Lipopeptide Biosurfactant from Acinetobacter junii B6: A Promising Natural Surfactant for Promoting Angiogenesis


Lipopeptide biosurfactants (LPBs) display unique properties with widespread therapeutic applications. Recently, the wound healing activity of LPBs has received more attention. However, few investigations have focused on the healing mechanisms of these compounds, particularly those that are associated with the angiogenic pathways. Therefore, the current study aimed at investigating the effect of a natural LPB produced by Acinetobacter. junii B6 on the angiogenic potential of human umbilical vein endothelial cells (HUVECs). The proliferation, migration, and three-dimensional tube forming potential of HUVECs were examined after treatment with LPB. By using western blotting, the expression of angiogenic-related genes such as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were also measured. LPB demonstrated no significant proliferative or cytotoxic effect on HUVECs at the concentrations lower than 600 µg/mL. Moreover, LPB at a concentration of 300 µg/mL caused a significant increase in the rates of migration and tube formation of HUVECs. LPB also enhanced the protein expression levels of HIF-1α and VEGF in HUVECs in a dose-dependent manner. The present results suggest that LPB might be considered a potential wound healing agent by modifying some angiogenic factors.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. Ayed HB, Bardaa S, Moalla D, Jridi M, Maalej H, Sahnoun Z, Rebai T, Jacques P, Nasri M, Hmidet NJPB (2015) Wound healing and in vitro antioxidant activities of lipopeptides mixture produced by Bacillus mojavensis A21. PROCESS BIOCHEM 50:1023–1030

    Article  Google Scholar 

  2. Beck LS, Deguzman L, Lee WP, Xu Y, McFatridge LA, Amento EPJGF (1991) TGF-β1 accelerates wound healing: reversal of steroid-impaired healing in rats and rabbits. GROWTH FACTORS 5:295–304

    CAS  Article  Google Scholar 

  3. Behnam B, Rezazadehkermani M, Ahmadzadeh S, Mokhtarzadeh A, Nematollahi-Mahani SN, Pardakhty A (2018) Microniosomes for concurrent doxorubicin and iron oxide nanoparticles loading; preparation, characterization and cytotoxicity studies. Artif Cells Nanomed Biotechnol 46:118–125

    CAS  Article  Google Scholar 

  4. Bradford MMJAb (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    CAS  Article  Google Scholar 

  5. Duarte C, Gudiña EJ, Lima CF, Rodrigues LR (2014) Effects of biosurfactants on the viability and proliferation of human breast cancer cells. AMB express 4:40

    Article  Google Scholar 

  6. Fan L, Li J, Yu Z, Dang X, Wang K (2014) The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration. BioMed research international 2014

  7. Griffith CK, Miller C, Sainson RC, Calvert JW, Jeon NL, Hughes CC, George SC (2005) Diffusion limits of an in vitro thick prevascularized tissue. Tissue Eng 11:257–266

    CAS  Article  Google Scholar 

  8. Gupta S, Raghuwanshi N, Varshney R, Banat IM, Srivastava AK, Pruthi PA, Pruthi VJB, Pharmacotherapy (2017) Accelerated in vivo wound healing evaluation of microbial glycolipid containing ointment as a transdermal substitute. BIOMED PHARMACOTHER 94:1186–1196

    CAS  Article  Google Scholar 

  9. Hemlata B, Selvin J, Tukaram K (2015) Optimization of iron chelating biosurfactant production by Stenotrophomonas maltophilia NBS-11. Biocatal. Agric Biotechnol 4:135–143

    Article  Google Scholar 

  10. Li J, Zhang YP, Kirsner RS (2003) Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. MICROSC RES TECHNIQ 60:107–114

    CAS  Article  Google Scholar 

  11. Lydon HL, Baccile N, Callaghan B, Marchant R, Mitchell CA, Banat, I.M.J.A.a., chemotherapy, (2017) Adjuvant antibiotic activity of acidic sophorolipids with potential for facilitating wound healing. Antimicrob. Agents Chemother 61:e02547-02516

    CAS  Article  Google Scholar 

  12. McCOLL BK, Stacker SA, Achen MGJA (2004) Molecular regulation of the VEGF family–inducers of angiogenesis and lymphangiogenesis. APMIS 112:463–480

    CAS  Article  Google Scholar 

  13. Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi M, Ghazi-Khansari M, Sharifi A (2015) Deferoxamine preconditioning to restore impaired HIF‐1α‐mediated angiogenic mechanisms in adipose‐derived stem cells from STZ‐induced type 1 diabetic rats. CELL PROLIFERAT 48:532–549

    CAS  Article  Google Scholar 

  14. Miralles Socías A, Valdés E, Cristina S, Sastre-Coll A, Moranta Mesquida D, Asensio Landa AJ, Andrés G-SJ (2005) High affinity binding of β-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: Norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain. Eur J Pharmacol 518:234–242

    Article  Google Scholar 

  15. Mirzamohammadi S, Mehrabani M, Tekiyehmaroof N, Sharifi A (2016a) Protective effect of 17β-estradiol on serum deprivation-induced apoptosis and oxidative stress in bone marrow-derived mesenchymal stem cells. Hum Exp Toxicol 35:312–322

    CAS  Article  Google Scholar 

  16. Mirzamohammadi S, Nematollahi MH, Mehrbani M, Mehrabani M (2016b) Ferulic acid pretreatment could improve prognosis of autologous mesenchymal stromal cell transplantation for diabetic neuropathy. Cytotherapy 18:925–927

    CAS  Article  Google Scholar 

  17. Naughton P, Marchant R, Naughton V, Banat, I.J.J.o.a.m., (2019) Microbial biosurfactants: current trends and applications in agricultural and biomedical industries. J. Appl. Microbiol. 127:12–28

    CAS  Article  Google Scholar 

  18. Ohadi M, Dehghannoudeh G, Forootanfar H, Shakibaie M, Rajaee M (2018) Investigation of the structural, physicochemical properties, and aggregation behavior of lipopeptide biosurfactant produced by Acinetobacter junii B6. Int J Biol Macromol 112:712–719

    CAS  Article  Google Scholar 

  19. Ohadi M, Dehghannoudeh G, Shakibaie M, Banat IM, Pournamdari M, Forootanfar H (2017a) Isolation, characterization, and optimization of biosurfactant production by an oil-degrading Acinetobacter junii B6 isolated from an Iranian oil excavation site. Biocatal Agric Biotechnol 12:1–9

    Article  Google Scholar 

  20. Ohadi M, Forootanfar H, Dehghannoudeh G, Eslaminejad T, Ameri A, Shakibaie M, Adeli-Sardou M (2020) Antimicrobial, anti-biofilm, and anti-proliferative activities of lipopeptide biosurfactant produced by Acinetobacter junii B6. Microb Pathog 138:103806

    CAS  Article  Google Scholar 

  21. Ohadi M, Forootanfar H, Rahimi HR, Jafari E, Shakibaie M, Eslaminejad T, Dehghannoudeh G (2017b) Antioxidant Potential and Wound Healing Activity of Biosurfactant Produced by Acinetobacter junii B6. Curr. Pharm. Biotechnol

  22. Raeiszadeh M, Pardakhty A, Sharififar F, Farsinejad A, Mehrabani M, Hosseini-Nave H, Mehrabani M (2018) Development, physicochemical characterization, and antimicrobial evaluation of niosomal myrtle essential oil. Int J Pharm Sci 13:250

    Google Scholar 

  23. Ruthenborg RJ, Ban J-J, Wazir A, Takeda N, Kim J-w (2014) Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1. Mol Cells 37:637

    Article  Google Scholar 

  24. Semenza GL, Agani F, Booth G, Forsythe J, Iyer N, Jiang B-H, Leung S, Roe R, Wiener C, Yu A (1997) Structural and functional analysis of hypoxia-inducible factor 1. Kidney international 51:553–555

    CAS  Article  Google Scholar 

  25. Stipcevic T, Piljac A, Piljac GJB (2006) Enhanced healing of full-thickness burn wounds using di-rhamnolipid. Burns 32:24–34

    Article  Google Scholar 

  26. Stipcevic T, Piljac T, Isseroff RRJ.J.o.d.s., (2005) Di-rhamnolipid from Pseudomonas aeruginosa displays differential effects on human keratinocyte and fibroblast cultures. J. Dermatol. Sci 40:141–143

    CAS  Article  Google Scholar 

  27. Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing, Journal of Investigative Dermatology Symposium Proceedings. Elsevier, pp. 40–46

  28. Wright JA, Richards T, Srai SK (2014) The role of iron in the skin and cutaneous wound healing. Front Pharmacol 5:156

    Article  Google Scholar 

  29. Yan L, Liu G, Zhao B, Pang B, Wu W, Ai C, Zhao X, Wang X, Jiang C, Shao D (2020) Novel Biomedical Functions of Surfactin A from Bacillus subtilis in Wound Healing Promotion and Scar Inhibition. J. Agric. Food Chem

  30. Zhao R, Liang H, Clarke E, Jackson C, Xue MJIj.o.m.s., (2016) Inflammation in chronic wounds. Int. J. Mol. Sci. 17:2085

    Article  Google Scholar 

  31. Zouari R, Moalla-Rekik D, Sahnoun Z, Rebai T, Ellouze-Chaabouni S, Ghribi-Aydi DJB, Pharmacotherapy (2016) Evaluation of dermal wound healing and in vitro antioxidant efficiency of Bacillus subtilis SPB1 biosurfactant. BIOMED PHARMACOTHER 84:878–891

    CAS  Article  Google Scholar 

Download references


We are indebted to Kerman University of Medical Sciences (KMU) for contributing to the survey (97000960).

Author information




Mehrnaz Mehrabani, Mandana Ohadi and Gholamreza Dehghannoudeh had significant involvement in the design, acquisition, analysis, and interpretation of the data. Hamid Forootanfar, Mohammad Hadi Nematollah, Mojdeh Esmaeili-Tarzi, Ibrahim M. Banat were significantly provided guidance in the overall design and delivery of the research. All authors were involved in revising the content, agree to take accountability for the integrity and accuracy of the work, and have read and approved the final manuscript.

Corresponding authors

Correspondence to Mandana Ohadi or Gholamreza Dehghannoudeh.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mehrabani, M., Esmaeili-Tarzi, M., Forootanfar, H. et al. Lipopeptide Biosurfactant from Acinetobacter junii B6: A Promising Natural Surfactant for Promoting Angiogenesis. Int J Pept Res Ther 27, 1197–1203 (2021).

Download citation


  • Lipopeptide biosurfactant
  • Acinetobacter junii
  • Angiogenesis
  • Wound healing