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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Neuroprotective Effect of Lithospermum officinale Callus Extract on Inflamed Primary Microglial Cells

Author(s): Maryam Kheyrollah, Mohsen Farhadpour, Farzaneh Sabouni and Kamahldin Haghbeen*

Volume 25, Issue 5, 2024

Published on: 04 September, 2023

Page: [637 - 644] Pages: 8

DOI: 10.2174/1389201024666230816154639

Price: $65

Abstract

Background: Plants that have therapeutic features for humans or animals are commonly referred to as "medicinal plants". They produce secondary metabolites with antioxidant, antimicrobial and/or anti-cancer effects. Lithospermum officinale, known as European stone seed, is a famous medicinal herb. However, due to the pyrrolizidine alkaloids (PzAl) in the root extract of L.officinal, there are therapeutic limitations to this herb.

Objective: This research was devoted to the evaluation of the anti-inflammatory capacity of methanolic extracts of L. officinale callus (LoE) (fresh cells) on rat microglial cells, the immune cells of the Central Nervous System, which play an essential role in the responses to neuroinflammation.

Methods: Primary microglia were obtained from neonatal Wistar rats (1 to 3-days old), and then treated with various concentration of CfA and methanolic extracts of 17 and 31-day-old L. officinale callus before LPS-stimulation. In addition to HPLC analysis of the extracts, viability, nitric oxide production, and evaluation of pro-inflammatory genes and cytokines in the inflamed microglia were investigated by MTT, Griess methos, qrt-PCR, and ELISA.

Results: Methanolic extract of the 17-day-old callus of L. officinale exhibited anti-inflammatory effects on LPS-stimulated microglial cells much higher than observed for CfA. The data were further supported by the decreased expression of Nos2, Tnf-α, and Cox-2 mRNA and the suppression of TNF-α and IL-1β release in the activated microglial cells pretreated with the effective dose of LoE (0.8 mg mL-1).

Conclusion: It was assumed that the better anti-neuroinflammatory performance of LoE than CfA in LPS-activated primary microglia could be a result of the synergism of the components of the extract and the lipophilic nature of RsA as the main phenolic acid of LoE. Considering that LoE shows a high antioxidant capacity and lacks PzAl, it is anticipated that LoE extract might be considered a reliable substitute to play a key role in the preparation of neuroprotective pharmaceutical formulas, which require in vivo research and further experiments.

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[1]
Mohtasham, A.Z.; Tanideh, N.; Seddighi, A.; Mokhtari, M.; Amini, M.; Shakouri, P.A.; Manafi, A.; Hashemi, S.S.; Mehrabani, D. The effect of lithospermum officinale, silver sulfadiazine and alpha ointments in healing of burn wound injuries in rat. World J. Plast. Surg., 2017, 6(3), 313-318.
[PMID: 29218280]
[2]
Ma, X.H.; Ma, Y.; Tang, J.F.; He, Y.L.; Liu, Y.C.; Ma, X.J.; Shen, Y.; Cui, G.H.; Lin, H.X.; Rong, Q.X.; Guo, J.; Huang, L.Q. The biosynthetic pathways of tanshinones and phenolic acids in Salvia miltiorrhiza. Molecules, 2015, 20(9), 16235-16254.
[http://dx.doi.org/10.3390/molecules200916235] [PMID: 26370949]
[3]
Al-Snai, A. Chemical constituents and pharmacological effects of Lithospermum officinale. IOSR J. Pharm., 2019, 9(8), 12-21.
[4]
Khosravi, E.; Mousavi, A.; Farhadpour, M.; Ghashghaie, J.; Ghanati, F.; Haghbeen, K. Pyrrolizidine alkaloids-free extract from the cell culture of lithospermum officinale with high antioxidant capacity. Appl. Biochem. Biotechnol., 2019, 187(3), 744-752.
[http://dx.doi.org/10.1007/s12010-018-2830-3] [PMID: 30054862]
[5]
Hosseinzadeh, H.; Shahandeh, S.; Shahsavand, S. Anxiolytic and hypnotic effects of aqueous and ethanolic extracts of aerial parts of Echium italicum L. in mice. Jundishapur J. Nat. Pharm. Prod., 2012, 7(2), 71-79.
[http://dx.doi.org/10.17795/jjnpp-4589] [PMID: 24624158]
[6]
Xiang, H.; Liu, C.; Xiao, Z.; Du, L.; Wei, N.; Liu, F.; Song, Y. Enoxaparin attenuates pyrrolizidine alkaloids‐induced hepatic sinusoidal obstruction syndrome by inhibiting oncostatin M expression. Liver Int., 2023, 43(3), 626-638.
[http://dx.doi.org/10.1111/liv.15475] [PMID: 36354295]
[7]
Schoental, R.; Cavanagh, J.B. Brain and spinal cord tumors in rats treated with pyrrolizidine alkaloids. J. Natl. Cancer Inst., 1972, 49(3), 665-671.
[PMID: 4647490]
[8]
Szwajgier, D.; Borowiec, K.; Pustelniak, K. The neuroprotective effects of phenolic acids: Molecular mechanism of action. Nutrients, 2017, 9(5), 477.
[http://dx.doi.org/10.3390/nu9050477] [PMID: 28489058]
[9]
Tsai, C.F.; Kuo, Y.H.; Yeh, W.L.; Wu, C.; Lin, H.Y.; Lai, S.W.; Liu, Y.S.; Wu, L.H.; Lu, J.K.; Lu, D.Y. Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in microglial cells. Int. J. Mol. Sci., 2015, 16(12), 5572-5589.
[http://dx.doi.org/10.3390/ijms16035572] [PMID: 25768341]
[10]
Magnani, C.; Isaac, V.L.B.; Correa, M.A.; Salgado, H.R.N. Caffeic acid: A review of its potential use in medications and cosmetics. Anal. Methods, 2014, 6(10), 3203-3210.
[http://dx.doi.org/10.1039/C3AY41807C]
[11]
Jiang, H.E.; Li, X.; Liu, C-J.; Wang, Y-F.; Li, C-S. Fruits of Lithospermum officinale L. (Boraginaceae) used as an early plant decoration (2500years BP) in Xinjiang, China. J. Archaeol. Sci., 2007, 34(2), 167-170.
[http://dx.doi.org/10.1016/j.jas.2006.04.003]
[12]
Subin, P.; Sabuhom, P.; Naladta, A.; Luecha, P.; Nualkaew, S.; Nualkaew, N. An evaluation of the anti-inflammatory effects of a thai traditional polyherbal recipe TPDM6315 in LPS-Induced RAW264.7 macrophages and TNF-α-induced 3T3-L1 adipocytes. Curr. Issues Mol. Biol., 2023, 45(6), 4891-4907.
[http://dx.doi.org/10.3390/cimb45060311] [PMID: 37367060]
[13]
Alhallaf, W.; Perkins, L.B. The anti-inflammatory properties of chaga extracts obtained by different extraction methods against LPS-induced RAW 264.7. Molecules, 2022, 27(13), 4207.
[http://dx.doi.org/10.3390/molecules27134207] [PMID: 35807453]
[14]
Liu, M.; Song, S.; Li, H.; Jiang, X.; Yin, P.; Wan, C.; Liu, X.; Liu, F.; Xu, J. The protective effect of caffeic acid against inflammation injury of primary bovine mammary epithelial cells induced by lipopolysaccharide. J. Dairy Sci., 2014, 97(5), 2856-2865.
[http://dx.doi.org/10.3168/jds.2013-7600] [PMID: 24612802]
[15]
Basu Mallik, S.; Mudgal, J.; Nampoothiri, M.; Hall, S.; Dukie, S.A.; Grant, G.; Rao, C.M.; Arora, D. Caffeic acid attenuates lipopolysaccharide-induced sickness behaviour and neuroinflammation in mice. Neurosci. Lett., 2016, 632, 218-223.
[http://dx.doi.org/10.1016/j.neulet.2016.08.044] [PMID: 27597761]
[16]
Chen, H.; Li, R. Introduction of diabetes mellitus and future prospects of natural products on diabetes mellitus; Structure and Health Effects of Natural Products on Diabetes Mellitus, 2021, pp. 1-15.
[http://dx.doi.org/10.1007/978-981-15-8791-7_1]
[17]
Gargouri, B.; Carstensen, J.; Bhatia, H.S.; Huell, M.; Dietz, G.P.H.; Fiebich, B.L. Anti-neuroinflammatory effects of Ginkgo biloba extract EGb761 in LPS-activated primary microglial cells. Phytomedicine, 2018, 44, 45-55.
[http://dx.doi.org/10.1016/j.phymed.2018.04.009] [PMID: 29895492]
[18]
Wang, T.; Qin, L.; Liu, B.; Liu, Y.; Wilson, B.; Eling, T.E.; Langenbach, R.; Taniura, S.; Hong, J.S. Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia. J. Neurochem., 2004, 88(4), 939-947.
[http://dx.doi.org/10.1046/j.1471-4159.2003.02242.x] [PMID: 14756815]
[19]
Zhang, Y.; Gao, W.; Yang, K.; Tao, H.; Yang, H. Salt-inducible kinase 1 (SIK1) is induced by alcohol and suppresses microglia inflammation via NF-κB signaling. Cell. Physiol. Biochem., 2018, 47(4), 1411-1421.
[http://dx.doi.org/10.1159/000490831] [PMID: 29929190]
[20]
Zhu, J.; Li, S.; Zhang, Y.; Ding, G.; Zhu, C.; Huang, S.; Zhang, A.; Jia, Z.; Li, M. COX-2 contributes to LPS-induced Stat3 activation and IL-6 production in microglial cells. Am. J. Transl. Res., 2018, 10(3), 966-974.
[PMID: 29636886]
[21]
Xu, Y.; Tang, D.; Wang, J.; Wei, H.; Gao, J. Neuroprotection of andrographolide against microglia-mediated inflammatory injury and oxidative damage in PC12 neurons. Neurochem. Res., 2019, 44(11), 2619-2630.
[http://dx.doi.org/10.1007/s11064-019-02883-5] [PMID: 31562575]
[22]
Arulselvan, P.; Masoumeh, T.F.; Woan, S.T.; Sivapragasam, G.; Sharida, F.; Mohd, E.N.; Suresh, K. Role of antioxidants and natural products in inflammation. Oxid. Med. Cell. Longev., 2016, 2016, 5276130.
[http://dx.doi.org/10.1155/2016/5276130]
[23]
Spagnuolo, C.; Moccia, S.; Russo, G.L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur. J. Med. Chem., 2018, 153, 105-115.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.001] [PMID: 28923363]
[24]
Job, N.; Thimmakondu, V.S.; Thirumoorthy, K. In silico drug design and analysis of dual amyloid-beta and tau protein-aggregation inhibitors for Alzheimer’s disease treatment. Molecules, 2023, 28(3), 1388.
[http://dx.doi.org/10.3390/molecules28031388] [PMID: 36771052]
[25]
Muchowski, P.J.; Wacker, J.L. Modulation of neurodegeneration by molecular chaperones. Nat. Rev. Neurosci., 2005, 6(1), 11-22.
[http://dx.doi.org/10.1038/nrn1587] [PMID: 15611723]
[26]
Long, H.Z.; Cheng, Y.; Zhou, Z.W.; Luo, H.Y.; Wen, D.D.; Gao, L.C. PI3K/AKT signal pathway: A target of natural products in the prevention and treatment of Alzheimer’s disease and Parkinson’s disease. Front. Pharmacol., 2021, 12, 648636.
[http://dx.doi.org/10.3389/fphar.2021.648636] [PMID: 33935751]
[27]
Breijyeh, Z.; Karaman, R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 2020, 25(24), 5789.
[http://dx.doi.org/10.3390/molecules25245789] [PMID: 33302541]
[28]
Montuori, E.; Hyde, C.A.C.; Crea, F.; Golding, J.; Lauritano, C. Marine natural products with activities against prostate cancer: Recent discoveries. Int. J. Mol. Sci., 2023, 24(2), 1435.
[http://dx.doi.org/10.3390/ijms24021435] [PMID: 36674949]
[29]
Xu, L.; Li, Y.; Dai, Y.; Peng, J. Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms. Pharmacol. Res., 2018, 130, 451-465.
[http://dx.doi.org/10.1016/j.phrs.2018.01.015] [PMID: 29395440]
[30]
Wang, C.; Zong, S.; Cui, X.; Wang, X.; Wu, S.; Wang, L.; Liu, Y.; Lu, Z. The effects of microglia-associated neuroinflammation on Alzheimer’s disease. Front. Immunol., 2023, 14, 1117172.
[http://dx.doi.org/10.3389/fimmu.2023.1117172] [PMID: 36911732]
[31]
Timmerman, R.; Burm, S.M.; Bajramovic, J.J. An overview of in vitro methods to study microglia. Front. Cell. Neurosci., 2018, 12, 242.
[http://dx.doi.org/10.3389/fncel.2018.00242] [PMID: 30127723]
[32]
Mohan, H.; Friese, A.; Albrecht, S.; Krumbholz, M.; Elliott, C.L.; Arthur, A.; Menon, R.; Farina, C.; Junker, A.; Stadelmann, C.; Barnett, S.C.; Huitinga, I.; Wekerle, H.; Hohlfeld, R.; Lassmann, H.; Kuhlmann, T.; Linington, C.; Meinl, E. Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination. Acta Neuropathol. Commun., 2014, 2(1), 178.
[http://dx.doi.org/10.1186/s40478-014-0168-9] [PMID: 25589163]
[33]
Denizot, F.; Lang, R. Rapid colorimetric assay for cell growth and survival. J. Immunol. Methods, 1986, 89(2), 271-277.
[http://dx.doi.org/10.1016/0022-1759(86)90368-6] [PMID: 3486233]
[34]
Green, L.C.; Wagner, D.A.; Glogowski, J.; Skipper, P.L.; Wishnok, J.S.; Tannenbaum, S.R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal. Biochem., 1982, 126(1), 131-138.
[http://dx.doi.org/10.1016/0003-2697(82)90118-X] [PMID: 7181105]
[35]
Mehrabadi, S.; Sadr, S.S. Assessment of probiotics mixture on memory function, inflammation markers, and oxidative stress in an Alzheimer’s disease model of rats. Iran. Biomed. J., 2020, 24(4), 220-228.
[http://dx.doi.org/10.29252/ibj.24.4.220] [PMID: 32306720]
[36]
Zhang, L.; Li, Y.J.; Wu, X.Y.; Hong, Z.; Wei, W.S. MicroRNA-181c negatively regulates the inflammatory response in oxygen-glucose-deprived microglia by targeting Toll-like receptor 4. J. Neurochem., 2015, 132(6), 713-723.
[http://dx.doi.org/10.1111/jnc.13021] [PMID: 25545945]
[37]
Oh, S.Y.; Kim, Y.H.; Bae, D.S.; Um, B.H.; Pan, C.H.; Kim, C.Y.; Lee, H.J.; Lee, J.K. Anti-inflammatory effects of gomisin N, gomisin J, and schisandrin C isolated from the fruit of Schisandra chinensis. Biosci. Biotechnol. Biochem., 2010, 74(2), 285-291.
[http://dx.doi.org/10.1271/bbb.90597] [PMID: 20139628]
[38]
Jafernik, K.; Ekiert, H.; Szopa, A. Schisandra henryi—a rare species with high medicinal potential. Molecules, 2023, 28(11), 4333.
[http://dx.doi.org/10.3390/molecules28114333] [PMID: 37298808]
[39]
Chen, R.; Yang, Y.; Xu, J.; Pan, Y.; Zhang, W.; Xing, Y.; Ni, H.; Sun, Y.; Hou, Y.; Li, N. Tamarix hohenackeri Bunge exerts anti-inflammatory effects on lipopolysaccharide-activated microglia in vitro. Phytomedicine, 2018, 40, 10-19.
[http://dx.doi.org/10.1016/j.phymed.2017.12.035] [PMID: 29496162]
[40]
Xie, Q.; Wu, G.Z.; Yang, N.; Shen, Y.H.; Tang, J.; Zhang, W.D. Delavatine A, an unusual isoquinoline alkaloid exerts anti-inflammation on LPS-induced proinflammatory cytokines production by suppressing NF-κB activation in BV-2 microglia. Biochem. Biophys. Res. Commun., 2018, 502(2), 202-208.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.144] [PMID: 29792864]
[41]
Yin, L.; Dai, Q.; Jiang, P.; Zhu, L.; Dai, H.; Yao, Z.; Liu, H.; Ma, X.; Qu, L.; Jiang, J. Manganese exposure facilitates microglial JAK2-STAT3 signaling and consequent secretion of TNF-a and IL-1β to promote neuronal death. Neurotoxicology, 2018, 64, 195-203.
[http://dx.doi.org/10.1016/j.neuro.2017.04.001] [PMID: 28385490]
[42]
dos-Santos-Pereira, M.; Guimarães, F.S.; Del-Bel, E.; Raisman-Vozari, R.; Michel, P.P. Cannabidiol prevents LPS‐induced microglial inflammation by inhibiting ROS/NF‐κB‐dependent signaling and glucose consumption. Glia, 2020, 68(3), 561-573.
[http://dx.doi.org/10.1002/glia.23738] [PMID: 31647138]
[43]
Ci, X.; Ren, R.; Xu, K.; Li, H.; Yu, Q.; Song, Y.; Wang, D.; Li, R.; Deng, X. Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 cells. Inflammation, 2010, 33(2), 126-136.
[http://dx.doi.org/10.1007/s10753-009-9166-7] [PMID: 20238486]
[44]
Stähli, A.; Maheen, C.U.; Strauss, F.J.; Eick, S.; Sculean, A.; Gruber, R. Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1. Int. J. Oral Sci., 2019, 11(1), 6.
[http://dx.doi.org/10.1038/s41368-018-0039-5] [PMID: 30783082]
[45]
Gupta, S.C.; Kim, J.H.; Prasad, S.; Aggarwal, B.B. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev., 2010, 29(3), 405-434.
[http://dx.doi.org/10.1007/s10555-010-9235-2] [PMID: 20737283]
[46]
Lu, Y.; Ding, X.; Wu, X.; Huang, S. Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage. Fundam. Clin. Pharmacol., 2020, 34(2), 229-237.
[http://dx.doi.org/10.1111/fcp.12508] [PMID: 31514224]
[47]
Yang, W.S.; Deok, J.; Young-Su, Y.; Jae, G.P.; Hyohyun, S.; Sang, H.M.; Sungyoul, H.; Jae, Y.C. IRAK1/4-targeted anti-inflammatory action of caffeic acid. Mediators Inflamm., 2013, 2013, 518183.

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