JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Amina Arken,Xinmin Zhao,Yanhua Gao,Adil Omar,Dan Tang,Ahmidin Waili,Zi Yang,Yahui Wang,Haji Akbar Aisa,Abulimiti Yili
Ethnopharmacological relevance Lamb abomasum is used as an edible medicinal source in traditional Chinese medicine for the treatment of gastrointestinal disorders . Lamb abomasum sourced biochemical drug Lamb's trip extract and Vitamin B12 capsule used for the clinical treatment of chronic gastritis , gastric ulcer , and reversal of intestinal metaplasia . Therefore, claimed to have prevention of gastric cancer activity. Aim of the study In this study, we aim to assess whether the glycoprotein has biological activity in the cure of gastric disorder and conduct a structure-activity relationship. Materials and methods Glycoproteins’ extraction conditions were optimized by the response surface method and purified with DEAE-cellulose and Sephadex G-50 chromatography. Two homogenous glycoproteins’ physiochemical structures were studied with electrophoresis , HPLC analysis, peroxide oxidation, and β-elimination, FT-IR, CD, LC-MS/MS, and EDS analysis. The antiinflammation activity of the glycoprotein was determined against COX-2 and LOX-15 enzyme inhibitory ability in vitro, and antitumor activity against HT-29 and HGC-25, and cytotoxicity on L-02 cells was determined in vivo with the MTT method. Results The abomasum was abundant in glycoprotein and the extraction yield of glycoprotein was up to 24.6 ± 2.1% under optimized conditions. Two homogeneous glycoproteins SAGP-I and SAGP-II determined to be ribose-conjugated and sulfated glycoproteins with a molecular weight of 15.6 kDa and 6.4 kDa. And according to the structural analysis, SAGP-I was a mucin-type ribose-conjugated glycoprotein with 14 O-glycosylation and one N- glycosylation site. SAGP-I and SAGP-II have remarkable anti-inflammatory activity against COX-2 enzyme with the IC 50 of 17.64 ± 1.25 μ g/mL and 16.14 ± 1.11 μ g/mL, respectively. Meanwhile, the two glycoproteins showed strong antitumor activity against HT-29 with the EC 50 of 19.19 ± 1.46 μ g/mL and 184.9 ± 5.6 μ g/mL, respectively. Conclusion The Highly purified glycoprotein SAGP-1 and SAGP-II showed anti-inflammatory activity against the COX-2 enzyme, and antitumor activity against HT-29 human colon cancer cells and noun-inhibitory activity against LOX-15 enzyme and HGC-25. Both glycoproteins are ribose conjugated and sulfated whose characters are related to their anti-inflammatory and anti-tumor activity. Such results suggest the possibility of anti-inflammatory and pre-cancer activity. And in some degree explains the pharmacy of abomasum's traditional use in gastric disorder and clinical use of lamb abomasum APIs drugs’ in gastric disorders and gastric cancer development. This study provides a preliminary basis for the further study of the per-cancer mechanism of lamb abomasum glycoprotein. And, would be the material basis of the clinical use of Lamb's trip extract and Vitamin B12 capsule.
研究领域:
药理学
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生物化学
·
民族药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Zhao Liu,Chen Zhang,Beiming Cui,Yijie Wang,Kaisheng Lim,Kai Li,Jean Paul Thiery,Jun Chen,Chun Loong Ho
Protein-based cancer therapies are considered an alternative to conventional anticancer regimens, providing multifunctional properties while showing low toxicity. However, its widespread use is limited by absorption and instability issues, resulting in higher dosage requirements and a prolonged onset of bioactivity to elicit the desired response. Here, we developed a non-invasive antitumor treatment using designed ankyrin repeat protein (DARPin)-anticancer protein-conjugate that specifically targets the cancer biomarker, epithelial cell adhesion molecule (EpCAM). The DARPin-anticancer proteins bind to EpCAM-positive cancer cells and improve the in vitro anticancer efficacy by over 100-folds within 24 h, where the DARPin-tagged human lactoferrin fragment (drtHLF4) IC50 value is within the nanomolar range. Orally administered drtHLF4 was readily absorbed into the systemic flow of the HT-29 cancer murine model, exerting its anticancer effect on other tumors in the host body. Orally administered drtHFL4 cleared HT29-colorectal tumors using a single dose, whereas intratumoral injection cleared HT29-subcutaneous tumors within three doses. This approach addresses the limitations of other protein-based anticancer treatments by providing a non-invasive anticancer therapy with improved potency and tumor-specificity.
研究领域:
癌症治疗
·
分子生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hongyan Lin,Shuaijun Cui,Xinye Xu,Qingqing Chen,Jiazi Ge,Dongxuan Ai,Jie Zhu,Yuheng Tao,Liqun Wang,Lingyu Ruan,Wenhao Ge
18β-Glycyrrhetinic acid (18β-GA) is the main active component of licorice and one of the most promising lead compounds in traditional Chinese herbal medicine. Previous studies have shown that 18β-GA can act as a PPARγ agonist to exert antitumor activity. However, the number of reported 18β-GA derivatives as PPARγ agonists is limited and they have significant toxic side effects, which greatly restricts their application and development. To obtain highly effective and low-toxic PPARγ agonists, through structure-activity relationship (SAR) analysis, we constructed a molecular library of 18β-GA derivatives containing 13,440 compounds and screened out 14 novel 18β-GA ester derivatives. The selected compounds were evaluated for their antitumor activity in vitro. The results showed that most of the compounds exhibited strong anti-proliferative activity against five human cancer cell lines, especially the human colon cancer cell line HT-29, without significant toxicity to normal cell lines. Among them, C1 had the strongest anti-proliferative activity against HT-29, with an IC 50 value of 12.25 μM, which was 12 times higher than that of its parent nucleus 18β-GA. C1 can block the cell cycle of HT-29 cells in G2/M phase, significantly inhibit their migration and induce their apoptosis. Molecular docking and dynamics simulation results suggested that C1 could stably bind to the active pocket of PPARγ. Further PPARγ activity analysis and drug-likeness prediction results indicated that C1 could act as a PPARγ agonist to exert antitumor effects and had certain drug-likeness, which is worthy of further study.
研究领域:
药理学
·
药物化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Shuang Luo,Xiangliang Deng,Qi Liu,Zengfeng Pan,Zhongxiang Zhao,Lian Zhou,Xia Luo
Emodin is an anthraquinone compound derived from Rheum officinale Baill . Several reports showed that emodin had efficacy on acute pancreatitis , keratitis , myocarditis , and rheumatoid arthritis . However, the potency of emodin on ulcerative colitis(UC) remains unclear. In this study, we investigated the effect of emodin on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Our results showed that emodin significantly alleviated the symptoms of DSS-induced UC in mice, involving prevented the loss of body weight and colon shortening, decreased the disease activity index (DAI), intestinal damages and the count of white blood cells (WBC) in peripheral blood. In addition, emodin treatment decreased the level of anti-flagellin antibody in serum and significantly down-regulated the expression of TLR5 and NF-κB p65 in colon of the UC mice. Further study in vitro showed that emodin down-regulated the expression of TLR5 and MyD88 , up-regulated the expression of IκB, inhibited the nuclear translocation of NF-κB p65 and decreased the release of IL-8 in flagellin-stimulated HT-29 cells. These results, for the first time, demonstrated that emodin had the therapeutic potential to ameliorate UC symptoms possibly via regulating the flagellin-TLR5 signaling pathway . Emodin may be a potential candidate ingredient for ulcerative colitis.
研究领域:
药理学
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免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yu Zhang,Yan Liu,Yinxing Zhou,Ziming Zheng,Wenqi Tang,Mengzi Song,Jinglin Wang,Kaiping Wang
Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro . SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2023
·
IF 2.8
Zepeng Chen,Qinglong Gu,Ruichao Chen
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.
研究领域:
炎症性肠病
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分子生物学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ya-Hui Yu,Kouadio Jean Eric-Parfait Kouame,Xiaozhen Liu,Xiangying Yu,Ming-Yu Jin,Long-Qing Li,Fengyuan Liu,Yuting Li,Jing-Kun Yan,Bing Li
The combination of selenium nanoparticles (SeNPs) with natural polysaccharides represents an effective strategy to address the limitations of SeNPs and providing a stable, highly bioactive form of Se. In this study, we explored the potential of longan polysaccharides (LP) in the preparation and stabilization of SeNPs. The morphology, stability, stabilization mechanism, and cytotoxicity of LP-SeNPs were investigated. The results showed that the LP-SeNPs were uniform spherical nanoparticles with a mean particle size of 100.4 ± 1.1 nm, and demonstrated excellent stability over a 14-day storage period, which was attributed to the interaction between the SeNPs and the hydroxyl groups present on the surface of LP. Meanwhile, LP-SeNPs have no toxic effect on rat intestinal epithelial (IEC-6) cells, while they are cytotoxic to human colon cancer (HCT-116 and HT-29) cells, including growth inhibition, morphological alteration, and the promotion of reactive oxygen species and mitochondrial membrane potential loss in a dose-dependent manner. LP-SeNPs induced apoptosis in HCT-116 and HT-29 cells by regulation of the apoptosis-related proteins including Bax, Bcl-2, caspase-3, and cytochrome c . Therefore, our results provide a theoretical basis for the development and application of LP and indicate the potential promise of LP-SeNPs as dietary Se supplements and health-promoting food ingredients.
研究领域:
食品科学
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生物医学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2023
·
IF 2.9
Qian Xiao-li,Meng Di,Liu Heng,Liu Chao-he,Zhou Ping,Yang Yin-he,Wang Jia-peng,Xiao Huai,Ding Zhong-tao
Objective To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. Methods Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. Results MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC 50 ) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC 50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC 50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G 1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. Conclusion Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
研究领域:
肿瘤学
·
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
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Rui Chang,Rongrong Fu,Yujiao Huang,Jibing Zhang,Changshun Feng,Rui Wang,Hui Yan,Guangyong Li,Xiaohong Chu,Fengjiao Yuan,Dianlong Jia,Jun Li
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 8
·1596
·
IF 3.06
Yi Ma,Yunhui Feng,Wanling Zeng,Huibo Luo
This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625–1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0–60 μg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1.Keywords:antioxidant;oxidative stress;anthocyanin;HT-29
研究领域:
食品科学
·
药理学
·
营养学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Kaiying Jia,Xueying Tao,Zhengqi Liu,Hui Zhan,Weijun He,Zhihong Zhang,Zheling Zeng,Hua Wei
In this study exopolysaccharide (EPS) of Enterococcus faecium WEFA23 from healthy infant's feces was yielded as high as 130 mg/L by fermentation. By purification the EPS was further fractioned into A23-1, A23-2, A23-3 and A23-4 on HiTrap Q HP and Superdex G-200 column. As the major purified fractions, A23-2 and A23-4 were analyzed for the preliminary structures and investigated for the biological properties in vitro. The molecular weight of A23-2 and A23-4 was 2.50 × 10 4 Da and 3.23 × 10 4 Da, respectively. A23-2 was composed of mannose, glucose and galactose with a ratio of 1.38:1.00:1.42, while A23-4 consisted of only mannose. The antioxidant ability of A23-2 was significantly higher than that of A23-4, as proved by scavenging test of DPPH radical, hydroxyl radical and superoxide radical. Both A23-2 and A23-4 exhibited strong inhibition against the adhesion of L . monocytogenes CMCC54007 on HT-29 cells no matter for the styles of competition, displacement and exclusion. Notably, for exclusion they had a maximal inhibition rate of 89.85 ± 0.46% and 90.81 ± 2.29%, respectively, at 200 μg/mL.
研究领域:
微生物学
·
食品科学
·
生物技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 77
·期 2
·283-294
·
IF 4.158
Jia Qinghui,Zhang Haihua,Su Yongmei,Liu Xin,Bai Jiangsong,Lang Wuying,Shi Qiumei,Feng Minshan
The ulcerative colitis (UC) is a typical inflammatory bowel disease (IBD) causing great damages, while strictosamide (STR) is a natural alkaloid that possesses strong anti-inflammatory property in infection and inflammation-related diseases. Our study is aimed at evaluating the anti-inflammatory activity of STR in the course of UC. Briefly, male Balb/c mice were treated with 3.5% dextran sulfate sodium (DSS) for 6 consecutive days to establish an acute model of UC, and the administration of gradient concentrations of STR was subsequently performed. Accordingly, colonic pathological alterations including the reduced ratio of colon weight/length, decreased disease activity index (DAI), and attenuated H&E damage were found in UC mice after STR treatment. Based on the analyses of real-time PCR and western blot, downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) was also determined in the colonic tissue of UC mice after the treatment of STR. ELISA and immunohistochemical staining further suggest the relief of inflammation in UC mice with decreased expressions of MPO and iNOS after STR treatment. In addition, STR was also validated to significantly inhibit NF-κB signaling in UC mice by western blot and Electrophoretic Mobility Shift Assay (EMSA). Meanwhile, restricted inflammation was also determined in STR-treated IEC6 and HT-29 cells. The utilization of PDTC, an inhibitor of NF-κB, further demonstrated that STR ameliorated the inflammation by inhibiting the NF-κB signaling in vitro. In summary, our study suggests that STR could be a potential candidate for IBD therapy.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
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）