Comparative pharmacokinetic analysis of sporoderm-broken and sporoderm-removed Ganoderma lucidum spore in rat by using a sensitive plasma UPLC-QqQ-MS method.

Previous studies have found that removing the sporoderm significantly enhanced antitumor and immunoregulatory activities of Ganoderma lucidum spore (GLS) compared with breaking the sporoderm. However, the pharmacokinetics of sporoderm-removed GLS (RGLS) and sporoderm-broken GLS (BGLS) remain elusive. To compare the pharmacokinetic differences between the two products, we developed a UPLC-QqQ MS method for determining nine representative triterpenoid concentrations. Chloramphenicol was used as an internal standard. The samples were separated on a reversed-phase column using acetonitrile-0.1% formic acid and water-0.1% formic acid as mobile phases. Nine triterpenoids were analyzed using multiple reaction monitoring mode. The results showed that the area under the concentration-time curve from dosing to time t of all nine components was increased in RGLS compared with BGLS. And the time to the maximum concentration in BGLS was delayed compared with that of RGLS. These indicated that the absorption of RGLS was better than that of BGLS, and the sporoderm might hinder the absorption of the active components. These results increase our understanding of the bioavailability of BGLS and RGLS and indicate that increased bioavailability is one of the main reasons for the enhanced efficacy of RGLS.

Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor.

A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.

Fast analysis of triterpenoids in Ganoderma lucidum spores by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

A rapid and reliable method was established for simultaneous determination of main triterpenoids in Ganoderma lucidum spores using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ-MS). The established method was validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to determine the contents of 10 main triterpenoids in different batches of G. lucidum spores. The analysis results showed that moderate levels of triterpenoids were found in G. lucidum spores. In addition, a MS full scan with a daughter ion scan experiment was performed to identify the potential derivatives of triterpenoids present in G. lucidum spores. As a result, a total of 22 triterpenoids from different G. lucidum spores were unequivocally or tentatively identified via comparisons with authentic standards and literatures. This method provides both qualitative and quantitative results without the need for repetitive UPLC-MS analyses, thereby increasing efficiency and productivity, making it suitable for high-throughput applications.

Inhibitory effects of Ganoderma lucidum spore oil on rheumatoid arthritis in a collagen-induced arthritis mouse model.

Holistic healthcare practitioners have now started to focus on specific traditional medicinal mushrooms to treat rheumatoid arthritis (RA). Ganoderma lucidum (GL) is one of the oldest mushrooms that have been used in ancient Chinese medicine to treat inflammatory ailments, including autoimmune diseases such as RA. Spores from this mushroom have specific effects on immunomodulation, aging, and cancer. However, the effect of G. lucidum spores (GLS) on arthritis remains unclear. Therefore, we investigated the effects of GLS oil in a collagen-induced rheumatoid arthritis (CIA) model. Metabolomics analysis revealed that GLS oil contains ten acids, of which oleic acid (52.12%) and linoleic acid (16.77%) predominated. The GLS oil-treated CIA mice had a significantly lower clinical score (p = 0.0384) for RA than the control CIA mice. Moreover, GLS oil reduced CIA-induced cartilage degeneration and synovial membrane inflammation in the knee. The GLS oil group showed significantly reduced knee eosinophilia (p = 0.0056). Immunostaining of neutrophils revealed that neutrophils infiltrated the CIA group; however, infiltrated neutrophils were significantly reduced in the GLS oil group in both the knees (p = 0.0006) and ankles (p = 0.0023). GLS oil treatment substantially suppressed LPS- or TNF-α-induced IL-6 mRNA expression in primary cultured chondrocytes. IL-6 immunohistochemistry results showed that the protein levels of IL-6 were attenuated in the GLS oil group compared to the CIA group. These findings suggest that GLS oil may be useful for the development of RA drugs. Further clinical research is required to identify significant improvements.

Modifications of Ganoderma lucidum spores into digestive-tissue highly adherent porous carriers with selective affinity to hydrophilic or hydrophobic drugs.

Ganoderma lucidum spores (GLSs) have been suggested to provide optimal structures for transporting orally bioavailable drugs. However, the double-layer wall and cavities of GLSs are naturally closed. This study aimed to modify GLSs into porous carriers by opening the layers and internal cavity with iturin A (IA) followed by potassium hydroxide (KOH) or hydrochloric acid (HCl). The (IA + KOH)- and (IA + HCl)-treated GLS carriers exhibited a high loading rate of 301.50 ± 2.33 and 268.18 ± 7.72 mg/g for the hydrophilic methylene blue (MB) and hydrophobic rifampicin (RF), respectively. The mechanisms underlying the modification involved the enhancement of the specific surface area with IA and the exposure of hydrophilic groups or hydrophobic groups of the GLSs with KOH or HCl. The sustained 48-h molecule-release profiles of the MB- and RF-loaded GLS carriers were best fitted using a first-order kinetics model in simulated gastric (or intestinal) fluid compared with other models. In mice, the designed GLS carriers had high adhesion capacities onto the mucosa of the digestive tract and long retention times (120 h), and even promoted the secretion of mucus and expression of several key intestinal barrier proteins. This study provided a new method to modify GLSs into oral carriers with selective drug affinity, high loading capacity, sustained drug release, and high adhesion to the digestive tract.

Ultrasonic-assisted supercritical fluid separation removing plasticizers from ganoderma lucidum spores' oil.

Ultrasonic-assisted supercritical fluid separation (USFS) was firstly applied to regulate solubility and remove plasticizers from ganoderma lucidum spores' oil to improve product safety. Separation efficiency was related with four variables, including temperature, pressure and ultrasonic power. The QD-T6A ultrasonic generator probe, which provided for the study with adjustable ultrasonic power 0 W to 800 W and the ultrasonic frequency was 40 kHz, was fixed at the entrance of the primary separation kettle. The optimal separation conditions were determined to be temperature as 15.0 °C, pressure as 18.0 MPa, and ultrasonic power as 360 W of ultrasonic power on the basis of response surface methodology (RSM). Experimental Di-n-butylphthalate (DBP) and Diethyl phthalate (DEP) content were 0.09 mg and 0.04 mg, respectively, which were below the limits for plasticizers. Meanwhile, the total triterpene and ganoderic acid A contents were 6.89 g and 1.10 g, respectively, comparable to conventional supercritical fluid extraction. The experiments with USFS at different power intensities revealed that ultrasonic at a power intensity of 36 W/L and the power density of 0.20 W/cm2 could resolve the separation contradiction between ganoderma lucidum spores' oil and plasticizers. This study revealed that USFS could be an innovation in the field of ultrasonic separation, with numerous potentials uses in pharmaceutical manufacturing.

A 26-week repeated dose toxicity evaluation of sporoderm-removed Ganoderma lucidum spores in rats.

Ganoderma lucidum spore powder is a traditional Chinese medicine with a variety of health benefits. Sporoderm-removed Ganoderma lucidum spores (RGLS) can be more effectively absorbed and utilized by the body. Due to the extensive clinical application and lack of long-term (>30 days) safety evaluation of RGLS, it is necessary to evaluate its repeated dose toxicity during a longer administration period. Here, we conducted a 26-week repeated dose toxicity test of RGLS in Sprague‒Dawley (SD) rats. The male and female rats were orally administered RGLS at doses of 0, 0.4, 1.2, and 4.0 g/kg once daily for a period of 26 weeks. The safety profile of RGLS was assessed through in vivo observations of survival, body weight, and food consumption; hematological, biochemical, and urine analyses; immunotoxicity assays; and histopathological examinations. The results showed that no significant systemic toxicity was observed following 26 weeks of repeated RGLS administration. Our data showed a no-observed adverse effect level (NOAEL) of 4.0 g/kg, which is approximately 20 times higher than the human equivalent dose. Our results support that RGLS can be considered a safe medicinal or food product that can be added to a healthy diet.

Manipulations of glucose/lipid metabolism and gut microbiota of resistant starch encapsulated Ganoderma lucidum spores in T2DM rats.

Our team previously demonstrated that Ganoderma lucidum spores (GLS) and resistant starch (RS) had hypoglycemic effects separately on type 2 diabetic mellitus (T2DM) rats. This work was to explore the effects of administering encapsulated GLS within RS (referred to as EGLS) in the T2DM rats, which were induced by streptozotocin (STZ). The EGLS was orally administered to rats for 28 days. The parameters of glycometabolism and lipometabolism were evaluated, and fecal microbiota composition was investigated. The results showed that EGLS significantly enhanced glycometabolism and lipometabolism parameters in T2DM rats, which might be associate with the enhancement of the glucose and lipid metabolism, insulin secretion, and glycogen synthesis and reduced lipogenesis. Furthermore, the intervention of EGLS also reduced the Proteobacteria community and improved dysfunctional gut microbiota. This study indicated EGLS may be a potential candidate for dietary intervention to modulate diabetes.

Triterpenoids from the spores of Ganoderma lucidum.

Recently a series of triterpenoids were isolated from ganoderma spores and have drawn the attention of chemists and pharmacists. The aim of this review is to summarize the triterpenoids and their bioactivities of ganoderma spores. The chemical and biological literatures of ganoderma spores dealing with the structural analysis and bioactivity assay were selected. Triterpenoids isolated from ganoderma spores showed significantly anti-HIV-1 protease, anti-tumor, and anti-complement activities. Triterpenoids are the main active constituents of ganoderma spores and show various bioactivities for its medicinal use. In addition, biological activities of ganoderma spores still need further assessment before they can be accepted not only by the traditional Asian medicine community, but also by western science and medicine.

Occupational asthma induced by ganoderma spores / 천식및알레르기

Occupational asthma induced by the inhalation of the spore of Ganoderma lucidum was demonstrated in a 43-year-old woman who had cultivated it indoors for 6 years. She had suffered from paroxysmal cough and rarely wheezing dyspnea for two years. Recently she also had chest tightness and paroxysmal and repeated cough immediately after the exposure to Ganoderma lucidum spores. Her pulmonary function was normal. But, her PC20 was 6.4mg/ml in MBPT (methacholine bronchial provocation test). She showed not only positive reaction to skin prick test but also dual asthmatic reaction to the bronchial challenge test with antigenic extract of Ganoderma lucidum spores.

Effect of Ganoderma lucidum spores on IL-1? and c-Fos in the brain tissue of epilepsy rats / 中国病理生理杂志

AIM: To observe the influence of Ganoderma lucidum spores on the cytokine IL-1? and c-Fos in the brain tissue of epilepsy rats. METHODS: The IL-1? level was examined by radioimmunoassay and the c-Fos expression was measured by immunohistochemical assay. RESULTS: Comparing the Ganoderma lucidum spores group with the epilepsy model group: c-Fos positive cell count in brain cortex and hippocampus in treatment group was obviously reduced. IL-1? level in brain tissue was also reduced obviously. CONCLUSION: Ganoderma lucidum spores effectively reduces cytokine IL-1? in brain tissue of epilepsy rats, improves the immunity dysfunction and plays a role in anti-epilepsy through suppressing c-Fos expression in epilepsy rats brain tissue and blocking of LRG.

Effect of Ganoderma lucidum spores powder on the expression of IGF-1, NF-?B and apoptosis of nerve cells in the brain from epileptic rat / 中国病理生理杂志

AIM: To investigate the effect of Ganoderma lucidum spores powder on the expression of insulin-like growth factor-1 (IGF-1), nuclear factor-?B (NF-?B) and apoptosis of nerve cells in rats with epilepsy established by pentetrazole. METHODS: The sub-eclampsia dosage of pentetrazole (PTZ) was used to make epilepsy model. Ganoderma lucidum spores powder group was given from stomach. The enduring time and latent period were recorded. The immune reactivity of IGF-1, NF-?B/P65 and apoptosis of nerve cells were measured with immunohistochemical staining and TUNEL method. RESULTS: In high power sight (?400), there were much more apoptosis cells in hippocampus and brain cortex of model group (18.80?2.13, 16.87?2.00) than those in control group (0.97?0.52, 0.58?0.25). The expressions of IGF-1, NF-?B in model group were higher than those in control group. Compared with model group, the latent period of Ganoderma lucidum spores powder group at the 17th, 21th, 25th days were longer (P