Safety evaluation of a polyherbal formulation: Acute and sub-acute toxicity study using Wistar Albino rats

Vaibhav Tripathi; Chandra Kishore Tyagi; Wasim Raja

doi:10.52756/ijerr.2023.v32.020

Vaibhav Tripathi Department of Pharmacology, College of Pharmacy, Sri Satya Sai University of Technology and Medical Sciences, Sehore, Madhya Pradesh, India https://orcid.org/0000-0003-2860-7296
Chandra Kishore Tyagi Department of Pharmacology, College of Pharmacy, Sri Satya Sai University of Technology and Medical Sciences, Sehore, Madhya Pradesh, India https://orcid.org/0009-0006-3406-8697
Wasim Raja Chhattisgarh Council of Science and Technology, Raipur, Chhattisgarh, India

DOI: https://doi.org/10.52756/ijerr.2023.v32.020

Keywords: VNC, Traditional formulation, Musculoskeletal diseases, Sub-acute toxicity, Surveillance group

Abstract

Vatrog Nashak Churna (VNC) is a traditional polyherbal formulation for musculoskeletal diseases. Although the safety and mechanism of toxicity of the individual herbs have been explored, the formulation remains undocumented in the literature. Research into its sub-acute toxicity will strengthen its pharmacological outline and encourage its investigation as a potential future treatment. Rats were split into three groups (n¼12) by OECD TG 407 (OECD, 2008). The limit test determined the necessary amount of VNC. The control groups were given an identical volume of vehicle, while the dosing and monitoring groups were given VNC (1000 mg/kg/day, p.o. for 14 days). The duration of the post-treatment surveillance period was extended by 14 days in order to evaluate reversibility. Deaths, toxic reactions, and weight shifts were all recorded. On days 15 and 29, the rats were killed while under anaesthesia so that blood samples could be collected to analyze for haematological and biochemical markers. Histopathological studies and evaluation of a wide range of biochemical and hematological parameters indicated that VNC has no appreciable harmful effect on body weight, erythropoiesis, or leucopoiesis. This study may assist scientists in determining appropriate levels for longer-term sub-chronic investigations so that VNC may be considered safe for short-term use. Sub-chronic and chronic toxicity tests must also assess long-term safety.

References

Aamir, K., Khan, H. U., Hossain, C. F., Afrin, M. R., Shaik, I., Salleh, N., ... & Arya, A. (2019). Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats. Peer. J., 7, e8045. https://doi.org/10.7717/peerj.8045

da Silva, A. R., Moreira, L. D. R., Brum, E. D. S., de Freitas, M. L., Boligon, A. A., Athayde, M. L., ... & Brandão, R. (2014). Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark ScutiabuxifoliaReissek in mice. Journal of Ethnopharmacology, 153(3), 908-916. https://doi.org/10.1016/j.jep.2014.03.063

Ganesan, M. R., Settu, D. K., Murkunde, Y., &Duraipandian, C. (2021). Pharmacological and pharmacokinetic effect of a polyherbal combination with Withaniasomnifera (L.) Dunal for the management of anxiety. Journal of Ethnopharmacology, 265, 113337. https://doi.org/10.1016/j.jep.2020.113337

Ghauri, A. O., Mohiuddin, E., Rehman, T., & Siddiqui, H. S. M. (2022). Acute and subacute toxicity studies of a poly herbal formulation used for diabetes. Pakistan Journal of Medical Sciences, 38(6), 1668. https://doi.org/10.12669%2Fpjms.38.6.5928

Jahromi, B., Pirvulescu, I., Candido, K. D., & Knezevic, N. N. (2021). Herbal medicine for pain management: efficacy and drug interactions. Pharmaceutics, 13(2), 251.

https://doi.org/10.3390/pharmaceutics13020251

Khan, S., Choudhary, S., Kumar, A., Tripathi, A. M., Alok, A., Adhikari, J. S., ... & Chaudhury, N. K. (2016). Evaluation of sesamol-induced histopathological, biochemical, haematological and genomic alteration after acute oral toxicity in female C57BL/6 mice. Toxicology Reports, 3, 880-894. https://doi.org/10.1016/j.toxrep.2016.03.005

Kunnumakkara, A. B., Hegde, M., Parama, D., Girisa, S., Kumar, A., Daimary, U. D., ... & Aggarwal, B. B. (2023). Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials. ACS Pharmacology & Translational Science, 6(4), 447-518. https://doi.org/10.1021/acsptsci.2c00012

Mane, V., Killedar, S., More, H., Gaikwad, A., & Tare, H. (2023). A Novel Rp-Hplc Gradient Elution Technique For Bioanalytical Method Development And Validation For Estimating Gallic Acid In Wistar Rat Plasma. International Journal of Applied Pharmaceutics, 15(2), 153–160. https://doi.org/10.22159/ijap.2023v15i2.47278

Mensah, M. L., Komlaga, G., Forkuo, A. D., Firempong, C., Anning, A. K., & Dickson, R. A. (2019). Toxicity and safety implications of herbal medicines used in Africa. Herbal Medicine, 63, 1992-0849.

Mirza, A. C., & Panchal, S. S. (2019). Safety evaluation of syringic acid: subacute oral toxicity studies in Wistar rats. Heliyon, 5(8). https://doi.org/10.1016/j.heliyon.2019.e02129

Nigatu, T. A., Afework, M., Urga, K., Ergete, W., & Makonnen, E. (2017). Toxicological investigation of acute and chronic treatment with Gnidiastenophylla Gilg root extract on some blood parameters and histopathology of spleen, liver and kidney in mice. BMC Research Notes, 10(1), 1-13. https://doi.org/10.1186/s13104-017-2964-3

OECD (2008). Acute Oral Toxicity: Up-and-Down Procedure (OECD TG 425). pp. 477–490.

OECD (2008). Repeated Dose 28-Day Oral Toxicity Study in Rodents (OECD TG 407). pp. 477–90.

Okaiyeto, K., &Oguntibeju, O. O. (2021). African herbal medicines: Adverse effects and cytotoxic potentials with different therapeutic applications. International Journal of Environmental Research and Public Health, 18(11), 5988. https://doi.org/10.3390/ijerph18115988

Olayode, O. A., Daniyan, M. O., & Olayiwola, G. (2020). Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarphetacayennensis in rats. Journal of Traditional and Complementary Medicine, 10(6), 544-554. https://doi.org/10.1016/j.jtcme.2019.05.001

Ozioma, E. O. J., & Chinwe, O. A. N. (2019). Herbal medicines in African traditional medicine. Herbal Medicine, 10, 191-214.

Pluncevic G. J., Gontarev, S., Dejanova, B., Todorovska, L., Stojmanova, D. S., &Manchevska, S. (2019). Red blood cell variables in children and adolescents regarding the age and sex. Iranian Journal of Public Health, 48(4), 704.

Porwal, M., Khan, N. A., & Maheshwari, K. K. (2017). Evaluation of acute and subacute oral toxicity induced by ethanolic extract of Marsdeniatenacissima leaves in experimental rats. Scientia Pharmaceutica, 85(3), 29. https://doi.org/10.3390/scipharm85030029

Prieto P, Burton J, Graepel R, Price A, Whelan M, Andrew W (2014). EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity, EUR 26704. Luxembourg (Luxembourg): Publications Office of the European Union; 2014. JRC90611. https://dx.doi.org/10.2788/86684

Rastogi, S., Pandey, M. M., Kumar, K., Rawat, A. K. S., &Pushpangadan, P. (2005). Pharmacognostical Evaluation of Roots of Pygmaeo premna herbacea (Roxb.) Mold. Natural Product Sciences, 11(2), 58-62.

Rehman, M. H. U., Saleem, U., Ahmad, B., & Rashid, M. (2022). Phytochemical and toxicological evaluation of Zephyranthes citrina. Frontiers in Pharmacology, 13, 1007310.

https://doi.org/10.3389/fphar.2022.1007310

Saif, M. W., Alexander, D., &Wicox, C. M. (2005). Serum alkaline phosphatase level as a prognostic tool in colorectal cancer: a study of 105 patients. The Journal of Applied Research, 5(1), 88.

Saka, W. A., Akhigbe, R. E., Popoola, O. T., & Oyekunle, O. S. (2012). Changes in serum electrolytes, urea, and creatinine in Aloe vera-treated rats. Journal of Young Pharmacists, 4(2), 78-81. https://doi.org/10.4103/0975-1483.96620

Smith, D., Anderson, D., Degryse, A. D., Bol, C., Criado, A., Ferrara, A., ... &Voipio, H. M. (2018). Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report. Laboratory Animals, 52(1_suppl), 5-57. https://doi.org/10.1177/0023677217744587

Sundaran, J., Vasanthi, M., Kamalapathy, M., Bupesh, G., & Sahoo, U. (2020). A short review on pharmacological activity of Cissus quadrangularis. Bioinformation, 16(8), 579. https://doi.org/10.6026%2F97320630016579

Varicola Karunasree, Veeresham, C., Rao, K. R. S., & Asres, K. (2012). Antioxidant, 5-Lipoxygenase inhibitory and anticancer activities of Soymidafebrifuga A. Juss. Mol. Clin. Pharmacol., 3, 134–42.

Yang, M. Y., Song, Z. Y., Gan, H. L., Zheng, M. H., Liu, Q., Meng, X. T., ... & Fan, H. Y. (2022). Non-clinical safety evaluation of salvianolic acid A: acute, 4-week intravenous toxicities and genotoxicity evaluations. BMC Pharmacology and Toxicology, 23(1), 83. https://doi.org/10.1186/s40360-022-00622-1