European Journal of Chemistry

Exploring medicinal potential and drug delivery solutions of Celastrol from the Chinese "Thunder of God Vine"

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Published: Jun 30, 2024
DOI: https://doi.org/10.5155/eurjchem.15.2.194-204.2534
Keywords:
Celastrol, Antioxidant, Triterpenoids, Medicinal chemistry, Traditional Chinese medicine (TCM)
Section
Review Article
Issue
Vol. 15 No. 2 (2024): June 2024
Dates
Received 2024-02-27
Accepted 2024-05-11
Published 2024-06-30
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Main Article Content

Zimo Ren
Department of Medical Division, School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China
https://orcid.org/0009-0007-2534-444X
Paolo Coghi
Department of Medical Division, School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China
https://orcid.org/0000-0002-0015-1453

Abstract

Tripterygium wilfordii (TRWI), known as 'Thunder of God Vine' or 'Lei Gong Teng' in traditional Chinese medicine (TCM), is a perennial vine that has been used for centuries for its potent therapeutic properties. This plant, which belongs to the Celastraceae family, has been documented in various TCM texts, where it has been attributed with a wide range of benefits, including anti-inflammatory, antirheumatic, and anti-autoimmune activities. Central to the medicinal potential of TRWI is celastrol, a triterpenoid with extensive pharmacological activities. Research on celastrol has revealed its effects on combating inflammation, oxidative stress, cancer proliferation, and neurological disorders. However, celastrol’s high toxicity, low water solubility, and limited stability pose challenges for its clinical application. In this review, we explore the chemical structure of celastrol, emphasizing its key pharmacological activities and the structure-activity relationships (SARs) that influence its efficacy and toxicity. Various studies have demonstrated that modifications at specific sites, such as the C-29 carboxylic group, C-6, and C-3, can enhance celastrol’s therapeutic potential while reducing adverse effects. Moreover, recent advances in drug delivery systems offer promising avenues to overcome the inherent limitations of celastrol. These include direct modifications such as PEGylation and indirect modifications through encapsulation in dendritic polymers, phytosomes, liposomes, and exosomes. Each method seeks to improve celastrol bioavailability, water solubility, and target capabilities, thus enhancing its clinical viability. The objective of this review is to synthesize current knowledge about celastrol’s therapeutic potential and discuss the future of its development in drug delivery and pharmaceutical applications. These findings could open the door to new treatment methods that combine traditional remedies with modern pharmacology, helping us unlock the complete potential of celastrol in clinical use.


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Ren, Z.; Coghi, P. Exploring Medicinal Potential and Drug Delivery Solutions of Celastrol from the Chinese "Thunder of God Vine". Eur. J. Chem. 2024, 15, 194-204.

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References

[1]. The Encyclopedia of Traditional Chinese Medicine 2.0 - ETCM2.0. http://www.tcmip.cn/ETCM2/front/#/ (accessed Jan 11, 2024).

[2]. Li, M.; Liang, Y. Li shizhen and the grand compendium of materia medica. J. Tradit. Chin. Med. Sci. 2015, 2, 215-216.
https://doi.org/10.1016/j.jtcms.2016.01.015

[3]. Kannaiyan, R.; Shanmugam, M. K.; Sethi, G. Molecular targets of celastrol derived from Thunder of God Vine: Potential role in the treatment of inflammatory disorders and cancer. Cancer Lett. 2011, 303, 9-20.
https://doi.org/10.1016/j.canlet.2010.10.025

[4]. Allison, A. C.; Cacabelos, R.; Lombardi, V. R. M.; Álvarez, X. A.; Vigo, C. Central nervous system effects of celastrol, a potent antioxidant and antiinflammatory agent. CNS Drug Rev. 2000, 6, 45-62.
https://doi.org/10.1111/j.1527-3458.2000.tb00137.x

[5]. Kim, Y.; Kim, K.; Lee, H.; Han, S.; Lee, Y.-S.; Choe, J.; Kim, Y.-M.; Hahn, J.-H.; Ro, J. Y.; Jeoung, D. Celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-allergic effect. Eur. J. Pharmacol. 2009, 612, 131-142.
https://doi.org/10.1016/j.ejphar.2009.03.071

[6]. Yang, G.; Wang, K.; Song, H.; Zhu, R.; Ding, S.; Yang, H.; Sun, J.; Wen, X.; Sun, L. Celastrol ameliorates osteoarthritis via regulating TLR2/NF-κB signaling pathway. Front. Pharmacol. 2022, 13, 963506.
https://doi.org/10.3389/fphar.2022.963506

[7]. Der Sarkissian, S.; Cailhier, J.; Borie, M.; Mansour, S.; Hamet, P.; Stevens, L.; Noiseux, N. Celastrol as a novel cardioprotective drug. Can. J. Cardiol. 2013, 29, S331.
https://doi.org/10.1016/j.cjca.2013.07.563

[8]. Sun, H.; Xu, L.; Yu, P.; Jiang, J.; Zhang, G.; Wang, Y. Synthesis and preliminary evaluation of neuroprotection of celastrol analogues in PC12 cells. Bioorg. Med. Chem. Lett. 2010, 20, 3844-3847.
https://doi.org/10.1016/j.bmcl.2010.05.066

[9]. Ng, J. P. L.; Han, Y.; Yang, L. J.; Birkholtz, L.-M.; Coertzen, D.; Wong, H. N.; Haynes, R. K.; Coghi, P.; Wong, V. K. W. Antimalarial and antitumour activities of the steroidal quinone-methide celastrol and its combinations with artemiside, artemisone and methylene blue. Front. Pharmacol. 2022, 13, 988748.
https://doi.org/10.3389/fphar.2022.988748

[10]. Liu, J.; Lee, J.; Salazar Hernandez, M. A.; Mazitschek, R.; Ozcan, U. Treatment of obesity with celastrol. Cell 2015, 161, 999-1011.
https://doi.org/10.1016/j.cell.2015.05.011

[11]. Jang, S. Y.; Jang, S.-W.; Ko, J. Celastrol inhibits the growth of estrogen positive human breast cancer cells through modulation of estrogen receptor α. Cancer Lett. 2011, 300, 57-65.
https://doi.org/10.1016/j.canlet.2010.09.006

[12]. Mi, C.; Shi, H.; Ma, J.; Han, L. I. Z.; Lee, J. J.; Jin, X. Celastrol induces the apoptosis of breast cancer cells and inhibits their invasion via downregulation of MMP-9. Oncol. Rep. 2014, 32, 2527-2532.
https://doi.org/10.3892/or.2014.3535

[13]. Li, X.; Ding, J.; Li, N.; Liu, W.; Ding, F.; Zheng, H.; Ning, Y.; Wang, H.; Liu, R.; Ren, S. Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents. Eur. J. Med. Chem. 2019, 179, 667-679.
https://doi.org/10.1016/j.ejmech.2019.06.086

[14]. Yadav, V. R.; Sung, B.; Prasad, S.; Kannappan, R.; Cho, S.-G.; Liu, M.; Chaturvedi, M. M.; Aggarwal, B. B. Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor. J. Mol. Med. 2010, 88, 1243-1253.
https://doi.org/10.1007/s00109-010-0669-3

[15]. Song, J.; He, G.-N.; Dai, L. A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes. Biomed. Pharmacother. 2023, 162, 114705.
https://doi.org/10.1016/j.biopha.2023.114705

[16]. Zhang, T.; Li, Y.; Yu, Y.; Zou, P.; Jiang, Y.; Sun, D. Characterization of celastrol to inhibit Hsp90 and Cdc37 interaction. J. Biol. Chem. 2009, 284, 35381-35389.
https://doi.org/10.1074/jbc.M109.051532

[17]. Jin, H. Z.; Hwang, B. Y.; Kim, H. S.; Lee, J. H.; Kim, Y. H.; Lee, J. J. Antiinflammatory constituents of Celastrus o rbiculatus inhibit the NF-κB activation and NO production. J. Nat. Prod. 2002, 65, 89-91.
https://doi.org/10.1021/np010428r

[18]. Sreeramulu, S.; Gande, S. L.; Göbel, M.; Schwalbe, H. Molecular mechanism of inhibition of the human protein complex Hsp90-Cdc37, a kinome chaperone-cochaperone, by triterpene celastrol. Angew. Chem. Int. Ed Engl. 2009, 48, 5853-5855.
https://doi.org/10.1002/anie.200900929

[19]. Clapham, D. E. Calcium signaling. Cell 2007, 131, 1047-1058.
https://doi.org/10.1016/j.cell.2007.11.028

[20]. Mooren, F. C.; Kinne, R. K. H. Cellular calcium in health and disease. Biochim. Biophys. Acta Mol. Basis Dis. 1998, 1406, 127-151.
https://doi.org/10.1016/S0925-4439(98)00006-4

[21]. Izquierdo, J.-H.; Bonilla-Abadía, F.; Cañas, C. A.; Tobón, G. J. Calcio, canales, señalización intracelular y autoinmunidad. Reumatol. Clin. 2014, 10, 43-47.
https://doi.org/10.1016/j.reuma.2013.05.008

[22]. Yoon, M. J.; Lee, A. R.; Jeong, S. A.; Kim, Y.-S.; Kim, J. Y.; Kwon, Y.-J.; Choi, K. S. Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells. Oncotarget 2014, 5, 6816-6831.
https://doi.org/10.18632/oncotarget.2256

[23]. de Seabra Rodrigues Dias, I. R.; Mok, S. W. F.; Gordillo-Martínez, F.; Khan, I.; Hsiao, W. W. L.; Law, B. Y. K.; Wong, V. K. W.; Liu, L. The calcium-induced regulation in the molecular and transcriptional circuitry of human inflammatory response and autoimmunity. Front. Pharmacol. 2018, 8, 962.
https://doi.org/10.3389/fphar.2017.00962

[24]. Wong, V. K. W.; Qiu, C.; Xu, S.-W.; Law, B. Y. K.; Zeng, W.; Wang, H.; Michelangeli, F.; Dias, I. R. D. S. R.; Qu, Y. Q.; Chan, T. W.; Han, Y.; Zhang, N.; Mok, S. W. F.; Chen, X.; Yu, L.; Pan, H.; Hamdoun, S.; Efferth, T.; Yu, W. J.; Zhang, W.; Li, Z.; Xie, Y.; Luo, R.; Jiang, Q.; Liu, L. Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats. Br. J. Pharmacol. 2019, 176, 2922-2944.
https://doi.org/10.1111/bph.14718

[25]. Bai, X.; Fu, R.-J.; Zhang, S.; Yue, S.-J.; Chen, Y.-Y.; Xu, D.-Q.; Tang, Y.-P. Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases. Biomed. Pharmacother. 2021, 139, 111551.
https://doi.org/10.1016/j.biopha.2021.111551

[26]. Hou, W.; Liu, B.; Xu, H. Celastrol: Progresses in structure-modifications, structure-activity relationships, pharmacology and toxicology. Eur. J. Med. Chem. 2020, 189, 112081.
https://doi.org/10.1016/j.ejmech.2020.112081

[27]. Lu, Y.; Liu, Y.; Zhou, J.; Li, D.; Gao, W. Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol. Med. Res. Rev. 2021, 41, 1022-1060.
https://doi.org/10.1002/med.21751

[28]. Xie, Y.; Kuan, H.; Wei, Q.; Gianoncelli, A.; Ribaudo, G.; Coghi, P. (2R,4aS,6aS,12bR,14aS,14bR)10-Hydroxy-N-(4-((6-methoxyquinolin-8-yl)amino)pentyl)-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide. Molbank 2023, 2023, M1716.
https://doi.org/10.3390/M1716

[29]. Klaić, L.; Morimoto, R. I.; Silverman, R. B. Celastrol analogues as inducers of the heat shock response. Design and synthesis of affinity probes for the identification of protein targets. ACS Chem. Biol. 2012, 7, 928-937.
https://doi.org/10.1021/cb200539u

[30]. Shan, W.-G.; Wang, H.-G.; Chen, Y.; Wu, R.; Wen, Y.-T.; Zhang, L.-W.; Ying, Y.-M.; Wang, J.-W.; Zhan, Z.-J. Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities. Bioorg. Med. Chem. Lett. 2017, 27, 3450-3453.
https://doi.org/10.1016/j.bmcl.2017.05.083

[31]. Pang, C.; Luo, J.; Liu, C.; Wu, X.; Wang, D. Synthesis and biological evaluation of a series of novel celastrol derivatives with amino acid chain. Chem. Biodivers. 2018, 15, e1800059.
https://doi.org/10.1002/cbdv.201800059

[32]. Coghi, P.; Ng, J. P. L.; Kadioglu, O.; Law, B. Y. K.; Qiu, A. C.; Saeed, M. E. M.; Chen, X.; Ip, C. K.; Efferth, T.; Liu, L.; Wong, V. K. W. Synthesis, computational docking and biological evaluation of celastrol derivatives as dual inhibitors of SERCA and P-glycoprotein in cancer therapy. Eur. J. Med. Chem. 2021, 224, 113676.
https://doi.org/10.1016/j.ejmech.2021.113676

[33]. Tang, K.; Huang, Q.; Zeng, J.; Wu, G.; Huang, J.; Pan, J.; Lu, W. Design, synthesis and biological evaluation of C(6)-modified celastrol derivatives as potential antitumor agents. Molecules 2014, 19, 10177-10188.
https://doi.org/10.3390/molecules190710177

[34]. Zhu, Y.; Chen, Z.; Huang, Z.; Yan, S.; Li, Z.; Zhou, H.; Zhang, X.; Su, Y.; Zeng, Z. AlCl3·6H2O-catalyzed Friedel-crafts alkylation of indoles by the para-quinone methide moiety of celastrol. Molecules 2017, 22, 742.
https://doi.org/10.3390/molecules22050742

[35]. Tang, K.; Huang, J.; Pan, J.; Zhang, X.; Lu, W. Design, synthesis and biological evaluation of C(6)-indole celastrol derivatives as potential antitumor agents. RSC Adv. 2015, 5, 19620-19623.
https://doi.org/10.1039/C4RA15414B

[36]. He, Q.-W.; Feng, J.-H.; Hu, X.-L.; Long, H.; Huang, X.-F.; Jiang, Z.-Z.; Zhang, X.-Q.; Ye, W.-C.; Wang, H. Synthesis and biological evaluation of celastrol derivatives as potential immunosuppressive agents. J. Nat. Prod. 2020, 83, 2578-2586.
https://doi.org/10.1021/acs.jnatprod.0c00067

[37]. Westerheide, S. D.; Bosman, J. D.; Mbadugha, B. N. A.; Kawahara, T. L. A.; Matsumoto, G.; Kim, S.; Gu, W.; Devlin, J. P.; Silverman, R. B.; Morimoto, R. I. Celastrols as inducers of the heat shock response and cytoprotection. J. Biol. Chem. 2004, 279, 56053-56060.
https://doi.org/10.1074/jbc.M409267200

[38]. Pokorny, J.; Borkova, L.; Urban, M. Click reactions in chemistry of triterpenes - advances towards development of potential therapeutics. Curr. Med. Chem. 2018, 25, 636-658.
https://doi.org/10.2174/0929867324666171009122612

[39]. Tornøe, C. W.; Christensen, C.; Meldal, M. Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 2002, 67, 3057-3064.
https://doi.org/10.1021/jo011148j

[40]. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A stepwise Huisgen cycloaddition process: Copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew. Chem. Int. Ed Engl. 2002, 41, 2596-2599.
https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4

[41]. Bozorov, K.; Zhao, J.; Aisa, H. A. 1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview. Bioorg. Med. Chem. 2019, 27, 3511-3531.
https://doi.org/10.1016/j.bmc.2019.07.005

[42]. Wu, P. The Nobel prize in chemistry 2022: Fulfilling demanding applications with simple reactions. ACS Chem. Biol. 2022, 17, 2959-2961.
https://doi.org/10.1021/acschembio.2c00788

[43]. Zhang, H.-J.; Zhang, G.-R.; Piao, H.-R.; Quan, Z.-S. Synthesis and characterisation of celastrol derivatives as potential anticancer agents. J. Enzyme Inhib. Med. Chem. 2018, 33, 190-198.
https://doi.org/10.1080/14756366.2017.1404590

[44]. Feng, Y.; Wang, W.; Zhang, Y.; Fu, X.; Ping, K.; Zhao, J.; Lei, Y.; Mou, Y.; Wang, S. Synthesis and biological evaluation of celastrol derivatives as potential anti-glioma agents by activating RIP1/RIP3/MLKL pathway to induce necroptosis. Eur. J. Med. Chem. 2022, 229, 114070.
https://doi.org/10.1016/j.ejmech.2021.114070

[45]. Shang, F.-F.; Wang, J. Y.; Xu, Q.; Deng, H.; Guo, H.-Y.; Jin, X.; Li, X.; Shen, Q.-K.; Quan, Z.-S. Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway. Eur. J. Med. Chem. 2021, 220, 113474.
https://doi.org/10.1016/j.ejmech.2021.113474

[46]. Fang, G.; Tang, B. Current advances in the nano-delivery of celastrol for treating inflammation-associated diseases. J. Mater. Chem. B Mater. Biol. Med. 2020, 8, 10954-10965.
https://doi.org/10.1039/D0TB01939A

[47]. Sun, Y.; Wang, C.; Li, X.; Lu, J.; Wang, M. Recent advances in drug delivery of celastrol for enhancing efficiency and reducing the toxicity. Front. Pharmacol. 2024, 15, 1137289.
https://doi.org/10.3389/fphar.2024.1137289

[48]. Ge, P.; Niu, B.; Wu, Y.; Xu, W.; Li, M.; Sun, H.; Zhou, H.; Zhang, X.; Xie, J. Enhanced cancer therapy of celastrol in vitro and in vivo by smart dendrimers delivery with specificity and biosafety. Chem. Eng. J. 2020, 383, 123228.
https://doi.org/10.1016/j.cej.2019.123228

[49]. Tan, Y.; Zhu, Y.; Zhao, Y.; Wen, L.; Meng, T.; Liu, X.; Yang, X.; Dai, S.; Yuan, H.; Hu, F. Mitochondrial alkaline pH-responsive drug release mediated by Celastrol loaded glycolipid-like micelles for cancer therapy. Biomaterials 2018, 154, 169-181.
https://doi.org/10.1016/j.biomaterials.2017.07.036

[50]. Niu, B.; Wu, Y.; Zhou, M.; Lin, R.; Ge, P.; Chen, X.; Zhou, H.; Zhang, X.; Xie, J. Precise delivery of celastrol by PEGylated aptamer dendrimer nanoconjugates for enormous therapeutic effect via superior intratumor penetration over antibody counterparts. Cancer Lett. 2023, 579, 216461.
https://doi.org/10.1016/j.canlet.2023.216461

[51]. Freag, M. S.; Saleh, W. M.; Abdallah, O. Y. Self-assembled phospholipid-based phytosomal nanocarriers as promising platforms for improving oral bioavailability of the anticancer celastrol. Int. J. Pharm. 2018, 535, 18-26.
https://doi.org/10.1016/j.ijpharm.2017.10.053

[52]. Fan, N.; Zhao, J.; Zhao, W.; Shen, Y.; Song, Q.; Shum, H. C.; Wang, Y.; Rong, J. Biodegradable celastrol-loaded albumin nanoparticles ameliorate inflammation and lipid accumulation in diet-induced obese mice. Biomater. Sci. 2022, 10, 984-996.
https://doi.org/10.1039/D1BM01637G

[53]. Ozpolat, B.; Sood, A. K.; Lopez-Berestein, G. Liposomal siRNA nanocarriers for cancer therapy. Adv. Drug Deliv. Rev. 2014, 66, 110-116.
https://doi.org/10.1016/j.addr.2013.12.008

[54]. Chen, X.; Hu, X.; Hu, J.; Qiu, Z.; Yuan, M.; Zheng, G. Celastrol-loaded galactosylated liposomes effectively inhibit AKT/c-met-triggered rapid hepatocarcinogenesis in mice. Mol. Pharm. 2020, 17, 738-747.
https://doi.org/10.1021/acs.molpharmaceut.9b00428

[55]. Aqil, F.; Kausar, H.; Agrawal, A. K.; Jeyabalan, J.; Kyakulaga, A.-H.; Munagala, R.; Gupta, R. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp. Mol. Pathol. 2016, 101, 12-21.
https://doi.org/10.1016/j.yexmp.2016.05.013

[56]. Zhao, Y.; Tan, Y.; Meng, T.; Liu, X.; Zhu, Y.; Hong, Y.; Yang, X.; Yuan, H.; Huang, X.; Hu, F. Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-κB signaling pathway using Celastrol-loaded micelles. Drug Deliv. 2018, 25, 341-352.
https://doi.org/10.1080/10717544.2018.1425778

[57]. Sanna, V.; Chamcheu, J. C.; Pala, N.; Mukhtar, H.; Sechi, M.; Siddiqui, I. A. Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment. Int. J. Nanomedicine 2015, 6835-6846.
https://doi.org/10.2147/IJN.S93752

[58]. Tian, Q.; Han, Q.; Zhu, X.; Zhang, L.; Chen, K.; Xie, Z.; Wang, P.; Wu, X.; Zhang, Z.; Zeng, H. Celastrol-conjugated carboxylmethyl chitosan for oral treatment of diet-induced obesity. J. Drug Deliv. Sci. Technol. 2021, 62, 102408.
https://doi.org/10.1016/j.jddst.2021.102408

[59]. Boridy, S.; Soliman, G. M.; Maysinger, D. Modulation of inflammatory signaling and cytokine release from microglia by celastrol incorporated into dendrimer nanocarriers. Nanomedicine (Lond.) 2012, 7, 1149-1165.
https://doi.org/10.2217/nnm.12.16

[60]. Gong, T.; Zhang, P.; Deng, C.; Xiao, Y.; Gong, T.; Zhang, Z. An effective and safe treatment strategy for rheumatoid arthritis based on human serum albumin and Kolliphor® HS 15. Nanomedicine (Lond.) 2019, 14, 2169-2187.
https://doi.org/10.2217/nnm-2019-0110

[61]. Fan, N.; Zhao, J.; Zhao, W.; Zhang, X.; Song, Q.; Shen, Y.; Shum, H. C.; Wang, Y.; Rong, J. Celastrol-loaded lactosylated albumin nanoparticles attenuate hepatic steatosis in non-alcoholic fatty liver disease. J. Control. Release 2022, 347, 44-54.
https://doi.org/10.1016/j.jconrel.2022.04.034

[62]. Zhu, S.; Luo, C.; Feng, W.; Li, Y.; Zhu, M.; Sun, S.; Zhang, X. Selenium-deposited tripterine phytosomes ameliorate the antiarthritic efficacy of the phytomedicine via a synergistic sensitization. Int. J. Pharm. 2020, 578, 119104.
https://doi.org/10.1016/j.ijpharm.2020.119104

[63]. Liu, S.; Chen, Q.; Yan, L.; Ren, Y.; Fan, J.; Zhang, X.; Zhu, S. Phytosomal tripterine with selenium modification attenuates the cytotoxicity and restrains the inflammatory evolution via inhibiting NLRP3 inflammasome activation and pyroptosis. Int. Immunopharmacol. 2022, 108, 108871.
https://doi.org/10.1016/j.intimp.2022.108871

[64]. Luo, P.; Zhang, Q.; Shen, S.; An, Y.; Yuan, L.; Wong, Y.-K.; Huang, S.; Huang, S.; Huang, J.; Cheng, G.; Tian, J.; Chen, Y.; Zhang, X.; Li, W.; He, S.; Wang, J.; Du, Q. Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma. Asian J. Pharm. Sci. 2023, 18, 100874.
https://doi.org/10.1016/j.ajps.2023.100874

[65]. Zheng, X.; Xing, Y.; Sun, K.; Jin, H.; Zhao, W.; Yu, F. Combination therapy with resveratrol and celastrol using folic acid‐functionalized exosomes enhances the therapeutic efficacy of sepsis. Adv. Healthc. Mater. 2023, 12, e2301325.
https://doi.org/10.1002/adhm.202301325

[66]. Effect of Different Ingestion Doses of Celastrol on Human Sperm Motility - Clinicaltrials.gov. https://clinicaltrials.gov/study/ NCT05413226 (accessed Jan 11, 2024).

[67]. A Sub-Chronic Evaluation of the Safety of Celastrol in Human Subjects - Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT05494112 (accessed Jan 11, 2024).

[68]. Kitzen, J. J. E. M.; de Jonge, M. J. A.; Lamers, C. H. J.; Eskens, F. A. L. M.; van der Biessen, D.; van Doorn, L.; ter Steeg, J.; Brandely, M.; Puozzo, C.; Verweij, J. Phase I dose-escalation study of F60008, a novel apoptosis inducer, in patients with advanced solid tumours. Eur. J. Cancer 2009, 45, 1764-1772.
https://doi.org/10.1016/j.ejca.2009.01.026

[69]. Ge, Y.; Xie, H.; Li, S.; Jin, B.; Hou, J.; Zhang, H.; Shi, M.; Liu, Z. Treatment of diabetic nephropathy with Tripterygium wilfordii Hook F extract: a prospective, randomized, controlled clinical trial. J. Transl. Med. 2013, 11, 134.
https://doi.org/10.1186/1479-5876-11-134

[70]. Zhu, W.; Li, Y.; Gong, J.; Zuo, L.; Zhang, W.; Cao, L.; Gu, L.; Guo, Z.; Li, N.; Li, J. Tripterygium wilfordii Hook. f. versus azathioprine for prevention of postoperative recurrence in patients with Crohn's disease: A randomized clinical trial. Dig. Liver Dis. 2015, 47, 14-19.
https://doi.org/10.1016/j.dld.2014.09.008

[71]. Goldbach-Mansky, R. Comparison of Tripterygium wilfordii hook F versus sulfasalazine in the treatment of rheumatoid arthritis: A randomized trial. Ann. Intern. Med. 2009, 151, 229-240.
https://doi.org/10.7326/0003-4819-151-4-200908180-00005

[72]. Liu, Y.; Tu, S.; Gao, W.; Wang, Y.; Liu, P.; Hu, Y.; Dong, H. Extracts of Tripterygium wilfordii hook F in the treatment of rheumatoid arthritis: A systemic review and meta-analysis of randomised controlled trials. Evid. Based. Complement. Alternat. Med. 2013, 2013, 1-11, 410793.
https://doi.org/10.1155/2013/410793

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This research was supported by Science and Technology Development Fund FDCT grants from Macau University of Science and Technology to PC (Project Code: 0005-2023-RIA1).
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