Toxicological Profiling of Natural Bioactive Compounds Using PubChem Database and Relevant Literature

Md. Sakib Al Hasan; Khadija Akter; Mohammad Aslam; Proma Mandal; Imam Hossen  Rakib; Nasimul Haque Shipon

doi:10.71193/jpci.20250008

Authors

Md. Sakib Al Hasan Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0004-7560-4041
Khadija Akter Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0000-6373-6929
Mohammad Aslam Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author
Proma Mandal Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0009-9115-1149
Imam Hossen Rakib Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0003-2552-8952
Nasimul Haque Shipon Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0001-7693-303X

DOI:

https://doi.org/10.71193/jpci.20250008

Keywords:

Toxicity analysis, Lethal dose 50, Bioactive compound, Natural sources

Abstract

Natural bioactive compounds have gained increasing attention for their pharmacological properties and therapeutic potential. However, understanding their toxicological profiles is crucial for assessing their safety and potential applications. This study aimed to assess the toxicological profiles of selected natural compounds using LD₅₀ values and literature-based evaluations. Toxicity data were collected from the PubChem database and scientific literature, covering various administration routes and model organisms. The toxicological assessment revealed varying LD₅₀ values among bioactive compounds, with toxicity influenced by structure, organism, and administration route. Compounds like ellagic acid, swertiamarin, and verbascoside exhibited high safety margins, whereas angelicin, xanthotoxol, and senegenin showed lower LD₅₀ values, indicating greater toxicity. Route of administration significantly influenced toxicity; for example, bakuchiol and osthol were more toxic via intraperitoneal or intravenous injection than oral administration. Literature findings further supported these trends, highlighting species and dose-dependent effects. Some compounds also showed model-specific toxicity despite therapeutic potential. Toxicity varied significantly depending on the route of administration; for example, bakuchiol and osthol exhibited higher toxicity when administered intraperitoneally or intravenously compared to oral administration, indicating the importance of the administration route in toxicity profiling.

Downloads

Download data is not yet available.

References

Al Hasan, M. S., Mia, E., Yana, N. T., Rakib, I. H., Bhuia, M. S., Chowdhury, R., & Islam, M. T. (2024). Allium cepa bioactive phytochemicals as potent ALK (Anaplastic lymphoma kinase) inhibitors and therapeutic agents against non-small cell lung cancer (NSCLC): A computational study. Pharmacological Research-Natural Products, 5, 100124.

Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., & Supuran, C. T. (2021). Natural products in drug discovery: advances and opportunities. Nature reviews Drug discovery, 20(3), 200-216.

Bernardini, S., Tiezzi, A., Laghezza Masci, V., & Ovidi, E. (2018). Natural products for human health: an historical overview of the drug discovery approaches. Natural product research, 32(16), 1926-1950.

Bhuia, M. S., Chowdhury, R., Hasan, R., Hasan, M. S. A., Ansari, S. A., Ansari, I. A., & Islam, M. T. (2025). trans‐Ferulic Acid Antagonizes the Anti‐Inflammatory Activity of Etoricoxib: Possible Interaction of COX‐1 and NOS. Biotechnology and Applied Biochemistry.

Blomme, E. A., & Will, Y. (2016). Toxicology strategies for drug discovery: present and future. Chemical research in toxicology, 29(4), 473-504.

Bulusu, K. C., Guha, R., Mason, D. J., Lewis, R. P., Muratov, E., Motamedi, Y. K., & Bender, A. (2016). Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives. Drug discovery today, 21(2), 225-238.

Cadar, E., Tomescu, A., Erimia, C. L., Mustafa, A., & Sîrbu, R. (2015). The impact of alkaloids structures from naturalcompounds on public health. European Journal of Social Science Education and Research, 2(2), 82-90.

Chinedu, E., Arome, D., Ameh, F. S., & Jacob, D. L. (2015). An approach to acute, subacute, subchronic, and chronic toxicity assessment in animal models. Toxicology International, 22(2), 83-87.

Chowdhury, R., Bhuia, M. S., Al Hasan, M. S., Hossain Snigdha, S., Afrin, S., Büsselberg, D., ... & Islam, M. T. (2024). Anticancer potential of phytochemicals derived from mangrove plants: Comprehensive mechanistic insights. Food Science & Nutrition, 12(9), 6174-6205.

Chung, H. J., Chung, M. J., Houng, S. J., Jeun, J., Kweon, D. K., Choi, C. H., ... & Lee, S. J. (2009). Toxicological evaluation of the isoflavone puerarin and its glycosides. European Food Research and Technology, 230, 145-153.https://doi.org/10.1007/s00217-009-1156-3

Dhanavathy, G., & Jayakumar, S. (2017). Acute and subchronic toxicity studies of Swertiamarin a lead compound isolated from Enicostemma Littorale. blume in wistar rats. Biosciences Biotechnology Research Asia, 14(1), 381-390. http://dx.doi.org/10.13005/bbra/2456

Etemad, L., Zafari, R., Vahdati-Mashhadian, N., Moallem, S. A., Shirvan, Z. O., & Hosseinzadeh, H. (2015). Acute, sub-Acute and cell toxicity of verbascoside.

Gad, S. C. (2016). Drug safety evaluation. John Wiley & Sons.

Hayes Jr, W. J. (1967). The 90-dose LD50 and a chronicity factor as measures of toxicity. Toxicology and Applied Pharmacology, 11(2), 327-335.

Henn, J. G., Steffens, L., de Moura Sperotto, N. D., de Souza Ponce, B., Veríssimo, R. M., Boaretto, F. B. M., Hassemer, G., Péres, V. F., Schirmer, H., Picada, J. N., Saffi, J., & Moura, D. J. (2019). Toxicological evaluation of a standardized hydroethanolic extract from leaves of Plantago australis and its major compound, verbascoside. Journal of ethnopharmacology, 229, 145–156. https://doi.org/10.1016/j.jep.2018.10.003

Jensen, P. R., & Fenical, W. (2000). Marine microorganisms and drug discovery: current status and future potential. Drugs from the Sea, 6-29.

Jia, K., Shi, P., Zhang, L., Yan, X., Xu, J., & Liao, K. (2025). Trans-cinnamic acid alleviates high-fat diet-induced renal injury via JNK/ERK/P38 MAPK pathway. The Journal of nutritional biochemistry, 135, 109769. https://doi.org/10.1016/j.jnutbio.2024.109769

Jiang, H., Zhang, Y., Zhang, Y., Wang, X., & Meng, X. (2022). An updated meta-analysis based on the preclinical evidence of mechanism of aconitine-induced cardiotoxicity. Frontiers in Pharmacology, 13, 900842.

Jităreanu, A., Tătărîngă, G., Zbancioc, A. M., & Stănescu, U. (2011). Toxicity of some cinnamic acid derivatives to common bean (Phaseolus vulgaris). Notulae Botanicae Horti Agrobotanici Cluj-Napoca, 39(2), 130-134.

Li, Y., Yu, M., Wei, Y., Zhou, Z., Guo, Y., Yuan, M., Jin, J., Li, J., Shen, H., & Wu, D. (2025). Risk assessment of developmental and neurotoxicity by the flavoring agent perillaldehyde: NAC (N-acetylcysteine) mitigation of oxidative stress-mediated inhibition of the Nrf2 pathway. Comparative biochemistry and physiology. Toxicology & pharmacology: CBP, 288, 110071. https://doi.org/10.1016/j.cbpc.2024.110071

Lin, X., Liu, J., Zou, Y., Tao, C., & Chen, J. (2022). Xanthotoxol suppresses non-small cell lung cancer progression and might improve patients' prognosis. Phytomedicine : international journal of phytotherapy and phytopharmacology, 105, 154364. https://doi.org/10.1016/j.phymed.2022.154364

Mensah, M. L., Komlaga, G., Forkuo, A. D., Firempong, C., Anning, A. K., & Dickson, R. A. (2019). Toxicity and Safety Implications of Herbal Medicines. Herbal medicine, 63.

Niu, Q. Q., Xi, Y. T., Zhang, C. R., Li, X. Y., Li, C. Z., Wang, H. D., Li, P., & Yin, Y. L. (2024). Potential mechanism of perillaldehyde in the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking. European journal of pharmacology, 985, 177092. https://doi.org/10.1016/j.ejphar.2024.177092

Noga, M., Michalska, A., & Jurowski, K. (2024). The estimation of acute oral toxicity (LD50) of G-series organophosphorus-based chemical warfare agents using quantitative and qualitative toxicology in silico methods. Archives of Toxicology, 98(6), 1809-1825.

Perumal, S., Gopal Samy, M. V., & Subramanian, D. (2021). Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio). Journal of biochemical and molecular toxicology, 35(9), e22843. https://doi.org/10.1002/jbt.22843

Punvittayagul, C., Wongpoomchai, R., Taya, S., & Pompimon, W. (2011). Effect of pinocembrin isolated from Boesenbergia pandurata on xenobiotic-metabolizing enzymes in rat liver. Drug metabolism letters, 5(1), 1–5. https://doi.org/10.2174/187231211794455226

Reichl, F. X., & Schwenk, M. (Eds.). (2014). Regulatory Toxicology (No. 15414). Springer Berlin Heidelberg.

Ren, X., Zhang, J., Zhao, Y., & Sun, L. (2022). Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway. Neuropsychiatric disease and treatment, 18, 513–524. https://doi.org/10.2147/NDT.S346238

Saboon, Chaudhari, S. K., Arshad, S., Amjad, M. S., & Akhtar, M. S. (2019). Natural compounds extracted from medicinal plants and their applications. Natural Bio-active Compounds: Volume 1: Production and Applications, 193-207.

Saganuwan, S. A. (2017). Toxicity studies of drugs and chemicals in animals: an overview. Bulgarian Journal of Veterinary Medicine, 20(4).

Sánchez Ruderisch, H., Schwarz, C., Shang, J., & Tebbe, B. (2002). Trioxsalen in the presence of UVA is able to induce nuclear factor kappa B binding activity in HaCaT keratinocytes. Skin pharmacology and applied skin physiology, 15(5), 335–341. https://doi.org/10.1159/000064538

Sethi, O. P., Anand, K. K., & Gulati, O. D. (1992). Evaluation of xanthotoxol for central nervous system activity. Journal of ethnopharmacology, 36(3), 239–247. https://doi.org/10.1016/0378-8741(92)90050-2

Sharifi-Rad, M., Lankatillake, C., Dias, D. A., Docea, A. O., Mahomoodally, M. F., Lobine, D., ... & Sharifi-Rad, J. (2020). Impact of natural compounds on neurodegenerative disorders: from preclinical to pharmacotherapeutics. Journal of Clinical Medicine, 9(4), 1061.

Tang, X., Han, J. Y., Pan, C., Li, C. Y., Zhao, Y., Yi, Y., Zhang, Y. S., Zheng, B. X., Yue, X. N., & Liang, A. H. (2024). Angelicin: A leading culprit involved in fructus Psoraleae liver injury via inhibition of VKORC1. Journal of ethnopharmacology, 328, 117917. https://doi.org/10.1016/j.jep.2024.117917

Tasaki, M., Umemura, T., Maeda, M., Ishii, Y., Okamura, T., Inoue, T., Kuroiwa, Y., Hirose, M., & Nishikawa, A. (2008). Safety assessment of ellagic acid, a food additive, in a subchronic toxicity study using F344 rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 46(3), 1119–1124. https://doi.org/10.1016/j.fct.2007.10.043

Tsuchiya, H. (2017). Anesthetic agents of plant origin: a review of phytochemicals with anesthetic activity. Molecules, 22(8), 1369.

Wang, W., Zhai, S., Yang, W., Gao, H., Chang, N., Zhang, M., Hou, Y., & Bai, G. (2024). Acacetin alleviates rheumatoid arthritis by targeting HSP90 ATPase domain to promote COX-2 degradation. Phytomedicine : international journal of phytotherapy and phytopharmacology, 135, 156171. https://doi.org/10.1016/j.phymed.2024.156171

Xu, Y. W., Yao, C. H., Gao, X. M., Wang, L., Zhang, M. X., Yang, X. D., Li, J., Dai, W. L., Yang, M. Q., & Cai, M. (2025). BAK ameliorated cerebral infarction/ischemia-reperfusion injury by activating AMPK/Nrf2 to inhibit TXNIP/NLRP3/caspase-1 axis. Neuroscience letters, 844, 138037. https://doi.org/10.1016/j.neulet.2024.138037

Yim, E. C., Kim, H. J., & Kim, S. J. (2014). Acute toxicity assessment of Osthol content in bio-pesticides using two aquatic organisms. Environmental health and toxicology, 29, e2014020. https://doi.org/10.5620/eht.e2014020

Yu, G., & Feng, X. (2024). Salidroside exerts anti-tumor effects in ovarian cancer by inhibiting STAT3/c-Myc pathway-mediated glycolysis. Biomolecules & biomedicine, 25(1), 82–93. https://doi.org/10.17305/bb.2024.10867