappen (1988) and Bhagarathi et al. (2002), lichens can quickly and easily desiccate up to 97% of their water content to develop into an anabiotic illness. Psoroma antarcticum was recently discovered by Park et al., 2018, in the South Maritime Shetland and the South Orkney Islands of Antarctica. The cup-shaped apothecia, smaller ascospores, and thalli with gray to black melanin are some of the distinctive characteristics of this new species, which is closely related to the lichen Psoroma hypnorum [19], [129].
Poikilohydric lichens are lichens that can withstand water deficiency for an extended period of time and resume physiological functions when the conditions are right [9], [19], [92], [197]. When a gene from lichens is transferred to other organisms that battle water scarcity everywhere in the world, its role can be understood [8], [19], [50], [204]. Different studies later shown that lichens' ability to endure drought was largely attributed to their antioxidant capability [19], [76], [196]. Further investigation found that the redox status of reduced glutathione and oxidized glutathione during drying and rehydration is sedated when three (3) lichens with the ability to endure drought are exposed to heat stress [19], [91]. For instance, the lichen species Endocarpon pusillum discovered that the antioxidant capacity under twenty percent (20%) of PEG-induced dehydration stress was associated to the up-regulation of the antioxidant enzyme, glutathione and thioredox in gene [19], [196]. The Endocarpon pusillum mycobiont region is characterized by a single Trx protein with the ability to function as a disulfide reductase and a chaperone in transgenic yeasts. As a result, the mycobiont is more resistant to drought than the phycobiont [19], 98].

Lichen Chemistry
According to estimates, lichens create 600 secondary metabolites, commonly referred to as lichen compounds [120], [121], [193]. Additionally, out of all these lichens, roughly 550 of these chemicals are only found in lichens and cannot be found in any other plant groupings. Additionally, the most crucial factor in the identification of lichen is chemotaxonomy. By using a color spot test, thin layer chromatography, or even high-performance liquid chromatography (HPLC), the compounds that lichen synthesizes can be detected [120], [121], [193].

Lichen Metabolites
Lichens can produce a vast variety of secondary metabolites, the most of which are unique. The various lichen chemical compounds will assemble on the external surfaces of the fungal hyphae where they are present. According to Lauterwein et al. (1995), lichens are capable of creating a wide range of physiologically active primary (intracellular) and secondary (extracellular) metabolites.

Bioactive Metabolites from Mycobionts
Usnic acid was identified by Ingolfsdottir in 2002 as having significant therapeutic potential among the common metabolites present in lichen. Usnic acid has been incorporated into various weight reduction solutions since it is a powerful stimulant for the metabolism of cellular energy. The lichen-derived substance Methyl-orcinol carboxylate is patented and used to treat methicillin-resistant Staphylococcus aureus. It also has the potential to treat pathogenic human fungi that are resistant to polyene and the antibiotic azole [83].
According to Carlin (1987) and Vráblková et al. (2006), lichens have an abundance of pigmentation that can change depending on the amount of irradiance during the course of the year. The pigments allow for the screening of ultraviolet B for melanin and parietin; Collema cyanobacterial lichen patent offers about 80% UVB irradiation protection [192]. Because anthraquinones are present in some lichen species, such as Heterodermia obscurata and Nephroma laevigatum, they can be used as colors. Additionally, in the paper industry, they serve as catalysts in the production of wood pulp [32], [115].

Bioactive Metabolites from Photobionts
According to Burja et al. (2001), certain cyanobacteria from both marine and freshwater ecosystems produce a wide range of peptides and are a plentiful supply of blended peptide polyketides. The Nostoc spp. strain IO-102I, which is associated with lichens, produces microcystins, one of the most often identified bioactive substances [126]. Carotenoids, another biologically active substance, are naturally occurring, economically important pigments that are frequently found in free-living green algae Trentepohlia and algal lichen symbionts [117]. In addition, cyanobacteria and green algae derived from lichens are an important source of beneficial qualities, particularly medicines [155].

Ecological Functions of Lichens
Like coral reefs, lichens also tend to create a variety of habitats for other kinds of creatures and boost the productivity of ecosystems in a variety of environments, from hot deserts to tropical forests [111], [131].  Nitrogen is thought to be a limiting element that helps many ecosystems produce successfully. The cyanobacteria in the cyanolichens contribute to nitrogen fixation by transforming atmospheric nitrogen into a form that plants can utilise. In the Pacific Northwest, the nitrogen-fixing lichen Lobaria oregana is widely known for its contributions to the ecosystems of old growth forests. In the Andrews Experimental Forest in Washington state, nitrogen fixing rates for L. oregana, which occupies several forests in California's northern coastal ranges, have been estimated to be as high as 16.5 kg/ha/year. Lichens have an important role as a supply of nitrogen for healthy desert ecosystems as part of biocrusts. For some species of vascular plants, biocrusts also help to boost the availability of nutrients in the soil.

Promote Seed Germination
Biocrusts have been documented as changing seed germination and subsequently influencing the composition of vascular plant communities by physical soil binding or chemical leachates. It has been documented that biocrusts in the western dry habitats prevent the germination of invasive annual grasses, and this may be the mechanism for the reciprocal exclusion of biocrusts and annual grasses. Many initiatives have started to create ways to spread biocrusts for restoring dry lands.

Microhabitat for Microfauna
Large colonies of arthropods and other tiny organisms like tardigrades can find a variety of habitats in lichens, notably in their foliose and fruticose forms. It has been discovered and proven that these communities have an impact on the bird populations that eat those arthropods. Numerous spiders, lizards, and (Richardson 1974), (Pettersson et al. 1995), (Young & insects have developed ways to blend in with the lichens. The peppered moth in England, which changed into a light form and became rare when it was subjected to predation, is considered the most renowned instance of lichen mimicry that has been recorded. Lichens were widely eliminated from populous areas during the industrial revolution as a result of air pollution. for studies and evaluations of air pollution, and their ability to accumulate metals makes them important for minerology. Lichens absorb various chemicals to which they are exposed. The composition of the lichen community can be used to infer pollution levels in the environment because many distinct lichen species exhibit varying levels of tolerance to air pollution. Additionally, additional environmental elements like the legacy of old-growth conditions found in forests can be inferred due to the presence or lack of specific species. Since lichens require clean, fresh air to properly support their growth, another significant characteristic of lichens is that they cannot tolerate pollution. Because of this, lichens are able to take in carbon dioxide and heavy metals from the atmosphere. As a result, lichens contribute significantly to biodegradation by dissolving contaminants such as polyester, lead, copper, radionuclides, etc. that are harmful to the environment. Lichens are also utilized to break down a variety of viruses and other environmental reservoirs that have the potential to infect humans, animals, and plants with severe infectious diseases. Sulfurous and nitrogenous oxides in some agroecosystems can harm delicate lichens. By observing and measuring the levels of pollutants in a specific lichen species, environmental scientists and researchers can use this property of lichen to estimate the degree of pollution in a given ecosystem. Because of this, lichens are regarded as superior biomonitors of healthy ecosystems. The abundance of epiphytic lichens and the build-up of heavy metals in the thalli of one species of corticolous lichen, Parmerlia caperata, were used by Loppi & Corsini, 2003, as indicators of air pollution in Pistoia, central Italy.

Ethnopharmacological Aspects of Lichens
Since the beginning of time, humans have been dependent on different plant species for many reasons, with health being the most important. Traditional knowledge (TK) incorporates the skills, practices, and cutting-edge technology of local and indigenous cultures from all over the world. Indigenous communities pass on their traditional knowledge verbally from generation to generation. Since its development, TK has been useful and usable in a variety of fields, including forestry, agriculture, horticulture, fisheries, and even health [134].
The most common sources of medicine are plants, and they have been carefully described in various traditional medical systems, including Tibetan medicine, Indian Ayurveda, Traditional Chinese Medicine (TCM), Western Medical Herbalism, and Indian Ayurveda [107]. 11,146 types of medicinal plants are used in Traditional Chinese Medicine. Ayurvedic pharmacopeia in the Indian subcontinent has between twelve and fifteen hundred (1200-1500) plant species, of which an estimated ten thousand (10,000) species are used for therapeutic purposes [166].
The ethnic applications of plants found in many parts of the world have been acknowledged in several literary works throughout the years, but because the ethnic uses of lichens are not widely recorded, they were disregarded. In the course of history and even in the modern world, many ethnobotanists have disregarded cryptogams. However, a number of temperate nations around the world, including those in Asia, Africa, Europe, and the United States, have been conducting in-depth research on lichens. Additionally, various Asian nations, such as India, China, Nepal, and Tibet examined and documented the ethnic features of lichens [33], [39], [93], [187], [195].
Studies on lichens have also shown that they are widely used as traditional foods, medicines, and sacred sacrifice fires known as "HAVAN" or "HOMA" in religion. They also serve a critical role in healthy ecosystems and human welfare. Lichens were then widely used by medical professionals during the medieval ages [39]. In an Egyptian vase from the 18th Dynasty (1700-1600 BC), the lichen Evernia furfuracea was employed as a medicine. Due to their wide availability and high nutritional content, lichens were predominantly employed as a food source in Europe. In the Atharveda (1500 B.C.), Shipal was the first to document the use of lichen as medicine [187]. Additionally, charrila, a crude medicine derived from Parmelia, is widely available in Indian marketplaces and is used to treat a variety of illnesses [30].
There are numerous reports of lichens being used extensively by different ethnic groups in India. Heterodermia diademata (Physciaceae) was used in the treatment of cuts and injuries, Parmelia cirrhata (Parmeliaceae) was used as a kitchen vegetable, Peltigera polydactyla (Peltigeraceae) was used to stop the bleeding, Stereocaulon himalayense (Stereocaulaceae) was found to be effective in the treatment of urinary trouble and blisters of the tongue. In 2016, Pathak et al. reported that villagers in Sikkim and Tamil Nadu, India, used the lichens Hypotrachyna cirrhata and Flavoparmelia caperata to treat various wound infections, burns, and bites. Shah documented the use of three (3) lichen species, primarily Parmotrema nilgherrense, Everniastrum nepalense, and Everniastrum cirrhatum, for domestic pharmaceutical purposes between the years 1998 and 2014. In addition, Buellia cf subsoriroides, which is useful as a substitute for "henna" in the Garhwal region of India, and Parmeli asancti-angeli, which is used by the Gond and Oraon tribes of Central India to treat white patches around the throat that result in a skin condition similar to ringworm [188]. In 2012, Vinayaka and Krishnamurthy recorded the ethnobotanical uses of six (6) lichen species from separate tribal communities in southern India, Parmotrema reticulatum, P. tinctorum, Ramalina pacifica which are widely utilized as food, Heterdermia diademata and P. cristiferum which as strong medicinal potentials, and last but not least, Usnea galbinifera used for pillow stuffing and decorative purposes. According to Kala (2002), the Bhotiya tribal group in Uttaranchal, India's high-altitude Garhwal Himalaya, employs lichens as a source for natural dye. In 2017, Devkota et al. listed seven (7) species of lichen that are used by nine distinct Nepalese populations, including Everniastrum cirrhatum, Parmotrema cetratum and E. nepalense that are used in food preparation, Heterodermia diademata and Ramalina species utilized for its therapeutic purposes, Usnea plicata which is used as a part of rituals, esthetic and bedding products, and Thamnolia vermicularis utilized as spiritual and esthetic.
Heterodermia diademata and Eupatorium odoratum were both utilized by the Limbu community of eastern Nepal to treat cuts and wounds, according to Limbu and Rai (2013). According to Kunwar et al. (2010), lichen decoction and extract can be used to cure moles in Nepal. Ahmadjian and Nilsson (1963) documented the lichen Cetraria islandica and it is widely advertised in Swedish apothecaries and is effective in treating lung disease, diabetes, and catarrh. Three sinensis. They also identified five lichen species that are used to make medicinal teas: Lethariella cashmeriana, L. semanderi, L. sinensis, Thamnolia vermicularis, and T. subulifor.
Similar to this, Song and Gang (2013) reported a large number of lichen species that are utilized by Chinese indigenous populations. Headaches and vertigo are treated by the lichen Cladonia amaurocraea. When someone is coughing up blood or has cuts or scalds, Cladonia cervicornis lichen is applied. Cladonia pyxidata extracts were used to treat bacterial skin infections, and Cladonia fenestralis is used to make a medicinal tea. Additionally, they list Rhizoplaca chrysoleuca, which is used to treat intestinal blockage, pain alleviation, burns and scalds, tuberculosis, and skin diseases. The lichen Bryoria asiatica is used to treat kidney disease, vertigo, heart palpitations, and problems urinating. Additionally, headaches, coughs, infections, pulmonary TB, and irritated lymphatic vessels are treated with Usnea ceratina. Usnea plicata can also be used to halt bleeding, relieve pain, and stop bloody feces. Drinking Cetraria islandica's decoction helps digestion and fortifies the stomach's walls. Other lichens, such as Parmotrema tinctorum, are used to treat swelling, ulcers, bleeding from wounds on the outside, and hazy eyesight. Contrarily, Punctelia borreri lichens are also used to treat exterior wounds, uterine bleeding, and blurred vision.

Pharmaceutical Properties, Therapeutic Potential and Biological Activities of Lichens
Lichens can live in some of the harshest environments on Earth, and many of their medical uses can be advantageous to academics and researchers. Lichen acids are the name given to the secondary metabolites that lichens manufacture. Lichen acids are formed by mycobionts and are dispersed over the surface of lichens as amorphous or crystals [165], [197]. Lichen acids have a variety of biological potential which includes antioxidant, anticancer [197], enzyme inhibitory [121], antiviral [43], antifungal [124], antidiabetic [49], allelopathy [59], antipyretic, crop growth inhibitory, cytotoxic, anti-hepatotoxic [168] and antiproliferative properties [52]. In the pharmaceutical industry, several lichens are also frequently employed as anti-infectives to create anti-mycobacterial, antiviral, and other anti-inflammatory drugs [19], [28].

Anti-Bacterial Activities
Some lichens, such as Usnea and Cladonia, which produce usnic acid and are used in the pharmaceutical manufacturing of ointments to treat burns and wounds, are employed for their antibacterial characteristics. Four ethanolic extracts produced by lichens that have strong antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Proteus vulgaris, Escherichia coli, Klebsiella pneumonia and Listeria monocytogenes. The active compounds xanthones derivatives of lichens have antibacterial activity against multi-drug resistant pathogenic microbes such as Enterococcus faecalis and Staphylococcus aureus. Recent research revealed that the synthesis of eco-friendly biogenic manufacturing of silver nanoparticles from the lichen Usnea longissimi. These synthetic nanoparticles, is more cost-effective and can avoid pollution from the atmosphere. The size of each synthetic nanoparticle between the 9.40-11.23 nm range are involved in the function of usnic acids, amines, phenols, aldehydes and ketones in reducing silver into a silver nanoparticle. The active nanoparticles possess gram-positive antimicrobial activity (Streptococcus pyrogenes, Streptococcus mutans, Corynebacterium diphtheriae and Corynebacterium xerosis) and gram-negative antimicrobial activity against strains (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneuomoniae). The lichen extract showed significant antibacterial activity against burn wound-associated MRSA clinical isolates. P. furfuracea and E. prunastri acetone extracts shown significant activity with MICs ranging from 0.039 to 0.15 mg/mL and a bacteriostatic effect. Additionally, one MRSA was bactericidally destroyed by R. farinacea extract, with MIC values for all MRSA strains ranging from 0.078 to 0.625 mg/mL. Usnic acid, which was R. farinacea main antibacterial ingredient, might cause this activity. Atranorin and fumarprotocetraric acid had much less effectiveness against MRSA strains than usnic acid. Usnic acid disrupted the bacterial membrane, exhibiting excellent antibacterial activity against clinical isolates of MRSA with MIC values between 25 and 50 μg/mL. Several lichenic compounds, including lobar acid, physodic acid, rhizocarpic acid, 3-hydroxyphysodic acid, hybocarpone, and (R)-(+)-usnic acid, were found to be effective against methicillin-and multidrug-resistant Staphylococcus aureus. These compounds were isolated from the lichen species Sterocaulon dactylophyllum, Hypogymnia physodes, Psilolechia lucida, Hypogymnia physodes, Lecanora conizaeoides, and Lecanora albescens. Despite the fact that the antibacterial activity of lichens has been extensively studied, whether in the form of raw extracts or purified compounds, the mechanism of action of these substances has not been thoroughly evaluated. (Kokubun et al., 2007), (Zambare and Christopher, 2012), (Gupta et al., 2012), (Manojlovic et al., 2012), (Pompilio et al., 2013), , (Manisha, 2018), (Plaza et al. 2018), (Resende et al., 2018), (Siddiqi et al., 2018), , (Essadeqy et al., 2020), (Bhagarathi et al., 2022) Antiviral Activities Chromatographic methods are used to purify usnic acid and parietin from the extract of the lichen Teloschistes chrysophthalmus. Use usnic acid and parietin purified products for their antiviral activity and virucidal effects (against Junin and Tacaribe arenaviruses, respectively) when appropriate. This experiment, known as a "virucidal assay," was carried out directly on the virus cell nuclei to check the effectiveness of the activities against the viral cell-inactivating traits. As a potential bioterrorism agent, the arenavirus JUNV (Junin virus) has been studied as a model system because it is known to induce hemorrhagic Argentine fever in humans. Usnic acid may reliably reduce the amount of JUNV produced by infected Vero cells by a dose of 9.9 and 20.6 micrometers, respectively. It is possible to use usnic acid in a dose-dependent manner to lower the output of JUNV from infected Vero cells (9.9 m and 20.6 m, respectively). (Damonte & Cote, 2002), (Rotz et al., 2002), (Fazio et al., 2007), (Zambare & Christopher, 2012),  Anti-Insecticidal Activities Over time, killing mosquito larvae has proven to be an effective method of reducing the mosquito population in various breeding grounds before they mature into adults. The most extensively used insecticides are based on

Tyrosinase-Inhibitory Actions
Tyrosinase is considered to be a key enzyme in various mammalian cells and it helps to avoid excessive melanin pigment production. Melanin possesses the property of absorbing ultraviolet radiation in order to safeguard the skin and also removing reactive oxygen species (ROS) in the skin of mammals. It therefore plays an integral role and widely utilized in the cosmetics and the medicinal sectors. The inhibition of the surplus of tyrosinase enzyme manufacturing is therefore necessary. Some species of lichens has the potential property to prevent the activity of tyrosinase. In some lichen species such as Graphis assamensis, Graphina multistriata, Graphis Phaeographopsisindica, and Graphis nakanishiana, are capable of tyrosinase inhibitory activity which occur considerably. Additionally, some edible and medicinal lichen species disclosed tyrosinase inhibition property (Usnea plicata and Umbilicaria esculenta). (Briganti et al., 2003), (Behera et al., 2006) (Kim & Cho, 2007), (Nguyen et al., 2016), (Zambare & Christopher, 2012).

Allelopathy Activities
Allelopathy is thought to be a natural process where one organism produces allelochemicals, secondary metabolites, that can have either positive or negative effects on another organism. Due to the presence of secondary usnic acid metabolites, the lichen extract has adverse allelopathic effects on bryophytes (moss Physcomitrella) by suppressing protonemic and gametophore development. Parmelia reticulate, a Himalayan lichen with allelopathic potential, can prevent the growth of weeds like Phalaris minor, which grows among wheat and barley plants. The effects of the secondary metabolites of saxicolous lichen usnic acid, parietin, and norstic acid as biocides to prevent ecotoxicity against the following micro-colonial bacteria Coniosporium perforans, Coniosporium apollinis, green algae Scenedesmus ecornis, and coccoid cyanobacteria Chroocococcus minutus were examined in a different study. shield yourself from radiation. There are many different kinds of sunscreen, including those for skin care, eyes, lips, and hair. Some higher plant species, mosses, and the majority of lichens can withstand desiccation. The photobiont component of the lichen contributes to the reduction of load segregation in Photosystem II (PSII) reaction centers, which helps to inhibit fluorescence emission. For instance, Parmelia sulcate, Peltigera neckeri, and Lobaria pulmonaria are three lichens that can block UV rays.

2013), (Clark & Hessler, 2015)
Anti-Hepatotoxic, Cytotoxic and Anticancer Activities Alcohol use can increase the levels of NADH/NADP in hepatocytes, which can stop the mitochondrial -oxidation of fatty acids. It can also increase the transit of lipids from the small intestine to the liver, which results in abnormal fat deposition in the body. The reindeer lichen, also known as Cladonia rangiferina, has been reported and studied for the treatment of fever, liver conditions, arthritis, convulsions, tuberculosis (TB), and constipation. Alcohol-related liver and tissue toxicity can be reduced by using the reindeer lichen extract. The pharmaceutical industry has recently placed a significant deal of emphasis on the anticancer potential of secondary lichen metabolites. Additionally, it is considered feasible to treat cervical cancer after receiving a pre-treatment of usnic acid (C18H16O7) and zinc sulfate (ZnSO4). Other varieties of lichen, such as Alectoria ochroleuca and Nephroma expallidum, are found in the Himalayas and Nepal and act as chemo preventives for cancer. The extract of Cetraria aculeata was discovered to have antigenotoxic potential in contrast to Salmonella typhimurium. In addition, certain lichens, such Collema flaccidum in particular, are members of the Collemataceae family and contain the active compounds bianthraquinone, colleflaccinosides, and glycosides, which have anticancer properties. With IC50 values of 12.72 and 15.66 μg/mL, the acetone extract of the Usnea barbata (usnic acid) lichen showed significant anti-cancer activity against human melanoma and human colon carcinoma cell lines. HepG2 cells can undergo apoptosis when exposed to the active ingredient usnic acid and its different derivatives (usenamines), which are taken from the lichen Usnea longissimi. The maximum cytotoxicity for the cell lines HCT-116 and SW480 was found in the ethyl acetate and acetone extracts from the lichens Pseudevernia furacea and Platismatia glauca, respectively IC50=21.2 ± 1.3 μg/mL and 51.3 ± 0.8 μg/mL. Subsequently, the lichen Stereocaulon alpnum gathered from the Antarctic region exhibit anticancer activities against human cervix adenocarcinoma (HeLa cells) and human colon carcinoma (HCT116 cells) cell lines because of the existence of lobaric acid and secondary metabolites of lobarstin. These secondary metabolites aid to improve the arresting of the cell cycle thus, causing important dose-and time-dependent reduction in the development of carcinogenic cells. P. furfuracea extract, when applied for 72 hours, was found to have the most impact on all cancer cell lines examined, particularly human prostate cancer (22RV1) cell lines. This outcome is consistent with that of the earlier work, which shown that E. prunastri and P. furfuracea extracts had cytotoxic effects on human melanoma (FemX) and human colon carcinoma (LS174), with IC50 values that are comparable to 55.09-120.89 µg/mL. Moreover, P. furfuracea demonstrated the most potent cytotoxic action. It was also shown that these extracts triggered cell death in LS174 and FemX cells by strongly arresting the cell cycle in the sub-G1 phase. Even at low concentrations, unprocessed lichen extracts or their constituent parts showed activity against many cancer cell lines. The IC50 values of three lichen extracts did not indicate strong cytotoxic activity IC50 > 30 µg/mL, while the physodic acid isolated from P. furfuracea vs. FemX and LS174 cancer cells with IC50 of 19.52 and 17.89 µg/mL demonstrated strong cytotoxic effect.

Antidiabetic Activities
Diabetes is a well-known physiological condition that is spreading throughout the world and causing a number of health-related difficulties. Currently, there are no medications available to treat diabetes. The most common type of diabetes, diabetes mellitus, accounts for 90% of cases and is characterized by chronic enzymatic hyperglycaemia. In the future, the field of lichens will be unbeatable for treating diabetes. The lichen Parmotremaha babianum contains anti-diabetic compounds that drastically lower blood glucose levels. Orally administered Cladonia humilis lichen extract significantly decreased blood glucose levels in rats with alloxan-induced hyperglycaemia. The natural substances in Ramalina sinensis are efficient against a variety of enzymes that participate in inhibitory processes. This particular lichen species has the potential to inhibit the activity of the -amylase enzyme resulting in a decrease in blood glucose level and prevent it from noninsulin dependent diabetes-type-2. The breakdown of starch by the -amylase enzyme leads to hyperglycaemia and this cause an increase in the blood glucose level. This lichen can suppress the -amylase enzyme activity leading in a drop in the blood glucose levels and prevent non-insulin dependent type-2 diabetes. When starch is broken down by the -amylase enzyme, the effect is an increase in blood glucose levels caused by hyperglycaemia.

Immuno-Modulatory Activities
Immunity can be activated or suppressed by a variety of modifications to the body's immune system and with the help of biological agents. Cetraria islandica, a lichen, has been employed in medicine to treat inflammatory conditions. Protolichesterinic and fumarprotocetraric, two chemicals, are produced, purified, and tested against dendritic cell maturation as determined by IL-10 and IL-12p40 secretion. When arthritis is treated with an aqueous lichen extract, the upregulated secretion results in the anti-inflammatory action. Lichens have taken part in numerous investigations exploring for novel natural antioxidants and their potential anti-chronic illness protective properties. The number of total phenols in the studied extracts demonstrated a strong in vitro antioxidant effect. This outcome was consistent with previously published research that shown a favorable relationship between the phenolic content and the antioxidant activity. Furthermore, there was no evidence of a connection between the lichen extract's flavonoid level and its antioxidant effects. Depsides, depsidones, and dibenzofurans are the main components of lichen that are in charge of the antioxidant properties. According to previous studies using acetone extracts of P. furfuracea and E. prunastri harvested in Serbia and Turkey, P. furfuracea extract had a larger antioxidant activity and the highest quantity of phenols than E. prunastri extract. Of the tested extracts, P. furfuracea extract demonstrated the best antioxidant power with the greatest concentration of polyphenolic compounds. The R. farinacea extract exhibited the highest ferric reducing power, but the least number of phenols, indicating that the presence of nonphenolic chemicals may be the cause of this extract's activity.

Production of Laboratory Materials
In order to create orcein, a biological stain, the lichen Rocella tinctoria is employed. Before litmus was made synthetically, the Rocella tinctoria could be used as a source of the pH indicator. Numerous colours used in laboratories, such as pH indicators, litmus tests, and other dyes, are derived from various lichen species.

Cosmetology
Some lichen species, such Ramalina and Evemia, are used to make incense sticks and as fragrant incense. Different types of scent are made using other lichen species, such as Lobularia pulmonaria and Evemia prunastri. The (Manisha, 2018), (BYJU'S, 2022), cosmetic industries use lichens as a natural medicine to cure a variety of rashes and skin conditions. Lichens were also acknowledged for their significant role in cosmetology. (Bhagarathi et al., 2022).

Conclusion
This review emphasizes the biology and chemistry of lichens and their ecological, ethnopharmacy, medicine pharmacy. Lichens have many roles, importance and benefits in the areas of food preparation, cosmetology, biological and ecological processes, pharmacological synthesis of drugs to treat different ailments and disorders of the human body; the full potential of lichens are not yet fully researched and documented in the scientific world. Lichens also play important roles in ecological process that contributes to the health and sustainability of ecosystems. Lichens play key roles in primary productivity as well as nitrogen fixation and promotes seed germination. Additionally, lichens serve as a suitable habitat for many microfauna (such as arachnids, insects and small reptiles like lizards) and macrofauna (like warm-blooded animals e.g., birds and squirrels). Lichens are considered as both pioneer and keystone species and they are very important in biomonitoring to detect air quality and pollution. Therefore, they can be used as indicator species by biomonitoring agencies, companies, other stakeholders to make strategic plans for environmental assessment. More research should be done when it comes to lichen biology and chemistry and their ecological, ethnopharmacological, pharmaceutical and therapeutic potential; especially in neotropical countries.