Exploring nanoformulation drug delivery of herbal actives for enhanced therapeutic efficacy: A comprehensive review

Abstract

Background: In this present review we have focused on nanoformulation drug delivery approach to deliver active drug constituents. As it can minimizes the limitations associated with conventional therapies such as rapid gastric emptying, high surface area, site specific controlled drug delivery high cellular uptake, improved bioavailability, cost effectiveness, patient compliance, and improved therapeutic efficacy of drug along with reduction in systemic and local toxicity by governing the drug release behaviour.

Purpose: Over the years, nanoparticles have emerged as an amazing dosage form owing to their advantages such as permeability across barriers, controlled drug release and higher stability. They can be linked to specific ligands which can allow the development of targeted therapies. Hence, targeted treatments of nanoformulations for asthma and sepsis may help to maximize therapeutic benefit and helps to lower their severity.

Conclusion: This review highlights the nanoformulations and their potential application in drug delivery. Mechanism of action of various phytoconstituents such as flavonoids and triterpenoids is also discussed. The flavonoid as well as triterpenoid loaded nanoparticles seems to be a promising drug delivery systems, especially on account of account of its management in inflammatory diseases.

Keywords

Nanoformulations / Flavanoids / Triterpenoids / Anti-inflammatory activity / Ursolic acid / Quercitin

References

[1] Ghasemian M , Owlia S , Owlia MB . Review of anti-inflammatory herbal medicines. Advances in Pharmacological Sciences. 2016; 2026.

[2] Bagad AS , Joseph JA , Bhaskaran N . Agarwal A “Comparative evaluation of antiinflammatory activity of curcuminoids, turmerones, and aqueous extract of Curcuma longa,”. Advances in Pharmacological Sciences. 2013; 2013: 805756. 7 pages.

[3] Ghasemian M , Owlia MB . A different look at pulsed glucocorticoid protocols; is high dose oral prednisolone really necessary just after initiation of pulse therapy? J Case Rep Pract. 2015; 3 (1): 1- 3.

[4] Wang S , Su R , Nie S , et al. Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. JNB (J Nutr Biochem). 2014; 25 (4): 363- 376. Elsevier Inc.

[5] Bennet D , Marimuthu M , Kim S , An J . Dual drug-loaded nanoparticles on selfintegrated scaffold for controlled delivery. Int J Nanomed. 2012; 7: 3399- 3419.

[6] Yu YB , Miyashiro H , Nakamura N , Hattori M , Park JC . Effects of triterpenoids and flavonoids isolated from Alnus firma on HIV-1 viral enzymes. Arch Pharm Res (Seoul). 2007; 30: 820- 826.

[7] Kumari A , Kumar V , Yadav SK . Plant extract synthesized PLA nanoparticles for controlled and sustained release of quercetin: a green approach. PLoS One. 2012; 7: e41230.

[8] Srinivas K , King JW , Howard LR , Monrad JK . Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. J Food Eng. 2010; 100: 208- 218.

[9] Bose S , Michniak-Kohn B . Preparation and characterization of lipid based nanosystems for topical delivery of quercetin. Eur J Pharmaceut Sci. 2012; 48: 442- 452.

[10] Li H , Zhao X , Ma Y , Zhai G , Li L , Lou H . Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Contr Release. 2009; 133: 238- 244.

[11] Kaps A , Gwiazdoń P , Chodurek E . E(Nanoformulations for delivery of pentacyclic triterpenoids in anticancer therapies. In: Molecules. 26. MDPI AG; 2021. Issue 6.

[12] Ghante MH , Jamkhande PG . Role of pentacyclic triterpenoids in chemoprevention and anticancer treatment: an overview on targets and underling mechanisms. J Pharmacopuncture. 2019; 22: 55- 67.

[13] Szakiel A , Paczkowski C , Pensec F , Bertsch C . Fruit cuticular waxes as a source of biologically active triterpenoids. Phytochemistry Rev. 2012; 11: 263- 284.

[14] Xia X , Liu H , Lv H , Zhang J , Zhou J , Zhao Z . Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles. Drug Des. Dev, Ther. 2017; 11: 1417- 1427.

[15] Yu D , Kan Z , Shan F , Zang J , Zhou J . Triple strategies to improve oral bioavailability by fabricating coamorphous forms of ursolic acid with piperine: enhancing watersolubility, permeability, and inhibiting cytochrome P450 isozymes. Mol Pharm. 2020; 17: 4443- 4462.

[16] Shao J , Fang Y , Zhao R , et al. Evolution from small molecule to nano-drug delivery systems: an emerging approach for cancer therapy of ursolic acid. Asian J Pharm Sci. 2020; 15: 685- 700.

[17] Patra JK , Das G , Fraceto LF , et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018; 16

[18] Yadav D , Suri S , Choudhary AA , Sikender M , Hemant Beg NM , et al. Novel approach: herbal remedies and natural products in pharmaceutical science as nano drug delivery systems. Int J Pharm Technol. 2011; 3: 3092- 3116.

[19] Yetisgin AA , Cetinel S , Zuvin M , Kosar A , Kutlu O . Therapeutic nanoparticles and their targeted delivery applications (2020). MDPI AG. Molecules. 2020: 25 (Issue 9).

[20] Mishra V , Bansal KK , Verma A , et al. Solid lipid nanoparticles: emerging colloidal nano drug delivery systems. In: Pharmaceutics. 10. MDPI AG; 2018. Issue 4.

[21] Satapathy MK , Yen TL , Jan JS , et al. Solid lipid nanoparticles (Slns): an advanced drug delivery system targeting brain through bbb. In: Pharmaceutics. 13. MDPI AG; 2021. Issue 8.

[22] Rizvi SZH , Shah FA , Khan N , et al. Simvastatin-loaded solid lipid nanoparticles for enhanced anti-hyperlipidemic activity in hyperlipidemia animal model. Int J Pharm. 2019; 560: 136- 143.

[23] Rawat R , Chouhan RS , Sadhu V , Sharma M . Clarithromycin-loaded submicron-sized carriers: pharmacokinetics and pharmacodynamic evaluation. Materials. 2019; 16 (9).

[24] Sharma M , Sharma S , Wadhwa J n . Improved uptake and therapeutic intervention of curcumin via designing binary lipid nanoparticulate formulation for oral delivery in inflammatory bowel disorder. Artif Cells, Nanomed Biotechnol. 2019; 47 (1): 45- 55.

[25] Roy A , SomeS Bulut O , Mandal AK , Yilmaz MD . Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity. RSC Adv. 2019; 9: 2673- 2702.

[26] Patil S , Chandrasekaran R . Biogenic nanoparticles: a comprehensive perspective in synthesis, characterization, application and its challenges. In: Journal of Genetic Engineering and Biotechnology. 18. Springer Science and Business Media Deutschland GmbH; 2020. Issue 1.

[27] Yetisgin AA , Cetinel S , Zuvin M , Kosar A , Kutlu O . Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020; 25: 2193.

[28] Shao J , Fang Y , Zhao R , et al. Evolution from small molecule to nano-drug delivery systems: an emerging approach for cancer therapy of ursolic acid. Asian J Pharm Sci. 2020; 15: 685- 700.

[29] Santos A , Veiga F , Figueiras A . Dendrimers as pharmaceutical excipients: synthesis, properties, toxicity and biomedical applications. Materials. 2019; 13: 65.

[30] Kahraman E , Gungor S , Ozsoy Y . Potential enhancement and targeting strategies of polymeric and lipid-based nanocarriers in dermal drug delivery. Ther Deliv. 2017; 8: 967- 985.

[31] Imperiale JC , Schlachet I , Lewicki M , Sosnik A , Biglione MM . Oral pharmacokinetics of a chitosan-based nano-drug delivery system of interferon alpha. Polymers. 2019; 11 (11).

[32] Chen L , Deng H , Cui H , et al. Oncotarget. Oncotarget. 2018; 9 (Issue 6): 7204.

[33] Medzhitov R . Inflammation new adventures of an old flame. 2010. Cell. 2010; 140: 771- 776.

[34] Ferrero-Miliani L , Nielsen O , Andersen P , Girardin S . Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1β generation. Clin Exp Immunol. 2007; 147: 227- 235.

[35] Nathan C , Ding A . Nonresolving inflammation. Cell. 2010; 140: 871- 882.

[36] Zhou Y , Hong Y , Huang H . Triptolide Attenuates Inflammatory Response in Membranous GlomeruloNephritis Rat via Downregulation of NF-Κb Signaling.

[37] Chertov O , Yang D , Howard O , Oppenheim JJ . Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev. 2000.

[38] Takeuchi O , Akira S . Pattern recognition receptors and inflammation. Cell. 2010; 140: 805- 882.

[39] Yatoo Mohd I , Gopalakrishnan A , Saxena A , et al. Anti-inflammatory drugs and herbs with special emphasis on herbal medicines for countering inflammatory diseases and disorders-a review. Recent Pat Inflamm Allergy Drug Discov. 2018; 12 (1): 39- 58.

[40] Vishal V , Sharma GN , Mukesh G , Ranjan B . A review on some plants having antiinflammatory activity. J Phytopharmacol. 2014; 3 (3): 214- 221.

[41] Bjorkman DJ . The effect of aspirin and nonsteroidal antiinflammatory drugs on prostaglandins. Am J Med. 1998; 105 (1B): 8S- 12S.

[42] Ricciotti E , Fitz Gerald GA . Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011; 31 (5): 986- 1000.

[43] Rainsford KD . Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2007; 42: 3- 27.

[44] Bermas BL . Non-steroidal anti inflammatory drugs, glucocorticoids and disease modifying anti-rheumatic drugs for the management of rheumatoid arthritis before and during pregnancy. Curr Opin Rheumatol. 2014; 26 (3): 334- 340.

[45] Shaikh S , Verma H , Yadav N , Jauhari M , Bullangowda J . Applications of steroid in clinical practice: a review. ISRN Anesthesiology. 2012.

[46] Juthani VV , Clearfield E , Chuck RS . Non-steroidal antiinflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery. Cochrane Database Syst Rev. 2017; 7: CD010516

[47] Moskovtchenko JF , Cognet JB . Classification of corticoids. Ann Anesthesiol Fr. 1976; 17 (4): 399- 405.

[48] Ayroldi E , Cannarile L , Migliorati G , Nocentini G , Delfino DV , Riccardi C . Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and nongenomic interference with MAPK signaling pathways. Faseb J. 2012; 26 (12): 4805- 4820.

[49] Celotti F , Laufer S . Anti-inflammatory drugs: new multitarget compounds to face an old problem. The dual inhibition concept. Pharmacol Res. 2001; 43 (5): 429- 436.

[50] Altavilla D , Squadrito F , Bitto A , et al. Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages. Br J Pharmacol. 2009; 157: 1410- 1418.

[51] Lin AS , Lin CR , Du YC , et al. Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of Acacia farnesiana. Planta Med. 2009; 75: 256- 261.

[52] Aggarwal BB , Prasad S , Reuter S , et al. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases. Curr Drug Targets. 2011; 12 (11): 1595- 1653.

[53] Choy KW , Murugan D , Leong XF , Abas R , Alias A , Mustafa MR . Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signaling in cardiovascular diseases: a mini review. Front Pharmacol. 2019; (OCT): 10.

[54] Pollastri S , Tattini M . Flavonols: old compounds for old roles. Ann Bot. 2011; 108: 1225- 1233.

[55] Barreca D , Gattuso G , Bellocco E , et al. Flavanones: citrus phytochemical with health-promoting properties. Biofactors. 2017; 43: 495- 506.

[56] Chekalina N , Burmak Y , Petrov Y , et al. Quercetin reduces the transcriptional activity of NF-kB in stable coronary artery disease. Indian Heart J. 2018; 70: 593- 597.

[57] Indra MR , Karyono S , Ratnawati R , Malik SG . Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in leptin-induced human umbilical vein endothelial cells (HUVECs). BMC Res. 2013; 6. 275- 275.

[58] Tang X-L , Liu J-X , Dong W , et al. Intervention Effect of Quercetin on Inflammatory Secretion of Cardiac Fibroblasts. 2014.

[59] Oyagbemi AA , Omobowale TO , Ola-Davies OE , et al. Luteolin-mediated Kim-1/NFkB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications. Biofactors. 2018; 44: 518- 531.

[60] Lv L , Lv L , Zhang Y , Kong Q . Luteolin Prevents LPS-Induced TNFalpha Expression in Cardiac Myocytes through Inhibiting NF-kappaB Sig. 2011. Lv L., Lv L., Zhang Y., and Kong Q.

[61] Garg S , Malhotra RK , Khan SI , et al. Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-kappaB mediated oxidative stress, apoptosis and inflammation. Phytomedicine. 2019; 56: 147- 155.

[62] Ren K , Jiang T , Zhou HF , Liang Y , Zhao GJ . Apigenin retards atherogenesis by promoting abca1-mediated cholesterol efflux and suppressing inflammation. Cell Physiol Biochem. 2018; 47: 2170- 2184.

[63] Xiong D , Hu W , Ye S-T , Tan Y-S . Isoliquiritigenin alleviated the Ang II-induced hypertensive renal injury through suppressing inflammation cytokines and oxidative stress-induced apoptosis via Nrf2 and NF-κB pathways. Biochem.Biophysical Res. Commun. 2018; 506: 161- 168.

[64] Lee W , Ku S-K , Bae J-S . Barrier protective effects of rutin in LPSinduced inflammation in vitro and in vivo. Food Chem Toxicol. 2012; 50: 3048- 3055.

[65] Rani N , Bharti S , Bhatia J , Nag T , Ray R , Chrysin Arya DS . A PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. Chem Biol Interact. 2016; 250: 59- 67.

[66] Han S , Wu H , Li W , Gao P . Protective effects of genistein in homocysteine-induced endothelial cell inflammatory injury. Mol Cell Biochem. 2015; 403: 43- 49.

[67] Suchal K , Malik S , Gamad N , et al. Kaempferol attenuates myocardial ischemic injury via inhibition of MAPK signaling pathway in experimental model of myocardial ischemia-reperfusion injury. Oxidative Med. Cell.Longevity. 2016; 2016, 1- 1.

[68] Kashyap D , Sharma AS , Tuli H , Punia S , Sharma K . Ursolic acid and oleanolic acid: pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat Inflamm Allergy Drug Discov. 2016; 10 (1): 21- 33.

[69] Mirza MA , Mahmood S , Hilles AR , et al. Quercetin as a therapeutic product: evaluation of its pharmacological action and clinical applications—a review. In: Pharmaceuticals. 16. Multidisciplinary Digital Publishing Institute (MDPI); 2023. Issue 11.

[70] Kwak JH , Seo JM , Kim NH , et al. Variation of quercetin glycoside derivatives in three onion (Allium cepa L.) varieties. Saudi J Biol Sci. 2017; 24: 1387- 1391.

[71] Shabir I , Pandey VK , Dar AH , et al. Nutritional profile, phytochemical compounds, biological activities, and utilisation of onion peel for food applications: a review. Sustainability. 2022; 14: 11958.

[72] Li Y , Yao J , Han C , et al. Quercetin, inflammation and immunity. Nutrients. 2016; 8: 167.

[73] Serafini M , Peluso I , Raguzzini A . Flavonoids as anti-inflammatory agents. Proc Nutr Soc. 2010; 69: 273- 278.

[74] Ferraz CR , Carvalho TT , Manchope MF , et al. Therapeutic potential of flavonoids in pain and inflammation: mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules. 2020; 25: 762.

[75] Cunha TM , Roman-Campos D , Lotufo CM , et al. Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/KATP signaling pathway. Proc Natl Acad Sci USA. 2010; 107: 4442- 4447.

[76] Sachs D , Cunha FQ , Ferreira SH . Peripheral analgesic blockade of hypernociception: activation of argi-nine/NO/CGMP/protein kinase G/ATP-Sensitive K+ channel pathway. Proc Natl Acad Sci USA. 2004; 101: 3680- 3685.

[77] Mu N , Ugli G , Teshaboy PA . Some flavonoids in the yarrow (Achillea Millefolium L.) plant and their effects on human health. AJSHR. 2021; 2 (5): 116- 120.

[78] Choy KW , Murugan D , Leong XF , Abas R , Alias A , Mustafa MR . Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signaling in cardiovascular diseases: a mini review. Front Pharmacol. 2019: 10 (OCT).

[79] Lv L , Lv L , Zhang Y , Kong Q . Luteolin prevents LPS-induced TNFalpha expression in cardiac myocytes through inhibiting NF-kappaB signaling pathway. Inflammation. 2011; 34: 620- 629.

[80] Aziz N , Kim MY , Cho JY . Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies. J Ethnopharmacol. 2018; 342- 358.

[81] Gawlik-Dziki U . Changes in the antioxidant activities of vegetables as a consequence of interactions between active compounds. J Funct Foods. 2012; 4: 872- 882.

[82] Ganeshpurkar A , Saluja AK . The pharmacological potential of rutin. Saudi Pharmaceut J. 2016; 25: 149- 164.

[83] Rauf A , Imran M , Patel S , Muzaffar R , Bawazeer SS . Rutin: exploitation of the flavonol for health and homeostasis. Biomed Pharmacother. 2017; 96: 1559- 1561.

[84] Farzaei MH , Singh AK , Kumar R , et al. Targeting inflammation by flavonoids: novel therapeutic strategy for metabolic disorders. Int J Mol Sci. 2019; 20: 4957.

[85] Almahy H , Abdel-Razik HH , Abdalla Almahy H , Abdel-razik Fouda H . Isolation of luteolin 8-c-β-glucopyranoside from the roots of Salvadora persica (Rutaceae). Chem. Pharm. Sc. 2013; 3 (1): 49- 53.

[86] Al-Khayri JM , Sahana GR , Nagella P , Joseph Bv , Alessa FM , Al-Mssallem MQ . Flavonoids as potential anti-inflammatory molecules: a review. In: Molecules. 27. MDPI; 2022. Issue 9.

[87] Choy KW , Murugan D , Leon X-F , Abas R , Alias A , Mustafa MR . Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signaling in cardiovascular diseases: a mini review. Front Pharmacol. 2019; 10: 1295.

[88] Grynkiewicz G , Demchuk OM . New perspectives for fisetin. In: Frontiers in Chemistry. 7. Frontiers Media S.A; 2019. vol. 7.

[89] Schmidt J . Ueber das Fisetin, den Farbstoff des Fisetholtzes. Chem Ber. 1886; 19: 1734- 1749.

[90] Choy KW , Murugan D , Leong XF , Abas R , Alias A , Mustafa MR . Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signaling in cardiovascular diseases: a mini review. Front Pharmacol. 2019: 10 (OCT).

[91] Garg S , Malhotra RK , Khan SI , et al. Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-kappaB mediated oxidative stress, apoptosis and inflammation. Phytomedicine. 2019; 56: 147- 155.

[92] Puniani E , Cayer C , Kent P , et al. Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolyticprinciple. Phytochemistry. 2015; 113: 73- 78.

[93] Jeong W , Hong SS , Kim N , et al. Bioactive triterpenoids from Callistemon lanceolatus. Arch Pharm Res (Seoul). 2009; 32: 845- 849.

[94] Lin CK , Tseng CK , Chen KH , Wu SH , Liaw CC , Lee JC . Betulinic acid exerts antihepatitis C virus activity via the suppression of NF-kappa B-and MAPK-ERK1/2-mediated COX-2 expression. Br J Pharmacol. 2015; 172: 4481- 4492.

[95] Yun Y , Han S , Park E , et al. Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages. Arch Pharm Res (Seoul). 2003; 26.

[96] Vyas N , Argal A . Isolation and characterization of oleanolic acid from roots of Lantana camara. Asian J Pharmaceut Clin Res. 2014; 7: 189- 191.

[97] Xia EQ , Wang BW , Xu XR , Zhu L , Song Y , Li HB . Microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait. Int J Mol Sci. 2011; 12: 5319- 5329.

[98] Yang EJ , Lee W , Ku SK , Song KS , Bae JS . Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs. Food Chem Toxicol. 2012; 50: 1288- 1294.

[99] Andersson U , Tracey KJ . HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011; 29: 139- 162.

[100] Lee W , Yang EJ , Ku SK , Song KS , Bae JS . Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo. Inflammation. 2013; 36: 94- 102.

[101] Woźniak Ł , Skąpska S , Marszałek K . Ursolic acid-a pentacyclic triterpenoid with a wide spectrum of pharmacological activities. In: Molecules. 20. MDPI AG; 2015: 20614- 20641. 11.

[102] Jąger S , Trojan H , Kopp T , Laszczyk MN , Scheffler A . Pentacyclic triterpene distribution in various plants—rich sources for a new group of multi-potent plant extracts. Molecules. 2009; 14: 2016- 2031.

[103] SzakielA Pączkowski C , Pensec F , Bertsch C . Fruit cuticular waxes as a source of biologically active triterpenoids. Phytochemistry Rev. 2012; 11: 263- 284.

[104] Zhao M , Wu F , Tang Z , et al. Anti-inflammatory and antioxidant activity of ursolic acid: a systematic review and meta-analysis. In: Frontiers in Pharmacology. 14. Frontiers Media SA; 2023.

[105] Saleem M . Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. In: Cancer Letters. 285. Elsevier Ireland Ltd; 2009: 109- 115. 2.

[106] Beveridge TH , Li TS , Drover JC . Phytosterol content in American ginseng seed oil. J Agric Food Chem. 2002; 50: 744- 750.

[107] Fernández MA , de las Heras B , García MD , Sáenz MT , Villar A . New insights into the mechanism of action of the anti-inflammatory triterpene lupeol. J Pharm Pharmacol. 2001; 53: 1533- 1539.

[108] Vasconcelos JF , Teixeira MM , Barbosa-Filho JM , Lúcio AS , Almeida JR , de Queiroz LP . The triterpenoid lupeol attenuates allergic airway inflammation in a murine model. Int Immunopharm. 2008; 8: 1216- 1221.

[109] Yamashita K , Lu H , Chen J Lu G , Sagara T Yokoyama Y , et al. Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin Chim Acta. 2002; 325: 91- 96.

[110] Lucetti DL , Lucetti ECP , Bandeira MAM , et al. Anti-inflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel. J Inflamm. 2010; 7.

[111] Meeran MFN , Goyal SN , Sharma K , Sharma C , Patil CR , Ojha SK . Pharmacological properties, molecular mechanisms, and pharmaceutical development of asiatic acid: a pentacyclic triterpenoid of therapeutic promise. In: Frontiers in Pharmacology. 9. Frontiers Media S.A; 2018. Issue SEP.

[112] Kamble SM , Patel HM , Goyal SN , et al. In silico evidence for binding of pentacyclic triterpenoids to keap1-nrf2 protein-protein binding site. Comb Chem High Throughput Screen. 2017; 20: 215- 234.

[113] Patil KR , Mohapatra P , Patel HM , et al. Pentacyclic triterpenoids inhibit IKKβ mediated activation of NF-κB pathway: in silico and in vitro evidences. PLoS One. 2015; 10: e0125709.

[114] Yang C , Guo Y , Huang T , et al. Asiatic acid protects against cisplatin-induced acute kidney injury via anti-apoptosis and anti-inflammation. Biomed Pharmacother. 2018; 107: 1354- 1362.

[115] Lozano-Mena G , Sánchez-González M , Juan ME , Planas JM . Maslinic acid, a natural phytoalexin-type triterpene from olives-a promising nutraceutical?InMolecules (2014). MDPI AG. 2014; 19 (8): 11538- 11559.

[116] Caglioti L , Cainelli G , Minutilli F . Constitution of maslinic acid. Chim Ind. 1961; 43: 278.

[117] Lu H , Xi C , Chen J , Li W . Determination of triterpenoid acids in leaves of Eriobotrya japonica collected at in different seasons. Zhongguo Zhongyao Zazhi. 2009; 34: 2353- 2355.

[118] Banno N , Akihisa T , Tokuda H , et al. Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica. Biol Pharm Bull. 2005; 28: 1995- 1999.

[119] Kim DH , Han KM , Chung IS , et al. Triterpenoids from the flower of Campsis grandiflora K. Schum. as human acyl-CoA: cholesterol acyltransferase inhibitors. Arch Pharm Res (Seoul). 2005; 28: 550- 556.

[120] Huang L , Guan T , Qian Y , et al. Anti-inflammatory effects of maslinic acid, a natural triterpene, in cultured cortical astrocytes via suppression of nuclear factor-kappa B. Eur J Pharmacol. 2011: 672- 1-3. 169- 174.

[121] Fang F . A Study of Chemical Constituents of the Leaves of Nerium Indicum Mill. Hefei, China: Anhui Agricultural University; 2013.

[122] Khan I , Kant C , Sanwaria A , Meena L . Acute cardiac toxicity of NeriumOleander/indicum poisoning (kaner) poisoning. Heart Views. 2010; 11 (3): 115- 116.

[123] AtayBalkan I , Goren AC , Kirmizibekme H , Yeşilada E . Evaluation of the in vitro antiinflammatory activity of Nerium oleander L. flower extracts and activity-guided isolation of the active constituents. Record Nat Prod. 2017; 12 (2): 128- 141.

[124] Jyotshna Chand Gupta A , Bawankule DU , Verma AK , Shanker K . Nanoemulsion preconcentrate of a pentacyclic triterpene for improved oral efficacy: formulation design and in-vivo antimalarial activity. J Drug Deliv Sci Technol. 2020; 57.

[125] Mioc M , Pavel IZ , Ghiulai R , et al. The cytotoxic effects of betulin-conjugated gold nanoparticles as stable formulations in normal and melanoma cells. Front Pharmacol. 2018; 9 (MAY).

[126] Dwivedi K , Mandal AK , Afzal O , et al. Emergence of nano-based formulations for effective delivery of flavonoids against topical infectious disorders, 2023. In: Gels. 9. Multidisciplinary Digital Publishing Institute; 2023. Issue 8). (MDPI).

[127] Sysak S , Czarczynska-Goslinska B , Szyk P , et al. Metal nanoparticle-flavonoid connections: synthesis, physicochemical and biological properties, as well as potential applications in medicine. In: Nanomaterials. 13. MDPI; 2023. Issue 9.

[128] Shao J , Fang Y , Zhao R , et al. Evolution from small molecule to nano-drug delivery systems: an emerging approach for cancer therapy of ursolic acid. Asian J Pharm Sci. 2020: 15 (Issue 6): 685- 700. Shenyang Pharmaceutical University.

[129] Wang L , Yin Q , Liu C , Tang Y , Sun C , Zhuang J . Nanoformulations of ursolic acid: a modern natural anticancer molecule. In: Frontiers in Pharmacology. 12. Frontiers Media S.A; 2021.

[130] Singh AK , Pandey H , Ramteke PW , Mishra SB . Nano-suspension of ursolic acid for improving oral bioavailability and attenuation of type II diabetes: a histopathological investigation. Biocatal Agric Biotechnol. 2019; 22.

[131] Guan F , Wang Q , Bao Y , Chao Y . Anti-rheumatic effect of quercetin and recent developments in nano formulation. RSC Adv. 2021; 11 (13): 7280- 7293. Royal Society of Chemistry

[132] Dwivedi K , Mandal AK , Afzal O , et al. Emergence of nano-based formulations for effective delivery of flavonoids against topical infectious disorders. In: Gels. 9. Multidisciplinary Digital Publishing Institute (MDPI); 2023. Issue 8.

[133] Sun D , Li N , Zhang W , et al. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo. J Nanoparticle Res. 2016; 18: 3.

[134] Vashisth P , Nikhil K , Pemmaraju SC , et al. Antibiofilm activity of quercetinencapsulated cytocompatible nanofibers against Candida albicans. J. Bioact. Compat. Polym. 2013; 28: 652- 665.

[135] Jannat K , Paul AK , Bondhon TA , et al. Nanotechnology applications of flavonoids for viral diseases. MDPI In Pharmaceutics. 2021; 13 (Issue 11). 2021

[136] Kumar TS , Rao NNM , Rawat R , et al. Galactopolymer architectures/functionalized graphene oxide nanocomposites for antimicrobial applications. J Polym Res. 2021; 28 (6).

[137] Sharma D , Gupta A , Sharma S , Singh Yadav J , Murti SR . Poly-electrolyte complex: a review of its potency in the management of inflammatory bowel diseases. J Pharm Negat Results. 2022; (ss13): 11072.

[138] Jubilee R , Komala M , Patel S . Therapeutic potential of resveratrol and lignans in the management of tuberculosis. In: Cell Biochemistry and Biophysics. Springer; 2024.

[139] Patel S , Jain S , Gururani R , Sharma S , Dwivedi J . Insights on synthetic strategies and structure-activity relationship of donepezil and its derivatives. In: Medicinal Chemistry Research. 33. Springer; 2024: 370- 405. 3.

RIGHTS & PERMISSIONS

2024 The Authors. Publishing services by Elsevier B.V. on behalf of Higher Education Press and KeAi Communications Co. Ltd.