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BRAIN RESEARCH · 2024 · IF 2.7

Ganoderic acid a decreased Aβ42-induced neurotoxicity in PC12 cells by reduced mitochondrial damage

Xiaoyuan Ding,Fan Liu,Haohao Wang,Yan Wang,Guohui Li,Xingen Zhang,Cheng Song,Fucheng Zhu,Dong Liu

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Accumulation of β-amyloid (Aβ) in the brain has been recognized as a key factor in the onset and progression of Alzheimer’s disease (AD).The accumulation of Aβ in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aβ42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aβ42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca 2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aβ42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aβ protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer’s disease.

CAS / MDL: 1303-00-0
研究领域: 神经科学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF FOOD QUALITY · 2020 · IF 1.763

Establishment and Application of a Method for the Determination of Ganoderic Acid A

Shengyun Li,Yaowu Yuan,Chenchen Yu,Hao Gao,Jianxin Tan,Yiling Tian

A method for the quantitative determination of ganoderic acid A was constructed using the principle of indirect competitive enzyme-linked immunosorbent assay (ELISA), and this method was used to determine the ganoderic A contents of Ganoderma lucidum samples in the market. The conjugate of ganoderic acid A and bovine serum albumin was used for four rounds of immunization on test rabbits to obtain rabbit antiganoderic acid A antibody IgG. The enzyme-labeled plate was coated with the conjugate of ganoderic acid A and ovalbumin. The first stage reaction in the indirect competitive ELISA was that the conjugate of ganoderic acid A in the sample competed with the conjugate coated on the enzyme-labeled plate to bind rabbit antibodies. The second stage reaction was the combination of goat anti-rabbit IgG–horseradish peroxidase and rabbit antiganoderic acid A antibody IgG. The results of the determination of ganoderic acid A standard by this method showed that the coefficient of variation of repeated wells in the group was <5%, the detection limit of ganoderic acid A was 0.6 μg/L, and ganoderic acid A had a substantial dose-response relationship in the content range of 0.9–72.9 μg/L (R2 = 0.994). This method was used to measure the ganoderic A content of 12 varieties of G. lucidum in the market and showed the obvious differences in the ganoderic acid A contents of the different varieties. This method is simple, fast, and of great importance to the quality control of Ganoderma products.

CAS / MDL: 6805-41-0
研究领域: 分析化学 · 药理学 · 真菌学
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF PHARMACY AND PHARMACOLOGY · 2024 · IF 2.8

Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin

Gong Enhui,Pan Jiongwei,Ye Zaiting,Cai Xiaoping,Zheng Hao,Yin Zhangyong,Jiang Yiwei,Wang Xin,Cao Zhuo

ObjectivesReportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung cancer cells.MethodsAfter the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative reverse transcription PCR (qRT-PCR). The DDP-resistant lung cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A.ResultsGA-A suppressed the viability, migration, and invasion while downregulating Beclin and autophagy marker LC3II/LC3I levels and upregulating P62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the apoptosis and regulated the circFLNA/miR-486-3p/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung cancer tumor growth and blocked autophagy.ConclusionGA-A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to DDP.

CAS / MDL: 68-12-2
研究领域: 肿瘤学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Artificial Cells Nanomedicine and Biotechnology · 2019 · IF 4.462

Self-assembled thermal gold nanorod-loaded thermosensitive liposome-encapsulated ganoderic acid for antibacterial and cancer photochemotherapy

Weiwei Zhang,Wenwen Yu,Xiaoyuan Ding,Chenyang Yin,Jing Yan,Endong Yang,Feng Guo,Dongdong Sun,Weiyun Wang

A novel nanoparticle (Au-LTSL-GA.A) uses the thermosensitive liposome (LTSL) to encapsulate ganoderic acid A (GA.A), which successfully transforms the polarity of GA.A and has excellent water solubility. The multifunctional Au-LTSL-GA.A, a self-assembled thermal nanomaterial, was used in antibacterial and anticancer applications in combination with near-infrared (NIR) irradiation. The designed Au-LTSL-GA.A nanoparticle was used as a nano-photosensitizer to achieve synergistic photochemotherapy based on the phototherapy sensitization property of Au nanorods (NRs) and antitumour activity of GA.A. In the antibacterial experiments, the Au-LTSL-GA.A + NIR irradiation had a broad-spectrum antibacterial effect, exhibiting a strong antibacterial activity against drug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) compared with the raw GA.A and LTSL-GA.A. In the anticancer experiments, Au-LTSL-GA.A + NIR irradiation, which combined phototherapy sensitization property of Au NRs with antitumour activity of GA.A, exhibited high anticancer activity against MCF-7 cells. The IC50 value of Au-LTSL-GA.A + NIR irradiation (12.1 ± 1.3 μg/mL) was almost similar to cisplatin in MCF-7 cells. The evaluation of the potential in vivo toxicity of Au-LTSL-GA.A revealed no toxicity in mice. The results of this study suggest that Au-LTSL-GA.A has a wide range of potential industrial and clinical applications, such as in antibacterial treatment and cancer photochemotherapy.

CAS / MDL: 1303-00-0
研究领域: 纳米医学 · 肿瘤学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Ganoderic acid A mitigates dopaminergic neuron ferroptosis via inhibiting NCOA4-mediated ferritinophagy in Parkinson’s disease mice

Qiang-Ming Li,Shu-Zhen Wu,Xue-Qiang Zha,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo

Ethnopharmacological relevance Ganoderma lucidum , a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson’s disease (PD). Aim of the study To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. Materials and methods PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP + ), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. Results GAA significantly mitigated MPP + /MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss ( p <0.01 or p <0.05). In contrast to MPP + /MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models ( p <0.01 or p <0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 ( p <0.01). Conclusion GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.

CAS / MDL: 36913-39-0
研究领域: 神经药理学 · 神经科学 · 民族药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FASEB JOURNAL · 2020 ·Vol. 34 ·期 6 ·8671-8685 · IF 4.966

Excessive supply of glucose elicits an NF-κB2-dependent glycolysis in lactating goat mammary glands

Jie Cai,Diming Wang,Shulin Liang,Jinrong Peng,Fengqi Zhao,Jianxin Liu

During lactation, an improper glucose supply often threatens mammary gland (MG) health. However, information is limited on the metabolic trajectories and molecules that regulate lactating MGs with an excessive glucose supply. Based on the network analysis of transcriptome and microRNAs, we found that the oversupply of glucose-induced severe glucose metabolic disorders in MGs of lactating goats, shifting lactose synthesis to acute fermentative glycolysis which caused increased flux of glucose metabolism into lactate. Moreover, NF-κB2 played a key role in regulating glycolysis, exhibiting a metabolic shift when MGs had an excessive supply of glucose. In primary mammary epithelial cells, fermentative glycolysis, and intracellular concentration of reactive oxygen species (ROS) were reduced by ganoderic acid A through blocking NF-κB2, while activation of NF-κB2 with phorbol myristate acetate (PMA) upregulated fermentative glycolysis and increased cellular ROS accumulation under excessive glucose. Thus, we established an NF-κB2-targeting method to reform the metabolic shift toward glycolysis caused by glucose oversupply by integrating NF-κB2 blockade and intracellular ROS scavenging.

研究领域: 动物生理学 · 分子生物学 · 营养学
✓ 已验证 DOI PubMed 高影响因子
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