INTRODUCTION:

Natural resources are a gift from the universe. Humans have been reliant on natural resources for their survival since their arrival on the planet. Natural compounds are nearly often the key to healing substances¹Medicinal plants have been utilised for centuries to treat patients all over the world². The Indian subcontinent uses both allopathic and ayurvedic medicine to treat a variety of symptoms and conditions. Due to their diverse ecosystems, India, China, and Nepal have a large number of fragrant and medicinal plants. Medicine has been made from mushrooms for countless years.

Gandoderma is a wood degrading mushrooms with hard fruiting bodies. Taxonomic studies reported 300 and above species in genus Gandoderma, majority of them being located in tropical areas. Gandoderma species are generally not listed among edible mushroom because their fruiting bodies are thick, corky and tough without the fleshy texture characteristics³ WiId Gandoderma is very rare and is rare to collect even if someone find it by chance, its effects are always lost because of aging and it becomes hard like leather⁴. The genus Gandoderma has around 219 species with 10-30 known species described under subgen Elfvingia⁵. It appears that the mycelium contains various physiologically active components, and the benefits of liquid cultivation over solid cultivation include the capacity to alter the cultivation medium to maximise mycelial growth, a shorter cultivation period and less contamination⁶. Gandoderma is a basidiomycete white rot fungus that has been utilised for ages in Asia for therapeutic purposes. It's a superb illustration of an ancient medicine that's still relevant in today's world⁷. The fungus must have to be among the most persuasive examples of old folk medicines being converted into new pharmacological leads, and it might be a wonderful example of the guiding concept⁸. Gandoderma is a complicated fungus that has had extensive relationships with humans throughout history⁹. Gandoderma species are important in the ecological breakdown of woody plants for nutrient mobilisation, and they have efficient lignocellulose-decomposing enzymes that used for bioenergy production and bioremediation. Gene clusters around 24 have been discovered in the genome of Gandoderma. It can be particularly helpful to utilise the CYP450 gene and genes at the mating type locus as examples of how to use genomic data to identify genes that are engaged in crucial biochemical and developmental processes.In particular, the analysis of the CYP450 gene and genes at the mating type loci in G. lucidum strain G.260125-1 can serve as good examples for utilising genomic information to find genes that are responsible for significant biochemical and development processes.Comparing the genetic makeup of infective and noninfectious; Gandoderma species might also reveal potential therapeutic targets^10,11,12,13. Numerous research were conducted to identify biologically active compounds in Gandoderma species using extracts of their fruiting bodies, spores, and cultured mycelia. Protein, triterpenes, steroids, polysaccharides, peptides, amino acids, alkaloids and inorganic elements are biologically significant constituents in Gandoderma species. Around 431 secondary chemical components reported from various Gandoderma species; 240 secondary metabolites and Volatile oils from G. lucidum have both been identified.Gandoderma species possess various pharmacological activities such as antiviral, immunomodulating, anti-inflammatory, antiandrogenic, cholesterol synthesis inhibitory, hypoglycemic, hepatoprotective, inhibition of lipid peroxidation antimicrobial and anti-aging activities^14,15. Because they breakdown woody cell walls with 12 selective delignification and simultaneous rot, all Ganoderma species induce tree white rot, and these are the therapeutic fungus with a long track record. Triterpenes and polysaccharides were isolated and investigated as antitumor and antiviral agents¹⁶.

MATERIAL AND METHODS:

This review is entirely based on secondary data, which was gathered from articles found on web portals and in print publications¹⁷. The publications were searched using keywords such as Gandoderma lucidum, ethnomedicine, traditional medicine; Ayurvedic, phytochemistry, and so forth. There were 71 papers in all that were gathered and evaluated, this data was given in a descriptive and tabular way that worked effectively.

RESULT AND DISCUSSION:

Taxonomy of Gandoderma lucidum:

Table 1: Taxonomic Classification of Gandoderma lucidum

S. No.	Taxonomic classification	Plant
1.	Kingdom	Fungi
2.	Division	Basidiomycota
3.	Class	Homobasidiomycetes/Agaricomycetes
4.	Order	Aphyllophorales
5.	Family	Polyporaceae/ Ganodermataceae
6.	Genus	Ganoderma
7.	Species	Lucidum
8.	Synonyms	Lingzhi, Reishi, Yeongji

Fig. 1: The fruit body (Frontal view) of Gandoderma lucidum

Fig. 2: The fruit body (Dorsal view) of Gandoderma lucidum

Distribution of Gandoderma lucidum:

Ganoderma lucidum (G.lucidum) is a reddish laccate Ganoderma species that grows on rotting hardwood trees in Europe and portions of China¹⁸. Wild populations have been discovered in California and Utah, however they were most likely introduced and naturalised by humans¹⁹.

The chemical constituents of G. lucidum:

It is an important herb in Asia and preclininal studies have established that the polysaccharide fractions have potent effects. Choline, betaine, cyclooctasulfur, and oleic acid were the alkaloids that were extracted from G. lucidum spores, respectively^20,21. Ganoderic acid B, C, E, C5, C6, G and ganoderenic acid D are unique constituents of Lingzhi, unique triterpene and carbohydrates pattern were reported through TLC, HPTLC, HPLC, FTIR in different species of this fungus such as G. lucidum and G.applanatum²². The best sources of ganoderic acid B were revealed to be the pilei or 2 caps, followed by the stipes or stems, and finally the spores. Four triterpenes were discovered to have higher quantities in the fruiting bodies than in the spores, and triterpene contents in spores with an 85 percent sporoderma-breaking rate were found to be higher than those obtained from spores with entire sporoderms. Six ganoderic alcohols, including lucidumol A and B, ganoderiola A and F, ganodermanontriol A, and ganodermanondiol, were successfully isolated. The spores had a 5-20 times higher total triterpene content than the fruiting bodies, while G. lucidum had a10 times higher average total triterpene content than G. sinense. Polysaccharides from Lingzhi and related species have been found to be made up of a variety of monosaccharides that can be separated using paper chromatography, including galactose, mannose, glucose, mannose, arabinose, xylose, fucose, rhamnose, glucuronic acid, and galacuronic acid^23,24,25,26. Four sesquiterpene compounds isolated from G.mastoporum are ganomastenol, ganomastenol B, acid about 40 in numbers, 14 ganoderiols and 5-ganolucidic acids are isolated from G. lucidum and two triterpenoids name 20 (21)- dehydrolucidenic acid A and methyl 20 (21)- dehydrolucidenate A and five new 20-hydoxylucidenic acids isolated from the basidiocarps of this species.Ergosterol and 24-methylcholesta-7,22-dien-3,15-diol first time isolated from G.lucidum. Other species of G.lucidum are known for the presence of triterpenoids and steroids, its structure is based on that of lanosterol, an important intermediate. The spores of this fungus have higher quantity of ganoderic alcohols and acids than basidiocarps. G.capense mycelia includesadenine, adenosine, uridine, and uracil. G. capense's mycelia produced two new pyrrole alkaloids, ganoine and ganodine, as well as a new purine alkaloids, ganoderpurine. Various Lingzhi plants have produced vitamins such as β-carotene, vital minerals and over 120 volatile flavour compounds, primarily alcohol, aldehydes, ketones, esters, and phenols.

The separation of 431secondary metabolites from the genus Ganoderma, with major constituents being lanostane type triterpenoids, steroids and their numerous derivatives^{27,28,29,30,31}. Polysaccharides and their hydrolyzates from different parts, species and different regions of Ganoderma could be differentiated clearly through fingerprint analysis method by Reverse Phase High Performance Chromatography (RP-HPLC) along with chemometrics means such as hierarchical cluster analysisn (HCA) and principal component component analysis (PCA).The differences and similarities may be applied to identification and quality control of Ganoderma materials from different origin used for the preparation of Traditional Chinese Medicine and health products of Ganoderma polysaccharides^32,33,34,35.
Spirolingzhines A-D, four meroterpenoids with a spiro (benzofuran-2,1’-cyclopentane) motif, lingzhines A-F, six meroterpenoids with diverse ring systems, along with two known compounds isolated from G. lingzhi. These secondary metabolites were found to promote proliferation of neural stem cells and they constitute a class of neural stem cell stimulators³⁶. Methanolic and aqueous extracts of G. lucidum slightly reduce cell viability and induce DNA fragmentation in leukemia human cell line NB4 cells. Immunomodulatory and antitumor activities shows due to the presence of several Polysaccharides of G.lucidum³⁷.

G. tsugae extracts induce G2/M cell cycle arrest, which has anti-tumor effects on adenocarcinoma cells. In animal model, no major physiological toxicities arising from treatment based on biochemical, haematological, and pathological investigations³⁸.

The polysaccharides from G. tsugae that were hot-alkali extracted were superior than hot-water extracted polysaccharides in their ability to inhibit the growth of IMR32 cells. Furthermore, Hep G2 cells were significantly inhibited from proliferating by both extracts³⁹.

G. pfeifferi contains triterpenoids and polysaccharides along with these it also contains unique sesquiterpenoids and other small molecular weight compounds. A novel chemical entity extracted and discovered from G. pfeifferi is ganomycine. These compounds have antibacterial capabilities against MRSA, other multi-resistant bacteria, antiviral qualities, UV protection abilities, and other features⁴⁰.

Mushroom polysaccharides were mostly glucans with configurations; -D- Glucans basidiomycetes structures, with a branched structure featuring -(1-3) connections in chain and extra -(1-6) branch points. G. lucidum polysaccharides are polysaccharides with three main chains that are mostly replaced in O-6 by nonreducing ends of -Glcp units and side chains of various lengths⁴¹.

Nonadecanoic acid has been isolated from several sources including a fungus, plants and marine sponge has cytotoxic activity against human macrophage cell line THO-1. Two C19:1 fatty acids (2-Naphthyl nonadecanoic acid and 2-Naphthyl cis -9-nonadecanoic acid) with different double bond positions have been detected in fish oil, fungus and limpet as minor components. C19: 1 fatty acids appears to have the properties of inhibition of myeloperoxidase release from neutrophils⁴².

G. tropicum was employed to treat coronary heart disease, liver protection and improving sleeping alternative to G. lucidum and G.sinensis. A new nortriterpenoid named 26-nor-11,23-dioxo-5α-laost-8-en-3β,7β, 15α,25-tetrol and a known compound lucidone D were isolated from G. lucidum⁴³.

The OH substituent at C-11 is a significant property of Ganoderma acids, and the carboxylic group in the side chain is required for the detection of -glucosidase inhibitory action, according to structure-activity connections. Furthermore, the OH substituent at C-3 and the double-bond moiety at C-20 and C-22 in the side chain of Ganoderma acids increase -glucosidase inhibitory action⁴⁴. The chloroform extract was separated on a Zorbax SB-C 18C Column and eluted with an acetonitrile-0.2 percent acetic acid gradient; total 32 triterpenoids along with 6 novels were identified⁴⁵.

Ethnomedicinal value:

Lingzhi used in the treatment of migraines, hypertension, arthritis, bronchitis, asthma, anorexia, gastritis, diabetes, hyperchlesterolaemia, nephritis, dysmenorrhea, constipation, lupus erythematosus, and cardiovascular issues. It is said to have properties like anticancer, anti-aging, anti-microbial, anti-viral and AIIDS. Consumption on a regular basis sustain human vitality and improve lifespan^46,47.

Mycelia and culture methanolic extract of G. lucidum and G. recinaceum inhibited the growth of Bacillus subtilis and also show the anti-inflammatory effects. G.lucidum basidiocarps reduced plasma cholesterol levels in rats and had superoxide scavenging properties, indicating its particularly efficient in hepatic and renal protection mechanisms. The immune system is boosted by Gandoderma species, which also have anti-inflammatory and anti-allergenic properties. The triterpenes in G.lucidum extracts suppressed intracellular signalling pathways and invasive activity in many cancer cells. Polysaccharides stimulate the immune system, causing cytokines production and immune cells' anti-cancer actions to be activated. Ganoderic acid X, is a powerful triterpene, has the capacity to block topoisomerases and sensitise cancer cells to apoptosis, making it a potential anti-cancer medication⁴⁸.

G. lucidum demonstrated the strongest 5α-reductase inhibitory activity among 19 edible and medicinal mushrooms, also useful in the treatment of prostatic hyperplasia. Platelet aggregation was produced by Gandodermic acid S, a triterpene derived from G.lucidum, which stimulated the hydrolysis of phosphatidylinositol 4, 5 bisphosphate. Ganoderol A, and B, ganoderal A and ganoderic acid Y are 26 oxygenosterols that impede cholesterol production and are found between lanosterol and lathosterol⁴⁹.

The anti-HIV-1 protease activity of triterpenes derived from G. lucidum spores, such as ganoderic acid, luciumol B, aganodermanodiol ganodermanontriol, and ganolucidic acid, was considerable ⁵⁰. Ganomycins A and B were the steroidal moieties isolated from G.pfeifferi has antibacterial action. Water soluble polysaccharides were successful in preventing DNA from strand breaking, demonstrating the anti-tumor and immune-modulating actions connected to its anti-oxidative characteristic. G. lucidum may have potential immune-modulating actions in patients with advanced colorectal cancer⁵¹.

Ling Zhi-8, a novel immunomodulatory protein isolated from G. lucidum mycelia, is a polypeptide with 110 amino acids residues and an acetylated amino terminus, with a molecular mass of 12 kDa and mitogenic activity. A 15-kDa antifungal protein is further produced by G. lucidum⁵². A lectin isolated from G.capense exhibited potent mitogenic activity towards mouse splenocytes and anti-proliferative activity towards leukaemia cells and hepatoma cells in-vitro. Spores and fruiting bodies of G.lucidum showed mitogenic activitybecause of the existence of bioactive proteins⁵³. G.extracts known to have a higher concentration of adenosine, had no pharmacological effects on platelet aggregation in haemophiliac patients who were HIV positive⁵⁴.

G. lucidum immune-modulating substances is a proteoglycan consisting of more than 90% carbohydrates; activated mouse macrophages as per the dosages, increased the values of IL-1β, IL-12p35 and IL-12p40 gene expression and significantly enhanced no production, activates the immune system by modulating cytokine production. These substances also interfere certain tumors growth⁵⁵.

By inhibiting 5-reductase and having the ability to bind to androgen receptors, ganoderol B and 5-reductase can prevent testosterone rat’s ventral prostate regrowth caused by testosterone is reduced by -induced LNCaP cell proliferation⁵⁶.

Androgen mediated disease such as prostate cancer, hirsutism, benign prostatic hyperplasia, acne and androgenic alopecia have become serious problems which occurs due to 5α-reductase activity, methanolic extract of the fruit body of G. lucidum significantly inhibited the testosterone induced growth of the ventral prostate hyperplasia. In castrated rats, the therapy with G. lucidum itself or its extract considerably reduces the growth of the ventral prostate brought on by testerone. Its dry powder was a particularly well-liked chemotherapy treatment for cancer in China⁵⁷.

Despite the fact that genetic analysis has provided a deeper understanding of the polygenic resistance of palm oil against Gandoderma species, finding on the gene regulation of oil palm defence pathways has not. Polygenic resistance comprising many genes of minor effect may provide reasonable resistance in palm oil. Identification of genes that contribute to this polygenic resistance could be useful for screening for disease resistance oil palm and marker-assisted breeding programme⁵⁸.

Prostate cells can be inhibited and osteoclastogenesis can be blocked by ganoderic acid DM from ethanol extracts of G. lucidum with 5-reductase inhibitory 18 and androgen receptor binding activity⁵⁹.

G. lucidum Fr, Krast extract had the greatest 5-reductase inhibitory action, and treatment with the fruit body or extract derived from it significantly prevented testosterone-induced ventral prostate development in castrated rats⁶⁰. Triterpene extract from mushroom G. lucidum markedly suppressed the inflammation response in LPS activated murine macrophages, as it suppressed LPS dependent secretion of TNF-α, IL-6 and PGE2 from RAW264.7 cells. It inhibits RAW264.7 cell proliferation by arresting the cell cycle in the G0/G1 and G2/M stages, in addition to its anti-inflammatory properties^{61, 62}.

In ischemic cortex, oral treatment of G. lucidum polysaccharides at various doses dramatically decreased cerebral infarct area, neurological functional impairments, and neuronal death. It was beneficial in reducing neuronal cell death and alleviating cell damage ⁶³.

G. lucidum ethanolic extract suppressed the proliferation of human uroepithelial cells by inducing apoptosis, and interleukins IL-2, IL-6, and IL-8 were considerably upregulated in dose-dependent manners by G. lucidum ethanolic extract, but not by its aqueous extract. Furthermore, cytokine increased expression was linked to increase the level of p50/p65 NF-kB activity generated by G. lucidum ethanolic extract. A powerful chemopreventive component present in the extract, higher IL-8 levels were also linked to neutrophil migration. Ethanolic extract may encourage the clearance of high-risk urothelial cells^64.

Triterpenoids tsugaric acid A and 3-oxo-5α-lanosta-8, 24-dien-21-oic acid isolated from Ganoderma tsugae, displayed significant inhibitory effects on formyl- Met-LeuPhe cytochalasin B (fMLP/CB) induced superoxide anion generation and release of β-glucuronidase stimulated with fMLP/CB from rat neutrophils and accumulation of NO in the culture media of cells in response to lipopolysaccharide/interferon-γ respectively.

Tsugaric acid A has a protective effect on keratinocytes against photodamage induced by ultraviolet B light and may be used this as a agent for skin care⁶⁵.

At an oral dosage of 80 mg/kg, G. lucidum extract significantly enhanced total sleep time and non-rapid eye movement sleep time while having no effect on slow wave sleep. TNF- (tumour necrosis factor) levels in blood, the hypothalamus, and the dorsal raphe nucleus all rose at the same time. Both were co-administered at doses of 12.5ng/rat i.c.v and 40mg/kg, i.g., respectively, and showed an additive hypnotic effect⁶⁶.

The chemical features of G. genus polysaccharides with reported antioxidant, antitumor, antibacterial and antimicrobial activities shown both in vitro and in vivo. The polysaccharides with a higher molecular weight have antioxidant activity. The bioactivity of polysaccharides is due to the glycosidic linkages, increased bioactivity potential, such as more (1→6)- β--branch points and additional (1→3)-β--linkages in the glucan's main chain⁶⁷.

Several components were isolated from G.orbiforme BCC 22324 cultures, indicating the presence of seven lanostane triterpenoids, ganorbiformins, and other recognised chemicals. The lanostanoids found in G. orbiforme include ganorbiformin A, a newly discovered counterpart, as well as other substances that share the same lanostane structure as known ganoderic acids. These molecules gave rise to the C-3 epimer of ganoderic acid T, which significantly inhibited Mycobacterium tuberculosis H37Ra (with a microbiological inhibitory concentration of 1.3µM)^68.

G. applanatum polysaccharides with varying molecular weights from fruit bodies (FGAP)and submerged fermentation system (SGAP). Carboxylate groups were identified in 27 polysaccharides separated from fruit bodies, but not in polysaccharides obtained from a submerged fermentation system. The structural difference, FGAP has stronger anticancer efficacy against Sarcoma 180 than SGAP as that of carboxylate groups may play a major role in FGAP's antitumor activity⁶⁹.

The Fudan-Yueyang fraction and polysaccharides of G. lucidum extract, all these lowers the triglycerides and low density lipoprotein cholesterol levels in human body, potentially reducing diabetes consequences including atherosclerosis and hyperlipidemia⁷⁰.

G. lucidum fruiting bodies grown on wheat straw are more antibacterial, antioxidant, and cytotoxic than fruiting bodies grown on oak sawdust, a more traditional substrate⁷¹.

CONCLUSION:

Gandoderma lucidum, also known as Lingzhi in Chinese, used to treat various ailments by people across the world for a long time. It is one of the extensively utilised medicinal herbs among Chinese, Japanese, and Korean populations in Asian countries. It has enormous commercial potential in addition to its disease-curing promise. We can even commercialise it since Asian countries have highly good circumstances for its manufacturing. Indeed, further research, study and investigation of medicinal plant is required to preserve excellent health through traditional methods.

DECLARATION OF CONFLICT OF INTEREST:

Thereare no conflicts of interest declared by authors.

REFERENCES:

1. Datta I C. Non-timber forest product of Nepal. Identification, Classification, Ethanic Use and Cultivation. 2007.

2. Gahatraj S, Bhusal B, Sapkota K, Dhami, B, Gautam D. Common medicinal plants of Nepal: A review of Triphala: Harro (Terminalia chebula, Barro (Terminalia bellirica) and Amala (Emblica officinalis). Journal of Pharmacognosy 2020; 4 (3): 5-13.

3. Jonathan SG, Kigigha LT, Ohimain E. Evaluation of the inhibitory potentials of eight higher Nigerian fungi against pathogenic microorganisms. African Journal of Biomedical Research 2008; 11: 197-202.

4. Sabulal B, Anil JJ, Balaji G. Secondary Metabolites from Ganoderma. Phytochemistry 2015; 114: 66-101.

5. Malarvizhi K, Pudupalayam TK. Ganoderma austral from southern India. Microbiological Research 2008; 163: 286-292.

6. Smith JE, Rowan NJ, Sullivan R. Medicinal mushrooms: a rapidly developing area of biotechnology for cancer therapy and other bioactivities. Biotechnology Letters 2002; 24: 1839-1845.

7. Russell R, Paterson M. Ganoderma- A therapeutics fungal biofactory. Phytochemistry 2006; 67: 1985-2001.

8. Ziegenbein FC, Hanssen HP, Konig WA. Secondary metabolites from Ganoderma lucidum and Spongiporus leucomallellus. Phytochemistry 2006; 67: 202-211.

9. Johnsston N. Medicinal mushroom cuts off prostate cancer cells blood supply. Drug Discovery Today 2005; 10: 23-24.

10. Ursula K, David RN, Chang LGY, Jianhui Z, Jianqin L. Genome analysis of medicinal Ganoderma spp. with plant-pathogenic and saprotrophic life-styles. Phytochemistry 2015; 114: 18-37.

11. Chen S, Xu JLC, Zhu Y, Nelson DR, Zhou SLC, Wang L, Guo X S, Luo HLY, Song J, Henrissar B, Levasseur A, Qian J, Li J, Li J, Luo X, Shi L. Genome sequence of the model medicinal mushroom Ganoderma lucidum. Nature Communication 2012; 3: 913-920.

12. Flood J, Bridge PD, Holderness M. Ganoderma disease of Perennial crops, CABI Publishing, Wallingford, UK December 2000.

13. Zhou XW, Cong WR, Su KQ, Zhang YM. Ligninolytic enzymes from Ganoderma spp.: Current status and potential applications. Critical Review of Microbiology 2013; 39: 416-426.

14. Soniamol J, Baby S, Varughese G, Thozhuthumparambal PS, Kainoor KJ. Antioxidative and Antiinflammatory activities of the chloroform extract of Ganoderma lucidum found in South India. Science Pharmaceuticals 2009; 77(1): 111-122.

15. Ko HH, Hung CF, Wang JP, Lin CN. Anti-inflammatory triterpenoids and steroids from Ganoderma lucidum and G. tsugae. Phytochemistry 2008; 69: 2ds34-239.

16. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Applied Microbiology and Biotechnology 2002; 60: 258-274.

17. Timilsina S, Bhattarai R, Miya M, Gautam D. Sissoo its Pathogenic Constraints and their management in Nepal: A review. Grassroot Journal of Natural Resources 2020; 3 (4): 1-17.

18. Loyd AL, Richter BS, Jusino MA, Truong C, Smith JA. Identifying the Mushroom of Immortality: Assessing the Ganoderma species composition in Commercial Reishi Product. Frontiers in Microbiology 2018; 9: 1557.

19. Loyd AL, Barnes CW, Held BW, Smith JA, Blanchette RA. Ellucidating lucidum: Distribution the diverse laccate Ganoderma species of the United States. PLOS ONE 2018;13 (7) : e 0199738.

20. Chen XH, Yang Z, Huang, XX, Gao M, Tang TW., Chan, SY.2006. Monitoring of immune responses to a herbal immune-modulator in patients with advanced colorectal cancer. International Immunopharmacology 2006; 6: 499-508.

21. Rosecke J, Konig WA. Constituents of various wood-rotting basidiomycetes. Phytochemistry 2000; 54: 603-610.

22. Huie CW, Di X. 2004. Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components. Journal of Chromatography B 2004; 812: 241-257.

23. Chen DH, Shiou WY, Wang KC, Huang SY, Shie YT, Tsai CM, Shie JF, Chen KD. Chemotaxonomy of triterpenoids pattern of HPLC of Gandoderma lucidum and Gandoderma tsugae. Journal of Chinses Chemical Society 1999; 46: 47-51.

24. Cole RJ, Schweikert MA. Handbook of Fungal Secondary Metabolites, volume 2, Academic Press, California 2003.

25. Cole RJ, Schweikert MA. Handbook of Fungal Secondary Metabolites, volume 3, Academic Press, California 2003.

26. Akihisa T, Tagata M, Ukiya M, Tokuda H, Suzuki T, Kimura Y. 2005. Oxygenated lanostane type triterpenoids from the fungus Ganoderma lucidum. Journal of Natural Products 2005; 68: 559-563.

27. Adams M, Christen M, Plitzko I, Zimmermann S, Brun R, Kaiser M, Hamburger M. 2010, Antiplasmodial lanostanes from the Ganoderma lucidum mushroom. Journal of Natural Products 2010; 73: 897-900.

28. Lee I, Kim H, Youn U, Kim J, Min B, Jung H, Na M, Hattori M, Bae K. Effect of lanostane triterpenes from the fruiting bodies of Ganoderma lucidum on adipocyte differentiation in 2T3-LI cells. Planta Medica 2010a; 76: 1558-1563.

29. Li C, Yin J, Guo F, Zhang D, Sun HH. Ganoderic acid Sz, a new lanostanoids from the mushroom Ganoderma lucidum. Natural Product Research 2005b; 19: 461-465.

30. Li C, Li Y, Sun HH. New ganoderic acids, bioactive triterpenoid metabolites from the mushroom Ganoderma lucidum. Natural Product Research 2006; 20: 985-999.

31. Li YB, Liu RM, Zhong JJ. A new ganoderic acid from Ganoderma lucidum mycelia and its stability. Fitoterapia 2013c; 84: 115-122.

32. Xiaomei S, Wang H, Xiaofenga H, Shangwei C, Song Z, Jun D. Fingerprint analysis of polysaccharides from different Ganoderma by HPLC combined with chemometrics methods. Carbohydrate Polymers 2014;114: 432-439.

33. Liu W, Wang HY, Pang XB, Yao WB, Goa XD. Characterization and antioxidant activity of two low molecular weight polysaccharides purified from the fruiting bodies of Ganoderma lucidum. International Journal of Biological Macromolecules 2010; 46: 451-457.

34. Xu ZT, Chen XU, Zhong ZF, Chen LD, Wang YT. Ganoderma lucidum polysaccharides: Immunomodulation and potential anti-tumor activities. The American Journal Journal of Chinese Medicine 2011; 39 (1): 15-27.

35. Zhang H, Li WJ, Nie SP, Chen Y, Wang YX, Xie MY. Structural characterization of a noval bioactive polysaccharide from Ganoderma atrum. Carbohydrate Polymers 2012; 88 (3):1047-1054.

36. Yong MY, Xin LW, Qi L, Li PJ, Cui PY, Bo H. Zhi LZ, Yong BC, Yong XC. Metabolites from the mushroom Ganoderma lingzhi as stimulators of neural stem cell proliferation. Phytochemistry 2015;114: 155-162.

37. Eva C, Jose LM, Pilar S, Cristina MT, Angel H, Jose CD. Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: Involvement of Akt and Erk. Jounal of Ethanopharmacology 2010; 128: 71-78.

38. Shih CH, Chien CO, Jhy WL, Tzu CC, Han PK, Jah YL, Chin SC, Song CL, Ching HS, Ming CK. Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G2/M cell cycle arrest. Journal of Ethanopharmacology 2008;120: 394-401.

39. Chien RC, Yen MT, Seng YH, Mau, JL. Chemical characteristics and anti-proliferation activities of Ganoderma tsugae Polysaccharides. Carbohydrate polymers 2015;128 (5): 90-98.

40. Ulrike L, Wolf DJ, Sabine W. Ganoderma pfeifferi- A European relative of Ganoderma lucidum. Phytochemistry 2015;114: 102-108.

41. Alex EA, Elaine RC, Rita CGS, Marina KK, Guilherme LS, Clarice AO, Philip AJG, Marcello L. An unusual water soluble β-glucan from the basidiocarp of the fungus Ganoderma resinaceum. Carbohydrate Polymers 2008; 78: 473-478.

42. Pei G, Tomoya H, Zhiqing C, Tadashi Y, Yoshihiro N, Akiko S. Isolation and Identification of C-19 fatty acids with anti-tumor activity from the spores of Ganoderma lucidum (reishi mushroom). Fitoterapia 2012; 83(3): 490-499.

43. Li LH, Qing YM, Sheng ZH, Zhi XM, Jian CG, Hao FD, You XZ. A new nortriterpenoid from the fruiting bodies of Ganoderma tropicum. Phytochemistry Letters 2014; 7: 11-13.

44. Sri F, Ryuichiro K, Kuniyoshi S. Structure-activity relationships of lanostane type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors. Bioorganic and Medicinal Chemistry Letters 2013; 23: 5900-5903.

45. Min Y, Xiaoming W, Shuhong G, Jiameng X, Jianghao S, Hui G, De G. Analysis of Triterpenoids in Ganoderma lucidum using liquid chromatography coupled with electrospray ionization mass spectrometry. Journal of the American Society for Mass Spectrometry 2017; 18: 927-939.

46. Lin CN, Tome WP, Won SJ. Novel cytotoxic principles of Formosan Ganoderma lucidum. Journal of Natural Product 1993; 54: 998-1002.

47. Kim BK, Cho HY, Kim JS, Kim HW, Choi EC. Studies on constituents of higher fungi of Korea Antitumor components of the cultured mycelia of Ganoderma lucidum. Korean Journal of Pharmacology1993; 24: 203-212.

48. Kuo MC, Weng CY, Ha CL, Wu, MJ. Ganoderma lucidum mycelia enhanced innata immunity by activating NF-Κb. Journal of Ethanopharmacology 2006; 103: 217-222.

49. Hajjaj H, Mace C, Roberts M, Niederberger P, Fay LB. Effect of 26-Oxygenosterole from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Applied Environmental Microbiology 2005; 71: 3653-3658.

50. Min BS, Nakamura N, Miyashiro H, Bae KW, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chemical Pharmaceutical Bulletin (Tokyo) 1998; 46: 1607-1612.

51. Kim KC, Kim IG. Ganoderma lucidum extract protects DNA from strand breakage caused by hydroxyl radical and UV irradiation. International Journal of Molecular Medicine1999b; 4: 273-277.

52. Tanaka S, Ko K, Kino K, Tsuchiya K, Yamashita A, Murasugi A, Sakuma S, Tsunoo H. Complete amino acid sequence of an immunomodulatory protein, ling zhi-8 (LZ-8). An immunomodulator from a fungus, Ganoderma lucidum, having similarity to immunoglobulin variable regions. Journal of Biological Chemistry 1989; 264: 16372-16377.

53. Ngai PHK, Ng TB. A mushroom (Ganoderma capense) lectin with spectacular thermostability, potent mitogenic activity on splenocytes and antiproliferative activity towards tumor cells. Biochemistry and Biophysics Research Communication 2004; 314: 988-993.

54. Gau JP, Lin CK, Lee, SS, Wang SR. The lack of antiplatelet effect of crude extracts from Ganoderma lucidum on HIV-positive hemophiliacs. American Journal of Chinese’s Medicines 1990; 18: 175-179.

55. Zhe J, Qingjiu T, Jinsong Z, Yan Y, Wei J, Yingjie P. Immunomodulation of RAW264.7 macrophages by GLIS, a proteopolysaccharide from Ganoderma lucidum. Journal of Ethanopharmacology 2007; 112: 445-450.

56. Jie L, Kuniyoshi S, Fumiko K, Shoichiro K, Ryuichiro K. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorganic and Medicinal Chemistry 2007; 15: 4966-4972.

57. Rumi F, Jie L, Kuniyoshi S, Fumiko K, Kiyoshi N, Shoichiro K, Chie U, Hisatoshi T, Shuhei K, Yoshitaro S, Ryuichiro K. Anti-androgenic activities of Ganoderma lucidum. Journal of Ethanopharmacology 2005; 102: 107-112.

58. Xiaomei S, Haohao W, Xiaofeng H, Shangwei Chen, Song Z, Jun D. Fingerprint analysis of Polysaccharides from different Ganoderma by HPLC combined with chemometrics methods. Carbohydrate Polymers 2014; 114: 432-439.

59. Jie L, Jun S, Kuniyoshi S, Akiko K, Toshio K, Ryuichiro K. Ganoderic acid DM: Anti-androgenic osteoclastogenesis inhibitor. Bioorganic and Medicinal Chemistry Letters 2009; 19: 2154-2157.

60. Ross RK, Bernstein L, Lobo RA. 5α-Reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 1992; 339: 887-889.

61. Jiang J, Slivova V, Sliva D. Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling. International Journal of Oncology 2006; 29: 695-703.

62. Shailesh D, Anita T, Daniel S. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. International Immunopharmacology. 2009; 9:1272-1280.

63. Zi YZ, Yu PT, Jun X, Pin W, Hui MJ, Zhong W, Masao M, Ding FC. Neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides on cerebral ischemic injury in rats. Journal of Ethanopharmacology 2010; 131: 154-164.

64. Yuen JWM, Gohel MDI, Ng CF. The differential immunological activities of Ganoderma lucidum on human pre-cancerous uroepithelial cells. Journal of Ethanopharmacology 2011; 135:711-718.

65. Horng HK, Chi FH, Jih PW, Chun NL. Antiinflammatory triterpenoids and steroids from Ganoderma lucidum and G. tsugae. Phytochemistry 2008; 69: 234-239.

66. Xiang YC, Su YC, Juan Z, Zi JW, Bin Y, Zhao FS, Xue QZ, Yong HZ. Extract of Ganoderma lucidum prolongs sleep time in rats. Journal of Ethanopharmacology 2012; 139: 796-800.

67. Isabel CFRF, Sandrina AH, Filipa SR, Dejan S, Maria JRP, Queirz MHV, Marina S. Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities. Phytochemistry 2014; 114: 38-55.

68. Masahiko I, Panida C, Surisa K, Kitlada S, Rattaket C. Lanostane triterpenes from cultures of the Basidiomycete Ganoderma orbiforme BCC 22324. Phytochemistry 2013; 87: 133-139.

69. Xiaobo S, Chen Z, Wei P, Jinping W, Weijun W. Carboxylate groups play a major role in antitumor activity of Ganoderma applanatum polysaccharide. Carbohydrate Polymers 2015; 123: 283-287.

70. Haou TM, Jung FH, Shui TC. Anti-diabetic effects of Ganoderma lucidum. Phytochemistry 2015; 114: 109-113.

71. Jasmina C, Jelena V, Mirjana S, Tatjana S, Jasmina G. Biological activity of Ganoderma lucidum basidiocarps cultivated on alternative and commercial substrate. Journal of Ethanopharmacology 2014; 155: 312-319.

Received on 29.06.2022 Modified on 18.08.2022

Res. J. Pharmacognosy and Phytochem. 2023; 15(1):46-52.

DOI: 10.52711/0975-4385.2023.00008