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image of Development and Validation of Bioenhancer-based Phospholipid Complexes with Exceptional Immunomodulatory and Antioxidant Potential

Abstract

Background

Combination therapy with polyphenol-rich natural spices has gained acceptance as a proactive approach for modulating human health owing to the COVID-19 pandemic. However, bioavailability is a significant hurdle in determining the actual potential of any herbal drug.

Aim & Objective

To improve the absorption of herbal drugs and to enhance their ability to affect the immune system, phospholipid complexes were developed for accommodating Curcumin with extracts of commonly found dietary spices like , , and aiming to have an effective immunomodulatory phytoformulation subduing the bioavailability limitation of Curcumin and delivery hurdle of phytoextracts for combination therapy. Since combination therapy with polyphenol-rich natural spices had surfaced as an effective mode of immunomodulation, phospholipid complexes were designed for encapsulating polyphenol-rich natural spices and Curcumin together and assessed for the most efficient phospholipid complexes with improved invitro therapeutic outcomes.

Method

A quick and easy procedure for assessing the developed formulation using High-Performance Thin-Layer Chromatography (HPTLC) was developed. Antioxidant potential was measured by DPPH and Lipid peroxidation. Further immunomodulation was assessed in macrophages by NO inhibition assay and phagocytosis capacity.

Result

The results showed that polyherbal phospholipid complexes exerted 2-fold enhanced antiradical properties (DPPH radical scavenging and inhibition of lipid peroxidation) as compared to Curcumin and significant inhibition of ROS in HO-induced human macrophages. Moreover, these polyherbal formulations were more effective in promoting macrophage proliferation, inhibiting LPS-induced NO production in macrophages, and enhancing phagocytosis in a dose-dependent manner.

Conclusion

Thus, phospholipid complexes offer a practical approach for developing nutraceuticals with augmented bioactivity of herbal components.

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/content/journals/cac/10.2174/0115734110340427250101133846
2025-01-31
2025-04-02
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References

  1. Wal P. Dwivedi J. Wal A. Kushwaha S. Diabetic patients with COVID-19 complications: Insights into prevalence, prognosis, combination medications, and underlying mechanisms. Curr. Diabetes Rev. 2023 19 7 e250822208008 10.2174/1573399819666220825164056 36028964
    [Google Scholar]
  2. Abe Y. Hashimoto S. Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol. Res. 1999 39 1 41 47 10.1006/phrs.1998.0404 10051376
    [Google Scholar]
  3. Atal C.K. Dubey R.K. Singh J. Biochemical basis of enhanced drug bioavailability by piperine: Evidence that piperine is a potent inhibitor of drug metabolism. J. Pharmacol. Exp. Ther. 1985 232 1 258 262 3917507
    [Google Scholar]
  4. Badmus J.A. Adedosu T.O. Fatoki J.O. Adegbite V.A. Adaramoye O.A. Odunola O.A. Lipid peroxidation inhibition and antiradical activities of some leaf fractions of Mangifera indica. Acta Pol. Pharm. 2011 68 1 23 29 21485698
    [Google Scholar]
  5. Ainsworth E.A. Gillespie K.M. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nat. Protoc. 2007 2 4 875 877 10.1038/nprot.2007.102 17446889
    [Google Scholar]
  6. Agnihotri N. Mishra P.C. Scavenging mechanism of curcumin toward the hydroxyl radical: A theoretical study of reactions producing ferulic acid and vanillin. J. Phys. Chem. A 2011 115 49 14221 14232 10.1021/jp209318f 22035040
    [Google Scholar]
  7. Chiou W.F. Chen C.F. Lin J.J. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide. Br. J. Pharmacol. 2000 129 8 1553 1560 10.1038/sj.bjp.0703191 10780958
    [Google Scholar]
  8. Banji D. Banji O.J.F. Dasaroju S. Annamalai A.R. Piperine and curcumin exhibit synergism in attenuating d-galactose induced senescence in rats. Eur. J. Pharmacol. 2013 703 1-3 91 99 10.1016/j.ejphar.2012.11.018 23200897
    [Google Scholar]
  9. Banji D. Banji O.J.F. Dasaroju S. Kumar CH K. Curcumin and piperine abrogate lipid and protein oxidation induced by d-galactose in rat brain. Brain Res. 2013 1515 1 11 10.1016/j.brainres.2013.03.023 23566814
    [Google Scholar]
  10. Murunikkara V. Rasool M. Trikatu, an herbal compound as immunomodulatory and anti-inflammatory agent in the treatment of rheumatoid arthritis – An experimental study. Cell. Immunol. 2014 287 1 62 68 10.1016/j.cellimm.2013.12.002 24394943
    [Google Scholar]
  11. Schepetkin I.A. Quinn M.T. Botanical polysaccharides: Macrophage immunomodulation and therapeutic potential. Int. Immunopharmacol. 2006 6 3 317 333 10.1016/j.intimp.2005.10.005 16428067
    [Google Scholar]
  12. Dwivedi J. Dwivedi M. Gupta S. Jadaun V. Yadav B. Parashar P. Dhar P. Dwivedi P. Ahmed H. Singh P. Pal A. Paliwal S.K. Dwivedi A.K. Rawat A.K.S. Synthesized phytomolecular hybrids as natural interventions to manage hyperlipidemia and to ameliorate diabetes in streptozotocin induced mice. Polycycl. Aromat. Compd. 2022 42 9 6136 6154 10.1080/10406638.2021.1982731
    [Google Scholar]
  13. Gnananath K. Sri Nataraj K. Ganga Rao B. Phospholipid complex technique for superior bioavailability of phytoconstituents. Adv Pharm Bull. 2017 7 1 35 42 10.15171/apb.2017.005 28507935
    [Google Scholar]
  14. Saoji S.D. Raut N.A. Dhore P.W. Borkar C.D. Popielarczyk M. Dave V.S. Preparation and evaluation of phospholipid-based complex of Standardized Centella Extract (SCE) for the enhanced delivery of phytoconstituents. AAPS J. 2016 18 1 102 114 10.1208/s12248‑015‑9837‑2 26563253
    [Google Scholar]
  15. Dwivedi J. Gupta A. Verma S. Paliwal S. Rawat A.K.S. Validated simultaneous high-performance thin-layer chromatographic analysis of ursolic acid, β -sitosterol, lupeol and quercetin in the methanolic fraction of ichnocarpus frutescens. J. Planar Chromatogr. Mod. TLC 2019 32 2 103 108 10.1556/1006.2019.32.2.4
    [Google Scholar]
  16. Dwivedi J. Gupta A. Paliwal S. Rawat A.K.S. Validated simultaneous HPTLC analysis of scopoletin and gallic acid in the methanolic fraction of Jatropha glandulifera. J. Planar Chromatogr. Mod. TLC 2020 33 5 457 462 10.1007/s00764‑020‑00063‑8
    [Google Scholar]
  17. Gupta A. Dwivedi J. Irshad S. Verma S. Pragyadeep S. Dwivedi H. Rawat A.K. Comparative pharmacognostical evaluation and HPTLC analysis of three different species of bauhinia leaves. Res. J. Pharm. Biol. Chem. Sci. 2018 9 5 347 356
    [Google Scholar]
  18. Tiwari S. Shukla P.K. Dwivedi J. Khatoon S. Simultaneous quantification of four active metabolites in Psidium guajava L. by a validated high-performance thin-layer chromatography method. J. Planar Chromatogr. Mod. TLC 2021 34 1 61 69 10.1007/s00764‑021‑00083‑y
    [Google Scholar]
  19. Lee T.Y. Lee K.C. Chen S.Y. Chang H.H. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κB pathways in lipopolysaccharide-stimulated mouse macrophages. Biochem. Biophys. Res. Commun. 2009 382 1 134 139 10.1016/j.bbrc.2009.02.160 19268427
    [Google Scholar]
  20. Ghasemzadeh A. Jaafar H.Z.E. Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules 2010 15 6 4324 4333 10.3390/molecules15064324 20657444
    [Google Scholar]
  21. Szabo M. Idiţoiu C. Chambre D. Lupea A. Improved DPPH determination for antioxidant activity spectrophotometric assay. Chem. Pap. 2007 61 3 214 216 10.2478/s11696‑007‑0022‑7
    [Google Scholar]
  22. Bors W. Saran M. Radical scavenging by flavonoid antioxidants. Free Radic. Res. Commun. 1987 2 4-6 289 294 10.3109/10715768709065294 3504810
    [Google Scholar]
  23. Ippoushi K. Azuma K. Ito H. Horie H. Higashio H. [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions. Life Sci. 2003 73 26 3427 3437 10.1016/j.lfs.2003.06.022 14572883
    [Google Scholar]
  24. Liu Y. Sheng Y. Yuan G. Wang Y. Wei H. Guan M. Pei J. Purification and physicochemical properties of different polysaccharide fractions from the water extract of Boschniakia rossica and their effect on macrophages activation. Int. J. Biol. Macromol. 2011 49 5 1007 1011 10.1016/j.ijbiomac.2011.08.024 21893087
    [Google Scholar]
  25. Jurenka J.S. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern. Med. Rev. 2009 14 2 141 153 19594223
    [Google Scholar]
  26. Majdalawieh A.F. Carr R.I. In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum). J. Med. Food 2010 13 2 371 381 10.1089/jmf.2009.1131 20210607
    [Google Scholar]
  27. Suresh D. Srinivasan K. Studies on the in vitro absorption of spice principles – Curcumin, capsaicin and piperine in rat intestines. Food Chem. Toxicol. 2007 45 8 1437 1442 10.1016/j.fct.2007.02.002 17524539
    [Google Scholar]
  28. Shoba G. Joy D. Joseph T. Majeed M. Rajendran R. Srinivas P. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 64 4 353 356 10.1055/s‑2006‑957450 9619120
    [Google Scholar]
  29. Aggarwal B.B. Sundaram C. Malani N. Ichikawa H. Curcumin: The Indian solid gold. Adv. Exp. Med. Biol. 2007 595 1 75 10.1007/978‑0‑387‑46401‑5_1 17569205
    [Google Scholar]
  30. Sharma R.A. Gescher A.J. Steward W.P. Curcumin: The story so far. Eur. J. Cancer 2005 41 13 1955 1968 10.1016/j.ejca.2005.05.009 16081279
    [Google Scholar]
  31. Sharma M. Sharma S. Sharma V. Sharma K. Yadav S.K. Dwivedi P. Agrawal S. Paliwal S.K. Dwivedi A.K. Maikhuri J.P. Gupta G. Mishra P.R. Rawat A.K.S. Oleanolic–bioenhancer coloaded chitosan modified nanocarriers attenuate breast cancer cells by multimode mechanism and preserve female fertility. Int. J. Biol. Macromol. 2017 104 Pt A 1345 1358 10.1016/j.ijbiomac.2017.06.005 28591594
    [Google Scholar]
  32. Kidd P.M. Bioavailability and activity of phytosome complexes from botanical polyphenols: The silymarin, curcumin, green tea, and grape seed extracts. Altern. Med. Rev. 2009 14 3 226 246 [DOI not available]. 19803548
    [Google Scholar]
  33. Maiti K. Mukherjee K. Gantait A. Saha B.P. Mukherjee P.K. Curcumin–phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int. J. Pharm. 2007 330 1-2 155 163 10.1016/j.ijpharm.2006.09.025 17112692
    [Google Scholar]
  34. Mohanty I. Senapati P. Jena M. Bioenhanced curcumin formulations: A comprehensive review. J. Funct. Foods 2018 40 70 81 10.1016/j.jff.2017.10.051
    [Google Scholar]
  35. Sharma M. Sharma S. Sharma V. Agarwal S. Dwivedi P. Paliwal S.K. Maikuri J.P. Dwivedi A.K. Gupta G. Mishra P.R. Rawat A.K.S. Design of folic acid conjugated chitosan nano-cur–bioenhancers to attenuate the hormone-refractory metastatic prostate carcinoma by augmenting oral bioavailability. RSC Advances 2016 6 30 25137 25148 10.1039/C5RA17599B
    [Google Scholar]
  36. Nair A.B. Al-Dhubiab B.E. Kumria R. Phytosomal drug delivery of Curcumin for functional foods: A bioenhanced therapeutic option. J. Funct. Foods 2022 91 104946 10.1016/j.jff.2022.104946
    [Google Scholar]
  37. Joshi M. Shirode A. Pore Y. Curcumin-phospholipid complexes: A promising approach for enhanced bioavailability and controlled delivery in inflammation. Int. J. Pharm. 2021 600 120493 10.1016/j.ijpharm.2021.120493
    [Google Scholar]
  38. Di Lorenzo A. Manti S. Morabito G. Antioxidant pharmacokinetics: The role of bioenhancers and nanotechnology-based delivery systems. Antioxidants 2019 8 12 553 10.3390/antiox8120553
    [Google Scholar]
  39. Kesarwani K. Gupta R. Mukerjee A. Bioavailability enhancers of herbal origin: An overview. Asian Pac. J. Trop. Biomed. 2013 3 4 253 266 10.1016/S2221‑1691(13)60060‑X 23620848
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: Curcumin ; immunomodulatory ; Piper nigrum ; antioxidant ; Piper longum ; Zingiber officinale
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