Academic literature on the topic 'Ganoderma species'

The effect of different cultivation methods on the content of ganoderic acids of 7 species, 10 strains of the Ganoderma genus (Ganoderma applanatum 1899; Ganoderma сarnosum 2502; Ganoderma lucidum 1904; Ganoderma resinaceum 2477, 2503; Ganoderma sinense 2516; Ganoderma tsugae 1848, 2024, 2566, Ganoderma oregonense 2560) genus fungi from the IBK Mushroom Culture Collection M.G. Kholodny Institute of Botany of National Academy of Sciences of Ukraine was investigated. It has been shown that the submerged cultivation method is more efficient for the accumulation of ganoderic acids for five strains. In the mycelium of the strain G. sinense 2516 was the highest content of ganoderic acids – 25.2 ± 1.5 mg / g. The productivity (yeld) of ganoderic acids synthesis is much higher with using the submerged culture cultivation method for mycelium of all used species and strains since the use of this method provides the accumulation of much more biomass in comparison with the static liquid cultivation method. The highest yield amount of ganoderic acids was in the mycelium of the G. tsugae 2024 and G. tsugae 2566 species, namely: 0.35 ± 0.019 and 0.36 ± 0.028 g / l. It was proved that the modified extraction method significantly reduces the extraction time of ganoderic acids. Extraction time is reduced from 14 to 2 days. For the G. sinense 2516 and G. tsugae 2024 strains was determined content of the ganoderic acids and their yield in dynamics of grows in the submerged culture on 6, 8, 10, 12, 14, 16, 18 and 20 day of cultivation. The highest amount of the ganoderic acids content was accumulated by the mycelium of the strain G. sinense 2516 – it was 26.4 ± 1.5 mg / g on the 14th day of cultivation. The highest yield of the ganoderic acids was in G. sinense 2516 on 14th day, and G. tsugae 2024 mycelium on the 16th day of cultivation with the next numbers 0.6 ± 0.031, 0.62 ± 0.033 and 0.62 ± 0.027 g/l.

ABSTRAKDi dunia, jamur Ganodermatelah dikenal sebagai jamur obat. Ganoderma lebih dikenal dengan sebutan jamur Lingzhi atau Reishi. Dari 2000 spesies Ganoderma, hanya 6 spesies yang telah diteliti memiliki efek potensial dalam bidang kesehatan, yaitu G. lucidum, G. applanatum, G. tsugae, G. oregonense, G. boninense, dan G. neojapanicum. Kandungan senyawa bioaktif yang terkandung di dalam Ganoderma terus dikembangkan dalam pemanfaatannya sebagai obat alternatif. Hal inilah yang menyebabkan jamur Ganoderma bebas dari efek samping.Enam spesies Ganoderma ini memiliki karakteristik dengan berbagai potensi kesehatan yang berbedabeda dan berkhasiat sebagai bahan obat. Dari keenam Ganoderma, hanya G. boninense yang memiliki toksisitas terhadap larva udang Artemia salina.Kata Kunci: Tipe-tipe Ganoderma sp, karakteristik fisik, senyawa bioaktif, manfaat Ganoderma sp. bagi kesehatanABSTRACTIn the world, the fungus Ganoderma has been known as a medicinal mushroom. Ganoderma is known as Lingzhi or Reishi mushroom. From 2000 Ganoderma species, only six species that have been studied have a potential effect on health, namely G. lucidum, G. applanatum, G. tsugae, G. oregonense, G. boninense, and G. neojapanicum. The content of bioactive compounds contained in Ganoderma continue to be developed in their usage as an alternative medicine. This is what causes the fungus Ganoderma is free from side effects. Six speciesof Ganoderma has characteristics with various health potentials that vary and efficacious as a drug ingredient. Of the six Ganoderma, only G. boninense has toxicity to the shrimp larvae of Artemia salina.Keywords: Types of Ganodermasp., physical characteristics, bioactive components, health benefits of Ganoderma sp.

Abstract From the economical point of view, the genus Ganoderma is one of the most important groups of Basidiomycetes due to their medicinal effects and also because they cause decay in a very wide range of tree species all over the world. In this study new data of the Hungarian Ganoderma species are published and the specimens in accessible Hungarian herbarium collections are processed and revised. The article includes the nomenclatural status, the morphological characters, the host preference, frequencies and the details of the fungarium samples of six Ganoderma species (Ganoderma adspersum, G. applanatum, G. carnosum, G. cupreolaccatum, G. lucidum, G. resinaceum) as well. In total 215 Ganoderma specimens are examined and 10 hosts of the six native Ganoderma species new for Hungary are presented. The Hungarian locality and time of the collection of the only Ganoderma carnosum (IZ3122) specimen and two new localities of this rare species is published here for the first time.

Species in the genus Ganoderma include several ecologically important and pathogenic fungal species whose medicinal and economic value is substantial. Due to the highly similar morphological features within the Ganoderma, identification of species has relied heavily on DNA sequencing using BLAST searches, which are only reliable if the GenBank submissions are accurately labeled. In this study, we examined 113 specimens collected from 1969 to 2016 from various regions in Korea using morphological features and multigene analysis (internal transcribed spacer, translation elongation factor 1-α, and the second largest subunit of RNA polymerase II). These specimens were identified as four Ganoderma species: G. sichuanense, G. cf. adspersum, G. cf. applanatum, and G. cf. gibbosum. With the exception of G. sichuanense, these species were difficult to distinguish based solely on morphological features. However, phylogenetic analysis at three different loci yielded concordant phylogenetic information, and supported the four species distinctions with high bootstrap support. A survey of over 600 Ganoderma sequences available on GenBank revealed that 65% of sequences were either misidentified or ambiguously labeled. Here, we suggest corrected annotations for GenBank sequences based on our phylogenetic validation and provide updated global distribution patterns for these Ganoderma species.

 У оквиру ове докторске дисертације испитан је хемијски састав и биолошке активности ЕtOH, H₂Oи CHCl₃  екстраката четири врсте гљива рода Ganoderma  (Basidiomycota):  G. applanatum,  G. lucidum,G. pfeifferi,  G. resinaceum  са територије Војводине.Хемијски састав анализираних врста је одређенприменом: ААЅ методе (састав макро-  имикроелемената у сувим остацима гљива) и LC-MS/MS технике (квантитативни састав фенолних једињења и флавоноида) при чему је детектовано 12 једињења. Спектрофотометријским методама је одређен садржај протеина, шећера, укупних фенола и флавоноида, код којих је највећи садржај протеина утврђен за ЕtOH екстракте  G. applanatum  и  G. pfeifferi. Испитивања биолошких активности екстраката обухватила су: одређивање   in vitro   и  in vivo антиоксидантне, антимикробне, антиинфламаторне, антипролиферативне и антијабето гене   aктивности.      Антиоксидантна активност (способност неутрализације слободних радикала и редукциони потенцијал) је одређена спектрофотометријским методама, при којој су најбољу активност остварили Н₂О екстракти  G. applanatum. Антимикробнa активност  анализираних екстраката одређена је испитивањем антибактеријског, антифунгалног и антивиралног потенцијала где се издвојила G. pfeifferi врста. Антиинфламаторни потенцијал EtOH и  CHCl₃ екстраката одређен је  ex vivo  методом мерењем способности инхибиције продукције медијатора инфламације  (продукти  метаболизма арахидонске киселине) при којој су бољу активност испољили CHCl₃ екстракти.Ефекат EtOH и H₂O екстраката врста рода Ganoderma   на раст MCF ћелијске линије испитан је MTT тестом, а посебно су се издвојили  EtOH  екстракти врста после 72h.Остварена антидијабетогена активност EtOH и Н₂О екстраката врста   G. pfeifferi   и  G. resinaceum  код алоксан-индукованог  D. mell itus-a  на  експерименталним  животињама  праћена je регенерацијом  ß- ћелија  Лангерхансових острваца панкреаса. Као потенцијални нефро-  и  хепатопротективни агенси се издвајају екстракти  G. resinaceum.Сумарно, укупни биопотенцијал анализираних врста рода  Ganoderma  на основу спроведених анализа хемијске   kарактеризације и биолошке активности упућује  на  могућност њихове потенцијалне примене као нутрацеутика и додатака исхрани, у будућности уз неопходност додатних микохемијских истраживања ових врста, посебно терпеноида и полисахарида, као и других биолошких активности као што је неуропротективна.
 U okviru ove doktorske disertacije ispitan je hemijski sastav i biološke aktivnosti EtOH, H₂Oi CHCl₃  ekstrakata četiri vrste gljiva roda Ganoderma  (Basidiomycota):  G. applanatum,  G. lucidum,G. pfeifferi,  G. resinaceum  sa teritorije Vojvodine.Hemijski sastav analiziranih vrsta je određenprimenom: AAЅ metode (sastav makro-  imikroelemenata u suvim ostacima gljiva) i LC-MS/MS tehnike (kvantitativni sastav fenolnih jedinjenja i flavonoida) pri čemu je detektovano 12 jedinjenja. Spektrofotometrijskim metodama je određen sadržaj proteina, šećera, ukupnih fenola i flavonoida, kod kojih je najveći sadržaj proteina utvrđen za EtOH ekstrakte  G. applanatum  i  G. pfeifferi. Ispitivanja bioloških aktivnosti ekstrakata obuhvatila su: određivanje   in vitro   i  in vivo antioksidantne, antimikrobne, antiinflamatorne, antiproliferativne i antijabeto gene   aktivnosti.      Antioksidantna aktivnost (sposobnost neutralizacije slobodnih radikala i redukcioni potencijal) je određena spektrofotometrijskim metodama, pri kojoj su najbolju aktivnost ostvarili N₂O ekstrakti  G. applanatum. Antimikrobna aktivnost  analiziranih ekstrakata određena je ispitivanjem antibakterijskog, antifungalnog i antiviralnog potencijala gde se izdvojila G. pfeifferi vrsta. Antiinflamatorni potencijal EtOH i  CHCl₃ ekstrakata određen je  ex vivo  metodom merenjem sposobnosti inhibicije produkcije medijatora inflamacije  (produkti  metabolizma arahidonske kiseline) pri kojoj su bolju aktivnost ispoljili CHCl₃ ekstrakti.Efekat EtOH i H₂O ekstrakata vrsta roda Ganoderma   na rast MCF ćelijske linije ispitan je MTT testom, a posebno su se izdvojili  EtOH  ekstrakti vrsta posle 72h.Ostvarena antidijabetogena aktivnost EtOH i N₂O ekstrakata vrsta   G. pfeifferi   i  G. resinaceum  kod aloksan-indukovanog  D. mell itus-a  na  eksperimentalnim  životinjama  praćena je regeneracijom  ß- ćelija  Langerhansovih ostrvaca pankreasa. Kao potencijalni nefro-  i  hepatoprotektivni agensi se izdvajaju ekstrakti  G. resinaceum.Sumarno, ukupni biopotencijal analiziranih vrsta roda  Ganoderma  na osnovu sprovedenih analiza hemijske   karakterizacije i biološke aktivnosti upućuje  na  mogućnost njihove potencijalne primene kao nutraceutika i dodataka ishrani, u budućnosti uz neophodnost dodatnih mikohemijskih istraživanja ovih vrsta, posebno terpenoida i polisaharida, kao i drugih bioloških aktivnosti kao što je neuroprotektivna.
Whitin this doctoral thesis the chemical composition and biological activity of EtOH, H ₂ O and CHCl₃ extracts of four fungal species which belong to genus Ganoderma  (phylum Basidiomycota) :  G. applanatum,  G. lucidum,  G. pfeifferi,  G. resinaceum  were determinated. The samples were collected from different localities in Vojvodina. Chemical characterization included: AAS methods (compositon of macro- and  microelements in d.w. of fungi) and LC-MS/MS technique (quantitative analysis of phenolic compounds and flavonoids) wherein the 12 selected phenolic compounds were detected. The total proteins, sugars, phenolics and flavonoids content were    determined using spectrophotometric methods. The highest protein content was determined in EtOH extracts of  G. applanatum   and G. pfeifferi  species. In order to assess the biological potential, the in vitro  and in vivo antioxidant, antimicrobial, anti-inflammatory, antiproliferative and antidiabetic activities of the extracts were investigated.    The antioxidant activity (the ability of neutralizing free radicals and reduction potential) estimated byspectrophotometric methods. The highest   antioxidant potential was noticed in H₂O extracts of  G. applanatum. Evaluation of antimicrobial activity included the estimation of antibacterial, antifungal and antiviral activity, whereby the  species  G. pfeifferi  showed the highest potential The anti-inflammatory activity of EtOH and  CHCl₃  extracts was determined by  ex vivo  method measuring the ability of production inhibition of inflammation mediators  (products of arachidonic acid metabolism), where the CHCl₃  extracts were exhibited better activity.   The effect of EtOH and H₂O extracts of  Ganoderma species on the growth of the cell line MCF-7, has been examined using MTT assay (stand out ethanolic extracts of analyzed species after 72h incubation period).   Achieved antidiabetic activity of EtOH and H₂O extracts of  G. pfeifferi   and G. resinaceum  at alloxan-i nduced D. mellitus in experimental animals was followed by regeneration of  cells of Langerhans pancreatic islets. Extracts of  G.   resinaceum  were allocated as a potential nephro- and  hepatoprotective agents.In summary, the overall biological potential of the analyzed species of the genus  Ganoderma  based on results for chemical and biological characterization indicate that they could be used  as a nutraceuticals and food supplements in the future, with further the necessity of additional mycochemical investigation (especially terpenoids and polysaccharides) and other biological activity such as neuroprotective.

Ganoderma root rot disease has been reported world wide causing the death of affected hosts. The taxonomy of the genus Ganoderma is considered to be in disarray due to the use of basidiocarp morphological characters to differentiate the species which resulted in many synonyms, species complexes and possible misidentifications of species within the genus. The use of sexual compatibility tests and molecular techniques became powerful diagnostic tools to elucidate the taxonomy of Ganoderma species. Application of these techniques has resolved some of the taxonomic problems but the use of certain species names in the genus is still causing contention among taxonomists. The literature surrounding the taxonomy and techniques used in the taxonomy of the root rot fungus Ganoderma are considered in this thesis. It is clear that the taxonomy of Ganoderma is very difficult and it is still largely obscured by species complexes and incorrect species identifications. It is also evident that a single species concept will not aid in the identification of Ganoderma species. Rather, a combination of concepts based on morphology, mating tests and DNA sequence data should be used in elucidating the taxonomy of Ganoderma. Morphological characteristics as well as nucleotide sequence analysis of three gene regions; the internally transcribed spacer (ITS), the mitochondrial small subunit (mtSSU) and the intergenic spacer (IGS-1), were used to identify the causal agent of Ganoderma root rot of J. mimosifolia in the suburb of Brooklyn, Pretoria, South Africa. Morphological observations and DNA-based phylogenies revealed that all isolates collected from infected trees belong to a single species that reside in the G. lucidum sensu lato complex. Acacia mangium is a leguminous tree that is grown as an exotic plantation species in Indonesia. These economically important trees are threatened by Ganoderma root rot disease. This disease is considered to be the most important cause of losses in A. mangium plantations. Phylogenetic analysis of ITS sequence data showed that G. philippii is the primary agent of Ganoderma root rot in A. mangium in Sumatra, Indonesia.
Dissertation (MSc)--University of Pretoria, 2011.
Microbiology and Plant Pathology
Unrestricted

碩士
中華大學
資訊工程學系
104
Ganoderma lingzhi has been used for medicinal fungi more than 2000 years in China. As medicinal fungi of health food has created considerable trading amount in many countries. However, the Ganoderma classification has been argued for long time. According to 《Shennong Bencaojing》and other classics that the Ganoderma species was classified by characteristic. Therefore, scholars did classification by fruiting bodies’ characteristic, mycelium, sporidia and other traits of Oriental Ganoderma. In early stage, scholars believed《Shennong Bencaojing》 described the Ganoderma lucidum same species as P. Karsten named by Ganoderma lucidum in 1881. However, Moncalvo et al. according to molecular markers compared Orient and Europe Ganoderma that they found both Ganoderma are might not same species in 1995. Thus, Oriental Ganoderma was renamed as Ganoderma lingzhi in 2012. In addition, classification problem of Ganoderma complex is also an important issue for many researchers competing to solve it. Different variety of Ganoderma have similar appearance that there are not distinguishing easily. In addition, European Ganoderma lucidum are different then Chinese Ganoderma lucidum. Therefore, This study wants to discover that Taiwanese Ganoderma lucidum same species as Chinese Ganoderma lucidum whether or not. We discuss this issue base on ITS2 sequence. We used two types Ganoderma lingzhi of cultivation and Ganoderma amboinense, as well as two types of wild species Trametes versicolor and Fomitopsis pinicola in Taiwan. We obtained the ITS2 sequence by purification and cultivation. Furthermore, we adopted Clustal W、Clustal X、Muscle and other tools for doing multiple sequence alignment. Moreover, we used “neighbor-joining tree” and “maximum likelihood tree” these two types kinship to build evolution tree by algorithm.

博士
國立臺灣大學
農業化學研究所
79
The fruiting body of the Ganoderma lucidum has always been greatly valued in traditional Chinese medioine and in recent years some compounds have been found to have antitimor activities in the metabolite. However world wide it is merely classified as a wood decaying fungi that causes white rots of a wide variety of trees and timber. Even in many scientific papers G. lucidum is mainly deseribed as phytopathogenic fungi. THe taxonomy system of the Ganoderma, used for the last 100 years is based on the morphology of the fruiting body. At present , a large variety of Ganoderma research is being conducted such as chemical composition,biological activity, artificial cultivation, cross-breeding, in connection with plant protection etc., therefore a much clearer identifieation system ofr cultures needs to be established. New parameters are needed to differentiate between Ganoderma interspeeies and intraspooies. The parameters described in this thesis are as follows: (1) macroscopic characteristics of the colony and fruiting body. (2) microscopic characteristios of the hyphae and basidiospores. (3) growth rate and optimum temperature. (4) extracellular hydrolytic enzymes assay by API-ZYM kets. (5) electrophoretic patterns of extracellular laccase isozywes. (6) di-mon mating and incompatibility test. (7) restrietion fragment length polymorphisms in total DNA. Using the above parameters, the following species found in Taiwan were identified : G. applanatum (Pers.) Pat., G. formosanum Chang & Chen, G. fornicatum (Fr.) Pat. G. lucidum (W. Curt.: Fr.) Karst., G. microsporum Hseu, G. neo-japonicum Imaz., G. tropicum (Jungh.) Bres., G. tsugae Murr. Also the relationship between 10 different isolates of G. lucidum were identified. The above parameters can be used for different levels of the taxonomy system. For genus identification, the morphology of the fruiting body and basidiospore. For species identification, the most important parameters are the restriction fragment length polymorphisms, di-mon mating and incompatibiligy test. Microscopy of hyphae espedially strains with or without chlamydospore, and the morphology of the colony can be used as supporting data. For variety identification, the RFLPs, extracellular hydrolytic enzymes assay by API-ZYM kets, laccase isozyme patterns, growth rate of colony and optimum temperature are used. These parameters can be used to clearly identify the relationship between isolates of the same species. When the morphology of different species is very similar, such as that of the G. Lucidum and G. tsugae, two new parameters must be used for more precise identification-the compatibility test and RFLPs results. 靈芝自古為我國滋補強壯的珍貴藥材，近年來由靈芝代謝物中發現具有抗腫瘤等生理 活性成分，而成為廣受重視的藥用真菌。但靈芝屬也是廣泛分佈的白腐型真菌，文獻 記載其中的代表種G.lucidum（W. Curt.: Fr. ）Karst. 亦為植物病原性真菌。由於 靈芝屬的分類仍以子實體的形態特徵為主，對於靈芝屬的相關研究中，無論就植病防 治、生理、藥理、化學成分，人工栽培及育種等項目皆需有明確的菌株鑑定系統，做 為人工培養菌絲體時異種間和同種內菌株類緣關係判斷的指標。 本論文中利⑴人工培養時菌落、子實體的巨觀特性，⑵菌絲體和擔孢子的微觀特性， ⑶菌落生長速率和最適生長溫度，⑷API-ZYM 分析細胞外酵素活性，⑸細胞外潻氧化 同功酵素電泳分析圖譜，⑹單一雙核體與單一單核體菌株間的親和性反應，⑺以 Random prtoe set GLH-2標記的Hind Ⅲ 限制水解基因片段多型性圖譜等結果為分 類指標時，可以明確區別自本省採集分離的G.applanatum（Pers.）Pat. G. formosanum Chang & Chen, G. fornicatum （Fr.）Pat., G. lucidum, G. neo-japonicum Imaz., G. tropicum （Jungh.）Bres., G. tsugae Murr. 等菌株外 ，並可探討10株不同來源的G. lucidum菌株間的類緣關係。 在此分類系統中所用各項指標適用於不同的分類階層。子實體和擔孢子的形態特性為 建立靈芝屬時的依據，故可用於異屬間之區別。對於靈芝屬內異種間菌株種源關係的 判斷時，以限制水解基因片段多型性圖譜和菌株間的親和性反應結果為主要指標， 而以菌落形態和菌絲體中厚膜孢子的有無等為輔助的參考指標。在同種內的不同品系 菌株間關係，可由限制水解基因片段多型性圖譜、API-ZYM 分析胞外酵素活性結果 、漆氧化同功酵素電泳圖譜、菌落生長速率和最適生長溫度等特性做為同種菌株間 類緣關係鑑別的參考。 利用此系統的分類結果顯示，今後對於子實體外型相似的菌種如G. lucidum和G. tsuqae等的分類鑒定時，必須配合菌絲體間親和性反應與限制水解基因片段的多型 性圖譜等結果加以確認。

碩士
國立臺灣大學
微生物與生化學研究所
93
Cellulose, hemicellulose, and lignin are most abundant macromolecules in nature. Lignin is hardest to be degraded for its complex constitutions. There are three enzymes have the ability to degrade lignin: laccase (1.10.3.2), manganese peroxidase (1.11.1.13), and lignin peroxidase (1.11.1.14). Whitr-rot fungi, such as Ganoderma spp., can degrade lignin. In this study, gene family, characteristics, and heterologous expression of laccase genes from Ganoderma spp. are discussed. The specific primers according to laccase conserved copper-binding regions used to amplify the laccase genes in the eleven strains of Ganoderma spp. The result shown that there are at least two laccase genes in each strain. Laccase cDNA of RZ.lac4、0814.lac1、1109.lac1 from G.. lucidum RZ、G. tsuage 1109、G. fornicatum 0814 were cloned and encodes for proteins with 520, 521, and 521 amino acids, including a 21-residue secrection signal peptide for each protein. Phenylalnine in additional residue 10 amino acids downstream of the conserved cysteine of each encoding protein shows that these proteins belong class 3 laccase and may have high redox potential of the cupric ion. The Mental-responsive elements (MREs) and stress-responsive promoter element (STRE) found in the promoter of RZ.lac4 suggest that RZ.lac4 might be regulated by mentals.(Abadulla et al. 2000) The cloned cDNA were expressed in Pichia pastoris KM71 under the control of the AOX1 promoter. The transformants were found to secrete active recombinant enzymes after induction with methanol. The optimal temperature of the recombinant proteins, reRZ.lac4, re0814.lac1, re1109, are 55, 60, and 65℃. The optimal pH for the recombinant proteins is 3.0.

碩士
國立臺灣大學
食品科技研究所
88
Studies on the Apoptotic Effects of Ganoderma Species on Human Hepatoma Cells. Shu-Mine Hung, Graduate Institute of Food Science and Technology, National Taiwan University Abstract Hepatocellular carcinoma (HCC) is the second cause of cancer mortality in Taiwan recently. The high mortality of HCC is due to poor early diagnosis and lack of effective therapy. Mevalonate is the obligatory precursor of isoprenoids in the multiple mevalonate-demanding pathways and is vital for diverse cell function. Previous studies have shown that the inhibition of mevalonate formation decreases cholesterol biosynthesis and inhibits protein isoprenylation including Ras and G-protein. Further reduction of mevalonate pool causes cell cycle arrest, inhibition of DNA replication, and cell apoptosis. As a working hypothesis of this study, we speculate that the demand of mevalonate to support hepatoma cells proliferation are higher than that for normal hepatocyte regeneration. The subsistence of hepatoma cells in the liver will be inhibited preferentially when hepatic pool of mevalonate for multiple mevalonate-demanding pathways are reduced. The study intends to inhibit the multiple mevalonate-demanding pathways by using the very liver specific, cholesterol-lowering drug lovastatin, a HMG-CoA reductase inhibitor. With the inhibition of the multiple mevalonate-demanding pathways by lovastatin, the cells will be arrested at the G0/G1 phase, a cell cycle stage closer to apoptosis. In this situation, the hepatoma cells are expected to be more sensitive to other apoptotic agents. Human hepatoma cell line Hep 3B was chosen as the in vitro model. Hep 3B cells are p53 and bcl-2 deficient, but can express the MDR-1 gene. Previous studies from this laboratory and others have strongly indicated that the Chinese medicinal fungus Ganoderma species, which are commonly used as adjuvant therapy in HCC patients, was chosen to elucidate the apoptotic effect. Bioassay guided active fraction with significant apoptotic effect in vitro was used for animal study to elucidate the pharmacological potential. In vivo study used Hep 3B/T2 hepatoma cell-implanted nude mice as the animal model. Results showed that GL-M1-0820, GL-M1-0820-M1, GL-M1-C-M-14, and GL-M1-C-1H2E-5-RH-5 were the fractions from Ganoderma spp. which reduced the viabilities of Hep 3B cells. Their IC50 values were 10.1 g/mL, 34.3 g/mL, 13.5 g/mL, and 7.3 g/mL, respectively. If pre-treated cells with 10 M lovastatin for 48 hr, Hep 3B cells became more sensitive to GL-M1-0820, GL-M1-0820-M1, and GL-M1-C-M-14 (subsequent treatment for for 72 hr). The IC50 values were 2.2 g/mL, 4.0 g/mL, and 7.1 g/mL, respectively. The results indicated that the combination treatment with lovastatin and Ganoderma fractions was more effective than those treated with Ganoderma fractions alone. Cell cycle determination by flow cytometry indicated that these active fractions arrested Hep 3B cells at G2/M. Animal study demonstrated that the tumor sizes of control (Ct, n=6), lovastatin (L, n=6), GL-M1-C-M-14 (C14, n=6), and sequential treatment of lovastatin and GL-M1-C-M-14 (LC14, n=6) groups were 3.04 ± 1.61 cm3, 2.24 ± 2.38 cm3, 1.28 ± 1.03 cm3 and 0.91 ± 0.71 cm3, respectively. The reduction of tumor size by combination treatment in a sequential manner was most effectively. In conclusion, growth-arrested human hepatoma cells (Hep 3B) became more sensitive to apoptotic agents if the mevalonate pool was reduced. The Chinese medicinal fungus Ganoderma contained apoptotic natural products, which are most likely oxygenated triterpenes, promoted hepatoma cell apoptosis in vitro and in vivo. This study may shed light on better chemotherapy to human HCC and potential application of Ganoderma as the adjuvant therapy for HCC.