Abstract:
:Tovophyllin A (TA) is a xanthone isolated from Garcinia mangostana L. (GM, Guttiferae) pericarps that possesses various beneficial bioactivities. However, its protective effects on acute lung injury (ALI) and lung carcinoma have not yet been explored. The current work was designed to investigate the protective potential of TA against ALI and explore the possible mechanism of action. Two different doses of TA were tested against lipopolysaccharide (LPS)-induced ALI in mice. Moreover, the cytotoxic potential of TA was assessed in epithelial lung (A549 cells) and breast (MCF7 cells) carcinomas utilizing a sulforhodamine B (SRB) assay. The results revealed that TA possessed the ability to protect against LPS-induced acute lung damage. TA attenuated LPS-induced pulmonary edema, as it lowered the protein content in the bronchoalveolar lavage fluid (BALF) and the lung W/D ratio. In addition, TA counteracted inflammatory cell infiltration into the lung tissue, as shown by the total and differential cell counts in the BALF and histopathological examination of the lungs. The oxidative burden in the pulmonary tissue was ameliorated in TA-treated animals as there were reductions in the malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels in the lung tissue. TA increased the levels of antioxidants such as reduced glutathione (GSH) and superoxide dismutase (SOD) in the lungs. Furthermore, TA inhibited the activation of nuclear factor-κB (NF-κB). In addition, TA had potent anti-inflammatory activity as it reduced the immunoexpression and levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Furthermore, TA showed significantly enhanced cytotoxic activity against the MCF-7 and A549 cell lines with IC50s of 6.1 and 2.2 µM, respectively, compared to doxorubicin (IC50s of 0.41 and 0.74 µM, respectively). In conclusion, TA ameliorates LPS-induced ALI through the suppression of oxidative stress and inflammation. These findings suggest the potential use of this compound as a future treatment for ALI.
journal_name
Inflammopharmacologyjournal_title
Inflammopharmacologyauthors
El-Agamy DS,Mohamed GA,Ahmed N,Elkablawy MA,Elfaky MA,Elsaed WM,Mohamed SGA,Ibrahim SRMdoi
10.1007/s10787-019-00609-1subject
Has Abstractpub_date
2020-02-01 00:00:00pages
153-163issue
1eissn
0925-4692issn
1568-5608pii
10.1007/s10787-019-00609-1journal_volume
28pub_type
杂志文章abstract::In 1952 I re-joined the Pharmacological Division of the Research Department of the Boots Co. in Nottingham UK to work on rheumatoid arthritis (RA) but with the distinct disadvantage that the Division was housed in a group of rambling buildings attached to a Victorian house. The Division had moved there at the beginnin...
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journal_title:Inflammopharmacology
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