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.

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.

Protective and Regenerative Effect of the Extract of Kombucha and the Fungus Ganoderma sichuanense on the Islets of Langerhans of Diabetic Rats

Objective: The present study consisted of challenging the extract of kombucha and the fungus Ganoderma reported as hypoglycemic and used as alternative treatments against diabetes on the number and morphology of islets of Langerhans. Material and Methods: 64 Wistar rats were used in 4 groups: one control, three experimental, streptozotocin, Kombucha y Ganoderma induced diabetes with streptozotocin. Divided into four post-induction stages at 2, 15, 30 and 45 days of treatment, sacrificing 4 rats at each stage, to perform the morphological analysis of the pancreas. Results: A decrease in the islets of Langerhans in size, volume and the number of cells within them was identified for the streptozotocin group from the second stage until almost disappearing due to diabetes, in the groups of Kombucha y Ganoderma the same was observed but they were recovered with the extract treatments and the average number of islets was similar in these groups, the group of Ganoderma. Conclusion: Under the conditions of this work, a protective and regenerative effect of both extracts is identified.

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.

Meroterpenoids from Ganoderma Species:A Review of Last Five Years

Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway.Ganoderma meroterpenoids(GMs)are a type of meroterpenoids containing a 1,2,4-trisubstituted phenyl and a polyunsaturated terpenoid part.Over last 5 years,great efforts have been made to conduct phytochemistry research on the genus Ganoderma,which have led to the isolation and identification of a number of GMs.These newly reported GMs showed diverse structures and a wide range of biological activities.This review gives an overview of new GMs from genus Ganoderma and their biological activities and biosynthetic pathway,focusing on the period from 2013 until 2018.

New alkaloids from the fruiting bodies of Ganoderma sinense

Four new alkaloids,sinensines B-E(1-4),together with one known alkaloid,sinensine(5),were isolated from the fruiting bodies of Ganoderma sinense.Their structures were elucidated on the basis of 1D and 2D NMR spectra analysis.The structure of sinensine E was confirmed by X-ray crystallographic analysis of its acetyl product(4a).

Ganoderma sp. X1固态发酵改善酒糟品质

白酒糟含有丰富的营养成分,可开发为高蛋白饲料饲喂动物,但木质素的存在降低了动物对酒糟的利用率。为提升酒糟的利用价值,研究了固态发酵条件下真菌Ganoderma sp.X1对酒糟木质素的降解。采用正交试验,分别优化了培养基含水量、培养温度、接种量等条件。结果显示,Ganoderma sp.X1发酵白酒糟的最适发酵条件为培养基含水量75%、发酵温度28℃、接种量10%。发酵至第15天,白酒糟中木质素降解率最高达47.10%,粗蛋白由11.41%增加到17.30%。在此基础上,采用单因素试验探究麸皮的添加对Ganoderma sp.X1降解白酒糟木质素的影响。结果表明,以酒糟∶麸皮(5∶5)为固态发酵基质,发酵至第10天,木质素降解率可达46.36%,粗蛋白增加至24.80%。因此,麸皮的添加可有效缩短发酵周期,同时提高发酵产物品质。

树舌(Ganoderma lipsiense)化学成分及药理学研究进展

树舌的化学成分包括多糖、甾体化合物、三萜、脂类、氨基酸、多肽、蛋白质类、生物碱类、酚类、内酯、香豆素类和甙类以及微量元素等。树舌具有广泛的药理活性,主要包括调节机体免疫系统、抗肿瘤、抗病毒、消炎抗菌、降血糖、调节血压、阻碍血小板凝集和强心作用。临床用于治疗腹水癌、神经系统疾病、肝炎、心脏病、糖尿病和糖尿病并发症,预防和治疗胃溃疡、急慢性胃炎、十二指肠溃疡、胃酸过多等胃病,具有较高的药用价值。本文对树舌的化学成分、药理作用及临床应用情况进行了综述。

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.

海南产灵芝Ganoderma sp.室内栽培方法研究

灵芝是一类木腐真菌,具有重要的药理价值,灵芝栽培方法研究能为实际应用提供技术支撑。本研究选择一株分离自海南五指山的灵芝进行室内栽培方法研究,并分析其出芝和菌盖形成的动态变化规律以及子实体的形态特征。结果表明,灵芝出芝动态具有显著的规律性,随着时间的进行,出芝逐渐减少;而菌盖形成没有明显的时间规律。此外,室内栽培灵芝出芝率及菌盖形成率较高,但子实体大小相对大田栽培灵芝小,反映了可通过增加栽培原料的营养成分提高灵芝子实体大小,为进一步推广应用室内栽培方法提供参考。

野生热带灵芝Ganoderma tropicum(Jungh.) Bres.菌种分离与驯化研究

以新鲜的野生热带灵芝子实体为材料,经过表面消毒后,分别接种到米饭培养基、CA培养基和PDA培养基上.结果表明,在这3种供试培养基上均能获得纯化的菌丝体.米饭培养基上的菌丝体的生长速度最快;其次为PDA培养基;CA培养基的菌丝体生长最慢.对子实体、担孢子和菌丝体的形态特征进行了系统的形态学观察,证实所分离和驯化的菌种为热带灵芝[Ganoderma tropicum(Jungh.) Bres.].用木屑作为主要原料制备培养料对热带灵芝进行了驯化栽培,实验结果表明,冬季较低温条件下形成的子实体多为鹿角状畸形芝;而在2月份中旬以后较高温度下形成的子实体多为正常的掌状子实体.笔者据此认为,在海口地区,热带灵芝宜在春末至秋末气温较高的季节栽培.

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.

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.

Characterization and Anti-tumor Activity of Glycopeptides from Ganoderma sinensis

The water-soluble part（GS） of Ganoderma sinense Zhao, Xu et Zhang was divided into high molecular（GS-H） and low molecular（GS-L） parts by Cellulose Super Filtration, and GS was also fractionated into four fractions, GS-1, 2, 3, and 4 by ethanol precipitation according to their molecular weights. Chemical analysis shows that GS and GS-1, 2, 3, 4 were complexes of polysaccharide and peptide. The fractions with molecular weights over 4000, GS-1, 2, 3, and GS-H show anti-tumor activities, however, the fractions with molecular weights lower than 4000, GS-4, and GS-L have no anti-tumor activity, indicating that the anti-tumor activity of Ganoderma Sinensis was caused by glucopeptides with molecular weight ranging from 4000 to 20000. Two purified glucopeptides, GS-6b and GS-7b were obtained from GS-H by ion-exchange and gel-permeation chromatography. Their molecular weights, glycosidic linkages, and configurations were detected by means of IR spectrum, sugar composition analysis, and methylation analysis. The polysaccharide parts of GS-6b and GS-7b had glucan backbone consisting of β-1→3 Glc, and side chain containing glucosyl, mannosyl, fucosyl, xylosyl, galactosyl, and glucuronic acid residues attached on 1-2, 1-4, 1-6 positions of the backbone of GS-6b, or 1-6, 1-4 positions of the backbone of GS-7b. The peptide parts in GS-6b and GS-7b were composed of 10 kinds of amino acids, including Asp, Ser, Arg, Gly, Thr, Pro, Ala, Val, Met, and Lys.

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.