ENZYME AND MICROBIAL TECHNOLOGY
·
2022
·
IF 3.705
Cheng Zeng,Xiangqing Ji,Yu Shi,Siyu Mu,Yicheng Huang,Meiqiao Zhong,Yan Han,Cuicui Duan,Xiaolei Li,Dan Li
To develop a new method for enzymatic preparation of minor ginsenosides , T. stercorarium β-glucosidase (Tsbgl) was characterized and its activities of deglycosylation towards natural ginsenosides were examined. The substrates of 1 mmol l −1 were incubated with the enzyme of 38.3 U ml −1 at 65 ℃ and pH 5.0. The K m values of Tsbgl for ginsenosides Rb 1 , Rg 1 and p NPG were 0.37 ± 0.03, 3.26 ± 0.19, and 1.24 ± 0.03 mmol l −1 , and the V max values were 183.63 ± 7.15, 85.03 ± 4.90, and 117.66 ± 1.96 μmol mg −1 min −1 , respectively. The molar conversion of ginsenosides Rb 1 , Rb 2 , Rb 3 , Rc, Re, Rg 1 , and Rf by Tsbgl within 6 h was 100%, 50.1%, 42.7%, 92.0%, 57.3%, 67.9%, and 76.8%, respectively. The yield of aglycone protopanaxadiol was 35.5 μmol l −1 h −1 for Rb 1 , while the yields of aglycone protopanaxatriol were 64.2 and 70.4 μmol l −1 h −1 for Rg 1 and Rf. Tsbgl with good organic solvent tolerance, mild reaction conditions and broad substrate specificity , could completely remove all outer glucosyls at the C-3 and C-20 hydroxyls of protopanaxadiol-type ginsenosides, and the C-6 and C-20 hydroxyls of protopanaxatriol-type ginsenosides through various pathways, providing a specific and efficient way to produce minor ginsenosides.
研究领域:
生物化学
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药理学
·
酶学
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DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Hongliu Xie,Fang Lin,Fei Shi,Elaine Johnstone,Yaqi Wang,Yang An,Jun Su,Jiayin Liu,Qinghai Dong,Jihua Liu
As one of the metabolites of ginseng, 20( S )-protopanaxadiol (PPD) is a compound with dammarane-type tetracyclic triterpene, which performs a wide range of anticancer activities. In this study, PPD was used as a lead. A series of compounds were synthesized respectively with 11 amino acids through esterification and were evaluated for their cytotoxicity against several cancer cell lines. One of the synthetic products (PL) exhibited potent inhibitory effect on Huh-7 cells relative to that of PPD in vitro. Subsequently, the Annexin V-FITC /PI staining assay was used to verify that PL induced apoptosis of Huh-7 cells in a dose-dependent manner. A UPLC-Q/TOF-MS analysis method was established and validated for assessing pharmacokinetic properties after the administration of PPD and PL in rats. The results showed that compared with PPD, T 1/2 of PL in rats was prolonged, and the peak time was delayed, resulting in broader tissue distribution of the compound in the body. In addition, the targets of PL against several cancers were predicted and analyzed via network pharmacology. Molecular docking simulations demonstrated that PL interacted with the active sites of the above targets. In conclusion, this study provided a theoretical basis for the development and clinical application of anti-tumor activity of PPD.
研究领域:
药理学
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肿瘤学
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中药化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2024
·Vol. 20
·期 6
·1041-1048
·
IF 2.9
Li Shizheng,Lv Yanwei,Liu Xiaoying,Yuan Yuan
Chronic wounds in diabetic patients have become a common complication. However, current wound management tends to yield unsatisfactory outcomes and may give rise to complications. Therefore, we prepare a nano-structured lipid carrier by incorporating a 20(S)-Protopanaxadiol (PPD)-loaded
lipid nanoparticles (PPD-N) into a silicone elastomer (PPD-NS) for treating chronic diabetic wounds and assess its therapeutic efficacy in promoting diabetic wound healing and vascular regeneration in a mouse model. Our findings revealed that the prepared PPD-N showed uniform distribution
with spherical morphology and an average diameter of approximately 130 nm. Moreover, PPD-NS exhibited a wound closure rate of 92.1% after 48 hours of treatment and demonstrated enhanced vascular regeneration. Therefore, it can be concluded that the prepared PPD-NS can effectively be used in
diabetic wound repair and vascular regeneration. This study provides a promising potential therapeutic option for diabetic wounds.
研究领域:
药学
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生物医学工程
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伤口护理
·
糖尿病研究
✓ 已验证
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Shuyun Zhu,Zhenjia Zheng,Hongwei Peng,Jing Sun,Xian-En Zhao,Huwei Liu
This work proposed a novel strategy based on quadruplex stable isotope derivatization for sensitive, accurate, speedy and green determination of panaxadiol (PD) and panaxatriol (PT). This strategy integrated with ultrasound-assisted dispersive liquid-liquid microextraction, microwave-assisted derivatization, and magnetic graphene oxide dispersive solid phase extraction as efficient sample pretreatment techniques, coupling with ultra-high performance liquid chromatography tandem mass spectrometry detection in multiple reaction monitoring mode for the analytical purpose of high-throughput, sensitivity, selectivity, green and accuracy. Quadruplex mass spectrometry sensitizing derivatization reagents, 3- N -( D 0 -/ D 3 -methyl-, and D 0 -/ D 5 -ethyl-)-2′-carboxyl chloride rhodamine 6 G, were designed, synthesized and applied for the high-throughput derivatization of hydroxyl‑containing PD and PT for the first time. The analogue derivatives of PD and PT standards using 3- N -propyl-2′-carboxyl chloride rhodamine 6 G as derivatization reagent were employed as the internal standards for the mass spectrometry quantitation to minimize matrix effect. All rhodamine 6 G derivatives of PD and PT were easily and selectively adsorbed by magnetic graphene oxide for efficient magnetic dispersive solid phase extraction before injection. Parameters of (micro-) extractions, derivatization and liquid chromatography-mass spectrometry conditions were all optimized in details. Method validation results consisting of linearity, accuracy, precision, repeatability, matrix effect, stability and limits of detection (LODs, 0.02 ng/mL for PD and 0.03 ng/mL for PT) were determined. The analytical performance of this method benefited from efficient integration of suitable sample pretreatment techniques and characteristic structure of rhodamine 6 G with four mass tags in derivatization reagents. The developed and validated method has been applied to the quantitation of PD and PT for the quality assessment of related foodstuffs and traditional Chinese medicinal materials.
研究领域:
分析化学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2014
·
IF 0.7
Xian-En ZHAO,Tao LÜ,Na WEI,Shu-Yun ZHU,Jin-Mao YOU
Commercial Rhodamine B was first reported as a derivatization reagent labeling hydroxyl compound for mass spectrometry sensitization. In virtue of the strategy of ultrasonic-assisted dispersive liquid-liquid microextraction (UA-DLLME) combined with Rhodamine B derivatization, a new method of ultrahigh performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS) was developed for the sensitive determination of Panaxadiol (PD). UA-DLLME and derivatization conditions were investigated. PD in cosmetics and ginseng was extracted by UA-DLLME (150 μL chloroform as extraction solvent, 500 μL ethanol as disperser solvent, 3 min). Using Rhodamine B as precolumn derivatization reagent, the stable derivative of PD was obtained in acetonitrile at 70 °C for 30 min under microwave radiation (800 W) with the catalyst of N, N ′-carbonyldiimidazole (CDI) and 4-dimethylaminopyridine (DMAP). And then the PD derivative was separated and detected within 3 min by multiple reaction monitoring (MRM) mode of UHPLC-MS/MS. The LOD was 4.0 ng L −1 , and the LOQ was 15.0 ng L −1 . This method had perfect linearity, precision and recovery results, and showed obvious advantages such as sensitivity and low matrix effect in comparison with the previously reported methods.
研究领域:
分析化学
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药物分析
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化妆品科学
✓ 已验证
DOI
高影响因子
Food Frontiers
·
2023
·
IF 9.9
Pengde Lu,Jinfen Chen,Ying Chen,Xingping Quan,Jiayue Liu,Yan Han,Yiyang Li,Li Yang,Jian-Bo Wan,Yonghua Zhao
Ulcerative colitis (UC) is a digestive disease with a high incidence and is difficult to be cured due to its complex etiology. It has evidenced that intestinal barrier dysfunction plays a predominant role in UC. 20( S )-protopanaxadiol saponins (PDS) isolated from Panax notoginseng possess anti-inflammatory and antioxidative activities, suggesting its potential of treating UC. Herein, the therapeutic effects of PDS against UC and underlying mechanisms in the aspect of intestinal barrier dysfunction were investigated in vivo and in vitro. The results showed PDS had protective effects against dextran sulfate sodium–induced colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening, and histological lesions. Additionally, PDS reduced the colonic activity of myeloperoxidase and the cytokine levels of TNF-α, IL-6, and IL-1β, decreased MDA production, and elevated colonic activities of SOD and GSH-Px in the colitis mice. The expressions of proteins related to tight junction (TJ), including ZO-1, claudin-5, occludin, caveolin-1 (Cav-1), and Nrf2 were downregulated, whereas that of Keap1 was upregulated after colitis induction. These changes were reversed by PDS. Cav-1 expression was downregulated in lipopolysaccharides (LPS)- and H 2 O 2 -induced HCT116 cells, and the expressions of ZO-1, claudin-5, and occludin were suppressed in HCT116 cells stimulated by LPS and H 2 O 2 combined with Cav-1 small interfering RNA transfection, which were ameliorated by PDS, suggesting PDS targeted Cav-1 against intestinal barrier damage. Collectively, PDS alleviates inflammatory injury and oxidative stress by regulating the Nrf2/Keap1 pathway, contributing to targeting Cav-1 against intestinal epithelial TJ proteins loss. It suggests PDS might be a promising therapeutic natural product for UC treatment.
研究领域:
药理学
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胃肠病学
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免疫学
·
分子生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
WenBin Liu,ZhengWei Tan,YueChao Zhao,YanNa Zhao,XiaoLing Yu,BoLin Wang,FengLin Shen,Ai Mi,JinJian Lan,RuiLan Gao
Panaxadiol saponin (PND) is a latent targeted drug for the treatment of aplastic anemia (AA). In this study, we examined the effects of PND on ferroptosis in iron-overload AA and Meg-01 cells. We utilized RNA-seq to analyze differentially expressed genes in iron-induced Meg-01 cells treated with PND. The effects of PND or combined with deferasirox (DFS) on iron deposition, labile iron pool (LIP), several ferroptosis events, apoptosis, mitochondrial structure, as well as ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR pathway-related markers in iron-induced Meg-01 cells were examined by Prussian-blue staining, flow cytometer, ELISA, Hoechst 33342 staining, transmission electron microscope, and Western blot assays, respectively. Additionally, an AA mice model with iron overload was established. Then, the blood routine was assessed, and the number of bone marrow-derived mononuclear cells (BMMNCs) in mice was counted. Also, serum iron, ferroptosis events, apoptosis, histology, T lymphocyte percentage, ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR signaling-related targets in primary megakaryocytes of AA mice with iron overload were assessed by commercial kits, TUNEL staining, hematoxylin and eosin (H&E) staining, Prussian blue staining, flow cytometer, and qRT-PCR analysis, respectively. PND suppressed iron-triggered iron overload, and apoptosis, and ameliorated mitochondrial morphology in Meg-01 cells. Importantly, PND ameliorated ferroptosis-, Nrf2/HO-1-, and PI3K/AKT/mTOR signaling-related marker expressions in iron-induced Meg-01 cells or primary megakaryocytes of AA mice with iron overload. Moreover, PND ameliorated body weight, peripheral blood cell counts, the number of BMMNCs, and histological injury in the iron-overload AA mice. Also, PND improved the percentage of T lymphocytes in the iron-overload AA mice. PND attenuates ferroptosis against iron-overload AA mice and Meg-01 cells via activating Nrf2/HO-1 and PI3K/AKT/mTOR pathway and is a promising novel therapeutic candidate for AA.
研究领域:
药理学
·
血液学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 7.088
Lei Pang,Jin Li,Zheng Liu,Yin-Sheng Quan,He Huan Sui,Yi Jia,Fener Chen,Jung Joon Lee,Peng Liu,Zhe-Shan Quan,Qing-Kun Shen,Hong-Yan Guo
An extensive study was performed to discover a series of novel 20( R )-panaxadiol derivatives with various substituents at the 3-OH position as nontoxic, brain-permeable, multi-target leads for treating Alzheimer's disease . In vitro analysis revealed that a compound bearing benzyl-substituted carbamate , which we denoted compound 14a , exhibited the most potent neuroprotective activity, with an EC 50 of 13.17 μM. The neuroprotective effect of compound 14a was slightly more potent than that of donepezil and much more potent than that of 20( R )-panaxadiol. Compound 14a at 7.5–120 μM exhibited low toxicity in various cell lines. In addition, compound 14a exhibited a wide range of biological activities , including inhibiting apoptosis ; inducing tau hyperphosphorylation ; affecting beta-amyloid (Aβ), β-secretase, reactive oxygen species , tumor necrosis factor-α, cyclooxygenase-2, and interleukin-1β production; and promoting Aβ 25-35 disaggregation. The effective permeability of compound 14a across the blood-brain barrier was 26.13 × 10 −6 cm/s, indicating that it can provide adequate exposure in the central nervous system. Further, compound 14a improved learning, memory, and novel object recognition in mice, and in vivo toxicity experiments confirmed a good therapeutic safety range. Thus, compound 14a is a promising multifunctional lead for treating Alzheimer's disease and offers new avenues for natural product-derived anti-Alzheimer's disease drugs.
研究领域:
药理学
·
神经科学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yanbo Hu,Yiming Li,Yuzhu Shen,Baochun Zhang,Jiaxin Liu,Yi Cao,Jun Zhao
In this study, six rare protopanaxadiol (PPD)-type ginsenosides, namely, F2, CK, C-Mc1, C-Mc, CO, and CY, were prepared using enzymatic hydrolysis. Firstly, major (PPD)-type ginsenosides, including Rb1, Rb2, Rc, and Rd, were biotransformed by employing single and combined β-glucosidases BaBgl1A and BaBgl3A. Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analyses revealed that ginsenosides F2, CO, and C-Mc1 could be produced by BaBgl1A, while rare ginsenosides CK, CY, and C-Mc could be produced by the combined use of BaBgl1A and BaBgl3A. Furthermore, optimal preparation conditions for these rare ginsenosides were elucidated, with yields exceeding 76.34%. Additionally, large quantities of rare ginsenosides were prepared to determine their structures. Characteristic absorption peaks in 13 C NMR spectra and ion peaks in MALDI-TOF-MS suggested that the six high-purity rare ginsenosides (i.e., F2, CO and C-Mc1, CK, CY, and C-Mc) could be produced at high-efficiency. The findings of this study offer insights into novel enzymolysis methods for the targeted preparation of rare PPD-type ginsenosides, thus widening the range of raw materials that could be directed to in-depth biological activity research.
研究领域:
生物化学
·
药理学
·
生物技术
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2024
·
IF 2.8
Song Zeyu,Li Zhenyuan,Pan Tao,Liu Teng,Gong Baifang,Wang Zhixia,Liu Ke,Fan Huaying
ObjectivesAcute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms.MethodsIn vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins.ResultsPPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system.ConclusionPPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.
研究领域:
药理学
·
肾病学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2020
·
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
·
糖尿病研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）