An Extract from the Medicinal Plant Phyllanthus acidus and Its Isolated Compounds Induce Airway Chloride Secretion: A Potential Treatment for Cystic Fibrosis

Sousa, Marisa; Ousingsawat, Jiraporn; Seitz, R; Puntheeranurak, Supaporn; Regalado, Ana; Schmidt, André; Grego, Tiago; Jansakul, Chaweewan; Amaral, Margarida D.; Schreiber, Rainer; Kunzelmann, Karl

doi:10.1124/mol.106.025262

Cited by 53 publications

(42 citation statements)

References 38 publications

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“…DHBA is produced during aspirin metabolism in humans and is present in many plants (19,20). DHBA has higher binding constants for iron than transferrin and lactoferrin (21).…”

mentioning

confidence: 99%

2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa

Ahire

Dicks

2014

Antimicrob Agents Chemother

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Pseudomonas aeruginosa forms biofilms in wounds, which often leads to chronic infections that are difficult to treat with antibiotics. Free iron enhances biofilm formation, delays wound healing, and may even be responsible for persistent inflammation, increased connective tissue destruction, and lipid peroxidation. Exposure of P. aeruginosa Xen 5 to the iron chelator 2,3-dihydroxybenzoic acid (DHBA), electrospun into a nanofiber blend of poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO), referred to as DF, for 8 h decreased biofilm formation by approximately 75%. This was shown by a drastic decline in cell numbers, from 7.1 log 10 CFU/ml to 4.8 log 10 CFU/ml when biofilms were exposed to DF in the presence of 2.0 mM FeCl 3 6H 2 O. A similar decline in cell numbers was recorded in the presence of 3.0 mM FeCl 3 6H 2 O and DF. The cells were more mobile in the presence of DHBA, supporting the observation of less biofilm formation at lower iron concentrations. DHBA at MIC levels (1.5 mg/ ml) inhibited the growth of strain Xen 5 for at least 24 h. Our findings indicate that DHBA electrospun into nanofibers inhibits cell growth for at least 4 h, which is equivalent to the time required for all DHBA to diffuse from DF. This is the first indication that DF can be developed into a wound dressing to treat topical infections caused by P. aeruginosa. Pseudomonas aeruginosa is a versatile opportunistic pathogen commonly associated with a number of nosocomial infections of the respiratory tract, urinary tract, and wounds (1, 2, 3). The antibiotic-induced killing of P. aeruginosa is extremely poor in chronic wounds such as leg ulcers or burn wounds (4). The species protects itself from antibiotics by forming biofilms (5-7) and by doing so develops resistance to antibiotics (6,8,9).Cystic fibrosis is one of the best-studied examples of chronic infections caused by biofilms of P. aeruginosa (10). Zhao et al. (11) have shown that biofilm formation by P. aeruginosa is stimulated by Psl exopolysaccharide on the cell surface. However, Singh et al. (12) and Banin et al. (13) attributed biofilm formation by Pseudomonas spp. to higher levels of free iron in the environment. Free iron may retard wound healing and may even be responsible for persistent inflammation, increased connective tissue destruction, and lipid peroxidation (14). These pose unique challenges in the development of antimicrobial drugs effective against P. aeruginosa.Lactoferrin, an iron chelator in mammals, inhibited biofilm formation (12,13,15). Similar results were obtained with synthetic iron chelators such as 2,2=-dipyridyl (2DP), diethylenetriaminepentaacetic acid (DTPA), EDTA, deferoxamine mesylate (DM), and ethylenediamine-N,N=-diacetic acid (EDDA) (16). As far as we could determine, the effect of the iron chelator 2,3-dihydroxybenzoic acid (DHBA) on biofilm formation by Pseudomonas spp. has not been reported.DHBA has been used orally as a noncytotoxic iron-chelating agent in patients suffering from ␤-thalassemia (17, 18). DHBA is produced during as...

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“…DHBA is produced during aspirin metabolism in humans and is present in many plants (19,20). DHBA has higher binding constants for iron than transferrin and lactoferrin (21).…”

mentioning

confidence: 99%

2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa

Ahire

Dicks

2014

Antimicrob Agents Chemother

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“…The induction of higher P. acidus at 1, 2 and 4% implies lack of cytotoxicity. It had earlier been reported that extract of P. acidus was non-cytotoxic (Sousa et al, 2007). This may be in connection with its richness in adenosine, a precursor for DNA synthesis during cell division.…”

Section: Myristica Fragransmentioning

confidence: 93%

“…The fruit of Phyllantus acidus contains 40 mg/100 g ascorbic acid, the acidic contents of lemon and grapefruits are similar to that of P. acidus (Duangpron and Siripong, 2009). P. acidus was reported to be rich in adenosine, and lacks cytotoxic effects (Sousa et al, 2007). However, there are limited reports on the possible toxicity of the juices of these plants in eukaryotic cells, coupled with the fact that there are no known published data on their cyto-geno toxicities in an in vivo genetic system as being reported presently.…”

Section: Introductionmentioning

confidence: 92%

Mutagenic and antimutagenic potentials of fruit juices of five medicinal plants in Allium cepa L.: Possible influence of DPPH free radical scavengers

Akinboro¹,

Mohamed²,

Asmawi³

et al. 2011

Afr. J. Biotechnol.

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Mutagenic and antimutagenic activities of freeze dried fruit juices (FDFJ) ofTesting the mutagenic activity, onions were suspended in solution of different concentrations of FDFJ alone in tap water for 48 h. Thereafter, root tips were prepared and observed for dividing cells and chromosomal aberrations using a light microscope. Antimutagenicity screening was similar to the mutagenic evaluation, except that the solution of FDFJ was combined with 0.1% cylophosphamide-CP. Free radicals (2,2-diphenyl-1-picrylhyrazyl) scavenging activity of the FDFJ was tested using butylated hydroxylanisole (BHA) and butylated hydroxytoluene (BHT) as the standards and their phenolic contents were evaluated by comparing with gallic acid equivalents (GAE). The free radicals scavenging power of M. fragrans at 1 mg/ml was almost similar to that of BHA and BHT and its phenolic content was 21 ± 6.0 mg GAE/g, the highest among the tested juices. A. cepa cell division was inhibited in a dose-dependent manner by the FDFJ of M. fragrans, while the induced chromosomal aberrations were non dose dependent. The cytotoxicity and chromosomal aberrations of CP were suppressed throughout the tested concentrations of M. fragrans, unlike the effects of other four juices. These results suggest that the observed activities of FDFJ of M. fragrans may be due to the quantity and quality of phenolic compounds with antioxidant activity, suggesting its use in preventing the DNAdamaging effects of mutagens.

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“…On the other hand, fruit is used as a laxative and the antioxidants present in fruit have a hepatoprotective effect on liver (Reddy, 2014;Jain et al, 2011). Extract has shown nematicidal activity against the pine wood nematode and have possibility to provide treatment of cystic fibrosis of the lungs (Sousa et al, 2007). Leaves are useful to treat blood vomiting, piles, small pox, fever, itching and gum infection (Subhadrabandhu, 2001).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological activities of methanol extract of Phyllanthus acidus pulp

Afrin¹,

Banik²,

Hossain³

2016

J. Med. Plants Res.

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The methanolic extract of Phyllanthus acidus pulp was screened in the present study to explore pharmacological activities on laboratory animals. The hypoglycemic activity was assessed by glucose tolerance test and the antidiarrheal activity was evaluated by castor oil induced diarrhea inhibition method. The analgesic and anesthetic activity was determined by Tail immersion method and Thiopental sodium induced sleeping time method, respectively. The extract showed significant (P<0.05) blood glucose activity at 500 mg/kg of body weight. The extract at both doses showed pronounced antidiarrheal activity and inhibited the average number of defecation by 54.24% (P<0.05) and 10.17% at both doses, respectively. In Tail-immersion test, the extract showed significant (P<0.05) analgesic activity at both doses. The extract also showed good CNS anesthetic activity to the experimental animal. It was concluded that from this study, the methanolic extract of P. acidus have potential different pharmacological activities and justify its use in folkloric medicines.

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An Extract from the Medicinal Plant Phyllanthus acidus and Its Isolated Compounds Induce Airway Chloride Secretion: A Potential Treatment for Cystic Fibrosis

Cited by 53 publications

References 38 publications

2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa

2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa

Mutagenic and antimutagenic potentials of fruit juices of five medicinal plants in Allium cepa L.: Possible influence of DPPH free radical scavengers

Pharmacological activities of methanol extract of Phyllanthus acidus pulp

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