Food Bioscience
·
2025
·
IF 5.9
Xiaoting Yu,Xunyu Song,Yannan Chen,Yueqi Lv,Mingqian Tan
Astaxanthin (AXT) with mitochondria-targeted ability is desired for effectively preventing oxidative stress in various intestinal diseases. However, it is challenging to prepare mitochondria-targeted AXT (Mito-AXT) using traditional covalent bond methods due to the fragile structure of AXT and harsh reaction conditions, which result in low production yields and poor biocompatibility. Herein, we proposed a strategy to enhance the mitochondria-targeted efficiency of AXT by combining it with lipophilic cationic compounds through a non-covalent approach. Mito-AXT was synthesized through electrostatic coupling between anionic sulfonate-modified AXT (AXT-SO 3 ) and cationic (3-carboxypropyl) triphenylphosphonium bromide (TPP). The synthetic strategy successfully preserved the inherent DPPH and hydroxyl radical trapping capacity of AXT and achieved the efficient preparation of Mito-AXT with a yield of 86.17%. The accumulation of cationic TPP in mitochondria after the disassembly of Mito-AXT surprisingly facilitated the enrichment of anionic AXT-SO 3 in mitochondria. Notably, Mito-AXT regulated the redox balance, mitochondrial membrane potential, and mitophagy in IEC-6 cells under oxidative stress, thereby preventing apoptosis, compared to TPP-modified AXT molecules formed by covalent bonds. Furthermore, biosecurity analysis confirmed that Mito-AXT exhibited excellent biocompatibility. The results provided a simple, effective, and safe way to enhance the mitochondria-targeted efficiency of AXT through Mito-AXT, thereby effectively regulating the mitochondrial homeostasis in intestinal cells under oxidative stress.
研究领域:
生物化学
·
药理学
·
细胞生物学
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产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 41
·期 9
·1208-1222
·
IF 5.064
Almoiliqy Marwan,Wen Jin,Xu Bin,Sun Yu-chao,Lian Meng-qiao,Li Yan-li,Qaed Eskandar,Al-Azab Mahmoud,Chen Da-peng,Shopit Abdullah,Wang Li,Sun Peng-yuan,Lin Yuan
Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg −1 · d −1 , ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1β, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKβ, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 μmol · L −1 ) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies.
研究领域:
药理学
·
分子生物学
·
细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Jin Wen,Bin Xu,Yuchao Sun,Mengqiao Lian,Yanli Li,Yuan Lin,Dapeng Chen,Yunpeng Diao,Marwan Almoiliqy,Li Wang
Intestinal ischemia-reperfusion (I/R) injury is a common pathological process with high clinical morbidity and mortality. Paeoniflorin , a monoterpene glucoside, is found to have diverse health beneficial effects including autophagy modulation, anti-inflammatory, anti-apoptotic, and anti-oxidative effects. Based on our pre-experiments, we proposed that paeoniflorin could ameliorate intestinal I/R injury and restore autophagy through activating LKB1/AMPK signal pathway. Our proposal was verified using rat intestinal I/R model in vivo and intestinal epithelial cell line (IEC-6 cells) hypoxia/reoxygenation (H/R) model in vitro. Our results showed that paeoniflorin pretreatment exerted protective effects in rat intestinal I/R injury by reducing intestinal morphological damage, inflammation, oxidative stress, and apoptosis . Paeoniflorin restored H/R-impaired autophagy flux by up-regulating autophagy-related protein p62/SQSTM1 degradation, LC3II and beclin-1 expression, and autophagosomes synthesis without significantly affecting control IEC-6 cells. Paeoniflorin pretreatment significantly activated LKB1/AMPK signaling pathway by reversing the decreased LKB1 and AMPK phosphorylation without affecting total LKB1 both in vivo and in vitro . LKB1 knockdown reduced AMPK phosphorylation, suppressed LC3II and Beclin-1 level, and decreased the degradation of SQSTM/p62, and the knockdown weakened the effects of paeoniflorin in restoring the impaired autophagy flux in H/R injured IEC-6 cells, suggesting that paeoniflorin mitigated the intestinal I/R-impaired autophagy flux by activating LKB1/AMPK signaling pathway. Our study may provide valuable information for further studies.
研究领域:
药理学
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病理生理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Shujun Wang,Wei Liu,Jin Wang,Xia Bai
Curculigoside (CUR) is natural ingredient from Curculigo orchioides Gaertn with multiple biological activities. However, whether CUR protects from ulcerative colitis (UC) and underlying mechanisms are unclear. Herein, mice challenged with dextran sulfate sodium (DSS) were established and administrated with CUR for 7 days. Then histological pathologies and ferroptosis regulators were determined in vivo . The ferroptotic IEC-6 cells were prepared to investigate the underlying mechanism of CUR. Results showed that CUR inhibited the disease activity index, histological damage and cell death in mice with colitis. We also found that ferroptosis was induced in mice with colitis, as evidenced by iron overload, GSH depletion, ROS and MDA production, accompanied by decreased expression of SOD and GPX4. CUR treatment significantly reversed these alterations of ferroptotic features in DSS-induced mice. Furthermore, similar effects of CUR on ferroptosis were observed in IEC-6 cells under the combined treatment of H 2 O 2 and iron chloride hexahydrate. Interestingly, we found that CUR could increase the selenium sensitivity and promote GPX4 transcription level in IEC-6 cells. Knockdown of GPX4 significantly blocked the protective effects of CUR on cell death, GSH and MDA contents as well as LDH activity in ferroptotic IEC-6 cells. Taken together, these findings suggest that CUR protects against ferroptosis in UC by the induction of GPX4, which presents a potential agent for UC treatment.
研究领域:
药理学
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胃肠病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Haibin Zhu,Liuming Xie,Weidong Zhang,Qiang Yu,Yi Chen,Jianhua Xie
Chemical modification provides an important idea for advancing and harnessing plant polysaccharides. It is well known that Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) , is an important industrial crop resource, and polysaccharide stands as one of the compounds displaying a wide range of bioactivities within the leaves of C. paliurus . The study found that C. paliurus polysaccharides (CPP) were subjected to phosphate modification to obtain two phosphorylated polysaccharides (P-CPPL and P-CPPH) with degrees of substitution (DS) of 0.10 and 0.18, correspondingly. The findings indicated that the phosphorylation changed the chemical composition, relative molecular weight, molar ratio of monosaccharide composition and microstructure of CPP, thus changing the thermal stability and bioactivities of CPP. In vitro bioassay results demonstrated that CPP and its phosphorylated derivatives showed antibacterial activity at high concentrations. In addition, phosphorylation changes the water solubility and spatial configuration of CPP, so that P-CPPL and P-CPPH can bind or interact with enzymes more effectively, thus improving the α-glucosidase inhibitory activity in vitro. In vitro cell experiment results demonstrate that CPP and its phosphorylated derivatives can protect IEC-6 cells from oxidative damage by restoring mitochondrial membrane potential levels and modulating the expression and activation of Caspase-3. In summary, phosphorylation provided an essential way of changing the chemical properties of polysaccharides and enhancing their functionalities.
研究领域:
药学化学
·
生物化学
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植物科学
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食品科学
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产品关联
DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 67
·期 6
·2200774
·
IF 6.575
Jiawen Lu,Ying Yang,Elisabeth Varga,Doris Marko,Qiang Yu,Jianhua Xie,Chang Li,Yi Chen
Scope The previous in vivo studies show Ganoderma atrum polysaccharide (PSG-F 2 ) has a protective effect against the acrylamide (AA)-induced intestinal oxidative damage in rats. Now, this study aims to explore the protective mechanism with IEC-6 cell model. Methods and results Based on RNA Sequencing (RNA-Seq), the study screens MAPK signaling pathway as one of the most crucial pathways for pretreatment with PSG-F 2 against AA-induced damage in IEC-6 cells. In total, six key MAPK signaling pathway-related proteins (p-P38/P38, p-ERK/ERK, and p-JNK/JNK), and three tight junction key proteins ( Zonula Occludens protein-1, Claudin -1, and Occludin ) are detected by Western blot and immunofluorescence, which verify the RNA-Seq data. Moreover, PD98059 interference inhibits critical proteins in the MAPK signaling pathway, thus uncovering the precise molecular mechanisms of MAPK/ERK signaling pathway involve in the protective effects of PSG-F 2 against AA-induced intestinal barrier damage. Conclusion These findings confirm that PSG-F 2 can be used as a daily dietary supplement to protect the intestinal cells from damage caused by thermal processing hazards AA.
研究领域:
分子生物学
·
细胞生物学
·
药理学
·
毒理学
·
营养学
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产品关联
DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Liu Wei,Zheng Yi-nan,Jiang Shuang,Ren Shen,Tang Shan,Zhang Jing,Wang Zi,Li Wei
Background: Based on the Maillard reaction principle of red ginseng, this
study innovatively synthesized a new amino acid derivative by combining arginine with
lactose through simulated synthesis and was separated and purified through repeated silica
gel and polyacrylamide gel (Bio-gel P-II) column chromatography.
Purpose: The work was aimed at elucidating the synthesis of a novel amino acid derivative
and investigating the intestinal protective activity of the novel amino acid derivative
and possible molecular mechanism by establishing the intestinal injury model induced
by cisplatin in mice.
Methods: The purity and molecular weight of the amino acid derivatives were determined
to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by
establishing cisplatin (20 mg/kg)-induced intestinal injury in vivo for 10 days and IEC-6
cell model. The biochemical indexes and histopathological analysis were used to evaluate
the oxidative stress and inflammatory and pathological changes of intestinal tissue in
mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB),
cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C,
phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified
through immunofluorescence staining and western blot analysis.
Results: The new amino acid derivatives of chemical structure were identified to be 1-
(arginine-Nαgroup)-1-deoxy-4-O-(β-D-galactopyranosyl)-D-fructose, named Argininylfructosyl-
galactose (AFGA, C18H34N4O12). The results showed that pretreatment with a
single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury,
and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells
(p<0.05, p<0.01) and could effectively reduce the secretion of TNF-α and IL-1β in
serum and the expression level of NF-κB protein in intestinal tissues (p<0.01). Meantime,
AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and
Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt
pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also
suggested a better binding ability with the above-mentioned related target proteins.
Conclusion: The results clearly revealed AFGA as a potential multifunctional therapeutic
agent with a clear protective effect against cisplatin-induced intestinal injury may be
related to the PI3K/Akt signaling pathway.
研究领域:
药理学
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毒理学
·
分子生物学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Wan Wang,Hang Shang,Jinzhe Li,Yue Ma,Cong Xu,Jiage Ma,Juncai Hou,Zhanmei Jiang
Polyphenols have received attention as dietary supplements for the relief of alcoholic liver disease (ALD) due to various bioactivities. Ethanol-induced rat small intestinal epithelial cell 6 (IEC-6) and alpha mouse liver 12 (AML-12) cell models were pretreated with four dietary polyphenols with different structures to explore their effects on cytotoxicity and potential protective mechanisms. The results showed that polyphenols had potential functions to inhibit ethanol-induced AML-12 and IEC-6 cell damage and oxidative stress, and restore ethanol-induced IEC-6 permeability and tight junction gene expression. Especially, dihydromyricetin (DMY) had the best protective effect on ethanol-induced cytotoxicity, followed by apigenin (API). Western blot results showed that DMY and API had the best ability to inhibit CYP2E1 and Keap1, and promote nuclear translocation of Nrf2, which might be the potential mechanism by which DMY and API attenuate ethanol-induced cytotoxicity. Moreover, the molecular docking results predicted that DMY and API could bind more tightly to the amino acid residues of CYP2E1 and Keap1, which might be one of the inhibitory modes of dietary polyphenols on CYP2E1 and Keap1. This study provided a rationale for the subsequent protective effect of dietary polyphenols on alcohol-induced liver injury in animal models and provided new clues on bioactive components for ALD-protection based on the gut-liver axis.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Dong Wang,Xiaona Lu,Enbo Wang,Liangang Shi,Chi Ma,Xiaodong Tan
The cellular and tissue damage induced by oxidative stress (OS) contribute to a variety of human diseases, which include gastrointestinal diseases. Salvianolic acid B (Sal B), which is a natural polyphenolic acid in Salvia miltiorrhiza , exhibits prominent antioxidant properties. However, its precise function and molecular mechanisms in protecting normal intestine epithelium from OS-induced damage are still poorly defined. In this study, we tried to clarify this relationship. Here, we found Sal B addiction in the rat intestinal epithelial cell, IEC-6, prevented H 2 O 2 -induced cell viability decrease and apoptosis induction, ameliorated H 2 O 2 -induced intestinal epithelial barrier dysfunction and mitochondrial dysfunction, and suppressed H 2 O 2 -induced production of ROS to varying degrees, ranging from 10% to 30%. Moreover, by employing an ischemia reperfusion model of rats, we also discovered that Sal B treatment reversed ischemia and a reperfusion-caused decrease in villus height and crypt depth, decreased proliferation of enterocytes, and increased the apoptotic index in the jejunum and ileum. Mechanistically, Sal B treatment up-regulated the phosphorylated level of Akt and GSK3β in enterocytes in vitro and in vivo , and PI3K inhibitor LY294002 treatment abrogated the protective effects of Sal B. Meanwhile, the inactivation of GSK3β reversed the oxidative stress-induced apoptosis and mitochondrial dysfunction in IEC-6 cells. Together, our results demonstrated that the damage of intestinal epithelial cells in in vitro and in vivo models were both attenuated by Sal B treatment, and such antioxidant activity might very possibly be attributed to the activation of Akt/GSK3β signaling.
研究领域:
药理学
·
胃肠病学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Suresh Veeraperumal,Hua-Mai Qiu,Chon-Seng Tan,Szu-Ting Ng,Wancong Zhang,Shijie Tang,Kit-Leong Cheong,Yang Liu
Ethnopharmacological relevance Lignosus rhinocerotis (Cooke) Ryvarden cultivar TM02, also known as tiger's milk mushroom, is regarded as important folk medicine in Malaysia, while is used for the treatment of liver cancer, chronic hepatitis, gastric ulcer in traditional Chinese medicine . However, there is no compilation of scientific evidence that its protection for gastric, and no attempts have been made to understand how polysaccharides in Lignosus rhinocerotis might promote intestinal mucosal wound healing. Aim of the study: This study aimed to investigate the effect and mechanism of β-glucan prepared from L. rhinocerotis using an enzymatic method on epithelial restitution during intestinal mucosal damage. Materials and methods Based on FT-IR, MALDI-TOF-MS, HPSEC-MALLS-RID, and AFM , the structure of polysaccharides from L. rhinocerotis was analysed. In addition, polysaccharides were used to test for wound healing activity in IEC-6 cells by measuring cell migration, proliferation, and expression of cell division control protein 42, Rac-1, RhoA, and Par-3. Results β-glucan was extracted using enzyme-assisted extraction, and a yield of approximately 8.5 ± 0.8% was obtained from the dried biomass. The β-glucan extracted by enzyme-assisted extraction (EAE) of polysaccharides was composed entirely of D-glucose with a total carbohydrate content of 95.5 ± 3.2%. The results of HPLC, FTIR, and MALDI-TOF-MS analyses revealed EAEP to be confirmed as β-glucan. The molecular weight of prepared β-glucan was found to be 5.315 × 10 4 g/mol by HPSEC-MALLS-RID. Furthermore, mucosal wound healing studies showed that the treatment of IEC-6 with a β-glucan concentration of 200 μg/mL promoted cell migration and proliferation, and it enhanced the protein expression of cell division control protein 42, Rac-1, RhoA, and Par-3. Conclusions The present study reveals that the prepared β-glucan accelerates intestinal epithelial cell proliferation and migration via activation of Rho-dependent pathway. Hence, β-glucan can be employed as a prospective therapeutic agent for the treatment of diseases associated with gastrointestinal mucosal damage, such as peptic ulcers and inflammatory bowel disease .
研究领域:
药理学
·
细胞生物学
·
胃肠病学
·
民族药理学
·
传统中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Lingrong Wen,Zhili Sheng,Jinping Wang,Yueming Jiang,Bao Yang
Ganoderma lucidum spore is widely accepted as functional food. Polysaccharides are the predominant bioactive components in G. lucidum spore and contribute much to its health benefits. However, their structural characteristics remain unclear. In this work, water-soluble polysaccharides (GLSP) were obtained by hot water extraction. Three monosaccharides, including arabinose (Ara), glucose (Glc) and galactose (Gal), were presented in GLSP. 1D and 2D NMR data revealed that GLSP were composed mainly by two polysaccharides, β-glucan and arabinogalactan. The arabinogalactan had a backbone of galactan with Ara f in the side chain. β-Glucan was the dominant polysaccharide in G. lucidum spore. The molecular weight was measured. GLSP could induce IEC-6 cells proliferation in a concentration-dependent manner. Moreover, GLSP possessed a strong anti-inflammatory activity through inhibiting the overproduction of NO and pro-inflammatory cytokines, like interleukin-6 (IL-6) and interleukin-1β (IL-1β) induced by LPS. These results implied the potential of GLSP on gut barrier protection.
研究领域:
药理学
·
免疫学
·
分子生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Lan Wang,Jin Mao,Qi Zhou,Qianchun Deng,Lei Zheng,Jie Shi
Curcumin is a hydrophobic substance with various beneficial biological activities. Its weak solubility and instability, however, now restrict its usage as a functional food. Herein, the purpose of this work is to fabricate curcumin-loaded bovine serum albumin/carboxymethylpachymaran nanoparticles (BMCNPs) to overcome these challenges. Under optimal conditions, the BMCNPs were spherically shaped with a surface charge of −31.4 mV, polydispersity index of 0.16 and particle size of 158.3 nm were characterized by electron microscopy and dynamic light scattering. The interactions between curcumin, bovine serum albumin (BSA), and carboxymethylpachymaran (CMP) were investigated. BMCNPs had a much better curcumin encapsulation efficiency (74.1%) as well as strong antioxidant activity, storage stability, and ionic strength tolerance. The in vitro release revealed that curcumin was more successfully sustained in the small intestine stage (68.7%) and that BMCNPs were able to prevent it from releasing too early in the stomach (21.4%). Not to mention, the results of the cytotoxicity test performed on the HT-29 and IEC-6 cell lines demonstrated the acceptable biocompatibility of BMCNPs.
研究领域:
药学
·
纳米技术
·
食品科学
·
生物技术
✓ 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）