Pharmacodynamics study of <i>Panax notoginseng</i> saponins zein lipoprotein nanoparticles for cerebral ischemia reperfusion injury in rats

LIANG Yiping; FU Wen; ZHANG Zhenhai; LYU Huixia

doi:10.11665/j.issn.1000-5048.20210308

Journal of China Pharmaceutical University > 2021 > 52(3): 318-324. > DOI: 10.11665/j.issn.1000-5048.20210308

LIANG Yiping, FU Wen, ZHANG Zhenhai, LYU Huixia. Pharmacodynamics study of Panax notoginseng saponins zein lipoprotein nanoparticles for cerebral ischemia reperfusion injury in rats[J]. Journal of China Pharmaceutical University, 2021, 52(3): 318-324. DOI: 10.11665/j.issn.1000-5048.20210308

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Pharmacodynamics study of Panax notoginseng saponins zein lipoprotein nanoparticles for cerebral ischemia reperfusion injury in rats

1.
Department of Pharmaceutics, School of pharmacy, China Pharmaceutical University, Nanjing 211198
2.
Jiangsu Provincial Academy of Traditional Chinese Medicine ,Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210028, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81673830)

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Received Date: January 20, 2021
Revised Date: April 26, 2021

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Abstract

Abstract

PLZ-NPs (PNS-lipid-zein nanoparticles) prepared by co-assembly of Panax notoginseng saponins, lecithin, β-sitosterol and zein were applied for in vitro cell experiment and oral gavage to study the protective effect of cerebral ischemia-reperfusion rats.PLZ-NPs were characterized by Malvin-particle size analyzer and transmission electron microscope (TEM), respectively. The toxicity of PLZ-NPs and free carrier were evaluated by MTT, and the uptake of nanoparticles in Caco-2 cells was analyzed by laser confocal and flow cytometry. The cerebral ischemia reperfusion rat model was established by MCAO method and then be given samples by gavage for 3 days. The brain tissues were taken to stain by 2, 3, 5-triphenyltetrazole chloride (TTC) and the biochemical indicators of MDA, inflammatory cytokines IL-1β and TNF-α, apoptosis-related proteins Bax and Bcl-2 from the harvested brain tissues were detected to evaluate the protective effect of PNS in PLZ-NPs on cerebral ischemia reperfusion. The particle size, PDI, and zeta potential of formed PLZ-NPs were (116.4 ± 0.81) nm, 0.048 and -(31.5 ± 0.31) mV, respectively. The results of MTT showed that the zein lipoprotein carrier was non-toxic to Caco-2 cells. The results of laser confocal and flow cytometry showed that FITC uptake of nanoparticles could be significantly improved in Caco-2 cells.The uptake from the nanoparticles at 4h was 1.76 times of that of the free FITC group.Compared with the model group, the TTC staining images of free drug PNS group and PLZ-NPs group showed certain reduction in the white infarct area.The contents of MDA, IL-1β, TNF-α and Bax were significantly decreased, while the content of Bcl-2 was significantly increased. Furthermore, all parameters of PLZ-NPs group showed better results than those of PNS group, and there was a significant difference (P < 0.05). All results indicated that the prepared PLZ-NPs had good stability and biological safety, and could significantly increase the uptake in intestinal epithelial cells, and effectively protect against the damage caused by cerebral ischemia reperfusion in rats.
- Panax notginseng saponins,
- zein,
- lipoprotein nanoparticles,
- cerebral ischemia-reperfusion

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References

[1]	. Chin J Integr Med，2017，23（6）：445-452.
[2]	Yu YL，Sun GB，Luo Y，et al. Cardioprotective effects of notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic Reticulum stress- related signaling pathways［J］. Sci Rep，2016，6：21730.
[3]	Yang X，Xiong X，Wang H，et al. Protective effects of Panax notoginseng saponins on cardiovascular diseases：a comprehensive overview of experimental studies［J］. Evid Based Complement Alternat Med，2014，2014：204840.
[4]	Zhai YS，Du SY，Xu B，et al. O/W partition coefficient of PNS and absorption kinetics of it in rat intestine［J］. China J Chin Mater Med（中国中药杂志），2010，35（8）：984-988.
[5]	Lai L，Liu HG，Qin Y，et al. Effects of absorption enhancers on small intestinal absorption of Panax notoginseng saponins［J］. Chin J New Drugs（中国新药杂志），2011，20（10）：909-913.
[6]	Liao ZG，Han XZ，Li X，et al. Physicochemical property and protective effect on acute myocardial ischemia in rats of Panax notoginseng saponins-loaded complex nano vesicles［J］. Chin J New Drugs （中国新药杂志），2013，48（11）：899-903.
[7]	Hasegawa H，Sung JH，Matsumiya S，et al. Main ginseng saponin metabolites formed by intestinal bacteria［J］. Planta Med，1996，62（5）：453-457.
[8]	Liu HF，Yang JL，Du FF，et al. Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats［J］. Drug Metab Dispos，2009，37（12）：2290-2298.
[9]	Guo YP，Shao L，Chen MY，et al. In vivo metabolic profiles of Panax notoginseng saponins mediated by gut microbiota in rats［J］. J Agric Food Chem，2020，68（25）：6835-6844.
[10]	Lai L，Liu HG，Lu SH，et al. Pharmacokinetics and correlation between in vivo absorption and in vitro release of Panax notoginseng saponins enteric microcapsule［J］. Chin J New Drugs（中国新药杂志），2012，21（6）：693-696.
[11]	Han M，Fu S，Fang XL. Screening of Panax notoginsenoside water in oil microemulsion formulations and their evaluation in vitro and in vivo［J］. Acta Pharm Sin（药学学报），2007，42（7）：780-786.
[12]	Liu Z，Zhang Q，Ding L，et al. Preparation procedure and pharmacokinetic study of water-in-oil nanoemulsion of Panax notoginseng saponins for improving the oral bioavailability［J］. Curr Drug Deliv，2016，13（4）：600-610.
[13]	Momany FA，Sessa DJ，Lawton JW，et al. Structural characterization of alpha-zein［J］. J Agric Food Chem，2006，54（2）：543-547.
[14]	Hong SS，Thapa RK，Kim JH，et al. Role of zein incorporation on hydrophobic drug-loading capacity and colloidal stability of phospholipid nanoparticles［J］. Colloids Surf B Biointerfaces，2018，171：514-521.
[15]	Li M，Yu M. Development of a nanoparticle delivery system based on zein/polysaccharide complexes［J］. J Food Sci，2020，85（12）：4108-4117.
[16]	Xie ZH，Zhang ZH，Lv H. Rapamycin loaded TPGS-Lecithins-Zein nanoparticles based on core-shell structure for oral drug administration［J］. Int J Pharm，2019，568：118529.
[17]	Cheng ZT，Yao K，Liu WW，et al. Preparation and characterization of composite delivery system of paclitaxel-loaded temperature sensitive liposome and siRNA-loaded gold nanostar［J］. J China Pharm Univ （中国药科大学学报），2017，48（4）：445-452.
[18]	Hao JM，Wang H，Li Q，et al. Preparation and in vitro studies of polysaccharide modified compound liposomes loaded with paclitaxe and doxorubicin［J］. J China Pharm Univ （中国药科大学学报），2017，48 （6）：680-686.
[19]	Bin Sayeed MS，Karim SMR，Sharmin T，et al. Critical analysis on characterization，systemic effect，and therapeutic potential of beta-sitosterol：a plant-derived orphan phytosterol［J］. Medicines （Basel），2016，3 （4）：29.
[20]	Huang LF，Chen CW，Zhang X，et al. Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation［J］. J Mol Neurosci，2018，64（1）：129-139.
[21]	Zhang Y，Chen WA，Huang SS，et al. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms［J］. Eur J Pharmacol，2016，771：145-151.
[22]	Zou S，Zhang MX，Feng LM，et al. Protective effects of notoginsenoside R1 on cerebral ischemia-reperfusion injury in rats［J］. Exp Ther Med，2017，14（6）：6012-6016.
[23]	Jin Z，Guo P，Li X，et al. Neuroprotective effects of irisin against cerebral ischemia/ reperfusion injury via Notch signaling pathway［J］. Biomed Pharmacother，2019，120：109452.
[24]	Lin J，Liang P，Huang Q，et al. Research progress of protective effect of Panax notoginseng saponins on cerebral ischemia injury［J］. World Latest Med Inf（世界最新医学信息文摘），2018，18（16）：97-99.
[25]	Bibi S，Kaur R，Henriksen-Lacey M，et al. Microscopy imaging of liposomes：from coverslips to environmental SEM［J］. Int J Pharm，2011，417（1/2）：138-150.
[26]	Majzoub RN，Ewert KK，Safinya CR. Cationic liposome—nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing［J］. Philos Trans A Math Phys Eng Sci，2016，374（2072）：20150129.
[27]	Almgren M ，Edwards K，Karlsson G. Cryo transmission electron microscopy of liposomes and related structures［J］. Colloids Surf A Physicochem Eng Asp，2000，174（1/2）：3-21.
[28]	Zhang CB，Shen MH，Teng FM，et al. Ultrasound-enhanced protective effect of tetramethylpyrazine via the ROS/HIF-1A signaling pathway in an in vitro cerebral ischemia/reperfusion injury model［J］. Ultrasound Med Biol，2018，44（8）：1786-1798.
[29]	He R，Jiang Y，Shi Y，et al. Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis［J］. Mater Sci Eng C Mater Biol Appl，2020，117：111314.
[30]	Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury［J］. Free Radic Biol Med，1990，9（6）：515-540.
[31]	Kvansakul M，Hinds MG. Structural biology of the Bcl-2 family and its mimicry by viral proteins［J］. Cell Death Dis，2013，4：e909.
[32]	Li M，Yu M. Development of a nanoparticle delivery system based on zein/polysaccharide complexes［J］. J Food Sci，2020，85（12）：4108-4117.
[33]	Pascoli M，Lima DR，Fraceto LF. Zein nanoparticles and strategies to improve colloidal stability：a mini-review［J］. Front Chem，2018，6：6.

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[10]	Inhibition of Paeonol on Arrhythmias Induced by Ischemia reperfusion in Rats[J]. Journal of China Pharmaceutical University, 1997, (4): 35-37.

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