MOLECULES
·
2019
·Vol. 24
·期 21
·3939
·
IF 3.06
Qin Shu,Jianan Wu,Qihe Chen
As a novel natural compound delivery system, liposomes are capable of incorporating lipophilic bioactive compounds with enhanced compound solubility, stability and bioavailability, and have been successfully translated into real-time clinical applications. To construct the soy phosphatidylcholine (SPC)–cholesterol (Chol) liposome system, the optimal formulation was investigated as 3:1 of SPC to Chol, 10% mannosylerythritol lipid-A (MEL-A) and 1% betulinic acid. Results show that liposomes with or without betulinic acid or MEL-A are able to inhibit the proliferation of HepG2 cells with a dose-effect relation remarkably. In addition, the modification of MEL-A in liposomes can significantly promote cell apoptosis and strengthen the destruction of mitochondrial membrane potential in HepG2 cells. Liposomes containing MEL-A and betulinic acid have exhibited excellent anticancer activity, which provide factual basis for the development of MEL-A in the anti-cancer applications. These results provide a design thought to develop delivery liposome systems carrying betulinic acid with enhanced functional and pharmaceutical attributes.Keywords:Liposomes;betulinic acid (BA);mannosylerythritol lipid-A (MEL-A);HepG2;anticancer activity
研究领域:
药剂学
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肿瘤学
·
药物递送系统
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Chen Haiyan,Li Rongji,Zhao Feng,Luan Li,Han Tiantian,Li Zhong
Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 μg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.
研究领域:
衰老研究
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分子生物学
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药理学
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DOI
PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2024
·
IF 6.1
Bo Wang,Xiaoshuang Li,Shuyi Han,Haixin Yang,Yaguang Zhan,Guizhi Fan
Nitric oxide (NO) and S-nitrosothiol (SNO) are signal molecules and the products of nitrogen metabolism. Nitrate (NO 3 − ) is the main nitrogen source, and nitrate transporters (NRTs) are responsible for NO 3 − absorption or transport. However, the interactive effect between NO 3 − /NRT and NO/SNO in tree plants remains ambiguous. In the present study, 25 mmol L −1 NO 3 − and 1 mmol L −1 NO donor sodium nitroprusside (SNP) treatment that was conducted for 24 h enhanced NO/SNO and NO 3 − metabolism, whereas 2.5 mmol L −1 NO 3 − and 80 μmol L −1 N6022 (a compound that increases SNO content) treatment reduced them in seedling leaves of Fraxinus mandshurica and Betula platyphylla . Among the nine NRT family members examined, the gene expression level of NRT2.1 had a greater response to NO/SNO and NO 3 − treatment in the seedling leaves of F. mandshurica and B. platyphylla . Meanwhile, FmNRT2.1 mediated NO and SNO production in seedling leaves of F. mandshurica using Agrobacterium -mediated transient transformation. These findings shed light on the reciprocal regulation between NO 3 − and NO/SNO in seedlings of F. mandshurica and B. platyphylla , and NRT2.1 may act as a key regulatory hub.
研究领域:
植物生理学
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分子生物学
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植物生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Ruoning Wang,Mengmeng Yang,Guoyuan Li,Xin Wang,Zhenhai Zhang,Hongzhi Qiao,Jun Chen,Zhipeng Chen,Xiaobin Cui,Junsong Li
Paclitaxel-betulinic acid hybrid nanosuspensions (PTX-BA-NP) with increased anti-breast cancer activity were developed. The resultant nanosuspensions (NP) had a mean particle size of 282.54 ± 5.4 nm, a polydispersity index of approximately 0.242 ± 0.02, a zeta potential of -19.7 ± 0.19 mV and a redispersibility index of 103.3 ± 0.01%. The cumulative dissolution percentage of PTX coarse powder and PTX-BA-NP dried powder at 60 min were 15.4% and 90.8%, respectively. MCF-7 cell-based testing showed that treatment with PTX-BA-NP led to more PTX-BA-NP accumulation in the cytoplasm of breast cancer cells, less cell cycle arrest in the G2-M phase, more cell cycle arrest in the G0-G1 phase, more apoptosis-induced cell death and stronger inhibition of cell migration than paclitaxel nanosuspensions (PTX-NP). Biodistribution studies showed that tumor accumulation levels at 12 h in the PTX-BA-NP group were approximately 2.67- and 2.33-fold higher than the levels in the Taxol® and PTX-NP groups, respectively. In vivo antitumor efficacy demonstrated that PTX-BA-NP exerted the strongest tumor inhibition among the four groups, with a tumor inhibition rate of 47.79 ± 2.28%, followed by PTX-NP (35.05 ± 5.55%), Taxol® (22.67 ± 6.01%) and betulinic acid nanosuspension (BA NP) (14.38 ± 6.02%). These findings indicate that PTX-BA-NP holds great promise for breast cancer therapy.
研究领域:
药学
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2024
·Vol. 25
·期 1
·1-16
·
IF 4.7
Wang Han,Du Xiaohui,Liu Wenwen,Zhang Congcong,Li Ying,Hou Jingwen,Yu Yi,Li Guiru,Wang Qi
BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs.MethodsWe established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment.ResultsBetulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts.ConclusionsBA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers.Graphical abstract
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Sun Chao-Yue,Cao Di,Ren Qian-Nan,Zhang Shan-Shan,Zhou Ning-Ning,Mai Shi-Juan,Feng Bing,Wang Hui-Yun
Aberrant activation of the Ras–ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non–small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Mitogen-activated protein kinases, and especially ERK that facilitates cancer cell survival, are also activated by BA treatment. As such, in the presence of ERK inhibitors (ERKi), lung cancer cells are much more sensitive to BA. However, the dual treatment of BA and ERKi results in increased protective autophagy and AKT phosphorylation. Accordingly, inhibition of AKT has a highly synergistic anticancer effect with co-treatment of BA and ERKi. Notably, autophagy inhibition by hydroxychloroquine (HCQ) increases the response of lung cancer cells to BA in combination with ERKi. In vivo, the three-drug combination (BA, ERKi, and HCQ), resulted in superior therapeutic efficacy than single or dual treatments in the xenograft mouse model. Thus, our study provides a combined therapy strategy that is a highly effective treatment for patients with NSCLC.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 6
·1-12
·
IF 2.4
Boyu Tan,Xiaoxu Lan,Yifan Zhang,Pai Liu,Qiyao Jin,Zhiqiang Wang,Zhidong Liang,Wei Song,Ye Xuan,Yunxiao Sun,Youjie Li
The present study aimed to investigate the effect and mechanism of Pulsatilla compounds on lung adenocarcinoma. The representative drug chosen was the compound 23‑HBA. GeneCards, Swiss target prediction, DisGeNET and TCMSP were used to screen out related genes, and MTT and flow cytometry assays were used to verify the inhibitory effect of Pulsatilla compounds on the proliferation of lung adenocarcinoma cells. Subsequently, the optimal target, peroxisome proliferator‑activated receptor (PPAR)‑γ, was selected using bioinformatics analysis, and its properties of low expression in lung adenocarcinoma cells and its role as a tumor suppressor gene were verified by western blot assay. The pathways related to immunity and inflammation, vascular function, cell proliferation, differentiation, development and apoptosis with the highest degree of enrichment and the mechanisms were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Finally, the clinical prognosis in terms of the survival rate of patients in whom the drug is acting on the target was analyzed using the GEPIA database. The results indicated that Pulsatilla compounds can inhibit the proliferation of lung adenocarcinoma cells by blocking the cell cycle at the G1 phase. Subsequently, the related PPAR‑γ gene was verified as a tumor suppressor gene. Further analysis demonstrated that this finding was related to the PPAR signaling pathway and mitochondrial reactive oxygen species (ROS) production. Finally, the clinical prognosis was found to be improved, as the survival rate of patients was increased. In conclusion, Pulsatilla compounds were indicated to inhibit the viability and proliferation of lung adenocarcinoma H1299 cells, and the mechanism of action was related to PPAR‑γ, the PPAR signaling pathway and mitochondrial ROS. The present study provides novel insight to further explore the treatment of lung adenocarcinoma.
研究领域:
肿瘤学
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药理学
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生物信息学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2024
·
IF 3.3
Yanrong Zhu,Lichen Yao,Yilei Guo,Jing Zhang,Yufeng Xia,Zhifeng Wei,Yue Dai
Tripterygium wilfordii (TW) preparations have been utilized in China for treating rheumatoid arthritis and autoimmune diseases. However, their clinical use is limited due to reproductive toxicity, notably premature ovarian failure (POF). Our study aimed to investigate the effect and mechanism of bergenin in attenuating POF induced by triptolide in mice. POF was induced in female ICR mice via oral triptolide administration (50 μg/kg) for 60 days. Mice received bergenin (25, 50, 100 mg/kg, i.g.) or estradiol valerate (EV) (0.1 mg/kg, i.g.) daily, 1 h before triptolide treatment. In vitro , ovarian granulosa cells (OGCs) were exposed to triptolide (100 nM) and bergenin (1, 3, 10 μM). Antioxidant enzyme activity, protein expression, apoptosis rate, and reactive oxygen species (ROS) levels were assessed. The results showed that triptolide-treated mice exhibited evident atrophy, along with an increase in atretic follicles. Bergenin (50, 100 mg/kg) and EV (0.1 mg/kg), orally administered, exerted significant anti-POF effect. Bergenin and EV also decreased apoptosis in mouse ovaries. In vitro , bergenin (1, 3, 10 μM) attenuated triptolide-induced OGCs apoptosis by reducing levels of apoptosis-related proteins. Additionally, bergenin reduced oxidative stress through downregulation of antioxidant enzymes activity and overall ROS levels. Moreover, the combined use with Sh-Nrf2 resulted in a reduced protection of bergenin against triptolide-induced apoptosis of OGCs. Together, bergenin counteracts triptolide-caused POF in mice by inhibiting Nrf2-mediated oxidative stress and preventing OGC apoptosis. Combining bergenin with TW preparations may effectively reduce the risk of POF.
研究领域:
药理学
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生殖生物学
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肿瘤学
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毒理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Zi Chao Wu,Xin Yu Liu,Jia Yan Liu,Jing Shu Piao,Ming Guan Piao
Aim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver.Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro.Results: BA-GC-NPs with diameters Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.
研究领域:
药学
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生物医学工程
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肝病学
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产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2021
·Vol. 112
·期 8
·3218-3232
·
IF 6.716
Dan-Hua He,Yu-Fei Chen,Yi-Le Zhou,Shi-Bing Zhang,Ming Hong,Xianjun Yu,Su-Fen Wei,Xiang-Zhen Fan,Si-Yi Li,Qi Wang,Yongzhi Lu,Yong-Qiang Liu
Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non–small cell lung cancer (NSCLC) through targeting Skp2-SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H-bonds with residue Lys145, decreases its stability by disrupting Skp1-Skp2 interactions, thereby inhibiting the Skp2-SCF E3 ligase and promoting the accumulation of its substrates; that is, E-cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2-SCF E3 ligase and upregulating p27 and E-cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2022
·
IF 3.784
Xiaomei Wu,Zhumei Wei,Hui Feng,Hongli Chen,Jiaxiu Xie,Yupeng Huang,Mengyao Wang,Chanjuan Yao,Jianchun Huang
Betulinic acid (BA) is a natural pentacyclic triterpenoid with broad-spectrum anticancer activity, which has great development potential as an anti-cancer drug. In this study, a novel hyaluronic acid (HA)-modified BA liposome (BA-L) was developed for use in targeted liver cancer therapy. The size, polymer dispersity index (PDI), zeta potential , and entrapment efficiency were measured. Cell viability, cell migration and clonogenicity, cellular uptake, immunohistochemistry of CD44, and protein expression of ROCK1/IP3/RAS were also investigated. BA, BA-L, and HA-BA-L had no inhibitory effect on the activity of LO2 normal hepatocytes, but they inhibited the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner, with HA-BA-L exhibiting the most prominent inhibitory effect. Compared with the BA-L group, the expression of CD44 in HepG2 cells in the HA-BA-L group was decreased. The results of WB showed that BA, BA-L, and HA-BA-L downregulated the expression of ROCK1, IP3, and RAS in HepG2 cells, and the expression level in the HA-BA-L group was significantly decreased. The easily prepared HA-BA-L was demonstrated to be an excellent CD44-mediated intracellular delivery system capable of targeting effects. Further mechanistic research revealed that the inhibition of HA-BA-L on HepG2 cells may be mediated by blocking the ROCK1/IP3/RAS signaling pathways.
研究领域:
药理学
·
肿瘤学
·
生物技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Water Supply
·
2022
·Vol. 22
·期 8
·6603-6614
·
IF 1.768
Zhang Fengrong,Zhang Binghan,Han Dandan,Fang Shaokang,Wu Lishun,Hou Wanguo
Using Al(OH) 3 and Mg(OH) 2 as raw materials, MgAl layered double hydroxides (LDHs) modified from birch leaves were prepared by the ball-milling–hydrothermal method, denoted as LDHs/BL, and used for the treatment of wastewater containing Cu(II). The morphology, crystal shape, and specific surface area of the samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and BET-specific surface area analyzer. The results showed that the prepared LDHs/BL composites had good crystal shape, large specific surface area, and suitable pore structure. Langmuir and Freundlich adsorption isotherm models were used to analyze the adsorption. The results showed that the adsorption conforms to the Freundlich adsorption isotherm model. Under the same adsorption conditions, the adsorption capacity of the LDHs/BL complex was higher than that of LDH, the removal efficiency of the former was 92%, and that of the latter was 68%. The adsorption mechanism includes metal precipitation and isomorphic replacement. More importantly, this study provides a green method to prepare LDHs. LDHs/BL composites are expected to be used as a new kind of environmental adsorbent for wastewater treatment. This work provides a new idea for the utilization of agricultural and forestry wastes. Nanocomposites of LDHs/BL were fabricated. The LDHs/BL nanocomposites exhibit enhanced sorption capacities for Cu(II). The nanocomposites are potential sorbents for wastewater treatment. The synthesis of LDHs/BL nanocomposites provides a win–win strategy.
研究领域:
环境科学
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材料科学
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化学工程
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纳米技术
·
废弃物管理
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）