Anti-Inflammatory Therapeutics: Conventional Concepts and Future with
Nanotechnology

Manju      Bernela; Priya      Kaushal; Naveen      Verma; Rajesh      Thakur; Munish      Ahuja; Pawan      Kaur
Abstract

Anti-inflammatory therapies currently in use mainly include steroidal and non-steroidal drugs. Contrary to their side effects, the steroid hormones glucocorticoids, which are synthetic versions of natural cortisol, are nevertheless often employed to treat a variety of inflammatory disorders. Other drug class of choice is non-steroidal drugs which mainly target COX-2 and hence the synthesis of prostaglandins, particularly PGE2. To cure both the short-term effects of chronic inflammatory disorders and the long-term symptoms of acute inflammation, pharmaceutical chemists are in continuous search for more potent and less toxic agents. Apart from these two drug classes, phytochemicals are gaining the attention of researchers as source of alternative antiinflammatory agents. However, every drug class has its own advantages or disadvantages thus requiring intervention of newer approaches. Currently, drugs used for anti-inflammatory therapies are costly with low efficacy, high health risk, and socio-economic impact due to the concern issue of their toxicity. Recently, nano-drug delivery system has been experiencing main interest as a new approach for targeting therapeutic agents to the target sites in a controlled, sustained manner and has various advantages as compared to the conventional drug delivery system like, increased solubility, bioavailability, improved pharmacokinetic profile of drugs, surface area and rate of dissolution and additionally, overcomes the problems related to hydrophobicity, toxicity. Present review summarized the intervention of nanotechnology to overcome the limitations/ risk associated with current anti-inflammatory drugs of different classes.
Graphical Abstract

[1]
Placha D, Jampilek J. Chronic inflammatory diseases, anti-inflammatory agents and their delivery nanosystems. Pharmaceutics  2021; 13(1): 64.
 [http://dx.doi.org/10.3390/pharmaceutics13010064] [PMID: 33419176]

[2]
Oyinloye B, Adenowo A, Kappo A. Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases. Pharmaceuticals (Basel)  2015; 8(2): 151-75.
 [http://dx.doi.org/10.3390/ph8020151] [PMID: 25850012]

[3]
Han VX, Patel S, Jones HF, et al. Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: A systematic review. Transl Psychiatry  2021; 11(1): 71.
 [http://dx.doi.org/10.1038/s41398-021-01198-w] [PMID: 33479207]

[4]
Koushki K, Shahbaz SK, Mashayekhi K, et al. Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-like receptor pathways. Clin Rev Allergy Immunol  2021; 60(2): 175-99.
 [http://dx.doi.org/10.1007/s12016-020-08791-9] [PMID: 32378144]

[5]
Doña I, Jurado-Escobar R, Perkins JR, et al. Eicosanoid mediator profiles in different phenotypes of nonsteroidal anti-inflammatory drug-induced urticaria. Allergy  2019; 74(6): 1135-44.
 [PMID: 30667070]

[6]
B Sánchez A. Calpena AC, Soriano JL, Gálvez P, Clares B. Anti-inflammatory nanomedicines: What does the future hold? Nanomedicine (Lond)  2020; 15(14): 1357-60.
 [http://dx.doi.org/10.2217/nnm-2020-0064] [PMID: 32515267]

[7]
Machado GC, Abdel-Shaheed C, Underwood M, Day RO. Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain. BMJ  2021; 372.

[8]
Patil KR, Mahajan UB, Unger BS, et al. Animal models of inflammation for screening of anti-inflammatory drugs: Implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci  2019; 20(18): 4367.
 [http://dx.doi.org/10.3390/ijms20184367] [PMID: 31491986]

[9]
Bamrungsap S, Zhao Z, Chen T, et al. Nanotechnology in therapeutics: A focus on nanoparticles as a drug delivery system. Nanomedicine (Lond)  2012; 7(8): 1253-71.
 [http://dx.doi.org/10.2217/nnm.12.87] [PMID: 22931450]

[10]
Singh D. Application of novel drug delivery system in enhancing the therapeutic potential of phytoconstituents. Asian J Pharm  2015; 9(4): S1-S12.

[11]
Pathak Y, Thassu D, Deleers M. Pharmaceutical applications of nanoparticulate drug-delivery systems Nanopart Drug Deliv Syst  2007; 185-212.

[12]
Rizvi SAA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J  2018; 26(1): 64-70.
 [http://dx.doi.org/10.1016/j.jsps.2017.10.012] [PMID: 29379334]

[13]
Thassu D, Pathak Y, Deleers M. Nanoparticulate drug-delivery
                    systems: An overview. CRC Press, Boca Raton, 2007.
 [http://dx.doi.org/10.1201/9781420008449.ch1]

[14]
Bhatia S. Natural polymer drug delivery systems: Nanoparticles, plants, and algae. Springer 2016.

[15]
Güven E. Nanotechnology-based drug delivery systems in orthopedics. Eklem Hastalik Cerrahisi  2021; 32(1): 267-73.
 [http://dx.doi.org/10.5606/ehc.2021.80360] [PMID: 33463450]

[16]
Aminu N, Bello I, Umar NM, Tanko N, Aminu A, Audu MM. The influence of nanoparticulate drug delivery systems in drug therapy. J Drug Deliv Sci Technol  2020; 60: 101961.
 [http://dx.doi.org/10.1016/j.jddst.2020.101961]

[17]
Kumar A, Zhou L, Zhi K, et al. Challenges in biomaterial-based drug delivery approach for the treatment of neurodegenerative diseases: Opportunities for extracellular vesicles. Int J Mol Sci  2020; 22(1): 138.
 [http://dx.doi.org/10.3390/ijms22010138] [PMID: 33375558]

[18]
Penta S, Ed. Advances in structure and activity relationship of coumarin derivatives. Academic Press 2015.

[19]
Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med  2019; 25(12): 1822-32.
 [http://dx.doi.org/10.1038/s41591-019-0675-0] [PMID: 31806905]

[20]
Zhao H, Wu L, Yan G, et al. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct Target Ther  2021; 6(1): 263.
 [http://dx.doi.org/10.1038/s41392-021-00658-5] [PMID: 34248142]

[21]
Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: A review. Vet World  2018; 11(5): 627-35.
 [http://dx.doi.org/10.14202/vetworld.2018.627-635] [PMID: 29915501]

[22]
Lordan R, Tsoupras A, Zabetakis I. Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents. Blood Rev  2021; 45: 100694.
 [http://dx.doi.org/10.1016/j.blre.2020.100694] [PMID: 32340775]

[23]
Jain P, Pandey R, Shukla SS. Inflammation: Natural resources and its applications. Springer India 2015.

[24]
Kennedy BK, Berger SL, Brunet A, et al. Geroscience: Linking aging to chronic disease. Cell  2014; 159(4): 709-13.
 [http://dx.doi.org/10.1016/j.cell.2014.10.039] [PMID: 25417146]

[25]
Gallo J, Raska M, Kriegova E, Goodman SB. Inflammation and its resolution and the musculoskeletal system. J Orthop Translat  2017; 10: 52-67.
 [http://dx.doi.org/10.1016/j.jot.2017.05.007] [PMID: 28781962]

[26]
Clares B, Ruiz MA, Gallardo V, Arias JL. Drug delivery to inflammation based on nanoparticles surface decorated with biomolecules. Curr Med Chem  2012; 19(19): 3203-11.
 [http://dx.doi.org/10.2174/092986712800784676] [PMID: 22612704]

[27]
Penta S, Ed. Advances in structure and activity relationship of coumarin derivatives. Academic Press 2015.

[28]
Yasir M, Goyal A, Bansal P, Sonthalia S. Corticosteroid adverse effects. Treasure Island, FL: StatPearls Publishing 2022.

[29]
Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res  2003; 110(5-6): 255-8.
 [http://dx.doi.org/10.1016/S0049-3848(03)00379-7] [PMID: 14592543]

[30]
Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol  1998; 38(1): 97-120.
 [http://dx.doi.org/10.1146/annurev.pharmtox.38.1.97] [PMID: 9597150]

[31]
Ornelas A, Zacharias-Millward N, Menter DG, et al. Beyond COX-1: The effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Rev  2017; 36(2): 289-303.
 [http://dx.doi.org/10.1007/s10555-017-9675-z] [PMID: 28762014]

[32]
Alfonso L, Ai G, Spitale RC, Bhat GJ. Molecular targets of aspirin and cancer prevention. Br J Cancer  2014; 111(1): 61-7.
 [http://dx.doi.org/10.1038/bjc.2014.271] [PMID: 24874482]

[33]
Li F, Liu S, Ouyang Y, et al. Effect of celecoxib on proliferation, collagen expression, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts. Eur J Pharmacol  2012; 678(1-3): 1-5.
 [http://dx.doi.org/10.1016/j.ejphar.2011.12.018] [PMID: 22209876]

[34]
Zhu J, Huang JW, Tseng PH, et al. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res  2004; 64(12): 4309-18.
 [http://dx.doi.org/10.1158/0008-5472.CAN-03-4063] [PMID: 15205346]

[35]
Weber A, Casini A, Heine A, et al. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: New pharmacological opportunities due to related binding site recognition. J Med Chem  2004; 47(3): 550-7.
 [http://dx.doi.org/10.1021/jm030912m] [PMID: 14736236]

[36]
Nishimori I, Minakuchi T, Onishi S, et al. Carbonic anhydrase inhibitors: Cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem  2007; 15(23): 7229-36.
 [http://dx.doi.org/10.1016/j.bmc.2007.08.037] [PMID: 17826101]

[37]
Lucas S. The pharmacology of indomethacin. Headache  2016; 56(2): 436-46.
 [http://dx.doi.org/10.1111/head.12769] [PMID: 26865183]

[38]
Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol  2011; 31(5): 986-1000.
 [http://dx.doi.org/10.1161/ATVBAHA.110.207449] [PMID: 21508345]

[39]
Brutzkus JC, Shahrokhi M, Varacallo M. Naproxen.In: Stat Pearls. Stat Pearls Publishing 2021.

[40]
Kantor TG, Kantor MD. Ketoprofen: A review of its pharmacologic and clinical properties. Pharmacotherapy  1986; 6(3): 93-102.
 [http://dx.doi.org/10.1002/j.1875-9114.1986.tb03459.x] [PMID: 3526298]

[41]
Liao HL, Ma TC, Li YC, Chen JT, Chang YS. Concurrent use of corticosteroids with licorice-containing TCM preparations in Taiwan: A National Health Insurance Database study. J Altern Complement Med  2010; 16(5): 539-44.
 [http://dx.doi.org/10.1089/acm.2009.0267] [PMID: 20438302]

[42]
Ramos Campos EV, Proença PLDF, Doretto-Silva L, Andrade-Oliveira V, Fraceto LF, de Araujo DR. Trends in nanoformulations for atopic dermatitis treatment. Expert Opin Drug Deliv  2020; 17(11): 1615-30.
 [http://dx.doi.org/10.1080/17425247.2020.1813107] [PMID: 32816566]

[43]
Leonard F, Srinivasan S, Liu X, et al. Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease. Eur J Pharm Biopharm  2020; 151: 61-72.
 [http://dx.doi.org/10.1016/j.ejpb.2020.03.020] [PMID: 32283213]

[44]
Nedelcu A, Mosteanu O, Pop T, Mocan T, Mocan L. Recent advances in nanoparticle-mediated treatment of inflammatory bowel diseases. Appl Sci (Basel)  2021; 11(1): 438.
 [http://dx.doi.org/10.3390/app11010438]

[45]
Lorscheider M, Tsapis N. ur-Rehman M, et al. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis. J Control Release  2019; 296: 179-89.
 [http://dx.doi.org/10.1016/j.jconrel.2019.01.015] [PMID: 30659904]

[46]
Lee H, Jeong SW, Jung E, Lee D. Dexamethasone-loaded H2O2-activatable anti-inflammatory nanoparticles for on-demand therapy of inflammatory respiratory diseases. Nanomedicine  2020; 30: 102301.
 [http://dx.doi.org/10.1016/j.nano.2020.102301] [PMID: 32942045]

[47]
Acharya S, Guru BR. Prednisolone encapsulated PLGA nanoparticles: Characterization, cytotoxicity, and anti-inflammatory activity on C6 glial cells. J Appl Pharm Sci  2020; 10(4): 14-21.

[48]
Acharya S, Praveena J, Guru BR. In vitro studies of prednisolone loaded PLGA nanoparticles-surface functionalized with folic acid on glioma and macrophage Cell lines. Ulum-i Daruyi  2020; 27(3): 407-17.
 [http://dx.doi.org/10.34172/PS.2020.94]

[49]
Gai X, Jiang Z, Liu M, et al. Therapeutic effect of a novel Nano-drug delivery system on membranous glomerulonephritis rat model induced by cationic bovine serum. AAPS PharmSciTech  2018; 19(5): 2195-202.
 [http://dx.doi.org/10.1208/s12249-018-1034-z] [PMID: 29725902]

[50]
Hunter L, Wood D, Dargan PI. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose. Open Access Emerg Med  2011; 3: 39-48.
 [http://dx.doi.org/10.2147/OAEM.S22795] [PMID: 27147851]

[51]
Guma A, Akhtar S, Najafzadeh M, Isreb M, Baumgartner A, Anderson D. Ex vivo/in vitro effects of aspirin and ibuprofen, bulk and nano forms, in peripheral lymphocytes of prostate cancer patients and healthy individuals. Mutat Res Genet Toxicol Environ Mutagen  2021; 861-862: 503306.
 [http://dx.doi.org/10.1016/j.mrgentox.2020.503306] [PMID: 33551100]

[52]
Crivelli B, Bari E, Perteghella S, et al. Silk fibroin nanoparticles for celecoxib and curcumin delivery: ROS-scavenging and anti-inflammatory activities in an in vitro model of osteoarthritis. Eur J Pharm Biopharm  2019; 137: 37-45.
 [http://dx.doi.org/10.1016/j.ejpb.2019.02.008] [PMID: 30772432]

[53]
Choi JS, Lee DH, Ahn JB, et al. Therapeutic effects of celecoxib polymeric systems in rat models of inflammation and adjuvant-induced rheumatoid arthritis. Mater Sci Eng C  2020; 114: 111042.
 [http://dx.doi.org/10.1016/j.msec.2020.111042] [PMID: 32993980]

[54]
El-Gogary RI, Khattab MA, Abd-Allah H. Intra-articular multifunctional celecoxib loaded hyaluronan nanocapsules for the suppression of inflammation in an osteoarthritic rat model. Int J Pharm  2020; 583: 119378.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.119378] [PMID: 32360505]

[55]
Mishra RK, Ahmad A, Kumar A, Vyawahare A, Raza SS, Khan R. Lipid-based nanocarrier-mediated targeted delivery of celecoxib attenuate severity of ulcerative colitis. Mater Sci Eng C  2020; 116: 111103.
 [http://dx.doi.org/10.1016/j.msec.2020.111103] [PMID: 32806257]

[56]
Pontes-Quero GM, Benito-Garzón L, Pérez Cano J, Aguilar MR, Vázquez-Lasa B. Modulation of inflammatory mediators by polymeric nanoparticles loaded with anti-inflammatory drugs. Pharmaceutics  2021; 13(2): 290.
 [http://dx.doi.org/10.3390/pharmaceutics13020290] [PMID: 33672354]

[57]
Abdollahi AR, Firouzian F, Haddadi R, Nourian A. Indomethacin loaded dextran stearate polymeric micelles improve adjuvant-induced arthritis in rats: Design and in vivo evaluation. Inflammopharmacology  2021; 29(1): 107-21.
 [http://dx.doi.org/10.1007/s10787-020-00776-6] [PMID: 33179175]

[58]
Quines CB, Pinton S, Gutierrez MEZ, et al. Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice. Neural Regen Res  2021; 16(4): 783-9.
 [http://dx.doi.org/10.4103/1673-5374.295339] [PMID: 33063743]

[59]
Cao Y, Khan A, Ghorbani F, et al. Predicting adsorption behavior and anti-inflammatory activity of naproxen interacting with pure boron nitride and boron phosphide fullerene-like cages. J Mol Liq  2021; 339: 116678.
 [http://dx.doi.org/10.1016/j.molliq.2021.116678]

[60]
Espinosa-Cano E, Aguilar MR, Portilla Y, Barber DF, San Román J. Anti-inflammatory polymeric nanoparticles based on ketoprofen and dexamethasone. Pharmaceutics  2020; 12(8): 723.
 [http://dx.doi.org/10.3390/pharmaceutics12080723] [PMID: 32751993]

[61]
Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: Results of a follow-up national survey. JAMA  1998; 280(18): 1569-75.
 [http://dx.doi.org/10.1001/jama.280.18.1569] [PMID: 9820257]

[62]
Bent S, Avins AL. An herb for every illness? Am J Med  1999; 106(2): 259-60.
 [PMID: 10230757]

[63]
Tyler VE. Herbal medicine: From the past to the future. Public Health Nutr  2000; 3(4a): 447-52.
 [http://dx.doi.org/10.1017/S1368980000000525] [PMID: 11276292]

[64]
Panyod S, Wu WK, Ho CT, et al. Diet supplementation with allicin protects against alcoholic fatty liver disease in mice by improving anti-inflammation and antioxidative functions. J Agric Food Chem  2016; 64(38): 7104-13.
 [http://dx.doi.org/10.1021/acs.jafc.6b02763] [PMID: 27584700]

[65]
Chen W, Qi J, Feng F, et al. Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int  2014; 68: 28-37.
 [http://dx.doi.org/10.1016/j.neuint.2014.01.015] [PMID: 24530793]

[66]
Orabi SH, Abd Eldaium D, Hassan A, Sabagh HSE, Abd Eldaim MA. Allicin modulates diclofenac sodium induced hepatonephro toxicity in rats via reducing oxidative stress and caspase 3 protein expression. Environ Toxicol Pharmacol  2020; 74: 103306.
 [http://dx.doi.org/10.1016/j.etap.2019.103306] [PMID: 31812117]

[67]
Samra YA, Hamed MF, El-Sheakh AR. Hepatoprotective effect of allicin against acetaminophen‐induced liver injury: Role of inflammasome pathway, apoptosis, and liver regeneration. J Biochem Mol Toxicol  2020; 34(5): e22470.
 [http://dx.doi.org/10.1002/jbt.22470] [PMID: 32040233]

[68]
Sun D, Sun C, Qiu G, et al. Allicin mitigates hepatic injury following cyclophosphamide administration via activation of Nrf2/ARE pathways and through inhibition of inflammatory and apoptotic machinery. Environ Sci Pollut Res Int  2021; 28(29): 39625-36.
 [http://dx.doi.org/10.1007/s11356-021-13392-w] [PMID: 33763830]

[69]
Edres HA, Taha NM, Lebda MA, Elfeky MS. The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats. Environ Sci Pollut Res Int  2021; 28(41): 58768-80.
 [http://dx.doi.org/10.1007/s11356-021-14800-x] [PMID: 34120280]

[70]
Verma N, Meena NK, Majumdar I, Paul J. Role of bromelain as herbal anti-inflammatory compound using in vitro and in vivo model of colitis. J Autoimmune Dis  2017; 3: 1-8.

[71]
Badriyya E, Salman SS, Pratiwi AR, Dillasamola D, Aldi Y, Husni E. Topical anti-inflammatory activity of bromelain. Pharmacogn J  2020; 12(6s): 1586-93.
 [http://dx.doi.org/10.5530/pj.2020.12.217]

[72]
Pothacharoen P, Chaiwongsa R, Chanmee T, et al. Bromelain extract exerts antiarthritic effects via chondroprotection and the suppression of TNF-α–induced NF-κB and MAPK signaling. Plants  2021; 10(11): 2273.
 [http://dx.doi.org/10.3390/plants10112273] [PMID: 34834636]

[73]
Majumder D, Debnath R, Nath P, et al. Bromelain and Olea europaea (L.) leaf extract mediated alleviation of benzo(a)pyrene induced lung cancer through Nrf2 and NFκB pathway. Environ Sci Pollut Res Int  2021; 28(34): 47306-26.
 [http://dx.doi.org/10.1007/s11356-021-13803-y] [PMID: 33893581]

[74]
Adu TS, Mabandla MV. Effects of bromelain on striatal neuroinflammation in rat model of Parkinsonism. Brain Disorders  2021; 3: 100018.
 [http://dx.doi.org/10.1016/j.dscb.2021.100018]

[75]
Hwang JH, Koh EJ, Lee YJ, et al. Anti‐inflammatory effect of caffeine by regulating NF‐κB activation in murine macrophage. FASEB J  2016; 30: lb256.

[76]
Fan YJ, Piao CH, Nguyen TV, Yu ZN, Chai OH, Song CH. Anti-allergic effects of caffeine in an allergic rhinitis mouse model. Anatomy Biol Anthropol  2020; 33(1): 11-9.
 [http://dx.doi.org/10.11637/aba.2020.33.1.11]

[77]
Toyoda T, Shi L, Takasu S, et al. Anti‐inflammatory effects of capsaicin and piperine on Helicobacter pylori‐induced chronic gastritis in mongolian gerbils. Helicobacter  2016; 21(2): 131-42.
 [http://dx.doi.org/10.1111/hel.12243] [PMID: 26140520]

[78]
Vasanthkumar T, Hanumanthappa M, Lakshminarayana R. Curcumin and capsaicin modulates LPS induced expression of COX-2, IL-6 and TGF-β in human peripheral blood mononuclear cells. Cytotechnology  2019; 71(5): 963-76.
 [http://dx.doi.org/10.1007/s10616-019-00338-x] [PMID: 31486959]

[79]
Zhang H, Bai Y, Gao M, et al. Hepatoprotective effect of capsaicin against concanavalin A-induced hepatic injury via inhibiting oxidative stress and inflammation. Am J Transl Res  2019; 11(5): 3029-38.
 [PMID: 31217872]

[80]
Loganes C, Lega S, Bramuzzo M, et al. Curcumin anti-apoptotic action in a model of intestinal epithelial inflammatory damage. Nutrients  2017; 9(6): 578.
 [http://dx.doi.org/10.3390/nu9060578] [PMID: 28587282]

[81]
Yang H, Du Z, Wang W, et al. Structure–activity relationship of curcumin: Role of the methoxy group in anti-inflammatory and anticolitis effects of curcumin. J Agric Food Chem  2017; 65(22): 4509-15.
 [http://dx.doi.org/10.1021/acs.jafc.7b01792] [PMID: 28513174]

[82]
Fouladi S, Masjedi M, Ghasemi RG, Hakemi M, Eskandari N. The in vitro impact of glycyrrhizic acid on CD4+ T lymphocytes through OX40 receptor in the patients with allergic rhinitis. Inflammation  2018; 41(5): 1690-701.
 [http://dx.doi.org/10.1007/s10753-018-0813-8] [PMID: 30003405]

[83]
Kim GH, Paik SS, Park YS, Kim HG, Kim IB. Amelioration of mouse retinal degeneration after blue LED exposure by glycyrrhizic acid-mediated inhibition of inflammation. Front Cell Neurosci  2019; 13: 319.
 [http://dx.doi.org/10.3389/fncel.2019.00319] [PMID: 31379505]

[84]
Huang X, Liu Y, Lu Y, Ma C. Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status. Int Immunopharmacol  2015; 26(1): 265-71.
 [http://dx.doi.org/10.1016/j.intimp.2015.03.026] [PMID: 25863235]

[85]
Lee A, Yun JM. Hesperetin inhibits pro‐inflammatory cytokine secretion induced by lipopolysaccharide in differentiated human THP‐1 monocytes under hyperglycemic conditions. FASEB J  2017; 31: lb339.

[86]
Nidhi B, Sharavana G, Ramaprasad TR, Vallikannan B. Lutein derived fragments exhibit higher antioxidant and anti-inflammatory properties than lutein in lipopolysaccharide induced inflammation in rats. Food Funct  2015; 6(2): 450-60.
 [http://dx.doi.org/10.1039/C4FO00606B] [PMID: 25469663]

[87]
Tan D, Yu X, Chen M, Chen J, Xu J. Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2. Mol Med Rep  2017; 16(4): 4235-40.
 [http://dx.doi.org/10.3892/mmr.2017.7040] [PMID: 28731190]

[88]
El-Kholy AA, Elkablawy MA, El-Agamy DS. Lutein mitigates cyclophosphamide induced lung and liver injury via NF-κB/MAPK dependent mechanism. Biomed Pharmacother  2017; 92: 519-27.
 [http://dx.doi.org/10.1016/j.biopha.2017.05.103] [PMID: 28575809]

[89]
Pap R, Pandur E, Jánosa G, Sipos K, Agócs A, Deli J. Lutein exerts antioxidant and anti-inflammatory effects and influences iron utilization of BV-2 microglia. Antioxidants  2021; 10(3): 363.
 [http://dx.doi.org/10.3390/antiox10030363] [PMID: 33673707]

[90]
Wang Q, Ou Y, Hu G, et al. Naringenin attenuates non‐alcoholic fatty liver disease by down‐regulating the NLRP3/NF‐κB pathway in mice. Br J Pharmacol  2020; 177(8): 1806-21.
 [http://dx.doi.org/10.1111/bph.14938] [PMID: 31758699]

[91]
Kataoka H, Saeki A, Hasebe A, Shibata K, Into T. Naringenin suppresses toll‐like receptor 2‐mediated inflammatory responses through inhibition of receptor clustering on lipid rafts. Food Sci Nutr  2021; 9(2): 963-72.
 [http://dx.doi.org/10.1002/fsn3.2063] [PMID: 33598179]

[92]
Noori S, Rezaei Tavirani M, Deravi N, Mahboobi Rabbani MI, Zarghi A. Naringenin enhances the anti-cancer effect of cyclophosphamide against MDA-MB-231 breast cancer cells via targeting the STAT3 signaling pathway. Iran J Pharm Res  2020; 19(3): 122-33.
 [PMID: 33680016]

[93]
Wali AF, Rashid S, Rashid SM, et al. Naringenin regulates doxorubicin-induced liver dysfunction: Impact on oxidative stress and inflammation. Plants  2020; 9(4): 550.
 [http://dx.doi.org/10.3390/plants9040550] [PMID: 32344607]

[94]
Gardi C, Bauerova K, Stringa B, et al. Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis. Arch Biochem Biophys  2015; 583: 150-7.
 [http://dx.doi.org/10.1016/j.abb.2015.08.008] [PMID: 26297952]

[95]
Yang Y, Zhang X, Xu M, Wu X, Zhao F, Zhao C. Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect. Int Immunopharmacol  2018; 54: 153-62.
 [http://dx.doi.org/10.1016/j.intimp.2017.11.013] [PMID: 29149703]

[96]
Lee S, Lee HH, Shin YS, Kang H, Cho H. The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells. Arch Pharm Res  2017; 40(5): 623-30.
 [http://dx.doi.org/10.1007/s12272-017-0898-x] [PMID: 28258480]

[97]
Cheng SC, Wu YH, Huang WC, Pang JHS, Huang TH, Cheng CY. Anti-inflammatory property of quercetin through downregulation of ICAM-1 and MMP-9 in TNF-α-activated retinal pigment epithelial cells. Cytokine  2019; 116: 48-60.
 [http://dx.doi.org/10.1016/j.cyto.2019.01.001] [PMID: 30685603]

[98]
Cianciulli A, Dragone T, Calvello R, et al. IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells. Int Immunopharmacol  2015; 24(2): 369-76.
 [http://dx.doi.org/10.1016/j.intimp.2014.12.035] [PMID: 25576658]

[99]
Zhou ZX, Mou SF, Chen XQ, Gong LL, Ge WS. Anti-inflammatory activity of resveratrol prevents inflammation by inhibiting NF κB in animal models of acute pharyngitis. Mol Med Rep  2018; 17(1): 1269-74.
 [PMID: 29115472]

[100]
Grujić-Milanović J, Jaćević V, Miloradović Z, et al. Resveratrol protects cardiac tissue in experimental malignant hypertension due to antioxidant, anti-inflammatory, and anti-apoptotic properties. Int J Mol Sci 2021; 22(9): 5006.
 [http://dx.doi.org/10.3390/ijms22095006] [PMID: 34066865]

[101]
Xing Z, He Q, Xiong Y, Zeng X. Systematic pharmacology reveals the antioxidative stress and anti-inflammatory mechanisms of resveratrol intervention in myocardial ischemia-reperfusion injury. Evid Based Complement Alternat Med  2021; 2021: 1-15.
 [http://dx.doi.org/10.1155/2021/5515396] [PMID: 34093716]

[102]
Zhang W, Yu H, Lin Q, Liu X, Cheng Y, Deng B. Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway. Aging (Albany NY)  2021; 13(7): 10659-71.
 [http://dx.doi.org/10.18632/aging.202830] [PMID: 33770763]

[103]
Velagapudi R, Kumar A, Bhatia HS, et al. Inhibition of neuroinflammation by thymoquinone requires activation of Nrf2/ARE signalling. Int Immunopharmacol  2017; 48: 17-29.
 [http://dx.doi.org/10.1016/j.intimp.2017.04.018] [PMID: 28458100]

[104]
Mohamed AE, El-Magd MA, El-Said KS, El-Sharnouby M, Tousson EM, Salama AF. Potential therapeutic effect of thymoquinone and/or bee pollen on fluvastatin-induced hepatitis in rats. Sci Rep  2021; 11(1): 15688.
 [http://dx.doi.org/10.1038/s41598-021-95342-7] [PMID: 34344946]

[105]
Boskabady M, Khazdair MR, Bargi R, et al. Thymoquinone ameliorates lung inflammation and pathological changes observed in lipopolysaccharide-induced lung injury. Evid Based Complement Alternat Med  2021; 2021: 1-10.
 [http://dx.doi.org/10.1155/2021/6681729] [PMID: 33859710]

[106]
Kim AH, Jang JH, Woo KW, et al. Chemical constituents of Dicentra spectabilis and their anti-inflammation effect. J Appl Biol Chem  2018; 61(1): 39-46.
 [http://dx.doi.org/10.3839/jabc.2018.006]

[107]
Yuan X, Han B, Feng ZM, Jiang JS, Yang YN, Zhang PC. Chemical constituents of Ligusticum chuanxiong and their anti-inflammation and hepatoprotective activities. Bioorg Chem  2020; 101: 104016.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104016] [PMID: 32599365]

[108]
Bajaj S, Fuloria S, Subramaniyan V, et al. Chemical characterization and anti-inflammatory activity of phytoconstituents from Swertia alata. Plants  2021; 10(6): 1109.
 [http://dx.doi.org/10.3390/plants10061109] [PMID: 34072717]

[109]
Li R, Huang T, Nie L, et al. Chemical constituents from staminate flowers of Eucommia ulmoides oliver and their anti‐inflammation activity in vitro. Chem Biodivers  2021; 18(8): e2100331.
 [http://dx.doi.org/10.1002/cbdv.202100331] [PMID: 34155779]

[110]
Yang M, Wang Y, Fan Z, et al. Chemical constituents and anti-inflammatory activity of the total alkaloid extract from Melodinus cochinchinensis (Lour.) Merr. and its inhibition of the NF-κB and MAPK signaling pathways. Phytomedicine  2021; 91: 153684.
 [http://dx.doi.org/10.1016/j.phymed.2021.153684] [PMID: 34400050]

[111]
Di Marzio L, Ventura CA, Cosco D, et al. Nanotherapeutics for anti-inflammatory delivery. J Drug Deliv Sci Technol  2016; 32: 174-91.
 [http://dx.doi.org/10.1016/j.jddst.2015.10.011]

[112]
Kamalakannan R, Mani G, Muthusamy P, Susaimanickam AA, Kim K. Caffeine-loaded gold nanoparticles conjugated with PLA-PEG-PLA copolymer for in vitro cytotoxicity and anti-inflammatory activity. J Ind Eng Chem  2017; 51: 113-21.
 [http://dx.doi.org/10.1016/j.jiec.2017.02.021]

[113]
Babu M, Jerard C, Michael BP, Suresh S, Ramachandran R. Mesoporous silica loaded caffeine inhibits inflammatory markers in lipopolysaccharide-activated rat macrophage cells. J Appl Pharm Sci  2018; 8(12): 124-31.
 [http://dx.doi.org/10.7324/JAPS.2018.81214]

[114]
Nitthikan N, Leelapornpisid P, Natakankitkul S, et al. Improvement of stability and transdermal delivery of bioactive compounds in green robusta coffee beans extract loaded nanostructured lipid carriers. J Nanotechnol  2018; 2018: 1-12.
 [http://dx.doi.org/10.1155/2018/7865024]

[115]
Hudita A, Galateanu B, Costache M, et al. In vitro cytotoxic protective effect of alginate-encapsulated capsaicin might improve skin side effects associated with the topical application of capsaicin. Molecules  2021; 26(5): 1455.
 [http://dx.doi.org/10.3390/molecules26051455] [PMID: 33800110]

[116]
Dewangan AK, Perumal Y, Pavurala N, Chopra K, Mazumder S. Preparation, characterization and anti-inflammatory effects of curcumin loaded carboxymethyl cellulose acetate butyrate nanoparticles on adjuvant induced arthritis in rats. J Drug Deliv Sci Technol  2017; 41: 269-79.
 [http://dx.doi.org/10.1016/j.jddst.2017.07.022]

[117]
Le KM, Trinh NT, Nguyen VDX, et al. Investigating the anti-inflammatory activity of curcumin-loaded silica-containing redox nanoparticles. J Nanomater  2021; 2021: 1-11.
 [http://dx.doi.org/10.1155/2021/6655375]

[118]
Di Pompo GD, Cortini M, Palomba R, et al. Curcumin-loaded nanoparticles impair the pro-tumor activity of acid-stressed MSC in an in vitro model of osteosarcoma. Int J Mol Sci  2021; 22(11): 5760.
 [http://dx.doi.org/10.3390/ijms22115760] [PMID: 34071200]

[119]
Zeeshan M, Ali H, Khan S, Mukhtar M, Khan MI, Arshad M. Glycyrrhizic acid-loaded pH-sensitive poly-(lactic-co-glycolic acid) nanoparticles for the amelioration of inflammatory bowel disease. Nanomedicine (Lond)  2019; 14(15): 1945-69.
 [http://dx.doi.org/10.2217/nnm-2018-0415] [PMID: 31355705]

[120]
Mohanty S, Sahoo AK, Konkimalla VB, Pal A, Si SC. Naringin in combination with isothiocyanates as liposomal formulations potentiates the anti-inflammatory activity in different acute and chronic animal models of rheumatoid arthritis. ACS Omega  2020; 5(43): 28319-32.
 [http://dx.doi.org/10.1021/acsomega.0c04300] [PMID: 33163815]

[121]
Saha S, Kundu J, Verma RJ, Chowdhury PK. Albumin coated polymer nanoparticles loaded with plant extract derived quercetin for modulation of inflammation. Materialia (Oxf)  2020; 9: 100605.
 [http://dx.doi.org/10.1016/j.mtla.2020.100605]

[122]
Choudhary A, Kant V, Jangir BL, Joshi VG. Quercetin loaded chitosan tripolyphosphate nanoparticles accelerated cutaneous wound healing in Wistar rats. Eur J Pharmacol  2020; 880: 173172.
 [http://dx.doi.org/10.1016/j.ejphar.2020.173172] [PMID: 32407724]

[123]
Diez-Echave P, Ruiz-Malagón AJ, Molina-Tijeras JA, et al. Silk fibroin nanoparticles enhance quercetin immunomodulatory properties in DSS-induced mouse colitis. Int J Pharm  2021; 606: 120935.
 [http://dx.doi.org/10.1016/j.ijpharm.2021.120935] [PMID: 34310954]

[124]
Juère E, Florek J, Bouchoucha M, et al. In vitro dissolution, cellular membrane permeability, and anti-inflammatory response of resveratrol-encapsulated mesoporous silica nanoparticles. Mol Pharm  2017; 14(12): 4431-41.
 [http://dx.doi.org/10.1021/acs.molpharmaceut.7b00529] [PMID: 29094948]

[125]
Sun L, Hu Y, Mishra A, et al. Protective role of poly(lactic‐co‐glycolic) acid nanoparticle loaded with resveratrol against isoproterenol‐induced myocardial infarction. Biofactors  2020; 46(3): 421-31.
 [http://dx.doi.org/10.1002/biof.1611] [PMID: 31926035]

[126]
Liu Y, Liang X, Zou Y, Peng Y, McClements DJ, Hu K. Resveratrol-loaded biopolymer core–shell nanoparticles: Bioavailability and anti-inflammatory effects. Food Funct  2020; 11(5): 4014-25.
 [http://dx.doi.org/10.1039/D0FO00195C] [PMID: 32322856]

[127]
Jain A, Pooladanda V, Bulbake U, et al. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomedicine  2017; 13(7): 2251-62.
 [http://dx.doi.org/10.1016/j.nano.2017.06.009] [PMID: 28647592]

[128]
Sharma S, Parveen R, Chatterji BP. Toxicology of nanoparticles in drug delivery. Curr Pathobiol Rep  2021; 9(4): 133-44.
 [http://dx.doi.org/10.1007/s40139-021-00227-z] [PMID: 34840918]

[129]
Sharifi S, Behzadi S, Laurent S, Laird Forrest M, Stroeve P, Mahmoudi M. Toxicity of nanomaterials. Chem Soc Rev  2012; 41(6): 2323-43.
 [http://dx.doi.org/10.1039/C1CS15188F] [PMID: 22170510]

[130]
Allen C. The question of toxicity of nanomaterials and nanoparticles. J Control Release  2019; 304: 288.
 [http://dx.doi.org/10.1016/j.jconrel.2019.06.008] [PMID: 31185234]

[131]
Bostan HB, Rezaee R, Valokala MG, et al. Cardiotoxicity of nano-particles. Life Sci  2016; 165: 91-9.
 [http://dx.doi.org/10.1016/j.lfs.2016.09.017] [PMID: 27686832]

[132]
Riego Sintes J, Roebben G, Linsinger T.  European Commission, Joint Research Centre. An overview of concepts and terms used in the European Commission's definition of nanomaterial.Publications Office 2019. Available from: https://data.europa.eu/doi/10.2760/459136

[133]
Khan HA, Shanker R. Toxicity of nanomaterials. BioMed Research International 2015.
 [http://dx.doi.org/10.1155/2015/521014]

[134]
Patel G, Patra C, Srinivas SP, Kumawat M, Navya PN, Daima HK. Methods to evaluate the toxicity of engineered nanomaterials for biomedical applications: A review. Environ Chem Lett  2021; 19(6): 4253-74.
 [http://dx.doi.org/10.1007/s10311-021-01280-1]
Cite As
Recent Advances in Inflammation & Allergy Drug Discovery

Anti-Inflammatory Therapeutics: Conventional Concepts and Future with Nanotechnology

Abstract

Graphical Abstract
