Chemical properties of Indonesian aloe vera and its hepatoprotective activity by targeting reactive oxygen species and TACE protein: comparison between gel and whole parts
Main Article Content
Keywords
aloe vera; aloe gel; hepatoprotective; TNF-α converting enzyme (TACE); squalene
Abstract
This study evaluated the chemical properties of Indonesian aloe vera and compared the hepatoprotective activity of aloe gel (AO) and whole plant (WAO) against H2O2-induced toxicity in HepG2 cells. Chemical characterization was performed using ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, liquid chromatography–high-resolution mass spectrometry (LC-HRMS), and high-performance liquid chromatography analyses, and compound interactions with tumor necrosis factor (TNF)-α converting enzyme (TACE/ADAM17) were examined. AO contained a higher level of O-acetyl polysaccharides (10.36 ± 0.63% by mass [b/b]) than WAO (6.39 ± 0.16% b/b). Aloin A was rich in WAO (1,342.3 ± 23.94 ppm b/b) but absent in AO. FTIR spectra were similar for both samples, while LC-HRMS profiling revealed phenolic, flavonoid, and terpenoid compounds in AO and WAO. Various concentrations of AO effectively inhibited H₂O₂-induced toxicity in HepG2 cells, with 200 μg/ mL showing the highest protective effect (22.44 ± 6.04%). In contrast, WAO reduced toxicity at lower concentrations but became cytotoxic at higher concentrations. Both extracts decreased intracellular reactive oxygen species (ROS) compared to H2O2 alone. At 200 μg/mL, AO and WAO reduced ROS level, compared to H2O2 alone, by 0.964±0.241 fold and 0.768±0.128 fold, respectively (P < 0.05). Docking studies showed squalene (C₃₀H₅₀) from AO exhibited the strongest affinity for TACE protein with a docking score of -1,16.6±2.54. Overall, AO extract may serve as a potent hepatoprotective agent.
References
Abdelhak, M. 2022. Soil improvement in arid and semiarid regions for sustainable development. In: Jhariya, M.K., Meena, R.S., Banerjee, A. and Meena, S.N. (eds.) Natural Resources Conservation and Advances for Sustainability. Elsevier, Amsterdam, The Netherlands, Chap. 4, pp. 73–90.
Adlakha, K., Koul, B. and Kumar, A. 2022. Value-added products of aloe species: panacea to several maladies. South African Journal of Botany 147: 1124–1135. https://doi.org/10.1016/j.sajb.2020.12.025
Akbari, B., Baghaei-Yazdi, N., Bahmaie, M. and Abhari, F.M. 2022. The role of plant-derived natural antioxidants in reduction of oxidative stress. BioFactors 48(3): 611–633. https://doi.org/10.1002/biof.1831
Al-Sheddi, Ebtesam S., Farshori, Nida N., Al-Oqail, Mai M., Alblwi, F., Ahmad, J., Al-Khedhairy, Abdulaziz A. and Siddiqui, Maqsood A. 2024. Hepatoprotective effect of date fruit extract against ethanol-induced apoptosis in human hepatoma (HepG2) cells. Tissue and Cell 90: 102519. https://doi.org/10.1016/j.tice.2024.102519
Añibarro-Ortega, M., Pinela, J., Barros, L., Ćirić, A., Silva, Soraia P., Coelho, E., Mocan, A., Calhelha, Ricardo C., Soković, M., Coimbra, M.A. and Ferreira, Isabel C.F.R. 2019. Compositional features and bioactive properties of aloe vera leaf (fillet, mucilage, and rind) and flower. Antioxidants 8(10): 444. https://doi.org/10.3390/antiox8100444
Artanti, N., Dewijanti, I.D., Muzdalifah, D., Windarsih, A., Suratno, S. and Handayani, S. 2023. Alpha-glucosidase inhibitory activity of the combination of Caesalpinia Sappan L. and Garcinia mangostana extract. Journal of Applied Pharmaceutical Science 13(5): 189–198. https://doi.org/10.7324/JAPS.2023.117478
Babu, S.N. and Noor, A. 2021. Bioactive constituents of the genus aloe and their potential therapeutic and pharmacological applications: a review. Journal of Applied Pharmaceutical Sciences 10(11): 133–145. https://doi.org/10.7324/JAPS.2020.101118
Bitencourt-Ferreira, G., Veit-Acosta, M. and Filgueira de Azevedo, W. 2019. Van der Waals potential in protein complexes. Methods in Molecular Biology 2053: 79–91. https://doi.org/10.1007/978-1-4939-9752-7_6
Borah, Pallab Kumar, Chakraborty, S., Jha, Anupam N., Rajkhowa, S. and Duary, R.K. 2016. In silico approaches and proportional odds model towards identifying selective ADAM17 inhibitors from anti-inflammatory natural molecules. Journal of Molecular Graphics & Modelling 70: 129–139. https://doi.org/10.1016/j.jmgm.2016.10.003
BPS Kab.Gunungkidul. 2019. Kecamatan Nglipar Dalam Angka 2019. Badan Pusat Statistik Kabupaten Gunungkidul, Indonesia. Available at: https://gunungkidulkab.bps.go.id/publication/2019/09/26/9f287b34d06165a6f6658d90/kecamatan-nglipar-dalam-angka-2019.html (Accessed 16/8/2024).
BPS Yogyakarta. 2020. Jumlah Curah Hujan dan Hari Hujan Menurut Bulan di D.I. Yogyakarta, 2019 – Tabel Statistik. Central Statistics Agency (BPS), Indonesia. Available at: https://yogyakarta.bps.go.id/id/statistics-table/1/OTMjMQ==/jumlah- (Accessed 12/9/2024).
Chaudhary, P., Janmeda, P., Docea, A.O., Yeskaliyeva, B., Abdull Razis, A.F., Modu, B., Calina, D. and Sharifi-Rad, J. 2023. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in Chemistry 11: 1158198. https://doi.org/10.3389/fchem.2023.1158198
Chinnadurai, A., Jesuraj, S., Eswaran, K., Doraiswamy, U., Nathan, B. and Sundar, B. 2024. Aloesin unveiled: molecular docking investigation of aloe vera as anti-inflammatory activity against tumour necrosis factor alpha. Indian Journal of Pharmaceutical Sciences 86(5): 1756–1764. https://doi.org/10.36468/pharmaceutical-sciences.1442
Chowdhury, T., Rahman, Md A., Nahar, K., Chowdhury, Md A.H. and Khan, Md S.I. 2018. Growth and yield performance of aloe vera grown in different soil types of Bangladesh: yield performance of aloe vera in different soils. Journal of the Bangladesh Agricultural University 16(3): 448–456. https://doi.org/10.3329/jbau.v16i3.39416
Ding, W.-J., Wu, X.-F., Zhong, J.-S. and Wan, J.-Z. 2014. Effects of temperature, pH and light on the stability of aloin A and characterisation of its major degradation products. International Journal of Food Science & Technology 49(7): 1773–1779. https://doi.org/10.1111/ijfs.12500
Dobbins, Dylan C., Marcelo-Silva, J. and Siebert, S.J. 2021. Screening the phytoextractability of trace metals by aloe cryptopoda baker and aloe vera (L.) burm. f. cultivated on mine tailings. South African Journal of Botany 140: 110–113. https://doi.org/10.1016/j.sajb.2021.03.042
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Filipič, M., Frutos, M.J., Galtier, P., Gott, D., Gundert-Remy, U., Kuhnle, G.G., Lambré, C., Leblanc, J.-C., Lillegaard, I.T., Moldeus, P., Mortensen, A., Oskarsson, A., Stankovic, I., Waalkens-Berendsen, I., Woutersen, R.A., Andrade, R.J., Fortes, C., Mosesso, P., Restani, P., Pizzo, F., Smeraldi, C., Papaioannou, A. and Wright, M. 2018. Safety of hydroxyanthracene derivatives for use in food. EFSA Journal 16(1): e05090. https://doi.org/10.2903/j.efsa.2018.5090
Fardsadegh, B. and Jafarizadeh-Malmiri, H. 2019. Aloe vera leaf extract mediated green synthesis of selenium nanoparticles and assessment of their in vitro antimicrobial activity against spoilage fungi and pathogenic bacteria strains. Green Processing and Synthesis 8(1): 399–407. https://doi.org/10.1515/gps-2019-0007
García, D., Perdomo, M.E. and Magomedov, I. 2023. Study case: correlational analysis of pH and weekly aloe growth. BIO Web of Conferences 63: 07007. https://doi.org/10.1051/bioconf/20236307007
Guo, X. and Mei, N. 2016. Aloe vera: a review of toxicity and adverse clinical effects. Journal of Environmental Science and Health. Part C: Environmental Carcinogenesis & Ecotoxicology Reviews 34(2): 77–96. https://doi.org/10.1080/10590501.2016.1166826
Gupta, V.K., Park, U., Siddiqi, N.J., Huh, Y.S. and Sharma, B. 2023. Amelioration of hepatotoxic and neurotoxic effect of cartap by aloe vera in Wistar rats. Toxics 11(5): 472. https://doi.org/10.3390/toxics11050472
Gupta, V.K., Siddiqi, Nikhat J., Ojha, A.K. and Sharma, B. 2019. Hepatoprotective effect of aloe vera against cartap- and malathion-induced toxicity in Wistar rats. Journal of Cellular Physiology 234(10): 18329–18343. https://doi.org/10.1002/jcp.28466
Handayani, S., Aprilia, D., Nisa, K., Rosyida, V.T., Wulanjati, M.P., Windarsih, A., Darsih, C., Frediansyah, A. and Haryanti, S. 2021. A mini-review: possible mechanisms of hepatoprotective effect of aloe vera gel. Indonesian Journal of Cancer Chemoprevention 12(3): 170–179. https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp170-179
Handayani, S., Ni’maturrohmah, D., Indrianingsih, A.W., Nisa, K., Windarsih, A., Darsih, C., Sefrienda, A.R., Suryani, A.E. and Haryanti, S. 2023. Molecular docking study of aloesin and its derivatives as potential antiaging agents. In: Proceedings of the 1st International Conference for Health Research – BRIN (ICHR 2022); Advances in Health Sciences Research. Atlantis Press, Dordrecht, The Netherlands, pp. 288–299. https://doi.org/10.2991/978-94-6463-112-8_28
Hayes, A., Wallace, P.P., Clemens, R., Singer, A.W. and Bauter, M.R. 2024. Evaluation of 90-day repeated dose oral toxicity of an aloe vera inner leaf gel beverage. Food and Chemical Toxicology 189: 114726. https://doi.org/10.1016/j.fct.2024.114726
Hermenean, A., Mariasiu, T., Navarro-González, I., Vegara-Meseguer, J., Miuțescu, E., Chakraborty, S. and Pérez-Sánchez, H. 2017. Hepatoprotective activity of chrysin is mediated through TNF-α in chemically induced acute liver damage: an in vivo study and molecular modeling. Experimental and Therapeutic Medicine 13(5): 1671–1680. https://doi.org/10.3892/etm.2017.4181
Hu, Y., Xiang, X., Zhang, Y., Tian, Z. and Wang, L. 2022. Aloin promotes oral squamous cell carcinoma cell apoptosis and autophagy through Akt/mTOR pathway. Quality Assurance and Safety of Crops & Foods 14(2): 58–65. https://doi.org/10.15586/qas.v14i2.978
Kaloni, D., Tiwari, A. and Biswas, S. 2019. Aloe vera as an antagonist for TNF-Α: In-silico study. International Journal of Innovative Science and Research Technology 4(10): 78–83.
Kaparakou, E.H., Kanakis, C.D., Gerogianni, M., Maniati, M., Vekrellis, K., Skotti, E. and Tarantilis, P.A. 2021. Quantitative determination of aloin, antioxidant activity, and toxicity of leaf gel products from Greece. Journal of the Science of Food and Agriculture 101(2): 414–423. https://doi.org/10.1002/jsfa.10650
Kassem, A., Abbas, L., Coutinho, O., Opara, S., Najaf, H., Kasperek, D., Pokhrel, K., Li, X. and Tiquia-Arashiro, S. 2023. Applications of Fourier transform-infrared spectroscopy in microbial cell biology and environmental microbiology: advances, challenges, and future perspectives. Frontiers in Microbiology 14: 1304081. https://doi.org/10.3389/fmicb.2023.1304081
Kim, S-T, Pressman, P., Clemens, R., Moore, A., Hamilton, R. and Wallace Hayes, A. 2023. The absence of genotoxicity of aloe vera beverages: a review of the literature. Food and Chemical Toxicology 174: 113628. https://doi.org/10.1016/j.fct.2023.113628
Lakshmi, C., Nair, S., Balachandran, S., Arul, D.D., Ronaldo, A.A. and Hubert, J.I. 2019. DFT Analysis on spectral and NLO Properties of (2E)-3-[4-(dimethylamino) phenyl]-1-(naphthalen-2-Yl) prop-2-en-1-one; a d-π-A chalcone derivative and its docking studies as a potent hepatoprotective agent. Chemical Data Collections 20: 100205. https://doi.org/10.1016/j.cdc.2019.100205
Lee, J.Y., Kim, H., Jeong, Y. and Kang, C.H. 2021. Lactic acid bacteria exert a hepatoprotective effect against ethanol-induced liver injury in HepG2 cells. Microorganisms 9(9): 1844. https://doi.org/10.3390/microorganisms9091844
Lestari, E.N.E., Nisa, K., Suryani, A.E. and Kusumaningsih, T. 2024. Encapsulation of Peperomia pellucida (L.) kunth leaf extract for postharvest preservation of Malang Apple (Malus sylvestris) at ambient storage. Food Bioscience 61: 104808. https://doi.org/10.1016/j.fbio.2024.104808
Liu, C., Cui, Y., Pi, F., Cheng, Y., Guo, Y. and Qian, H. 2019. Extraction, purification, structural characteristics, biological activities and pharmacological applications of acemannan, a polysaccharide from aloe vera: a review. Molecules (Basel, Switzerland) 24(8): 1554. https://doi.org/10.3390/molecules24081554
Mazlan, O, Aizat, W. Mohd., Nataqain Baharum, S., Azizan, K.A. and Noor, N. Mohd. 2018. Metabolomics analysis of developing Garcinia mangostana seed reveals modulated levels of sugars, organic acids and phenylpropanoid compounds. Scientia Horticulturae 233: 323–330. https://doi.org/10.1016/j.scienta.2018.01.061
Meiyanto, E., Putri, D.D.P., Susidarti, R.A., Murwanti, R., Sardjiman, S., Fitriasari, A., Husnaa, U., Purnomo, H. and Kawaichi, M. 2014. Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibition of HER2 and NF-kB Activation. Asian Pacific Journal of Cancer Prevention 15(1): 179–184. https://doi.org/10.7314/APJCP.2014.15.1.179
Metcalfe, C. 2019. Quantitation of aloe vera polysaccharides by O-acetyl and UV-Vis spectrophotometry: first action 2018.14. Journal of AOAC International 102(4): 1091–1094. https://doi.org/10.5740/jaoacint.18-0400
Mogadem, A., Naqvi, A., Almamary, Mohamed A., Ahmad, W.A., Jemon, K. and El-Alfy, S.H. 2022. Hepatoprotective effects of flexirubin, a novel pigment from Chryseobacterium artocarpi against carbon tetrachloride-induced liver injury: an in vivo study and molecular modeling. Toxicology and Applied Pharmacology 444: 116022. https://doi.org/10.1016/j.taap.2022.116022
Nair, Hema C., Joseph, A. and Gopinathan, V.P. 2018. GIS based landform classification using digital elevation model: a case study from two river basins of southern western ghats, Kerala, India. Modeling Earth Systems and Environment 4(4): 1355–1363. https://doi.org/10.1007/s40808-018-0490-5
Padmanabhan, P. and Jangle, S.N. 2014. Hepatoprotective activity of herbal preparation (Hp-4) against alcohol-induced hepatotoxicity in mice. International Journal of Applied Sciences and Biotechnology 2(1): 50–58. https://doi.org/10.3126/ijasbt.v2i1.9346
Qu, J, Huang, P., Zhang, L., Qiu, Y., Qi, H., Leng, A. and Shang, D. 2020. Hepatoprotective effect of plant polysaccharides from natural resources: a review of the mechanisms and structure-activity relationship. International Journal of Biological Macromolecules 161: 24–34. https://doi.org/10.1016/j.ijbiomac.2020.05.196
Quispe, C., Villalobos, M., Bórquez, J. and Simirgiotis, M. 2018. Chemical composition and antioxidant activity of aloe vera from the pica oasis (Tarapacá, Chile) by UHPLC-Q/Orbitrap/MS/MS. Journal of Chemistry 2018: e6123850. https://doi.org/10.1155/2018/6123850
Sahoo, S, Rath, D., Kar, D.M. and Pattanaik, S. 2023. Hepatoprotective potency of Litsea glutinosa (L.) C.B. rob. leaf methanol extract on H2O2-induced toxicity in HepG2 cells. Journal of Ethnopharmacology 304: 116076. https://doi.org/10.1016/j.jep.2022.116076
Sheng, Y.Y., Xiang, J., Wang, K.R., Li, Z.Y., Li, K., Lu, J.L., Ye, J.H., Liang, Y.R. and Zheng, X.Q. 2022. Extraction of squalene from tea leaves (Camellia sinensis) and its variations with leaf maturity and tea cultivar. Frontiers in Nutrition 9: 755514. https://www.frontiersin.org/articles/10.3389/fnut.2022.755514
Shokri, F, Ziarati, P. and Mousavi, Z. 2016. Removal of selected heavy metals from pharmaceutical effluent by aloe vera L. Biomedical and Pharmacology Journal 9(2): 705–713. https://doi.org/https://dx.doi.org/10.13005/bpj/993
Srinivas, A.N., Suresh, D., Vishwanath, P.M., Satish, S., Santhekadur, P.K., Koka, S. and Kumar, D.P. 2024. TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis. Molecular Oncology 18(8): 1940–1957. https://doi.org/10.1002/1878-0261.13646
Sultana, T, Chowdhury, A.H., Rahman, A., Saha, B.K., Chowdhury, T., Islam, Mohammed A. and Fancy, R. 2021. Phosphorous use efficiency and its requirement for aloe vera cultivated on silty loam soils. Communications in Soil Science and Plant Analysis 52(3): 268–285. https://doi.org/10.1080/00103624.2020.1862152
Suryani, A.E., Nisa, K., Handayani, S., Darsih, C., Wuryastuty, H and Yanuartono, Y. 2025. The UHPLC-HRMS profiling, in vitro-antioxidant and pancreatic lipase inhibitory activities of peronema canescens leaves extract and fractions from Indonesia. Journal of Applied Pharmaceutical Science 15(5): 075–089. https://doi.org/10.7324/JAPS.2025.214965
Wu, L. and Pan, Y. 2019. Reactive oxygen species mediate TNF-α-induced inflammatory response in bone marrow mesenchymal cells. Iranian Journal of Basic Medical Sciences 22(11): 1296–1301. https://doi.org/10.22038/ijbms.2019.37893.9006
Yang, Yu, Wu, J.-j., Xia, J., Wan, Y., Xu, J.-F., Zhang, L., Liu, D., Chen, L., Tang, F., Ao, H. and Peng,C. 2022. Can aloin develop to medicines or healthcare products? Biomedicine & Pharmacotherapy 153: 113421. https://doi.org/10.1016/j.biopha.2022.113421
Yimam, M., Jiao, P., Moore, B., Hong, M., Cleveland, S., Chu, M., Jia, Q., Lee, Y-C, Kim, H-J, Nam, J-B, Kim, M-R, Hyun, E-J, Jung, G. and Do, S.G. 2016. Hepatoprotective activity of herbal composition SAL, a standardize blend comprised of Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis. Journal of Nutrition and Metabolism 2016: 3530971. https://doi.org/10.1155/2016/3530971
Zhou, B, Alania, Y., Reis, M., Jing, S-Xi, McAlpine, James B., Bedran-Russo, Ana K., Chen, S-N, Ferreira, D. and Pauli, G.F. 2022. Seco B-type oligomers from Pinus massoniana expand the procyanidin chemical space and exhibit dental bioactivity. Journal of Natural Products 85(12): 2753–2768. https://doi.org/10.1021/acs.jnatprod.2c00664
Zhou, X. and Zhao, X. 2021. Gastrodin represses hydrogen peroxide-induced oxidative stress in retinal pigment epithelial cells through p38MAPK/iNOS pathway. Quality Assurance and Safety of Crops & Foods 13(4): 24–30. https://doi.org/10.15586/qas.v13i4.969
