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Current Drug Delivery

Author(s): Marjan Heidarzadeh, Mehriar Amininasab*, Seyed Mahdi Rezayat* and Seyyedeh Elaheh Mousavi*

DOI: 10.2174/0115672018258030230920035222

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Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies

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Abstract

Introduction: In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs.

Method: The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR.

Results: Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α).

Conclusion: Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Graphical Abstract

[1]
Sivandzade, F.; Cucullo, L. Regenerative stem cell therapy for neurodegenerative diseases: An overview. Int. J. Mol. Sci., 2021, 22(4), 2153.
[http://dx.doi.org/10.3390/ijms22042153] [PMID: 33671500]
[2]
Ruz, C.; Alcantud, J.L.; Vives, M.F.; Duran, R.; Bandres-Ciga, S. Proteotoxicity and neurodegenerative diseases. Int. J. Mol. Sci., 2020, 21(16), 5646.
[http://dx.doi.org/10.3390/ijms21165646] [PMID: 32781742]
[3]
Teleanu, D.M.; Niculescu, A.G.; Lungu, I.I.; Radu, C.I.; Vladâcenco, O.; Roza, E.; Costăchescu, B.; Grumezescu, A.M.; Teleanu, R.I. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int. J. Mol. Sci., 2022, 23(11), 5938.
[http://dx.doi.org/10.3390/ijms23115938] [PMID: 35682615]
[4]
Kwon, H.S.; Koh, S.H. Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes. Transl. Neurodegener., 2020, 9(1), 42.
[http://dx.doi.org/10.1186/s40035-020-00221-2] [PMID: 33239064]
[5]
Chen, N.; Wang, X.C.; Fan, L.L.; Zhu, Y.H.; Wang, Q.; Chen, Y.B. Berberine ameliorates lipopolysaccharide-induced cognitive impairment through SIRT1/NRF2/NF-κB signaling pathway in C57BL/6J Mice. Rejuvenation Res., 2022, 25(5), 233-242.
[http://dx.doi.org/10.1089/rej.2022.0023] [PMID: 36029207]
[6]
Zuo, L.; Prather, E.R.; Stetskiv, M.; Garrison, D.E.; Meade, J.R.; Peace, T.I.; Zhou, T. Inflammaging and oxidative stress in human diseases: From molecular mechanisms to novel treatments. Int. J. Mol. Sci., 2019, 20(18), 4472.
[http://dx.doi.org/10.3390/ijms20184472] [PMID: 31510091]
[7]
Mas-Bargues, C.; Escrivá, C.; Dromant, M.; Borrás, C.; Viña, J. Lipid peroxidation as measured by chromatographic determination of malondialdehyde. Human plasma reference values in health and disease. Arch. Biochem. Biophys., 2021, 709, 108941.
[http://dx.doi.org/10.1016/j.abb.2021.108941] [PMID: 34097903]
[8]
Fujii, J.; Homma, T.; Osaki, T. Superoxide radicals in the execution of cell death. Antioxidants, 2022, 11(3), 501.
[http://dx.doi.org/10.3390/antiox11030501] [PMID: 35326151]
[9]
Degan, D.; Ornello, R.; Tiseo, C.; Carolei, A.; Sacco, S.; Pistoia, F. The role of inflammation in neurological disorders. Curr. Pharm. Des., 2018, 24(14), 1485-1501.
[http://dx.doi.org/10.2174/1381612824666180327170632] [PMID: 29589534]
[10]
Boyd, R.J.; Avramopoulos, D.; Jantzie, L.L.; McCallion, A.S. Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases. J. Neuroinflammation, 2022, 19(1), 223.
[http://dx.doi.org/10.1186/s12974-022-02584-x] [PMID: 36076238]
[11]
Wongrakpanich, S.; Wongrakpanich, A.; Melhado, K.; Rangaswami, J. A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly. Aging Dis., 2018, 9(1), 143-150.
[http://dx.doi.org/10.14336/AD.2017.0306] [PMID: 29392089]
[12]
Agbor, G.A.; Dell’Agli, M.; Kuiate, J.R.; Ojo, O. Editorial: The role of medicinal plants and natural products in modulating oxidative stress and inflammatory related disorders. Front. Pharmacol., 2022, 13, 957296.
[http://dx.doi.org/10.3389/fphar.2022.957296] [PMID: 35814237]
[13]
Rodríguez-Yoldi, M.J. Anti-inflammatory and antioxidant properties of plant extracts. Antioxidants, 2021, 10(6), 921.
[http://dx.doi.org/10.3390/antiox10060921] [PMID: 34200199]
[14]
Rehman, M.U.; Wali, A.F.; Ahmad, A.; Shakeel, S.; Rasool, S.; Ali, R.; Rashid, S.M.; Madkhali, H.; Ganaie, M.A.; Khan, R. Neuroprotective strategies for neurological disorders by natural products: An update. Curr. Neuropharmacol., 2019, 17(3), 247-267.
[http://dx.doi.org/10.2174/1570159X16666180911124605] [PMID: 30207234]
[15]
Khoshandam, A.; Imenshahidi, M.; Hosseinzadeh, H. Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review. Phytother. Res., 2022, 36(11), 4063-4079.
[http://dx.doi.org/10.1002/ptr.7589] [PMID: 36221815]
[16]
Imenshahidi, M.; Hosseinzadeh, H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother. Res., 2019, 33(3), 504-523.
[http://dx.doi.org/10.1002/ptr.6252] [PMID: 30637820]
[17]
Ai, X.; Yu, P.; Peng, L.; Luo, L.; Liu, J.; Li, S.; Lai, X.; Luan, F.; Meng, X. Berberine: A review of its pharmacokinetics properties and therapeutic potentials in diverse vascular diseases. Front. Pharmacol., 2021, 12, 762654.
[http://dx.doi.org/10.3389/fphar.2021.762654] [PMID: 35370628]
[18]
Zhou, M.; Deng, Y.; Liu, M.; Liao, L.; Dai, X.; Guo, C.; Zhao, X.; He, L.; Peng, C.; Li, Y. The pharmacological activity of berberine, a review for liver protection. Eur. J. Pharmacol., 2021, 890, 173655.
[http://dx.doi.org/10.1016/j.ejphar.2020.173655] [PMID: 33068590]
[19]
Li, Z.; Zhang, W. Protective effect of berberine on renal fibrosis caused by diabetic nephropathy. Mol. Med. Rep., 2017, 16(2), 1055-1062.
[http://dx.doi.org/10.3892/mmr.2017.6707] [PMID: 29067464]
[20]
Shou, J.W.; Li, X.X.; Tang, Y.S.; Lim-Ho Kong, B.; Wu, H.Y.; Xiao, M.J.; Cheung, C.K.; Shaw, P.C. Novel mechanistic insight on the neuroprotective effect of berberine: The role of PPARδ for antioxidant action. Free Radic. Biol. Med., 2022, 181, 62-71.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.01.022] [PMID: 35093536]
[21]
Eissa, L.A.; Kenawy, H.I.; El-Karef, A.; Elsherbiny, N.M.; El-Mihi, K.A. Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats. Chem. Biol. Interact., 2018, 294, 91-100.
[http://dx.doi.org/10.1016/j.cbi.2018.08.016] [PMID: 30138605]
[22]
Babalghith, A.O.; Al-kuraishy, H.M.; Al-Gareeb, A.I.; De Waard, M.; Al-Hamash, S.M.; Jean-Marc, S.; Negm, W.A.; Batiha, G.E.S. The role of berberine in Covid-19: Potential adjunct therapy. Inflammopharmacology, 2022, 30(6), 2003-2016.
[http://dx.doi.org/10.1007/s10787-022-01080-1] [PMID: 36183284]
[23]
Xu, X.; Zhang, L.; Zhao, Y.; Xu, B.; Qin, W.; Yan, Y.; Yin, B.; Xi, C.; Ma, L. Anti inflammatory mechanism of berberine on lipopolysaccharide induced IEC 18 models based on comparative transcriptomics. Mol. Med. Rep., 2020, 22(6), 5163-5180.
[http://dx.doi.org/10.3892/mmr.2020.11602] [PMID: 33174609]
[24]
Javed Iqbal, M.; Quispe, C.; Javed, Z.; Sadia, H.; Qadri, Q.R.; Raza, S.; Salehi, B.; Cruz-Martins, N.; Abdulwanis Mohamed, Z.; Sani Jaafaru, M.; Abdull Razis, A.F.; Sharifi-Rad, J. Nanotechnology-based strategies for berberine delivery system in cancer treatment: Pulling strings to keep berberine in power. Front. Mol. Biosci., 2021, 7, 624494.
[http://dx.doi.org/10.3389/fmolb.2020.624494] [PMID: 33521059]
[25]
Teleanu, D.; Chircov, C.; Grumezescu, A.; Volceanov, A.; Teleanu, R. Blood-brain delivery methods using nanotechnology. Pharmaceutics, 2018, 10(4), 269.
[http://dx.doi.org/10.3390/pharmaceutics10040269] [PMID: 30544966]
[26]
Raju, M.; Kulkarni, Y.A.; Wairkar, S. Therapeutic potential and recent delivery systems of berberine: A wonder molecule. J. Funct. Foods, 2019, 61, 103517.
[http://dx.doi.org/10.1016/j.jff.2019.103517]
[27]
Kashyap, D.; Tuli, H.S.; Yerer, M.B.; Sharma, A.; Sak, K.; Srivastava, S.; Pandey, A.; Garg, V.K.; Sethi, G.; Bishayee, A. Natural product-based nanoformulations for cancer therapy: Opportunities and challenges. Semin. Cancer Biol., 2021, 69, 5-23.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.014] [PMID: 31421264]
[28]
René, C.A.; Parks, R.J. Delivery of therapeutic agents to the central nervous system and the promise of extracellular vesicles. Pharmaceutics, 2021, 13(4), 492.
[http://dx.doi.org/10.3390/pharmaceutics13040492] [PMID: 33916841]
[29]
Liu, Y.; Chen, Z.; Li, A.; Liu, R.; Yang, H.; Xia, X. The phytochemical potential for brain disease therapy and the possible nanodelivery solutions for brain access. Front. Oncol., 2022, 12, 936054.
[http://dx.doi.org/10.3389/fonc.2022.936054] [PMID: 35814371]
[30]
Amirmahani, N.; Mahmoodi, N.O.; Mohammadi Galangash, M.; Ghavidast, A. Advances in nanomicelles for sustained drug delivery. J. Ind. Eng. Chem., 2017, 55, 21-34.
[http://dx.doi.org/10.1016/j.jiec.2017.06.050]
[31]
Azadi, R.; Mousavi, S.E.; Kazemi, N.M.; Yousefi-Manesh, H.; Rezayat, S.M.; Jaafari, M.R. Anti-inflammatory efficacy of Berberine Nanomicelle for improvement of cerebral ischemia: Formulation, characterization and evaluation in bilateral common carotid artery occlusion rat model. BMC Pharmacol. Toxicol., 2021, 22(1), 54.
[http://dx.doi.org/10.1186/s40360-021-00525-7] [PMID: 34600570]
[32]
Azadi, R.; Musavi, S.E.; Motekef, N.; Rezayat, S.M.; Jafari, M. Preparation and characterization of berberine loaded micelle formulations with approach to oral drug delivery. Trends Pharmacol. Sci., 2020, 6(4), 255-262.
[33]
Dong, Z.; Yuan, Y. Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Inhibition by ST1926. Int. J. Mol. Med., 2018, 41(6), 3405-3421.
[http://dx.doi.org/10.3892/ijmm.2018.3574] [PMID: 29568857]
[34]
Skrzypczak-Wiercioch, A.; Sałat, K. Lipopolysaccharide-induced model of neuroinflammation: Mechanisms of action, research application and future directions for its use. Molecules, 2022, 27(17), 5481.
[http://dx.doi.org/10.3390/molecules27175481] [PMID: 36080253]
[35]
Thomas, R.C.; Bath, M.F.; Stover, C.M.; Lambert, D.G.; Thompson, J.P. Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system. Peptides, 2014, 61, 56-60.
[http://dx.doi.org/10.1016/j.peptides.2014.08.009] [PMID: 25161013]
[36]
Sohrabi, M.J.; Dehpour, A.R.; Attar, F.; Hasan, A.; Mohammad-Sadeghi, N.; Meratan, A.A.; Aziz, F.M.; Salihi, A.; Shekha, M.S.; Akhtari, K.; Shahpasand, K.; Hojjati, S.M.M.; Sharifi, M.; Saboury, A.A.; Rezayat, S.M.; Mousavi, S.E.; Falahati, M. Silymarin-albumin nanoplex: Preparation and its potential application as an antioxidant in nervous system in vitro and in vivo. Int. J. Pharm., 2019, 572, 118824.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118824] [PMID: 31715345]
[37]
Sahibzada, M.U.K.; Sadiq, A.; Faidah, H.S.; Khurram, M.; Amin, M.U.; Haseeb, A.; Kakar, M. Berberine nanoparticles with enhanced in vitro bioavailability: Characterization and antimicrobial activity. Drug Des. Devel. Ther., 2018, 12, 303-312.
[http://dx.doi.org/10.2147/DDDT.S156123] [PMID: 29491706]
[38]
Kwon, M.; Lim, D.Y.; Lee, C.H.; Jeon, J.H.; Choi, M.K.; Song, I.S. Enhanced intestinal absorption and pharmacokinetic modulation of berberine and its metabolites through the inhibition of P-Glycoprotein and intestinal metabolism in rats using a berberine mixed micelle formulation. Pharmaceutics, 2020, 12(9), 882.
[http://dx.doi.org/10.3390/pharmaceutics12090882]
[39]
Raju, M.; Kunde, S.S.; Auti, S.T.; Kulkarni, Y.A.; Wairkar, S. Berberine loaded nanostructured lipid carrier for Alzheimer’s disease: Design, statistical optimization and enhanced in vivo performance. Life Sci., 2021, 285, 119990.
[http://dx.doi.org/10.1016/j.lfs.2021.119990] [PMID: 34592234]
[40]
Bose, A.; Roy Burman, D.; Sikdar, B.; Patra, P. Nanomicelles: Types, properties and applications in drug delivery. IET Nanobiotechnol., 2021, 15(1), 19-27.
[http://dx.doi.org/10.1049/nbt2.12018] [PMID: 34694727]
[41]
Pishva, S.P.; Mousavi, S.E.; Mousavi, Z.; Jaafari, M.R.; Dehpour, A.R.; Rezayat Sorkhabadi, S.M. The effect of berberine nanomicells on hepatic cirrhosis in bile duct ligated rats. International Pharmacy Acta, 2018, 1(1), 146-146.
[http://dx.doi.org/10.22037/ipa.v1i1.20455]
[42]
Wang, Y.; Pi, C.; Feng, X.; Hou, Y.; Zhao, L.; Wei, Y. The influence of nanoparticle properties on oral bioavailability of drugs. Int. J. Nanomedicine, 2020, 15, 6295-6310.
[http://dx.doi.org/10.2147/IJN.S257269] [PMID: 32943863]
[43]
Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med., 2018, 54(4), 287-293.
[http://dx.doi.org/10.1016/j.ajme.2017.09.001]
[44]
Batista, C.R.A.; Gomes, G.F.; Candelario-Jalil, E.; Fiebich, B.L.; de Oliveira, A.C.P. Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int. J. Mol. Sci., 2019, 20(9), 2293.
[http://dx.doi.org/10.3390/ijms20092293] [PMID: 31075861]
[45]
Zhao, J.; Bi, W.; Xiao, S.; Lan, X.; Cheng, X.; Zhang, J.; Lu, D.; Wei, W.; Wang, Y.; Li, H.; Fu, Y.; Zhu, L. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci. Rep., 2019, 9(1), 5790.
[http://dx.doi.org/10.1038/s41598-019-42286-8] [PMID: 30962497]
[46]
Ishijima, T.; Nakajima, K. Inflammatory cytokines TNFα, IL-1β, and IL-6 are induced in endotoxin- stimulated microglia through different signaling cascades. Sci. Prog., 2021, 104(4)
[http://dx.doi.org/10.1177/00368504211054985] [PMID: 34821182]
[47]
Zhang, Z.; Li, X.; Li, F.; An, L. Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice. Int. Immunopharmacol., 2016, 38, 426-433.
[http://dx.doi.org/10.1016/j.intimp.2016.06.031] [PMID: 27376853]