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.

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.

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.

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.

The Pharmacological Effects of Triterpenoids from <i>Ganoderma lucidum</i>and the Regulation of Its Biosynthesis

Ganoderma lucidum is a wildly used medicinal mushroom and has been used in East Asia because of its health-benefit effects. G. lucidum contains various compounds with different biological activities, which include anti-tumour, anti-viral, and anti-malaria effect. Ganoderic acid (GA) is a triterpenoid from G. lucidum. The biosynthesis of GA in G. lucidum is induced by stressors including various elicitors or signaling molecules, and artificially placing elicitors would enhance GA production. In this paper, bioactivities and potential applications of GAs would be focused, and the elicitation strategies for GA production are also highlighted based on the fundamental role of ROS, JA, Ca2+ and NO, which would shed light to developing a novel approach to manipulating the biosynthesis of GA in the future.

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.

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。

不同金属离子和pH对白腐菌Ganoderma lucidum产漆酶的影响

在发酵培养基中添加不同浓度金属离子,研究Zn2+,Cu2+,Mn2+,Mg2+和Fe2+等金属离子的浓度和p H对白腐菌Ganoderma lucidum生产漆酶的影响.结果表明:Zn2+、Cu2+和Mn2+对G.lucidum生产漆酶有不同程度促进作用,其中Cu2+的促进作用最大,Mg2+在高浓度时促进产酶,Fe2+则抑制漆酶的生产;p H为5时最利于漆酶的生产,酶活可达到140 000 U/L.

Triterpenoids from the Fruiting Body of Ganoderma lucidum

自赤芝［Ｇａｎｏｄｅｒｍａｌｕｃｉｄｕｍ（Ｆｒ．）Ｋａｒｓｔ］的二氯甲烷溶解部分分离得到一个新的三萜内酯化合物，命名为灵芝内酯（ｇａｎｏｌａｃｔｏｎｅ）。根据光谱（ＵＶ，ＩＲ，１ＨＮＭＲ，１３ＣＮＭＲ，ＭＳ和２ＤＮＭＲ）解析，确定其结构为１式。同时还从赤芝子实体中分到三个已知化合物，即灵芝醇Ａ（ｇａｎｏｄｅｒｉｏｌＡ，２），灵芝醇Ｂ（ｇａｎｏｄｅｒｉｏｌＢ，３）和灵芝三醇（ｇａｎｏｄｅｒｍａｔｒｉｏｌ４）。

Ganoderma Lucidum polysaccharide peptides protect kidney from renal ischemia reperfusion injury via counteracting oxidative stress

OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to determine whether GLPP could attenuate RIRI via counteracting the oxidative stress.METHODS Mice subjected to uninephrectomy with the right kidney ischemia for 35 min and reperfusion for 24 hwere used to explore the protective activity of GLPP against RIRI.In GLPP-treated group,100mg·kg-1·d-1 of GLPP were intraperitoneally injected for 7dbefore the procedure.In vitro,NRK-52 Ecells subjected to hypoxia-reoxygenation(H/R)and tunicamycin were used to explore the protective effect of GLPP against oxidative stress.The mechanisms in which GLPP protected kidney from RIRI were studied using a series of physiological and molecular biological methods.RESULTS Kidneys undergone ischemia-reperfusion showed renal dysfunction and characteristic morphological changes including cellular necrosis,brush border loss,cast formation,vacuolization and tubular dilatation while these damages were significantly attenuated by GLPP treatment.The abnormal levels of MPO,MDA and SOD caused by renal ischemia-reperfusion were significantly reversed by GLPP treatment.More apoptotic cells were found in the renal ischemia-reperfusion group than the sham group whereas GLPP reduced apoptotic cells in the ischemia-reperfusion mice by21.75%(P<0.01).The GLPPs(25-1μg·mL)alleviated H/R induced cell viability loss by 20.12%(P<0.01)andΔφm dissipation by 27.3%(P<0.01)in vitro as well and its pretreatment dramatically reduced H/R and tunicamycin induced cell injury.CONCLUSION Our study found that GLPP had a protective effect on RIRI via its anti-oxidative capacity,which suggests that GLPP may be developed as a candidate drug for preventing acute kidney injury.

Bioactive components,pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil:A review

Ganoderma lucidum is a Chinese medicinal fungus with a long history of use in healthcare and disease treatment.G.lucidum spores(GLS)are tiny germ cells released from the mushroom cap during the mature stage of growth.They contain all the genetic active substances of G.lucidum.G.lucidum spore oil(GLSO)is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO_(2)extraction technology.GLSO contains fatty acids,Ganoderma triterpenes,sterols and other bioactive compounds.Previous studies have demonstrated that GLSO has a wide range of pharmacological properties,including anti-tumor,anti-aging,neuroprotection,immunomodulation,hepatoprotection and modulation of metabolic diseases.This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components,extraction and processing techniques,pharmacological effects and safety evaluation.This provides a solid foundation for further research and application of GLSO.

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.

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.

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.

Influence of Ganoderma lucidum spores on the levels of neuropeptide Y and somatostatin in brains of seizure rats

BACKGROUND： Previous research has revealed that somatostatin can induce epilepsy, and that the levels of neuropeptide Y may increase and become more active in brain areas with epileptic seizures. OBJECTIVE： To observe the effect of Ganoderma luciclum spore powder on the neuropeptide Y and somatostatin content in the cerebral cortex and hippocampal regions of seizure rats induced by pentylenetetrazol （PTZ）. Furthermore, to verify any effect of Ganoderma lucidum spore powder on inhibition of epileptic seizures. DESIGN, TIME AND SETTING： A randomized group animal study was performed in August 2007 in the School of Basic Medical Sciences, Jiamusi University （Jiamusi, Heilongjiang, China）. MATERIALS： Thirty healthy, male, Wistar rats, aged 12 weeks and weighing 180-220 g, were taken as the experimental animals. PTZ （Sigma Company, United States） was used to induce epilepsy. Ganoderma lucidum spores （Leyss, ex Fr variety） were purchased from Jiamusi City Wild Growing Case of the Ganoderma Lucidum （China）. Rabbit anti-somatostatin antibodies and secondary antibodies were purchased from Wuhan Boster Company （China）. Neuropeptide Y radioimmunoassay kit was purchased from Beijing Furui Biotechnology Company （China）. METHODS： Thirty rats were randomly divided into three groups： a control group, an epilepsy model group and a Ganoderma lucidum spore-treated group. Each group contained 10 animals. Rats in the epilepsy model group were treated with intraperitoneal injections of PTZ and gastric perfusion of physiologic saline. In the Ganoderma lucidum spore-treated group, intraperitoneal injection of PTZ and gastric perfusion of Ganoderma lucidum spore powder were administered. The blank control group was only administered with the physiological saline by intraperitoneal injection and gastric perfusion. MAIN OUTCOME MEASURES： Immunohistochemical staining and radioimmunoassay methods were used to observe the changes of somatostatin and neuropeptide Y content in brain tissue of epileptic rats, as well as the morphology of neurons. RESULTS： All 30 rats were involved in the result analysis, without any loss. The number of somatostatin immunoreacted positive cells in the cerebral cortex and hippocampus was significantly increased in the epilepsy model group compared to the blank control group （P 〈 0.01）. The number of somatostatin immunoreacted positive cells in cerebral cortex and hippocampus was significantly decreased in the Ganoderma lucidum spore-treated group compared to the epilepsy model group （P 〈 0.01）. The contents of neuropeptide Y in cerebral cortex and hippocampus were significantly increased in the epilepsy model group compared to the blank control group （P 〈 0.01）. The contents of neuropeptide Y in the cerebral cortex and hippocampus were significantly decreased in the Ganoderma lucidum spore-treated group compared to the epilepsy model group （P 〈 0.05）. The epilepsy seizures in the Ganoderma lucidum spore-treated group were obviously reduced compared to the epilepsy model group. CONCLUSION： Ganoderma lucidum spore powder was able to reduce the somatostatin and neuropeptide Y content in the cerebral cortex and hippocampus effectively, so as to achieve an anti-epileptic function and protect neurons from being damaged.

Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms

Aim： To evaluate the safety and efficacy of an extract of Ganoderma lucidum that shows the strongest 5α-reductase inhibitory activity among the extracts of 19 edible and medicinal mushrooms by a double-blind, placebo-controlled, randomized and dose-ranging study in men with lower urinary tract symptoms （LUTS）. Methods： In this trial, we randomly assigned 88 men over the age of 49 years who had slight-to-moderate LUTS to 12 weeks of treatment with G. lucidum extract （6 mg once a day） or placebo. The primary outcome measures were changes in the International Prostate Symptom Score （IPSS） and variables of uroflowmetry. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, laboratory values and the reported adverse effects. Results： G. lucidum was effective and significantly superior to placebo for improving total IPSS with 2.1 points decreasing at the end of treatment （mean difference, -1.18 points; 95% confidence interval, -1.74 to -0.62; P 〈 0.0001）. No changes were observed with respect to quality of life scores, peak urinary flow, mean urinary flow, residual urine, prostate volume, serum prostate-specific antigen or testosterone levels. Overall treatment was well tolerated with no severe adverse effects. Conclusion： The extract of G. lucidum was well tolerated and improved IPSS scores. These results encouraged a further, large-scale evaluation of phytotherapy for a long duration using the extract of G. lucidum on men with LUTS.

Effects of Ganoderma lucidum spore powder on astrocyte expression and glutamine synthetase activity in the hippocampal region of epileptic rats

BACKGROUND： Recent studies have demonstrated that astrocyte dysfunction plays a central role in inhibiting epileptic seizures and that regulation of astrocyte function may be a new target for treatment of epilepsy. OBJECTIVE： To observe the effects of Ganoderma lucidum spore powder （GLSP） on astrocyte morphology and glutamine synthetase （COS） activity in the hippocampal region of epileptic rats. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Function Laboratory, College of Basic Medicine, Jiamusi University between October and December 2006. MATERIALS： A total of 30 Sprague Dawley （SD） rats were randomized to three groups （n = 10）： control, model, and GLSP. GLSP was sourced from Jiamusi Wild Ganoderma Lucidum Planting Base and prepared to 30 g/L with physiological saline before use. Pentylenetetrazol （PTZ） （10 g/L） was provided by Sigma Company, USA. METHODS： The control group received intraperitoneal （i.p.） and intragastric （i.g.） physiological saline. Following epilepsy induction by i.p. administration of PTZ （35 mg/kg）, rats from the mode/and GLSP groups were ig injected with physiological saline and GLSP （300 mg/kg）, respectively. Each compound was administered once per day, for a total of 28 successive days. Epileptic seizure convulsions were graded 0-5. A higher grade indicated more severe epilepsy. Only those rats showing stage 2 or higher convulsions at least 5 times successively were included in further experiments. MAIN OUTCOME MEASURES： Immediately alter injection, seizure activity was monitored for 30 minutes to determine the latent period and seizure duration; simultaneously, astrocyte numbers and GS activity in the hippocampal region of rats with epilepsy were detected by immunohistochemistry. RESULTS： All 30 rats were included in the final analysis. On day 28, following PTZ administration epileptic seizures were not found in the control group. In the GLSP group, rats exhibited rhythmic head nodding or facial spasms, and the latent period was significantly longer than that of the model group （P 〈 0.05）. In the model group, the majority of rats exhibited myoclonus or generalized convulsions, and epileptic seizure duration was slightly （but not significantly） longer than that in the GLSP group （P 〉 0.05）. Within 2-3 minutes of PTZ injection, the model group exhibited grade 4 or 5 epileptic seizures, and the GLSP group mostly showed grade 2 or 3, and occasionally grade 4 or 5, epileptic seizures. All rats recovered within 30 minutes. The model group exhibited significantly increased astrocytes （P 〈 0.05）, with thicker cellular processes and a higher number of cellular processes, and significantly decreased GS activity （P 〈 0.05） tban the control group. The astrocyte count was significantly decreased but GS activity was significantly increased in the GLSP group when compared with the model group （P 〈 0.05）; however, astrocyte appearance was similar in both groups （P 〈 0.05）. CONCLUSION： GLSP can effectively inhibit astrocyte numbers and elevate GS activity in the hippocampal region of rats with epilepsy, thereby reducing epileptic seizures.

Ganoderma lucidum spore powder modulates Bcl-2 and Bax expression in the hippocampus and cerebral cortex,and improves learning and memory in pentylenetetrazole-kindled rats

We studied the effects of Ganoderma lucidum spore powder on Bax and Bcl-2 expression and neuronal apoptosis in pentylenetetrazole-kindled epileptic rats. Sixty adult rats were randomly divided into a control group, an epileptic group （kindled） and three medication groups （150,300 450 mg/kg given to kindled rats）. Bax and Bcl-2 immunohistochemistry and TUNEL labeling showed that the number of Bax- and TUNEL-positive cells in the hippocampus and cerebral cortex decreased significantly in the high-dose medication group, while the number of Bcl-2 immunoreactive cells increased. The Morris water maze test showed that high-dose treatment significantly shortened escape latency and increased spatial probe trial performance. Our findings indicate that a high dose of Ganoderma lucidum spore powder upregulates the expression of antiapoptotic Bcl-2 protein in the hippocampus and cerebral cortex, inhibits proapoptotic Bax expression, and decreases seizure-induced neuronal apoptosis. Further, Ganoderma lucidum appears to protect against epilepsy-related learning and memory impairments.

Spectrum-effect relationship of immunologic activity of Ganoderma lucidum by UPLC-MS/MS and component knock-out method

This study was designed to elucidate the immunoregulation of Ganoderma lucidum.HPLC fingerprint and spectrum-effect relationship of G.lucidum were established to predict the active compounds and BP neural network model was established to predict the efficacy.Then the target compounds were identified by high resolution mass spectrometry.The results indicated that there are both enhanced immunity and immunosuppressive components in G.lucidum.BP neural network was trained with the common peak area and immune effi cacy index of G.lucidum fi ngerprint as samples,and a combined evaluation system of G.lucidum fi ngerprint effi cacy was established.The correlation coeffi cient R of BP network model was 0.98643,and the error of pharmacodynamic prediction results was in the ideal range.Eight compounds were identifi ed by high resolution mass spectrometry.The compounds related to immune activity in G.lucidum were determined in this study.