WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2011
·Vol. 28
·期 3
·857-863
·
IF 1.214
Ye Li,Zhang Chunyan,Li Jiyang,Shi Xunlong,Feng Meiqing
Calcium is a known signalling molecule in eukaryotic cells and plays a central role in the regulation of many cellular processes. In the following study, we report on the effect of external calcium treatments on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7. We observed that the intracellular calcium content of P . bainier 229-7 mycelia was increased in response to exposure to high external Ca 2+ concentrations. Both ginsenoside Rd biotransformation and β-glucosidase activity were both found to be dependent on the external calcium concentration. At an optimal Ca 2+ concentration of 45 mM, maximal ginsenoside Rd bioconversion rate of 92.44% was observed and maximal β-glucosidase activity of 0.1778 U was reached in a 72-h biotransformation. The Ca 2+ channel blocker Verapamil blocked the trans-membrane influx of calcium and decreased ginsenoside Rd biotransformatiom. In addition, β-glucosidase activity and ginsenoside Rd content decreased by 36.0 and 29.2% respectively after a 72-h incubation in the presence of 0.05 mM Calmodulin (CaM) antagonist Perphenazine. These results suggest that both Ca 2+ channels and CaM are involved in ginsenoside Rd biotransformation via regulation of β-glucosidase activity. This is the first report regarding the effects of calcium signal transduction on biotransformation and enzyme activity in fungi.
研究领域:
药理学
·
微生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yingying Song,Xiaojuan Zhang,Xinyan Han,Gaorui Wang,Mengxue Wang,Hui Wu,Xiaojun Wu
Ethnopharmacological relevance The traditional Chinese herb Panax ginseng recorded in "Shennong Herbal Classic" is renowned for its purported vascular regulatory properties and immune-enhancing capabilities. Ginsenoside Rb1 (Rb1), a prominent bioactive compound in Panax, has demonstrated significant neuropharmacological activities. However, its impact on multiple sclerosis (MS) and blood-brain barrier (BBB) damage remains inadequately investigated. Aim of the study Inflammation and BBB disruption are pivotal to MS. Tightly packed brain capillary endothelial cells are fundamental to the structural and functional integrity of the BBB. Rb1 has been shown to alleviate BBB damage in stroke rats, but its effect on BBB damage in MS is not well understood. The objective of this study was to examine the role and mechanism of Rb1 on BBB injury in experimental autoimmune encephalomyelitis (EAE) mice. Materials and methods The BBB protection effect and mechanism of Rb1 were evaluated in LPS-treated bEnd.3 cells and EAE model mice. The mRNA expression levels of the inflammatory factor and the protein expressions of matrix metalloproteinases 9 (MMP9), zona occludens 1 (ZO-1), inhibitor of NF-κB (IκBα), occludin, Jun-amino-terminal kinase (JNK), and nuclear factor-κB (NF-κB) in bEnd.3 cells and mouse cerebral cortex were quantified. The permeability of bEnd.3 cells was examined by measuring trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. Results Rb1 administration in the early stages of EAE postponed the disease's onset and lessened its severity. Rb1 inhibited the destruction of the BBB in brain cortex of EAE mice. Rb1 reduced the lipopolysaccharide (LPS)-induced hyperpermeability of bEnd.3 cells and prevented the downregulation of TJ proteins. In addition, in LPS-induced bEnd.3 cells, Rb1 decreased the overproduction of reactive oxygen species. Moreover, Rb1 suppressed the phosphorylation of JNK, ERK, NF-κB, and IκB in vivo and in vitro. Furthermore, the JNK agonist anisomycin was observed to partially abolish the protective effect of Rb1 in bEnd.3 cells treated with LPS. Conclusions Taken together, we demonstrated that Rb1 improved demyelination and BBB damage in EAE mice by modulating JNK/ERK/NF-κB signaling pathway. This study can offer a theoretical foundation for the use of Rb1 in the treatment of EAE by preventing BBB injury.
研究领域:
神经药理学
·
免疫学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Wang Guoli,Lei Cong,Tian Ya,Wang Yingping,Zhang Lianxue,Zhang Ronghua
Panax ginseng C.A. Meyer (Araliaceae), a popular tonic and dietetic herbal medicine, has been traditionally prescribed in China and other countries to treat affective disorders. The medicinal parts of ginseng, the roots and flower buds, have become increasingly popular as dietary supplements due to the current holistic healthcare trend. We have investigated for the first time the antidepressive actions of the different medicinal parts, namely, the main roots, fibrous roots, and flower buds (in water extract and powder), of garden-cultivated ginseng through behavioral and drug-induced tests in mice. The water extracts, but not the powders of ginseng fibrous roots, flower buds, and main roots (1.5 g of crude drug per kilogram, p.o.), significantly reduced the immobility time in the forced swim test (FST) and tail suspension test (TST); moreover, the water extracts enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response and antagonized the action of reserpine in the mouse. We then explored the antidepressive mechanism of action of the ginsenoside Rb1 (Rb1) related to the brain-derived neurotrophic factor (BDNF) and its downstream proteins in mice exposed to chronic unpredictable mild stress (CUMS). Treatment with Rb1 (20 mg/kg, p.o.) for 21 days significantly attenuated the CUMS-induced decrease in the activities of BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), extracellular regulatory protein kinase (ERK), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the mouse hippocampal CA3 region and prefrontal cortex (PFC). Interestingly, treatment with the novel TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) did not alter the level of BDNF but significantly blocked the antidepressive effects of Rb1 on proteins downstream of BDNF in CUMS-treated mice. These results suggest that BDNF–TrkB–CREB signaling may be involved in the antidepressive mechanism of the action of Rb1.
研究领域:
药理学
·
神经科学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Wei Liangli,Yuan Yuqi,Yang Ziteng,Li Yuqing,Wang Tingting,Hu Shenglin,Cai Biao,Wang Guangyun
The neuroprotective function of ginsenoside Rb1 (GRb1) in cerebral ischemia–reperfusion (I/R) was lately emphasized. However, whether GRb1 plays a regulatory role on endoplasmic reticulum (ER) stress-associated pathway in cerebral I/R damage is still unclear. The aim of this study is to explore the function of GRb1 in cerebral ischemia-induced ER stress and the underlying mechanism related to IRE1/TRAF2/JNK pathway. Longa method, cerebral infarct volume, and HE staining were used to evaluate the efficacy of GRb1 in mice with a mouse model of middle cerebral artery occlusion reperfusion (MCAO/R). We also investigated the effect and mechanism of GRb1 against ischemic stroke using in vitro oxygen–glucose deprivation reperfusion (OGD/R) model. We found that GRb1 could improve neurological scores, infarct volume, and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis and ER stress, and this effect was attenuated by GRb1. In addition, GRb1 significantly reduced I/R-induced IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation. The present study also confirmed that GRb1 significantly improved OGD/R-induced PC12 cells injury. GRb1 could decrease ER stress in OGD/R-injured PC12 cells, which was reflected by the decreased expression of GRP78 and CHOP. The ER stress inducer tunicamycin partially prevented the effects of GRb1 on cell viability, ER stress, and apoptosis after OGD/R, whereas the ER stress inhibitor 4-PBA exerted the opposite effect. Moreover, GRb1 markedly decreased IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation in the presence of OGD/R insult. Furthermore, JNK inhibitor SP600125 and IRE1 inhibitor DBSA pretreatment further promoted the inhibition of GRb1 on ER stress induction and cell damage induced by OGD/R. Molecular docking further elucidated that the mechanism by which GRb1 improves cerebral ischemia maybe related to its direct binding to the kinase domain of IRE1, which in turn inhibited the phosphorylation of IRE1. Collectively, these results demonstrated that GRb1 reduced ischemic stroke-induced apoptosis through the ER stress-associated IRE1/TRAF2/JNK pathway and GRb1 has the potential as a protective drug for the treatment of cerebral ischemia.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Fu Zhihui,Wang Xiaohui,Lu Xuan,Yang Ying,Zhao Lingling,Zhou Lin,Wang Kaikai,Fu Hanlin
Ginsenoside Rb1 is a potential anti-inflammatory natural molecule, but its therapeutic efficacy was tremendously hampered by the low solubility and non-targeted delivery. In this study, we innovatively developed a mannose (Man)-modified albumin bovine serum albumin carrier (Man-BSA) to overcome the previously mentioned dilemmas of Rb1. The constructed Man-BSA@Rb1 NPs could improve the solubility and increase the cellular uptake of Rb1, finally leading to the enhanced anti-inflammatory effects. The robust therapeutics of Man-BSA@Rb1 NPs were measured in terms of nitrite, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, which might be achieved by potently inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in lipopolysaccharide (LPS)-induced Raw264.7 cells. Moreover, the therapeutic efficacy of Man-BSA@Rb1 NPs was further confirmed in the d-Gal/LPS-induced liver injury model. The results indicated that Man-BSA may offer a promising system to improve the anti-inflammatory therapy of Rb1.
研究领域:
药理学
·
纳米技术
·
炎症研究
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Shihui Li,Juan-Juan Li,Ying-Ying Zhao,Meng-Meng Chen,Shan-Shan Su,Shun-Yu Yao,Ze-Han Wang,Xin-Yue Hu,Wen-Chao Geng,Wei Wang,Ke-Rang Wang,Dong-Sheng Guo
The complexity and progressive nature of diseases require the exploitation of multifunctional materials. However, introducing a function inevitably increases the complexity of materials, which complicates preparation and decreases reproducibility. Herein, we report a supramolecular integration of multifunctional nanomaterials based on mannose-modified azocalix[4]arene (ManAC4A) and ginsenoside Rb1 (Rb1), which showed advances of simplicity and reproducibility. ManAC4A possesses reactive oxygen species (ROS) scavenging capacity and hypoxia-responsiveness, together with macrophage-targeting and induction functionality. Collectively, the Rb1@ManAC4A assembly simply prepared by two components is integrated with multifunction, including triple targeting (ELVIS targeting, macrophage-targeting, and hypoxia-targeted release) and triple therapy (ROS scavenging, macrophage polarization, and the anti-inflammatory effect of Rb1). The spontaneous assembly and recognition of ManAC4A, with its precise structure and molecular weight, facilitated the simple and straightforward preparation of Rb1@ManAC4A, leading to excellent batch consistency. Progress in simplicity and reproducibility, as directed by this research, will catalyze the clinical translation of multifunctional materials.
研究领域:
纳米技术
·
药学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Linhui Qin,Jianping Wang,RongRong Zhao,Xiao Zhang,Yingwu Mei
Ginsenoside-Rb1 (Rb1), a major active component of ginseng, has many benefits for cardiovascular disease and diabetes mellitus (DM), but the effect and mechanism on diabetic cardiomyopathy are not clear. In the present study, we found that Rb1-feeding significantly improved cardiac dysfunction and abnormal cardiomyocytes calcium signaling caused by diabetes. This improved calcium signaling was because Rb1 reduced Ca2+ leakage caused by overactivated ryanodine receptor 2 (RyR2) and increased Ca2+ uptake by sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA 2a). Furthermore, we found that Rb1 not only enhanced energy metabolism like metformin and eliminated O-GlcNAcylation of calcium handling proteins to regulate calcium signaling but also directly inhibited RyR2 activity to regulate calcium signaling. The present study indicated that as a health supplement or drug, Rb1 was a relatively effective auxiliary therapeutic substance for diabetic cardiomyopathy.
研究领域:
药理学
·
心脏病学
·
糖尿病
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Jiawen Luo,Huizhen Fan,Chenying Shu,Yiming Lin,Hanqing Li,Shunv Cai,Xin Li,Yanfei Mao,Min Lu,Pingbo Xu
Inflammatory diseases (IDs), characterized by chronic inflammation, are linked to conditions such as bacterial and viral infections, arthritis, and neurodegenerative disorders. Current treatments offer only temporary relief, highlighting the need for more effective therapies. Ginsenoside Rb1 (Rb1), with potent anti-inflammatory and antioxidant properties, can self-assemble into nanoparticles. To enhance targeted therapy for IDs, this study explores the effects of cationic modifications on Rb1 self-assemblies (GRb1). Among the various modifications, polyethylenimine (PEI) (GRb1@PEI) is the most effective at enhancing GRb1's ability to specifically target macrophages. In a murine model of LPS-induced sepsis-related acute lung injury (ALI), PEI facilitates the delivery of Rb1 to sites of inflammation. There, Rb1 inhibits the TNF-α signaling pathway, which helps normalize inflammatory markers and reduce immune cell recruitment. Additionally, GRb1@PEI serves as a multifunctional carrier for antibiotics with diverse physicochemical properties, enhancing bacterial clearance and alleviating inflammation and immune responses in blood infection-associated ALI and bacterial pneumonia models. Among four cationic polymer-modified GRb1 variants, this study demonstrates that GRb1@PEI is the most efficient multifunctional nanocarrier for targeted anti-inflammatory therapy of inflammatory diseases, providing important guidance for future therapeutic development.
研究领域:
药剂学
·
免疫学
·
纳米医学
·
炎症研究
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STEROIDS
·
2015
·
IF 2.639
Xinxin Zhang,Zengjun Guo,Jing Li,Yoichiro Ito,Wenji Sun
A specific high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS method) was established for determining the concentration of protodioscin (PG) in rat plasma after intragastric administration of its standard form. Ginsenoside Rb 1 was selected as the internal standard (IS). The plasma sample was prepared using one-step deproteinization procedure by adding three parts of acetonitrile to precipitate proteins. The chromatographic separation was accomplished on an Inersil ODS-3 C 18 column (250 × 4.6 mm, 5 μm) with a mobile phase composed with acetonitrile and water containing 0.1% formic acid under a gradient elution mode at a flow rate of 1 mL min −1 . A 3:1 portion of the eluent after a microsplit was detected on a triple quadrupole tandem mass spectrometer coupled with electrospray ionization (ESI) in positive ion and multiple reaction monitoring (MRM) scanning modes. The mass transitions were selected as 888.1 → 1050.2 for PG and 948.2 → 1110.3 for IS, respectively. After careful validation, the plasma samples were always stable under different storage conditions. These analytical results rendered sensitive, selective, and reliable values by this established method which displayed high accuracy, adequate extracted recoveries, and almost negligible matrix effects. This method was applied to the pharmacokinetic studies on PG level in the rat plasma and its pharmacokinetic effect. The results of our studies suggest that the present method may be a useful tool for further clinical study of PG.
研究领域:
分析化学
·
药物代谢
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2022
·
IF 10.787
Xue-Chun Ni,Hong-Fei Wang,Yuan-Yuan Cai,Dai Yang,Raphael N. Alolga,Baolin Liu,Jia Li,Feng-Qing Huang
Astrocytes activation in response to stroke results in altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective potential. This work aimed to investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and mitochondrial transfer. We prepared conditioned astrocytes-derived medium for co-culture with neurons and examined the role of Rb1 in mitochondrial transfer from astrocytes to neurons. The neuroprotective potential of Rb1 was further confirmed in vivo using a mouse model of brain ischemia. In response to oxygen-glucose deprivation and reperfusion (OGD/R), astrocytes were reactivated and produced reactive oxygen species (ROS), an action that was blocked by Rb1. Mechanistically, Rb1 inhibited NADH dehydrogenase in mitochondrial complex I to block reverse electron transport-derived ROS production from complex I, and thus inactivated astrocytes to protect the mitochondria. Mitochondrial signal, mitochondrial membrane potential and ATP production detected in conditioned astrocyte-derived medium indicated that Rb1 protected functional mitochondria and facilitated their transfer. When neurons were injured by OGD/R insult, co-culturing with conditioned medium increased mitochondrial membrane potential and oxygen consumption rate within the neurons, indicating the protection conferred on them by Rb1 via mitochondrial transfer from astrocytes. Using the ischemic mouse brain model, CD38 knockdown in the cerebral ventricles diminished the neuroprotective effects of Rb1, providing evidence in support of the role of astrocyte mitochondrial transfer. Transient inhibition of mitochondrial complex I by Rb1 reduced mitochondrial ROS production and consequently avoided astrocyte activation. Astrocyte mitochondrial transfer therefore seemed a means by which Rb1 could promote neuronal survival and function. Different from the neurocentric view, these findings suggest the astrocytes may be a promising target for pharmacological interventions in ischemic brain injury.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2025
·
IF 3.2
Yao Wang,Hua Dong-Ming,Wang Wen-kai,Zhang Zhao-zhou,Guan Yun-Feng,Wang Yan
ObjectiveTo investigate the mechanism of ginsenoside Rb1 (G-Rb1) against colorectal cancer under chronic stress.MethodsA chronic restraint stress (CRS) model and a colorectal cancer (CRC) subcutaneous xenograft model were established. Western blot analysis quantified β2-adrenergic receptor (β2-AR), cAMP response element-binding protein 1 (CREB1), and p-CREB1 expression. Additionally, glycolytic enzymes GLUT1, HK2, and PFKP were analyzed via Western blot and RT-qPCR, with glucose uptake, lactate, ATP, and stress hormone levels assessed by flow cytometry, kits, and ELISA.Key findingsCompared to the control group, the stress group exhibited increased tumor volume and mass, along with elevated expression of β2-AR, p-CREB1, and upregulated expression levels of GLUT1, HK2, and PFKP. Additionally, glucose, lactate, and epinephrine levels were higher in the stress group. In comparison to the stress group, G-Rb1 treatment demonstrated reduced tumor volume and mass, decreased p-CREB1 expression, as well as downregulated protein and mRNA levels of GLUT1, HK2, and PFKP. Glucose, lactate, and epinephrine levels also showed a reduction in the G-Rb1-treated groups.ConclusionsG-Rb1 suppresses the growth of colorectal cancer under chronic stress, potentially through downregulation of the β2-AR/CREB1 signaling pathway, thereby reducing glycolytic activity in colorectal cancer under chronic stress.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ginseng Research
·
2026
·
IF 5.6
Hongbo Zhu,Hang Li,Yinong Shi,Jinhui Liu,Hua Zhi,Xuelu Zhao,Zhiwen Wang,Fumin Ping
Background Pressure injuries (PIs) remain a therapeutic challenge due to persistent inflammation and ferroptosis-driven tissue damage. Ginsenoside Rb1, a key bioactive component of Panax ginseng, demonstrates anti-inflammatory and anti-ferroptotic properties, but its clinical application is limited by poor bioavailability and rapid degradation in wound environments. Purpose This study aimed to develop a chitosan/alginate nanocomposite hydrogel loaded with ginsenoside Rb1 (Rb1@CS@ALG) to enhance Rb1 delivery and investigate its therapeutic mechanisms in PI repair, focusing on SIRT1-AMPK-mediated ferroptosis inhibition and angiogenesis promotion. Methods The pH-responsive Rb1@CS@ALG hydrogel was synthesized and characterized (TEM/DLS/HPLC). In vitro studies evaluated ferroptosis markers (GPX4, SLC7A11), ROS levels, and cell migration in HaCaT cells under ischemia-reperfusion. A rat PI model (n=6/group) assessed wound closure rates, histopathology (H&E/Masson's), and protein expression (CD31/Col I). RNA-seq analyzed differential gene expression. Results The hydrogel showed sustained Rb1 release (82.3% at 24 h) and pH-dependent drug delivery. Treatment upregulated GPX4/SLC7A11 (2.3-fold) while reducing ROS (58%) and ACSL4 (45%) via SIRT1-AMPK activation (p-AMPK↑2.9-fold). In vivo, it accelerated wound closure by 75% (vs. controls, p<0.001), increased angiogenesis (CD31↑3.1-fold), and improved collagen organization (Col I/III ratio↑2.7-fold). RNA-seq confirmed enrichment in ferroptosis and extracellular matrix pathways. Conclusion This study establishes ginsenoside Rb1 as a potent therapeutic agent for PIs when delivered via nanocomposite hydrogel, with dual mechanisms of ferroptosis inhibition and angiogenesis activation. The findings provide a scientific foundation for applying ginseng-derived compounds in chronic wound management.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）