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Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Edema | Research article

A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile

Authors: Yousra Shafiq, Syed Baqir Shyum Naqvi, Ghazala H. Rizwani, Muhammad Arif Asghar, Rabia Bushra, Sana Ghayas, Ahad Abdul Rehman, Muhammad Asif Asghar

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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Abstract

Background

Nerium oleander (L.) is well known traditionally used medicinal plant with several pharmacological activities. However, the anti-bacterial, anti-inflammatory activity and in vivo toxicity potential of floral parts of this plant are not reported. Therefore the present study was designed to investigate these activities of Nerium oleander ethanolic flower extract (NOEE) in different animal models.

Methods

Antimicrobial activity of plant extract was compared with five different antibiotics using the disk diffusion method. The time-killing kinetic assay and bacterial killing mechanism of NOEE were also performed. Anti-inflammatory activity was assessed using granuloma induced by cotton-pellet, rat paw edema induced by carrageenan and levels of different inflammatory biomarkers on healthy Wistar rats. The protein and mRNA expressions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also measured. Acute (14 days) and sub-acute (28 days) oral toxicity studies were also performed on healthy Sprague Dawley rats.

Results

NOEE produced highly significant (P < 0.005) and significant (P < 0.05) zones of inhibition at 30 mg/mL and 20 mg/mL respectively against most of the tested bacterial strains. NOEE produced a more drop in viable counts of Gram-negative isolates within 20 min. After 12 h exposure with NOEE, the SEM images of MRSA showed the destruction of cell membrane. NOEE showed highly significant (P < 0.005) anti-inflammatory activity in cotton-pellet and carrageenan inflammatory models. In addition, treatment with NOEE also decreased the production of NO, PGE2, TNF-α and IL-1β in the rat paw after treated with carrageenan. Similarly, NOEE also suppressed the inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) mRNA expressions. It is also showed highly significant reduction in total leukocyte count (73.09%) and C-reactive protein levels (54.60%). NOEE also inhibited COX-1, COX-2, 5-LO and 12-LO in a highly significant manner. Moreover, acute and sub-acute toxicity studies of NOEE in rats confirm the toxicity with hepatotoxicity at higher doses (2000 mg/kg) i.e. four times greater than the therapeutic dose.

Conclusion

It is concluded that crude flower extract of N. oleander is a potent antimicrobial and anti-inflammatory agent with no toxicity potential at therapeutic doses.
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Literature
6.
go back to reference Rehman AA, Riaz A, Asghar MA, Raza ML, Ahmed S, Khan K. In vivo assessment of anticoagulant and antiplatelet effects of Syzygium cumini leaves extract in rabbits. BMC Complement Altern Med. 2019;19:1–8.CrossRef Rehman AA, Riaz A, Asghar MA, Raza ML, Ahmed S, Khan K. In vivo assessment of anticoagulant and antiplatelet effects of Syzygium cumini leaves extract in rabbits. BMC Complement Altern Med. 2019;19:1–8.CrossRef
7.
go back to reference Ullah I, Khan JA, Shahid M, Khan A, Adhikari A, Hannan PA, et al. Pharmacological screening of Monotheca buxifolia (Falc.) a. DC. For antinociceptive, anti-inflammatory and antipyretic activities. BMC Complement Altern Med. 2016;16:1–8.CrossRef Ullah I, Khan JA, Shahid M, Khan A, Adhikari A, Hannan PA, et al. Pharmacological screening of Monotheca buxifolia (Falc.) a. DC. For antinociceptive, anti-inflammatory and antipyretic activities. BMC Complement Altern Med. 2016;16:1–8.CrossRef
8.
go back to reference Naz R, Ayub H, Nawaz S, Islam ZU, Yasmin T, Bano A, et al. Antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from Punjab, Pakistan. BMC Complement Altern Med. 2017;17:1–13.CrossRef Naz R, Ayub H, Nawaz S, Islam ZU, Yasmin T, Bano A, et al. Antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from Punjab, Pakistan. BMC Complement Altern Med. 2017;17:1–13.CrossRef
9.
go back to reference Shafiq Y, Naqvi SBS, Rizwani GH, Abbas T, Sharif H, Ali H, et al. Assessment of killing kinetics assay and bactericidal mechanism of crude methanolic bark extract of Casuarina equisetifolia. Pak J Pharm Sci. 2018;31(5):2143–8.PubMed Shafiq Y, Naqvi SBS, Rizwani GH, Abbas T, Sharif H, Ali H, et al. Assessment of killing kinetics assay and bactericidal mechanism of crude methanolic bark extract of Casuarina equisetifolia. Pak J Pharm Sci. 2018;31(5):2143–8.PubMed
17.
go back to reference Govind P. Protective effect of Nerium indicum on ccl4 induced hepatotoxicity in rat. Int J Biomed Res. 2010;1(4):147–52. Govind P. Protective effect of Nerium indicum on ccl4 induced hepatotoxicity in rat. Int J Biomed Res. 2010;1(4):147–52.
18.
go back to reference Derwich E, Benziane Z, Boukir A. Antibacterial activity and chemical composition of the essential oil from flowers of Nerium oleander. Electron J Environ Agricult Food Chemist. 2010;9(6):1074-1084. Derwich E, Benziane Z, Boukir A. Antibacterial activity and chemical composition of the essential oil from flowers of Nerium oleander. Electron J Environ Agricult Food Chemist. 2010;9(6):1074-1084.
19.
go back to reference Ibrahim AM, Ghareeb MA. Preliminary phytochemical screening, total phenolic content, in vitro antioxidant and molluscicidal activities of the methanolic extract of five medicinal plants on Biomphalaria alexandrina snails. J Herbs Spices Med Plants. 2020;26(1):40–8.CrossRef Ibrahim AM, Ghareeb MA. Preliminary phytochemical screening, total phenolic content, in vitro antioxidant and molluscicidal activities of the methanolic extract of five medicinal plants on Biomphalaria alexandrina snails. J Herbs Spices Med Plants. 2020;26(1):40–8.CrossRef
20.
go back to reference Torres-Rêgo M, Furtado AA, Bitencourt MAO, de Souza Lima MCJ, de Andrade RCLC, de Azevedo EP, et al. Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae). BMC Complement Altern Med. 2016;16:1–10.CrossRef Torres-Rêgo M, Furtado AA, Bitencourt MAO, de Souza Lima MCJ, de Andrade RCLC, de Azevedo EP, et al. Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae). BMC Complement Altern Med. 2016;16:1–10.CrossRef
22.
go back to reference Mumtaz N, Naqvi SBS, Asghar MA, Asghar MA. Assessment of antimicrobial activity of Sphaeranthus indicus L. against highly resistant pathogens and its comparison with three different antibiotics. J Dis Glob Health. 2017;10:67–73. Mumtaz N, Naqvi SBS, Asghar MA, Asghar MA. Assessment of antimicrobial activity of Sphaeranthus indicus L. against highly resistant pathogens and its comparison with three different antibiotics. J Dis Glob Health. 2017;10:67–73.
23.
go back to reference Hsueh P-R, Ko W-C, Wu J-J, Lu J-J, Wang F-D, Wu H-Y, et al. Consensus statement on the adherence to clinical and laboratory standards institute (CLSI) antimicrobial susceptibility testing guidelines (CLSI-2010 and CLSI-2010-update) for Enterobacteriaceae in clinical microbiology laboratories in Taiwan. J Microbiol Immunol Infect. 2010;43(5):452–5. https://doi.org/10.1016/S1684-1182(10)60070-9.CrossRefPubMed Hsueh P-R, Ko W-C, Wu J-J, Lu J-J, Wang F-D, Wu H-Y, et al. Consensus statement on the adherence to clinical and laboratory standards institute (CLSI) antimicrobial susceptibility testing guidelines (CLSI-2010 and CLSI-2010-update) for Enterobacteriaceae in clinical microbiology laboratories in Taiwan. J Microbiol Immunol Infect. 2010;43(5):452–5. https://​doi.​org/​10.​1016/​S1684-1182(10)60070-9.CrossRefPubMed
28.
go back to reference Mumtaz N, Asghar MA, Naqvi SBS, Asghar MA, Raza ML, Rehman AA. Time kill assay and bactericidal mechanism of action of ethanolic flowers extract of Sphaeranthus indicus. RADS J Pharm Pharmaceut Sci. 2019;7(1):27–33. Mumtaz N, Asghar MA, Naqvi SBS, Asghar MA, Raza ML, Rehman AA. Time kill assay and bactericidal mechanism of action of ethanolic flowers extract of Sphaeranthus indicus. RADS J Pharm Pharmaceut Sci. 2019;7(1):27–33.
35.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402–8.CrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402–8.CrossRef
36.
go back to reference Hijazi MA, El-Mallah A, Aboul-Ela M, Ellakany A: Evaluation of analgesic activity of Papaver libanoticum extract in mice: involvement of opioids receptors Evidence-Based Complementary and Alternative Medicine 2017, 2017. Hijazi MA, El-Mallah A, Aboul-Ela M, Ellakany A: Evaluation of analgesic activity of Papaver libanoticum extract in mice: involvement of opioids receptors Evidence-Based Complementary and Alternative Medicine 2017, 2017.
38.
go back to reference Oecd: OECD Guidelines for the Testing of Chemicals: Organization for Economic; 1994. Oecd: OECD Guidelines for the Testing of Chemicals: Organization for Economic; 1994.
39.
41.
go back to reference Namian P, Talebi T, Germi KG, Shabani F. Screening of biological activities (antioxidant, antibacterial and antitumor) of Nerium oleander leaf and flower extracts. Vacuum. 2013;10(11):378-384. Namian P, Talebi T, Germi KG, Shabani F. Screening of biological activities (antioxidant, antibacterial and antitumor) of Nerium oleander leaf and flower extracts. Vacuum. 2013;10(11):378-384.
45.
go back to reference Pacheco SM, Azambuja JH, de Carvalho TR, Soares MSP, Oliveira PS, da Silveira EF, et al. Glioprotective effects of lingonberry extract against altered cellular viability, acetylcholinesterase activity, and oxidative stress in lipopolysaccharide-treated astrocytes. Cell Mol Neurobiol. 2018;38(5):1107–21. https://doi.org/10.1007/s10571-018-0581-x.CrossRefPubMed Pacheco SM, Azambuja JH, de Carvalho TR, Soares MSP, Oliveira PS, da Silveira EF, et al. Glioprotective effects of lingonberry extract against altered cellular viability, acetylcholinesterase activity, and oxidative stress in lipopolysaccharide-treated astrocytes. Cell Mol Neurobiol. 2018;38(5):1107–21. https://​doi.​org/​10.​1007/​s10571-018-0581-x.CrossRefPubMed
50.
go back to reference Lubberts E, van den Berg WB: Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. Madame Curie Bioscience Database [Internet] 2013. Lubberts E, van den Berg WB: Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. Madame Curie Bioscience Database [Internet] 2013.
53.
go back to reference Toriyabe M, Omote K, Kawamata T, Namiki A. Contribution of interaction between nitric oxide and cyclooxygenases to the production of prostaglandins in carrageenan-induced inflammation. J Am Soc Anesthesiol. 2004;101(4):983–90.CrossRef Toriyabe M, Omote K, Kawamata T, Namiki A. Contribution of interaction between nitric oxide and cyclooxygenases to the production of prostaglandins in carrageenan-induced inflammation. J Am Soc Anesthesiol. 2004;101(4):983–90.CrossRef
58.
go back to reference Bazan N, Botting JH, Vane JR: New targets in inflammation: inhibitors of COX-2 or adhesion molecules proceedings of a conference held on April 15–16, 1996, in New Orleans, USA, supported by an educational grant from Boehringer Ingelheim: Springer Science & Business Media; 2012. Bazan N, Botting JH, Vane JR: New targets in inflammation: inhibitors of COX-2 or adhesion molecules proceedings of a conference held on April 15–16, 1996, in New Orleans, USA, supported by an educational grant from Boehringer Ingelheim: Springer Science & Business Media; 2012.
Metadata
Title
A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile
Authors
Yousra Shafiq
Syed Baqir Shyum Naqvi
Ghazala H. Rizwani
Muhammad Arif Asghar
Rabia Bushra
Sana Ghayas
Ahad Abdul Rehman
Muhammad Asif Asghar
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Edema
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-021-03308-z

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