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Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund’s complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines

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Abstract

Geranium essential oil (GEO) has been widely used in aromatherapy and traditional medicines. Nanoencapsulation, a novel technique has emerged to overcome the environmental degradation and less oral bioavailability of essential oils. This work was undertaken to encapsulate geranium essential oil in chitosan nanoparticles (GEO-CNPs) by ionic gelation technique and to explore anti-arthritic and anti-inflammatory potential in FCA-induced arthritic model in rats. The GEO was characterized by gas chromatography flame ionization detector (GCFID) and the nanosuspension was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-rays diffraction (XRD). The Wistar albino rats (n = 32) were separated into four groups; Group 1 and 2 were considered as normal and arthritic controls. Group 3 was positive control that received oral celecoxib for 21 days while Group 4 was treated with oral GEO-CNPs after the induction of arthritis. Hind paw ankle joints diameters were weekly measured throughout the study and significant decrease (5.5 ± 0.5 mm) was observed in GEO-CNPs treatment group in comparison to arthritic group (9.17 ± 0.52 mm). Blood samples were drawn at end for evaluation of hematological, biochemical and inflammatory biomarkers. A significant upregulation of red blood cells and hemoglobin while downregulation of white blood cells, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and rheumatoid factor (RF) was observed. Ankles were transected for the histopathological and radiographic examination after animals were sacrificed which confirmed the alleviation of necrosis along cellular infiltration. It was concluded that GEO-CNPs were found to possess excellent therapeutic potential and promising candidates to reduce FCA-induced arthritis.

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Data availability

The datasets generated and analyzed throughout the study are available on request.

References:

  • Abelan US, de Oliveira AC, Cacoci ÉSP, Martins TEA, Giacon VM, Velasco MVR, Lima CRRC (2022) Potential use of essential oils in cosmetic and dermatological hair products: a review. J Cosmet Dermatol 21(4):1407–1418

    PubMed  Google Scholar 

  • Akhtar B, Muhammad F, Aslam B, Saleemi MK, Sharif A (2020) Biodegradable nanoparticle based transdermal patches for gentamicin delivery: formulation, characterization and pharmacokinetics in rabbits. J Drug Deliv Sci Technol 57:101680

    CAS  Google Scholar 

  • Al-Jumaili A, Bazaka K, Jacob MV (2017) Retention of antibacterial activity in geranium plasma polymer thin films. Nanomaterials (basel) 7(9):270

    PubMed  Google Scholar 

  • Androutsopoulou C, Christopoulou SD, Hahalis P, Kotsalou C, Lamari FN, Vantarakis A (2021) Evaluation of essential oils and extracts of rose geranium and rose petals as natural preservatives in terms of toxicity, antimicrobial, and antiviral activity. Pathogens 10(4):494

    CAS  PubMed  PubMed Central  Google Scholar 

  • Anwar M, Muhammad F, Akhtar B, Rehman S, Saleemi MK (2020) Nephroprotective effects of curcumin loaded chitosan nanoparticles in cypermethrin induced renal toxicity in rabbits. Environ Sci Pollut Res 27:1–9

    Google Scholar 

  • Barkat M, Laib I (2012) Antioxidant activity of the essential oil from the flowers of Lavandula stoechas. J Pharmacogn Phytother 4(7):96–101

    CAS  Google Scholar 

  • Boukhatem MN, Sudha T, Darwish NHE, Nada HG, Mousa SA (2022) Rose-scented geranium essential oil from Algeria (Pelargonium graveolens L’Hérit.): assessment of antioxidant, anti-inflammatory and anticancer properties against different metastatic cancer cell lines. Ann Pharm Fr 80(3):383–396

    CAS  PubMed  Google Scholar 

  • Cardia GFE, Silva-comar FM, da Rocha EMT, Silva-Filho SE, Zagotto M, Uchida NS, Amaral V, Bersani-Amado CA, Cuman RKN (2021) Pharmacological, medicinal and toxicological properties of lavender essential oil: a review. Res Soc Dev 10(5):e23310514933

    Google Scholar 

  • Chen W, Viljoen AM (2010) Geraniol—a review of a commercially important fragrance material. S Afr J Bot 76(4):643–651

    CAS  Google Scholar 

  • Cimino C, Maurel OM, Musumeci T, Bonaccorso A, Drago F, Souto EMB, Pignatello R, Carbone C (2021) Essential oils: pharmaceutical applications and encapsulation strategies into lipid-based delivery systems. Pharmaceutics 13(3):327

    CAS  PubMed  PubMed Central  Google Scholar 

  • Das S, Singh VK, Dwivedy AK, Chaudhari AK, Upadhyay N, Singh P, Sharma S, Dubey NK (2019) Encapsulation in chitosan-based nanomatrix as an efficient green technology to boost the antimicrobial, antioxidant and in situ efficacy of Coriandrum sativum essential oil. Int J Biol Macromol 133:294–305

    CAS  PubMed  Google Scholar 

  • De Cassia da Silveira e Sa R, Andrade LN, de Sousa DP (2013) A review on anti-inflammatory activity of monoterpenes. Molecules 18(1):1227–1254

    PubMed  PubMed Central  Google Scholar 

  • Dzamic AM, Sokovic MD, Mihailo S, Grujic S, Mileski KS, Marin PD (2014) Chemical composition, antifungal and antioxidant activity of Pelargonium graveolens essential oil. J Appl Pharm Sci 4(03):001–005

    Google Scholar 

  • Ekambaram S, Perumal SS, Subramanian V (2010) Evaluation of antiarthritic activity of Strychnos potatorum Linn seeds in Freund’s adjuvant induced arthritic rat model. BMC Complement Altern Med 10:1–9

    Google Scholar 

  • Esmaeili A, Asgari A (2015) In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles. Int J Biol Macromol 81:283–290

    CAS  PubMed  Google Scholar 

  • Garcia LGS, da Rocha MG, Lima LR, Cunha AP, de Oliveira JS, de Andrade ARC, Ricardo NMPS, Pereira-Neto WA, Sidrim JJC, Rocha MFG, Vieira RS, Brilhante RSN (2020) Essential oils encapsulated in chitosan microparticles against Candida albicans biofilms. Int J Biol Macromol 166:621–632

    PubMed  Google Scholar 

  • Garg U, Chauhan S, Nagaich U, Jain N (2019) Current advances in chitosan nanoparticles based drug delivery and targeting. Adv Pharm Bull 9(2):195–204

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gasparyan AY, Stavropoulos-Kalinoglou A, Mikhailidis DP, Douglas KM, Kitas GD (2011) Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications. Rheumatol Int 31(2):153–164

    CAS  PubMed  Google Scholar 

  • Hadidi M, Pouramin S, Adinepour F, Haghani S, Jafari SM (2020) Chitosan nanoparticles loaded with clove essential oil: Characterization, antioxidant and antibacterial activities. Carbohydr Polym 236:116075

    CAS  PubMed  Google Scholar 

  • Hasheminejad N, Khodaiyan F, Safari M (2019) Improving the antifungal activity of clove essential oil encapsulated by chitosan nanoparticles. Food Chem 275:113–122

    CAS  PubMed  Google Scholar 

  • Hosseini SF, Zandi M, Rezaei M, Farahmandghavi F (2013) Two-step method for encapsulation of oregano essential oil in chitosan nanoparticles: preparation, characterization and in vitro release study. Carbohydr Polym 95(1):50–56

    CAS  PubMed  Google Scholar 

  • Hu J, Liu S, Deng W (2020) Dual responsive linalool capsules with high loading ratio for excellent antioxidant and antibacterial efficiency. Colloids Surf B Biointerfaces 190:110978

    CAS  PubMed  Google Scholar 

  • Hwang J, Rodgers K, Oliver JC, Schluep T (2008) Alpha-methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy. Int J Nanomed 3(3):359–371

    CAS  Google Scholar 

  • Katerji M, Filippova M, Duerksen-Hughes P (2019) Approaches and methods to measure oxidative stress in clinical samples: research applications in the cancer field. Oxid Med Cell Longev 2019:1–29

    Google Scholar 

  • Keawchaoon L, Yoksan R (2011) Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles. Colloids Surf B Biointerfaces 84(1):163–171

    CAS  PubMed  Google Scholar 

  • Kirkova M, Alexandova A, Kesiova M, Tsvetanova E, Georgieva A, Todorov S (2007) Potential antioxidant activity of celecoxib and amtolmetin guacil: in vitro studies. Auton Autacoid Pharmacol 27:13–18

    CAS  PubMed  Google Scholar 

  • Krasselt M, Baerwald C (2019) Celecoxib for the treatment of musculoskeletal arthritis. Expert Opin Pharmacother 20(14):1689–1702

    CAS  PubMed  Google Scholar 

  • Kumar V, Leekha A, Kaul A, Mishra AK, Verma AK (2020) Role of folate-conjugated glycol-chitosan nanoparticles in modulating the activated macrophages to ameliorate inflammatory arthritis: in vitro and in vivo activities. Drug Deliv Transl Res 10:1057–1075

    CAS  PubMed  Google Scholar 

  • Lammari N, Louaer O, Meniai AH, Elaissari A (2020) Encapsulation of essential oils via nanoprecipitation process: overview, progress. Challenges Prospect Pharm 12(5):431

    CAS  Google Scholar 

  • Ma Y, Hong FF, Yang SL (2021) Role of prostaglandins in rheumatoid arthritis. Clin Exp Rheumatol 39(1):162–172

    CAS  PubMed  Google Scholar 

  • Manan M, Saleem U, Akash MSH, Qasim M, Hayat M, Raza Z, Ahmad B (2020) Antiarthritic potential of comprehensively standardized extract of Alternanthera bettzickiana: invitro and in vivo studies. ACS Omega 5(31):19478–19496

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matshetshe KI, Parani S, Manki SM, Oluwafemi OS (2018) Preparation, characterization and in vitro release study of β-cyclodextrin/chitosan nanoparticles loaded Cinnamomum zeylanicum essential oil. Int J Biol Macromol 118(Pt A):676–682

    CAS  PubMed  Google Scholar 

  • Mohammadi A, Hosseini SM, Hashemi M (2020) Emerging chitosan nanoparticles loading-system boosted the antibacterial activity of Cinnamomum zeylanicum essential oil. Ind Crops Prod 155:112824

    CAS  Google Scholar 

  • Mohammed MA, Syeda JTM, Wasan KM, Wasan EK (2017) An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics 9(4):53

    PubMed  PubMed Central  Google Scholar 

  • Munekata PES, Pateiro M, Rodríguez-Lázaro D, Domínguez R, Zhong J, Lorenzo JM (2020) The role of essential oils against pathogenic Escherichia coli in food products. Microorganisms 8(6):924

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nemeth E, Ganz T (2014) Anemia of inflammation. Hematol Oncol Clin North Am 28(4):671–681

    PubMed  PubMed Central  Google Scholar 

  • Noriega P (2020) Terpenes in essential oils: bioactivity and applications. Terpenes and terpenoids. IntechOpen, London, pp 1–13

    Google Scholar 

  • Pereira I, Severino P, Santos AC, Silva AM, Souto EB (2018) Linalool bioactive properties and potential applicability in drug delivery systems. Colloids Surf B Biointerfaces 171:566–578

    CAS  PubMed  Google Scholar 

  • Perri F, Coricello A, Adams JD (2020) Monoterpenoids: the next frontier in the treatment of chronic pain? J MDPI 3(2):195–214

    CAS  Google Scholar 

  • Pirmardvand CS, Varshosaz J, Taymouri S (2018) Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis and treatment. Artif Cells Nanomed Biotechnol 46(sup2):502–551

    Google Scholar 

  • Pradhan A, Bagchi A, De S, Mitra S, Mukherjee S, Ghosh P, Ghosh A, Chatterjee M (2019) Role of redox imbalance and cytokines in mediating oxidative damage and disease progression of patients with rheumatoid arthritis. Free Radic Res 53(7):768–779

    CAS  PubMed  Google Scholar 

  • Rajkumar V, Gunasekaran C, Paul CA, Dharmaraj J (2020) Development of encapsulated peppermint essential oil in chitosan nanoparticles: characterization and biological efficacy against stored-grain pest control. Pestic Biochem Physiol 170:104679

    CAS  PubMed  Google Scholar 

  • Rawat C, Kukal S, Dahiya UR, Kukreti R (2019) Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management. J Neuroinflammation 16(1):197

    PubMed  PubMed Central  Google Scholar 

  • Russo E, Gaglianone N, Baldassari S, Parodi B, Cafaggi S, Zibana C, Donalisio M, Cagno V, Lembo D, Caviglioli G (2014) Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles. Colloids Surfaces B Biointerfaces 118:117–125

    CAS  PubMed  Google Scholar 

  • Saleem MU, Muhammad F, Sharif A, Arshad MI, Akhtar K, Javed Y, Akhtar B (2022) Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund’s complete adjuvant-induced arthritic rats. Inflammopharmacology 3:1079–1091

    Google Scholar 

  • Senthil Kumar KJ, Gokila Vani M, Wang CS, Chen CC, Chen YC, Lu LP, Huang CH, Lai CS, Wang SY (2020) Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain. Epithelial Cells Plants (basel) 9(6):770

    PubMed  Google Scholar 

  • Shetta A, Kegere J, Mamdouh W (2019) Comparative study of encapsulated peppermint and green tea essential oils in chitosan nanoparticles: encapsulation, thermal stability, in-vitro release, antioxidant and antibacterial activities. Int J Biol Macromol 126:731–742

    CAS  PubMed  Google Scholar 

  • Silva J, Abebe W, Sousa SM, Duarte VG, Machado MI, Matos FJ (2023) Analgesic and anti-inflammatory effects of essential oils of Eucalyptus. J Ethnopharmacol 89(2–3):277–283

    Google Scholar 

  • Sotelo-Boyás M, Correa-Pacheco Z, Bautista-Baños S, Gómez GYY (2017) Release study and inhibitory activity of thyme essential oil-loaded chitosan nanoparticles and nanocapsules against foodborne bacteria. Int J Biol Macromol 103:409–414

    PubMed  Google Scholar 

  • Tahir A, Ahmad RA, Imran M, Ahmad MH, Khan MK, Muhammad N, Nisa MU, Nadeem MT, Yasmin A, Tahir HS, Zulifqar A, Javed M (2021) Recent approaches for utilization of food components as nano-encapsulation: a review. Int J Food Prop 24(1):1074–1096

    CAS  Google Scholar 

  • Van Delft MAM, Huizinga TWJ (2020) An overview of autoantibodies in rheumatoid arthritis. J Autoimmun 110:102392

    PubMed  Google Scholar 

  • Wu J, Shu Q, Niu Y, Jiao Y, Chen Q (2018) Preparation, characterization, and antibacterial effects of chitosan nanoparticles embedded with essential oils synthesized in an ionic liquid containing system. J Agric Food Chem 66(27):7006–7014

    CAS  PubMed  Google Scholar 

  • Zhu M, Yuan K, Lu Q, Zhu Q, Zhang S, Li X, Zhao L, Wang H, Luo G, Wang T, Huang G, Xu A (2019) Emodin ameliorates rheumatoid arthritis by promoting neutrophil apoptosis and inhibiting neutrophil extracellular trap formation. Mol Immunol 112:188–197

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan

    Rana Dawood Naseer

  2. Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan

    Faqir Muhammad, Bilal Aslam & Muhammad Naeem Faisal

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  1. Rana Dawood Naseer
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  2. Faqir Muhammad
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  3. Bilal Aslam
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  4. Muhammad Naeem Faisal
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Contributions

All authors contributed as FM assisted in study conception and design. BA contributed in material preparation and data collection. The data analysis was performed by RDN and MNF. The manuscript drafting was carried out by RDN and FM. All authors suggested improvement in final manuscript by commenting. All authors approved and read the manuscript.

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Correspondence to Faqir Muhammad.

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Naseer, R.D., Muhammad, F., Aslam, B. et al. Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund’s complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines. Inflammopharmacol 31, 1893–1912 (2023). https://doi.org/10.1007/s10787-023-01233-w

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