Using Quality by Design Tools to Study Gel Formulation from Brassica juncea Leaves and Conducting its In vitro, In vivo, Molecular Docking, and ADMET Analyses
- Authors: Kanakal M.1, Abbas S.1, Khan A.1, Sultana S.2, Fatima H.3, Tabasssum R.2, Ahmed M.3, Sultana R.3, Mohammed J.4, Salfi R.3
-
Affiliations:
- Faculty of Pharmacy, QUEST International University
- , Shadan Womens College of Pharmacy
- Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to be University)
- , Sri Indu Institute of Pharmacy
- Issue: Vol 23, No 3 (2024)
- Pages: 187-204
- Section: Medicine
- URL: https://archivog.com/1871-5230/article/view/644683
- DOI: https://doi.org/10.2174/0118715230309053240718122527
- ID: 644683
Cite item
Full Text
Abstract
Introduction:This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflamma-tory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Ab-sorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to en-sure the therapeutic potential and safety of the drug development process. The Quality by De-sign tool has been applied to optimize formulation development.
Methods:The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm.
Results:The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70%), standard (47.86%), and (39.72%) were found.
Conclusion:The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory ther-apeutic effects. ADMET analysis ensures the therapeutic effects and their safety.
About the authors
Mahibub Kanakal
Faculty of Pharmacy, QUEST International University
Email: info@benthamscience.net
Syed Abbas
Faculty of Pharmacy, QUEST International University
Email: info@benthamscience.net
Abdullah Khan
Faculty of Pharmacy, QUEST International University
Email: info@benthamscience.net
Saleha Sultana
, Shadan Womens College of Pharmacy
Email: info@benthamscience.net
Humaira Fatima
Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to be University)
Email: info@benthamscience.net
Ruheena Tabasssum
, Shadan Womens College of Pharmacy
Email: info@benthamscience.net
Mohammed Ahmed
Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to be University)
Email: info@benthamscience.net
Rokeya Sultana
Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to be University)
Email: info@benthamscience.net
Jaffer Mohammed
, Sri Indu Institute of Pharmacy
Email: info@benthamscience.net
Roshan Salfi
Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to be University)
Author for correspondence.
Email: info@benthamscience.net
References
- Tian, Y.; Deng, F. Phytochemistry and biological activity of mustard ( Brassica juncea ): A review. CYTA J. Food, 2020, 18(1), 704-718. doi: 10.1080/19476337.2020.1833988
- Lin, L.Z.; Sun, J.; Chen, P.; Harnly, J. UHPLC-PDA-ESI/HRMS/MS(n) analysis of anthocyanins, flavonol glycosides, and hydroxycinnamic acid derivatives in red mustard greens (Brassica juncea Coss variety). J. Agric. Food Chem., 2011, 59(22), 12059-12072. doi: 10.1021/jf202556p PMID: 21970730
- Verma, S.; Tiwari, B.K.; Jaiswal, N.; Pandey, F.K. Evaluation of antimicrobial activity of Brassica juncea leaves against different strains of bacteria. Bio Science Research Bulletin, 2022, 38(1), 26-34. doi: 10.5958/2320-3161.2022.00003.7
- Muhammad, A.P.; Pinkey, R.; Ramesh, C.; Chaitra, G. Evaluation of Antidiarrheal properties of ethanol extract of Brassica juncea in experimental animals. J. Drug Deliv. Ther., 2021, 11(2-S), 19-23. doi: 10.22270/jddt.v11i2-S.4615
- Flourat, A.L.; Willig, G.; Teixeira, A.R.S.; Allais, F. Eco-friendly extraction of sinapine from residues of mustard production. Front. Sustain. Food Syst., 2019, 3, 12. doi: 10.3389/fsufs.2019.00012
- Kwon, H.Y.; Choi, S.I.; Park, H.I.; Choi, S.H.; Sim, W.S.; Yeo, J.H.; Cho, J.H.; Lee, O.H. Comparative analysis of the nutritional components and antioxidant activities of different Brassica juncea cultivars. Foods, 2020, 9(6), 840. doi: 10.3390/foods9060840 PMID: 32604920
- Dua, A.; Chander, S.; Agrawal, S.; Mahajan, R. Antioxidants from defatted Indian Mustard (Brassica juncea) protect biomolecules against in vitro oxidation. Physiol. Mol. Biol. Plants, 2014, 20(4), 539-543. doi: 10.1007/s12298-014-0260-4 PMID: 25320478
- Lakshmanan, D.K.; Murugesan, S.; Rajendran, S.; Ravichandran, G.; Elangovan, A.; Raju, K.; Prathiviraj, R.; Pandiyan, R.; Thilagar, S. Brassica juncea (L.) Czern. leaves alleviate adjuvant-induced rheumatoid arthritis in rats via modulating the finest disease targets - IL2RA, IL18 and VEGFA. J. Biomol. Struct. Dyn., 2022, 40(18), 8155-8168. doi: 10.1080/07391102.2021.1907226 PMID: 33792526
- Parikh, H.; Pandita, N.; Khanna, A. Phytoextract of Indian mustard seeds acts by suppressing the generation of ROS against acetaminophen-induced hepatotoxicity in HepG2 cells. Pharm. Biol., 2015, 53(7), 975-984. doi: 10.3109/13880209.2014.950675 PMID: 25489640
- Chandrashekar, S.; Vijayakumar, R.; Chelliah, R.; Daliri, E.B.M.; Madar, I.H.; Sultan, G.; Rubab, M.; Elahi, F.; Yeon, S.J.; Oh, D.H. In vitro and in silico screening and characterization of antimicrobial napin bioactive protein in Brassica juncea and Moringa oleifera. Molecules, 2021, 26(7), 2080. doi: 10.3390/molecules26072080 PMID: 33916405
- Yokozawa, T.; Kim, H.Y.; Cho, E.J.; Choi, J.S.; Chung, H.Y. Antioxidant effects of isorhamnetin 3,7-di-O-β-D-glucopyranoside isolated from mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes. J. Agric. Food Chem., 2002, 50(19), 5490-5495. doi: 10.1021/jf0202133 PMID: 12207497
- Zou, Y.; Kim, A.R.; Kim, J.E.; Choi, J.S.; Chung, H.Y. Peroxynitrite scavenging activity of sinapic acid (3,5-dimethoxy-4-hydroxycinnamic acid) isolated from Brassica juncea. J. Agric. Food Chem., 2002, 50(21), 5884-5890. doi: 10.1021/jf020496z PMID: 12358454
- Jung, H.A.; Woo, J.J.; Jung, M.J.; Hwang, G.S.; Choi, J.S. Kaempferol glycosides with antioxidant activity from Brassica juncea. Arch. Pharm. Res., 2009, 32(10), 1379-1384. doi: 10.1007/s12272-009-2006-3 PMID: 19898800
- Mayengbam, S.; Aachary, A.; Thiyam-Holländer, U. Endogenous phenolics in hulls and cotyledons of mustard and canola: A comparative study on its sinapates and antioxidant capacity. Antioxidants, 2014, 3(3), 544-558. doi: 10.3390/antiox3030544 PMID: 26785070
- Xian, Y.F.; Hu, Z.; Ip, S.P.; Chen, J.N.; Su, Z.R.; Lai, X.P.; Lin, Z.X. Comparison of the anti-inflammatory effects of Sinapis alba and Brassica juncea in mouse models of inflammation. Phytomedicine, 2018, 50, 196-204. doi: 10.1016/j.phymed.2018.05.010 PMID: 30466979
- Hassan, S.A.; Hagrassi, A.M.E.; Hammam, O.; Soliman, A.M.; Ezzeldin, E.; Aziz, W.M. Brassica juncea L. (Mustard) extract silver nanoparticles and knocking off oxidative stress, proinflammatory cytokine and reverse DNA genotoxicity. Biomolecules, 2020, 10(12), 1650. doi: 10.3390/biom10121650 PMID: 33317112
- Kwak, Y.; Lee, J.; Ju, J. Anti-cancer activities of Brassica juncea leaves in vitro. EXCLI J., 2016, 15, 699-710. PMID: 28337101
- Gasmi, A.; Gasmi Benahmed, A.; Shanaida, M.; Chirumbolo, S.; Menzel, A.; Anzar, W.; Arshad, M.; Cruz-Martins, N.; Lysiuk, R.; Beley, N.; Oliinyk, P.; Shanaida, V.; Denys, A.; Peana, M.; Bjørklund, G. Anticancer activity of broccoli, its organosulfur and polyphenolic compounds. Crit. Rev. Food Sci. Nutr., 2023, 1-19. doi: 10.1080/10408398.2023.2195493 PMID: 37129118
- Sheu, M.J.; Yeh, M.C.; Tsai, M.C.; Wang, C.C.; Chang, Y.L.; Wang, C.J.; Huang, H.P. Glucosinolates extracts from Brassica juncea ameliorate hfd-induced non-alcoholic steatohepatitis. Nutrients, 2023, 15(16), 3497. doi: 10.3390/nu15163497 PMID: 37630688
- Sharma, A. Phytochemical and elemental analysis of Brassica juncea L. leaves using GC-MS and SEM-EDX. Res. J. Pharm. Technol., 2015, 8(12), 1662-1664.
- Sharma, A.; Rai, P.K.; Prasad, S. GCMS detection and determination of major volatile compounds in Brassica juncea L. leaves and seeds. Microchem. J., 2018, 138, 488-493. doi: 10.1016/j.microc.2018.01.015
- Bassan, P.; Bhushan, S.; Kaur, T.; Arora, R.; Arora, S.; Vig, A.P. Extraction, profiling and bioactivity analysis of volatile glucosinolates present in oil extract of Brassica juncea var. raya. Physiol. Mol. Biol. Plants, 2018, 24(3), 399-409. doi: 10.1007/s12298-018-0509-4 PMID: 29692548
- Oulad El Majdoub, Y.; Alibrando, F.; Cacciola, F.; Arena, K.; Pagnotta, E.; Matteo, R.; Micalizzi, G.; Dugo, L.; Dugo, P.; Mondello, L. Chemical characterization of three accessions of Brassica juncea L. extracts from different plant tissues. Molecules, 2020, 25(22), 5421. doi: 10.3390/molecules25225421 PMID: 33228167
- Ibrahim, R.M.; M Eltanany, B.; Pont, L.; Benavente, F.; ElBanna, S.A.; Otify, A.M. Unveiling the functional components and antivirulence activity of mustard leaves using an LC-MS/MS, molecular networking, and multivariate data analysis integrated approach. Food Res. Int., 2023, 168, 112742. doi: 10.1016/j.foodres.2023.112742 PMID: 37120197
- Jain, P.; Taleuzzaman, M.; Kala, C.; Kumar Gupta, D.; Ali, A.; Aslam, M. Quality by design (Qbd) assisted development of phytosomal gel of aloe vera extract for topical delivery. J. Liposome Res., 2021, 31(4), 381-388. doi: 10.1080/08982104.2020.1849279 PMID: 33183121
- Taleuzzaman, M.; Sartaj, A.; Kumar Gupta, D.; Gilani, S.J.; Mirza, M.A. Phytosomal gel of Manjistha extract (MJE) formulated and optimized with central composite design of quality by design (QbD). J. Dispers. Sci. Technol., 2023, 44(2), 236-244. doi: 10.1080/01932691.2021.1942036
- Mohapatra, S.; Mirza, M.A.; Ahmad, S.; Farooq, U.; Ansari, M.J.; Kohli, K.; Iqbal, Z. Quality by design assisted optimization and risk assessment of black cohosh loaded ethosomal gel for menopause: Investigating Different Formulation and Process variables. Pharmaceutics, 2023, 15(2), 465. doi: 10.3390/pharmaceutics15020465 PMID: 36839787
- Dhawan, S.; Nanda, S. Implementation of quality by design (QbD) concept for the development of emulsion based nanotailored gel for improved antiphotoageing potential of Silymarin. J. Drug Deliv. Sci. Technol., 2023, 81, 104201. doi: 10.1016/j.jddst.2023.104201
- Taleuzzaman, M.; Jain, P.; Verma, R.; Iqbal, Z.; Mirza, M.A. Eugenol as a potential drug candidate: A review. Curr. Top. Med. Chem., 2021, 21(20), 1804-1815. doi: 10.2174/1568026621666210701141433 PMID: 34218781
- Moradi, S.Z.; Momtaz, S.; Bayrami, Z.; Farzaei, M.H.; Abdollahi, M. Nanoformulations of herbal extracts in treatment of neurodegenerative disorders. Front. Bioeng. Biotechnol., 2020, 8, 238. doi: 10.3389/fbioe.2020.00238 PMID: 32318551
- Bonifácio, B.V.; Silva, P.B.; Ramos, M.A.; Negri, K.M.; Bauab, T.M.; Chorilli, M. Nanotechnology-based drug delivery systems and herbal medicines: A review. Int. J. Nanomedicine, 2014, 9, 1-15. PMID: 24363556
- Verma, S.; Singh, S. Current and future status of herbal medicines. Vet. World, 2008, 2(2), 347-350. doi: 10.5455/vetworld.2008.347-350
- Ashenafi, E.; Abula, T.; Abay, S.M.; Arayaselassie, M.; Taye, S.; Muluye, R.A. Analgesic and anti-inflammatory effects of 80% methanol extract and solvent fractions of the leaves of vernonia auriculifera hiern. (Asteraceae). J. Exp. Pharmacol., 2023, 15, 29-40. doi: 10.2147/JEP.S398487 PMID: 36733956
- Mota, A.H.; Prazeres, I.; Mestre, H.; Bento-Silva, A.; Rodrigues, M.J.; Duarte, N.; Serra, A.T.; Bronze, M.R.; Rijo, P.; Gaspar, M.M.; Viana, A.S.; Ascensão, L.; Pinto, P.; Kumar, P.; Almeida, A.J.; Reis, C.P. A newfangled collagenase inhibitor topical formulation based on ethosomes with sambucus nigra l. Extract. Pharmaceuticals, 2021, 14(5), 467. doi: 10.3390/ph14050467 PMID: 34063413
- Andleeb, M.; Shoaib Khan, H.M.; Daniyal, M. Development, characterization and stability evaluation of topical gel loaded with ethosomes containing Achillea millefolium L. extract. Front. Pharmacol., 2021, 12, 603227. doi: 10.3389/fphar.2021.603227 PMID: 33912036
- Alam, P.; Shakeel, F.; Foudah, A.I.; Alshehri, S.; Salfi, R.; Alqarni, M.H.; Aljarba, T.M. Central composite design (CCD) for the optimisation of ethosomal gel formulation of Punica granatum extract: In vitro and in vivo evaluations. Gels, 2022, 8(8), 511. doi: 10.3390/gels8080511 PMID: 36005111
- Khogta, S.; Patel, J.; Barve, K.; Londhe, V. Herbal nano-formulations for topical delivery. J. Herb. Med., 2020, 20, 100300. doi: 10.1016/j.hermed.2019.100300
- Naseri, M.; Mojab, F.; Khodadoost, M.; Kamalinejad, M.; Davati, A.; Choopani, R.; Hasheminejad, A.; Bararpoor, Z.; Shariatpanahi, S.; Emtiazy, M. The study of anti-inflammatory activity of oil-based dill (Anethum graveolens L.) extract used topically in formalin-induced inflammation male rat paw. Iran. J. Pharm. Res., 2012, 11(4), 1169-1174. PMID: 24250550
- Moni, J.N.R.; Adnan, M.; Tareq, A.M.; Kabir, M.I.; Reza, A.S.M.A.; Nasrin, M.S.; Chowdhury, K.H.; Sayem, S.A.J.; Rahman, M.A.; Alam, A.H.M.K.; Alam, S.B.; Sakib, M.A.; Oh, K.K.; Cho, D.H.; Capasso, R. Therapeutic potentials of Syzygium fruticosum fruit (Seed) reflected into an array of pharmacological assays and prospective receptors-mediated pathways. Life, 2021, 11(2), 155. doi: 10.3390/life11020155 PMID: 33671381
- Németh, Z.; Csóka, I.; Semnani Jazani, R.; Sipos, B.; Haspel, H.; Kozma, G.; Kónya, Z.; Dobó, D.G. Quality by design-driven zeta potential optimisation study of liposomes with charge imparting membrane additives. Pharmaceutics, 2022, 14(9), 1798. doi: 10.3390/pharmaceutics14091798 PMID: 36145546
- Singh, U.; Jialal, I. Anti‐inflammatory effects of α‐tocopherol. Ann. N. Y. Acad. Sci., 2004, 1031(1), 195-203. doi: 10.1196/annals.1331.019 PMID: 15753145
- Reiter, E.; Jiang, Q.; Christen, S. Anti-inflammatory properties of α- and γ-tocopherol. Mol. Aspects Med., 2007, 28(5-6), 668-691. doi: 10.1016/j.mam.2007.01.003 PMID: 17316780
- Loganathan, Y.; Jain, M.; Thiyagarajan, S.; Shanmuganathan, S.; Mariappan, S.K.; Kizhakedathil, M.P.J.; Saravanakumar, T. An Insilico evaluation of phytocompounds from Albizia amara and Phyla nodiflora as cyclooxygenase-2 enzyme inhibitors. Daru, 2021, 29(2), 311-320. doi: 10.1007/s40199-021-00408-6 PMID: 34415547
- Krishnamoorthy, K.; Subramaniam, P. Phytochemical profiling of leaf, stem, and tuber parts of Solena amplexicaulis (Lam.) gandhi using GC-MS. Int. Sch. Res. Notices, 2014, 2014, 1-13. doi: 10.1155/2014/567409 PMID: 27379314
- Othman, A.R.; Abdullah, N.; Ahmad, S.; Ismail, I.S.; Zakaria, M.P. Elucidation of in-vitro anti-inflammatory bioactive compounds isolated from Jatropha curcas L. plant root. BMC Complement. Altern. Med., 2015, 15(1), 11. doi: 10.1186/s12906-015-0528-4 PMID: 25652309
- Umar, M.I.; Asmawi, M.Z.; Sadikun, A.; Abdul Majid, A.M.S.; Atangwho, I.J.; Khadeer Ahamed, M.B.; Altaf, R.; Ahmad, A. Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract. Pharm. Biol., 2014, 52(11), 1411-1422. doi: 10.3109/13880209.2014.895017 PMID: 25026347
- Ahmad, M.M.; Akhtar, N.; Khan, S.; Rashid, M.; Athar, M.T.; Ullah, Z.; Taleuzzaman, M. Discovery of novel isonipecotic acid-based heteroaryl amino acid derivatives as potential anticonvulsant agents: Design, synthesis, in-silico ADME study, and molecular docking studies. J. Pharm. Bioallied Sci., 2023, 15(4), 205-211. doi: 10.4103/jpbs.jpbs_478_23 PMID: 38235051
- Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216. doi: 10.1038/s41573-020-00114-z PMID: 33510482
- Dzobo, K. The role of natural products as sources of therapeutic agents for innovative drug discovery; Comprehensive Pharmacology, 2022, p. 408. doi: 10.1016/B978-0-12-820472-6.00041-4
Supplementary files
