Ganoderic Acid Research Articles

Comparing of antioxidant ability, α-glucosidase inhibition and cytotoxicity of three fruiting body shapes of Ganoderma lingzhi

In the process of artificial culture, Ganoderma mushrooms will appear with several different shapes of fruiting bodies, even though they share the same species. The differences in shape can influence and create differences in bioactivity and active ingredients. This study looked at the biological activities of ethanol crude extracts from three shape kinds of fruiting bodies of Ganoderma lingzhi mushroom and herb tablets made from kidney-shaped fruiting body including antioxidant, α-glucosidase inhibition and cytotoxic activity in some cell lines. Besides, the content of ganoderic acid A was also evaluated among the tested samples. The results showed that different shapes of G. lingzhi could possess differences in bioactivities. The shapes with elongated fruiting body stem including antler- and intermediate form, have better antioxidant and α-glucosidase inhibitory capacity than the common kidney shape. Furthermore, the antler and intermediate forms' cytotoxic activity against cell lines including fibroblast, NCI H469 and Hep G2, were higher than the kidney-shaped mushroom extracts. Similarly, the results of ganoderic acid A content from the extracts of antler- and intermediate form samples were also higher than that of the other form. Meanwhile, the herb tablets had the same pattern to the kidney-shaped extract in several activities. The ganoderic acid A content of the tablet sample was lower than that of three samples extracted from different mushroom shapes. Interestingly, the tablets showed the best-reducing power among the investigated samples.

Isolation, vibrational analysis, quantum chemical studies, nature of bonding, and molecular docking studies of triterpenoid isolates from Ganoderma lucidum as potent typhoid fever agent

The bacteria Salmonella Typhi is the source of the dangerous and perhaps fatal disease known as typhoid fever. Typhoid fever treatment is difficult despite the availability of potent medications due to the rise of multi-drug resistance strains. Herein, the extraction, LC-MS and FT-IR spectral characterization, density functional theory (DFT) and molecular docking investigation of 3,15-dihydroxy-11-toxolanost-8,24-dien-26-oic acid (C30H45O5) [MDC_1], Ganoderic acid F (C32H41O9) [MDC_2], and Ganolucidic acid E (C30H43O5) [MDC_3] isolated compounds from G. lucium against Salmonella Typhi enzyme, DNA gyrase B is presented along with the influence of solvation in polar and non-polar solvents. The FT-IR spectral results show that the triterpenoid extract of G. lucidum contains oxygen atoms, which mainly exist in functional groups (such as CO, O–H, C–O) and are consistent with the general molecular structures of triterpenoids. The reactivity parameters in the gas phase show that MDC_1 and MDC_3 have higher energy gaps whereas MD_2 has the lowest energy gap, indicating that it is more reactive than the other complexes. The energy gap of the compounds in solvent also shows a little shift, compared to the energy gap in Ethanol and Heptane, respectively. The results of the molecular docking study revealed several small molecules with strong binding affinities for the protein targets, suggesting that they could be used as potential therapeutics for typhoid fever. Therefore, this study suggests that molecular docking is a powerful tool for identifying novel therapeutics against tropical diseases such as typhoid fever.

Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation.

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus's ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from -7.4 to -8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from -6.2 to -8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.

The Development of Novel Ganoderic-Acid-Encapsulated Nanodispersions Using the Combination of Ultrasonic Cavitation and Solvent Evaporation through Response Surface Optimization

Ganoderic Acid (GA), a major bioactive compound isolated from the East Asian medicinal mushroom Ganoderma tsugae, is traditionally believed to have significant medicinal properties. GA is poorly soluble in water, which poses several challenges in terms of its formulation. In this study, Ganoderma tsugae extracts obtained through ethanol extraction were encapsulated in nanodispersions via ultrasonic cavitation and solvent evaporation to increase their bioavailability. The preparation route was thoroughly analyzed using Response Surface Methodology (RSM) to determine the interactions between the variables. Based on the results, the Hydrophilic–Lipophilic Balance (HLB) and the evaporation temperature significantly influenced the resulting particle size. In the optimized nanodispersions, GA was incorporated into a hydrophobic core with a particle size no greater than 200 nm and a very narrow particle distribution (namely, a polydispersity index of 0.289). Due to the high negative zeta potential (−45.9 mV), a very slow particle growth rate of 0.239% over short-term storage (14 days) was achieved. In addition, the zeta average remained virtually unchanged for 14 days at room temperature in solutions at different pH levels. In summary, this paper provides the first-ever demonstration that ultrasound cavitation in conjunction with solvent evaporation can be used to generate GA nanodispersions.

Retracted: Ganoderic Acid A Inhibits High Glucose-Induced Oxidative Stress and Extracellular Matrix Accumulation in Rat Glomerular Mesangial Cells.

[This retracts the article DOI: 10.1155/2022/5249910.].

Ganoderenic acid D-loaded functionalized graphene oxide-based carrier for active targeting therapy of cervical carcinoma

Ganoderenic acid D (GAD), extracted from the Chinese herb Ganoderma lucidum, was loaded onto a graphene oxide-polyethylene glycol-anti-epidermal growth factor receptor (GO-PEG-EGFR) carrier to develop a targeting antitumor nanocomposite (GO-PEG@GAD). The carrier was fabricated from PEG and anti-EGFR aptamer modified GO. Targeting was mediated by the grafted anti-EGFR aptamer, which targets the membrane of HeLa cells. Physicochemical properties were characterized by transmission electron microscopy, dynamic light scattering, X-ray powder diffraction, and Fourier transform infrared spectroscopy. High loading content (77.3 % ± 1.08 %) and encapsulation efficiency (89.1 % ± 2.11 %) were achieved. Drug release continued for approximately 100 h. The targeting effect both in vitro and in vivo was confirmed by confocal laser scanning microscopy (CLSM) and imaging analysis system. The mass of the subcutaneous implanted tumor was significantly decreased by 27.27 ± 1.23 % after treatment with GO-PEG@GAD compared with the negative control group. Moreover, the in vivo anti-cervical carcinoma activity of this medicine was due to activation of the intrinsic mitochondrial pathway.

Mushrooms and Lichens the Factory of Important Secondary Metabolites: Review

Mushrooms and lichens are plentiful source of nutritional and medicinal compounds. However, medicinal uses of the mushrooms and lichens still need to be worked out for their biological activities. Mushrooms and Lichens have reserved their position centuries ago as food and medicine. They are rich in nutrients and in biologically active compounds that belong to different chemical classes. Capabilities of different members of mushrooms and Lichens have encouraged researchers to investigate further applications of these macrofungi and lichens in fields of food and pharmaceutical industries and also other than food and pharmaceutical industries. This review, aims to put together Lentinan, schizophyllan, Betulinans A and B, ganoderic acid, cordycepin and usnic acid under light spot through representing their importance as biological activities exerted by ever one. Further studies and investigations are fortified in order to find more about these interesting natural products.

Hyperoxic storage increases the content of the active components in the post-harvest Ganoderma lucidum fruiting body

This study investigates the effect of hyperoxic storage on the antioxidant properties and bioactive substance metabolism of post-harvest Ganoderma lucidum fruiting bodies. During storage, the fruiting bodies experienced weight loss, which positively correlated with oxygen content. Oxygen treatment facilitated the increase of antioxidant enzyme activity and the decrease of membrane peroxidation. The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were increased by 58 %, 149 %, and 64 %, respectively; malondialdehyde (MDA) content was reduced by 39.91 % compared to the control group when the fruiting bodies were stored in 80% oxygen for 5 d. Meanwhile, the contents of Ganoderma polysaccharides and ganoderic acid increased with time, attaining maximum values of 121 g kg−1 and 8.23 g kg−1 on 4th d and 5th d, respectively, which were 36 % and 32 % higher than the control group. When the fruiting bodies were stored in 40 % and 80 % oxygen, the expression of key enzyme genes involved in the metabolism of Ganoderma polysaccharides and ganoderic acid, such as phosphoglucose metatase (PGM), uridinediphosphate glucose pyrophosphorylase (UGP), β-1,3-glucan synthase (GLS), hydroxymethylglutaryl-CoA reductase (HMGR), squalene synthase (SQS), lanosterol synthase (LS) and squalene epoxidase (SE), was found to be upregulated.

A Gene from Ganoderma lucidum with Similarity to nmrA of Filamentous Ascomycetes Contributes to Regulating AreA

Fungal AreA is a key nitrogen metabolism transcription factor in nitrogen metabolism repression (NMR). Studies have shown that there are different ways to regulate AreA activity in yeast and filamentous ascomycetes, but in Basidiomycota, how AreA is regulated is unknown. Here, a gene from Ganoderma lucidum with similarity to nmrA of filamentous ascomycetes was identified. The NmrA interacted with the C-terminal of AreA according to yeast two-hybrid assay. In order to determine the effect of NmrA on the AreA, 2 nmrA silenced strains of G. lucidum, with silencing efficiencies of 76% and 78%, were constructed using an RNA interference method. Silencing nmrA resulted in a decreased content of AreA. The content of AreA in nmrAi-3 and nmrAi-48 decreased by approximately 68% and 60%, respectively, compared with that in the WT in the ammonium condition. Under the nitrate culture condition, silencing nmrA resulted in a 40% decrease compared with the WT. Silencing nmrA also reduced the stability of the AreA protein. When the mycelia were treated with cycloheximide for 6 h, the AreA protein was almost undetectable in the nmrA silenced strains, while there was still approximately 80% of the AreA protein in the WT strains. In addition, under the nitrate culture, the content of AreA protein in the nuclei of the WT strains was significantly increased compared with that under the ammonium condition. However, when nmrA was silenced, the content of the AreA protein in the nuclei did not change compared with the WT. Compared with the WT, the expression of the glutamine synthetase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 94% and 88%, respectively, under the ammonium condition, while the expression level of the nitrate reductase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 100% and 93%, respectively, under the nitrate condition. Finally, silencing nmrA inhibited mycelial growth and increased ganoderic acid biosynthesis. Our findings are the first to reveal that a gene from G. lucidum with similarity to the nmrA of filamentous ascomycetes contributes to regulating AreA, which provides new insight into how AreA is regulated in Basidiomycota.

Synthetic consortium of Ganoderma lucidum and Lactobacillus plantarum for enhanced natural products biosynthesis

Microbial coculture holds immense promise for biomanufacturing. Herein, we designed a synthetic consortium of G. lucidum and L. plantarum for enhanced natural product biosynthesis. The spatio-temporal alignment of the strains revealed an implicit disposition for transient and long-term mutualistic co-existence in the shared environment. The consortium assembly and biomass growth were driven by an intuitive toggle-switching of carbon/nitrogen sources and TOR signaling. Extracellular electron transfer propelled by redox shuttles facilitated the distribution of high-energy electrons and enhanced the consortium's robustness. The ROS-scavenging activity of antioxidant enzymes maintained the cells' viability via intracellular ROS removal. The CAT, GPX, and APX enzymes catalyzed the reduction of H2O2 to H2O and O2, thereby protecting the cells against the toxic effects of ROS. Small-signaling molecules stimulated the biosynthesis of bioactive natural products in the coculture. Over-expression of target genes further enhanced ganoderic acids and exopolysaccharides bioproduction in the coculture system. The study provides insight into the physicochemical and molecular forces that drive cooperative interaction and stimulate natural product biosynthesis in G. lucidum and L. planatarum consortium.

IN-SILICO DOCKING STUDIES OF CARBONIC ANHYDRASE INHIBITORS IN THE MANAGEMENT OF NEUROPATHIC PAIN

Background: In the present study, the in-silico docking studies of carbonic anhydrase inhibitors with 4RUX i.e. The crystal Structure of Human carbonic Anhydrase II protein was performed in the management of neuropathic pain. Materials and Methods: The crystal structure of protein PDB ID: 4RUX was downloaded from the RCSB PDB database and the ligand molecules of carbonic anhydrase inhibitors were drawn from Marvin Sketch. Docking studies between ligand and protein to predict binding interactions by using AutoDock 4.2 and the receptor-ligand complex interaction viewed by using Biovia Drug Discovery studio. Result: Carbonic anhydrase inhibitors showed binding energy ranging between -5.41 to -8.63. Ganoderic acid A showed better binding energy -8.63 kcal/mol than the standard Acetazolamide -6.22 kcal/mol. Conclusion: The result clearly indicates that among carbonic anhydrase inhibitors, Ganoderic acid A and Morindone show better hydrogen bonding and binding affinity towards carbonic anhydrase II (PDB ID: 4RUX). Thus, conclude that among carbonic anhydrase inhibitors Ganoderic acid A (obtained from Ganoderma lucidium) and Morindone (both obtained from Morinda citrifolia (NONI)} provide the better pharmacological effect.

Ganoderic Acid A Enhances Tumor Suppression Function of Oxaliplatin via Inducing the Cytotoxicity of T Cells.

Various natural products have been demonstrated for their anti-tumor activities. As a natural triterpenoid, the effects of ganoderic acid A on oxaliplatin chemotherapy for cancer treatment remain unclear. A xenograft mouse model of colon cancer was constructed using the HT-29 cells. Ganoderic acid A was intravenously administered with or without oxaliplatin. The CCK-8 method was performed to assess cell viability. Flow cytometry was used to determine cell apoptosis and subtyping of T cells. Cytotoxicity of the T cells was assayed using a lymphocyte-tumor co-culture system in vitro. Ganoderic acid A enhanced tumor suppression of oxaliplatin in the xenograft model, while single administration showed no obvious anti-tumor effect. Ganoderic acid A didn't affect cell proliferation and apoptosis of HT-29 cells treated by oxaliplatin in vitro. Additionally, ganoderic acid A co-administered with oxaliplatin didn't impact T cell subtyping in the xenograft model. Cytotoxicity of T cells in co-administered mice was remarkably enhanced compared with oxaliplatin-treated mice. Our findings reveal that ganoderic acid A synergistically enhances tumor suppression of oxaliplatin possibly via increasing the cytotoxicity of T cells.

Exploring the components and mechanisms of Shen-qi-wang-mo granule in the treatment of retinal vein occlusion by UPLC-Triple TOF MS/MS and network pharmacology

This study aimed to explore the substance basis and mechanisms of Shen-qi-wang-mo Granule (SQWMG), a traditional Chinese medicine prescription that had been clinically utilized to treat retinal vein occlusion (RVO) for 38 years. Components in SQWMG were analyzed by UPLC-Triple-TOF/MS and a total of 63 components were identified with ganoderic acids (GA) being the largest proportion. Potential targets of active components were retrieved from SwissTargetPrediction. RVO-related targets were acquired from related disease databases. Core targets of SQWMG against RVO were acquired by overlapping the above targets. The 66 components (including 5 isomers) and 169 targets were obtained and concluded into a component-target network. Together with biological enrichment analysis of targets, it revealed the crucial role of the “PI3K-Akt signaling pathway”, “MAPK signaling pathway” and their downstream factor iNOS and TNF-α. The 20 key targets of SQWMG in treating RVO were acquired from the network and pathway analysis. The effects of SQWMG on targets and pathways were validated by molecular docking based on AutoDock Vina and qPCR experiment. The molecular docking showed great affinity for these components and targets, especially on ganoderic acids (GA) and alisols (AS), which were both triterpenoids and qPCR exhibited remarkably reduced inflammatory factor gene expression through regulation of these two pathways. Finally, the key components were also identified from rat serum after treatment of SQWMG.

Biosynthesis of a Novel Ganoderic Acid in Saccharomyces cerevisiae and Research of its Antitumor Activity

Biosynthesis of a Novel Ganoderic Acid in Saccharomyces cerevisiae and Research of its Antitumor Activity

Advances in the biosynthesis, diversification, and hyperproduction of ganoderic acids in Ganoderma lucidum

Advances in the biosynthesis, diversification, and hyperproduction of ganoderic acids in Ganoderma lucidum

Modeling and optimization of the protocol of complex chromatography separation of cyclooxygenase-2 inhibitors from Ganoderma lucidum spore.

The spores of the medicinal fungus Ganoderma lucidum possess hepatoprotective properties. The main components, triterpenes, are particularly beneficial, making the screening and preparation of active triterpenes from Ganoderma lucidum significant. We aimed to screen and verify cyclooxygenase-2 inhibitors from G. lucidum spores, establish a rapid online hyphenated technique for the preparation of active ingredients, and analyze the structures of the active ingredients. Ultrafiltration LC combined with an enzyme inhibition assay and molecular docking was employed to screen and evaluate cyclooxygenase-2 ligands, which were prepared by pressurized liquid extraction coupled online with countercurrent chromatography and semi-preparative LC. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. Six cyclooxygenase-2 inhibitors, namely, ganoderic acids I, C2 , G, B, and A and ganoderenic acid A, were screened and evaluated. They were prepared using the online hyphenated technique, following which their structures were identified. This study provides opportunities for the discovery and development of new therapeutic drugs from other natural resources, as the present instrumental setup achieved efficient and systematic extraction and isolation of natural products compared with reference separation methods, thus exhibiting significant potential for industrial applications.

Novel Ganoderma triterpenoid saponins from the biotransformation-guided purification of a commercial Ganoderma extract

Ganoderma sp. contains high amounts of diverse triterpenoids; however, few triterpenoid saponins could be isolated from the medicinal fungus. To produce novel Ganoderma triterpenoid saponins, biotransformation-guided purification (BGP) process was applied to a commercial Ganoderma extract. The commercial Ganoderma extract was partially separated into three fractions by preparative high-performance liquid chromatography, and the separated fractions were then directly biotransformed by a Bacillus glycosyltransferase (BsUGT489). One of the biotransformed products could be further purified and identified as a novel saponin: ganoderic acid C2 (GAC2)-3-O-β-glucoside by nucleic magnetic resonance (NMR) and mass spectral analyses. Based on the structure of the saponin, the predicted precursor should be the GAC2, which was confirmed to be biotransformed into four saponins, GAC2-3-O-β-glucoside, GAC2-3,15-O-β-diglucoside and two unknown GAC2 monoglucosides, revealed by NMR and mass spectral analyses. GAC2-3-O-β-glucoside and GAC2-3,15-O-β-diglucoside possessed 17-fold and 200-fold higher aqueous solubility than that of GAC2, respectively. In addition, GAC2-3-O-β-glucoside retained the most anti-α-glucosidase activity of GAC2 and was comparable with that of the anti-diabetes drug (acarbose). The present study showed that the BGP process is an efficient strategy to survey novel and bioactive molecules from crude extracts of natural products.

Ganoderic Acid A and Its Amide Derivatives as Potential Anti-Cancer Agents by Regulating the p53-MDM2 Pathway: Synthesis and Biological Evaluation

The mechanisms of action of natural products and the identification of their targets have long been a research hotspot. Ganoderic acid A (GAA) is the earliest and most abundant triterpenoids discovered in Ganoderma lucidum. The multi-therapeutic potential of GAA, in particular its anti-tumor activity, has been extensively studied. However, the unknown targets and associated pathways of GAA, together with its low activity, limit in-depth research compared to other small molecule anti-cancer drugs. In this study, GAA was modified at the carboxyl group to synthesize a series of amide compounds, and the in vitro anti-tumor activities of the derivatives were investigated. Finally, compound A2 was selected to study its mechanism of action because of its high activity in three different types of tumor cell lines and low toxicity to normal cells. The results showed that A2 could induce apoptosis by regulating the p53 signaling pathway and may be involved in inhibiting the interaction of MDM2 and p53 by binding to MDM2 (KD = 1.68 µM). This study provides some inspiration for the research into the anti-tumor targets and mechanisms of GAA and its derivatives, as well as for the discovery of active candidates based on this series.

RETRACTED: Analysis of Conocurvone, Ganoderic acid A and Oleuropein molecules against the main protease molecule of COVID-19 by in silico approaches: Molecular dynamics docking studies

Traditional medicines against COVID-19 have taken important outbreaks evidenced by multiple cases, controlled clinical research, and randomized clinical trials. Furthermore, the design and chemical synthesis of protease inhibitors, one of the latest therapeutic approaches for virus infection, is to search for enzyme inhibitors in herbal compounds to achieve a minimal amount of side-effect medications. Hence, the present study aimed to screen some naturally derived biomolecules with anti-microbial properties (anti-HIV, antimalarial, and anti-SARS) against COVID-19 by targeting coronavirus main protease via molecular docking and simulations. Docking was performed using SwissDock and Autodock4, while molecular dynamics simulations were performed by the GROMACS-2019 version. The results showed that Oleuropein, Ganoderic acid A, and conocurvone exhibit inhibitory actions against the new COVID-19 proteases. These molecules may disrupt the infection process since they were demonstrated to bind at the coronavirus major protease's active site, affording them potential leads for further research against COVID-19.

A Review on the Sources, Structures, and Pharmacological Activities of Lucidenic Acids.

Ganoderma lucidum has long been used as a multi-purpose plant and functional food. The pharmacological properties of G. lucidum are primarily attributed to its polysaccharides and triterpenoids. Ganoderic and lucidenic acids are the two major triterpenoids groups in G. lucidum. Despite the discovery of 22 types of lucidenic acids, research on lucidenic acids is significantly less extensive compared to that on ganoderic acid. To the best of our knowledge, for the first time, in this review, we aimed to summarize the sources, contents, chemical structures, and pharmacological effects, including anti-cancer, anti-inflammatory, antioxidant, anti-viral, neuroprotective, anti-hyperlipidemic, anti-hypercholesterolemic, and anti-diabetic properties, of lucidenic acids. Studies on lucidenic acids are still preliminary and have several limitations. Therefore, more in-depth studies with optimal designs are essential for the development of lucidenic acids as medicines, functional foods, and nutraceuticals.