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 reportin...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.展开更多
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...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.展开更多
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. O...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.展开更多
Comparative test of 4 Ganoderma lucidum varieties from different sources showed that the mycelium of Chizhi 1 grew fast with thick and dense hyphae,round and solid cap,and high spore powder yield.Chizhi 1 was proved t...Comparative test of 4 Ganoderma lucidum varieties from different sources showed that the mycelium of Chizhi 1 grew fast with thick and dense hyphae,round and solid cap,and high spore powder yield.Chizhi 1 was proved to be an excellent variety because of its strong resistance and high spore powder yield.Different cultivation materials were chosen and combined to form 3 cultivation formulations.The results showed that Formulation(3),in which basswood was soaked in nutrient solution for 24 h,presented fast mycelial growth and high spore powder output,and therefore was proved to be a high-yield formulation of Ganoderma lucidum spore powder.展开更多
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...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 multicomponents 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 zebra fish assay,RGLSP exhibited more potent inhibitory activities against tumors transpla nted into the zebra fish 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 polysaccha rides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents,and thereby enhance the antitumor activity.展开更多
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 in...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.展开更多
基金supported by grants from the Pilot Project(4th Round)to Reform Public Development of Beijing Municipal Medical Research Institute(No.2021-1)the Science Foundation of Peking University Cancer Hospital(No.17-01).
文摘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.
基金Grant from Research Funds of Education Department of Guangxi Zhuang Autonomous Region, No. 200810LX340 Youjiang Medical College for Nationalities, No. 0802002
文摘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.
基金Innovation Scientific Research Foundation for Postgraduates in Heilongjiang Province, No. YJSCX2007-0082HLJScience and Technology Research Foundation of Heilongjiang Provincial Department of Education, No. 11521276Natural Science Foundation of Heilongjiang Province, No.D200803
文摘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.
文摘Comparative test of 4 Ganoderma lucidum varieties from different sources showed that the mycelium of Chizhi 1 grew fast with thick and dense hyphae,round and solid cap,and high spore powder yield.Chizhi 1 was proved to be an excellent variety because of its strong resistance and high spore powder yield.Different cultivation materials were chosen and combined to form 3 cultivation formulations.The results showed that Formulation(3),in which basswood was soaked in nutrient solution for 24 h,presented fast mycelial growth and high spore powder output,and therefore was proved to be a high-yield formulation of Ganoderma lucidum spore powder.
基金supported by Key R&D Foundation of Zhejiang Province(No.2017C02011 and No.2019C02100)the Zhejiang Key Agricultural Enterprise Institute Project(No.2017Y20001)。
文摘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 multicomponents 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 zebra fish assay,RGLSP exhibited more potent inhibitory activities against tumors transpla nted into the zebra fish 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 polysaccha rides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents,and thereby enhance the antitumor activity.
基金the Grant from Natural Science Foundation of Heilongjiang Province, No.D2004-10
文摘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.