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Objective:To investigate the clinical efficacy and mechanism of Ganoderma lucidum hypoglycemic formula in the treatment of insulin resistance in patients with type 2 diabetes mellitus (T2DM) with liver and kidney yin deficiency. Methods:A total of 86 patients with T2DM with liver and kidney yin deficiency who were diagnosed and treated at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine from January 2021 to February 2022 were included in this study. These patients were divided into a control group and a treatment group, with 43 patients in each group using a 1:1 ratio using the sealed envelope method. Both groups were treated with standardized Western medicine. The treatment group was also treated with the Ganoderma lucidum hypoglycemic formula. All patients were followed up for 12 weeks. The clinical symptoms, curative effect, glucose and lipid metabolism, inflammatory factors, oxidative stress change, and safety were compared between the two groups. Results:The total response rate in the treatment group was 88.4% (38/43), which was significantly higher than 53.5% (23/43) in the control group ( χ2 = 12.69, P < 0.001). After treatment, the traditional Chinese medicine syndrome score, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, total cholesterol, triglyceride, tumor necrosis factor α, and interleukin-6 decreased in each group. The amplitudes of decrease of the above indexes were greater in the treatment group compared with the control group (all P < 0.05). C-peptide in the fasting state, C-peptide at 2 hours after a diet, and superoxide dismutase increased in each group. The amplitudes of increase of the three indexes were greater in the treatment group compared with the control group (all P < 0.05). Conclusion:Ganoderma lucidum hypoglycemic formula can greatly improve insulin resistance and glucose and lipid metabolism in T2DM patients with liver and kidney yin deficiency. The underlying mechanism may be to further reduce the inflammatory response and anti-oxidative stress by down-regulating tumor necrosis factor α and interleukin-6 levels and up-regulating superoxide dismutase level, thereby effectively alleviating insulin resistance in T2DM.
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OBJECTIVE To establish a quantitative analysis of multi-components by single marker （QAMS） method for simultaneous determination of 10 ganoderic acids in Ganoderma lucidum. METHODS Using ganoderic acid A as internal reference， high-performance liquid chromatography （HPLC） method was adopted to calculate relative correction factors of the other 9 components， such as ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C， ganoderenic acid D； the contents of above ganoderic acids were calculated with relative correction factors， and compared with the results of external standard method. RESULTS The linear relationship of ganoderic acid A， ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C and ganoderenic acid D were 0.032-3.996， 0.040-4.971， 0.037-4.568， 0.028-3.558， 0.033-4.177， 0.044-5.440， 0.032-3.944， 0.040-4.994， 0.045-5.593 and 0.035-4.342 mg/mL （all R 2≥0.999 2）， respectively. RSDs of precision， stability （24 h） and reproducibility tests were all lower than 2%. Their average recovery rates were 99.43%， 100.25%， 98.50%， 99.88%， 100.59%， 99.64%， 98.50%， 99.40%， 99.64% and 99.76%， respectively （RSD＜2%， n＝6）. Relative correction factors of ganoderic acid B， ganoderic acid C2， ganoderic acid D， ganoderic acid F， ganoderic acid H， ganoderenic acid A， ganoderenic acid B， ganoderenic acid C and ganoderenic acid D were 1.788 5， 1.288 2， 1.126 4， 1.698 5， 0.885 4， 5.468 1， 4.210 9， 5.780 8， 4.290 3， respectively. Relative errors between the content obtained by QAMS method and external standard method for G. lucidum from different origins were within ±12%. CONCLUSIONS It is feasible that the contents of 10 ganoderic acids are determined simultaneously by QAMS method， using ganoderic acid A as internal reference. This method shows good precision and reproducibility and can be used for the quality control of G. lucidum.
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ObjectiveTo investigate the effect of Ganoderma lucidum polysaccharides （GLP） on the proliferation， migration， cycle， and apoptosis of hepatocellular carcinoma SKHEP1 and Huh7 cells and to explore the underlying mechanism. MethodSK-HEP-1 and Huh-7 cells were classified into the blank group and low-， medium-， and high-dose GLP groups （3.5， 7， 14 g·L-1）. The proliferation of the cells was examined by cell counting kit-8 （CCK8） assay， and the migration by scratch assay. Cell cycle was measured by flow cytometry and apoptosis was detected based on Hoechst33258 staining. In addition， the expression of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （pPI3K）， and phosphorylated Akt （pAkt） in the cells was determined by Western blot. ResultCompared with the blank group， the three doses of GLP reduced the proliferation and migration of SKHEP1 and Huh7 cells （P<0.05）， increased the percentage of cells in G1 phase （P<0.05）， and decreased percentage of cells in S and G2 phase （P<0.05）. In addition， the three doses can induce apoptosis of both SK-HEP-1 and Huh-7 cells， particularly the high dose. Moreover， the three doses of GLP lowered the levels of pPI3K and pAkt （P<0.05）. ConclusionGLP significantly inhibited the malignant phenotype of SK-HEP-1 and Huh-7 cells through the PI3K/Akt signaling pathway.
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In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.
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Bayes Theorem , Data Mining , Drug Industry , Powders , Reishi , Spores, FungalABSTRACT
Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites, in which triterpenoids are the major constituents. This paper introduced the germplasm resources of genus Ganoderma from textual research, its distribution and identification at the molecular level. Also we overviewed G. lucidum in the components, the biological activities and biosynthetic pathways of ganoderic acid, aiming to provide scientific evidence for the development and utilization of G. lucidum germplasm resources and the biosynthesis of ganoderic acid.
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With the population aging， the morbidity and mortality of cancer patients continue to rise. At present， the treatment methods for tumors include surgery， chemotherapy， radiotherapy， targeted therapy， and immunotherapy. However， most chemotherapeutic drugs can cause severe side effects and drug resistance. Therefore， as an alternative therapy， traditional Chinese medicine （TCM） treatment can effectively relieve the clinical symptoms of tumor patients， improve the quality of life， inhibit or stabilize the development of tumors， and prolong the survival period of patients. Due to the good safety of Chinese medicine， its potential anti-cancer activity has attracted increasing attention. Ganoderma lucidum， a treasure of Chinese medicinal material， is a medicinal fungus with a history of more than 2 000 years in China. So far， many studies have proposed the anti-cancer properties of G. lucidum. G. lucidum has extensive pharmacological activities， such as anti-tumor， anti-atherosclerosis， and anti-aging. It can also regulate immunity， protect the liver and the heart， and reduce blood glucose and lipid. The chemical composition of G. lucidum is complex. At present， it is proved to contain polysaccharides， triterpenoids， alkaloids， nucleosides， amino acids， and various trace elements. The anti-tumor mechanisms of polysaccharides and triterpenoids in G. lucidum are mainly achieved by apoptosis induction， immune regulation， anti-angiogenesis， and induction of cell cycle arrest. Currently， it has been widely used in the adjuvant treatment of complex tumors such as lung cancer， liver cancer， cervical cancer， prostate cancer， breast cancer， and colon cancer. The present study reviewed the bioactivities and mechanisms of triterpenoids and polysaccharides in G. lucidum in recent years and highlighted the anti-tumor effects and mechanisms to provide references for the further development and utilization of G. lucidum.
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@#Models of acute and chronic liver injury in mice were established using carbon tetrachloride (CCl4) and ethanol to explore the protective effects of Ganoderma lucidum spore glycopeptide on liver injury.Different dosage of Ganoderma lucidum spore glycopeptide (65,130,260 mg/kg) were given by gavage.The liver index and the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined.The contents of liver interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) were tested by enzyme-linked immunosorbent assay (ELISA).The pathological injury of liver tissue was observed by HE staining.The results showed that Ganoderma lucidum spore glycopeptide could significantly reduce the liver index and the contents of serum AST and ALT in mice of acute and chronic liver injury.In mice of chronic liver injury induced by CCl4, Ganoderma lucidum spore glycopeptide could significantly decrease the contents of liver IL-6, TNF-α and iNOS, and alleviate the pathological damage of liver tissue.Results suggested that Ganoderma lucidum spore glycopeptide might reduce acute and chronic liver injury with anti-inflammatory effects in mice.
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Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.
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OBJECTIVE@#Ganoderma lucidum spore (GLS) is gaining recognition as a medicinal part of G. lucidum and has been reported to possess various pharmacological properties, such as antitumor activity. In this work, wall-broken GLS powder (BGLSP) and wall-removed GLS powder (RGLSP), two kinds of GLS powder with different manufacturing techniques, were compared in terms of contents of active constituents and in vivo and in vitro antitumor effects.@*METHODS@#The ultraviolet and visible spectrophotometry method was used to determine the contents of polysaccharides and total triterpenoids in BGLSP and RGLSP. Seventeen individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multi-components by single marker. The antitumor effects of BGLSP and RGLSP were evaluated using in vitro cell viability assay against human gastric carcinoma SGC-7901, lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901, A549 and Ramos.@*RESULTS@#The results showed that the contents of polysaccharides, total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of BGLSP. Although both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner, the inhibitory effects of RGLSP were much better than those of BGLSP. In the in vivo zebrafish assay, RGLSP exhibited more potent inhibitory activities against tumors transplanted into the zebrafish compared with BGLSP, and the inhibition rates of RGLSP reached approximately 78%, 31% and 83% on SGC-7901, A549 and Ramos, respectively.@*CONCLUSION@#The results indicated that the antitumor effects of GLS were positively correlated with the contents of the polysaccharides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents, and thereby enhance the antitumor activity.
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Ganoderic triterpenoids (GTs) are the primary bioactive constituents of the Basidiomycotina fungus,
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Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 μg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.
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Animals , Mice , Endothelial Cells/metabolism , Intercellular Adhesion Molecule-1/genetics , NF-kappa B/metabolism , Neoplasms , Polysaccharides , Reishi , Signal Transduction , T-Lymphocytes , Tumor Necrosis Factor-alphaABSTRACT
Objective: To screen the upstream regulatory transcription factors of farnesyl diphosphate synthase (FPS) in the triterpenoid synthesis pathway in Ganoderma lucidum. Methods: In this study, the FPS promoter was cloned and connected to the pAbAi plasmid to construct bait vector pAbAi-FPS, which was transformed into Y1H yeast competent cells to construct bait yeast. The yeast one-hybrid cDNA library was constructed by using SMART technology, then the purified ds-cDNA and pGADT7-Rec were co-transformed into bait yeast strain to screen the upstream transcriptional regulatory factors of PFS. Results: The bait vector containing pAbAi-FPS was constructed and the bait strain was screened, the cDNA library was constructed and transformed to the bait strain. A total of 37 positive clones were screened and sequenced. The sequences of conserved domain were predicted and performed blast search against the whole-genome database to identify their function. As a result, a total of 18 upstream regulatory factors were screened out including three transcription factors, five ribosomal proteins, and 10 other transcription regulators. Conclusion: The results indicated that transcription factors GlSNF2, GlMHR, and GlZn2Cys6 were candidate genes for regulating the expression of FPS, and this study offered data for further study on the regulation mechanism of FPS expression.
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Objective: To dig out and analyze the medication rule of optic atrophy treatment by TCM master Pin-zheng Liao using the Traditional Chinese Medicine Inheritance Support System, and summarize and explore its potential new prescription. Methods: A total of 90 TCM prescriptions for the treatment of optic atrophy by Pin-zheng Liao were collected. Based on frequency statistics, association rule, entropy clustering method rule analysis and other data mining methods, the law and characteristics of drugs were excavated. Results: A total of 113 herbs were included in 90 prescriptions, the most frequently used Chinese herbs were Lycium barbarum, Ganoderma lucidum, etc. Tonic drugs were used the most, the medicated herbs were usually sweet and peace, the Chinese herbs which belong to the liver channel were the most in channel tropism drugs. Seventeen combinations of commonly used drugs were obtained by association rule analysis. Based on entropy clustering method rule analysis, 10 potential new prescriptions were obtained. Conclusion: TCM master Pin-zheng Liao believes that optic atrophy is closely related to liver, spleen and idney. Blood stasis and vein obstruction is the main pathogenesis of the disease. The drugs with effects of activating blood circulation and dredging the meridians, tonifying liver and kidney were recommended for the treating.
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Ganoderma lucidum is a traditional folk common rare medicinal herb, which plays an important role in maintaining human health. Among them, G. lucidum polysaccharide is one of the main bioactive components of G. lucidum, which has various pharmacological effects such as anti-cancer, immunomodulatory, antibacterial, antioxidant, and scavenging free radicals. Due to the complex etiology and pathogenesis of central nervous system diseases, the clinical manifestations are diverse, and the individual response to treatment varies widely, which brings great challenges to clinical treatment. The characteristics and mechanism of the central neuroprotective effect of G. lucidum polysaccharide are reviewed in this paper from the aspects of Alzheimer's disease, anti-epileptic, modulating microglia inflammatory response, etc., in order to provide relevant evidence for its clinical application.
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OBJECTIVE： To study the imp rovement effects of Ganoderma lucidum polysaccharides crude extract on estradiol-induced thymus atrophy in mice. METHODS ：Totally 60 female ICR mice were randomly divided into normal control group（normal saline ），model group （normal saline ），G. lucidum polysaccharides crude extract high-dose and low-dose groups （400，100 mg/kg，by crude drug ），with 15 mice in each group. Except for normal control group ，other groups were given estradiol intraperitoneally （0.1 mg/mice，6 times）every other day to establish thymic atrophy model. The next day after modeling finished，they were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. Twenty-four hours after last medication，organ（thymus，spleen）index，MDA content and GST activity in plasma were determined. HE staining was adopted to observe the pathological changes of thymus and spleen tissue in mice. The thymus cell apoptosis was examined by TUNEL assay ， and the T cell subsets in peripheral blood were detected by flow cytometry. RESULTS ：Compared with normal control group ，the thymus index ，proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were decreased significantly in model group （P＜0.01）；spleen index ，MDA content in plasma and thymocyte apoptosis level as well as the proportion of CD 3+CD8+T cell in peripheral blood were all increased significantly （P＜0.05 or P＜0.01）. Thymic cortex and medullary boundary of mice was blurred；the intercellular space was enlarged ；some cells were damaged and apoptotic in cortex ；no pathological changes were found in the spleen. Compared with model group ，thymus index and GST activity in plasma as well as proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were all increased significantly in G. lucidum polysaccharides crude extract high-dose group（P＜0.05 or P＜0.01）；while MDA content in plasma ，the apoptosis level of thymocytes were all decreased significantly （P＜0.01 or P＜0.05）；and the pathological changes of thymus were improved significantly. MDA content in plasma was decreased significantly in G. lucidum polysaccharides crude extract low-dose group （P＜0.01），and other indexes/pathological changes were not obvious. CONCLUSIONS ：High dose （400 mg/kg）of G. lucidum polysaccharides crude extract can improve the thymus atrophy induced by estradiol in mice.
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In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1∶20 solid - liquid ratio and 55 ℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+ T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.
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OBJECTIVE@#To investigate the effects of Ganoderma lucidum polysaccharides (GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism.@*METHODS@#Primary human skin fibroblasts were cultured. The viability of fibroblasts treated with 0, 10, 20, 40, 80, and 160 μg/mL of GL-PS, respectively were detected by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-Htetrazolium bromide (MTT). The migration ability of fibroblasts treated with 0, 10, 20, and 40 μg/mL of GL-PS were measured by transwell assay. The secretion of the C-terminal peptide of procollagen type I (CICP) and transforming growth factor-β1 (TGF-β1) in the cell supernatant was tested by enzyme-linked immunosorbent assay. The expression of β-catenin was detected by Western blot. Furthermore, the Kunming mouse model with full-layer skin resection trauma was established, and was treated with 10, 20, and 40 mg/mL of GL-PS, respectively as external use. The size of the wound was measured daily, complete healing time in each group was recorded and the percentage of wound contraction was calculated.@*RESULTS@#Compared with the control group, 10, 20, and 40 μg/mL of GL-PS significantly increased the viability of fibroblasts, promoted the migration ability of fibroblasts, and up-regulated the expressions of CICP and TGF-β1 in fibroblasts (Plt;0.05 or Plt;0.01). The expression of β-catenin in fibroblasts treated with 20 and 40 μg/mL of GL-PS was significantly higher than that of the control group (Plt;0.01). Furthermore, after external use of 10, 20, and 40 mg/mL of GL-PS, the rates of wound healing in mice were significantly higher and the wound healing time was significantly less than the control group (Plt;0.05 or Plt;0.01).@*CONCLUSION@#A certain concentration of GL-PS may promote wound healing via activation of the Wnt/β-catenin signaling pathway and up-regulation of TGF-β1, which might serve as a promising source of skin wound healing.
Subject(s)
Animals , Humans , Male , Mice , Cell Movement , Cell Survival , Cells, Cultured , Collagen Type I , Fibroblasts , Polysaccharides , Pharmacology , Reishi , Chemistry , Skin , Wounds and Injuries , Transforming Growth Factor beta1 , Physiology , Wound Healing , beta Catenin , PhysiologyABSTRACT
Ganoderic acid(GA) is one of main bioactive components produced by Ganoderma lucidum,which a traditional Chinese herbal medicine and a kind of tracyclic triterpene lanosterol derivatives with highly oxidized structure. It has a variety of important pharmacological activities,such as anticancer,immunoregulation,anti-oxidation,anti-diabetes and anti-HIV. At present,the studies of GA mainly focus on biosynthesis,fermentation control,isolation and purification,structure identification and pharmacological effects.However,there are a fewer pharmacokinetic studies of GA,although it is closely related to the clinical application. Recent studies have shown that GA can be absorbed rapidly by gastrointestinal tract and distributed in various tissues and organs after oral intake. GA is metabolized by liver at phase Ⅰ and phase Ⅱ,and then mainly excreted by bile. In this paper,the pharmacokinetic characteristics of GA and its absorption,distribution,metabolism and excretion(ADME) will be systematically summarized,in order to provide scientific basis for the application and development studies of Ganoderma triterpenoid drugs and their rational clinical use.
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Humans , Lanosterol , Pharmacokinetics , Reishi , Chemistry , Triterpenes , PharmacokineticsABSTRACT
@#To investigate the antitumor activity induced by Ganoderma lucidum spore oil on different tumor cells. Human hepatoma cells(HepG2), human non-small cells lung cancer cells(A549)and human colon cancer cells(HCT116)were selected and tested. Cell viability was determined by MTT assay. Western blot analysis was performed to measure the expression of NF-κB and Caspase-3 activity in order to elucidate the mechanism of apoptotic activity caused by Ganoderma lucidum spore oil and to screen out the most sensitive cancer cell lines to Ganoderma lucidum spore oil. MTT assay demonstrated that Ganoderma lucidum spore oil had a strong inhibitory effect on the growth of three cancer cell lines. Among these cells, A549 cells were most sensitive to Ganoderma lucidum spore oil, followed by HepG2 cells and then by HCT116 cells. The results of Western blot showed that Ganoderma lucidum spore oil could promote the activation of NF-κB pathway, and that the activation of NF-κB signaling pathway in cancer cells treated by Ganoderma lucidum spore oil was stronger in A549 cells, HepG2 cells, HCT116 cells respectively. The detection of Caspase-3 activity showed that ganoderma spore oil could activate Caspase-3 dependent apoptosis pathways, which was more important in A549 cells, HepG2 cells and HCT116 cells. This study found that Ganoderma lucidum spore oil had inhibitory effects on A549, HepG2 and HCT116 cells growth and that its antitumor activity was in time-dose dependence. The mechanism may be related to the activation of NF-κB pathway and the Caspase-3 apoptotic pathway, which could accelerate apoptosis and necrosis of tumor cells. Among the three kinds of cancer cells, A549 cells was most sensitive to Ganoderma lucidum spore oil, followed by the HepG2 cells, and then by HCT116 cells.
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Objective To study the structure of active polysaccharide peptide purified from Ganoderma lucidum aqueous extract, and used as a reference substance for the determination of polysaccharide peptide content in G. lucidum products. Methods GL-PPSQ2 was obtained by hot water extraction, separation and purification with membrane ultrafiltration and gel-filtration chromatography. The physicochemical determination and spectral date were used for structural identification. The content of polysaccharide peptide was detected by HPLC with UV detector, water was used as mobile phase and the flow rate was 1 mL/min. Results GL-PPSQ2 was a pure polysaccharide peptide with purity above 97%, molecular weight of 5.0 × 104, polysaccharide content of 87.17%, and yield of 0.49%. The monosaccharides composition analysis showed that GL-PPSQ2 was glucose-based polysaccharide with a small amount of mannose, which contained 16 kinds of amino acids with the total amount of amino acids of 5.04%. Based on the methylation analysis, 1D and 2D NMR spectroscopy, the repeating unit of GL-PPSQ2 was composed of →3)-β-D-Glcp-(1→backbone, with four repeating units connected a long chain branch at O-6 which was composed of α-D-Glcp-(1→, →4,6)-β-D-Glcp-(1→, →4)- β-D-Glcp-(1→ and →6)-β-D-Glcp-(1→ in sequence. Conclusion The active polysaccharide peptide was isolated and purified by membrane technology and gel chromatography. The method was simple and rapid, which provided a scientific basis for the quality control of polysaccharide peptide in G. lucidum extract and its products.