查找使用阿拉丁产品的科研文献

The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives

En-bo Cai,Li-min Yang,Cai-xia Jia,Wei-yuan Zhang,Yan Zhao,Wei Li,Xing-zhuo Song,Man-ling Zheng

The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

Electrochemical behavior of arctigenin at a novel voltammetric sensor based on Iodide/SWCNTs composite film modified electrode and its sensitive determination

Wenjing Wang,Lu Wang,Lina Zou,Gaiping Li,Baoxian Ye

Arctigenin was determinated by an electrochemical method for the first time based on a novel voltammetric sensor, which was prepared by simple dipping-drying of SWCNTs on glassy carbon electrode (GCE) initially and then electrochemical deposition of Iodide. The resulting Iodide/SWCNTs/GCE displayed a significant voltammetric response to arctigenin due to the electrocatalytic ability of Iodide for arctigenin and a large specific surface area, excellent electric conductivity of SWCNTs. Meanwhile, the redox mechanism of arctigenin on Iodide/SWCNTs/GCE was also studied. The wide linear range of 3   ×   10 −   8   mol   L −   1 to 5   ×   10 −   6   mol   L −   1 and low detection limit of 1   ×   10 −   8   mol   L −   1 for the determination of arctigenin were achieved together with high sensitivity, selectivity, good stability. To examine the practical analytical utility of the proposed electrode, the real sample Fructus Arctii was examined and the result was found satisfactory.

Arctigenin protects mice from thioglycollate-induced acute peritonitis

Jingyi Zhao,Ying Chen,Lijun Dong,Xin Li,Ruijie Dong,Dongmei Zhou,Chengzhi Wang,Xiangdong Guo,Jieyou Zhang,Zhenyi Xue,Qing Xi,Lijuan Zhang,Guangze Yang,Yan Li,Rongxin Zhang

Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa . In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b + Ly6G + neutrophils and F4/80 + macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice.

All-Fiber SPR Microfluidic Chip for Arctigenin Detection

Yong Wei,Chunbiao Liu,Yonghui Zhang,Chen Shi,Yixiong Tang,Chunlan Liu,Yudong Su,Chen Wang,Yu Zhang,Zhihai Liu

Synthesis and pharmacological activity evaluation of arctigenin monoester derivatives

Qiulian Chen,Limin Yang,Mei Han,Enbo Cai,Yan Zhao

Arctigenin (ARG), a nature medicine with many pharmacological activities , was poorly soluble in water and placed restriction on practical usage. Six novel arctigenin monoester derivatives were obtained from the reflux reaction with arctigenin, carboxylic acids (crotonic acid, furoic acid, 2-naphthalene acid and indol-3-acetic acid), EDCI and DMAP in dichloromethane at 60   °C for 4–6   h and their properties on nitrite scavenging assay were investigated in vitro. Based on the results, the one of the most effective derivatives, arctigenin β-indolylacetate (ARG6), was selected to study anti-tumor activity in vivo at doses of 20 and 40   mg/kg. The results showed that comparison with ARG group, ARG6 exhibited more anti-tumor activity in H22 tumor-bearing mice. Furthermore, ARG6 exhibited less damage to the liver, kidney, spleen and thymus when compared with those in positive group. Biochemical parameters of ALT , AST, BUN and Cre showed ARG6 had little toxicity to mice as well. ARG6 significantly improved serum cytokine levels of IL-2, IL-6, IFN-γ and TNF-α, and decreased VEGF compared with ARG. Moreover, H & E staining, TUNEL assay and immunohistochemical of tumor issues also indicated that ARG6 exhibited anti-tumor activity in vivo. In brief, the present study provide a method to improve ARG anti-tumor activity and provide a reference for new anti-tumor agent.

Metabolic activation, hepatic protein covalent binding, and cytotoxicity of arctigenin

Yuqin Chen,Zixia Hu,Guode Zhao,Mei Li,Ziying Jiang,Liangjia Xu,Jiannan Zheng,Weiwei Li,Ying Peng,Jiang Zheng

Arctigenin (ATG) is an important component isolated from the fruit of the medicinal plant Arctium lappa L., with anti-inflammatory, antiviral and anti-tumor properties. Although ATG has been reported to induce hepatotoxicity in beagle dogs and SD rats, and the underlying mechanisms remained unclear. The aim of this study was to investigate the metabolic activation of ATG and to define the potential correlation between the metabolic activation of ATG and its hepatotoxicity. A quinone methide intermediate was identified in vitro and in vivo , and CYP3A dominated the metabolic activation. ATG was found to show significant cytotoxicity at 50 μM in cultured mouse primary hepatocytes. The ATG-derived quinone methide metabolite assaulted cysteine residue of hepatic protein to form protein covalent binding. The observed protein modification was most likely associated with the cytotoxicity of ATG observed.

Evaluation on the antiviral activity of arctigenin against spring viraemia of carp virus

Yu-Feng Shen,Lei Liu,Wei-Chao Chen,Yang Hu,Bin Zhu,Gao-Xue Wang

Spring viraemia of carp virus (SVCV) causes high morality in several economically important cyprinid fishes, but there is no approved therapy up to now. To address the urgent need for therapeutics to combat SVCV infection, we investigated the anti-SVCV activities of 12 natural compounds and 7 common antiviral agents using epithelioma papulosum cyprini (EPC) cells in this study. From the 19 compounds, we identified arctigenin (ARG) has the highest inhibition on SVCV replication, with maximum inhibitory percentage on SVCV   >   90%. And the 48   h half maximal inhibitory concentrations (IC 50 ) of ARG on SVCV glycoprotein and nucleoprotein were 0.29 (0.22–0.39) and 0.35 (0.29–0.41)   mg/L respectively. In addition, ARG significantly reduced SVCV-induced apoptosis and recovered SVCV-activated caspase-3/8/9 activity. Further, cellular morphological damage induced by SVCV was blocked by ARG treatment. Mechanistically, ARG did not affect SVCV infectivity. Moreover, ARG could not induce reactive oxygen species (ROS) generation, which plays an antiviral role on SVCV. Interestingly, SVCV-induced autophagy which is necessary for virus replication was inhibited by ARG treatment. These results indicated that the inhibition of ARG on SVCV replication was, at least in part, via blocking SVCV-induced autophagy. Taken together, ARG has the potential to work as an agent for protecting economically important fishes against SVCV.

Effect of a new arctigenin derivative against Gyrodactylus kobayashii through inhibition of ATP production

Xiaoping Tan,Yang Hu,Shenye Qu,Gaoxue Wang,Tianqiang Liu

Noxious pathogens always lead to high rates of mortality, which results in severe economic losses in aquaculture. Currently, gyrodactylosis treatments mainly rely on unapproved chemicals, which are not always satisfactory. According to the previous study, arctigenin is an efficient natural product for controlling gyrodactylosis. For the sake of seeking high-efficiency compounds, a new arctigenin derivative (CCA) was synthesized. Next, we evaluated the anthelmintic activity of CCA in vitro and in vivo , and studied the mechanism of action. The number of Gyrodactylus kobayashii significantly reduced as compared with the control group, the EC 50 value at 24 and 48-h after CCA treatment was 0.616 and 0.451 mg/L, respectively, with EC 100 at CCA concentration of 3 mg/L after 1 h bath treatment. In vitro results showed that CCA can rapidly reduce the amount of G. kobayashii and inhibit its mobility that could normally lead to death. The concentration and duration of CCA were positively correlated with the mortality of G. kobayashii . In addition, CCA displayed 100% efficacy against G. kobayashii at 4.0 mg/L after only 20 min exposure. Acute toxicity assay demonstrated that the LC 50 of CCA against goldfish was 5.012 mg/L, which was 8.13 times higher than that of the EC 50 . Furthermore, the results of confocal microscope study revealed that CCA leaded to the epidermal structure and dissolved muscles of worms. Moreover, the ATP level of worms were decreased sharply after both in vitro and in vivo exposures with CCA. The anthelminthic mechanism of CCA against gyrodactylids was related to epidermal structure damages and energy insufficient. From the previous study, the EC 50 of CCA against G. kobayashii (0.616 mg/L) was much lower than the EC 50 (1.85 mg/L) of arctigenin ( Tu et al., 2018 ). In summary, CCA is more effective than arctigenin and has great potential in control of Gyrodactylus infections.

Arctigenin triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in PC-3M cells

Bai-ling Sun,En-bo Cai,Yan Zhao,Yu Wang,Li-min Yang,Jing-Yao Wang

Arctigenin(ARG) , a natural lignans compound isolated from Arctium lappa L. In this study, the anti-tumor effect of ARG on prostate cancer cell PC-3M and the mechanism of apoptosis and autophagy induced by PI3K/Akt/mTOR signaling pathway were discussed, and further confirmed by the joint treatment of ARG and PI3K inhibitor LY294002. Here, the effect of ARG on cell viability was evaluated in PC-3M cells by CCK-8 assay. After the treatment of ARG, colony formation assay was used to detect the anti-proliferation effect. Annexin V-FITC/PI kit and DAPI staining were used to detect the apoptosis level, and cell cycle changes were analyzed by flow cytometry. The expression of autophagy was detected by acridine orange staining. In addition, the expression levels of apoptosis and autophagy-related proteins were analyzed by western blot. The result showed that different concentrations of ARG inhibited the proliferation of PC-3M cells. DAPI staining and flow cytometry showed that ARG induced PC-3M cell apoptosis and arrested cell in G0/G1 phase. Acridine orange staining showed that ARG induced autophagy in PC-3M cells. Western blot experiments showed that ARG inhibited the expression of Bcl-2 , promoted the expression of Bax and cleaved caspase-3. At the same time, the expression of autophagy-related proteins LC3B-II and Beclin-1 increased after ARG treatment, but P62 decreased. In addition, further studies have shown that treatment with LY294002 enhanced the effects of ARG on the expression of proteins associated with apoptosis and autophagy , indicating that ARG may induce apoptosis and autophagy through PI3K/Akt/mTOR pathway.

Arctigenin ameliorates renal impairment and inhibits endoplasmic reticulum stress in diabetic db/db mice

Jing Zhang,Peng Cao,Jingjing Gui,Xin Wang,Jun Han,Yuwei Wang,Guodong Wang

Aims Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. Endoplasmic reticulum (ER) plays an important role in the development and progression of DN. Arctigenin (ATG), a lignan extract from Fructus Arctii , exhibits anti-inflammatory, anticarcinogenic, anti-oxidative stress and immunomodulatory properties. The present research aimed to investigate whether ATG could protect against diabetes-related renal injury and inhibit ER stress in db / db mice. Main methods Male db / db mice were randomly divided into two groups: DN group and ATG treatment group (DN + ATG). db / m mice were defined as the normal control group (NC). ATG was dissolved in 0.5% carboxymethyl cellulose sodium salt solution and administered orally at a dose of 80 mg/kg to mice in the DN + ATG group once daily for 8 consecutive weeks. HK2 cells were used to determine the effects of ATG on ER stress and cell apoptosis in vitro . Key findings ATG administration significantly reduced blood glucose, urine albumin excretion, and urine albumin to creatinine ratio, and attenuated renal pathological injury when compared with untreated db / db mice. These changes were accompanied by decreased expression of both ER stress-related markers and caspase 12 level in the kidneys of db / db mice. In vitro , high glucose activated ER stress signal transduction pathway and induced cell apoptosis in HK2 cells, which were blocked by ATG. Significance Our results suggest that ATG exerts renoprotective effects on diabetes-related renal injury in db / db mice and cytoprotective effects on high glucose induced cell apoptosis and inhibits ER stress.

Evaluation on antiviral activity of a novel arctigenin derivative against multiple rhabdoviruses in aquaculture

Yu-Feng Shen,Yi-Hang Liu,Bo-Yang Li,Tian-Qiang Liu,Gao-Xue Wang

Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro . By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BOA (IC 50 = 1.11 μM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2−6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.

Arctigenin exhibits hepatoprotective activity in Toxoplasma gondii-infected host through HMGB1/TLR4/NF-κB pathway

Yu-Nan Lu,Xu-Dong Zhao,Xiang Xu,Jing Piao,Fumie Aosai,Ying-Biao Li,Long-Xie Shen,Su-Yun Shi,Guang-Hua Xu,Juan Ma,Hu-Nan Piao,Xuejun Jin,Lian-Xun Piao

Toxoplasmosis is a parasitic zoonosis with the highest incidence in humans. Severe lesions due to acute toxoplasmosis have been recorded in the visceral organs including the liver, where hepatocytes and Kupffer cells are important innate immune cells. Arctigenin (AG) is a bioactive ingredient of Arctium lappa L. and increasing evidence suggests that AG exhibits anti-oxidant, anti-inflammatory and anti- Toxoplasma gondii ( T. gondii ) effects. However, the role of AG in acute liver damage induced by T. gondii infection remains unclear. In this study, we analyzed the effects of AG against T. gondii -induced liver damage by establishing an in vitro infection model using a murine liver cell line (NCTC-1469 cells) and an in vivo mouse model with acute T. gondii infection of virulent RH strain. In the current study, AG effectively attenuated hepatocytes apoptosis and inhibited the reproduction of T. gondii . The results of in vitro and in vivo studies showed that AG significantly reduced alanine aminotransferase/aspartate aminotransferase activities and lessened pathological damage of liver. Moreover, AG suppressed T. gondii -induced inducible nitric oxide synthase production. AG also attenuated liver inflammation by inhibiting T. gondii -induced activation of the high-mobility group box1/toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway. These findings demonstrated that AG exhibited prominent hepatoprotective activities in toxoplasmic liver injury with anti-inflammatory effects by inhibiting the HMGB1/TLR4/NF-κB signaling axis. Thus, this study provides the basis for the development of new drugs to treat toxoplasmic hepatitis.