Publications by authors named "Xinghan Zheng"

3 Publications

  • Page 1 of 1

Apoptotic activities of brusatol in human non-small cell lung cancer cells: Involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response.

Toxicology 2021 03 16;451:152680. Epub 2021 Jan 16.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China.

Brusatol occurs as a characteristic bioactive principle of Brucea javanica (L.) Merr., a traditional medicinal herb frequently employed to tackle cancer in China. This work endeavored to unravel the potential anti-cancer activity and action mechanism of brusatol against non-small cell lung cancer (NSCLC) cell lines. The findings indicated that brusatol remarkably inhibited the growth of wild-type NSCLC cell lines (A549 and H1650) and epidermal growth factor receptor-mutant cell lines (PC9 and HCC827) in a dose- and time-related fashion, and profoundly inhibited the clonogenic capability and migratory capacity of PC9 cells. Treatment with brusatol resulted in significant apoptosis in PC9 cells, as evidenced by Hoechst 33342 staining and flow cytometric analysis. The apoptotic effect was closely related to induction of G0-G1 cell cycle arrest, stimulation of reactive oxygen species (ROS) and malondialdehyde, decrease of glutathione levels and disruption of mitochondrial membrane potential. Furthermore, pretreatment with N-acetylcysteine, a typical ROS scavenger, markedly ameliorated the brusatol-induced inhibition of PC9 cells. Western blotting assay indicated that brusatol pronouncedly suppressed the expression levels of mitochondrial apoptotic pathway-associated proteins Bcl-2 and Bcl-xl, accentuated the expression of Bax and Bak, and upregulated the protein expression of XIAP, cleaved caspase-3/pro caspase-3, cleaved caspase-8/pro caspase-8, and cleaved PARP/total PARP. In addition, brusatol significantly suppressed the expression of Nrf2 and HO-1, and abrogated tBHQ-induced Nrf2 activation. Combinational administration of brusatol with four chemotherapeutic agents exhibited marked synergetic effect on PC9 cells. Together, the inhibition of PC9 cells proliferation by brusatol might be intimately associated with the modulation of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. This novel insight might provide further evidence to buttress the antineoplastic efficacy of B. javanica, and support a role for brusatol as a promising anti-cancer candidate or adjuvant to current chemotherapeutic medication in the therapy of EGFR-mutant NSCLC.
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http://dx.doi.org/10.1016/j.tox.2021.152680DOI Listing
March 2021

Rhamnocitrin extracted from Nervilia fordii inhibited vascular endothelial activation via miR-185/STIM-1/SOCE/NFATc3.

Phytomedicine 2020 Dec 19;79:153350. Epub 2020 Sep 19.

Mathematical Engineering Academy of Chinese Medicine; Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China. Electronic address:

Background: Vascular endothelial activation is pivotal for the pathological development of various infectious and inflammatory diseases. Therapeutic interventions to prevent endothelial activation are of great clinical significance to achieve anti-inflammatory strategy. Previous studies indicate that the total flavonoids from the endemic herbal medicine Nervilia fordii (Hance) Schltr exerts potent anti-inflammatory effect and protective effect against endotoxin lipopolysaccharide (LPS)-induced acute lung injury, and shows clinical benefit in severe acute respiratory syndromes (SARS). However, the exact effective component of Nervilia fordii and its potential mechanism remain unknown.

Purpose: The aim of this study was to investigate the effect and mechanism of rhamnocitrin (RH), a flavonoid extracted from Nervilia fordii, on LPS-induced endothelial activation.

Methods: The in vitro endothelial cell activation model was induced by LPS in human umbilical vein endothelial cells (HUVECs). Cell viability was measured to determine the cytotoxicity of RH. RT-PCR, Western blot, fluorescent probe and immunofluorescence were conducted to evaluate the effect and mechanism of RH against endothelial activation.

Results: RH was extracted and isolated from Nervilia fordii. RH at the concentration from 10 M-10 M inhibited the expressions of interlukin-6 (IL-6) and -8 (IL-8), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) in response to LPS challenge. Mechanistically, RH repressed calcium store-operated Ca entry (SOCE) induced by LPS, which is due to downregulation of stromal interaction molecule-1 (STIM-1) following upregulating microRNA-185 (miR-185). Ultimately, RH abrogated LPS-induced activation of SOCE-mediated calcineurin/NFATc3 (nuclear factor of activated T cells, cytoplasmic 3) signaling pathway.

Conclusion: The present study identifies RH as a potent inhibitor of endothelial activation. Since vascular endothelial activation is a pivotal cause of excessive cytokine production, leading to cytokine storm and severe pathology in infectious diseases such as SARS and the ongoing COVID-19 pneumonia disease, RH might suggest promising therapeutic potential in the management of cytokine storm in these diseases.
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http://dx.doi.org/10.1016/j.phymed.2020.153350DOI Listing
December 2020

Protective Effect of (L.) Lam. Fruit on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice: Role of Keap1/Nrf2 Pathway and Gut Microbiota.

Front Pharmacol 2019 3;10:1602. Epub 2020 Feb 3.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

(BG), a medicinal mangrove, and its fruit (a food material) (BGF), have traditionally been used to treat diarrhea (also known as ulcerative colitis) in folk medicine. However, the mechanism of action against colitis remains ambiguous. This study aimed to investigate the potential efficacy and mechanism of BGF on experimental colitis. Colitis was induced by oral intake of dextran sulfate sodium (DSS) and treated with aqueous extract of BGF (25, 50 and 100 mg/kg) for a week. The Disease Activity Index (DAI), colon length, and histological changes of colon were analyzed. The inflammatory and oxidative stress status was explored. The protein expression of Nrf2 and Keap1 in the colon was detected by Western blotting. The mRNA expression of Nrf2 downstream genes (, , and ) was determined by RT-PCR. Furthermore, the effect on intestinal flora was analyzed. Results indicated that BGF was rich in pinitol, and showed strong antioxidative activity . Compared with the DSS model, BGF effectively reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, and decreased the histological scores, which was superior to salicylazosulfapyridine (SASP) with smaller dosage. Moreover, BGF not only abated the levels of MDA and inflammatory mediators (TNF-α, IL-6, IL-1β, and IFN-γ), increased the level of IL-10, but also prevented the depletion of SOD and GSH. BGF upregulated the protein level of nuclear Nrf2 and mRNA levels of , , and , while significantly inhibited the protein expression of Keap1 and cytosolic Nrf2. Besides, BGF promoted the growth of probiotics (, , and ) in the gut, and inhibited the colonization of pathogenic bacteria ( and ), which contributed to the maintenance of intestinal homeostasis. BGF possessed protective effect against DSS-induced colitis. The potential mechanism of BGF may involve the amelioration of inflammatory and oxidative status, activation of Keap1/Nrf2 signaling pathway, and maintenance of micro-ecological balance of the host. This study provides experimental evidence for the traditional application of BGF in the treatment of diarrhea, and indicates that BGF may be a promising candidate against colitis.
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http://dx.doi.org/10.3389/fphar.2019.01602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008401PMC
February 2020
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