APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2024
·Vol. 108
·期 1
·1-13
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IF 3.9
Wu Zongzhan,Dou Wenyu,Yang Xiaolin,Niu Tengfei,Han Zhuzhen,Yang Li,Wang Rufeng,Wang Zhengtao
Abstract Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase Pl GH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli . Sequence analysis revealed that Pl GH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of Pl GH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p -nitrophenyl- β - d -glucopyranoside as a substrate, respectively. The K m and k cat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s −1 , respectively. Pl GH3 exhibits a highly specific activity on hydrolyzing the 28- O - β - d -glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus . This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. Key points • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis.
研究领域:
生物化学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
·
IF 4.8
Tianyao Li,Jiaxin Chen,Zhouyuan Xie,Jiansong Fang,Qiqing Wu,Xinyue Cao,Ziying Chen,Yiyun Wang,Qiqi Fan,Qi Wang,Jinman Liu
Introduction Ginseng, known as the “king of herbs,” has long been used in traditional Chinese medicine due to its beneficial properties, including anti-aging, anti-inflammatory, and anti-apoptotic effects. Ginsenosides, the active compounds in ginseng, have shown promise in treating neurodegenerative diseases such as Alzheimer’s disease (AD). This study investigates the therapeutic potential of Ginsenoside Ro and its underlying mechanisms in AD treatment. Methods In this study, male APP/PS1 transgenic mice were divided into five groups and treated with Ginsenoside Ro or ginseng for one month. Cognitive function and anxiety were assessed through behavioral tests, including the open field test (OFT) and Morris water maze (MWM). To evaluate Aβ deposition, neuronal apoptosis, neuroinflammation, and the MAPK pathway, various techniques were employed: Thioflavin-T staining, Nissl staining, immunofluorescence, Western blot, and qRT-PCR analyses. Results Ginsenoside Ro significantly improved cognitive function and reduced anxiety in APP/PS1 mice. It also decreased Aβ deposition and ameliorated neuronal apoptosis in the cerebral cortex. The treatment regulated the expression of pro-apoptotic proteins (Bax and Caspase3) and increased the anti-apoptotic protein Bcl-2. Additionally, Ginsenoside Ro reduced neuroinflammation by decreasing IBA1-positive microglia and GFAP-positive astrocytes and lowering pro-inflammatory cytokines while enhancing anti-inflammatory cytokine IL-10. Furthermore, the phosphorylation levels of p38 and JNK in the MAPK pathway were significantly reduced, suggesting a key mechanism for its therapeutic effects. Discussion These findings provide strong evidence supporting Ginsenoside Ro as a potential therapeutic agent for Alzheimer’s disease. Its effects appear to be mediated through the modulation of the IBA1/GFAP-MAPK pathway, which may offer new insights into AD treatment strategies.
研究领域:
神经科学
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药理学
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中医药
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2020
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IF 3.263
Shumin Jiang,Xueli Wu,Yi Wang,Jingtao Zou,Xiaoping Zhao
Dipeptidyl Peptidase-4 (DPP-4) is a specific enzyme hydrolyzing the incretin hormone glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) to reduce insulin secretion, meanwhile DPP-4 inhibitors play an important role in diabetic therapy. In present study, 14 potential inhibitors were screened with an inhibition over 50% on DPP-4 activity from Xiao-Ke-An formula (XKA) and 12 of them exhibited a dose-dependently inhibitory effect at concentrations of 5–50 μmol/l. We found 10 DPP-4 inhibitors restrained differentiation of 3T3-L1 pre-adipocytes as well as reducing the triglycerides and total cholesterol content in 3T3-L1 adipocytes. Furthermore, 7 DPP-4 inhibitors promoted the glucose consumption in insulin-resistance BNL CL.2 cells. Thereinto, ginsenoside Rk 1 up-regulated the protein kinase B (AKT) and glycogen synthase kinase-3 (GSK-3β) phosphorylation expression, while kukoamine B and coptisine hydrochloride obviously increased the phosphorylation of AKT protein and columbamine , panaxadiol , ginsenoside Ro , timosaponin AI significantly promoted the phosphorylation of GSK-3β protein. It's our first effort to confirm those seven compounds could serve as DPP-4 inhibitors to attenuate DPP-4 activities, accompanied with the ability to adjust glucolipid metabolism. Moreover, activating the AKT/GSK-3β signaling pathway to ameliorate insulin resistant may be the anti-diabetic mechanism of XKA.
研究领域:
药理学
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糖尿病研究
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分子生物学
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DOI
PubMed
高影响因子
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