Chemical characterization and encapsulation of Ganoderma pfeifferi extract with cytotoxic properties
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic-ecollection
Document type Journal Article
PubMed
39917618
PubMed Central
PMC11799868
DOI
10.3389/fphar.2025.1526502
PII: 1526502
Knihovny.cz E-resources
- Keywords
- HeLa, antiproliferative activity, applanoxidic acids, bioactivity, reishi mushroom,
- Publication type
- Journal Article MeSH
Mushrooms of the genus Ganoderma are known for diverse biological activities, demonstrated both traditionally and experimentally. Their secondary metabolites have shown cytotoxic potential across different cancer cell lines. Besides exploration of the most active components in different species or genotypes, new formulation techniques are in development. In recent years, there has been a growing interest in the use of nanomaterials because of significant potential for pharmacology applications as substance carriers. Applying nanoparticles may enhance the medicinal effect of the mushroom substances. This study investigated the cytotoxic properties of Ganoderma species methanolic extracts against the HeLa cancer cell line. Notably, the extract obtained from Ganoderma pfeifferi demonstrated the highest activity and was further used for encapsulation within synthesized mesoporous silica nanoparticles MCM-41. Subsequently, the cytotoxic effect of the loaded MCM-41 to the free form of extract was compared. The obtained results indicate successful encapsulation, and similar activity comparing encapsulated form to free extracts (IC50 16.6 μg/mL and 20.5 μg/mL, respectively). In addition, the four unique compounds were identified as applanoxidic acid A, applanoxidic acid G, ganoderone A, and ganoderone B in the G. pfeifferi. This study is an essential prerequisite for further steps like nanoparticle functionalization for sustained or on-command delivery of these natural extracts.
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Ahmad R., Muhammad R., Aslam K., Ahmed A., Mohammad A., Deya S., et al. (2021). Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties. Phytotherapy Res. 35 (11), 6030–6062. 10.1002/ptr.7215 PubMed DOI
Beck J. S., Vartuli J. C., Roth W. J., Leonowicz M. E., Kresge C. T., Schmitt K. D., et al. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. J. Am. Chem. Soc. 114 (27), 10834–10843. 10.1021/ja00053a020 DOI
Chairul T. T., Hayashi Y., Nishizawa M., Tokuda H., Chairul S. M., Hayashi Y., et al. (1991). Applanoxidic acids A, B, C and D, biologically active tetracyclic triterpenes from Ganoderma applanatum. Phytochemistry 30 (12), 4105–4109. 10.1016/0031-9422(91)83476-2 DOI
Chang S. T., Wasser S. P. (2018). Current and future research trends in agricultural and biomedical applications of medicinal mushrooms and mushroom products (review). Int. J. Med. Mushrooms 20 (12), 1121–1133. 10.1615/IntJMedMushrooms.2018029378 PubMed DOI
Cheung P. C. K. (2010). The nutritional and health benefits of mushrooms. Nutr. Bull. 35 (4), 292–299. 10.1111/j.1467-3010.2010.01859.x DOI
Cör D., Knez Ž., Hrnčič M. K. (2018). Antitumour, antimicrobial, antioxidant and antiacetylcholinesterase effect of Ganoderma lucidum terpenoids and polysaccharides: a review. Molecules 23 (3), 649. 10.3390/molecules23030649 PubMed DOI PMC
Elkhateeb W. A. (2023). Therapeutic values of Ganoderma oregonense and Ganoderma pfeifferi, mushrooms: a review. Open Access J. Pharm. Res. 7 (1). 10.23880/oajpr-16000276 DOI
Estepa-Fernández A., Alfonso M., Aucejo Á. M., Fernández A. G., Viso A. L., Lozano‐Torres B., et al. (2021). Senolysis reduces senescence in veins and cancer cell migration. Adv. Ther. 4 (10). 10.1002/adtp.202100149 DOI
Ferlay J., Colombet M., Soerjomataram I., Parkin D. M., Piñeros M., Znaor A., et al. (2021). Cancer statistics for the year 2020: an overview. Int. J. Cancer 149 (4), 778–789. 10.1002/ijc.33588 PubMed DOI
Galappaththi M. C. A., Patabendige N. M., Premarathne B. M., Hapuarachchi K. K., Tibpromma S., Dong-Qin D., et al. (2022). A review of Ganoderma triterpenoids and their bioactivities. Biomolecules 13 (1), 24. 10.3390/biom13010024 PubMed DOI PMC
Galiana I., Lozano-Torres B., Sancho M., Alfonso M., Bernardos A., Bisbal V., et al. (2020). Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a NanoSenolytic. J. Control. Release 323 (July), 624–634. 10.1016/j.jconrel.2020.04.045 PubMed DOI
González A. G., León F., Rivera A., Muñoz C. M., Bermejo J. (1999). Lanostanoid triterpenes from Ganoderma l ucidum . J. Nat. Prod. 62 (12), 1700–1701. 10.1021/np990295y DOI
Guedikian R., Kim B., Singh G., Alexander R. (2023). Ganoderma lingzhi (Reishi mushroom)-induced acute liver injury in the setting of alcohol use: a case report and review of the literature. Cureus 15, e45953. 10.7759/cureus.45953 PubMed DOI PMC
Guillén-Meléndez G. A., Pérez-Hernández R. A., Chávez-Montes A., Castillo-Velázquez U., Loera-Arias M. de J., Montes-de-Oca-Saucedo C. R., et al. (2024). Nanoencapsulation of extracts and isolated compounds of plant origin and their cytotoxic effects on breast and cervical cancer treatments: advantages and new challenges. Toxicon 244 (June), 107753. 10.1016/j.toxicon.2024.107753 PubMed DOI
Gündoğdu S., Özenver N. (2023). “Anticancer potential of Ganoderma lucidum and its underlying mechanisms,” in Mushrooms with therapeutic potentials (Singapore: Springer Nature Singapore; ), 221–240. 10.1007/978-981-19-9550-7_7 DOI
Jambhrunkar S., Qu Z., Popat A., Yang J., Owen N., Acauan L., et al. (2014). Effect of surface functionality of silica nanoparticles on cellular uptake and cytotoxicity. Mol. Pharm. 11 (10), 3642–3655. 10.1021/mp500385n PubMed DOI
Johra F. T., Hossain S., Jain P., Tabassum Bristy A., Emran T., Ahmed R., et al. (2023). Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in long evans rats. Sci. Rep. 13 (1), 9909. 10.1038/s41598-023-35228-y PubMed DOI PMC
Kailasapathy K. (2009). Encapsulation technologies for functional foods and nutraceutical product development. CABI Rev. 2009 (January), 1–19. 10.1079/PAVSNNR20094033 DOI
Khan H., Reyes J. V. M., Seen T., Irefej B., Ahmad S. (2023). Herbal supplement-induced liver injury: a case report. Cureus, January 15, e33663. 10.7759/cureus.33663 PubMed DOI PMC
Kiddane A. T., Kang M.-J., Ho T. C., Getachew A. T., Prakash Patil M., Chun B.-S., et al. (2022). Anticancer and apoptotic activity in cervical adenocarcinoma HeLa using crude extract of Ganoderma applanatum. Curr. Issues Mol. Biol. 44 (3), 1012–1026. 10.3390/cimb44030067 PubMed DOI PMC
Koninti R. K., Palvai S., Satpathi S., Basu S., Hazra P. (2016). Loading of an anti-cancer drug into mesoporous silica nano-channels and its subsequent release to DNA. Nanoscale 8 (43), 18436–18445. 10.1039/C6NR06285G PubMed DOI
Kresge C. T., Leonowicz M. E., Roth W. J., Vartuli J. C., Beck J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359 (6397), 710–712. 10.1038/359710a0 DOI
Kuo P.-C., Thang T. D., Huang G.-J., Ngoc N. T. B., Nguyen T. N., Yang M.-L., et al. (2016). Chemical constituents of Ganoderma pfeifferi and their inhibitory effect on nitric oxide production. Chem. Nat. Compd. 52 (5), 948–950. 10.1007/s10600-016-1829-7 DOI
Lérida-Viso A., A Estepa F., Morellá-Aucejo Á., Lozano-Torres B., Alfonso M., Blandez J. F., et al. (2022). Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice. Pharmacol. Res. 183 (September), 106356. 10.1016/j.phrs.2022.106356 PubMed DOI
Lérida-Viso A., Estepa-Fernández A., García-Fernández A., Martí-Centelles V., Martínez-Máñez R. (2023). Biosafety of mesoporous silica nanoparticles; towards clinical translation. Adv. Drug Deliv. Rev. 201 (October), 115049. 10.1016/j.addr.2023.115049 PubMed DOI
Li X., Wang B., Zhou S., Chen W., Chen H., Liang S., et al. (2020). Surface chemistry governs the sub-organ transfer, clearance and toxicity of functional gold nanoparticles in the liver and kidney. J. Nanobiotechnology 18 (1), 45. 10.1186/s12951-020-00599-1 PubMed DOI PMC
Lindequist U., Jülich W.-D., Witt S. (2015). Ganoderma pfeifferi – a European relative of Ganoderma lucidum. Phytochemistry 114 (June), 102–108. 10.1016/j.phytochem.2015.02.018 PubMed DOI
Liu R.-M., Zhong J.-J. (2011). Ganoderic acid mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine 18 (5), 349–355. 10.1016/j.phymed.2010.08.019 PubMed DOI
Mazandarani A., Ali T., Mohammadnejad J., Yazdian F. (2023). Targeted anticancer drug delivery using chitosan, carbon quantum dots, and aptamers to deliver ganoderic acid and 5‐fluorouracil. Chem. and Biodivers. 20 (9), e202300659. 10.1002/cbdv.202300659 PubMed DOI
Money N. P. (2016). Are mushrooms medicinal? Fungal Biol. 120 (4), 449–453. 10.1016/j.funbio.2016.01.006 PubMed DOI
Mothana R. A. A., Awadh Ali N. A., Jansen R., Wegner U., Mentel R., Lindequist U. (2003). Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi. Fitoterapia 74 (1–2), 177–180. 10.1016/S0367-326X(02)00305-2 PubMed DOI
Mothana R. A. A., Jansen R., Jülich W.-D., Lindequist U. (2000). Ganomycins A and B, new antimicrobial farnesyl hydroquinones from the basidiomycete Ganoderma pfeifferi . J. Nat. Prod. 63 (3), 416–418. 10.1021/np990381y PubMed DOI
Muñoz B., Rámila A., Pérez-Pariente J., Díaz I., Vallet-Regí M. (2003). MCM-41 organic modification as drug delivery rate regulator. Chem. Mater. 15 (2), 500–503. 10.1021/cm021217q DOI
Niedermeyer T. H. J., Jira T., Lalk M., Lindequist U. (2013). Isolation of farnesylhydroquinones from the basidiomycete Ganoderma pfeifferi. Nat. Prod. Bioprospecting 3 (4), 137–140. 10.1007/s13659-013-0036-5 DOI
Niedermeyer T. H. J., Lindequist U., Mentel R., Gördes D., Schmidt E., Thurow K., et al. (2005). Antiviral terpenoid constituents of Ganoderma p feifferi . J. Nat. Prod. 68 (12), 1728–1731. 10.1021/np0501886 PubMed DOI
Noguchi M., Kakuma T., Tomiyasu K., Kurita Y., Kukihara H., Konishi F., et al. (2008). Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study. Asian J. Androl. 10 (4), 651–658. 10.1111/j.1745-7262.2008.00336.x PubMed DOI
Ogawa M. (2017). Mesoporous silica layer: preparation and opportunity. Chem. Rec. 17 (2), 217–232. 10.1002/tcr.201600068 PubMed DOI
Pang Z., Zhou G., Ewald J., Chang Le, Hacariz O., Basu N., et al. (2022). Using MetaboAnalyst 5.0 for LC–HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data. Nat. Protoc. 17 (8), 1735–1761. 10.1038/s41596-022-00710-w PubMed DOI
Paolino D., Mancuso A., Cristiano M. C., Froiio F., Lammari N., Celia C., et al. (2021). Nanonutraceuticals: the new frontier of supplementary food. Nanomaterials 11 (3), 792. 10.3390/nano11030792 PubMed DOI PMC
Pastorin G. (2009). Crucial functionalizations of carbon nanotubes for improved drug delivery: a valuable option? Pharm. Res. 26 (4), 746–769. 10.1007/s11095-008-9811-0 PubMed DOI
Patel S., Goyal A. (2012). Recent developments in mushrooms as anti-cancer therapeutics: a review. 3 Biotech. 2 (1), 1–15. 10.1007/s13205-011-0036-2 PubMed DOI PMC
Peters R. J. B., Bouwmeester H., Gottardo S., Amenta V., Arena M., Brandhoff P., et al. (2016). Nanomaterials for products and application in agriculture, feed and food. Trends Food Sci. and Technol. 54 (August), 155–164. 10.1016/j.tifs.2016.06.008 DOI
Poyatos-Racionero E., Guarí-Borràs G., Ruiz-Rico M., Morellá-Aucejo Á., Aznar E., Barat J. M., et al. (2021). Towards the enhancement of essential oil components’ antimicrobial activity using new zein protein-gated mesoporous silica microdevices. Int. J. Mol. Sci. 22 (7), 3795. 10.3390/ijms22073795 PubMed DOI PMC
Prado A. G. S., Moura A. O., Nunes A. R. (2011). Nanosized silica modified with carboxylic acid as support for controlled release of herbicides. J. Agric. Food Chem. 59 (16), 8847–8852. 10.1021/jf202509g PubMed DOI
Priyanka S., Patel S., Ranjitsinh D., Patel A. (2019). Camptothecin encapsulated into functionalized MCM-41: in vitro release study, cytotoxicity and kinetics. Mater. Sci. Eng. C 98 (May), 1014–1021. 10.1016/j.msec.2019.01.065 PubMed DOI
Rama Shankar G. S., Lavekar S. D., Sharma B. K. (2012). Traditional healing practice and folk medicines used by Mishing community of North East India. J. Ayurveda Integr. Med. 3, 124–129. 10.4103/0975-9476.100171 PubMed DOI PMC
Roth G. A., Abate D., Hassen Abate K., Abay S. M., Abbafati C., Abbasi N., et al. (2018). Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease study 2017. Lancet 392 (10159), 1736–1788. 10.1016/S0140-6736(18)32203-7 PubMed DOI PMC
Ru-Ming L. I. U., Ying-Bo L. I., Jian-Jiang ZHONG. (2012). Anti-proliferation and induced mitochondria-mediated apoptosis of ganoderic acid mk from Ganoderma lucidum mycelia in cervical cancer HeLa cells. Lat. Am. J. Pharm. 31 (1), 43–50.
Sarma D., Datta B., Saha A. (2018). Bioactive compounds with special references to anticancer property of oyster mushroom Pleurotus ostreatus. Jour. of Pharma. and Phy. 7 (August):2694–2698.
Schmaljohann D. (2006). Thermo- and PH-responsive polymers in drug delivery. Adv. Drug Deliv. Rev. 58 (15), 1655–1670. 10.1016/j.addr.2006.09.020 PubMed DOI
Sharma C., Bhardwaj N., Sharma A., Singh Tuli H., Batra P., Beniwal V., et al. (2019). Bioactive metabolites of Ganoderma lucidum: factors, mechanism and broad spectrum therapeutic potential. J. Herb. Med. 17–18 (September), 100268. 10.1016/j.hermed.2019.100268 DOI
Shiao M.-S. (2003). Natural products of the medicinal FungusGanoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem. Rec. 3 (3), 172–180. 10.1002/tcr.10058 PubMed DOI
Sun-Young P., Barton M., Pendleton P. (2012). Controlled release of allyl isothiocyanate for bacteria growth management. Food control 23 (2), 478–484. 10.1016/j.foodcont.2011.08.017 DOI
Vallet-Regi M., Balas F., Arcos D. (2007). Mesoporous materials for drug delivery. Angew. Chem. Int. Ed. 46 (40), 7548–7558. 10.1002/anie.200604488 PubMed DOI
Vallet-Regi M., Rámila A., del Real R. P., Pérez-Pariente J. (2001). A new property of MCM-41: drug delivery system. Chem. Mater. 13 (2), 308–311. 10.1021/cm0011559 DOI
Varghese R., Dalvi Y. B., Lamrood P. Y., Shinde B. P., Nair C. K. K. (2019). Historical and current perspectives on therapeutic potential of higher basidiomycetes: an overview. 3 Biotech. 9 (10), 362. 10.1007/s13205-019-1886-2 PubMed DOI PMC
Vicente C.-N., María A., Pedro A., Elena A., Dolores M. M., Ramón M.-M. (2024). In-depth study of factors affecting the formation of MCM-41-type mesoporous silica nanoparticles. Microporous Mesoporous Mater. 363 (January), 112840. 10.1016/j.micromeso.2023.112840 DOI
Wanmuang H., Leopairut J., Kositchaiwat C., Wananukul W., Bunyaratvej S. (2007). Fatal fulminant hepatitis associated with Ganoderma lucidum (lingzhi) mushroom powder. J. Med. Assoc. Thail. = Chotmaihet Thangphaet 90 (1), 179–181. PubMed
Wasser S. P. (2011). Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl. Microbiol. Biotechnol. 89 (5), 1323–1332. 10.1007/s00253-010-3067-4 PubMed DOI
Yuan D., He H., Wu Y., Fan J., Cao Y. (2019). Physiologically based pharmacokinetic modeling of nanoparticles. J. Pharm. Sci. 108 (1), 58–72. 10.1016/j.xphs.2018.10.037 PubMed DOI PMC
Yue Q.-X., Song X.-Y., Ma C., Feng L.-X., Guan S.-H., Wu W.-Y., et al. (2010). Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine 17 (8–9), 606–613. 10.1016/j.phymed.2009.12.013 PubMed DOI
Yuen M.-F., Philip Ip, Ng W.-K., Lai C.-L. (2004). Hepatotoxicity due to a formulation of Ganoderma lucidum (lingzhi). J. Hepatology 41 (4), 686–687. 10.1016/j.jhep.2004.06.016 PubMed DOI
Zhu H.-S., Yang X.-L., Wang L.-B., Zhao D.-X., Chen L. (2000). Effects of extracts from sporoderm-broken spores of Ganoderma lucidum on HeLa cells. Cell Biol. Toxicol. 16 (3), 201–206. 10.1023/A:1007663006548 PubMed DOI