Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis

Qi, Liang; Cai, Wuyang; Zhao, Yulan; Xu, Huanbai; Tang, Huirong; Chen, Daijie; Qian, Feng; Sun, Lei

doi:10.1016/j.phrs.2020.104884

Cited by 99 publications

(46 citation statements)

References 41 publications

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“…(3) ISO: administered ISO daily for 2 weeks intraperitoneally (10 mg/kg); (4) ISO + LYC: in addition to receiving LYC for 4 weeks, these mice were given ISO simultaneously for 2 weeks (LYC, 5 mg/kg; ISO, 10 mg/kg). The way of our administering lycorine was in accordance with researches conducted by Qing Liang, Geng-Rui Xu and Katharina Schimmel [26,28,29]. An overview of the animal treatments is given in Figure 1(a).…”

Section: Animal Modelmentioning

confidence: 99%

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

Jiang

et al. 2021

Bioengineered

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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.

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Section: Animal Modelmentioning

confidence: 99%

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

Jiang

et al. 2021

Bioengineered

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“…These studies suggested that NLRP3 inflammasome plays a key role in the development of DM. NLRP3 inflammasome is known to participate in transforming growth factor β1, bleomycin and lipopolysaccharide-induced pulmonary inflammation and fibrosis [ 23 , 24 , 25 , 26 , 27 ], further indicating that pulmonary fibrosis and NLRP3 inflammasome are closely related. Chen et al observed pulmonary fibrosis accompanied by the increase of NLRP3 in a rat DM model at 12 weeks [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury

et al. 2021

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To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased ( P <0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats ( P <0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased ( P <0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group ( P <0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

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“…Natural products play a very important role in the prevention and treatment of diseases [22,23]. Ly, an active natural product, has been reported to have a wide range of anti-tumor activities [24,25].…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights into Tumor Targeted Therapy by Carrier-Free Lycorine Nanoparticles in Vitro and in Vivo

Zhou¹,

Qiu²,

Liu³

et al. 2021

Preprint

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Lycorine (Ly) is a promising natural compound with extensive antitumor activities. However, due to poor aqueous solubility and low bioavailability, the research and development of Ly anticancer drugs has been greatly restricted. Recently, the carrier-free nanoparticles have emerged as an outstanding drug delivery system. In this study, we prepared a DSPE-PEG modifying Ly nanoparticle (DS-Ly NPs) to overcome these drawbacks. We find that compared with Ly, DS-Ly NPs can significantly inhibit cell viability. Meanwhile, DS-Ly NPs treatment results in higher promotion of apoptotic and autophagic capacities, as well as inhibition of migration and invasion. Furthermore, DS-Ly NPs exhibits a better antitumor effect in AOM/DSS induced colorectal tumors and orthotopic hepatocellular tumors than Ly in repression of multiple oncogenic processes, which may benefit from the advantages of carrier-free nanoparticle. Beside, we showed that DS-Ly NPs can prolong the blood circulation time better than Ly. Taken together, these results have demonstrated that carrier-free nanoparticle provides a new therapeutic strategy for treating cancer.

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Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis

Cited by 99 publications

References 41 publications

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury

Molecular Insights into Tumor Targeted Therapy by Carrier-Free Lycorine Nanoparticles in Vitro and in Vivo

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