Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

Ganoderma lucidum spore oil enhances the effect of paclitaxel,improves the tolerance to paclitaxel and prolongs the survival in Lewis tumor-bearing mice

Purpose:This study aims to investigate whether Ganoderma lucidum spore oil(GLSO)could enhance the effect of paclitaxel(PTX),improve the tolerance to PTX and prolong the overall survival of Lewis tumor-bearing mice,which has never been reported before.Methods:The tumor,spleen,and thymus were weighed at the end of the experiment.Whole blood was collected for hematological index analysis,and the intact femur was removed to determine the bone marrow nucleated cell count(BMN).The percentage of lymphocytes in the spleen of mice was detected by flow cytometry,the activity of NK cells was detected by LDH assay,and the proliferation index of lymphocytes was determined by CCK-8 assay.The overall and mean survival time and life extension rate were calculated using SPSS software.Results:Our data showed that GLSO could enhance the anti-tumor effect of PTX and prolong the survival of mice.The underlying mechanisms of the above effects might be related to the toxic reduction effect of GLSO by relieving hematotoxicity,myelosuppression and immunosuppression.Specifically,GLSO could increase the number of blood cells and bone marrow cells,alleviate the thymic index,and elevate the number and activity of NK cells in mice treated with PTX.Conclusion:GLSO may enhance the efficacy of PTX by boosting the activity of immune NK cells and prolong survival by counteracting PTX-induced bone marrow alterations and improving hematopoiesis.These findings suggested the promising role of GLSO in combination with PTX to extend the survival and increase the tolerance of patients in clinical chemotherapy of lung cancer.

Extraction of Astragalus Polysaccharides and Ganoderma lucidum Mycelia Polysaccharides and Their in Vitro Antioxidative Effects

[Objectives]To explore the extraction and in vitro antioxidant effects of astragalus polysaccharides(APS)and Ganoderma lucidum mycelia polysaccharides(GLMPS).[Methods]By studying the polysaccharides of the herbal medicinal material Astragalus membranaceus and the fungal medicinal material Ganoderma lucidum mycelia,two polysaccharides were mixed according to different proportions and concentrations by using the principle of traditional Chinese medicine compound combination.The effect of polysaccharides on the scavenging ability of hydroxyl radical system was determined by salicylic acid method.[Results]When the compound ratios of GLMPS and APS were 1∶1,1∶4,1∶5,4∶1,and 5∶1,the scavenging effect of compound polysaccharides was better than that of single-component polysaccharides,and with the increase of concentration,the scavenging effect increased.When the ratio of GLMPS and APS was 5∶1,the hydroxyl radical scavenging rate of the compound polysaccharide reached 59.77%,which was 18.72%higher than that of single GLMPS and 28.58%higher than that of single APS.The scavenging effect of compound polysaccharide is closely related to the compound ratio and concentration.[Conclusions]APS and GLMPS can obtain better hydroxyl radical scavenging ability than single-component polysaccharides through compounding in appropriate proportions.In addition,within a suitable concentration range,as the concentration increases,the scavenging ability also increases.

Phytochemical Contents and Antioxidant Properties of Ganoderma lucidum Polysaccharides in Relation to Growth Stage and Culture Substrate

[Objectives]To determine physicochemical characteristics and antioxidant activity of Ganoderma lucidum polysaccharides(GLP)in different growth stages and culture media.[Methods]Five polysaccharides(GLP1,GLP2,GLP3,GLPW and GLPB)were extracted and purified from the fruiting body of G.lucidum at three growth stages and culture substrates(wood culture and bag culture).The chemical components and antioxidant activity of the five polysaccharides were determined.[Results]GLP1 contained the highest content of neutral sugar(87.65%)and GLP3 had the highest uronic acid content.All the samples mainly comprised glucose,galactose,mannose,xylose and arabose with different ratios.Moreover,their antioxidant activities were investigated on the basis of DPPH radical,ABTS radical,SOD-like activity,and antihaemolytic activity.Results indicated in all three growth stages GLP2 had the greatest antioxidant properties.In addition,the antioxidant activity of GLPW was significantly higher than that of GLPB.[Conclusions]Overall,by comparison,G.lucidum in growth stage two may have potential health benefits,and wood culture may be a superior choice of artificial cultivation due to their abundance of active polysaccharides.

Aqueous-soluble components of sporoderm-removed Ganoderma lucidum spore powder promote ferroptosis in oral squamous cell carcinoma

Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment.However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum(G. lucidum) on oral squamous cell carcinoma(OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder(A-GSP).Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway.Cellular Fe2+, glutathione(GSH), malondialdehyde(MDA), reactive oxygen species(ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy(TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth.Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe2+influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acylco A synthetase long chain family member 4(ACSL4) increase and glutathione peroxidase 4(GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo, A-GSP exerted a ferroptosismediated tumor-suppressing effect without observable adverse reactions.Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.

Volatile Components and Antitumor Activity of Ganoderma lucidum Spore Oil and Its Molecular Distillation Components

[Objectives]To compare the effects of molecular distillation on the flavor and antitumor activity of Ganoderma lucidum spore oil.[Methods]G.lucidum spore oil was separated and purified by molecular distillation technology,and the volatile components of different components of molecular distillation were analyzed by gas chromatography-ion mobility spectrometry(GC-IMS)technology.Human liver carcinoma cells(HepG2),human breast cancer cells(MCF-7),and human cervical cancer cells(Hela)were selected as the tumor cell lines to be tested,and the cell viability was detected by the MTT assay.[Results]Molecular distillation effectively reduced small molecular substances produced by oil oxidation in G.lucidum spore oil,such as heptanal,octanal,linalool,hexanal,E-2-octanal,3-ethylpyridine,etc.Among the heavy components,the content of esters was relatively high,mainly including ethyl levulinate,ethyl crotonate,and amyl butyrate.The MTT cytotoxicity test indicated that G.lucidum spore oil and its molecular distillation components had certain inhibitory effects on the growth of three tumor cells,and G.lucidum spore oil crude oil had the most significant antitumor activity.G.lucidum spore oil crude oil,heavy component,and light component had the most significant antitumor activity on HepG2 cells,followed by MCF-7 cells,and the weakest antitumor activity on Hela cells.The quality of G.lucidum spore oil became higher after molecular distillation,and the rancid smell was reduced,and molecular distillation had little effect on the antitumor activity of G.lucidum spores.[Conclusions]Molecular distillation technology can be applied to the refining of G.lucidum spore oil to improve product quality.

Studies on Active Polysaccharides from Ganoderma lucidum vith Immune Activity

从云头状灵芝[Ganoderma Lucidum(Leyss.ex Fr.)Karst.]中分离得到三种灵芝多糖BN3A，BN3B及BN3C，它们均表现明显免疫调节作用。从灵芝多糖BN3B及BN3C中各分离得到四个多糖均一体，对其中主要成分BN3C1，BN3C3，BN3B1及BN3B3进行了物理及化学研究，它们的平均分子量依次为1.6×10^4，2.5×10^4，3.5×10^4及4.0×10^4。经完全酸水解、红外光谱测定、过碘酸氧化、甲酸生成、Smith降解等证明，BN3B1及BN3C1均为β－（1→6)(1→3）甙键相连的葡聚糖。BN3B3为阿拉伯半乳聚糖。BN3C3为由葡萄糖和阿拉伯糖组成的肽多糖。它们均为β－（1→6）（1→3）甙键相连。

Antitumor Activity of the Ganoderma Lucidum Spore Alcohol Extract in Vitro

Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A comparision was made between the sporodermbroken(SB)and sporoderm nonbroken(SN)GLSAE It was showed that both GLSAE SB and GLSAE SN could inhibit the proliferation of these cancer cells,but the activity of GLSAE SB was much higher than that of GLSAE SN These results suggested that Ganoderma lucidum spore could probably be used for tumor treatment

Studies on the Triterpenoid Constituents of the Spores from Ganoderma lucidum Karst

Five compounds were isolated from the ether-soluble fraction of the spores of Gano- derma lucidum.On the basis of their chemical properties and spectral data(MS,UV,IR,~1H and ^(13)CNMR),they were identified as 3,7,11,12,15,23-hexaoxo-5α-lanosta-8-en-26-oic acid(Ⅰ),gano- deric acid B(Ⅱ),C(Ⅲ),D(Ⅳ)and ganodermanontriol(Ⅴ).Compound Ⅰ is a new natural product, named ganosporeric acid A.Compounds Ⅱ,Ⅲ,Ⅳ and Ⅴ are known compounds and were obtained for the first time from the spores of Ganoderma lucidum.Pharmacological experiments showed that ganosporeric acid A has an activity for lowering the levels GPT in mice with liver injury by CCl_4 and GaNI and exhibits heptoprotective effects.

Fermentation Production of Ganoderma lucidum by Bacillus subtilis Ameliorated Ceftriaxone-induced Intestinal Dysbiosis and Improved Intestinal Mucosal Barrier Function in Mice

Objective This study aimed to develop a type of Ganoderma lucidum(G.lucidum)-probiotic fermentation broth that can effectively improve the intestinal mucosal barrier function of mice with ceftriaxone-induced intestinal dysbiosis.Methods By means of absorbance of optical density(OD)value and phenol-concentrated sulfuric acid measurement of polysaccharide content,the probiotic species can grow on the medium of G.lucidum were screened out,and the concentration of the medium of G.lucidum was determined,and the fermentation broth was prepared for subsequent experiments.Thirty-two SPF grade male BALB/c mice were randomly divided into four groups(eight mice in each group),namely control group(CON),intestinal mucosal barrier damage model group(CS),fermentation broth intervention group(FT)and G.lucidum medium intervention group(GL),respectively.The intestinal dysregulation model was induced by intra-gastric administration of 0.2 mL ceftriaxone sodium(twice a day for seven consecutive days).From day 8,the FT group and GL group were gavage with 0.2 mL fermentation broth and G.lucidum medium,respectively.On day 15,all mice were sacrificed.To draw the weight curve and measure the cecal index;pathological examination of colon tissues with HE staining;serum levels of LPS,IL-10,TNF and IL-6 were detected by ELISA.Flow cytometry was used to analyze the changes of CD3+T cells,CD4+T cells,CD8+T cells and macrophages in spleen.16S rRNA sequencing was performed to detect the intestinal microbiota structure of mice.Results Bacillus subtilis can decompose and utilize G.lucidum fruiting body medium,and the suitable concentration of G.lucidum fruiting body medium is 33.2 mg/mL.The effect of Bacillus subtilis-G.lucidum fermentation broth on the damage of intestinal mucosal barrier caused by ceftriaxone sodium was reduced,the body weight of mice recovered and colon swelling improved,colon histopathological injury was alleviated,inflammatory cell infiltration was alleviated,serum IL-10 increased significantly,LPS、TNF-αand IL-6 decreased significantly compared with model group,and the proportion of T cells and intestinal dysbiosis was improved.Conclusions The experimental results suggest that Bacillus subtilis-G.lucidum fermentation broth can effectively improve the intestinal barrier function damage,immune dysfunction and intestinal dysbiosis caused by antibiotic overdose,and has a certain regulatory effect on intestinal mucosal barrier function.

Effects of Lingzhi (Ganoderma lucidum) on Hemorrheology Parameters and Symptoms of Hypertensive Patients with Hyperlipidemia and Sequelae of Cerebral Thrombosis

The effects of Lingzhi(Ganoderma lucidum)on hemorrheology parameters and symptoms of hypertensive patients with hyperlipidemia,sequelae of cerebral thrombosis and coronary heart disease are studied.The Lingzhi extract was given to 33 patients(15 male,18 female,65±8 years old)in dosage of 110mg qid po for 2 weeks.The blood viscosity was im- proved after treatment.The results showed that whole blood viscosity(at high shear rate and low shear rate)and plasma viscosity were significantly decreased(P<0.01).Lingzhi showed the effect of reducing blood pressure simultaneously.Several symptoms were also improved. However,there were no significant changes in haematocrit and erythrocyte sedimentation rate (P>0.05).In a few cases there occurred adverse reactions of palpitation and restlessness.

Isolation and Structural Determination of a Glucan from the Spores of Ganoderma lucidum

A water soluble, (1 -->6)-branched, (1 -->4) linked D-glucan (LB-B1), [alpha](D)(21) = +174.2 degrees (c 0.87, H2O), was obtained from a hot-water extract of the sporoderm-broken spores of Ganoderma lucidun (Fr.) Karst by HPSEC, with 0.001 mol/L sodium hydroxide as the eluant, the molecular weight (Mw) of LB-B1 was estimated to be 9.3 x 10(3). From the results of total hydrolysis, methylation analysis, acetolysis and 1D, 2D-NMR experimentation, it was concluded that LB-B1 was composed of repeating units with the following structure: alpha -D-Glc(p)-(1 -->6)-alpha -D-Glc(p)-(1 -->6)-alpha -D-Glc(p) 1 down arrow 6 (-->4)-alpha -D-Glc(p)-(1 -->4)-alpha -D-Glc(p)-(1 -->4)-alpha -D-Glc(p)-(1 -->4)-alpha -D-Glc(p)-(1 -->4-)-alpha -D-Glc(p)-(1 -->)(n)

Determination of ganoderic acids in rat plasma after oral administration of total triterpenoids from Ganoderma lucidum

To investigate the absorption of total triterpenoids from Ganoderma lucidum in rats. HPLC-DAD and LC-MS methods were used to identify ganoderic acids in rat plasma after oral administration of total triterpenoids from G. lucidum by comparing their HPLC retention behaviors, UV absorption spectra, and mass spectra with authentic samples. Five ganoderic acids, ganoderic acid C2, C6, G, B and A were simultaneously detected in rat plasma. Ganoderic acids can be directly absorbed into circulation after oral administration of total triterpenoids from G. lucidum in rats.

New Sesquiterpene Esters from the Culture Filtrate of Calcarisporium arbuscula Isolated from Ganoderma lucidum

从四川野生赤芝 (Ganodermalucidum (Leyss.exFr.)Karst.)的一共生菌CalcarisporiumarbusculaPreuss的发酵过滤液中分离得到 3个新的倍半萜酯类化合物 ,分别命名为calcarisporinB2 (1)、B3 (2 )和B4(3) ,通过物理方法和波谱分析确定了它们的结构。

中国产Ganoderma lucidum的系统发育学分析及栽培技术研究(英文)

灵芝是一类木腐真菌,广泛存在于热带雨林中。根据形态特征、rDNA-ITS和mt SSU的系统发育学分析,课题组将从Cyclobalanopsis bambusaefolia分离出来的菌株命名为G.lucidum,该菌株可人工培养。系统发育学分析表明,这些菌株类群与亚洲灵芝为一个独立的分支;此外,该研究采用传统椴木栽培技术,实现了分离菌株的人工栽培。人工栽培灵芝子实体粗厚,木栓质,边缘淡黄,在成熟的过程中逐渐变褐。

响应面法优化Ganoderma lucidum产漆酶种子培养基

以菌丝体生物量为指标,采用响应面法对产漆酶的灵芝菌UIM281的种子培养基组成进行了研究。首先采用单因素实验确定影响UIM281菌丝体生长的碳源、氮源及无机盐的种类和浓度范围。在此基础上,应用Box-Behnken设计对影响菌丝体生物量的显著因素进行优化,最终建立了以菌丝体生物量为响应值的二次回归方程模型,获得了最适的菌丝体增殖种子培养基。结果表明,在VB10.1g/L的条件下最佳种子培养基组成为:玉米粉18.0g/L,豆饼粉12.3g/L,MgSO4·7H2O 1.8g/L,在28℃,150r/min条件下振荡培养6d后,可获得24.18g/L菌丝体,可为漆酶发酵培养提供质优量大的接种体。

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum （by intragastric administration） in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-a and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-tiinflammatory actions.

In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachlorideinduced liver injury

AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.

SOLUTION PROPERTIES OF ANTITUMOR CARBOXYMETHYLATED DERIVATIVES OF α-(1→3)-D-GLUCAN FROM GANODERMA LUCIDUM

Fractions of a water insoluble α-(1→3)-D-glucan (GL) extracted from Ganoderma lucidum were carboxy-methylated (CM) to obtain water-soluble carboxymethylated derivatives (CM-GL) having a degree of substitution (DS) of0.38～0.51. Weight-average molecular weight M_w and intrinsic viscosity [η] of the samples CM-GL were measured by gelpermeation chromatography combined with laser light scattering (GPC-LLS) and viscometry. The CM-GL exhibits a stifferchain in aqueous solution at 25℃ than the original glucan, The antitumor activities against Ehrlich ascites carcinoma (EAC,5×10~6) of the carboxymethylated derivatives from the α-glucan and curdlan, a β-glucan, are significantly higher than thoseof the original glucans. The effects of the relatively low molecular weight, expanded chains and better water-solubility of theCM-GL on the enhancement of antitumor activity could not be neglected. The chain stiffness decreased speedily withincrease of temperature from 40 to 60℃ or NaOH concentration from 0.1 to 0.4 in the solution, respectively, and the changeof the chain stiffness is reversible.

Effect of Ganoderma lucidum spore on expression of insulin-like growth factor-1, nuclear factor-kappa B, and neuronal apoptosis in the epileptic rat brain

BACKGROUND：It has been reported that Ganoderma lucidum spore powder, a very well known Chinese traditional medicine, can affect immunoregulation, free radical scavenging, and anti-hypoxia responses. OBJECTIVE： To investigate the effect of Ganoderma lucidum spore powder on expression of insulin-like growth factor-1 （IGF-1）, nuclear factor-κB （NF-κB） and neuronal apoptosis in rats with pentylenetetrazol （PTZ）-induced epilepsy. DESIGN, TIME AND SETTING： A cellular and molecular biology experiment with randomized controlled study design was performed at the Central Laboratory of Basic Medical College of Jiamusi University from June to August 2005. MATERIALS： Thirty healthy, adult, male, Wistar rats were selected and randomly divided into 3 groups （10 rats per group）： control, epilepsy model, and Ganoderma lucidum spore powder. A sub-eclampsia PTZ dose （35 mg/kg） was intraperitoneally injected to induce epilepsy in the latter two groups. Wild Ganoderma lucidum spore powder （30 g/L） was provided by the wild Ganoderma lucidum plant nursery at Jiamusi, China. Immunohistochemical detection and terminal deoxynucleotidyl transferase-mediate dUTP nick end-labeling （TUNEL） kits were purchased from Wuhan Boster Biological Technology Co., Ltd., China. METHODS： Ganoderma lucidum spore powder was intragastrically administered at a dose of 10.0 mL/kg, once a day for 28 days. In the epilepsy and control groups, an equivalent volume of normal saline was intragastrically administered. MAIN OUTCOME MEASURES： Immunoreactivity for IGF-1 and NF-κB/P65 were detected by immunohistochemical staining. Neuronal apoptosis was detected using TUNEL methods. RESULTS： The hippocampus and cerebral cortex of rats with PTZ-induced epilepsy exhibited a higher number of apoptotic cells at high magnification （×400）, compared with the control group. Expression of IGF-1 and NF-κB were higher in the epilepsy group, compared with the control group （P 〈 0.01）. In Ganoderma lucidum spore-treated rats, fewer apoptotic cells were observed in the hippocampus and cerebral cortex, expression of NF-κB/P65 was lower, and immunoreactivity to IGF-1 increased more distinctly, compared with the epilepsy group. In addition, seizure latency was longer on 17, 21, and 25 days post-PTZ treatment in the Ganoderma lucidum spore powder group, compared with the epilepsy group （P 〈 0.05-0.01）. CONCLUSION： Ganoderma lucidum spore powder down-regulated expression of NF-κB in brain tissues of rats with PTZ-induced epilepsy, increased immunoreactivity to IGF-1, and inhibited neuronal apoptosis. These results indicated that Ganoderma lucidum spore powder has a neuroprotective effect.