Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Scutellaria baicalensis Extract-phospholipid Complex: Preparation and Initial Pharmacodynamics Research in Rats

Author(s): Shibin Chen*, Qiujie Xie, Ming Yang, Yajun Shi, Junhui Shi and Xiaobin Zeng*

Volume 23, Issue 6, 2022

Published on: 29 July, 2021

Page: [847 - 860] Pages: 14

DOI: 10.2174/1389201022666210729142257

open access plus

Abstract

Background: Baicalin, a flavonoid glycoside compound present in Scutellaria baicalensis, has shown a wide spectrum of biological activities, but its liposolubility, water-solubility and mucosal permeability are all very poor, which leads to the low concentration in brain and poor bioavailability by oral or intravenous injective administration.

Objective: The primary objective of this study was to formulate the Scutellaria baicalensis extract (SBE) with phospholipid to yield Scutellaria baicalensis extract-phospholipid complex (SBEPC) , and to evaluate its pharmacodynamics in the middle cerebral artery occlusion (MCAO).

Methods: The optimal preparation technology of SBEPC was obtained through single-factor test and central composite design-response surface methodology (CCD-RSM), and was characterized with various analytical techniques including SEM, FT-IR and NMR. The storage conditions of SBEPC were established through stability study and the MCAO rat model was investigated through conducting pharmacodynamic studies to screen the appropriate administration and dose of SBEPC as well as to verify the neuroprotective effect of SBEPC on cerebral ischemia-reperfusion injury.

Results: The optimized preparation conditions of SBEPC were summarized as follows: the ratio of phospholipids to drug was 2:1, the drug concentration was 3.5 mg/ml, the reaction temperature was 50 °C, and the entrapment efficiency was over 93.00%. Stability studies have demonstrated that SBEPC should be stored under 40 °C in a dry and ventilated place away from light and below 37% humidity. Furthermore, pharmacodynamic studies have found that, compared with SBE, SBEPC could introduce drugs into the brain and better exert the neuroprotective effect on MCAO rats, and the optimal administration and dose concentration of SBEPC were nasal administration and 40 mg/ml, respectively.

Conclusion: These findings demonstrate that SBEPC is successfully prepared by CCD-RSM. SBEPC can enhance drugs' ability to enter the brain and improve the bioavailability of drugs in brain, and can effectively exert the neuroprotective effect on cerebral ischemia-reperfusion injury as compared with SBE.

Keywords: Scutellaria baicalensis extract-phospholipid complex, central composite design-response surface methodology, stability study, pharmacodynamics, cerebral ischemia.

« Previous Next »
Graphical Abstract

[1]
Liao, H.; Ye, J.; Gao, L.; Liu, Y. The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review. Biomed. Pharmacother., 2021, 133, 110917.
[http://dx.doi.org/10.1016/j.biopha.2020.110917] [PMID: 33217688]
[2]
Yang, F.; Feng, C.; Yao, Y.; Qin, A.; Shao, H.; Qian, K. Antiviral effect of baicalin on Marek’s disease virus in CEF cells. BMC Vet. Res., 2020, 16(1), 371.
[http://dx.doi.org/10.1186/s12917-020-02595-x] [PMID: 33008383]
[3]
Orzechowska, B.U.; Wróbel, G.; Turlej, E.; Jatczak, B.; Sochocka, M.; Chaber, R. Antitumor effect of baicalin from the Scutellaria baicalensis radix extract in B-acute lymphoblastic leukemia with different chromosomal rearrangements. Int. Immunopharmacol., 2020, 79, 106114.
[http://dx.doi.org/10.1016/j.intimp.2019.106114] [PMID: 31881375]
[4]
Yang, B.; Bai, H.; Sa, Y.; Zhu, P.; Liu, P. Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells. J. Cancer, 2020, 11(8), 2303-2317.
[http://dx.doi.org/10.7150/jca.37242] [PMID: 32127957]
[5]
Lei, K.; Shen, Y.; He, Y.; Zhang, L.; Zhang, J.; Tong, W.; Xu, Y.; Jin, L. Baicalin represses C/EBPβ via its antioxidative effect in Parkinson’s disease. Oxid. Med. Cell. Longev., 2020, 2020, 8951907.
[http://dx.doi.org/10.1155/2020/8951907] [PMID: 32566108]
[6]
Gao, X.; Guo, M.; Zhang, Z.; Shen, P.; Yang, Z.; Zhang, N. Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice. Oncotarget, 2017, 8(12), 19894-19901.
[http://dx.doi.org/10.18632/oncotarget.15193] [PMID: 28184027]
[7]
Jiang, M.; Li, Z.; Zhu, G. Protective role of flavonoid baicalin from Scutellaria baicalensis in periodontal disease pathogenesis: A literature review. Complement. Ther. Med., 2018, 38, 11-18.
[http://dx.doi.org/10.1016/j.ctim.2018.03.010] [PMID: 29857875]
[8]
Ma, C.; Wang, X.; Xu, T.; Zhang, S.; Liu, S.; Zhai, C.; Wang, Z.; Mu, J.; Li, C.; Cheng, F.; Wang, Q. An integrative pharmacology-based analysis of refined Qingkailing injection against cerebral ischemic stroke: A novel combination of baicalin, geniposide, cholic acid, and hyodeoxycholic acid. Front. Pharmacol., 2020, 11, 519.
[http://dx.doi.org/10.3389/fphar.2020.00519] [PMID: 32457601]
[9]
Liang, W.; Huang, X.; Chen, W. The effects of baicalin and baicalein on cerebral ischemia: A review. Aging Dis., 2017, 8(6), 850-867.
[http://dx.doi.org/10.14336/AD.2017.0829] [PMID: 29344420]
[10]
Dai, J.; Qiu, Y.M.; Ma, Z.W.; Yan, G.F.; Zhou, J.; Li, S.Q.; Wu, H.; Jin, Y.C.; Zhang, X.H. Neuroprotective effect of baicalin on focal cerebral ischemia in rats. Neural Regen. Res., 2018, 13(12), 2129-2133.
[http://dx.doi.org/10.4103/1673-5374.241464] [PMID: 30323141]
[11]
Li, N.; Feng, L.; Tan, Y.; Xiang, Y.; Zhang, R.; Yang, M. Preparation, characterization, pharmacokinetics and biodistribution of baicalin-loaded liposome on cerebral ischemia-reperfusion after i.v. administration in rats. Molecules, 2018, 23(7), 1747.
[http://dx.doi.org/10.3390/molecules23071747] [PMID: 30018228]
[12]
Wu, J.; Wang, B.; Li, M.; Shi, Y.H.; Wang, C.; Kang, Y.G. Network pharmacology identification of mechanisms of cerebral ischemia injury amelioration by baicalin and geniposide. Eur. J. Pharmacol., 2019, 859, 172484.
[http://dx.doi.org/10.1016/j.ejphar.2019.172484] [PMID: 31229537]
[13]
Xiang, Y.; Long, Y.; Yang, Q.; Zheng, C.; Cui, M.; Ci, Z.; Lv, X.; Li, N.; Zhang, R. Pharmacokinetics, pharmacodynamics and toxicity of baicalin liposome on cerebral ischemia reperfusion injury rats via intranasal administration. Brain Res., 2020, 1726, 146503.
[http://dx.doi.org/10.1016/j.brainres.2019.146503] [PMID: 31605698]
[14]
Zhang, Y.; Liu, S.; Wan, J.; Yang, Q.; Xiang, Y.; Ni, L.; Long, Y.; Cui, M.; Ci, Z.; Tang, D.; Li, N. Preparation, characterization and in vivo study of borneol-baicalin-liposomes for treatment of cerebral ischemia-reperfusion injury. Int. J. Nanomedicine, 2020, 15, 5977-5989.
[http://dx.doi.org/10.2147/IJN.S259938] [PMID: 32904394]
[15]
Mahomoodally, M.F.; Sadeer, N.; Edoo, M.; Venugopala, K.N. The potential application of novel drug delivery systems for phytopharmaceuticals and natural extracts – current status and future perspectives. Mini Rev. Med. Chem., 2020.
[http://dx.doi.org/10.2174/1389557520666200730160911] [PMID: 32744974]
[16]
Mahapatra, D.K.; Patil, S.; Patil, A.G. The progressive journey of phytosomes in herbal based pharmacotherapeutics. Curr. Bioact. Compd., 2020, 16(6), 853-886.
[http://dx.doi.org/10.2174/1573407215666190417121237]
[17]
Patel, J.; Patel, R.; Khambholja, K.; Patel, N. An overview of phytosomes as an advanced herbal drug delivery system. Asian J. Pharm. Sci., 2009, 4(6), 363-371.
[18]
Wu, H.; Long, X.; Yuan, F.; Chen, L.; Pan, S.; Liu, Y.; Stowell, Y.; Li, X. Combined use of phospholipid complexes and self-emulsifying microemulsions for improving the oral absorption of a BCS class IV compound, baicalin. Acta Pharm. Sin. B, 2014, 4(3), 217-226.
[http://dx.doi.org/10.1016/j.apsb.2014.03.002] [PMID: 26579386]
[19]
Chen, L.; Long, X.Y.; Huang, S.H.; Wu, H.Y.; Pan, S.J. Drug delivery systems of baicalin, baicalin-phospholipid complex and self-microemulsifying drug across Caco-2 cell model. Zhong Yao Cai, 2012, 35(5), 757-761.
[PMID: 23213740]
[20]
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.
[http://dx.doi.org/10.1208/s12248-015-9837-2] [PMID: 26563253]
[21]
Nandhini, S.; Ilango, K. Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach. Res. Pharm. Sci., 2020, 16(1), 103-117.
[http://dx.doi.org/10.4103/1735-5362.305193] [PMID: 33953779]
[22]
Udapurkar, P.P.; Bhusnure, O.G. Development, characterization and optimization of kutki phospholipid complex using central composite design and response surface methodology. Int. J. Pharm. Sci. Res., 2020, 11(9), 4655-4666.
[http://dx.doi.org/10.13040/IJPSR.0975-8232.11(9).4655-66]
[23]
Wang, Y.; Shi, Y.; Zou, J.; Zhang, X.; Wang, M.; Guo, D.; Lv, G.; Su, J.; Wang, T. The intranasal administration of Carthamus tinctorius L. extract/phospholipid complex in the treatment of cerebral infarction via the TNF-α/MAPK pathway. Biomed. Pharmacother., 2020, 130, 110563.
[http://dx.doi.org/10.1016/j.biopha.2020.110563] [PMID: 32745908]
[24]
Song, Y.; Zhuang, J.; Guo, J.; Xiao, Y.; Ping, Q. Preparation and properties of a silybin-phospholipid complex. Pharmazie, 2008, 63(1), 35-42.
[PMID: 18271301]
[25]
Wu, J.M.; Chen, D.W.; Liu, Y.L. Study on the preparation of baicalin complex with phospholipid. Zhongguo Zhongyao Zazhi, 2001, 26(3), 166-169.
[http://dx.doi.org/10.1691/ph.2008.7132] [PMID: 12525034]
[26]
Huang, Z.; Chen, L.; Wang, X.; Wang, M. Preparation of high-quality soybean concentrated phospholipids. Food Ind., 2020, 41(3), 61-64.
[27]
Shi, Y.; Wu, P.; Xu, R.; Lin, Y.; Ma, H.; Yang, M. Basic property of baicalin-phospholipid complex. Zhong Cao Yao, 2012, 43(1), 78-82.
[28]
Ma, C.; Wang, X.; Xu, T.; Yu, X.; Zhang, S.; Liu, S.; Gao, Y.; Fan, S.; Li, C.; Zhai, C.; Cheng, F.; Wang, Q. Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 inflammasome signalling pathway. BMC Complement. Altern. Med., 2019, 19(1), 320.
[http://dx.doi.org/10.1186/s12906-019-2703-5] [PMID: 31747940]
[29]
Xu, M.; Chen, X.; Gu, Y.; Peng, T.; Yang, D.; Chang, R.C.C.; So, K.F.; Liu, K.; Shen, J. Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury. J. Ethnopharmacol., 2013, 150(1), 116-124.
[http://dx.doi.org/10.1016/j.jep.2013.08.020] [PMID: 23973788]
[30]
Liu, Z.; Zhang, L.; He, Q.; Liu, X.; Okeke, C.I.; Tong, L.; Guo, L.; Yang, H.; Zhang, Q.; Zhao, H.; Gu, X. Effect of baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia-reperfusion in rats. Int. J. Pharm., 2015, 489(1-2), 131-138.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.049] [PMID: 25895718]
[31]
Zhou, Z.Q.; Li, Y.L.; Ao, Z.B.; Wen, Z.L.; Chen, Q.W.; Huang, Z.G.; Xiao, B.; Yan, X.H. Baicalin protects neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Neural Regen. Res., 2017, 12(10), 1625-1631.
[http://dx.doi.org/10.4103/1673-5374.217335] [PMID: 29171427]
[32]
Xing, J.; Chen, X.; Zhong, D. Absorption and enterohepatic circulation of baicalin in rats. Life Sci., 2005, 78(2), 140-146.
[http://dx.doi.org/10.1016/j.lfs.2005.04.072] [PMID: 16107266]
[33]
Li, N.; Je, Y.J.; Yang, M.; Jiang, X.H.; Ma, J.H. Pharmacokinetics of baicalin-phospholipid complex in rat plasma and brain tissues after intranasal and intravenous administration. Pharmazie, 2011, 66(5), 374-377.
[http://dx.doi.org/10.1691/ph.2011.0783] [PMID: 21699072]
[34]
Shi, Y.J.; Yang, M.; Shi, J.H.; Liu, J.Y.; Tang, M. [Study on formulation of Scutellaria baicalensis extract phospholipid complex nasal preparation]. Zhong Yao Cai, 2013, 36(10), 1697-1701.
[PMID: 24761683]
[35]
Li, N.; Ma, J.H.; Yang, M.; Ye, Y.J.; Xu, R.C. Intranasal adminsitration of baicalin-phospholipid complex improves brain targeting and ischemic-reperfusion injuries. J. Pharm. Sci. Technol., 2012, 4(7), 958-971.

Rights & Permissions Print Cite
Article Metrics
30
1
© 2024 Bentham Science Publishers | Privacy Policy