Pharmaceutics
·
2023
·Vol. 15
·期 10
·2499
·
IF 5.4
Qi Zhang,Mengyuan Xia,Chenxuan Zheng,Yinghong Yang,Junjie Bao,Wenjuan Dai,Xuefeng Mei
Coenzyme Q10 (CoQ10) exists in two forms, an oxidized form and a reduced form. Ubiquinol is the fully reduced form of CoQ10. Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect. However, ubiquinol has an important stability problem which hampers its storage and formulation. It can be easily transformed into its oxidized form—ubiquinone—even at low temperature. In this work, we designed, synthesized, and characterized a new cocrystal of ubiquinol with vitamin B3 nicotinamide (UQ-NC). Compared to the marketed ubiquinol form, the cocrystal exhibited an excellent stability, improved dissolution properties, and higher bioavailability. The cocrystal remained stable for a long period, even when stored under stressed conditions. In the dissolution experiments, the cocrystal generated 12.6 (in SIF) and 38.3 (in SGF) times greater maximum ubiquinol concentrations above that of the marketed form. In addition, in the PK studies, compared to the marketed form, the cocrystal exhibited a 2.2 times greater maximum total coenzyme Q10 concentration and a 4.5 times greater AUC than that of the marketed form.Keywords:ubiquinol;cocrystal;polymorph;stability;bioavailability
研究领域:
药剂学
·
生物化学
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DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 4
·429
·
IF 6.6
Meijie Song,Qianqian Xu,Rifat Nowshin Raka,Chunhua Yin,Xiaolu Liu,Hai Yan
Coenzyme Q10 (CoQ10), a high-value-added nutraceutical antioxidant, exhibits an excellent ability to prevent cardiovascular disease. Here, a novelCereibacter azotoformansstrain, designated YS02, was isolated for its ability to produce CoQ10 and genetically characterized by whole genome sequencing (WGS). The CoQ10 biosynthesis and metabolism differences of YS02 under various culture conditions were also systematically investigated. Phylogenetic analysis based on 16 S rRNA genes, along with taxonomic verification using average nucleotide identity (ANI) analysis, confirmed its classification asC. azotoformans. Enzymatic genesdxs,dxr,idi, ubiA, andubiGwere annotated in YS02, which are critical genetic hallmarks for CoQ10 biosynthesis. Under aerobic–dark cultivation, YS02 grows well, and CoQ10 production can reach 201 mg/kg. A total of 542 small-molecule metabolites were identified from YS02 in aerobic–dark and anaerobic–light cultivation via ultra-high performance liquid chromatography–coupled quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS). Additionally, 40 differential metabolites were screened through multivariate statistical analysis. Metabolic pathway analysis revealed that the biosynthesis of phenylalanine, tyrosine, and tryptophan might be latent factors influencing CoQ10 production discrepancies within YS02 under both cultural modes. These findings represent new insights into the metabolic mechanism of YS02 and underscore its potential as an alternative strain source for industrial CoQ10 production, enriching the existing resources.
研究领域:
微生物学
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生物化学
·
营养学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Xuan Ma,Hui Chen,Lixing Cao,Shuang Zhao,Chong Zhao,Shutao Yin,Lihong Fan,Hongbo Hu
Ferroptosis is a new form of iron-dependent cell death . A growing body of evidence suggests that abnormal ferroptosis is involved in developing neurodegenerative diseases. 18β-glycyrrhetinic acid (GA) is a major bioactive component of licorice with multiple biological activities including neuroprotection. Give the role of ferroptosis in the neurodegenerative diseases, we hypothesized that the neuroprotective effect of GA might be associated with its ability to protect neuro-cells from ferroptosis. Results demonstrated that GA was able to prevent a well-known ferroptosis inducer ferroptosis inducer 56 (FIN56)-triggered ferroptosis in HT22 mouse neuronal cell. Further mechanistic investigation revealed that the protection of GA on ferroptosis is attributed its inhibiting effect on cellular labile iron accumulation and up-regulating coenzyme Q10 (CoQ10) levels. The findings of the present study uncovered a novel mechanism involved in the neuroprotective effect of GA, and imply that GA could be developed as a novel agent to manage ferroptosis-related diseases.
研究领域:
神经科学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2020
·
IF 7.053
Wenqi Cao,Linfan Shi,Gengxin Hao,Jun Chen,Wuyin Weng
Microfluidized gelatin hydrolysates (MGH) with decreasing molecular weight from MGH-A to MGH-E were prepared, and their emulsion properties were investigated. The molecular weight, particle size, and emulsifying activity of MGH decreased as gelatin degraded by enzymatic hydrolysis with neutral protease increased. Dramatic decreases in the surface hydrophobicity and emulsifying stability of MGH were observed as the content of peptide fractions of 18 and 23 kDa increased. The average droplet sizes of emulsions based on MGH-A, MGH-B, MGH-C, and MGH-D were 622.1, 558.8, 389.7, and 1058.9 nm, respectively, and the MGH-E-based emulsion exhibited creaming. While the flow index of the MGH-A-based emulsion was greater than 1, those of the other emulsions were less than 1. Optical and confocal laser scanning microscopic images showed fine and uniform droplet distributions without flocculation or coalescence in the MGH-A-, MGH-B-, and MGH-C-based emulsions. The encapsulation efficiency (EE) of co-enzyme Q 10 (CoQ 10 ) in the spray-dried encapsulation prepared from MGH-B was 84.3%, and EE generally decreased with increasing or decreasing degradation degree of MGH. No obvious differences were observed among the surface images of encapsulations prepared using MGH-A, MGH-B, and MGH-C, and aggregated distributions were found in the MGH-D- and MGH-E-based encapsulations. The storage stability and in vitro bioaccessibility of CoQ 10 encapsulated by MGH-E were poorer than those of CoQ 10 encapsulated by the other wall materials. The results of the current study indicate that molecular weight and particle size have significant effects on the emulsion and encapsulation properties of MGH.
研究领域:
食品科学
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生物化学
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DOI
高影响因子
JOURNAL OF SOLUTION CHEMISTRY
·
2014
·Vol. 43
·期 3
·585-607
·
IF 1.083
Peng Xin,Sun Yinhe,Qi Wei,Su Rongxin,He Zhimin
UV–vis absorption, fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopic methods were employed to reveal the mechanism of the binding between coenzyme Q 10 (CoQ 10 ) and human serum albumin (HSA) under simulated physiological conditions (pH = 7.4). The binding parameters were calculated by the fluorescence quenching method. The results demonstrate that the fluorescence quenching of HSA by CoQ 10 is mainly static quenching due to the formation of HSA–CoQ 10 complexes, and the number of binding sites ( n ) is equal to 1. The thermodynamic parameters (Δ H
0 = −43.18 kJ·mol −1 , Δ S
0 = −47.05 J·mol −1 ·K −1 , Δ G
0 = −29.15 kJ·mol −1 ) indicate that the enthalpy-driven binding process is favorable, and the main binding forces between CoQ 10 and HSA are hydrogen bonds and van der Waals forces. The competitive experiments using different site markers indicate that subdomain IIA (site I) of HSA is the primary binding site for CoQ 10 . The average binding distance ( r ) between HSA and CoQ 10 is 4.29 nm, which was estimated according to the Förster’s theory of non-radiation energy transfer. In addition, the UV–vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid fluorescence, CD spectra, and FT-IR spectroscopy data show slight conformational changes of HSA in the presence of CoQ 10 . These findings provide valuable binding information between HSA and CoQ 10 , which may be beneficial to pharmacokinetics research and could be used to design the dosage form of CoQ 10 .
研究领域:
生物化学
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药理学
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DOI
高影响因子
Drug Research
·
2017
·Vol. 68
·期 05
·270-279
·
IF 0
Shuoye Yang
Long-circulating liposomal delivery systems of encapsulated Coenzyme Q10 (CoQ10), a ubiquinone anti-cataract agent, were developed with different molar ratios of PEGylated lipids and/or cholesterol. The resulting samples were contrasted through observation of morphology, analysis of particle size and Zeta potential, and in vivo pharmacokinetics. A protamine aggregation method with high selectivity was developed to determine the encapsulation efficiency (EE), after which the liposome formulation was further optimized by applying a Box Behnken design (BBD) using EE as the evaluation index. The results showed that liposomes had a large, unilamellar structure, and that particle sizes of cholesterol-containing liposomes increased along with the increase of cholesterol molar percentage, while the size of PEGylated vesicles decreased slightly as PEG-lipid contents increasing. The optimum formulation and optimal values of each influencing factor were quantitatively obtained, and the measured value was highly consistent with the predicted results. In vivo evaluation performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) demonstrated that liposomal encapsulation largely prolonged half-lives and improved bioavailability for vectors prepared with either lipid component, and the liposomes composed of both cholesterol and PEG-lipid possessed the best pharmacokinetic properties. The results suggest that incorporating high contents of cholesterol and PEG modification could be a potentially useful method for enhancing the length of circulation and the sustained release effect for liposome-encapsulated chemicals.
研究领域:
药剂学
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生物医学工程
·
药物代谢动力学
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DOI
PubMed
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
·
2015
·
IF 1.257
Huibin Li,Fang Chen
The aim of this work was to prepare coenzyme Q10 (CoQ10) long-circulating liposomes, and establish the quality standard to determine the content and entrapment efficiency. CoQ10 long-circulating liposomes were prepared by the film dispersion method, HPLC assay for the determination of CoQ10 was developed. Free drugs and liposomes were separated using the protamine aggregation method and entrapment efficiency was determined. The liposomes were homogeneous and the mean diameter was 166.0 nm, Zeta potential was −22.2 mV. The content and entrapment efficiency of CoQ10 were 98.2% and 93.2% for three batches of liposomes, respectively. The lyophilized form of liposomes prepared by freeze-drying showed stable quality characteristics during storage. The formulation and preparative method can be used to prepare CoQ10 long-circulating liposomes with high entrapment efficiency and high quality, the determination method of drug content and entrapment efficiency were effective and rapid and can be used for quality evaluation of liposomes.
研究领域:
药剂学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2021
·Vol. 35
·期 7
·e22778
·
IF 3.652
Delu Zheng,Chenli Cui,Chen Shao,Yanqiu Wang,Chengsong Ye,Gaoyou Lv
Coenzyme Q10 (CoQ10) has been reported to improve bone density and the number of trabeculae in postmenopausal osteoporosis, but the mechanism remains to be elucidated. We aimed to investigate the effects of CoQ10 on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and the underlying molecular mechanisms. RAW264.7 cells were treated with different concentrations of RANKL to differentiate into osteoclasts, and then these cells were treated with different concentrations of CoQ10 with or without H 2 O 2 . Tartrate-resistant acid phosphatase staining was performed to detect osteoclasts. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined by flow cytometry, and the effects of CoQ10 on protein and messenger RNA expression of mitochondrial apoptosis-associated proteins and osteoclast marker proteins were measured by quantitative reverse transcription polymerase chain reaction and western blot, respectively. Furthermore, enzyme-linked immunosorbent assay was conducted to analyze the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). RANKL significantly induced osteoclastogenesis in RAW264.7 cells, with the greatest efficiency at 50 ng/ml. CoQ10 had no significant effects on cell viability but it significantly increased the percentages of cell apoptosis. Mechanically, CoQ10 statistically decreased the levels of Bcl-2 and cytochrome C in mitochondria and upregulated the levels of Bax, cleaved caspase 3, and cytochrome C in the cytoplasm. Moreover, CoQ10 significantly decreased RANKL-induced osteoclastogenesis regardless of exposure to H 2 O 2 . In addition, CoQ10 statistically reduced MDA activity and elevated the activities of SOD and CAT, as well as the expression of oxidative stress-related proteins. CoQ10 may inhibit RANKL-induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells. Highlights 1 Osteoclastic are efficiently differentiated at 50 ng/ml of RANKL in RAW264.7 cells. 2 Coenzyme Q10 (CoQ10) promotes mitochondrial apoptosis in RANKL-treated RAW264.7 cells. 3 CoQ10 inhibits mitochondrial oxidative stress in RANKL-treated RAW264.7 cells. 4 CoQ10 inhibits RANKL-induced osteoclastogenesis.
研究领域:
药理学
·
细胞生物学
·
骨质疏松症
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Yuan Liu,Yaxin Yao,Wenjing Tao,Feng Liu,Songbai Yang,Ayong Zhao,Dan Song,Xiangchen Li
Bisphenol A (BPA) is a widely distributed environmental endocrine disruptor. The accumulation of BPA has been proved that produce various toxic effects both on human and animals. However, the strategies to reduce the damage of BPA on the body and related mechanisms remain to be studied. Coenzyme Q10 (CoQ10), as a powerful antioxidant, is ubiquitous in many eukaryotic cells, which can improve the integrity of lysosomal membrane, lysosomal degradation function and promote autophagy. Here, we examined the ability of CoQ10 to alleviate oxidative stress and apoptosis in BPA-induced damages in C2C12 cells, and how to alleviate it. Our results showed that BPA treatment significantly reduced cell viability, increased the number of cell apoptosis and ROS production, decreased mitochondrial membrane potential, and inhibited the gene expression of mitochondria biogenesis. Moreover, we demonstrated that exposure to BPA increased expression levels of autophagy protein (LC3-II, p62), inhibited autophagy flux, and disrupted the acidic pH environment of lysosomes. Importantly, CoQ10 supplementation effectively restored these abnormalities caused by BPA. CoQ10 significantly decreased the apoptotic incidence and ROS levels, improved mitochondrial membrane potential. Moreover, CoQ10 improved lysosome function and enhanced autophagy flux. Taken together, our results indicate that CoQ10 supplementation is a feasible and effective way to promote the level of autophagy by improving lysosomal function, thereby reducing the apoptosis caused by BPA accumulation. This study aims to provide evidence for the role of CoQ10 in repairing BPA-induced cell damage in clinical practice.
研究领域:
毒理学
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细胞生物学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Benkai Qin,Lei Liu,Yangyang Pan,Yingchun Zhu,Xiaohe Wu,Shiyong Song,Guang Han
Coenzyme Q10 (CoQ10) is widely used in preventive or curative treatment of cardiovascular diseases. However, CoQ10 exhibits an extremely low solubility in aqueous medium as well as a poor oral bioavailability. Therefore, solanesyl poly(ethylene glycol) succinate (SPGS) and CoQ10 were formulated as CoQ10-SPGS micelles with a high content of CoQ10 to improve the bioavailability of CoQ10 in rat. Findings indicate that, in the CoQ10-SPGS micelles, SPGS is self-assembled into stable nanosized micelles with a CoQ10 loading capacity of more than 39%. The CoQ10-SPGS micelles exhibit an enhanced photostability upon exposure to simulated sunlight. In vivo experiments demonstrate that, as compared to that of the coarse suspensions of CoQ10, there was three-fold enhancement of oral bioavailability for CoQ10-loaded SPGS micelles depending on varying molecular weight of SPGS. In the encapsulation of CoQ10 by SPGS micelles, the self-assembled nanocarriers with strong muco-adhesive properties lead to increases in the solubility and oral absorption of lipophilic CoQ10 nanoparticles.
研究领域:
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2024
·
IF 1.9
Zheng Delu,Cui Chenli,Ye Chengsong,Shao Chen,Zha Xiujing,Xu Ying,Liu Xu,Wang Can
Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.
研究领域:
细胞生物学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 3.8
Haiyan Zhu,Yijing Yang,Yenan Duan,Xin Zheng,Zixiong Lin,Jie Zhou
Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events , particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis ; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability , disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the −1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
·
肾脏生理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）