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Review Article

A Comprehensive Review of n-butylidenephthalide: The Potential Therapeutic Effect and Possibility for Targeted Therapy

In Press, (this is not the final "Version of Record"). Available online 06 June, 2024
Author(s): Swati*, Kangkan Sarma, Ruchi Bhardwaj, Laxita Chauhan, Ritika Sharma and Payel Mal
Published on: 06 June, 2024

Article ID: e060624230782

DOI: 10.2174/0122103155287645240528114302

Price: $95

Abstract

n-Butylidene phthalide (N-BP) is a natural derivative obtained from the chloroform extract of Angelica Sinensis. In conventional medicine, it treats different ailments. Various pharmacological properties are associated with it, including anticancer, anti-inflammatory, and neuroprotective properties. Based on its reported pharmacokinetic profile, n-BP has low oral bioavailability and is rapidly absorbed and eliminated from the body. The compound has diverse pharmacological effects with lower stability, bioavailability, rapid absorption, and elimination. Furthermore, a targeted drug delivery system using a nanocarrier can improve pharmacokinetic-molecular profiling, specificity, efficacy, personal approach, and drug resistance. This review summarizes and emphasizes the pharmacokinetics, and pharmacology of n-butylidene phthalide, and the molecular targeting approach to treat cancer, inflammation, Parkinsonism, excitotoxicity, and Alzheimer’s.

[1]
Ko, W.C. A newly isolated antispasmodic--butylidenephthalide. Jpn. J. Pharmacol., 1980, 30(1), 85-91.
[http://dx.doi.org/10.1254/jjp.30.85] [PMID: 7401411]
[2]
Lin, L.C.; Wang, C.B.; Koh, V.C.; Ko, W.C. Synthesis, properties and molecular structure of alkylidenephthalides. J. Instit. Chem. Academia Sinica., 1984, 31, 9-15.
[3]
Yen, S.Y.; Chuang, H.M.; Huang, M.H.; Lin, S.Z.; Chiou, T.W.; Harn, H.J. n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma. Int. J. Mol. Sci., 2017, 18(2), 372.
[http://dx.doi.org/10.3390/ijms18020372] [PMID: 28208648]
[4]
Hsueh, K.W.; Chiou, T.W.; Chiang, S.F.; Yamashita, T.; Abe, K.; Borlongan, C.V.; Sanberg, P.R.; Huang, A.Y.H.; Lin, S.Z.; Harn, H.J. Autophagic down-regulation in motor neurons remarkably prolongs the survival of ALS mice. Neuropharmacology, 2016, 108, 152-160.
[http://dx.doi.org/10.1016/j.neuropharm.2016.03.035] [PMID: 27059126]
[5]
Chuang, H.M.; Su, H.L.; Li, C.; Lin, S.Z.; Yen, S.Y.; Huang, M.H.; Ho, L.I.; Chiou, T.W.; Harn, H.J. The role of butylidenephthalide in targeting the microenvironment which contributes to liver fibrosis amelioration. Front. Pharmacol., 2016, 7, 112.
[http://dx.doi.org/10.3389/fphar.2016.00112] [PMID: 27199755]
[6]
Wu, Y.C.; Hsieh, C.L. Pharmacological effects of Radix Angelica Sinensis (Danggui) on cerebral infarction. Chin. Med., 2011, 6(1), 32.
[http://dx.doi.org/10.1186/1749-8546-6-32] [PMID: 21867503]
[7]
Moisan, A.; Lee, Y.K.; Zhang, J.D.; Hudak, C.S.; Meyer, C.A.; Prummer, M.; Zoffmann, S.; Truong, H.H.; Ebeling, M.; Kiialainen, A.; Gérard, R.; Xia, F.; Schinzel, R.T.; Amrein, K.E.; Cowan, C.A. White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat. Cell Biol., 2015, 17(1), 57-67.
[http://dx.doi.org/10.1038/ncb3075] [PMID: 25487280]
[8]
Gnad, T.; Scheibler, S.; von Kügelgen, I.; Scheele, C.; Kilić, A.; Glöde, A.; Hoffmann, L.S.; Reverte-Salisa, L.; Horn, P.; Mutlu, S.; El-Tayeb, A.; Kranz, M.; Deuther-Conrad, W.; Brust, P.; Lidell, M.E.; Betz, M.J.; Enerbäck, S.; Schrader, J.; Yegutkin, G.G.; Müller, C.E.; Pfeifer, A. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature, 2014, 516(7531), 395-399.
[http://dx.doi.org/10.1038/nature13816] [PMID: 25317558]
[9]
Yeh, J.C.; Cindrova-Davies, T.; Belleri, M.; Morbidelli, L.; Miller, N.; Cho, C.W.C.; Chan, K.; Wang, Y.T.; Luo, G.A.; Ziche, M.; Presta, M.; Charnock-Jones, D.S.; Fan, T.P. The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo. Angiogenesis, 2011, 14(2), 187-197.
[http://dx.doi.org/10.1007/s10456-011-9202-8] [PMID: 21327473]
[10]
Liu, W.S.; Lin, P.C.; Chang, L.F.; Harn, H.J.; Shiuan, D.; Chiou, T.W.; Jeng, J.R. Inhibitory effect of n-butylidenephthalide on neointimal hyperplasia in balloon injured rat carotid artery. Phytother. Res., 2011, 25(10), 1494-1502.
[http://dx.doi.org/10.1002/ptr.3377] [PMID: 21365711]
[11]
Fu, R.H.; Hran, H.J.; Chu, C.L.; Huang, C.M.; Liu, S.P.; Wang, Y.C.; Lin, Y.H.; Shyu, W.C.; Lin, S.Z. Lipopolysaccharide-stimulated activation of murine DC2.4 cells is attenuated by n-butylidenephthalide through suppression of the NF-κB pathway. Biotechnol. Lett., 2011, 33(5), 903-910.
[http://dx.doi.org/10.1007/s10529-011-0528-5] [PMID: 21267764]
[12]
Che-Ming, Teng; Wen-Ying, Chen; Wun-Chang, Ko; Ouyang, C Antiplatelet effect of butylidenephthalide. Biochim. Biophys. Acta, Gen. Subj., 1987, 924(3), 375-382.
[http://dx.doi.org/10.1016/0304-4165(87)90151-6] [PMID: 3109495]
[13]
Chan, S.S.K.; Jones, R.L.; Lin, G. Synergistic interaction between the Ligusticum chuanxiong constituent butylidenephthalide and the nitric oxide donor sodium nitroprusside in relaxing rat isolated aorta. J. Ethnopharmacol., 2009, 122(2), 308-312.
[http://dx.doi.org/10.1016/j.jep.2009.01.002] [PMID: 19186210]
[14]
Ko, W.C.; Liao, C.C.; Shih, C.H.; Lei, C.B.; Chen, C.M. Relaxant effects of butylidenephthalide in isolated dog blood vessels. Planta Med., 2002, 68(11), 1004-1009.
[http://dx.doi.org/10.1055/s-2002-35671] [PMID: 12451491]
[15]
Chan, S.S.K.; Choi, A.O.K.; Jones, R.L.; Lin, G. Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. Eur. J. Pharmacol., 2006, 537(1-3), 111-117.
[http://dx.doi.org/10.1016/j.ejphar.2006.03.015] [PMID: 16624277]
[16]
Mimura, Y.; Kobayashi, S.; Naitoh, T.; Kimura, I.; Kimura, M. The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells. Biol. Pharm. Bull., 1995, 18(9), 1203-1206.
[http://dx.doi.org/10.1248/bpb.18.1203] [PMID: 8845805]
[17]
Wei, C.; Lin, C.; Yu, Y.; Lin, C.; Lin, P.; Wu, M.; Chen, C.; Chang, W.; Lin, S.; Chen, Y.S.; Harn, H. n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2α and telomerase activity. Acta Pharmacol. Sin., 2009, 30(9), 1297-1306.
[http://dx.doi.org/10.1038/aps.2009.124] [PMID: 19701232]
[18]
Huang, M.H.; Lin, S.Z.; Lin, P.C.; Chiou, T.W.; Harn, Y.W.; Ho, L.I.; Chan, T.M.; Chou, C.W.; Chuang, C.H.; Su, H.L.; Harn, H.J. Brain tumor senescence might be mediated by downregulation of S-phase kinase-associated protein 2 via butylidenephthalide leading to decreased cell viability. Tumour Biol., 2014, 35(5), 4875-4884.
[http://dx.doi.org/10.1007/s13277-014-1639-0] [PMID: 24464249]
[19]
Pang, C.Y.; Chiu, S.C.; Harn, H.J.; Zhai, W.J.; Lin, S.Z.; Yang, H.H. Proteomic-based identification of multiple pathways underlying n-butylidenephthalide-induced apoptosis in LNCaP human prostate cancer cells. Food Chem. Toxicol., 2013, 59, 281-288.
[http://dx.doi.org/10.1016/j.fct.2013.05.045] [PMID: 23770345]
[20]
Chiu, S.C.; Chen, S.P.; Huang, S.Y.; Wang, M.J.; Lin, S.Z.; Harn, H.J.; Pang, C.Y. Induction of apoptosis coupled to endoplasmic reticulum stress in human prostate cancer cells by n-butylidenephthalide. PLoS One, 2012, 7(3), e33742.
[http://dx.doi.org/10.1371/journal.pone.0033742] [PMID: 22470469]
[21]
Zhou, Q.M.; Zhang, J.J.; Li, S.; Chen, S.; Le, W.D. n ‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD 1 G93A mouse model of amyotrophic lateral sclerosis. CNS Neurosci. Ther., 2017, 23(5), 375-385.
[http://dx.doi.org/10.1111/cns.12681] [PMID: 28229532]
[22]
Chen, X.Q.; Qiu, K.; Liu, H.; He, Q.; Bai, J.H.; Lu, W. Application and prospects of butylphthalide for the treatment of neurologic diseases. Chin. Med. J., 2019, 132(12), 1467-1477.
[http://dx.doi.org/10.1097/CM9.0000000000000289] [PMID: 31205106]
[23]
Lin, Y.L.; Liu, Y.K.; Tsai, N.M.; Hsieh, J.H.; Chen, C.H.; Lin, C.M.; Liao, K.W. A Lipo-PEG-PEI complex for encapsulating curcumin that enhances its antitumor effects on curcumin-sensitive and curcumin-resistance cells. Nanomedicine, 2012, 8(3), 318-327.
[http://dx.doi.org/10.1016/j.nano.2011.06.011] [PMID: 21704596]
[24]
Chao, W.W.; Lin, B.F. Bioactivities of major constituents isolated from Angelica sinensis (Danggui). Chin. Med., 2011, 6(1), 29.
[http://dx.doi.org/10.1186/1749-8546-6-29] [PMID: 21851645]
[25]
Swati.; Pandey, H.K.; Singh, A. Chemical Composition and in vitro Antioxidant Activity of Pleurospermum angelicoides Collected from Western Himalayan Region. J. Essent. Oil-Bear. Plants, 2020, (4), 843-848.
[26]
Lee, J.H.; Lin, S.Y.; Liu, J.W.; Lin, S.Z.; Harn, H.J.; Chiou, T.W. n-Butylidenephthalide Modulates Autophagy to Ameliorate Neuropathological Progress of Spinocerebellar Ataxia Type 3 through mTOR Pathway. Int. J. Mol. Sci., 2021, 22(12), 6339.
[http://dx.doi.org/10.3390/ijms22126339] [PMID: 34199295]
[27]
Kaouadji, M.; De Pachtere, F.; Pouget, C.; Chulia, A.J.; Lavaitte, S. Three additional phthalide derivatives, an epoxymonomer and two dimers, from Ligusticumwallichii rhizomes. J. Nat. Prod., 1986, 49(5), 872-877.
[http://dx.doi.org/10.1021/np50047a018]
[28]
Luo, C.; Li, D.L.; Wang, Y.; Guo, S.S.; Du, S.S. Bioactivities of 3-Butylidenephthalide and n-Butylbenzene from the Essential Oil of Ligusticum jeholense against Stored-product Insects. J. Oleo Sci., 2019, 68(9), 931-937.
[http://dx.doi.org/10.5650/jos.ess19080] [PMID: 31413242]
[29]
Lee, H.W.; Choi, J.H.; Park, S.Y.; Choo, B.K.; Chun, J.M.; Lee, A.; Kim, H.K. Constituents comparison of components in native and cultivated species of Angelica tenuissima Nakai. Hanguk Yakyong Changmul Hakhoe Chi, 2008, 16(3), 168-172.
[30]
Adil, M.; Ren, X.; Jeong, B.R. Light elicited growth, antioxidant enzymes activities and production of medicinal compounds in callus culture of Cnidium officinale Makino. J. Photochem. Photobiol. B, 2019, 196, 111509.
[http://dx.doi.org/10.1016/j.jphotobiol.2019.05.006] [PMID: 31128431]
[31]
Sun, X.; Niu, L.; Li, X.; Lu, X.; Li, F. Characterization of metabolic profile of mosapride citrate in rat and identification of two new metabolites: Mosapride N-oxide and morpholine ring-opened mosapride by UPLC–ESI-MS/MS. J. Pharm. Biomed. Anal., 2009, 50(1), 27-34.
[http://dx.doi.org/10.1016/j.jpba.2009.03.011] [PMID: 19362796]
[32]
Chen, X.; Kong, L.; Su, X.; Fu, H.; Ni, J.; Zhao, R.; Zou, H. Separation and identification of compounds in Rhizoma chuanxiong by comprehensive two-dimensional liquid chromatography coupled to mass spectrometry. J. Chromatogr. A, 2004, 1040(2), 169-178.
[http://dx.doi.org/10.1016/j.chroma.2004.04.002] [PMID: 15230523]
[33]
Lao, S.C.; Li, S.P.; Kan, K.K.W.; Li, P.; Wan, J.B.; Wang, Y.T.; Dong, T.T.X.; Tsim, K.W.K. Identification and quantification of 13 components in Angelica sinensis (Danggui) by gas chromatography–mass spectrometry coupled with pressurized liquid extraction. Anal. Chim. Acta, 2004, 526(2), 131-137.
[http://dx.doi.org/10.1016/j.aca.2004.09.050]
[34]
Li, H.X.; Ding, M.Y.; Yu, J.Y. Separation and identification of the phthalic anhydride derivatives of Liqusticum Chuanxiong Hort by GC-MS, TLC, HPLC-DAD, and HPLC-MS. J. Chromatogr. Sci., 2002, 40(3), 156-161.
[http://dx.doi.org/10.1093/chromsci/40.3.156] [PMID: 11954653]
[35]
Gauvin, A.; Ravaomanarivo, H.; Smadja, J. Comparative analysis by gas chromatography-mass spectrometry of the essential oils from bark and leaves of Cedrelopsis grevei Baill, an aromatic and medicinal plant from Madagascar. J. chromat., 2004, 1029, 279-282.
[36]
Gach, J.; Olejniczak, T.; Krężel, P.; Boratyński, F. Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide. Int. J. Mol. Sci., 2021, 22(14), 7600.
[http://dx.doi.org/10.3390/ijms22147600] [PMID: 34299220]
[37]
Wang, S.; Shi, Y.; Chen, Q.; He, L. A GC-SIM-MS method for the determination of butylidenephthalide in rat plasma and tissue: application to the pharmacokinetic and tissue distribution study. Anal. Lett., 2008, 41(11), 1975-1987.
[http://dx.doi.org/10.1080/00032710802209243]
[38]
Yan, R.; Ling Ko, N.; Ma, B.; Kau Tam, Y.; Lin, G. Metabolic conversion from co-existing ingredient leading to significant systemic exposure of Z-butylidenephthalide, a minor ingredient in Chuanxiong Rhizoma in rats. Curr. Drug Metab., 2012, 13(5), 524-534.
[http://dx.doi.org/10.2174/1389200211209050524] [PMID: 22554277]
[39]
Yan, R.; Ko, N.L.; Li, S.L.; Tam, Y.K.; Lin, G. Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat. Drug Metab. Dispos., 2008, 36(2), 400-408.
[http://dx.doi.org/10.1124/dmd.107.017707] [PMID: 18039808]
[40]
Zhao, H.R.; Feng, S.X. Pharmacokinetics of butylidene phthalide in the volatile oil from Angelica sinensis (Oliv.) Diels in rabbits. Huaxi Yaoxue Zazhi, 2009, 24(2), 162-164.
[41]
Tsai, N.M.; Chen, Y.L.; Lee, C.C.; Lin, P.C.; Cheng, Y.L.; Chang, W.L.; Lin, S.Z.; Harn, H.J. The natural compound n ‐butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. J. Neurochem., 2006, 99(4), 1251-1262.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04151.x] [PMID: 16987298]
[42]
Nam, K.N.; Kim, K.P.; Cho, K.H.; Jung, W.S.; Park, J.M.; Cho, S.Y.; Park, S.K.; Park, T.H.; Kim, Y.S.; Lee, E.H. Prevention of inflammation‐mediated neurotoxicity by butylidenephthalide and its role in microglial activation. Cell Biochem. Funct., 2013, 31(8), 707-712.
[http://dx.doi.org/10.1002/cbf.2959] [PMID: 23400915]
[43]
Chang, K.F.; Huang, X.F.; Lin, Y.L.; Liao, K.W.; Hsieh, M.C.; Chang, J.T.; Tsai, N.M. Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma. BioMed Res. Int., 2021, 2021, 1-14.
[http://dx.doi.org/10.1155/2021/8817875] [PMID: 33791383]
[44]
Liu, S.P.; Harn, H.J.; Chien, Y.J.; Chang, C.H.; Hsu, C.Y.; Fu, R.H.; Huang, Y.C.; Chen, S.Y.; Shyu, W.C.; Lin, S.Z. n-Butylidenephthalide (BP) maintains stem cell pluripotency by activating Jak2/Stat3 pathway and increases the efficiency of iPS cells generation. PLoS One, 2012, 7(9), e44024.
[http://dx.doi.org/10.1371/journal.pone.0044024] [PMID: 22970157]
[45]
Su, Y.J.; Huang, S.Y.; Ni, Y.H.; Liao, K.F.; Chiu, S.C. Anti-tumor and radiosensitization effects of N-butylidenephthalide on human breast cancer cells. Molecules, 2018, 23(2), 240.
[http://dx.doi.org/10.3390/molecules23020240] [PMID: 29370116]
[46]
Pan, Y-H.; Lin, S-Z.; Chiu, T-L. Biodegradable controlled-release polymer containing butylidenephthalide to treat a recurrent cervical spine glioblastoma with promising result: A compassionate trial report. Anticancer Drugs, 2022, 33(4), 394-399.
[http://dx.doi.org/10.1097/CAD.0000000000001275]
[47]
Liao, K.F.; Chiu, T.L.; Huang, S.Y.; Hsieh, T.F.; Chang, S.F.; Ruan, J.W.; Chen, S.P.; Pang, C.Y.; Chiu, S.C. Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition. Cell. Physiol. Biochem., 2018, 48(6), 2231-2246.
[http://dx.doi.org/10.1159/000492641] [PMID: 30114701]
[48]
Sarma, K.; Akther, M.H.; Ahmad, I.; Afzal, O.; Altamimi, A.S.A.; Alossaimi, M.A.; Jaremko, M.; Emwas, A.H.; Gautam, P. Adjuvant novel nanocarrier-based targeted therapy for lung cancer. Molecules, 2024, 29(5), 1076.
[http://dx.doi.org/10.3390/molecules29051076] [PMID: 38474590]
[49]
Chiu, S.C.; Chiu, T.L.; Huang, S.Y.; Chang, S.F.; Chen, S.P.; Pang, C.Y.; Hsieh, T.F. Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells. BMC Complement. Altern. Med., 2017, 17(1), 523.
[http://dx.doi.org/10.1186/s12906-017-2034-3] [PMID: 29207978]
[50]
Falls, K.C.; Sharma, R.A.; Lawrence, Y.R.; Amos, R.A.; Advani, S.J.; Ahmed, M.M.; Vikram, B.; Coleman, C.N.; Prasanna, P.G. Radiation-drug combinations to improve clinical outcomes and reduce normal tissue toxicities: Current challenges and new approaches: Report of the symposium held at the 63rd annual meeting of the radiation research society, 15–18 October 2017; Cancun, Mexico. Radiat. Res., 2018, 190(4), 350-360.
[http://dx.doi.org/10.1667/RR15121.1] [PMID: 30280985]
[51]
Majeed, H.; Gupta, V. Adverse effects of radiation therapy; StatPearls Publishing: Treasure Island, FL, USA, 2023.
[52]
Liu, C.A.; Harn, H.J.; Chen, K.P.; Lee, J.H.; Lin, S.Z.; Chiu, T.L. Targeting the Axl and mTOR Pathway Synergizes Immunotherapy and Chemotherapy to Butylidenephthalide in a Recurrent GBM. J. Oncol., 2022, 2022, 1-14.
[http://dx.doi.org/10.1155/2022/3236058] [PMID: 35646111]
[53]
Steven, A.; Fisher, S.A.; Robinson, B.W. Immunotherapy for lung cancer. Respirology, 2016, 21(5), 821-833.
[http://dx.doi.org/10.1111/resp.12789] [PMID: 27101251]
[54]
Sharma, K. Lung Cancer Therapy: Synergistic Potential of PD-1/PD-L1 and CTLA-4 Inhibitors.Immunotherapy Against Lung Cancer; Bhatt, S.; Eri, R.E.; Goh, B.H.; Paudel, K.R.; Andreoli Pinto, T.J; Dua, K., Ed.; Springer: Singapore, 2024.
[http://dx.doi.org/10.1007/978-981-99-7141-1_15]
[55]
Singh, A.P.; Biswas, A.; Shukla, A.; Maiti, P. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduct. Target. Ther., 2019, 4(1), 33.
[http://dx.doi.org/10.1038/s41392-019-0068-3] [PMID: 31637012]
[56]
Wang, J.; Seebacher, N.; Shi, H.; Kan, Q.; Duan, Z. Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget, 2017, 8(48), 84559-84571.
[http://dx.doi.org/10.18632/oncotarget.19187] [PMID: 29137448]
[57]
Chamundeeswari, M.; Jeslin, J.; Verma, M.L. Nanocarriers for drug delivery applications. Environ. Chem. Lett., 2019, 17(2), 849-865.
[http://dx.doi.org/10.1007/s10311-018-00841-1]
[58]
Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol., 2015, 6, 286.
[http://dx.doi.org/10.3389/fphar.2015.00286] [PMID: 26648870]
[59]
Skupin-Mrugalska, P. Liposome-based drug delivery for lung cancer. Nanotechnology-Based Targeted Drug Delivery Systems for Lung Cancer; Academic Press, 2019, pp. 123-160.
[http://dx.doi.org/10.1016/B978-0-12-815720-6.00006-X]
[60]
Lin, Y-L Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme, 2015.
[http://dx.doi.org/10.2147/IJN.S85790]
[61]
Gao, H.W.; Chang, K.F.; Huang, X.F.; Lin, Y.L.; Weng, J.C.; Liao, K.W.; Tsai, N.M. Antitumor effect of n-butylidenephthalide encapsulated on B16/F10 melanoma cells in vitro with a polycationic liposome containing PEI and polyethylene glycol complex. Molecules, 2018, 23(12), 3224.
[http://dx.doi.org/10.3390/molecules23123224] [PMID: 30563276]
[62]
Thangam, R.; Patel, K.D.; Kang, H.; Paulmurugan, R. Advances in engineered polymer nanoparticle tracking platforms towards cancer immunotherapy—current status and future perspectives. Vaccines (Basel), 2021, 9(8), 935.
[http://dx.doi.org/10.3390/vaccines9080935] [PMID: 34452059]
[63]
Huang, X.F.; Chen, P.T.; Lin, Y.L.; Lee, M.S.; Chang, K.F.; Liao, K.W.; Sheu, G.T.; Hsieh, M.C.; Tsai, N.M. Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells. Clin. Transl. Oncol., 2021, 23(6), 1142-1151.
[http://dx.doi.org/10.1007/s12094-020-02500-w] [PMID: 32989675]
[64]
Yen, S.Y.; Chen, S.R.; Hsieh, J. Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion. Oncogene, 2016, 35, 2156-2165.
[http://dx.doi.org/10.1038/onc.2015.277]
[65]
Hsieh, M.T.; Wu, C.R.; Lin, L.W.; Hsieh, C.C.; Tsai, C.H. Reversal caused by n-butylidenephthalide from the deficits of inhibitory avoidance performance in rats. Planta Med., 2001, 67(1), 38-42.
[http://dx.doi.org/10.1055/s-2001-10631] [PMID: 11270720]
[66]
Chen, M.; Ko, W.C. Lack of effect of Z-butylidenephthalide on presynaptic N-type Ca2+ channels in isolated guinea-pig ileum. Naunyn Schmiedebergs Arch. Pharmacol., 2016, 389(2), 159-166.
[http://dx.doi.org/10.1007/s00210-015-1183-5] [PMID: 26497186]
[67]
Kost, B.; Brzeziński, M.; Cieślak, M.; Królewska-Golińska, K.; Makowski, T.; Socka, M.; Biela, T. Stereocomplexed micelles based on polylactides with β-cyclodextrin core as anti-cancer drug carriers. Eur. Polym. J., 2019, 120, 109271.
[http://dx.doi.org/10.1016/j.eurpolymj.2019.109271]
[68]
Chiou, T-W.; Harn, H-J.; Lin, S-Z. Anticancer formulation. US Patent 9585864B2, 2017.
[69]
Askar, M.A.; Thabet, N.M.; El-sayyad, G.S. El-Batal. A. I., kodous, M. A. E., et al., Dual Hyaluronic Acid and Folic Acid Targeting pHSensitive Multifunctional 2DG@DCA@MgO-NanoCore-Shell-Radiosensitizer for Breast Cancer Therapy Research Square, 2021.
[http://dx.doi.org/10.21203/rs.3.rs-910507/v1]
[70]
Chen, Y.S.; Chiu, Y.H.; Li, Y.S.; Lin, E.Y.; Hsieh, D.K.; Lee, C.H.; Huang, M.H.; Chuang, H.M.; Lin, S.Z.; Harn, H.J.; Chiou, T.W. Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors. Int. J. Nanomedicine, 2019, 14, 3601-3613.
[http://dx.doi.org/10.2147/IJN.S193617] [PMID: 31190814]
[71]
Dobson; Yiu, H.H.; Dobson, J. Magnetic nanoparticles for gene and drug delivery. Int. J. Nanomedicine, 2008, 3(2), 169-180.
[http://dx.doi.org/10.2147/IJN.S1608] [PMID: 18686777]
[72]
Wu, C-Y.; Chen, Y-C. Riboflavin immobilized Fe3O4 magnetic nanoparticles carried with n-butylidenephthalide as targeting-based anticancer agents. Nanomed. Biotechnology, 2019, 47(1), 210-220.
[http://dx.doi.org/10.1080/21691401.2018.1548473]
[73]
Neha Desai, ; Momin, M.; Khan, T.; Gharat, S.; Ningthoujam, R.S.; Omri, A. Metallic nanoparticles as drug delivery system for the treatment of cancer. Expert Opin. Drug Deliv., 2021, 18(9), 1261-1290.
[http://dx.doi.org/10.1080/17425247.2021.1912008] [PMID: 33793359]
[74]
Chandrakala, V.; Aruna, V.; Angajala, G. Review on metal nanoparticles as nanocarriers: current challenges and perspectives in drug delivery systems. Emergent mater., 2022, 5(6), 1593-1615.
[http://dx.doi.org/10.1007/s42247-021-00335-x]
[75]
Hsing, M.T.; Hsu, H.T.; Chang, C.H.; Chang, K.B.; Cheng, C.Y.; Lee, J.H.; Huang, C.L.; Yang, M.Y.; Yang, Y.C.; Liu, S.Y.; Yen, C.M.; Yang, S.F.; Hung, H.S. Improved delivery performance of n-butylidenephthalide-polyethylene glycol-gold nanoparticles efficient for enhanced anti-cancer activity in brain tumor. Cells, 2022, 11(14), 2172.
[http://dx.doi.org/10.3390/cells11142172] [PMID: 35883615]
[76]
Chou, Y.Y.; Chien, J.Y.; Ciou, J.W.; Huang, S.P. The Protective Effects of n-Butylidenephthalide on Retinal Ganglion Cells during Ischemic Injury. Int. J. Mol. Sci., 2022, 23(4), 2095.
[http://dx.doi.org/10.3390/ijms23042095] [PMID: 35216208]
[77]
Lin, Y.L.; Huang, X.F.; Chang, K.F.; Liao, K.W.; Tsai, N.M. Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma. Int. J. Nanomedicine, 2020, 15, 749-760.
[http://dx.doi.org/10.2147/IJN.S235815] [PMID: 32099363]
[78]
Ortega, M.J.; Parra-Torrejón, B.; Cano-Cano, F.; Gómez-Jaramillo, L.; González-Montelongo, M.C.; Zubía, E. Synthesis and Antioxidant/Anti-Inflammatory Activity of 3-Arylphthalides. Pharmaceuticals (Basel), 2022, 15(5), 588.
[http://dx.doi.org/10.3390/ph15050588] [PMID: 35631414]
[79]
Wang, H.; Zhou, Y.; Sun, Q.; Zhou, C.; Hu, S.; Lenahan, C.; Xu, W.; Deng, Y.; Li, G.; Tao, S. Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment. Front. Bioeng. Biotechnol., 2021, 9, 630352.
[http://dx.doi.org/10.3389/fbioe.2021.630352] [PMID: 33681167]
[80]
Brusini, R.; Varna, M.; Couvreur, P. Advanced nanomedicines for the treatment of inflammatory diseases. Adv. Drug Deliv. Rev., 2020, 157, 161-178.
[http://dx.doi.org/10.1016/j.addr.2020.07.010] [PMID: 32697950]
[81]
Cheng, G.; Liu, Y.; Ma, R.; Cheng, G.; Guan, Y.; Chen, X.; Wu, Z.; Chen, T. Anti-Parkinsonian Therapy: Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials. Nano-Micro Lett., 2022, 14(1), 105.
[http://dx.doi.org/10.1007/s40820-022-00847-z] [PMID: 35426525]
[82]
Fu, R.H.; Harn, H.J.; Liu, S.P.; Chen, C.S.; Chang, W.L.; Chen, Y.M.; Huang, J.E.; Li, R.J.; Tsai, S.Y.; Hung, H.S.; Shyu, W.C.; Lin, S.Z.; Wang, Y.C. n-butylidenephthalide protects against dopaminergic neuron degeneration and α-synuclein accumulation in Caenorhabditis elegans models of Parkinson’s disease. PLoS One, 2014, 9(1), e85305.
[http://dx.doi.org/10.1371/journal.pone.0085305] [PMID: 24416384]
[83]
Chi, K.; Fu, R.H.; Huang, Y.C.; Chen, S.Y.; Hsu, C.J.; Lin, S.Z.; Tu, C.T.; Chang, L.H.; Wu, P.A.; Liu, S.P. Adipose-derived Stem Cells Stimulated with n -Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson’s Disease. Cell Transplant., 2018, 27(3), 456-470.
[http://dx.doi.org/10.1177/0963689718757408] [PMID: 29756519]
[84]
Silva, S.; Almeida, A.; Vale, N. Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs. Pharmaceutics, 2021, 13(4), 508.
[http://dx.doi.org/10.3390/pharmaceutics13040508] [PMID: 33917696]
[85]
Kuo, Y.C.; Rajesh, R. Current development of nanocarrier delivery systems for Parkinson’s disease pharmacotherapy. J. Taiwan Inst. Chem. Eng., 2018, 87, 15-25.
[http://dx.doi.org/10.1016/j.jtice.2018.03.028]
[86]
Jagaran, K.; Singh, M. Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease. Int. J. Mol. Sci., 2022, 23(16), 9361.
[http://dx.doi.org/10.3390/ijms23169361] [PMID: 36012619]
[87]
Mishra, N.; Ashique, S.; Garg, A.; Rai, V.K.; Dua, K.; Goyal, A.; Bhatt, S. Role of siRNA-based nanocarriers for the treatment of neurodegenerative diseases. Drug Discov. Today, 2022, 27(5), 1431-1440.
[http://dx.doi.org/10.1016/j.drudis.2022.01.003] [PMID: 35017085]
[88]
Bukke, V.N.; Archana, M.; Villani, R.; Romano, A.D.; Wawrzyniak, A.; Balawender, K.; Orkisz, S.; Beggiato, S.; Serviddio, G.; Cassano, T. The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy. Int. J. Mol. Sci., 2020, 21(20), 7452.
[http://dx.doi.org/10.3390/ijms21207452] [PMID: 33050345]
[89]
Chang, C.Y.; Chen, S.M.; Lu, H.E.; Lai, S.M.; Lai, P.S.; Shen, P.W.; Chen, P.Y.; Shen, C.I.; Harn, H.J.; Lin, S.Z.; Hwang, S.M.; Su, H.L. N-butylidenephthalide attenuates Alzheimer’s disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons. Sci. Rep., 2015, 5(1), 8744.
[http://dx.doi.org/10.1038/srep08744] [PMID: 25735452]
[90]
Wang, R.; Reddy, P.H. Role of Glutamate and NMDA Receptors in Alzheimer’s Disease. J. Alzheimers Dis., 2017, 57(4), 1041-1048.
[http://dx.doi.org/10.3233/JAD-160763] [PMID: 27662322]
[91]
Baracaldo-Santamaría, D.; Avendaño-Lopez, S.S.; Ariza-Salamanca, D.F.; Rodriguez-Giraldo, M.; Calderon-Ospina, C.A.; González-Reyes, R.E.; Nava-Mesa, M.O. Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease. Int. J. Mol. Sci., 2023, 24(10), 9067.
[http://dx.doi.org/10.3390/ijms24109067] [PMID: 37240413]
[92]
Penney, J.; Ralvenius, W.T.; Tsai, L.H. Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol. Psychiatry, 2020, 25(1), 148-167.
[http://dx.doi.org/10.1038/s41380-019-0468-3] [PMID: 31391546]
[93]
Yang, H.H.; Chiang, I.T.; Liu, J.W.; Hsieh, J.; Lee, J.H.; Lu, H.E.; Tso, H.S.; Deng, Y.C.; Kao, J.C.; Wu, J.R.; Harn, H.J.; Chiou, T.W. Anti-Excitotoxic Effects of N-Butylidenephthalide Revealed by Chemically Insulted Purkinje Progenitor Cells Derived from SCA3 iPSCs. Int. J. Mol. Sci., 2022, 23(3), 1391.
[http://dx.doi.org/10.3390/ijms23031391] [PMID: 35163312]
[94]
Long, Y.; Li, D.; Yu, S.; Shi, A.; Deng, J.; Wen, J.; Li, X.; Ma, Y.; Zhang, Y.; Liu, S.; Wan, J.; Li, N.; Yang, M.; Han, L. Medicine–food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer’s disease and related complications. Food Funct., 2022, 13(17), 8783-8803.
[http://dx.doi.org/10.1039/D2FO01287A] [PMID: 35983893]

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