Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-κB pathway, Klotho, and miR-499a.

Aceclofenac Citronellol Collagen D-Limonene HMGB-1 Nanoemulgel Nanoemulsion Optimization Osteoarthritis Pseudo-ternary phase diagram

Journal

Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061

Informations de publication

Date de publication:
19 Mar 2024
Historique:
accepted: 09 02 2024
medline: 19 3 2024
pubmed: 19 3 2024
entrez: 19 3 2024
Statut: aheadofprint

Résumé

The majority of conventional osteoarthritis (OA) treatments are based on molecular adjustment of certain signaling pathways associated with osteoarthritis (OA) pathogenesis, however there is a significant need to search for more effective and safe treatments. This study centers around formulating Aceclofenac (ACF) with high bioavailability in combination with Citronellol oil and collagen. The optimal concentrations of Citronellol oil/D-Limonene oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were studied for thermophysical stability. Thermodynamically stable formula were analyzed for droplet size, zeta potential, and in-vitro permeation. Then, collagen based nanoemulsion were prepared to capitalize on its efficacy in reducing osteoarthritis side effects and characterized for nano size properties. Formulae F10 and F10C were chosen as optimum nanosize formula. Hense, they were prepared and characterized as nanoemulgel dosage form. The nanoemulgel formulae F10NEG1 and F10CNEG1 showed reasonable viscosity and spreadability, with complete drug release after 4 h. These formulae were chosen for further In vivo anti-OA study. Collagen based ACF/citronellol emugel were able to modulate HMGB-1/RAGE/NF-κB pathway, mitigating the production of inflammatory cytokine TNF-α. They were also able to modulate Klotho and miR-499, reducing serum CTXII and COMP, by reducing the cartilage destruction. Histological investigations validated the efficacy, safety, and superiority of Aceclofenac in combination with Citronellol oil and collagen (F10CNEG1) over solo the treated group (F10NEG1 and blank). Hence, the findings of the current work encourage the use of this promising combined formula in treatment of OA patients.

Identifiants

pubmed: 38502267
doi: 10.1007/s13346-024-01548-3
pii: 10.1007/s13346-024-01548-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Patel PB, Patel TK. Efficacy and safety of aceclofenac in osteoarthritis: A meta-analysis of randomized controlled trials. European journal of rheumatology. 2017;4:11–8.
pubmed: 28293447 pmcid: 5335881 doi: 10.5152/eurjrheum.2017.160080
Iolascon G, Giménez S, Mogyorósi D. A Review of Aceclofenac: Analgesic and Anti-Inflammatory Effects on Musculoskeletal Disorders. J Pain Res. 2021;14:3651–63.
pubmed: 34876850 pmcid: 8643213 doi: 10.2147/JPR.S326101
Melo M, Guimarães A, Santana M, Siqueira R, Lima A, Dias A, Santos M, Onofre A, Quintans J, Sousa D, Almeida JR, Estevam C, Araujo B, Quintans-Júnior L. Anti-inflammatory and redox-protective activities of citronellal. Biol Res. 2011;44:363–8.
pubmed: 22446600 doi: 10.4067/S0716-97602011000400008
Santos PL, Matos JPSCF, Picot L, Almeida JRGS, Quintans JSS, Quintans-Júnior LJ. Citronellol, a monoterpene alcohol with promising pharmacological activities - A systematic review. Food Chem Toxicol. 2019;123:459–69.
pubmed: 30453001 doi: 10.1016/j.fct.2018.11.030
Noh K, Shin BS, Kwon KI, Yun HY, Kim E, Jeong TC, Kang W. Absolute bioavailability and metabolism of aceclofenac in rats. Arch Pharmacal Res. 2015;38:68–72.
doi: 10.1007/s12272-014-0350-4
Shaik N, Toleti M, Kanaru D, Latha K. Solubility Enhancement of Aceclofenac by Solid Dispersion. American Journal of PharmTech Research. 2018;8:107–30.
doi: 10.46624/ajptr.2018.v8.i3.010
Dhule KD, Nandgude TD. Lipid nano-system based topical drug delivery for management of rheumatoid arthritis: an overview. Adv Pharm Bull. 2023;13:663–77.
pubmed: 38022817 pmcid: 10676558 doi: 10.34172/apb.2023.075
Yong Wang X-PZaJ-WR. Transdermal Drug Delivery System of Aceclofenac for Rheumatoid Arthritis and the Effect of Permeation Enhancers: In vitro and in vivo Characterization. Int J Pharmacol. 2015;11:456–62.
doi: 10.3923/ijp.2015.456.462
Sudip Das KSG. A Comprehensive Review on Natural Products as Chemical Penetration Enhancer. Journal of Drug Delivery and Therapeutics. 2021;11:176–87.
doi: 10.22270/jddt.v11i5-S.5077
Fan L, Huang J, Ma S. Recent advances in delivery of transdermal nutrients: A review. Exp Dermatol. 2024;33: e14966.
pubmed: 37897113 doi: 10.1111/exd.14966
Tang Q, Xu F, Wei X, Gu J, Qiao P, Zhu X, Yin S, Ouyang D, Dong J, Yao J. Investigation of β-caryophyllene as terpene penetration enhancer: Role of stratum corneum retention. Eur J Pharm Sci. 2023;183: 106401.
pubmed: 36750147 doi: 10.1016/j.ejps.2023.106401
Schafer N, Balwierz R, Biernat P, Ochędzan-Siodłak W, Lipok J. Natural ingredients of transdermal drug delivery systems as permeation enhancers of active substances through the stratum corneum. Mol Pharmaceutics. 2023;20:3278–97.
doi: 10.1021/acs.molpharmaceut.3c00126
Gómez-Favela MA, Santos-Ballardo DU, Bergés-Tiznado ME, Ambriz-Pérez DL. Nanoformulations applied to the delivery of terpenes. Phytochemical Nanodelivery Systems as Potential Biopharmaceuticals: Elsevier; 2023. p. 221–56.
Lee MS, Bui HTD, Kim SJ, Lee JB, Yoo HS. Liposome-assisted penetration and antiaging effects of collagen in a 3D skin model. J Cosmet Dermatol. 2024;23:236–43.
pubmed: 37415450 doi: 10.1111/jocd.15912
Mobasheri A, Mahmoudian A, Kalvaityte U, Uzieliene I, Larder CE, Iskandar MM, Kubow S, Hamdan PC, de Almeida CS, Favazzo LJ, van Loon LJC, Emans PJ, Plapler PG, Zuscik MJ. A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis? Curr Rheumatol Rep. 2021;23:1–15.
doi: 10.1007/s11926-021-01042-6
Wang L, Chen X, Wang S, Ma J, Yang X, Chen H, Xiao J. Ferrous/ferric ions crosslinked type II collagen multifunctional hydrogel for advanced osteoarthritis treatment. Adv Healthc Mater. 2024;13:2302833–41.
doi: 10.1002/adhm.202302833
Wang H. A Review of the Effects of Collagen Treatment in Clinical Studies. Polymers. 2021;13:3868–88.
pubmed: 34833168 pmcid: 8620403 doi: 10.3390/polym13223868
García-Coronado JM, Martínez-Olvera L, Elizondo-Omaña RE, Acosta-Olivo CA, Vilchez-Cavazos F, Simental-Mendía LE, Simental-Mendía M. Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials. Int Orthop. 2019;43:531–8.
pubmed: 30368550 doi: 10.1007/s00264-018-4211-5
Vishwakarma G, Panwar AS, Dongre N. Emulgel: A novel technique for transdermal drug delivery. Research Journal of Topical and Cosmetic Sciences. 2023;14:20–8.
doi: 10.52711/2321-5844.2023.00005
Das S, Solra M, Rana S. Emulsion Gel: a Dual Drug Delivery Platform for Osteoarthritis Treatment. Regenerative Engineering and Translational Medicine. 2023;9:279–94.
doi: 10.1007/s40883-022-00282-x
Hussain A, Samad A, Singh SK, Ahsan MN, Haque MW, Faruk A, Ahmed FJ. Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation. Drug Deliv. 2016;23:642–7.
pubmed: 25013957 doi: 10.3109/10717544.2014.933284
Mohamed JMM, Nasreen A, Mohaini A, Ahmad M, El-Sherbiny M, Eldesoqui MB, Dawood AF, AlMadani M, Ibrahim AM, El-Mansi AA. Optimization of capsaicin microemulgel: a comprehensive in vitro evaluation and pseudo ternary diagram. Chemical Papers; 2024. p. 1–10.
Wang Z, Pal R. Enlargement of nanoemulsion region in pseudo-ternary mixing diagrams for a drug delivery system. J Surfactants Deterg. 2014;17:49–58.
doi: 10.1007/s11743-013-1497-6
Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, Talegaonkar S. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech. 2009;10:69–76.
pubmed: 19148761 pmcid: 2663668 doi: 10.1208/s12249-008-9178-x
Sun H, Liu K, Liu W, Wang W, Guo C, Tang B, Gu J, Zhang J, Li H, Mao X, Zou Q, Zeng H. Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs. Int J Nanomed. 2012;7:5529–43.
doi: 10.2147/IJN.S36071
Solanki S, Dahima R. Formulation and evaluation of aceclofenac mouth-dissolving tablet. Journal of advanced pharmaceutical technology & research. 2011;2:128–31.
doi: 10.4103/2231-4040.82951
Gul U, Khan MI, Madni A, Sohail MF, Rehman M, Rasul A, Peltonen L. Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride: in vitro and ex vivo evaluation. Drug Deliv. 2022;29:600–12.
pubmed: 35174738 pmcid: 8856056 doi: 10.1080/10717544.2022.2039805
Shaji J, Shah A. Development and characterization of tenoxicam encapsulated niosomes for enhanced transdermal delivery. International journal of pharmaceutical scinces and research. 2016;7:307–15.
Salim N, Basri M, Rahman MB, Abdullah DK, Basri H. Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for enhanced topical delivery of ibuprofen. Int J Nanomed. 2012;7:4739–47.
Qi P, Zhou Y, Wang D, He Z, Li Z. A new collagen solution with high concentration and collagen native structure perfectly preserved. RSC Adv. 2015;5:87180–6.
doi: 10.1039/C5RA14423J
Giongo J, Vaucher R, Ourique A, Steffler MCR, Frizzo C, Hennemman B, Santos R, Lopes L, Rech V, Nishihira V, Raffin R, Gomes P, Steppe M. Development of nanoemulsion containing Pelargonium graveolens oil: Characterization and stability study. Int J Pharm Pharm Sci. 2016;8:271–6.
doi: 10.22159/ijpps.2016v8i12.15108
Rathnam G, Narayanan N, Ilavarasan R. Carbopol-based gels for nasal delivery of progesterone. AAPS PharmSciTech. 2008;9:1078–82.
pubmed: 18850277 pmcid: 2628265 doi: 10.1208/s12249-008-9144-7
Shirsand S, Para M, Nagendrakumar D, Kanani K, Keerthy D. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system. International journal of pharmaceutical investigation. 2012;2:201–7.
pubmed: 23580936 pmcid: 3618636 doi: 10.4103/2230-973X.107002
Goci E, Haloci E, Xhulaj S, Malaj L. Formulation and in vitro evaluation of diclofenac sodium gel. Int J Pharm Pharm Sci. 2014;6:259–61.
Shukr M, Metwally G. Evaluation of Topical Gel Bases Formulated with Various Essential Oils for Antibacterial Activity against Methicillin-Resistant Staphylococcus Aureus. Trop J Pharm Res. 2013;12:877–84.
doi: 10.4314/tjpr.v12i6.3
Chen H, Chang XL, Weng T, Zhao X, Gao Z, Yang Y, Xu H, Yang X. A study of microemulsion systems for transdermal delivery of triptolide. Journal of controlled release : official journal of the Controlled Release Society. 2004;98:427–36.
pubmed: 15312998 doi: 10.1016/j.jconrel.2004.06.001
Shinde U, Pokharkar S, Modani S. Design and evaluation of microemulsion gel system of nadifloxacin. Indian J Pharm Sci. 2012;74:237–47.
pubmed: 23439454 pmcid: 3574534 doi: 10.4103/0250-474X.106066
Council NR, Studies DEL, Research ILA. Animals CUGCUL. Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Academies Press; 2011.
Abdelbari MA, El-Gazar AA, Abdelbary AA, Elshafeey AH, Mosallam S. Brij
pubmed: 37156309 doi: 10.1016/j.ijpharm.2023.123024
Tang X, Zhou Z, Shen B, Yang J, Kang P, Li J, Crook N, Li Q, Min L, Pei F. Serum levels of TNF-α, IL-1β, COMP, and CTX-II in patients with Kashin-Beck disease in Sichuan. China Rheumatology international. 2012;32:3503–9.
pubmed: 22068351 doi: 10.1007/s00296-011-2172-8
Khalil AS, Hellenbrand D, Reichl K, Umhoefer J, Filipp M, Choe J, Hanna A, Murphy WL. A Localized Materials-Based Strategy to Non-Virally Deliver Chondroitinase ABC mRNA Improves Hindlimb Function in a Rat Spinal Cord Injury Model. Adv Healthcare Mater. 2022;11: e2200206.
doi: 10.1002/adhm.202200206
Mahmood T, Yang PC. Western blot: technique, theory, and trouble shooting. N Am J Med Sci. 2012;4:429–34.
pubmed: 23050259 pmcid: 3456489 doi: 10.4103/1947-2714.100998
Abd El-Aal S, AbdElrahman M, Reda A, Afify H, Ragab G, El-Gazar A, Abdelhamid S. Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF. Neurotoxicology. 2022;92:77–90.
pubmed: 35843304 doi: 10.1016/j.neuro.2022.07.005
Gad AM. Study on the influence of caffeic acid against sodium valproate–induced nephrotoxicity in rats. J Biochem Mol Toxicol. 2018;32: e22175.
pubmed: 29968957 doi: 10.1002/jbt.22175
Lu Y, Xi J, Zhang Y, Li C, Chen W, Hu X, Zhang M, Zhang F, Wei H, Li Z, Wang Z. MicroRNA-214-5p protects against myocardial ischemia reperfusion injury through targeting the FAS ligand. Archives of medical science : AMS. 2020;16:1119–29.
pubmed: 32864001 doi: 10.5114/aoms.2019.85405
Jeong DH, Ullah HMA, Goo MJ, Ghim SG, Hong I, Kim AY, Jeon SM, Choi MS, Elfadl A, Chung MJ, Lee E-J, Kim Y, Kim JH, Kim SY, Jeong K-S. Effects of oral glucosamine hydrochloride and mucopolysaccharide protein in a rabbit model of osteoarthritis. Int J Rheum Dis. 2017;21:620–8.
pubmed: 29205898 doi: 10.1111/1756-185X.13239
Altimimi A, Obaid Hossain A, Altimimi A. Immunohistological Study of ER, PR, and Her2/neu Status in Breast Carcinoma. Indian Journal of Public Health Research and Development. 2020;10:968–73.
Chen D. Osteoarthritis: A complicated joint disease requiring extensive studies with multiple approaches. Journal of orthopaedic translation. 2022;32:130.
pubmed: 35591933 pmcid: 9072797 doi: 10.1016/j.jot.2022.02.009
Abou-Raya A, Rizk M, AbdelGhani E, AbdelMegid N. Identification of serum micro-RNAs of early knee osteoarthritis in a cohort of Egyptian patients. Alexandria Journal of Medicine. 2023;59:1–14.
doi: 10.1080/20905068.2022.2140987
El Miedany Y, El Gaafary M, Gadallah N, Mahran S, Fathi N, Abu Zaid MH, Tabra SAH, Hassan W, Elwakil W. Osteoporosis treatment gap in patients at risk of fracture in Egypt: a multi-center, cross-sectional observational study. Arch Osteoporos. 2023;18:58–64.
pubmed: 37127804 doi: 10.1007/s11657-023-01252-8
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323–30.
pubmed: 24553908 doi: 10.1136/annrheumdis-2013-204763
Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019;37(Suppl 120):3–6.
pubmed: 31621562
Raza K, Kumar M, Kumar P, Malik R, Sharma G, Kaur M, Katare OP. Topical delivery of aceclofenac: challenges and promises of novel drug delivery systems. Biomed Res Int. 2014;2014: 406731.
pubmed: 25045671 pmcid: 4086417 doi: 10.1155/2014/406731
Donthi MR, Munnangi SR, Krishna KV, Saha RN, Singhvi G, Dubey SK. Nanoemulgel: a novel nano carrier as a tool for topical drug delivery. Pharmaceutics. 2023;15:164–92.
pubmed: 36678794 pmcid: 9863395 doi: 10.3390/pharmaceutics15010164
Maulvi FA, Dalwadi SJ, Thakkar VT, Soni TG, Gohel MC, Gandhi TR. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technol. 2011;207:47–54.
doi: 10.1016/j.powtec.2010.10.009
Mehanna MM, Abla KK, Elmaradny HA. Tailored Limonene-Based Nanosized Microemulsion: Formulation, Physicochemical Characterization and In Vivo Skin Irritation Assessment. Advanced pharmaceutical bulletin. 2021;11:274–85.
pubmed: 33880349
Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123–7.
pubmed: 28324579 doi: 10.1007/s13205-014-0214-0
Mohyeldin SM, Mehanna MM, Elgindy NA. Superiority of liquid crystalline cubic nanocarriers as hormonal transdermal vehicle: comparative human skin permeation-supported evidence. Expert Opin Drug Deliv. 2016;13:1049–64.
pubmed: 27167758 doi: 10.1080/17425247.2016.1182490
Sis H, Birinci M. Effect of nonionic and ionic surfactants on zeta potential and dispersion properties of carbon black powders. Colloids Surf, A. 2009;341:60–7.
doi: 10.1016/j.colsurfa.2009.03.039
Yati K, Srifiana Y, Putra F. Effect of optimization of Tween 80 and propylene glycol as a surfactant and cosurfactant on the physical properties of aspirin microemulsion. International Journal of Applied Pharmaceutics. 2017;9:127–9.
doi: 10.22159/ijap.2017.v9s1.71_78
Ali HH, Hussein AA. Oral nanoemulsions of candesartan cilexetil: formulation, characterization and in vitro drug release studies. AAPS Open. 2017;3:4.
doi: 10.1186/s41120-017-0016-7
Morteza-Semnani K, Saeedi M, Akbari J, Eghbali M, Babaei A, Hashemi SMH, Nokhodchi A. Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer. Drug Deliv Transl Res. 2022;12:1455–65.
pubmed: 34275091 doi: 10.1007/s13346-021-01025-1
Yan C, Fu D, McClements DJ, Xu P, Zou L, Zhu Y, Cheng C, Liu W. Rheological and microstructural properties of cold-set emulsion gels fabricated from mixed proteins: Whey protein and lactoferrin. Food Res Int. 2019;119:315–24.
pubmed: 30884662 doi: 10.1016/j.foodres.2019.02.012
Khan BA, Ahmad S, Khan MK, Hosny KM, Bukhary DM, Iqbal H, Murshid SS, Halwani AA, Alissa M, Menaa F. Fabrication and Characterizations of Pharmaceutical Emulgel Co-Loaded with Naproxen-Eugenol for Improved Analgesic and Anti-Inflammatory Effects. Gels (Basel, Switzerland). 2022;8:608–25.
pubmed: 36286109
Arora R, Aggarwal G, Sl H, Kaur K. Nanoemulsion based hydrogel for enhanced transdermal delivery of ketoprofen. Adv Pharm. 2014; 1–12.
Sionkowska A, Lewandowska K, Adamiak K. The Influence of UV Light on Rheological Properties of Collagen Extracted from Silver Carp Skin. Materials (Basel, Switzerland). 2020;13:4453–63.
pubmed: 33049939 doi: 10.3390/ma13194453
Li Y, Qiao C, Shi L, Jiang Q, Li T. Viscosity of Collagen Solutions: Influence of Concentration, Temperature, Adsorption, and Role of Intermolecular Interactions. Journal of Macromolecular Science, Part B. 2014;53:893–901.
doi: 10.1080/00222348.2013.852059
Dantas MG, Reis SA, Damasceno CM, Rolim LA, Rolim-Neto PJ, Carvalho FO, Quintans-Junior LJ, Almeida JR. Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol. TheScientificWorldJOURNAL. 2016;2016:1–4.
Palumbo A, Atzeni F, Murdaca G, Gangemi S. The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33. Int J Mol Sci. 2023;24:12143–67.
pubmed: 37569519 pmcid: 10418664 doi: 10.3390/ijms241512143
Lee J, Hong YS, Jeong JH, Yang EJ, Jhun JY, Park MK, Jung YO, Min JK, Kim HY, Park SH, Cho ML. Coenzyme Q10 ameliorates pain and cartilage degradation in a rat model of osteoarthritis by regulating nitric oxide and inflammatory cytokines. PLoS ONE. 2013;8:69362–70.
doi: 10.1371/journal.pone.0069362
Ma H, Qin S, Zhao S. Osteoarthritis is prevented in rats by verbascoside via nuclear factor kappa B (NF-κB) pathway downregulation. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2020;26:e921276–e921271.
pubmed: 32249762 doi: 10.12659/MSM.921276
Jeong JW, Lee HH, Kim J, Choi EO, Hwang-Bo H, Kim HJ, Kim MY, Ahn KI, Kim GY, Lee KW, Kim KY, Kim SG, Hong SH, Park C, Cha HJ, Choi YH. Mori Folium water extract alleviates articular cartilage damages and inflammatory responses in monosodium iodoacetate-induced osteoarthritis rats. Mol Med Rep. 2017;16:3841–8.
pubmed: 29067461 pmcid: 5646961 doi: 10.3892/mmr.2017.7075
Choudhary D, Kothari P, Tripathi AK, Singh S, Adhikary S, Ahmad N, Kumar S, Dev K, Mishra VK, Shukla S, Maurya R, Mishra PR, Trivedi R. Spinacia oleracea extract attenuates disease progression and sub-chondral bone changes in monosodium iodoacetate-induced osteoarthritis in rats. BMC Complement Altern Med. 2018;18:69–85.
pubmed: 29463254 pmcid: 5819303 doi: 10.1186/s12906-018-2117-9
Bai B, Li Y. Combined detection of serum CTX-II and COMP concentrations in osteoarthritis model rabbits: an effective technique for early diagnosis and estimation of disease severity. J Orthop Surg Res. 2016;11:149–56.
pubmed: 27876074 pmcid: 5120436 doi: 10.1186/s13018-016-0483-x
Hu Z, Xiao M, Cai H, Li W, Fang W, Long X. Glycyrrhizin regulates rat TMJOA progression by inhibiting the HMGB1-RAGE/TLR4-NF-κB/AKT pathway. J Cell Mol Med. 2022;26:925–36.
pubmed: 34953035 doi: 10.1111/jcmm.17149
Piras S, Furfaro AL, Domenicotti C, Traverso N, Marinari UM, Pronzato MA, Nitti M. RAGE Expression and ROS Generation in Neurons: Differentiation versus Damage. Oxid Med Cell Longev. 2016;2016:9348651.
pubmed: 27313835 pmcid: 4897723 doi: 10.1155/2016/9348651
Gu Y, Ren K, Jiang C, Wang L, Yao Q. Regulation of cartilage damage caused by lack of Klotho with thioredoxin/peroxiredoxin (Trx/Prx) system and succedent NLRP3 activation in osteoarthritis mice. American journal of translational research. 2019;11:7338–50.
pubmed: 31934282 pmcid: 6943451
Wu J, Zou M, Ping A, Deng Z, Cai L. MicroRNA-449a upregulation promotes chondrocyte extracellular matrix degradation in osteoarthritis. Biomedicine Pharmacother. 2018;105:940–6.
doi: 10.1016/j.biopha.2018.06.074
Baek D, Lee KM, Park KW, Suh JW, Choi SM, Park KH, Lee JW, Kim SH. Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models. Molecular therapy Nucleic acids. 2018;13:322–33.
pubmed: 30326428 pmcid: 6197768 doi: 10.1016/j.omtn.2018.09.015
Brito RG, Guimarães AG, Quintans JS, Santos MR, De Sousa DP, Badaue-Passos D Jr, de Lucca W, Jr., Brito FA, Barreto EO, Oliveira AP, Quintans LJ, Jr. Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents. J Nat Med. 2012;66:637–44.
pubmed: 22350215 doi: 10.1007/s11418-012-0632-4
Jayaganesh R, Pugalendhi P, Murali R. Effect of citronellol on NF-kB inflammatory signaling molecules in chemical carcinogen-induced mammary cancer in the rat model. J Biochem Mol Toxicol. 2020;34:22441–9.
doi: 10.1002/jbt.22441
Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K. Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003;74:222–35.
pubmed: 12966366 doi: 10.1016/S0009-9236(03)00167-X
Vrouwe JPM, Burggraaf J, Kloppenburg M, Stuurman FE. Challenges and opportunities of pharmacological interventions for osteoarthritis: A review of current clinical trials and developments. Osteoarthritis and cartilage open. 2021;3: 100212.
pubmed: 36474768 pmcid: 9718290 doi: 10.1016/j.ocarto.2021.100212
Negi S, Tandel N, Sharma P, Kumar R, Tyagi RK. Aceclofenac and methotrexate combination therapy could influence Th1/Th17 axis to modulate rheumatoid-arthritis-induced inflammation. Drug Discov Today. 2023;28: 103671.
pubmed: 37330038 doi: 10.1016/j.drudis.2023.103671
Martel-Pelletier J, Cloutier J-M, Pelletier J-P. Effects of Aceclofenac and Diclofenac on Synovial Inflammatory Factors in Human Osteoarthritis. Clin Drug Investig. 1997;14:226–32.
doi: 10.2165/00044011-199714030-00011
Lu J, Zhang T, Sun H, Wang S, Liu M. Protective effects of dioscin against cartilage destruction in a monosodium iodoacetate (MIA)-indcued osteoarthritis rat model. Biomed Pharmacother. 2018;108:1029–38.
pubmed: 30372803 doi: 10.1016/j.biopha.2018.09.075

Auteurs

Reem Abd Elhameed Aldeeb (RAE)

Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt. reem.eldeeb@must.edu.eg.

Sherihan Salaheldin Abdelhamid Ibrahim (SSA)

Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University, Alexandria, Egypt.

Islam Ahmed Khalil (IA)

Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.

Ghada Mohamed Ragab (GM)

Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.

Amira Ahmed El-Gazar (AA)

Department of Pharmacology and Toxicology, Faculty of Pharmacy, 6th of October University, 12585, Egypt.

Amal Anwar Taha (AA)

Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.

Doaa Hussien Hassan (DH)

Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.

Asmaa Ahmed Gomaa (AA)

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, 12585, Egypt.

Mona Kamal Younis (MK)

Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.

Classifications MeSH