2.1. Fungi

Fungi are ubiquitous, occurring eukaryotic, heterotrophic organisms found worldwide in diverse habitats. Fungi have been used as remedies and in everyday life for thousands of years. Nearly 3000 years ago, fungi were used to treat intestinal ailments [8]. Fungi, especially endophytic fungi, are among the novel bioresources of natural bioactive compounds with their major biotechnological potential in the food industry, medicine, and agriculture. Numerous valuable bioactive compounds with a range of the bioactivities, such as antimicrobial, cytotoxic, and anticancer, have been successfully discovered from endophytic fungi [9]. Existing drugs of fungal origin include β-lactam antibiotics, cyclosporine A, ergot alkaloids, griseofulvin, lovastatin, and taxol; however, increasingly more novel natural products of the varied chemical structure be produced by fungi [10,11].

2.2. Bacteria

Bacteria are another important bioresources for the isolation and screening of bioactive compounds. Bioactive compounds such as alkaloids, flavonoids, peptides, polyketones, quinols, steroids, terpenoids, and phenols have been known to be produced by bacteria, especially endophytes [22-24]. These compounds have agricultural, industrial, and medical applications [25]. Christina et al. [26] reviewed a diverse range of bioactive compounds, especially from different endophytic bacteria. Pseudomonas viridiflava is known to produce ecomycins. Ecomycins possess bioactivities against various human and plant pathogenic fungi [27]. Pseudomycins are peptide antifungal compounds reported from Pseudomonas syringae [28]. Ghiasvand et al. [29] reported harmine, myricetin, and achillin, from Paenibacillus polymyxa.

2.3. Actinomycetes

Actinomycetes are an untapped source of potential bioactive compounds. The diverse range of actinomycetes have been isolated and used for the production of key drugs and biomedical agents [30]. Penicillin, cephalosporins, carbapenems, thienamycin, cephamycin, and nocardicin are some of the important β-lactam antibiotics reported from actinomycetes [31]. Balachandar et al. [32] reported the presence of 3, octadecene (E), behnic alcohol phenol, 2,4-bis(1,1-dimethyl ethyl) 1-nonadecene, 1-heneicosanol, milbemycin 3-eicosene (E), and 1-docosanol from vermicast isolated actinomycetes. Janardhan et al. [33] reported (Z)-1-([1-hydroxypenta-2,4-dien1-yl] oxy) anthracene-9,10-dione from Nocardiopsis alba.

2.4. Microalgae

Microalgae have been explored for their ability to produce bioactive compounds with promising applications as antibacterial, antiviral, antifungal, and antialgal agents [34]. Numerous secondary metabolites with antioxidant, antitumor, anticancer, and anti-inflammatory activities, including β-carotene, astaxanthin, lutein, zeaxanthin, violaxanthin, and fucoxanthin have been reported from microalgae [35]. Diatoms are rich sources of fucoxanthin [36]. Fucoxanthin has inhibitory effects on cancer cells by having proapoptotic activities [37,38]. The major algal species used to produce astaxanthin belongs to the genus Haematococcus. Some of the species of Chlorella, such as Chlorella zofingiensis, is also known producer of astaxanthin [39] [Tables 1 and 2].

Table 1: Diversity of bioactive producing microbes and their activities.

Table 2: Structures of bioactive compounds from microbes.

Bioactive compound producing microbes	Bioactive compound	Structure	References
Alternaria spp.	Linoleic acid (9,12-octadecadienoic acid (Z,Z)		Manganyi et al. [18]
Alternaria spp.	Cyclodecasiloxane		Manganyi et al. [18]
Armillaria mellea	Vanillic acid		Erbiai et al. [229]
Armillaria mellea	Cinnamic acid		Erbiai et al. [229]
Aspergillus minisclerotigens	Dihydropyran		Nuraini et al. [19]
Aspergillus oryzae	4H-Pyran4-one,5-hydroxy-2-(hydroxymethyl-(CAS) Kojic acid		Nuraini et al. [19]
Cochliobolus sativus	Cochlioquinone A		Do Nascimento et al. [224]
Cochliobolus sativus	Isocochlioquinone A	-	Do Nascimento et al. [224]
Cochliobolus sativus	Anhydrocochlioquinone A	-	Do Nascimento et al. [224]
Fomitopsis meliae	Dodecane		Kumar and Prasher [21]
Fomitopsis meliae	Ethyl 2-thiopheneacetate		Kumar and Prasher [21]
Fomitopsis meliae	Tetradecane		Kumar and Prasher [21]
Fomitopsis meliae	Hexadecane		Kumar and Prasher [21]
Fomitopsis meliae	Octadecane		Kumar and Prasher [21]
Fomitopsis meliae	Benzaldehyde		Kumar and Prasher [21]
Fomitopsis meliae	4-(1-methylethyl)-		Kumar and Prasher [21]
Fomitopsis meliae	Griseofulvin		Kumar and Prasher [21]
Kytococcus schroeteri	Berberine		Ghiasvand et al. [29]
Kytococcus schroeteri	Camptothecin		Ghiasvand et al. [29]
Macrolepiota procera	Protocatechuic acid		Erbiai et al. [229]
Microbacterium maritypicum	Harmine		Ghiasvand et al. [29]
Microbacterium maritypicum	Myricetin		Ghiasvand et al. [29]
Microbacterium maritypicum	Achillin		Ghiasvand et al. [29]
Paenibacillus polymyxa	Sanguinarine		Ghiasvand et al. [29]
Paenibacillus polymyxa	Daunorubicin		Ghiasvand et al. [29]
Pleurotus sajor-caju	Linoleic acid		Krümmel et al. [14]
Pleurotus sajor-caju	Chlorogenic acid		Krümmel et al. [14]
Pleurotus sajor-caju	Vanillic acid		Krümmel et al. [14]

4.1. Solvent Extraction

Solvent extraction is one of the most popular and traditional techniques for extracting metabolites from microorganisms. To improve extraction efficiency, raw materials are frequently blended into powder form. For the extraction, non-polar and polar solvents such as ether, ethanol, chloroform, benzene, water, ethyl acetate, and hexane, also their mixtures in various ratios, were used [51]. Because of its ease of use and low price, this technique has been widely adopted. Nevertheless, certain organic solvents, which are commonly employed in enormous quantities during processing and extraction, are highly hazardous and/or combustible. As a result, users must adhere to proper handling rules to ensure environmental compliance and users’ safety.

It is worth noting that organic solvents can cause bioactive compounds to degrade thermally [52]. Furthermore, the extraction procedure takes a lot of time and requires a lot of effort. Other advanced methods, such as soxhlet, ultrasound, and microwave extraction, have been developed to address these issues. Researchers have developed more advanced techniques like microwave-assisted extraction (MAE), pulsed-electric field extraction (PEF), pressurized liquid extraction (PLE), ultrasound-assisted extraction (UAE), and supercritical fluid extraction to overcome the shortcomings of conventional extraction methods [53]. It has been reveled that when, the extraction time was halved, and the thermal decomposition of compounds was prevented.

4.2. Soxhlet Extraction

It is a standard extraction method used to compare the results of other liquid-solid extraction methods [54]. The Soxhlet apparatus is a type of condenser used in this technique, which was developed in 1879 [55]. The traditional Soxhlet extractor is made up of a thimble-holder and a distillation flask. The solvent vaporizes and reaches the matrix when it attains boiling point, solubilizing suitable compounds. The solvent then strikes the condenser’s cooling pipes and condenses back into the original flask with the extracted compounds. This procedure is repeated until the entire extraction has been completed [55,56].

This method of extraction has a number of advantages. To begin with, the continuous renewal of the solvent in touch with the matrix creates an imbalance between the compounds in the test and the absence of them in the solvent, endorsing compound extraction. Second, the system’s temperature is maintained all throughout the procedure. The final crude extract from Soxhlet extraction need not necessitate filtration or centrifugation because they are nicely isolated from the initial biomass. Finally, because the basic equipment is relatively inexpensive and simple, it enables the treatment of numerous samples in parallel at a minimal price and with simple operational processes [57].

Nevertheless, there are some drawbacks to Soxhlet extraction, such as the vast concentrations of organic solvents needed, the long time it takes to finish the last cycles [57], the high temperatures used to heat up the solvents, which can deteriorate the compounds [55], and the fact that this process cannot be speeded up by introducing agitation [58].

Nonetheless, Soxhlet extraction has evolved over time to make up for some of these drawbacks, such as automating the process and trying to minimize extraction times. More recently, Soxhlet extraction has been paired with innovative technologies such as supercritical fluid-Soxhlet extraction, automated Soxhlet extraction, and high-pressure Soxhlet extraction, or by using auxiliary energies such as microwaves or ultrasounds, which results in higher efficiency [57,59].

4.3. Distillation

Distillation is among the oldest extraction methods still being used today. Its primary use is to separate liquid mixtures by using the boiling points of every component in the sample, followed by condensation steps [60]. Although distillation methods are still widely used, they have a number of disadvantages. The requirement for large amounts of energy to be consumed over long durations, including the use of high temperatures can deteriorate the ingredients of concern. Furthermore, the huge quantities of solvent are requisite, as well as the lengthy extraction times [57,61].

4.4. Infusions

Infusions are very brief macerations in which the plant is immersed in boiling or cold water for a short period [58]. Maceration entails breaking down the sample into smaller pieces to enhance the surface area available for mixing with the solvents. Both diffusion and the removal of the concentrated solution from the sample’s surface are made easier by the agitation involved in the maceration process. This method has been used to obtain bioactive compounds and essential oils for a long time [62]. Since infusions are very susceptible to fungus and bacterial growth due to the vast volume of water they consist of, they have a really limited lifespan and must be used right away. As a result, infusions are very seldom used in the industrial sector [63].

4.5. Green Extraction Techniques

Large volumes of organic solvents are often used in conventional extraction techniques, endangering the environment from chemical exposure. The idea of “green chemistry” was created to lessen the risks associated with chemicals, limit their use, and limit environmental exposure. By enabling to use nature without harming it, green chemistry also supports environmental sustainability. This idea has been used in synthesis, catalysis, separation, and monitoring, among other chemical processes. Waste, energy, and hazard are the three most important aspects of green chemistry, according to Anastas and Warner’s twelve principles [64]. The goal of these green extraction processes, according to Jacotet-Navarro et al. [65], is to obtain a quicker extraction rate, more efficient energy use, enhanced heat and mass transfer, smaller equipment, and fewer processing steps [65].

4.6. Supercritical Fluid Extraction

Supercritical extraction is characterized by pressure and temperature changes that transform the gas into a supercritical fluid with indistinguishable gas and liquid phases [66]. The extraction procedure is divided into several stages. Initially, the plant matrix absorbs the supercritical solvent, bulging the cellular structure and dilation the inter-cellular channels. As a result, the resistance to mass transfer decreases. Furthermore, the matter is being transferred from the internal matrix to the surface at the same time. Following that, these molecules are transported from the surface to the supercritical solvent before being excluded from the solvent [67].

The exclusion of harmful residues in the final product, high selectivity, short durations, high stability of the product acquired, low solvent consumption, and the fact that the residual biomass can be treated with other strategies to proceed with the extraction are all advantages of this method. This method can also be used to eliminate unwanted compounds such as pesticides, pollutants, and toxins [68]. Supercritical fluid extraction is an efficient and environmentally beneficial process. The most used solvent for supercritical fluid extraction is carbon dioxide (CO₂); however, methane, ethylene, fluorocarbons, nitrogen, and xenon are also utilized [69]. This technique has been used to collect biologically active substances from marine invertebrates and microalgae (such as crawfish, starfish, crustaceans, shrimp, crab, urchin, squid), macroalgae and cyanobacteria [70]. Dunaliella salina a microalga belonging to the class Chlorophyta contains fatty acids and β-carotene. In order to extract these molecules, supercritical CO₂ (SC-CO₂) was used at different operative conditions [71].

4.7. MAE

In 1986, Ganzler et al. published the first description of MAE [72]. Microwaves are electromagnetic fields that oscillate perpendicularly between 300 MHz and 300 GHz. The solute is dissolved by the solvent as it diffuses into the solid matrix, but the concentration is constrained by the solid’s physical characteristics [73].

This technique has several advantages, including rapid temperature rise, high efficiency, improved process monitoring, short extraction time, and low energy consumption and cost [74]. The breakdown of some compounds as a result of the heat produced by irradiation is one drawback of MAE. The MAE’s efficiency is determined by factors such as the power of microwave irradiation, the nature of the extractant, the temperature, and the extraction time, as well as the matrices’ characteristics and the solvent-food relationship. Due to the local heating that contributes to matrix rupture, the extraction efficiency is usually directly proportional to the microwave power. However, microwave power has a limit, which can result in a decrease in extraction efficiency [56]. Compound extraction, on the other side, is influenced by the solvent used. A combination of organic solvents and water has been found to increase extraction effectiveness. Contrarily, compared to MAE which exclusively employs organic solvents, the inclusion of water in organic solvents causes the extractant to penetrate the matrix molecules more deeply, enhancing microwave heating and improving overall efficiency and extraction time [75].

The toxicity of the solvent is also an essential aspect to consider when selecting an appropriate extractant for MAE [76]. According to some theories, the selectivity and efficiency of MAE are affected by the dielectric constant of the solvent mixture [77]. The agitator effect influences the extraction process, which mitigates the adverse effects of the S/F ratio on extraction recovery [78].

4.8. UAE

UAE involves the mechanism of diffusion across cells and cell breakage caused by mass transfer. To extract the chemical components, UAE uses a sound wave at 20 kHz-100 MHz to compress and expand the cells [79]. By rupturing plant cell walls, ultrasounds can expedite mass and heat transfer and improve the release of the target substances from a range of natural sources [80].

Compared to other extraction techniques, ultrasound is relatively simple to use; it is flexible, versatile, and requires a low investment. Polysaccharides, peptides, essential oils, dyes, proteins, pigments, and bioactive compounds have all been extracted using ultrasound [81]. This phenomenon can occur in either an indirect or direct manner [82].

Among the benefits of this technology are reduced solvent consumption, time and temperature, low investment for equipment, and ease of implementation, allowing it to be used industrially in local companies [83]. Heating can degrade the additives present in the sample, which is one of the main disadvantages of UAE [84]. Compared to traditional methods, UAE uses less solvent and is more efficient and cost-effective at extracting polyphenols and other compounds.

4.9. PLE

PLE, commonly called pressurized fluid extraction, and accelerated solvent extraction, was first introduced by Ganzler et al. [71], enhanced solvent extraction or Pressurized Hot Water Extraction [85]. PLE operates at high temperatures (50–200°C) and high pressures (1450–2175 psi) to maintain the solvent liquid above the typical boiling point [86]. The polarity of the solvent is reduced at high temperatures, but the solubility and mass transfer rate are increased due to an increase in the dielectric constant. A very little solvent is needed because the liquid is pushed into the extracting cells under high pressure, and the extraction yield is higher as a result. Additionally, automated methods shorten extraction times and do not need solvents [87]. Using pressurized liquid extraction, pheophytins, and the carotenoid diatoxanthin were removed from Euglena cantabrica [88].

4.10. PEF

PEF is a non-thermal technique that extracts bioactive compounds using a short electric field pulse. During PEF, the electric field distorts or destroys the cell membrane, transferring electric potential to the cells [89]. Its mode of action is based on causing cell membrane permeability in a short period and with minimal energy consumption. This is performed by using well-known techniques for preservation, enzyme, and microbial inactivation, which involve administering brief pulses (μs to ms) of moderate electric voltage (usually 0.5–20 kV/cm) to a substrate of interest positioned between two electrodes [90]. Because of these properties, various studies have been conducted to improve the extraction performance of bioactive compounds such as anthocyanins, polyphenols, and vegetable oil from plant tissues and byproducts, as well as the soluble intracellular matter of microorganisms [91]. On the other hand, in plant systems and cell cultures, low to light PEF treatment intensities are frequently regarded as an efficient pretreatment technique for raising secondary metabolites extraction efficiency [92]. Several procedures, such as pressing, extraction, drying, and diffusion, have used PEF. This method accelerates mass transfer while speeding up extraction by disrupting the membrane of the raw materials. The distortion or damage of the cell membrane is important for increasing permeability and proving to be beneficial over traditional extraction methods [50].

7.1. Antiviral Activity

Microalgae are quite possibly the most encouraging hotspots for new useful food items, because of their capacity to incorporate polyunsaturated unsaturated lipids, colors, and regular cancer prevention agents [109]. In a study, four strains of microalgae prospected were refined, and their antiviral effect was assessed in vitro against MAYV. The cell reasonability tests were done on VERO cells (Verda Reno Cells) to evaluate the lethality of the concentrates by CC50 designation and the deactivation limit of the MAYV as assessed by TCID50. The outcomes demonstrated that all the microalgae strains introduced adversary of the Mayaro movement and the overall strength was greater than ribavirin, the current antiviral. In addition, the basic portrayal by TLC and NMR 1H inquiry demonstrated in the concentrated configuration of terpenoid atoms and the greater part occurrence of unsaturated aliphatic particles [110].

Another study analyzed the polyunsaturated fatty acids. Carotenoids and cancer prevention agent movement of Phaeodactylum tricornutum, Nannochloropsis oculata, and Porphyridium cruentum activity got from SC-CO₂ and subcritical n-butane extraction techniques SC-CO₂ strategy was particular in removing immersed unsaturated fats saturated fatty acids for all microalgae species contemplated [110,111]. To add up to carotenoids and cancer prevention agent action utilizing DPPH scavenging test, a critical connection coefficient (R2 = 0.80) was found among the concentrates autonomous of the extraction strategy tried. This shows that carotenoid mixtures may be a significant supporter of the cell reinforcement limits of these microalgae. Polysaccharide-rich fractions isolated from D. salina and Haematococcus pluvialis extracts exhibit higher antiviral activity against herpes simplex virus type 1 [112]. Oscillatoria agardhii, Nostoc ellipsosporum reported lectins (Agglutinin OAA, Cyanovirin-N) which showed anti-influenza A-B viruses, anti-HIV1 and HIV2 properties [113,114].

Every year, marine fungi produce between 150 and 200 novel compounds, such as sesquiterpenes, alkaloids, polyketides, and aromatic compounds [115]. Recent studies have shown the enormous potential of marine fungi as a viable source for the creation of novel antivirals against a variety of significant viruses, such as the influenza virus, the human immunodeficiency virus, and herpes simplex viruses [116]. Till date, Pleurotus citrinopileatus exhibits the highest anti-HIV-RT activity with IC₅₀ (0.93). Pholiota adipose and Schizophyllum commune have lentins bioactive compounds with inhibitory activity toward HIV-1RT with low IC₅₀ values [117]. Trichoderma spp. of fungi, when tested against the human Enterovirus 71, SCSIO41004 (which contains 5-acetyl-2-methoxy-1,4,6-trihydroxy-anthraquinone) significantly inhibited viral growth [118]. Isolated polyketides from the fungus Diaporthe spp. SCSIO 41011 exhibited strong antiviral activity against three different strains of the influenza A virus [119]. Isoprenylated cyclohexanols present in Truncatella angustata have shown inhibition activity against HIV and H1N1 virus [120].

7.2. Anticancer Activity

Triterpenes from Ganoderma lucidum are known to initiate apoptosis of DU-145 cells in prostate malignant growth cells. Triterpenes had restrained the development of HT-29 cells by capturing cell cycle at the G0/G1 stage and furthermore accepted the modified cell passing Type II. Triterpenes from G. lucidum (GLT) restrain the development of prostate disease cells, stifle the relocation and intrusion and actuate apoptosis through the restraint of MMP articulation [121]. Triterpenes had likewise been displayed to hinder the development of growths in a xenograft model of colon disease [122]. Triterpenoids acquired from polyporus mushrooms, for example, ganolucidic corrosive E, ganoderenic corrosive D, iucidumol A, ganodermanontriol, 15-hydroxy ganoderic acis 5, 7-oxo-ganoderic corrosive Z, and ganoderic corrosive DM showed diminished cell development in three human carcinoma cell lines CaCo2, HEPA C12 and HeLa cells [123].

In another review, seven parts of triterpenoids were assessed for the anticancer exercises on malignant growth cell lines. Ganoderic corrosive D had shown high cytotoxic movement against Hep G2, Hela, and Caco-2 cell lines [124]. In a comparative report, lanostane triterpenoids were cleansed from Inonotus obliquus, for example, inotodiol, 3b,22dihydroxylanosta-7,6 (11), 24-triene, 3bhydroxylanosta-8,24-dien-21-al, 22R-epoxylanost-8ene-3b,24S-diol, lanosterol, trametenolic corrosive, inonotsulides A, B, and C, inonotsuoxides An and B, inonotsutriols A, B, and C, lanosta-8,23E-diene-3b,22R,25-triol and lanosta-7:9(11), 23E-triene-3b,22R,25-triol, spiroinonotsuoxodiol, inonotsudiol An and inonotsuoxodiol A, and inonotsutriols D and E had shown enemy of growth impact [125]. Triterpenes of the fruiting varieties of Fomitopsis pinicola and Fumaria officinalis were compared to the cell lines HeLa, A549, hepatocellular liver carcinoma (HepG2), and MCF7. These triterpenes show a significant influence on disease cells by inhibiting the expression of VEGF, IL4, and IFN gamma growth factors [126].

Polysaccharides cleansed from G. lucidum had shown antitumor action against different malignant growth cell lines. These mixtures hinder the development of Hep2 cells by the guideline of hepatic miRNAs and safe related miRNA. It has been seen that polysaccharides in blend with 5-fluorouracil showed synergistic cytotoxicity, apoptosis, and cell cycle capture against human colon malignant growth cells [127]. The polysaccharide from the maitake mushroom (Grifola frondosa), Part D, has demonstrated anticancer activity. When human breast cancer cells (MCF7) were exposed to maitake (D part) extract at various fixations, a significant decrease in the viability of the malignant growth cell line was observed. Due to the overexpression of BAK-1 and cytochrome C records, the apoptotic activity in a portion of the subordinate way significantly increased [128].

In a comparable report, the D-part of polysaccharides has likewise exhibited a direct effect on human and canine growth disease cell lines. This portion impacts the cell expansion through a tweak of quality articulation, cell passing, and metastasis in MCF7 human bosom disease cells. It was additionally exhibited that this compound has been able to straightforwardly follow up on the mammary growth cells and to module cell processes that are associated with the turn of events and movement of disease in people [129]. Polysaccharide compound se-gp11 was purged from Se-advanced G. frondosa which is made out of mannose, glucose, and galactose. This compound repressed the development of Hepa growth by expanding interleukin-2 and serum rot factor alpha which increment the heaviness of the thymus and spleen [130]. Polysaccharide GP11, which was removed from G. frondosa, inhibited the growth of Heps cells as well as exerted indirect cytotoxicity against HepG-2 cells. This substance stimulated the production of several distinct factors, including interleukin-1β, nitric oxide (NO), and tumor necrosis factor (TNF-α). It was hypothesized that the TLR-4-intervened up-regulation of the production of NO and TNF-α was responsible for the anticancer effect of GP11 polysaccharide by strengthening the host insusceptible framework [131].

GFG-3a is an original glycoprotein refined from G. frondosa had shown cell apoptosis and capture of the cell cycle at S gradually works in human gastric malignant growth SGC-7901 cells [132]. Polysaccharide peptide compound krestin refined from tinea versicolor goes about as an adjuvant in the counteraction of bosom malignant growth. This compound had likewise been announced for antitumor impacts in growth-bearing transgenic mice and had critical hindrances of bosom disease development [133]. A polysaccharide removes (Khz) decontaminated from the intertwined mycelia of Polyporus umbellatus and G. lucidum had shown hindrance to the development of A549 cellular breakdown in the lung cells. A high sub-atomic weight novel polysaccharide PL-N1) was secluded from Phellinus linteus mycelium remove. This polysaccharide contains arabinose, xylose, glucose, and galactose and has shown antitumor exercises and critical hindrance against the development of HepG2 malignant growth cell lines [134]. Two polysaccharides filtered from Grifola umbellata GUMP-1-1 and GUMP-1-2 had shown huge restraint of cancer development in hepatoma H22 relocated mice [135]. Water-dissolvable intracellular polysaccharides were removed from refined mycelia of Phellinus igniarius, and their decontaminated ethanol part had shown anticancer exercises against Su480 and HepG2 cell lines [136].

Numerous mixes that have been restricted from mushrooms contain anticancer workouts. Grifolin, a substance extracted from the crisp fruiting bodies of Albatrellus intersection, had been shown to inhibit the growth of various disease-related cell lines in vitro by up-guiding DAPK1 [137]. The anticancer and cancer prevention agent action of low atomic weight subfractions disconnected from auxiliary metabolites created by the wood corrupting growth Cerrena unicolor was additionally revealed against human colon disease cells [138]. Anticancer movement of this compound additionally covered nasopharyngeal and osteosarcoma disease by the enlistment of apoptosis and concealment of the ERK1/2 pathway [139]. This compound can hinder DNMT1 articulation which helps in the working of mitochondrial oxidative phosphorylation edifices in nasopharyngeal carcinoma [140]. Isosullin acquired from the oil ether concentrate of Saillus flavus had shown apoptosis and G0/G1 capture of the cell cycle in KS62 cell lines [141]. This compound had likewise answered to fundamentally diminish the cell practicality, G1 capture, and apoptosis in the SMMC-772 liver cell lines. This compound had the potential for cellular breakdown in the lung therapy because of the acceptance of apoptosis in H446 malignant growth cell lines [142,143].

Ergone and polyporusterone B disconnected from P. umbellatus had shown anticancer movement against HepG2, Hep-2, and Hela disease cells. However, ergone had shown particular cytotoxic action against these malignant growth cell lines [144]. Ergosterol peroxide and trametenolic corrosive disconnected from Chaga mushroom had shown cytotoxicity in human prostatic carcinoma cell PC3 and bosom carcinoma MDA-MB-231 cell lines [145]. The ergosterol peroxide got from I. obliquus showed against malignant growth impacts in colorectal disease by down-guideline of the β-catenin pathway. This compound had shown apoptosis in CRC cell lines, and furthermore repressed colitis-related colon disease in AOM/DSS-treated mice [146].

Hispolon, a phenolic compound removed from I. obliquus could initiate apoptosis of bosom and bladder-malignant growth cells [147]. A vigorously glycosylated protein, proteoglycan, which was cleansed from P. linteus had shown antitumor impact on human disease cells by the hindrance of expansion of human colon adenocarcinoma (HT-29), human HepG2, human cellular breakdown in the lungs (NCIH 460), and human bosom adenocarcinoma (MCF-7) cells [148]. The polysaccharide compound of T. versicolor at a centralization of 20 mg/L had shown critical restraint of hepatoma malignant growth cell line (QGY) by influencing articulation of cell cycle-related qualities (p53, Bcl-2, and Fas,) and actuated apoptosis [149]. Trametenolic corrosive, a bioactive compound filtered from Trametes lactinea (Berk.) Pat, had likewise known to show cytotoxic exercises against gastric malignant growth cell lines [150]. GA3P (d-galactan sulfate) isolated from Gymnodinium microalgae had reported growth inhibition of different cell lines (HCC2998, KM-12, HT-29, WiDr, HCT-15, and HCT-116) [151]. A glycolipid mono galactosyl diacylglycerol had reported activity toward the HT-29 human colon adenocarcinoma tumors. Violaxanthin isolated from Chlorella ellipsoidea had proapoptotic and anti-proliferative activity against the HCT-116 colon cancer cell line [152].

7.3. Antifungal Activity

A melodramatic shift approaching a more sustainable, environmentally stable, and natural way of living has been observed in recent years. Besides, many demerits and ill-effects related to existing antimicrobial agents, it is no wonder that a considerable number of humans, particularly those belonging to developing nations, are using naturally accessible bioactive alternatives for their health-care systems [153]. A substantial number of natural drugs can be obtained either from microbes or by their interaction with hosts [154]. Among the many antimicrobial agents’ antifungal peptides have also been extracted from numerous sources. It was in 1948 when scientists isolated antifungal compounds from Bacillus subtilis [155], the studies on the biosynthesis and their mode of action of antifungal substances began to limelight [156]. Antifungal compounds have been extracted from three kinds of microbes: Actinomycetes, bacteria, and fungi. Bacteria constitute the largest source among these three and Bacillus amyloliquefaciens, Bacillus cereus and B. subtilis are more widely utilized in research. B. cereus have the tendency to produce bacereutin, cispentacin, azoxybacilin, and mycocerein, which show strong activity against the proliferation of Candida albicans, Saccharomyces spp., Aspergillus species, and many other fungi [157]. Chernin et al. [158] reported the antifungal compound, namely pyrrolnitrin from Enterobacter agglomerans which shows antimicrobial action against a number of pathogenic fungi such as Aspergillus niger, Candida spp., dermatophytes, and other phytopathogenic fungi. Antifungal compounds extracted from a strain of B. amyloliquefaciens sybc H47 had shown a significant effect on a number of pathogenic fungi-like Aspergillus niger, Candida albicans Fusarium oxysporum and Penicillium citrinum [159]. In addition, many fungi, such as Aspergillus have also been known to synthesize antifungal compounds like echinocandins which are resistant to mycosis [160]. In recent years, the remarkable antifungal activity of marine actinomycetes has invited the attention of many researchers globally [161].

Various studies have been done on Streptomyces species which in known to have marked antifungal activity in addition to antiviral, antibacterial, and antiparasitic properties [162,163]. The crude extract of seven phyllospheric bacteria was tested against P. oryzae which demonstrated excellent antifungal activity [164]. Enormous tactics have been utilized to deal with numerous deadly fungal infections. Amphotericin B which is produced by Streptomyces nodusus, a Gram-positive bacteria, is a first-line drug used against the commented problem and it works by disrupting the membrane system. Another great approach is the use of combinatorial therapy, which can lessen the risk of the antifungal battle against monotherapy [165]. Recently, the extract from macroalgae viz. Gracilariopsis persica has demonstrated excellent antifungal activity against four pathogenic fungi [166]. Recently, bioactive compounds from Lactobacillus harbinensis K V9.3.1Np were identified using nuclear magnetic resonance and mass spectrometry. This was accompanied by checking the activity against Penicillium expansum and Yarrowia lipolytica, which revealed a polyamine and benzoic acid as active compounds from L. harbinensis K.V9.3.1Np [167].

7.4. Antibacterial Activity

Soil is the best medium for the growth of microorganisms that produce antibiotics that can further be incredibly used in the treatment of bacterial diseases in humans. The demand for such kinds of antibiotics has been growing day by day [168,169]. Bacterial isolates from B. cereus and Klebsiella pneumoniae were discovered to have antibacterial action toward Escherchia coli, Salmonella typhi and Staphylococcus aureus and thus these could be used for the production of the broad range of antibiotics [170]. Lactic acid bacteria are known to produce antibacterial compounds such as bacteriocin, hydrogen peroxide, diacetyl, and organic acids, which are efficient against harmful bacteria. Bacteriocins are generally peptides that are antagonists for bacteria; however, their number is quite less in comparison to the developed antimicrobial peptides [171,172]. Lactobacillus pentosus ST712BZ produces bacteriocin, which is effective against the proliferation of E. coli, E. faecalis, K. pneumoniae, Lactobacillus casei, Lactobacillus curvatus and Pseudomonas aeruginosa [173,174]. Bacteriocin properties of Serraticin A from Serratia proteomaculans have been reported [175]. The compound works by interfering with the synthesis of DNA [176]. Three methoxyphenol phytometabolites, namely eugenol, capsaicin, and vanillin exhibited antibacterial and antioxidant activities against Brochothrix thermosphacta, Shewanella putrefaciens, Lactobacillus and E. coli, P. aeruginosa, and S. aureus [177]. The isolates from Streptomyces spp. exhibited strong antibacterial activity against E. coli, S. aureus, P. aeruginosa, and B. cereus [178]. Nisin and gramicidin are the famous antimicrobial peptides extracted B. subtilis, Bacillus brevis, and Lactococcus lactis [179]. Antibacterial peptides constitute a large share of AMPs and have an extensive inhibitory effect on some common pathogenic bacteria, like Listeria monocytogenes, S. aureus Acinetobacter baumannii, and E. coli [180,181]. In addition, a total of 64 fungal families were reported to show antibacterial activity against 32 species of bacteria from over the world [182]. Antibacterial activity of endophyte fungi strains against the growth of pathogenic bacteria like S. aureus and E. coli has been studied [183].

7.5. Antimalarial Activity

Malaria is a disease which is widespread in subtropical and tropical regions, including parts of America, Asia, and Africa. An estimated 241 million malaria cases and 6,27,000 malaria deaths have been reported worldwide in 2020. Plasmodium falciparum, one of the five species of infectious malaria parasites is the most dangerous one because it causes dreadful infection even death. The available drugs against P. falciparum are increasingly losing efficacy because of the growing emergence of resistance, so there is an ongoing need to develop new, effective, and affordable antimalarial agents [184]. Ferreira et al. [185] studied 285 fungal isolates and their antimicrobial and antimalarial activities were examined. These endophytic fungal isolates were grown in solid-state fermentation and their crude extracts were recovered in dichloromethane. Chromatographic fractionation and NMR were used to analyze the bioactive extracts, which showed five fungi producing antimicrobial and antimalarial compounds. Extracts of endophyte Diaporthemiriciae produced epoxycytochalasin H which displayed high antimalarial activity against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. The compound epoxycytochalasin H with high anti-malarial activity against the chloroquine-resistant strains of P. falciparum has IC₅₀ approximately 3.5-fold lower than that with chloroquine. Bioactive compounds from Streptomyces, a Gram-positive bacterium, have been used as a most popular source of antibiotics [186]. Trioxacarcins A, B, C, and D isolated from marine Streptomyces have been tested against P. falciparum. Of these, Trioxacarcins A and D had a high antiplasmodial activity with IC₅₀ value1.6 ± 0.1 and 2.3 ± 0.2 ng/mL, respectively comparable to artemisinin with IC₅₀ value 0.7 ± 0.1 ng/mL [187] Trioxacarcin B with IC₅₀ value 102 ± 4.9 ng/mL has anti plasmodial activity about 100 times less than that of trioxacarcins A and Dwhereastrioxacarcin C with IC₅₀ value is >5000 ng/mL has been found to be inactive. Coronamycin from endophytic Streptomyces spp. growing inside an epiphytic vine, Monstera spp., showed an antiplasmodial activity against P. falciparum with IC 50 of 9.0 ng/mL [188]. A series of unique wide-spectrum antibiotics called munumbicins A, B, C, and D of which Munumbicin D showed activity against P. falciparum(with IC₅₀ of 4.5±0.07 ng/mL) [189].

Similarly, Kakadumycin A, Munumbicins E-4, and E-5 also showed antimalarial activity [190,191]. In vivo testing of Gancidin- W isolated from Streptomyces spp. SUK 10 on P. berghei NK 65 infected mice showed a remarkable 80% inhibition of malarial parasite at 6.25 and 3.125 µg/kg body weight [192]. McCarthy et al. [193] screened the role of marine microbes as potential antimalarial agents. They identified 17 dominant extracts produced by the actinomycetes, fungi and Gram-negative bacteria out of 2365 tested samples due to their inhibitory action against the multidrug chloroquine-resistant P. falciparum and their cytotoxic nature toward the mammalian cells. Parapini et al. [194] screened a group of 14 different inhibitors of Rac1 as potent antimalarial agents. Their study showed E-Hop-016 as the potent inhibitor of P. falciparum in vitro but did not impede the parasitic invasion of erythrocytes. An outcome of the results depicted the role of E-Hop-016 in affecting the intraerythrocytic growth of the parasite.

7.6. Antidiabetic Activity

Diabetes mellitus is a collection of non-communicable metabolic disorders characterized by a persistently high blood glucose level resulting from decreased insulin production, insulin action, or even both. Diabetes mellitus, if left untreated, can cause serious health problems, which include cardiovascular disease, blindness, chronic kidney disease, neuropathy, stroke, and even death [195-197]. American diabetes association, 1997, classified Diabetes mellitus as Type 1 Diabetes mellitus, which results from the destruction of beta cells of the pancreas due to an autoimmune disorder accounting for 3–10% of cases, Type 2 Diabetes mellitus which occurs due to the body’s ineffective use of insulin and accounts for 85–90% cases and Gestational Diabetes (2–5% cases) which occurs during pregnancy [198]. Several researchers have reported that gut microbiota such as Bifidobacterium, Lactobacillus, Bacteroides, Roseburia, Faecalibacterium, Clostridium cluster IV and subcluster XIVa and Akkermansia have shown promising results against T2DM [199-201]. Jayant and Vijayakumar [202], reported in vitro anti oxidant and anti-diabetic potential of ten fungal endophytes isolated from Ficus religiosa viz., Aspergillus aculeatus, Penicillium spp., Aspergillus sydowii, Curvularia lunata, Cephaliophora irregularis, Diaporthe spp., Aspergillus quadrilineatus, A. flavus, A. versicolor and Aspergillus spp.

The antidiabetic and antioxidant potential of the fungal extracts were determined by inhibition of DPPH and enzyme α-amylase. Interestingly, all the extracts displayed moderate DPPH and α-amylase inhibitory activity with Curvularia lunata being the lead. In another study made by Ushasri et al. [203], it was reported that ethanol and acetone extracts of endophyte Syncephalastrum racemosum extracted from the sea weed Gracilaria corticata exhibited maximal α-amylase inhibitory action. Besides these, several wild edible mushrooms possess various nutritional and pharmacologically active components such as fibers, alkaloids, lectins, proteins, polysaccharides, and polyphenols which show antitumor, anti-inflammatory, immunomodulatory, antioxidant, antihypercholesterolemic, antihypertensive, hypoglycemic, antimicrobial and various other properties [204-207]. Anti-diabetic action of six medicinal and edible mushrooms such as Agaricus blazei, Coprinus comatus, Cordyceps militaris, I. obliquus, Morchella conica and P. linteus has been reported [208]. In addition, hypogycemic potential of several mushroom species viz., Lentinus swartzii, Tremella fuciformis (glucuronoxylomannan [209], Wolfiporia extensa (dehydrotumulosic acid, dehydrotrametenolic acid, and pachymic acid) [210], G. lucidum (G. lucidum polysaccharides) [211], Ganoderma applanatum (Exo-polymer (GAE) [212] and Collybia confluens (Exo-polymer (CCE) [212], Auricularia auricula-judae (Polysaccharide (FA) [213], Agaricus campestris, Agaricus subrufescens (Beta-glucans and Oligosaccharides [AO]) [214], I. obliquus, Hericium erinaceus, Agrocybe aegerita, C. comatus (Vanadium) [215], Cordyceps sinensis (Polysaccharide CSP-1) [216], G. frondosa (Alpha-glucan, MT-alpha-glucan) have been reported [217-221].

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