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Chemical Compounds and Computational Prediction of Their Inhibitory Effects on the HIV-1 gp120 Receptor by Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), with Antler-Like Morphology of Fruiting Bodies

Cheng PG, Teoh TC, Rizman-Idid M

Int J Med Mushrooms, 2021;23(7):63-77.
PMID: 34375519 DOI: 10.1615/IntJMedMushrooms.2021038682

In this study, crude extracts of Ganoderma lucidum (NGCs) were compared to the crude extracts of G. lucidum that has antler-like fruiting bodies (AGCs) for their cytotoxicity, inhibitory effects on the attachment of human immunodeficiency virus (HIV)-1 glycoprotein 120 (gp120) to cluster of differentiation 4 (CD4), identification and molecular docking simulations of chemical compounds to predict the best ligand inhibitor and the binding mechanism. Results showed that AGCs had a higher percentage of inhibition (54.3% ± 6.2%) at 150 ppm and higher cytotoxicity (half maximal cytotoxic concentration [CC50] < 300 ppm) than NGCs (CC50 < 400 ppm). Quadrupole time-of-flight (QTOF) liquid chromatography- mass spectrometry (LC-MS) results successfully identified 32 chemical compounds in AGCs and NGCs, comprising mostly ganoderic acids (62%) and their derivatives. Molecular docking simulations of ganolucidic acid A/D and ganoderic acid A/B predicted the strongest binding affinity via hydrogen bonding, suggesting the inhibition of HIV-1 gp120 attachment to CD4. The highest and lowest occupied molecular orbital (HOMO and LUMO, respectively) gap energies of ganoderic acids tended to have less negative HOMO energy and smaller HOMO-LUMO gap energy, implying increased interactions of ligands to the gp120 protein receptor. AGCs showed higher inhibition against HIV-1 gp120 than NGCs due to a higher abundance of ganoderic and ganolucidic acids, whereby both acids contributed the highest number of hydrogen bonds and polar interactions from the hydroxyl and carboxylic functional groups.
The identification of active compounds in Ganoderma lucidum var. antler extract inhibiting dengue virus serine protease and its computational studies

Lim WZ, Cheng PG, Abdulrahman AY, Teoh TC

J Biomol Struct Dyn, 2020 Sep;38(14):4273-4288.
PMID: 31595837 DOI: 10.1080/07391102.2019.1678523

The number of global dengue incidences is alarmingly high in recent years. The global distribution of four dengue serotypes has also added economic burden in the dengue-endemic countries. To discover the potent dengue virus inhibitors in the antler form of Ganoderma lucidum (Lingzhi or Reishi), the water extraction of normal G. lucidum and its antler form were conducted and the chemical compounds were identified by LC-MS. Six distinct chemical compounds identified in high abundance were hesperetin, thymidine, lucidenic acid, 11-aminoundecanoic acid, 5-carboxyvanillic acid and ganocin B. The water extracts of G. lucidum in its antler form inhibited the DENV2 NS2B-NS3 protease activity at 84.6 ± 0.7%, higher than the normal G. lucidum. Then, molecular docking was performed on the homology model built from an in-house sequence. Docking simulation results showed that hesperetin and ganocin B were the best leads to bind at the catalytic triad of DENV2 NS2B-NS3pro via hydrogen bonding, van der Waals and pi-pi interactions. Extensive overlapping of HOMO-LUMO orbitals at the ringed regions of hesperetin helped to facilitate the entry of ligand to the catalytic triad cleft. LC-MS, molecular docking and density functional theory analyses confirmed that hesperetin was the strongest inhibitor against NS2B-NS3 protease. Communicated by Ramaswamy H. Sarma.
Development of antler-type fruiting bodies of Ganoderma lucidum and determination of its biochemical properties

Sudheer S, Taha Z, Manickam S, Ali A, Cheng PG

Fungal Biol, 2018 05;122(5):293-301.
PMID: 29665955 DOI: 10.1016/j.funbio.2018.01.007

Following the importance of antler-type fruiting bodies of Ganoderma lucidum, in this study, the impact of main growth parameters such as ventilation and light on the development of antler-type fruiting bodies has been investigated together with the determination of physico-chemical properties of antler fruiting bodies. For this, the primordia bags of G. lucidum were kept under controlled ventilation to adjust the CO2 produced by the mushrooms owing to its respiration under light and dark conditions. The bioactive compounds such as phenolics, flavonoids, water-soluble polysaccharides and ganoderic acid showed a two-fold increase in the antler-type fruiting bodies as compared to normal kidney-shaped fruiting bodies. It is assumed from this study that the antler type fruiting bodies are developed due to restricted ventilation which causes an increase in the level of CO2 gas in the air as a result of respiration of mushroom. The shape and colour of antler fruiting bodies again dependent on the light provided in the growth chamber. This study also proves that with the manipulation of light and ventilation antler-type fruiting bodies of G. lucidum could be developed with higher quantity of bioactive compounds and with higher antioxidant potential.
Determination of the Biological Efficiency and Antioxidant Potential of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Cultivated Using Different Agro-Wastes in Malaysia

Sudheer S, Alzorqi I, Ali A, Cheng PG, Siddiqui Y, Manickam S

Int J Med Mushrooms, 2018;20(1):89-100.
PMID: 29604916 DOI: 10.1615/IntJMedMushrooms.2017024588

This study investigates the cultivation of Ganoderma lucidum using different agricultural biomasses from Malaysia. Five different combinations of rubber wood sawdust, empty fruit bunch fiber, and mesocarp fiber from oil palm, alone and in combination, were used to cultivate G. lucidum. Although all the substrate combinations worked well to grow the mushroom, the highest biological efficiency was obtained from the combination of empty fruit bunch fiber with sawdust. A total yield of 27% was obtained from empty fruit bunch fiber with sawdust, followed by sawdust (26%), empty fruit bunch fiber (19%), mesocarp fiber with sawdust (19%), and mesocarp fiber (16%). The quality of mushrooms was proved by proximate analysis and detection of phenolic compounds and flavonoids. The antioxidant activity verified by DPPH, ferric-reducing ability of plasma, and ABTS analyses revealed that the empty fruit bunch fiber with sawdust had higher activity than the other substrates.
Fulltext Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

Cheng PG, Phan CW, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR

Evid Based Complement Alternat Med, 2013;2013:671252.
PMID: 24348715 DOI: 10.1155/2013/671252

Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.
Fulltext Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression

Chong PS, Poon CH, Roy J, Tsui KC, Lew SY, Phang MWL, et al.

Chin Med, 2021 Dec 07;16(1):132.
PMID: 34876186 DOI: 10.1186/s13020-021-00546-8

BACKGROUND: Depression is a severe neuropsychiatric disorder that affects more than 264 million people worldwide. The efficacy of conventional antidepressants are barely adequate and many have side effects. Hericium erinaceus (HE) is a medicinal mushroom that has been reported to have therapeutic potential for treating depression.
METHODS: Animals subjected to chronic restraint stress were given 4 weeks HE treatment. Animals were then screened for anxiety and depressive-like behaviours. Gene and protein assays, as well as histological analysis were performed to probe the role of neurogenesis in mediating the therapeutic effect of HE. Temozolomide was administered to validate the neurogenesis-dependent mechanism of HE.
RESULTS: The results showed that 4 weeks of HE treatment ameliorated depressive-like behaviours in mice subjected to 14 days of restraint stress. Further molecular assays demonstrated the 4-week HE treatment elevated the expression of several neurogenesis-related genes and proteins, including doublecortin, nestin, synaptophysin, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated extracellular signal-regulated kinase, and phosphorylated cAMP response element-binding protein (pCREB). Increased bromodeoxyuridine-positive cells were also observed in the dentate gyrus of the hippocampus, indicating enhanced neurogenesis. Neurogenesis blocker temozolomide completely abolished the antidepressant-like effects of HE, confirming a neurogenesis-dependent mechanism. Moreover, HE induced anti-neuroinflammatory effects through reducing astrocyte activation in the hippocampus, which was also abolished with temozolomide administration.
CONCLUSION: HE exerts antidepressant effects by promoting neurogenesis and reducing neuroinflammation through enhancing the BDNF-TrkB-CREB signalling pathway.