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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2024 ·Vol. 28 ·期 16 ·e70032 · IF 4.3

Lycorine (Lycoris radiata)—a unique natural medicine on breast cancer

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.

CAS / MDL: 476-28-8
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 中药学
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SAUDI PHARMACEUTICAL JOURNAL · 2017 · IF 2.302

Study on apoptosis effect of human breast cancer cell MCF-7 induced by lycorine hydrochloride via death receptor pathway

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.

CAS / MDL: 2188-68-3
研究领域: 肿瘤学 · 分子生物学 · 药理学
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PLANTA MEDICA · 2024 · IF 2.1

Anti-inflammatory Principles of the Plant Family Amaryllidaceae

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.

CAS / MDL: 476-28-8
研究领域: 药理学 · 植物学 · 药物化学
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JOURNAL OF SEPARATION SCIENCE · 2014 ·Vol. 37 ·期 20 ·3007-3012 · IF 2.594

Simultaneous determination of galanthamine and lycorine in Lycoris radiata by a capillary electrophoresis with an electrochemiluminescence method

Yanchao Wang,Guimei Zhu,Xia Li,Zaibin Hao

A novel capillary electrophoresis with electrochemiluminescence determination method was developed for the determination of two alkaloids based on the electrochemiluminescence signal enhancement effect of the tertiary amine group on tris(2,2′-bipyridyl)ruthenium(II). A linear relationship between the electrochemiluminescence peak area and concentrations of galanthamine and lycorine in the range of 0.07 ∼ 17 μg/mL and 0.07 ∼ 18 μg/mL was obtained and the detection limit was 0.008 and 0.002 μg/mL, respectively. The method is selective, simple, and convenient. It had been successfully applied to the analysis of galanthamine and lycorine in Lycoris radiata samples purchased from a local market.

研究领域: 分析化学 · 药学
✓ 已验证 DOI PubMed 高影响因子
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ACTA PHYSIOLOGIAE PLANTARUM · 2021 ·Vol. 43 ·期 6 ·1-12 · IF 2.354

Molecular cloning and functional characterization of tyrosine decarboxylases from galanthamine-producing Lycoris radiata

Hu Jiawei,Li Wei,Liu Zhan,Zhang Guolin,Luo Yinggang

Tyrosine decarboxylase (TyDC), a pyridoxal-5′-phosphate (PLP)-dependent aromatic amino acid decarboxylase, catalyzes the decarboxylation of l -tyrosine (Tyr) to generate the important biogenic tyramine. This amine was reported to be a biosynthetic precursor of the Amaryllidaceae alkaloids, a group of pharmaceutically important natural products. Herein, we cloned two TyDC-encoding genes from Lycoris radiata , a galanthamine (GAL, a characteristic Amaryllidaceae alkaloid)-producing and medicinally and ornamentally important perennial herbaceous plant. Heterologous expression of LrTyDC s in Escherichia coli and the following purification gave recombinant LrTyDCs to homogeneity for enzymatic reactions. Tyramine was detected and validated by HPLC–DAD and HRESIMS analyses of the LrTyDC-catalyzed reaction mixture, which revealed the catalytic decarboxylation activity of LrTyDCs. The transcriptional LrTyDC s were detected in all tissues of L. radiata by quantitative real-time PCR analyses. The present works demonstrated that TyDC-catalyzed decarboxylation reaction is a key step to generate the non-catechol biosynthetic precursor of the Amaryllidaceae alkaloids.

研究领域: 植物生化 · 药用植物学 · 分子生物学
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MOLECULES · 2012 ·Vol. 17 ·期 9 ·10108-10118 · IF 2.386

Ameliorative Effects of Curculigoside from Curculigo orchioides Gaertn on Learning and Memory in Aged Rats

Bao-Yuan Hou

This study was designed to evaluate the ameliorating effects of curculigoside fromCurculigo orchioidesGaertn on learning and memory in aged rats. In the present study, the ameliorating effects of curculigoside were determined through animal behaviour studies (including step-down test and Y-maze test), and the possible mechanisms were explored by evaluation of the activity of acetylcholinesterase (AchE) and determination of the expression of BACE1. Oral adminstration of the curculigoside (20, 40 mg/kg/day) for 14 days can significantly improve the latency and number of errors in aged rats based on the behaviour study results. In addition, the activity of AchE can be decreased by treatment of the curculigoside (10, 20, 40 mg/kg/day). Moreover, the expression of BACE1 can be down-regulated in the hippocampus of aged rats treated with curculigoside. The results of our present work have indicated that curculigoside can improve cognitive function in aged animals, possibly by decreasing the activity of AchE in the cerebra and inhibiting the expression of BACE1 in the hippocampus. In conclusion, our results suggested that curculigoside can be possible developed as a new drug for the treatment of Alzheimer’s disease in the future.Keywords:curculigoside;Curculigo orchioides;Alzheimer’s disease;behaviour study;ameliorative effects on learning and memory

CAS / MDL: 51-34-3 142057-80-5
研究领域: 药理学 · 神经科学
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INDUSTRIAL CROPS AND PRODUCTS · 2018 · IF 3.849

Aphicidal activities of Amaryllidaceae alkaloids from bulbs of Lycoris radiata against Aphis citricola

He Yan,Na Xie,Chenquan Zhong,Anqi Su,Xiaoli Hui,Xin Zhang,Zhao Jin,Zhipeng Li,Juntao Feng,Jun He

Aphids are one of the most destructive and economically important pests of plants on earth, causing severe financial losses worldwide. The extensive and unscientific use of insecticides has resulted in a universal zooming insecticide resistance among aphids across regions and substantial detrimental influences on the environment. This study investigates the insecticidal activity of alkaloids from L. radiata against A. citricola . The crude extract of Lycoris radiate showed a remarkable aphicidal activity against A. citricola . Ten known amaryllidaceous alkaloids were obtained according to the bioassay-guided isolation. The structures of these known alkaloids were identified as amabiline ( 1 ), deoxydihydrotazettine ( 2 ), deoxytazettine ( 3 ), 3-epimacronine ( 4 ), galanthamine ( 5 ), 11-hydroxygalanthamine ( 6 ), N -allylnorgalanthamine ( 7 ), 11 β -hydroxygalanthamine ( 8 ), lycorine ( 9 ) and colchicine ( 10 ). The results of aphicidal bioassay against A. citricola showed that compounds 1 - 9 exhibited considerable aphicidal activity with LD 50 values of 67.44, 76.33, 78.30, 96.70, 17.47, 32.60, 4.92, 20.33, 70.41 ng/aphid. N -Allylnorgalanthamine ( 7 ) possessed the highest aphicial activity, which was comparable with the commercial pesticide methomyl (2.91 ng/aphid). The results of in vivo AChE assay revealed that N -allylnorgalanthamine showed an obvious inhibitory effect on AChE in A. citricola in a time- and dose-dependent manner. The in vitro inhibition of AChE activity by N -allylnorgalanthamine was remarkable with an IC 50 value of 2.1 × 10 −8 M, which was 10 4 times stronger than the positive control methomyl with an IC 50 value of 4.2 × 10 –4 M. Meanwhile, N -allylnorgalanthamine can lead to an increase of the activities of SOD and CAT. The present work comprises the first report on insecticidal action of Amaryllidaceae alkaloids. N -Allylnorgalanthamine displayed a significant inhibition on AChE in Aphis citricola both in vivo and vitro . The insecticidal L. radiata extracts can be possibly used for controlling pests and isolated compounds, designing for new pesticides, can be the promising temples.

CAS / MDL: 16752-77-5
研究领域: 植物化学 · 昆虫学 · 农药科学
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CELL BIOCHEMISTRY AND BIOPHYSICS · 2024 · IF 1.8

Potential Action Mechanism of Erianin in Relieving MNNG-triggered Chronic Atrophic Gastritis

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 · 胃肠病学 · 药理学 · 细胞生物学
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2011 · IF 2.325

Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge

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.

CAS / MDL: 476-28-8
研究领域: 药理学 · 免疫学 · 分子生物学
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY · 2023 ·Vol. 396 ·期 6 ·1247-1255 · IF 3.6

Induction of apoptosis in glioma cells by lycorine via reactive oxygen species generation and regulation of NF-κB pathways

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.

CAS / MDL: 85622-93-1 476-28-8
研究领域: 肿瘤学 · 药理学 · 细胞生物学 · 神经科学
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3 Biotech · 2020 ·Vol. 10 ·期 8 ·1-10 · IF 1.798

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway

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 · 免疫学 · 肺病学 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant

Wei Li,Yun Yang,Chong Qiao,Guolin Zhang,Yinggang Luo

Galanthamine (GAL), the well-known Amaryllidaceae alkaloid, is a clinically used drug for the treatment of Alzheimer's disease. L-Phenylalanine (Phe) and trans -cinnamic acid (CA) were enzymatically transformed into the catechol portion of GAL. Herein, a Phe ammonia-lyase-encoding gene LrPAL3 and a cinnamate 4-hydroxylase-encoding gene LrC4H were cloned from Lycoris radiata , a GAL-producing plant. LrPAL3 was overexpressed in Escherichia coli and purified to homogeneity. LrPAL3 catalyzes the forward deamination conversion of L-Phe into trans -CA. The 3-chloro- and 4-fluoro-L-Phe were deaminated to generate the corresponding 3-chloro- and 4-fluoro- trans -CA by LrPAL3. LrPAL3-catalyzed reverse hydroamination was confirmed by the conversion of trans -CA into L-Phe with exceptional regio- and stereo-selectivity. LrC4H was overexpressed in E. coli with tCamCPR , a cytochrome P450 reductase-encoding gene. LrC4H catalyzes the regioselective para -hydroxylation on trans -CA to form p -coumaric acid. The transcriptional levels of both LrPAL3 and LrC4H were positively associated with the GAL contents within the leaves and flowers of L. radiata , which suggested that their expression and function are co-regulated and involved in the biosynthesis of GAL. The present investigations on the biosynthetic genes of GAL will promote the development of synthetic biology platforms for this kind of important drug via metabolic engineering.

CAS / MDL: 63-91-2
研究领域: 植物生物化学 · 分子生物学 · 药理学 · 合成生物学
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