SAUDI PHARMACEUTICAL JOURNAL
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2017
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IF 2.302
Yubin Ji,Miao Yu,Zheng Qi,Di Cui,Guosong Xin,Bing Wang,Weiling Jia,Lin Chang
As research was conducted on the early apoptosis of human breast cancer cell MCF-7 caused by lycorine hydrochloride and the expression of the related apoptosis proteins. The early-period apoptosis rate of human breast cancer cell MCF-7 was tested with the AnnexinV/PI double staining and flow cytometry. The Western Blotting method was also used to detect the protein expression conditions of Fas, FasL, Caspase-8 and Bid. The results showed that the higher the dose, the higher the rate of apoptosis and that the rate of apoptosis was dependent on the dose; the relative protein activity of Fas, FasL, Caspase-8 and bid gradually rose with the increase of lycorine dosage and the activities revealed certain dose-independence. Results showed that lycorine hydrochloride could induce the apoptosis of human breast cancer cell MCF-7 through the death receptor pathway.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2011
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IF 2.325
Jingjing Kang,Yushun Zhang,Xiang Cao,Jie Fan,Guilan Li,Qi Wang,Ying Diao,Zhihui Zhao,Lan Luo,Zhimin Yin
As a natural alkaloid extracted from Amaryllidaceae , lycorine shows various biological effects on tumor cells. Here we show that lycorine dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also inhibited NO, PGE 2 , TNF-α and IL-6 release from LPS-treated RAW264.7 cells. RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. Moreover, lycorine decreased LPS-induced mortality in mice. Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed significantly by lycorine. In addition, lycorine did not interfere with the phosphorylation of ERK1/2, JNK1/2 and NF-κB pathways. In conclusion, lycorine inhibits LPS-induced production of pro-inflammatory mediators and increases the survival rate of mice after LPS challenge, suggesting that lycorine could play an anti-inflammatory role in response to LPS.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
·Vol. 396
·期 6
·1247-1255
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IF 3.6
Su Jie,Yin Wei,Huo Mengmeng,Yao Qing,Ding Liqiong
Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC 50 ) values of lycorine on C6 glioma cells at 48 h was 2.85 μM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.
研究领域:
肿瘤学
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药理学
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细胞生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2024
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IF 1.8
Jiang Qianqian,Fan Guoxia,Wu Kaiwei
Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N’-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.
研究领域:
肿瘤学
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胃肠病学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
3 Biotech
·
2020
·Vol. 10
·期 8
·1-10
·
IF 1.798
Ge Xin,Meng Xianglin,Fei Dongsheng,Kang Kai,Wang Qiubo,Zhao Mingyan
Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.
研究领域:
药理学
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免疫学
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肺病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
·Vol. 28
·期 16
·e70032
·
IF 4.3
Qinbing Xue,Bing Wang,Jie Feng,Chaoyu Li,Miao Yu,Yan Zhao,Zheng Qi
Breast cancer (BC) is one of the most common types of cancer among women worldwide. Lycorine ( Lycoris radiata ), a small molecule derived from the traditional Chinese herb Amaryllidaceae plants, has appeared potential effect on inhibiting the growth of cancer cells and inducing apoptosis in various types of cancer with minor side effects. To discuss the therapeutic effects and molecular mechanisms of lycorine on BC established by lycorine-treated S180 tumour-bearing mice in vivo. Furthermore, both the mitotic and microtubule assembly dynamics genes were performed by qPCR assays, and the protein expression associated with mitotic arrest was investigated by western blot. Lycorine was demonstrated to reduce sarcoma growth of S180 tumour-bearing mice and inhibit the proliferation of MCF-7 cells in concentration-dependent manner. Moreover, lycorine induced M phase cell cycle arrest via interfering with the mitotic apparatus regulated the expression of 20 genes and 15 proteins in cell cycle progression. Furthermore, this study confirmed that the potential effect of lycorine on BC might be mediated by cell cycle arrest in M phase for the first time. These results would be the consequence of exploitation of lycorine as a potential drug for BC therapy, however further preclinical and clinical studies are still needed.
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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中药学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Pingping Tuo,Risheng Zhao,Ning Li,Shuang Yan,Gege Yang,Chunmei Wang,Jinghui Sun,Haiming Sun,Mengyang Wang
Background Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. Methods Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. Results LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. Conclusion Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.
研究领域:
心脏病学
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药理学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Autophagy
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2020
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IF 9.77
Zu-Guo Zheng,Si-Tong Zhu,Hui-Min Cheng,Xin Zhang,Gang Cheng,Pyone Myat Thu,Supeng Perry Wang,Hui-Jun Li,Ming Ding,Lei Qiang,Xiao-Wei Chen,Qing Zhong,Ping Li,Xiaojun Xu
SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases.Abbreviation: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1
研究领域:
药理学
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代谢
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
PLANTA MEDICA
·
2024
·
IF 2.1
Jerald J. Nair,Johannes van Staden
There is considerable interest in the utilisation of plants against inflammation. Over 50 species of the plant family Amaryllidaceae are known for such usage in traditional medicine. This review was undertaken to identify the chemical principles responsible for these anti-inflammatory effects. It describes the findings from in vitro, in vivo and in silico studies, as well as the probes made on the mechanisms of action. The literature search returned over 600 hits, of which around 130 were chosen for their relevance to the text. Over 140 compounds have thus far been screened for anti-inflammatory effects. These were mostly isoquinoline alkaloids but also included other classes of secondary metabolites such as chromones, flavonoids and triterpenoids. In vitro studies were carried out in mononuclear cells such as lymphocytes, monocytes, neutrophils and macrophages, against which no serious side effects were observed. The constituents were also effective against inflammation induced by physical and chemical stimuli in a variety of murine test subjects. Chief among the compounds were the isoquinoline alkaloids lycorine and narciclasine, which displayed potent effects against pain, swelling, asthma and arthritis, amongst others. From a mechanistic perspective, several of the compounds were shown to mediate in inflammatory pathways, notably via the modulation of both pro-inflammatory (such as NF-κB, TNF-α and IL-1) and anti-inflammatory (such as IL-10 and TGF-β) factors. Useful insights also emerged from active-site docking studies of some of the compounds. The Amaryllidaceae affords a rich and diverse platform for the discovery of potential anti-inflammatory drugs.
研究领域:
药理学
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植物学
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药物化学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2023
·
IF 7.4
Huadong Zhao,Ying Chen,Lu Qian,Luyang Du,Xue Wu,Ye Tian,Chao Deng,Shuai Liu,Wenwen Yang,Chenxi Lu,Yan Zhang,Jun Ren,Yang Yang
Cardiac dysfunction is a common complication in patients with sepsis triggering high morbidity and mortality. Lycorine (LYC), the main effective monomer component extracted from Lycoris bulbs, possesses antiviral, anti-inflammatory, analgesic , liver protection properties. In this study, the effect of LYC pre- and post-treatment as well as the underlying mechanism were evaluated in the cecal ligation and puncture (CLP) model of Balb/c mice. The survival rate, anal temperature, sepsis score, blood biochemical/routine indicators, cardiac function, sepsis-related pathophysiological processes, and AMPK signaling in septic mice were observed by echocardiography , histological staining, western blot , qPCR, and etc. LYC pretreatment attenuated myocardial injury in septic mice by improving survival rate, sepsis score, blood biochemical/routine indicators, cardiac function and structure, inhibiting inflammation and oxidative stress , improving mitochondrial function, modulating endoplasmic reticulum stress , and activating AMPK pathway. In particular, AMPK deficiency and AMPK inhibitor (Compound C) partially reversed the protective effects of LYC in septic mice. In addition, LYC posttreatment also has slight protective phenotypes on septic myocardial injury, but the effect is not as ideal as pretreatment. Taken together, these findings suggest that LYC may be a potential drug for the treatment of sepsis.
研究领域:
药理学
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免疫学
·
心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Ji Wu,Yang Fu,Ying-xing Wu,Zu-xiang Wu,Zhen-hua Wang,Ping Li
Alleviating cardiac dysfunction improves the prognosis of heart failure patients. Lycorine is an alkaloid with several beneficial biological properties. Here, we used mice to evaluate the effect of lycorine on cardiac dysfunction elicited by isoproterenol. Mice were divided into four groups: control, lycorine, isoproterenol, and isoproterenol + lycorine. Mice in the combined group were treated daily with 10 mg/kg isoproterenol intraperitoneally for 2 weeks and 5 mg/kg lycorine was given simultaneously intraperitoneally for 4 weeks. Cardiac structure and function were assessed by echocardiography, hematoxylin and eosin staining, and Masson’s trichrome staining. Isoproterenol-induced cardiac dysfunction and histopathological injury that was significantly improved by treatment with lycorine. Western blotting and the quantitative real-time polymerase chain reaction were used to explore the molecular mechanisms of these effects. Levels of the inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, were increased by treatment with isoproterenol; these increases were significantly reduced by lycorine, with involvement of the NF-κB signaling pathway. The fibrotic factors, collagen I and collagen III, were increased by isoproterenol and decreased by treatment with lycorine through inhibiting activation of the Smad signaling pathway. In addition, lycorine alleviated oxidative stress as evidenced by a reduction in total reactive oxygen species in the isoproterenol + lycorine group compared to the isoproterenol group. Lycorine exerted an anti-apoptotic effect as evidenced by upregulating Bcl-2 and downregulating Bax. Overall, our findings demonstrate that lycorine protects against cardiac dysfunction induced by isoproterenol by inhibiting inflammation, fibrosis, oxidative stress, and apoptosis.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Qiong Liu,Aizhen Zhao,Xiaopeng Wu,Xin Zhang,Xiaoru Li,Wenwen Yang,Wangrui Lei,Hui Liu,Huadong Zhao,Shuai Jiang,Yang Yang,Mingzhi Shen
Background Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms. Methods In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure. Purpose This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice. Results Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury. Conclusion In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.
研究领域:
心脏病学
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药理学
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分子生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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