JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yassmin Raafat Hassan,Riham A. El-Shiekh,Hala M. El Hefnawy,Osama G. Mohamed,Karema Abu-Elfotuh,Ahmed M. Hamdan,Alshaymaa Darwish,Ayah M.H. Gowifel,Ashootosh Tripathi,Camilia George Michael
Ethnopharmacological relevance Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill., also known as “African mango” or “bush mango”, belonging to family Irvingiaceae, has been mostly used as food and traditional medicine for weight loss and to enhance the health. Aim of the study The overconsumption of high-fat and high-carbohydrate (HFHC) food induces oxidative stress, leading to neurological and cognitive dysfunction . Consequently, there is an immediate need for effective treatment. Hence, this study explored the efficacy of orlistat , metformin , and I. gabonensis seeds' total aqueous extract (IG SAE) in addressing HFHC-induced cognitive impairment by mitigating oxidative stress and their underlying mechanistic pathways. Materials and methods Initially, the secondary metabolite profile of IG SAE is determined using high-performance liquid chromatography coupled with a mass detector (UHPLC/MS). The in vivo study involves two phases: an established model phase with control (10 rats on a standard diet) and HFHC diet group (50 rats) for 3 months. In the study phase, HFHC is divided into 5 groups. The first subgroup receives HFHC diet only, while the remaining groups each receive HFHC diet with either Orlistat, metformin, or IG SAE at doses of 100 mg/kg and 200 mg/kg, respectively, for 28 days. Results More than 150 phytoconstituents were characterized for the first holistic approach onto IG metabolome. Characterization of IG SAE revealed that tannins dominate metabolites in the plant. Total phenolics and flavonoids were estimated to standardize our extract (77.12 ± 7.09 μg Gallic acid equivalent/mg extract and 8.039 ± 0.53 μg Rutin equivalent/mg extract, respectively). Orlistat, metformin, and IG SAE successfully reduced the body weight, blood glucose level, lipid profile, oxidative stress and neurotransmitters levels leading to improved behavioral functions as well as histological alternation. Also, IG SAE halted inflammation, apoptosis, and endoplasmic reticulum stress, together with promoting autophagy, via modulation of PI3K/AKT/GSK-3β/CREB, PERK/CHOP/Bcl-2 and AMPK/SIRT-1/m-TOR pathways. Conclusion Metformin, orlistat, and IG SAE offer a promising multi-target therapy to mitigate HFHC diet-induced oxidative stress, addressing cognitive function. This involves diverse molecular mechanisms, particularly the modulation of inflammation, ER stress, and both PI3K/AKT/GSK-3β/CREB and AMPK/SIRT-1/m-TOR pathways. Furthermore, the higher dose of IG SAE demonstrated effects comparable to orlistat and metformin across most studied parameters.
研究领域:
民族药理学
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药理学
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神经科学
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代谢组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Di Wu,Jiebing Yang,Zhen Xing,Haobo Han,Tingting Wang,Aijun Zhang,Yan Yang,Quanshun Li
In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG 5k -Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment.
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产品关联
DOI
PubMed
高影响因子
CELL TRANSPLANTATION
·
2020
·
IF 3.341
Jing hui Bai,Jian Xu,Jian Zhao,Rui Zhang
Ganoderma lucidum is a popular traditional Chinese medicine used in China to improve health. Previous researches have revealed that the polysaccharide from G. lucidum could exert diversity activities, including immunomodulation, antioxidant, and antitumor effects. However, the effect of enzymatically hydrolyzed G. lucidum polysaccharide (EGLP) in colorectal cancer (CRC) progression remains unknown. The present research aimed to investigate the antitumor mechanism of EGLP in human colon cancer cells. For this purpose, the cytotoxic effects of EGLP were measured by the (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. The apoptosis was evoked upon EGLP treatment, which was assayed using flow cytometry. The results indicated that EGLP may induce apoptosis in human colon cancer cell (HCT-116) cells via the upregulation of BCL-2 associated X protein (Bax), phospho-extracellular regulated protein kinases (P-ERK), and cleaved caspase-3 expression and downregulation of B-cell lymphoma-2 (Bcl-2), phospho-serine/threonine kinase 1 (p-Akt1), and cyclo-oxygen-ase (COX-2) expression. The obtained findings indicated EGLP as a new therapeutic agent in fighting CRC.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
npj Science of Food
·
2025
·Vol. 9
·期 1
·1-12
·
IF 7.8
Zhang Hongyi,Ma Qiaoling,Wang Weichao,Wang Bin,Liu Jiawen,Wang Fu,Hu Yuan,Chen Lin,Liu Youping,Wang Qi,Chen Hongping
Oysters are recognized for flavor and health benefits, but their shells are regarded as waste, contributing to resource inefficiency. This study investigates the chemical composition and pharmacological activity of oyster shells, using a fraction partitioning approach to separate the oyster shells water extract (WE) into two fractions: WE of extra-membranous (WEE, <1000 kDa) and intra-membranous (WEI, >1000 kDa). Using UPLC-Q-Exactive MS, 231 components were identified such as organic acids, amino acids. ELISA analysis revealed that high-dose WEE significantly increased serum T3, T4, FT3, and FT4 levels while reducing TSH, and improved thyroid tissue lesions. Network pharmacology identified 291 drug-disease intersection targets enriched in the PI3K/AKT pathway. Furthermore, the RT-qPCR and WB results showed that high-dose WEE protected against propylthiouracil-induced goitre by inhibiting the PI3K/AKT/Bcl-2 pathway. This study evaluated the anti-goitre potential properties of WE and provided a theoretical basis for further development of oyster shells as a functional food source.
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PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 40
·期 11
·1526-1533
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IF 2.997
Yalei Yu,Youyou Zhang,Jie Zhang,Chuhuai Guan,Liang Liu,Liang Ren
Cantharidin is of high medicinal value but has strong toxicity. Nowadays, multiple research has focused on the mechanism of its antitumor activity while research on toxicological profiles associated with cantharidin poisoning is still limited. Its hepatotoxicity has attracted attention recently for the crucial role of the liver in detoxification. Here, we aim to find a potential mechanism for cantharidin-induced acute hepatotoxicity with a view to assisting subsequent research or clinical use or detoxification. Twenty-one male Sprague-Dawley rats were randomly divided into control, low-dose (1.34 mg/kg) and high-dose (2.67 mg/kg) cantharidin exposure groups. We used hematoxylin-eosin to observe pathological changes and used immunofluorescent staining, western blotting and real-time quantitative polymerase chain reaction to detect the expression of the markers. The main pathological changes in livers of cantharidin-treated rats were necrosis, inflammatory infiltration and hemorrhage. We found coexpression of tumor necrosis factor alpha (TNF-α), IkappaB kinase-alpha (IKK-α) and caspase3 by immunofluorescent staining in livers of cantharidin-treated rats. Compared with the control, the levels of TNF-α, IKK-α and caspase3 increased significantly in the experimental groups ( P < .05). The ratio of B-cell lymphoma-2 (Bcl-2)/Bax increased in the low-dose group but decreased in the high-dose group ( P < .05). Cantharidin exposure raised IKK-α mRNA and caspase3 mRNA levels ( P < .05). In conclusion, the participation of TNF-α, IKK-α, Bcl-2, Bax and caspase3 uncovered a novel mechanism underlying cantharidin-induced acute hepatotoxicity, and the mechanism needs to be studied further.
研究领域:
药理学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Express
·
2023
·Vol. 13
·期 3
·447-450
·
IF 0.7
Zhang Ying,Shen Huijun,Shi Wudan
Chronic myelocytic leukemia (CML) refers to a malignant proliferative disease of the bone marrow characterized by abnormalities of multipotent stem cells on the Philadelphia chromosome and accounts for approximately 20% of all leukemias. Imatinib is widely used in the treatment of CML
patients because of its unique mechanism of action and high specificity. In this study, imatinib-loaded hydrogels were prepared from the natural polysaccharide hyaluronic acid and carboxymethyl chitosan. SEM results showed that the hydrogels had a macroporous structure with interconnected
pores inside. CCK-8 results indicated that the hydrogels could significantly reduce the viability of leukocytes. In addition, the hydrogel increased the expression of BCL-2 with increasing dose and is promising to be used as a drug carrier material for leukemia treatment.
研究领域:
药学
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血液学
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生物材料学
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产品关联
DOI
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 33
·期 8
·085103
·
IF 3.874
Xiuli Zhang,Ruqing Gao,Huiyu Yan,Zijian Zhao,Jun Zhang,Weiming You
Bcl-2, an anti-apoptotic protein, is always overexpressed in tumor cells to suppress the pro-apoptotic function of Bax, thereby prolonging the life of the tumor. However, BH3 proteins could directly activate Bax via antagonizing Bcl-2 to induce apoptosis in response to the stimulation. Thus, mimicking BH3 proteins with a peptide is a potential strategy for anti-cancer therapy. Unfortunately, clinical translation of BH3-mimic peptide is hindered by its inefficacious cellular internalization and proteolysis resistance. Herein, we translated a BH3-mimic peptide into a peptide-auric spheroidal nanocluster (BH3-AuNp), in which polymeric BH3-Auric precursors [Au1+-S-BH3]n are in situ self-assembled on the surface of gold nanoparticles by a one-pot synthesis. Expectedly, this strategy could improve the anti-proteolytic ability and cytomembrane penetrability of the BH3 peptide. As a result, BH3-AuNp successfully induced the apoptosis of two cancer cell lines by an order of magnitude compared to BH3. This therapeutic and feasible peptide nano-engineering strategy will help peptides overcome the pharmaceutical obstacles, awaken its biological functions, and possibly revive the research about peptide-derived nanomedicine.
研究领域:
生物化学
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Liao Zixin,Zhong Rui,Li Wan jing,Wong Yee Shan,Liu Jiaxin,Venkatraman Subbu S.,Wang Hong,Cao Ye
Triple-negative breast cancer (TNBC) bone metastasis remains a significant clinical challenge owing to limited drug across the blood - bone marrow barrier as well as the chemotherapy resistance. Overexpression of the anti-apoptosis protein B-cell lymphoma-2 (Bcl-2) and activation of ATP-binding cassette transporter-mediated drug efflux pathway contribute substantially to paclitaxel (PTX) resistance, leading to poor therapeutic outcomes. Herein, we developed a biomimetic bone-targeted nanotherapeutic by integrating neutrophil “hitchhiking” technology with hyaluronic acid (HA)-modified lipid nanoparticles co-loaded with PTX and Bcl-2 small interfering RNA (siRNA) (BP-HLNP@NEs) for the therapy of TNBC bone metastasis. Leveraging neutrophil-mediated bone marrow homing and HA-CD44 receptor-mediated active targeting, BP-HLNP@NEs efficiently traversed the blood-bone marrow barrier, enhanced accumulation within metastatic bone lesions, and reduced off-target toxicity in the liver and spleen. Following cellular internalization, the co-delivered PTX and Bcl-2 siRNA synergistically suppressed tumor growth by silencing Bcl-2 expression, inhibiting the NF-κB/P-glycoprotein resistance pathway, restoring chemosensitivity, and activating caspase-mediated apoptosis. In orthotopic bone metastatic TNBC models, BP-HLNP@NEs markedly inhibited tumor progression, reduced secondary lung metastasis, preserved bone architecture, and elicited antitumor immune responses. Collectively, this biomimetic delivery platform overcomes both biological delivery barriers and chemoresistance, providing a promising therapeutic strategy for the treatment of TNBC bone metastasis. Graphical
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DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Xiao-Man Ji,Xin-Xin Dong,Jia-Peng Li,Guang-Jie Tai,Shu Qiu,Wei Wei,Ceaser Wankumbu Silumbwe,Davaadagva Damdinjav,Joseph Nicolao Otieno,Xiao-Xue Li,Ming Xu
Vascular aging is a major contributor to age-related cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) induced early arterial aging and excessive senescent cells (SCs) burden in vessels. Inhibiting cellular senescence or eliminating SCs could effectively improve aging-related CVDs. Fisetin, a flavonoid extracted from cotinus coggygria scop, has shown potential in alleviating aging by clearing SCs. This study investigated the unexplored mechanisms and efficacy of fisetin in alleviating T2DM-related aortic aging. The T2DM mouse model was induced using a high-fat diet and low-dose streptozotocin injection. Chronic fisetin treatment's protective effects against aortic aging were assessed via senescence-associated beta-galactosidase (SA-β-Gal) staining, histopathology, and vasomotor function. RNA-sequencing and western blotting identified relevant signaling pathways and protein expression. Fisetin's effects on SCs and senescence-associated secretory phenotype (SASP) factors were evaluated through cell viability, apoptosis, and co-culture assays. Docking simulations suggested fisetin as a potential Phosphoinositide 3-kinase (Pi3k) inhibitor. In vivo, chronic fisetin treatment reduced aortic SCs burden, alleviating T2DM-related and natural aortic aging. In vitro, fisetin selectively induced apoptosis of senescent endothelial cells via regulating the Pi3k-Protein Kinase B (Akt)-B-cell lymphoma (Bcl)-2/Bcl-xl pathway and suppressed SASP and its detrimental effects. Furthermore, fisetin combined with metformin therapy showed superior anti-aging effects on T2DM-related aortic aging compared to metformin monotherapy. In conclusion, chronic fisetin treatment alleviates T2DM-related aortic aging via clearing the SCs burden and abrogating the SASP factors. Fisetin combined with metformin therapy might be a potential therapeutic strategy for T2DM-related CVDs.
研究领域:
药理学
·
心血管疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Shiwei Zhou,Yingying Wang,Jun-Jie Zhu
B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) are often used to monitor the apoptosis of tumor cells and evaluate cancer drug effect. In this work, a novel sandwich-type dual-signal-marked electrochemical biosensor was fabricated for simultaneous detection of Bcl-2 and Bax proteins. Reduced graphene oxide (RGO) layers were used as substrate to immobilize Bcl-2 and Bax antibodies for further capturing target antigens. CdSeTe@CdS quantum dots (QDs) and Ag nanoclusters (NCs) with antibody modification and mesoporous silica amplification were used as signal probes, which were proportional to the amount of Bcl-2 and Bax antigens. Mesoporous SiO2 can provide a larger surface area, more effectively charged by ethylene imine polymer or poly(diallyldimethylammonium chloride) to adsorb more probes. The Bcl-2 and Bax proteins were determined indirectly by the detection of oxidation peak currents of Cd and Ag using anodic stripping voltammetry, showing a good linear relationship in the protein concentration range from 1 ng/mL to 250 ng/mL. The detection limit of trace protein level was ∼0.5 fmol. The biosensor was further introduced to investigate Bcl-2 and Bax expressions from nilotinib-treated chronic myeloid leukemia K562 cells. With the increase of drug dosage and incubation time, the up-regulation for Bax and down-regulation for Bcl-2 were observed, which indicated that the apoptosis level of K562 cells could be regulated by Bcl-2 family. The ratio of Bax/Bcl-2 was further calculated for evaluation of its drug effect and apoptosis level. The limited cell amount for detection reached less than 1 × 103 cells, much lower than traditional methods. Furthermore, completely independent detection step and stable acid solutions containing Ag+ and Cd2+ for long-time storage contribute to reducing the error from the sample differences and avoiding the potential errors from the photodegradation of fluorescent probes, enzymolysis of DNA, or inactivation of enzyme during an excess experimental period.
研究领域:
生物化学
·
生物技术
·
癌症研究
·
电化学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
·
2021
·
IF 2.9
Yonglu Li,Yaxuan Wang,Xin Yu,Ting Yu,Xiaodong Zheng,Qiang Chu
Lung cancer with high mortality is regarded as a challenging global problem with unsatisfied curative effects. Clinically, the chemotherapy drugs are often faced with side-effects and tumor resistance. Radix Tetrastigma (RT) is a traditional Chinese herb and now regarded as a kind of functional food. In this study, A549-bearing nude mice control was adopted to evaluate the anti-tumor capacity of RT. Results demonstrated that RT showed excellent anti-tumor ability with no side-effect on mice compared to chemotherapy drug (5-Fu).Further studies proved that RT down-regulated the proliferation-related proteins (PCNA, Ki67) and vascular endothelial growth factor (VEGF). Additionally, RT up-regulated the ratio of Bax/Bcl-2, which caused the over-expression of Caspase-9, leading to the activation of downstream protein caspase-3, eventually resulting in apoptosis of A549 in solid tumor. These results together suggest that RT inhibits the non-small cell lung cancer (NSCLC) via Bax/Bcl2/Caspase-9/Caspase-3 pathway. Furthermore, the anti-A549 abilities of the main flavonoid components from RT were compared, and kaempferol-3-O-rutinoside would play a role in RT’s outstanding anti-NSCLC ability.
研究领域:
肿瘤学
·
药理学
·
中药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Physical Chemistry C
·
2016
·
IF 4.509
Xiaojun Zhou,Liang Chen,Wei Nie,Weizhong Wang,Ming Qin,Xiumei Mo,Hongsheng Wang,Chuanglong He
The combination of chemotherapy and gene therapy could induce the enhanced therapeutic efficacy in the cancer therapy. To achieve this goal, a new mesoporous silica nanoparticles (MSNs)-based codelivery system was developed for targeted simultaneous delivery of doxorubicin (DOX) and Bcl-2 small interfering RNA (siRNA) into breast cancer cells. The multifunctional MSNs (MSNs-PPPFA) were prepared by modification of polyethylenimine–polylysine copolymers (PEI-PLL) via the disulfide bonds, to which a targeting ligand folate-linked poly(ethylene glycol) (FA-PEG) was conjugated. The multifunctional MSNs-PPPFA nanocarrier has the ability to encapsulate DOX into the mesoporous channels of MSNs, while simultaneously carrying siRNA via electrostatic interaction between cationic MSNs-PPPFA and anionic siRNA. The resulting MSNs-PPPFA nanoparticles were characterized with various techniques. The drug release results reveal that DOX released from DOX-loaded MSNs-PPPFA are both pH- and redox-responsive, and the results of cell viability and hemolysis assays show that the functional nanocarrier has excellent biocompatibility. Importantly, the folate-conjugated MSNs-PPPFA showed significantly enhanced intracellular uptake in the folate receptor overexpressed MDA-MB-231 breast cancer cells than nontargeted counterparts and thus results in more DOX and siRNA being codelivered into the cells. Furthermore, the delivery of Bcl-2 siRNA obviously downregulate the Bcl-2 protein expression, and thus targeted codelivery of DOX and Bcl-2 siRNA by DOX@MSNs-PPPFA/Bcl-2 siRNA in MDA-MB-231 cells could induce remarkable cell apoptosis as indicated by the results of cell viability and cell apoptosis assays. These results indicate that the constructed DOX@MSNs-PPPFA/Bcl-2 siRNA codelivery system is promising for targeted treatment of breast cancer.
研究领域:
纳米技术
·
药学
·
癌症研究
·
分子生物学
✓ 已验证
DOI
高影响因子
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