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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2017 · IF 2.603

Describing the holistic toxicokinetics of hepatotoxic Chinese herbal medicines by a novel integrated strategy: Dioscorea bulbifera rhizome as a case study

Ling-Li Wang,Dong-Sheng Zhao,Wei Shi,Zhuo-Qing Li,Zi-Tian Wu,Ping Li,Hui-Jun Li

It is vital to monitor the holistic toxicokinetics of toxic Chinese herbal medicines (CHMs) for safety. Although an integrated strategy based on the area under the curve (AUC) has been proposed to characterize the pharmacokinetic/toxicokinetic properties of CHMs, improvement is still needed. This study attempted to use 50% inhibitory concentration (IC 50 ) as weighting coefficient to investigate holistic toxicokinetics of the major diosbulbins i.e. diosbulbin A (DA), diosbulbin B (DB), and diosbulbin C (DC) after oral administration of Dioscorea bulbifera rhizome (DBR) extract. Firstly, the cytotoxicities of the three diosbulbins on human hepatic L02 cells were evaluated and the IC 50 values were calculated. Then, integrated toxicokinetics of multiple diosbulbins based on AUC and IC 50 were determined. Finally, correlations between integrated plasma concentrations and hepatic injury biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were analyzed. As a result, integrated plasma concentrations were correlated well with TBA and the correlation between TBA and IC 50 -weighting integrated plasma concentrations was better than that of AUC-weighting integrated plasma concentrations. In conclusion, the newly developed IC 50 -weighting method is expected to generate more reasonable integrated toxicokinetic parameters, which will help to guide the safe usage of DBR in clinical settings.

CAS / MDL: 103-90-2
研究领域: 中药学 · 毒理学 · 生物医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Evidence-based Complementary and Alternative Medicine · 2014 · IF 2.175

The Spectroscopy Study of the Binding of an Active Ingredient of Dioscorea Species with Bovine Serum Albumin with or without Co2+ or Zn2+

He-Dong Bian,Xia-Lian Peng,Fu-Ping Huang,Di Yao,Qing Yu,Hong Liang

Diosgenin (DIO) is the active ingredient of Dioscorea species. The interaction of DIO with bovine serum albumin (BSA) was investigated through spectroscopic methods under simulated physiological conditions. The fluorescence quenching data revealed that the binding of DIO to BSA without or with Co2+ or Zn2+ was a static quenching process. The presence of Co2+ or Zn2+ both increased the static quenching constants KSV and the binding affinity for the BSA-DIO system. In the sight of the competitive experiment and the negative values of ΔH0 and ΔS0, DIO bound to site I of BSA mainly through the hydrogen bond and Van der Waals’ force. In addition, the conformational changes of BSA were studied by Raman spectra, which revealed that the secondary structure of BSA and microenvironment of the aromatic residues were changed by DIO. The Raman spectra analysis indicated that the changes of conformations, disulfide bridges, and the microenvironment of Tyr, Trp residues of BSA induced by DIO with Co2+ or Zn2+ were different from that without Co2+ or Zn2+.

CAS / MDL: 34215-57-1
研究领域: 生物化学 · 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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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2015 · IF 2.979

Simultaneous determination of four furostanol glycosides in rat plasma by UPLC–MS/MS and its application to PK study after oral administration of Dioscorea nipponica extracts

Min Liao,Cong Dai,Mengping Liu,Jiefeng Chen,Zuanguang Chen,Zhiyong Xie,Meicun Yao

A novel, sensitive and rapid ultra-performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method for simultaneous quantification of four furostanol glycosides in rat plasma was established and validated. Ginsenoside Rb1 was used as an internal standard. Plasma samples were pretreated by liquid–liquid extraction with n -butanol and chromatographed on a C18 column (2.1   ×   50   mm i.d., 2.6   μm) using a gradient elution program consisting of acetonitrile and water (containing 0.03% formic acid and 0.1   mM lithium acetate) at a flow rate of 0.4   mL/min. Lithium adduct ions were employed to enhance the response of the analytes in electrospray positive ionization mode and multiple reaction monitoring transitions were performed for detection. All calibration curves exhibited good linearity ( r   >   0.999) over the range of 10–20,000   ng/mL for protodioscin and 2–4000   ng/mL for protogracillin, pseudoprotodioscin and pseudoprotogracillin. The recoveries of the whole analytes were more than 80.3% and exhibited no severe matrix effect. Meanwhile, the intra- and inter-day precisions were all less than 10.7% and accuracies were within the range of −8.1–12.9%. The four saponins showed rapid excretion and relative high plasma concentrations when the validated method was applied to the PK study of Dioscorea nipponica extracts by intragastric administration at low, medium and high dose to rats. Moreover, the T 1/2 and AUC 0– t of each compound turned out to behave in a dose-dependent pattern by comparing them at different dose levels.

研究领域: 分析化学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2020 ·Vol. 21 ·期 6 ·2466-2474 · IF 2.1

Total saponin of Dioscorea collettii attenuates MSU crystal‑induced inflammation via inhibiting the activation of the NALP3 inflammasome and caspase‑1 in THP‑1 macrophages

Lu Wang,Liran Zhu,Chenfangyuan Duan,Lu Li,Guangliang Chen

Total saponins extracted from Dioscorea collettii (TSD), extracts of the Chinese herb Dioscorea, are thought to exhibit therapeutic benefit in gouty arthritis. However, its exact mechanism remains unclear. The current study aimed to elucidate the underlying mechanisms by investigating the effects of TSD on the inflammation induced by monosodium urate (MSU) crystals in THP‑1 macrophages. The viability of THP‑1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)‑1β, IL‑18 and tumor necrosis factor (TNF)‑α, released by the cells were quantitatively measured using ELISA kits. The results revealed that the protein level of cluster of differentiation 11b increased in THP‑1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP‑1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNF‑α, IL‑18 and IL‑1β, secreted by THP‑1 macrophages. As the release of IL‑1β and IL‑18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase‑1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosis‑associated speck‑like, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasome‑related proteins were also decreased by TSD in rotenone induced THP‑1 macrophages, TSD inhibited the activation of caspase‑1 and rotenone‑induced NALP3 inflammasome activation in THP‑1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystal‑induced inflammation by inhibiting rotenone‑induced activation of the NALP3 inflammasome and caspase‑1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.

CAS / MDL: 64-86-8 83-79-4
研究领域: 药理学 · 免疫学 · 炎症研究 · 中医药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2022 · IF 6.656

Development of a mechanism-based biomarker for Dioscorea bulbifera L. exposure and hepatotoxicity in rats

Zixia Hu,Yanjia Zhao,Yi Yang,Wei Li,Rong Tan,Linhua Zhao,Xiaolin Tong,Ying Peng,Jiang Zheng

Background Dioscorea bulbifera L. (DBL) is a common herbal medicine where furanoterpenoid diosbulbin B (DSB) is a major component responsible for its hepatotoxicity . The metabolic oxidation of the furan moiety of DSB, resulting in covalent binding to hepatic protein , is considered to initiate its liver injury. Purpose We aimed to develop a mechanism-based plasma protein adduction-based biomarker to determine DBL exposure and to predict the onset of hepatotoxicity induced by DBL. Methods Rats were intragastrically treated with DBL extract, and the plasma samples were collected. Plasma ALT and AST were measured with commercial kits. Plasma protein modification was determined by immunoblot assay. Assessment of DSB-induced protein adduction was achieved by LC-MS/MS analysis of complete proteolytic digestion of adducted protein to pyrroline derivative A4 using pronase enzyme . The structure of the resulting pyrroline derivatives was confirmed by NMR. Results Plasma protein of rats treated with DBL extract was covalently modified by the metabolite of DSB. Pyrroline derivative A4 was detected in proteolytic digestion of plasma obtained from rats administered DBL extract. The protein adduction elevated with the increase in the dosage of DBL extract. A detectable level of plasma was observed 10 days after withdrawal of DBL extract post 30-day continuous administration. In addition, the elevation trend of plasma ALT was found to be proportional to the accumulation trend of pyrroline derivative A4. Conclusion DSB-derived plasma protein adduction correlated well with the exposure of DBL in rats. The protein adduction may be used as a good biomarker for diagnosis of DBL-induced liver injury and a useful indicator for DBL medication plans.

CAS / MDL: 56-87-1
研究领域: 药理学 · 毒理学 · 分析化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2021 · IF 7.514

Isolation and structure characterization of a low methyl-esterified pectin from the tuber of Dioscorea opposita Thunb.

Wei Tang,Dan Liu,Jun-Qiao Wang,Xiao-Jun Huang,Jun-Yi Yin,Fang Geng,Shao-Ping Nie

A low methyl-esterified pectin (33.2% methyl-esterification degree) was isolated from the tuber of Dioscorea opposita Thunb., which was an edible and medicinal material in China. This pectin ( M w of 1.3 × 10 4 g/mol) contained the ~59.1% homogalacturonan (HG) and ~38.1% highly branched rhamnogalacturonan I (RG-I) region with possible side chains embracing arabinogalactan II, arabinan or arabinogalactan I. The fragments including HG backbone consisting of → 4)-α-Gal p A-(1 → and → 4)-α-Gal p A-6- O -methyl-(1 → with molar ratio of ~2:1, and repeating unit of arabinogalactan II side chain composed of α-Ara f -(1 → and → 3,6)-β-Gal p -(1→, were speculated through methylation analysis and NMR spectra. However, the linkage pattern for RG-I backbone and side chains were indiscernible due to limited resolution of NMR spectra. Besides, the pectin adopted a flexible chain conformation in 0.1 M NaNO 3 solution. These results provided a structural basis for study on polysaccharide from D. opposite , which was benefit for development of functional food of yam.

CAS / MDL: 76-05-1
研究领域: 食品科学 · 植物化学 · 多糖结构
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2019 · IF 3.579

Chinese yam (Dioscorea opposita Thunb.) alleviates antibiotic-associated diarrhea, modifies intestinal microbiota, and increases the level of short-chain fatty acids in mice

Nan Zhang,Tisong Liang,Quan Jin,Cai Shen,Yifan Zhang,Pu Jing

Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic treatment. The study was to evaluate effects of Chinese yam ( Dioscorea opposita Thunb.) on AAD, and changes of intestinal microbiota and short-chain fatty acids (SCFA). AAD model was established using Balb/c mice by gavage with ampicillin for 5 days, followed by a 10-day administration of low, medium, and high dosage of Chinese yam, containing allantoin (4.35 mg/g) and polysaccharides (85.51 mg/g). The results showed that Chinese yam accelerated the recovery from acute diarrhea, reverse AAD-induced body weight loss and cecal enlargement. The high-dosage Chinese yam increased probiotic Bifidobacteria and Lactobacilli by 47% and 21% and decreased potential pathogen Enterococcus and Clostridium perfringens by 8% and 27% on day 15 ( P  < .05). Bacterial community analysis revealed that Chinese yam contributed to repair the ampicillin-induced intestinal microbiota disorder, enrich the abundance of Bacteroides spp. and Clostridium spp. Additionally, Chinese yam supplementation increased the production of SCFA.

CAS / MDL: 97-59-6
研究领域: 药理学 · 微生物学 · 营养学
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JOURNAL OF INORGANIC BIOCHEMISTRY · 2022 · IF 4.336

Synthesis of phytonic silver nanoparticles as bacterial and ATP energy silencer

Liting Huang,Renxiang Chen,Jieer Luo,Murtaza Hasan,Xugang Shu

Recently, silver nanoparticles have been widely applied in various fields as inorganic antimicrobial agents. This present study adopted a facile, environmentally friendly and cost-effective method to green synthesized silver nanoparticles via the extract of Dioscorea cirrhosa tuber (DCTE-Ag NPs). Green synthesized Ag nanoparticles were characterized by using the transmission electron microscope , X-ray diffraction analysis (XRD), UV–visible spectroscopy (UV–Vis), fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), etc. The results authenticate that the green synthesized Ag NPs were spherical in shape with an average size of 13.87 ± 2.38 nm and have crystalline properties. According to the antibacterial test, the average width of the inhibition zone of green synthesized Ag NPs against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) were 14.17 ± 0.84 mm and 13.01 ± 0.72 mm, respectively. The antibacterial property of Ag NPs was further evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and the results indicated that they exhibited outstanding antimicrobial activity . Besides, DCTE-Ag NPs has the good bacteriostasis function, which can damage bacterial cells membrane to leak the intracellular contents and inhibit the activity of Na + /K + -ATP-ase to hinder energy conversion.

CAS / MDL: 7761-88-8
研究领域: 纳米技术 · 材料科学 · 微生物学 · 药学 · 环境科学
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TOXICOLOGY AND APPLIED PHARMACOLOGY · 2022 · IF 4.46

DNA damage by reactive oxygen species resulting from metabolic activation of 8-epidiosbulbin E acetate in vitro and in vivo

Shiyu Zhang,Ying Liu,Ting Liu,Jie Pan,Rong Tan,Zixia Hu,Bowen Gong,Yufen Liao,Peng Luo,Qibing Zeng,Weiwei Li,Jiang Zheng

8-Epidiosbulbin E acetate (EEA), a furan-containing diterpenoid lactone , is one of main component of Dioscorea bulbifera L. (DBL). It has been reported that EEA induces severe hepatotoxicity in mice and that its hepatotoxicity is associated with metabolic activation. The present study demonstrated that exposure to EEA (50, 100 or 200 μM) induced DNA damage, including significant DNA fragmentation, increases of tail DNA and olive tail moment, H2AX phosphorylation and PARP-1 activation, in cultured mouse primary hepatocytes. Similar observation was obtained in mice administered EEA at 50, 100 or 200 mg/kg. Pre-treatment with 10 μM ketoconazole (KTC), 200 μM vitamin C (VC), or 200 μM glutathione ethyl ester (GSH-OEt) reversed the over-production of reactive oxygen species (ROS) induced by EEA and attenuated susceptibility of hepatocytes to EEA-induced cytotoxicity and DNA damage in mouse primary hepatocytes. In contrast, pre-treatment with 1.0 mM L-buthionine sulfoximine (BSO) potentiated over-production of ROS, cytotoxicity and DNA damage induced by EEA. In summary, EEA induced DNA damage in cultured primary hepatocytes and the liver of mice. ROS, possibly along with DNA alkylation , participated in the observed DNA damage.

研究领域: 毒理学 · 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
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Screening and identification of lipase inhibitors extracted from Dioscorea nipponica Makino by UV–vis and HPLC coupled to UPLC-Q-TOF-MS/MS

Peiyi Jin,Linzhou Chen,Jinjian Zhong,Tiefeng Yuan,Lin Gan,Jilong Huang,Liping Wang,Huajun Fan,Chen Lin

Dioscoreae nipponica Makino ( D. nipponica ) as the rhizome of dioscoreaceae rich in steroidal saponins, has been reported to have the hypolipidemic effects etc. However, it is still unclear which exact active components are primary responsible for the beneficial effects. This study was conducted to fish out the lipase inhibitors from D. nipponica , and evaluate the inhibitory activity on porcine pancreatic lipase (PPL) through in vitro kinetic assay using p -nitrophenyl palmitate as substrate. Accordingly, the ethanolic extract was subjected to D101 macroporous resin purification for spectrophotometric screening, high performance liquid chromatography (HPLC) separation and structural characterization by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Through orlistat validation, the PPL inhibitory activity and IC 50 value of the extract were respectively 68.34 ± 1.47 % and 107.05 μg/mL under the optimized inhibition conditions. From 6 steroidal saponins identified, the inhibitory components named the protodioscin, protogracillin, dioscin and gracillin were fished out by grouping separation and HPLC analysis. Furthermore, dioscin and gracillin with the parent structure of diogenin were confirmed as the major inhibitors by virtue of stability tests based on transformation of protodioscin and protogracillin. Finally, the inhibitory mechanism of the major inhibitors toward PPL was further clarified by kinetic analysis and molecular docking analysis. The proposed method not only revealed the PPL inhibitory components in D. nipponica , but also provided an effective approach to hierarchical screening of PPL inhibitors from natural plants.

研究领域: 药理学 · 生物化学 · 分析化学 · 天然产物
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CARBOHYDRATE CHEMISTRY · 2021 · IF 1.667

Structural characterization of an alkali-extracted polysaccharide from Dioscorea opposita Thunb. with initial studies on its anti-inflammatory activity

Xuewei Jia,Xuanjing Wang,Yuanshang Liu,Yiyan Sun,Bingjie Ma,Zhenjie Li,Chunping Xu

An alkali-extracted polysaccharide (HY-B) was isolated and purified from Dioscorea opposita Thunb. (Huai Yam). Its chemical structure was analyzed with FT-IR, GC-MS and 1 D, 2 D-NMR spectrometry. It was proved that HY-B is mainly composed of α-1,4-linked glucose, which is similar to starch, but the starch-iodine color test proved that it was not starch. The chain conformation of HY-B was analyzed by SEC-MALLS-RI and TEM, indicated that HY-B exists in a random coil conformation. Its molecular weight is 18.7 kDa, and the molecular size is about 100 nm. MTT assays indicated that HY-B was nontoxic to RAW 264.7 cells in vitro. The results of anti-inflammatory studies showed that HY-B could inhibit the production of NO and TNF-α in RAW 264.7 macrophage stimulated by lipopolysaccharides (LPSs). This work provided the important information about the anti-inflammatory active component of Huai Yam and its potential applications in the food and health industries.

研究领域: 药理学 · 生物化学 · 分子生物学 · 食品科学
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