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Mini-Reviews in Medicinal Chemistry

Author(s): Haimeng Luo, Xiaoyun Ji, Mengyu Zhang, Yaoyao Ren, Rui Tan*, Hezhong Jiang* and Xiaoqing Wu*

DOI: 10.2174/0113895575298364240409064833

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Aloe-emodin: Progress in Pharmacological Activity, Safety, and Pharmaceutical Formulation Applications

Page: [1784 - 1798] Pages: 15

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Abstract

Aloe-emodin (AE) is an anthraquinone derivative and a biologically active component sourced from various plants, including Rheum palmatum L. and Aloe vera. Known chemically as 1,8-dihydroxy-3-hydroxymethyl-anthraquinone, AE has a rich history in traditional medicine and is esteemed for its accessibility, safety, affordability, and effectiveness. AE boasts multiple biochemical and pharmacological properties, such as strong antibacterial, antioxidant, and antitumor effects. Despite its array of benefits, AE's identity as an anthraquinone derivative raises concerns about its potential for liver and kidney toxicity. Nevertheless, AE is considered a promising drug candidate due to its significant bioactivities and cost efficiency. Recent research has highlighted that nanoformulated AE may enhance drug delivery, biocompatibility, and pharmacological benefits, offering a novel approach to drug design. This review delves into AE's pharmacological impacts, mechanisms, pharmacokinetics, and safety profile, incorporating insights from studies on its nanoformulations. The goal is to outline the burgeoning research in this area and to support the ongoing development and utilization of AE-based therapies.

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[1]
Siddiqui, A.J.; Jahan, S.; Singh, R.; Saxena, J.; Ashraf, S.A.; Khan, A.; Choudhary, R.K.; Balakrishnan, S.; Badraoui, R.; Bardakci, F.; Adnan, M. Plants in anticancer drug discovery: From molecular mechanism to chemoprevention. BioMed Res. Int., 2022, 2022, 1-18.
[http://dx.doi.org/10.1155/2022/5425485] [PMID: 35281598]
[2]
Kitic, D.; Miladinovic, B.; Randjelovic, M.; Szopa, A.; Sharifi-Rad, J.; Calina, D.; Seidel, V. Anticancer potential and other pharmacological properties of Prunus armeniaca L.: An updated overview. Plants, 2022, 11(14), 1885.
[http://dx.doi.org/10.3390/plants11141885] [PMID: 35890519]
[3]
Nwozo, O.S.; Effiong, E.M.; Aja, P.M.; Awuchi, C.G. Antioxidant, phytochemical, and therapeutic properties of medicinal plants: A review. Int. J. Food Prop., 2023, 26(1), 359-388.
[http://dx.doi.org/10.1080/10942912.2022.2157425]
[4]
Gu, X.; Hao, D.; Xiao, P. Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020. Chin. Herb. Med., 2022, 14(2), 171-186.
[http://dx.doi.org/10.1016/j.chmed.2022.03.004] [PMID: 36117669]
[5]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 2007, 70(3), 461-477.
[http://dx.doi.org/10.1021/np068054v] [PMID: 17309302]
[6]
Şeker Karatoprak, G.; Küpeli Akkol, E.; Yücel, Ç.; Bahadır Acıkara, Ö.; Sobarzo-Sánchez, E. Advances in understanding the role of aloe emodin and targeted drug delivery systems in cancer. Oxid. Med. Cell. Longev., 2022, 2022, 1-20.
[http://dx.doi.org/10.1155/2022/7928200] [PMID: 35087619]
[7]
Yu, J.; Zhao, X.; Yan, X.; Li, W.; Liu, Y.; Wang, J.; Wang, J.; Yang, Y.; Hao, Y.; Liang, Z.; Tao, Y.; Yuan, Y.; Du, Z. Aloe-emodin ameliorated MI-induced cardiac remodeling in mice via inhibiting TGF-β/SMAD signaling via up-regulating SMAD7. Phytomedicine, 2023, 114, 154793.
[http://dx.doi.org/10.1016/j.phymed.2023.154793] [PMID: 37011420]
[8]
Wamer, W.G.; Vath, P.; Falvey, D.E. In vitro studies on the photobiological properties of aloe emodin and aloin A. Free Radic. Biol. Med., 2003, 34(2), 233-242.
[http://dx.doi.org/10.1016/S0891-5849(02)01242-X] [PMID: 12521605]
[9]
Hao, D.; Liu, C. Chinese herbal medicines will illuminate the post-epidemic era. Chin. Herb. Med., 2022, 14(2), 169-170.
[http://dx.doi.org/10.1016/j.chmed.2022.03.005] [PMID: 35382001]
[10]
Panigrahi, G.K.; Verma, N.; Singh, N.; Asthana, S.; Gupta, S.K.; Tripathi, A.; Das, M. Interaction of anthraquinones of Cassia occidentalis seeds with DNA and Glutathione. Toxicol. Rep., 2018, 5, 164-172.
[http://dx.doi.org/10.1016/j.toxrep.2017.12.024] [PMID: 29326881]
[11]
Zhao, L.C.; Liang, J.; Li, W.; Cheng, K.M.; Xia, X.; Deng, X.; Yang, G.L. The use of response surface methodology to optimize the ultrasound-assisted extraction of five anthraquinones from Rheum palmatum L. Molecules, 2011, 16(7), 5928-5937.
[http://dx.doi.org/10.3390/molecules16075928] [PMID: 21765390]
[12]
Españo, E.; Kim, J.; Kim, J.K. Utilization of Aloe compounds in combatting viral diseases. Pharmaceuticals, 2022, 15(5), 599.
[http://dx.doi.org/10.3390/ph15050599] [PMID: 35631425]
[13]
Xu, Y.; Yu, X.; Gui, J.; Wan, Y.; Chen, J.; Tan, T.; Liu, F.; Guo, L. Ultrasonic solvent extraction followed by dispersive solid phase extraction (d-spe) cleanup for the simultaneous determination of five anthraquinones in Polygonum multiflorum by UHPLC-PDA. Foods, 2022, 11(3), 386.
[http://dx.doi.org/10.3390/foods11030386] [PMID: 35159536]
[14]
Kabi, A.K.; Gujjarappa, R.; Gujjarappa, R.; Garg, A.; Roy, A.; Sahoo, A.; Gupta, S.; Malakar, C.C. Tailored Functional Materials. Springer Proceedings in Materials; Springer Nature Singapore; Springer: Singapore, 2022, pp. 61-80.
[http://dx.doi.org/10.1007/978-981-19-2572-6_5]
[15]
Kabi, A.K.; Gujjarappa, R.; Garg, A.; Sahoo, A.; Roy, A.; Gupta, S.; Malakar, C.C. Tailored Functional Materials. In: Springer Proceedings in Materials; Springer Nature Singapore; Springer: Singapore, 2022; 15, pp. 81-98.
[http://dx.doi.org/10.1007/978-981-19-2572-6_6]
[16]
Zhang, S.; Xuan, L. New phenolic constituents from the stems of Spatholobus suberectus. Helv. Chim. Acta, 2006, 89(6), 1241-1245.
[http://dx.doi.org/10.1002/hlca.200690121]
[17]
Forno-Bell, N.; Bucarey, S. A.; García, D.; Iragüen, D.; Chacón, O.; San Martín, B. Antimicrobial effects caused by aloe barbadensis miller on bacteria associated with mastitis in dairy cattle. Nat. Prod. Commun., 2019, 14(12), 1934578X1989667.
[http://dx.doi.org/10.1177/1934578X19896670]
[18]
Wang, Q.; Xu, Y.; Xu, J.; Wang, X.; Shen, C.; Zhang, Y.; Liu, X.; Yu, B.; Zhang, J. Molecular cloning and expression of a glycosyltransferase from Bacillus subtilis for modification of morin and related polyphenols. Biotechnol. Lett., 2017, 39(8), 1229-1235.
[http://dx.doi.org/10.1007/s10529-017-2352-z] [PMID: 28484911]
[19]
Xiang, H.; Cao, F.; Ming, D.; Zheng, Y.; Dong, X.; Zhong, X.; Mu, D.; Li, B.; Zhong, L.; Cao, J.; Wang, L.; Ma, H.; Wang, T.; Wang, D. Aloe-emodin inhibits Staphylococcus aureus biofilms and extracellular protein production at the initial adhesion stage of biofilm development. Appl. Microbiol. Biotechnol., 2017, 101(17), 6671-6681.
[http://dx.doi.org/10.1007/s00253-017-8403-5] [PMID: 28710559]
[20]
Wasserman, L.; Avigad, S.; Beery, E.; Nordenberg, J.; Fenig, E. The effect of aloe emodin on the proliferation of a new merkel carcinoma cell line. Am. J. Dermatopathol., 2002, 24(1), 17-22.
[http://dx.doi.org/10.1097/00000372-200202000-00003] [PMID: 11803275]
[21]
Qian, C.; Wang, M.; Wang, L.; Wang, H.; Li, Y.; Tang, X.; Zhou, Y.; Wang, Z.; Yang, Z.; Shi, Y. Functionalized periodic mesoporous organosilica nanoparticles for combinational chemo-photothermal antitumor therapy. ACS Appl. Nano Mater., 2022, 5(7), 9646-9656.
[http://dx.doi.org/10.1021/acsanm.2c01863]
[22]
Dong, X.; Zeng, Y.; Liu, Y.; You, L.; Yin, X.; Fu, J.; Ni, J. Aloe‐emodin: A review of its pharmacology, toxicity, and pharmacokinetics. Phytother. Res., 2020, 34(2), 270-281.
[http://dx.doi.org/10.1002/ptr.6532] [PMID: 31680350]
[23]
Wu, F.; Wang, Y.; Mei, Q.; Chen, Q.; Sun, C.; Lv, X.; Feng, L.; Wang, C.; Zhang, Y.; Fang, B.; Huo, X.; Tian, X.; Ma, X. UGTs-mediated metabolic interactions contribute to enhanced anti-inflammation activity of Jinhongtang. J. Ethnopharmacol., 2023, 304, 116016.
[http://dx.doi.org/10.1016/j.jep.2022.116016] [PMID: 36535328]
[24]
Li, R.R.; Liu, X.F.; Feng, S.X.; Shu, S.N.; Wang, P.Y.; Zhang, N.; Li, J.S.; Qu, L.B. Pharmacodynamics of five anthraquinones (Aloe-emodin, emodin, rhein, chysophanol, and physcion) and reciprocal pharmacokinetic interaction in rats with cerebral ischemia. Molecules, 2019, 24(10), 1898.
[http://dx.doi.org/10.3390/molecules24101898] [PMID: 31108858]
[25]
Ali, M.Y.; Jannat, S.; Jung, H.A.; Min, B.S.; Paudel, P.; Choi, J.S. Hepatoprotective effect of Cassia obtusifolia seed extract and constituents against oxidative damage induced by tert -butyl hydroperoxide in human hepatic HepG2 cells. J. Food Biochem., 2018, 42(1), e12439.
[http://dx.doi.org/10.1111/jfbc.12439]
[26]
Kuruca, S.E.; Çandöken, E.; Akev, N. Investigation of aloe-emodin and aloe vera gel extract on apoptosis dependent pathways in leukemia and lymphoma cell lines. İstanbul. J. Pharm., 2020, 50(1), 42-48.
[http://dx.doi.org/10.26650/IstanbulJPharm.2019.0039]
[27]
Kim, H.J.; Choi, J.W.; Ree, J.; Lim, J.S.; Lee, J.; Kim, J.I.; Thapa, S.B.; Sohng, J.K.; Park, Y.I. Aloe emodin 3-O-glucoside inhibits cell growth and migration and induces apoptosis of non-small-cell lung cancer cells via suppressing MEK/ERK and Akt signalling pathways. Life Sci., 2022, 300, 120495.
[http://dx.doi.org/10.1016/j.lfs.2022.120495] [PMID: 35341826]
[28]
Wu, Y.Y.; Zhang, J.H.; Gao, J.H.; Li, Y.S. Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo. Biochem. Biophys. Res. Commun., 2017, 490(3), 601-607.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.084] [PMID: 28629998]
[29]
Shen, F.; Ge, C.; Yuan, P. Aloe-emodin induces autophagy and apoptotic cell death in non-small cell lung cancer cells via Akt/mTOR and MAPK signaling. Eur. J. Pharmacol., 2020, 886, 173550.
[http://dx.doi.org/10.1016/j.ejphar.2020.173550] [PMID: 32926915]
[30]
Peng, M.; Zheng, Z.; Chen, S.; Fang, L.; Feng, R.; Zhang, L.; Tang, Q.; Liu, X. Sensitization of non-small cell lung cancer cells to gefitinib and reversal of epithelial–mesenchymal transition by Aloe-Emodin via PI3K/Akt/TWIS1 signal blockage. Front. Oncol., 2022, 12, 908031.
[http://dx.doi.org/10.3389/fonc.2022.908031] [PMID: 35677158]
[31]
Chaudhary, A.; Bhardwaj, S.K.; Khan, A.; Srivastava, A.; Sinha, K.K.; Ali, M.; Haque, R. Combinatorial effect of arsenic and herbal compounds in telomerase-mediated apoptosis induction in liver cancer. Biol. Trace Elem. Res., 2022.
[http://dx.doi.org/10.1007/s12011-022-03430-0] [PMID: 36192614]
[32]
Gao, R.; Wu, X.; Huang, Z.; Wang, B.; Li, F.; Xu, H.; Ran, L. Anti-tumor effect of aloe-emodin on cervical cancer cells was associated with human papillomavirus E6/E7 and glucose metabolism. OncoTargets Ther., 2019, 12, 3713-3721.
[http://dx.doi.org/10.2147/OTT.S182405] [PMID: 31190872]
[33]
Du, M.; Shen, P.; Tan, R.; Wu, D.; Tu, S. Aloe-emodin inhibits the proliferation, migration, and invasion of melanoma cells via inactivation of the Wnt/beta-catenin signaling pathway. Ann. Transl. Med., 2021, 9(23), 1722.
[http://dx.doi.org/10.21037/atm-21-5437] [PMID: 35071416]
[34]
Acevedo-Duncan, M.; Russell, C.; Patel, S.; Patel, R. Aloe–emodin modulates PKC isozymes, inhibits proliferation, and induces apoptosis in U-373MG glioma cells. Int. Immunopharmacol., 2004, 4(14), 1775-1784.
[http://dx.doi.org/10.1016/j.intimp.2004.07.012] [PMID: 15531293]
[35]
Mijatovic, S.; Maksimovic-Ivanic, D.; Radovic, J.; Miljkovic, D.; Harhaji, L.; Vuckovic, O.; Stosic-Grujicic, S.; Mostarica Stojkovic, M.; Trajkovic, V. Anti-glioma action of aloe emodin: The role of ERK inhibition. Cell. Mol. Life Sci., 2005, 62(5), 589-598.
[http://dx.doi.org/10.1007/s00018-005-4425-8] [PMID: 15747063]
[36]
Ismail, S.; Haris, K.; Abdul Ghani, A.R.I.; Abdullah, J.M.; Johan, M.F.; Mohamed Yusoff, A.A. Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin. J. Asian Nat. Prod. Res., 2013, 15(9), 1003-1012.
[http://dx.doi.org/10.1080/10286020.2013.818982] [PMID: 23869465]
[37]
Jiang, D.; Ding, S.; Mao, Z.; You, L.; Ruan, Y. Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells. Cancer Cell Int., 2021, 21(1), 238.
[http://dx.doi.org/10.1186/s12935-021-01942-8] [PMID: 33902610]
[38]
Li, Q.; Wen, J.; Yu, K.; Shu, Y.; He, W.; Chu, H.; Zhang, B.; Ge, C. Aloe-emodin induces apoptosis in human oral squamous cell carcinoma SCC15 cells. BMC Complement. Altern. Med., 2018, 18(1), 296.
[http://dx.doi.org/10.1186/s12906-018-2353-z] [PMID: 30404637]
[39]
Nowak-Perlak, M.; Bromke, M.A.; Ziółkowski, P.; Woźniak, M. The comparison of the efficiency of emodin and aloe-emodin in photodynamic therapy. Int. J. Mol. Sci., 2022, 23(11), 6276.
[http://dx.doi.org/10.3390/ijms23116276] [PMID: 35682955]
[40]
Abdellatef, A.A.; Fathy, M.; Mohammed, A.E.S.I.; Bakr, M.S.A.; Ahmed, A.H.; Abbass, H.S.; El-Desoky, A.H.; Morita, H.; Nikaido, T.; Hayakawa, Y. Inhibition of cell-intrinsic NF-κB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus. J. Nat. Med., 2021, 75(4), 840-853.
[http://dx.doi.org/10.1007/s11418-021-01526-w] [PMID: 33988779]
[41]
Chiu, T-H.; Lai, W-W.; Hsia, T-C.; Yang, J-S.; Lai, T-Y.; Wu, P-P.; Ma, C-Y.; Yeh, C-C.; Ho, C-C.; Lu, H-F.; Wood, W.G.; Chung, J-G. Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells. Anticancer Res., 2009, 29(11), 4503-4511.
[PMID: 20032398]
[42]
Chen, Y-Y.; Chiang, S-Y.; Lin, J-G.; Yang, J-S.; Ma, Y-S.; Liao, C-L.; Lai, T-Y.; Tang, N-Y.; Chung, J-G. Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res., 2010, 30(3), 945-951.
[PMID: 20393018]
[43]
Akev, N.; Candoken, E.; Erdem Kuruca, S. Comparative study on the anticancer drug potential of a lectin purified from aloe vera and aloe-emodin. Asian Pac. J. Cancer Prev., 2020, 21(1), 99-106.
[http://dx.doi.org/10.31557/APJCP.2020.21.1.99] [PMID: 31983171]
[44]
Hu, Y.; Huang, W.; Luo, Y.; Xiang, L.; Wu, J.; Zhang, Y.; Zeng, Y.; Xu, C.; Meng, X.; Wang, P. Assessment of the anti-inflammatory effects of three rhubarb anthraquinones in LPS-Stimulated RAW264.7 macrophages using a pharmacodynamic model and evaluation of the structure-activity relationships. J. Ethnopharmacol., 2021, 273, 114027.
[http://dx.doi.org/10.1016/j.jep.2021.114027] [PMID: 33741438]
[45]
Yang, M.; Shrestha, S.K.; Soh, Y.; Heo, S.M. Effects of aloe-emodin on alveolar bone in Porphyromonas gingivalis -induced periodontitis rat model: A pilot study. J. Periodontal Implant Sci., 2022, 52(5), 383-393.
[http://dx.doi.org/10.5051/jpis.2104060203] [PMID: 36302645]
[46]
Jiang, L.; Yi, T.; Shen, Z.; Teng, Z.; Wang, J. Aloe-emodin attenuates Staphylococcus aureus pathogenicity by interfering with the oligomerization of α-Toxin. Front. Cell. Infect. Microbiol., 2019, 9, 157.
[http://dx.doi.org/10.3389/fcimb.2019.00157] [PMID: 31157174]
[47]
Zhang, Y.X.; Li, J.S.; Peng, W.W.; Liu, X.; Yang, G.M.; Chen, L.H.; Cai, B.C. Comparative pharmacokinetics of aloe-emodin, rhein and emodin determined by liquid chromatography-mass spectrometry after oral administration of a rhubarb peony decoction and rhubarb extract to rats. Pharmazie, 2013, 68(5), 333-339.
[http://dx.doi.org/10.1691/ph.2013.2855] [PMID: 23802430]
[48]
Arosio, B.; Gagliano, N.; Fusaro, L.M.P.; Parmeggiani, L.; Tagliabue, J.; Galetti, P.; De Castri, D.; Moscheni, C.; Annoni, G. Aloe-Emodin quinone pretreatment reduces acute liver injury induced by carbon tetrachloride. Pharmacol. Toxicol., 2000, 87(5), 229-233.
[http://dx.doi.org/10.1034/j.1600-0773.2000.pto870507.x] [PMID: 11129503]
[49]
Chen, C.; Cao, T.; Li, Y.; Hu, Y.; Yang, H.; Yin, S. Synthesized derivatives of aloe-emodin as proliferation inhibitors for human breast adenocarcinoma, human nonsmall cell lung carcinoma, and human cervix carcinoma. Chem. Nat. Compd., 2020, 56(1), 30-33.
[http://dx.doi.org/10.1007/s10600-020-02937-z]
[50]
Yu, B.; Wang, M.; Xu, H.; Gao, R.; Zhu, Y.; Ning, H.; Dai, X. Investigating the role of dahuang in hepatoma treatment using network pharmacology, molecular docking, and survival analysis. BioMed Res. Int., 2022, 2022, 1-15.
[http://dx.doi.org/10.1155/2022/5975223] [PMID: 35872841]
[51]
Jiang, H.; Tang, W.; Song, Y.; Jin, W.; Du, Q. Induction of apoptosis by metabolites of rhei radix et rhizoma (Da Huang): A review of the potential mechanism in hepatocellular carcinoma. Front. Pharmacol., 2022, 13, 806175.
[http://dx.doi.org/10.3389/fphar.2022.806175] [PMID: 35308206]
[52]
Haris, K.; Ismail, S.; Idris, Z.; Abdullah, J.M.; Yusoff, A.A.M. Expression profile of genes modulated by Aloe emodin in human U87 glioblastoma cells. Asian Pac. J. Cancer Prev., 2014, 15(11), 4499-4505.
[http://dx.doi.org/10.7314/APJCP.2014.15.11.4499] [PMID: 24969876]
[53]
Liu, Y.; Meng, P.; Zhang, H.; Liu, X.; Wang, M.; Cao, W.; Hu, Z.; Zhang, Z. Inhibitory effect of aloe emodin mediated photodynamic therapy on human oral mucosa carcinoma in vitro and in vivo. Biomed. Pharmacother., 2018, 97, 697-707.
[http://dx.doi.org/10.1016/j.biopha.2017.10.080] [PMID: 29102913]
[54]
Rolta, R.; Yadav, R.; Salaria, D.; Trivedi, S.; Imran, M.; Sourirajan, A.; Baumler, D.J.; Dev, K. In silico screening of hundred phytocompounds of ten medicinal plants as potential inhibitors of nucleocapsid phosphoprotein of COVID-19: An approach to prevent virus assembly. J. Biomol. Struct. Dyn., 2021, 39(18), 7017-7034.
[http://dx.doi.org/10.1080/07391102.2020.1804457] [PMID: 32851912]
[55]
Wu, F.; Zhang, B.; Zhang, Y.; Zhao, T.; Wang, Y.; Tian, X.; Sun, C.; Fang, B.; Huo, X.; Ma, X. Simultaneous determination of ten active components from jinhongtang granule in rat plasma by LC–MS/MS and its application to a comparative pharmacokinetic study in normal and sepsis rats in vivo and in vitro. J. Chromatogr. Sci., 2022, bmac043.
[http://dx.doi.org/10.1093/chromsci/bmac043] [PMID: 35913259]
[56]
Qi, J.; Dong, F.; Wang, K.; Zhang, S.; Liu, Z.; Wang, W.; Sun, F.; Zhang, H.; Wang, X. Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) against COVID-19. J. Med. Microbiol., 2022, 71(5)
[http://dx.doi.org/10.1099/jmm.0.001528] [PMID: 35584000]
[57]
Li, L.; Wang, X.; Guo, X.; Li, Y.; Song, Q.; Li, A. Network pharmacology and computer-aided drug design to explored potential targets of Lianhua Qingwen and Qingfei Paidu decoction for COVID-19. Front. Pharmacol., 2022, 13, 1013428.
[http://dx.doi.org/10.3389/fphar.2022.1013428] [PMID: 36210820]
[58]
Sharanya, C.S.; Arun, K.G.; Sabu, A.; Haridas, M. Aloe emodin shows high affinity to active site and low affinity to two other sites to result consummately reduced inhibition of lipoxygenase. Prostaglandins Other Lipid Mediat., 2020, 150, 106453.
[http://dx.doi.org/10.1016/j.prostaglandins.2020.106453] [PMID: 32380176]
[59]
Parvez, M.K.; Al-Dosari, M.S.; Alam, P.; Rehman, M.; Alajmi, M.F.; Alqahtani, A.S. The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera. Phytother. Res., 2019, 33(11), 2960-2970.
[http://dx.doi.org/10.1002/ptr.6471] [PMID: 31410907]
[60]
Bhimaneni, S.; Kumar, A. Abscisic acid and aloe-emodin against NS2B-NS3A protease of Japanese encephalitis virus. Environ. Sci. Pollut. Res. Int., 2022, 29(6), 8759-8766.
[http://dx.doi.org/10.1007/s11356-021-16229-8] [PMID: 34490576]
[61]
Deng, Z.; Bheemanaboina, R.R.Y.; Luo, Y.; Zhou, C.H. Aloe emodin-conjugated sulfonyl hydrazones as novel type of antibacterial modulators against S. aureus 25923 through multifaceted synergistic effects. Bioorg. Chem., 2022, 127, 106035.
[http://dx.doi.org/10.1016/j.bioorg.2022.106035] [PMID: 35870413]
[62]
Hu, X.; Ma, Y.; Liu, Z.; Zhao, M.; Dong, S.; Yang, H.; Dai, C. Microcalorimetric evaluation of the effects of three anthraquinone derivatives from Chinese Rhubarb and the synergistic effect of the mixture on Staphylococcus aureus. J. Therm. Anal. Calorim., 2020, 141(2), 739-749.
[http://dx.doi.org/10.1007/s10973-019-09082-y]
[63]
Le, T.D.; Phasupan, P.; Nguyen, L.T. Antimicrobial photodynamic efficacy of selected natural photosensitizers against food pathogens: Impacts and interrelationship of process parameters. Photodiagn. Photodyn. Ther., 2020, 32, 102024.
[http://dx.doi.org/10.1016/j.pdpdt.2020.102024] [PMID: 32980551]
[64]
Li, J.; Qin, M.; Liu, C.; Ma, W.; Zeng, X.; Ji, Y. Antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii clinical isolates mediated by aloe-emodin: An in vitro study. Photodiagn. Photodyn. Ther., 2020, 29, 101632.
[http://dx.doi.org/10.1016/j.pdpdt.2019.101632] [PMID: 31870894]
[65]
Wang, Y.; Li, J.; Geng, S.; Wang, X.; Cui, Z.; Ma, W.; Yuan, M.; Liu, C.; Ji, Y. Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: An in vivo study. Photodiagn. Photodyn. Ther., 2021, 34, 102311.
[http://dx.doi.org/10.1016/j.pdpdt.2021.102311] [PMID: 33930578]
[66]
Ma, W.; Liu, C.; Li, J.; Hao, M.; Ji, Y.; Zeng, X. The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans. Photochem. Photobiol. Sci., 2020, 19(4), 485-494.
[http://dx.doi.org/10.1039/c9pp00352e] [PMID: 32232258]
[67]
Deng, Z.; Sun, H.; Bheemanaboina, R.R.Y.; Luo, Y.; Zhou, C.H. Natural aloe emodin-hybridized sulfonamide aminophosphates as novel potential membrane-perturbing and DNA-intercalating agents against Enterococcus faecalis. Bioorg. Med. Chem. Lett., 2022, 64, 128695.
[http://dx.doi.org/10.1016/j.bmcl.2022.128695] [PMID: 35314326]
[68]
Ma, W.; Zhang, M.; Cui, Z.; Wang, X.; Niu, X.; Zhu, Y.; Yao, Z.; Ye, F.; Geng, S.; Liu, C. Aloe‐emodin‐mediated antimicrobial photodynamic therapy against dermatophytosis caused by Trichophyton rubrum. Microb. Biotechnol., 2022, 15(2), 499-512.
[http://dx.doi.org/10.1111/1751-7915.13875] [PMID: 34165875]
[69]
Li, T.; Lu, Y.; Zhang, H.; Wang, L.; Beier, R.C.; Jin, Y.; Wang, W.; Li, H.; Hou, X. Antibacterial activity and membrane-targeting mechanism of aloe-emodin against Staphylococcus epidermidis. Front. Microbiol., 2021, 12, 621866.
[http://dx.doi.org/10.3389/fmicb.2021.621866] [PMID: 34484130]
[70]
de Souza Collares Maia Castelo-Branco, D.; dos Santos Araújo, G.; Fonseca, X.M.Q.C.; de Melo Guedes, G.M.; da Rocha, M.G.; Brilhante, R.S.N.; de Aguiar Cordeiro, R.; Sidrim, J.J.C.; Pereira-Neto, W.A.; Rocha, M.F.G. Anthraquinones from Aloe spp. inhibit Cryptococcus neoformans sensu stricto: Effects against growing and mature biofilms. Biofouling, 2021, 37(8), 809-817.
[http://dx.doi.org/10.1080/08927014.2021.1958793] [PMID: 34634964]
[71]
Canche-Escamilla, G.; Colli-Acevedo, P.; Borges-Argaez, R.; Quintana-Owen, P.; May-Crespo, J.F.; Cáceres-Farfan, M.; Yam Puc, J.A.; Sansores-Peraza, P.; Vera-Ku, B.M. Extraction of phenolic components from an Aloe vera (Aloe barbadensis Miller) crop and their potential as antimicrobials and textile dyes. Sustain. Chem. Pharm., 2019, 14, 100168.
[http://dx.doi.org/10.1016/j.scp.2019.100168]
[72]
Tao, L.; Xie, J.; Wang, Y.; Wang, S.; Wu, S.; Wang, Q.; Ding, H. Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H2O2-induced cytotoxicity in PC12 cells. Bioorg. Med. Chem. Lett., 2014, 24(23), 5385-5389.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.049] [PMID: 25453793]
[73]
Gao, Y.; Zhang, X.; Li, X.; Qi, R.; Han, Y.; Kang, Y.; Cai, R.; Peng, C.; Qi, Y. Aloe-emodin, a naturally occurring anthraquinone, is a highly potent mast cell stabilizer through activating mitochondrial calcium uniporter. Biochem. Pharmacol., 2021, 186, 114476.
[http://dx.doi.org/10.1016/j.bcp.2021.114476] [PMID: 33607072]
[74]
Cheng, G.; Pi, Z.; Zhuang, X.; Zheng, Z.; Liu, S.; Liu, Z.; Song, F. The effects and mechanisms of aloe‐emodin on reversing adriamycin‐induced resistance of MCF ‐7/ADR cells. Phytother. Res., 2021, 35(7), 3886-3897.
[http://dx.doi.org/10.1002/ptr.7096] [PMID: 33792091]
[75]
Reza Nazifi, S.M.; Asgharshamsi, M.H.; Dehkordi, M.M.; Zborowski, K.K. Antioxidant properties of Aloe vera components: A DFT theoretical evaluation. Free Radic. Res., 2019, 53(8), 922-931.
[http://dx.doi.org/10.1080/10715762.2019.1648798] [PMID: 31357895]
[76]
Ren, G.; Sun, H.; Li, G.; Fan, J.; Wu, Y.; Cui, G. Molecular docking and muiltple spectroscopy investigation on the binding characteristics of aloe-emodin to pepsin. J. Mol. Struct., 2019, 1195, 369-377.
[http://dx.doi.org/10.1016/j.molstruc.2019.05.084]
[77]
Dou, F.; Liu, Y.; Liu, L.; Wang, J.; Sun, T.; Mu, F.; Guo, Q.; Guo, C.; Jia, N.; Liu, W.; Ding, Y.; Wen, A. Aloe-emodin ameliorates renal fibrosis via inhibiting pi3k/akt/mtor signaling pathway in vivo and in vitro. Rejuvenation Res., 2019, 22(3), 218-229.
[http://dx.doi.org/10.1089/rej.2018.2104] [PMID: 30215298]
[78]
Lu, L.; Li, Y. Aloe-emodin ameliorates diabetic nephropathy by targeting interferon regulatory factor 4. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-9.
[http://dx.doi.org/10.1155/2022/2421624] [PMID: 35518350]
[79]
Sapkota, M.; Shrestha, S.K.; Yang, M.; Park, Y.R.; Soh, Y. Aloe-emodin inhibits osteogenic differentiation and calcification of mouse vascular smooth muscle cells. Eur. J. Pharmacol., 2019, 865, 172772.
[http://dx.doi.org/10.1016/j.ejphar.2019.172772] [PMID: 31697934]
[80]
Nasiri, N.; Babaei, S.; Moini, A.; Eftekhari-Yazdi, P. Controlling semi-invasive activity of human endometrial stromal cells by inhibiting NF-kB signaling pathway using aloe-emodin and aspirin. J. Reprod. Infertil., 2021, 22(4), 227-240.
[http://dx.doi.org/10.18502/jri.v22i4.7648] [PMID: 34987984]
[81]
Furkan, M.; Alam, M.T.; Rizvi, A.; Khan, K.; Ali, A. Shamsuzzaman; Naeem, A. Aloe emodin, an anthroquinone from Aloe vera acts as an anti aggregatory agent to the thermally aggregated hemoglobin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2017, 179, 188-193.
[http://dx.doi.org/10.1016/j.saa.2017.02.014] [PMID: 28242448]
[82]
Yu, Y.; Liu, H.; Yang, D.; He, F.; Yuan, Y.; Guo, J.; Hu, J.; Yu, J.; Yan, X.; Wang, S.; Du, Z. Aloe-emodin attenuates myocardial infarction and apoptosis via up-regulating miR-133 expression. Pharmacol. Res., 2019, 146, 104315.
[http://dx.doi.org/10.1016/j.phrs.2019.104315] [PMID: 31207343]
[83]
Zhao, W.; Yuan, Y.; Feng, B.; Sun, Y.; Jiang, H.; Zhao, W.; Zheng, Y.; Zhao, L.; Chen, T.; Bai, Y.; Hang, P.; Chen, Y.; Du, Z. Aloe-emodin relieves zidovudine-induced injury in neonatal rat ventricular myocytes by regulating the p90rsk/p-bad/bcl-2 signaling pathway. Environ. Toxicol. Pharmacol., 2021, 81, 103540.
[http://dx.doi.org/10.1016/j.etap.2020.103540] [PMID: 33161113]
[84]
Galli, C.L.; Cinelli, S.; Ciliutti, P.; Melzi, G.; Marinovich, M. Aloe-emodin, a hydroxyanthracene derivative, is not genotoxic in an in vivo comet test. Regul. Toxicol. Pharmacol., 2021, 124, 104967.
[http://dx.doi.org/10.1016/j.yrtph.2021.104967] [PMID: 34062205]
[85]
Hu, J.; Lloyd, M.; Hobbs, C.; Cox, P.; Burke, K.; Pearce, G.; Streicker, M.A.; Gao, Q.; Frankos, V. Absence of genotoxicity of purified Aloe vera whole leaf dry juice as assessed by an in vitro mouse lymphoma tk assay and an in vivo comet assay in male F344 rats. Toxicol. Rep., 2021, 8, 511-519.
[http://dx.doi.org/10.1016/j.toxrep.2021.03.007] [PMID: 33747796]
[86]
Liu, D.; Yang, D.; Zhou, C.; Wu, J.; Zhang, G.; Wang, P.; Wang, F.; Meng, X. Aloe-emodin induces hepatotoxicity by the inhibition of multidrug resistance protein 2. Phytomedicine, 2020, 68, 153148.
[http://dx.doi.org/10.1016/j.phymed.2019.153148] [PMID: 32028185]
[87]
Quan, Y.; Gong, L.; He, J.; Zhou, Y.; Liu, M.; Cao, Z.; Li, Y.; Peng, C. Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish. Toxicol. Lett., 2019, 306, 66-79.
[http://dx.doi.org/10.1016/j.toxlet.2019.02.007] [PMID: 30771440]
[88]
Li, R.; Li, W.; You, Y.; Guo, X.; Peng, Y.; Zheng, J. Metabolic activation and cytotoxicity of aloe-emodin mediated by sulfotransferases. Chem. Res. Toxicol., 2019, 32(6), 1281-1288.
[http://dx.doi.org/10.1021/acs.chemrestox.9b00081] [PMID: 31046239]
[89]
Hu, Y.; Quan, Z.; Li, D.; Wang, C.; Sun, Z. Inhibition of CYP3A4 enhances aloe-emodin induced hepatocyte injury. Toxicol. In vitro, 2022, 79, 105276.
[http://dx.doi.org/10.1016/j.tiv.2021.105276] [PMID: 34875353]
[90]
Yu, C.P.; Shia, C.S.; Lin, H.J.; Hsieh, Y.W.; Lin, S.P.; Hou, Y.C. Analysis of the pharmacokinetics and metabolism of aloe‐emodin following intravenous and oral administrations in rats. Biomed. Chromatogr., 2016, 30(10), 1641-1647.
[http://dx.doi.org/10.1002/bmc.3735] [PMID: 27061721]
[91]
Gecibesler, I.H.; Disli, F.; Bayindir, S.; Toprak, M.; Tufekci, A.R.; Sahin Yaglıoglu, A.; Altun, M.; Kocak, A.; Demirtas, I.; Adem, S. The isolation of secondary metabolites from Rheum ribes L. and the synthesis of new semi-synthetic anthraquinones: Isolation, synthesis and biological activity. Food Chem., 2021, 342, 128378.
[http://dx.doi.org/10.1016/j.foodchem.2020.128378] [PMID: 33508903]
[92]
Siddamurthi, S.; Gutti, G.; Jana, S.; Kumar, A.; Singh, S.K. Anthraquinone: A promising scaffold for the discovery and development of therapeutic agents in cancer therapy. Future Med. Chem., 2020, 12(11), 1037-1069.
[http://dx.doi.org/10.4155/fmc-2019-0198] [PMID: 32349522]
[93]
Zhang, Q.; Wang, J.; Lan, F.; Zhai, H.; Li, F.; Ma, T.; Li, D.; Hou, H. Synthesis and DNA interaction of aloe-emodin α-amino phosphate derivatives. J. Mol. Struct., 2023, 1279, 134950.
[http://dx.doi.org/10.1016/j.molstruc.2023.134950]
[94]
Freag, M.; Elnaggar, Y.; Abdelmonsif, D.; Abdallah, Y.; Stealth, O. Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: In vitro and in vivo studies. Int. J. Nanomedicine, 2016, 11, 4799-4818.
[http://dx.doi.org/10.2147/IJN.S111736]
[95]
Fang, X.; Chen, Z.; Zhou, W.; Li, T.; Wang, M.; Gao, Y.; Ma, S.; Feng, Y.; Du, S.; Lan, P.; Chen, H.; Wei, J.; Zhang, S.; Li, Z.; Liu, X.; Zhang, H.; Guo, X.; Luo, J. Boosting glioblastoma therapy with targeted pyroptosis induction. Small, 2023, 19(30), 2207604.
[http://dx.doi.org/10.1002/smll.202207604] [PMID: 37066699]
[96]
Huang, N.; Yan, X. Preparation of aloe-emodin microcapsules and its effect on antibacterial and optical properties of water-based coating. Polymers, 2023, 15(7), 1728.
[http://dx.doi.org/10.3390/polym15071728] [PMID: 37050342]
[97]
Li, K.T.; Duan, Q.Q.; Chen, Q.; He, J.W.; Tian, S.; Lin, H.D.; Gao, Q.; Bai, D.Q. The effect of aloe emodin–encapsulated nanoliposome‐mediated r‐caspase‐3 gene transfection and photodynamic therapy on human gastric cancer cells. Cancer Med., 2016, 5(2), 361-369.
[http://dx.doi.org/10.1002/cam4.584] [PMID: 26686868]
[98]
Wu, M.; Ling, W.; Wei, J.; Liao, R.; Sun, H.; Li, D.; Zhao, Y.; Zhao, L. Biomimetic photosensitizer nanocrystals trigger enhanced ferroptosis for improving cancer treatment. J. Control. Release, 2022, 352, 1116-1133.
[http://dx.doi.org/10.1016/j.jconrel.2022.11.026] [PMID: 36402233]
[99]
Chen, R.; Wang, S.; Zhang, J.; Chen, M.; Wang, Y. Aloe-emodin loaded solid lipid nanoparticles: Formulation design and in vitro anti-cancer study. Drug Deliv., 2015, 22(5), 666-674.
[http://dx.doi.org/10.3109/10717544.2014.882446] [PMID: 24512431]