Toxicological Evaluation of Polyherbal Insty Granules: An Evidence of Preclinical Safety
Abstract
Insty, a polyherbal formulation, is widely used to treat upper respiratory ailments, especially cold and cough. However, no toxicological evaluation of the formulation has been conducted to date at the preclinical level as per regulatory guidelines. With this in mind, this study aimed to assess its preclinical toxicity (acute, repeated dose, reproductive, and genotoxicity) along with the phytochemical estimation of important constituents. Briefly, acute toxicity in mice was evaluated by oral administration of a limited dose of 1 or 5 g/kg. Mice were observed for signs of toxicity (mortality or morbidity) for 2 weeks. In case of repeated dose toxicity, the rats were orally gavaged with Insty (1 g/kg) consecutively for 28 days, followed by hematology, hepatic, and renal function tests. Furthermore, a two-generation (F0-F2) reproductive toxicity study was performed in rats at the clinically used dose of Insty i.e. 0.24 g/kg. This includes the calculation of viability, reproductive health indices, and histopathology of the testis and ovary. The granules were also subjected to genotoxic evaluation using the micronucleus test after 2 weeks of administration (1 and 5 g/kg). High-performance liquid chromatography (HPLC) was used to measure important phytochemicals, such as salicin, glycyrrhizin, and vasicine. Our data showed no signs of mortality or morbidity in the acute toxicity tests. The hematological, hepatic, and renal parameters also did not reveal any significant differences compared to the control. In the case of reproductive toxicity assessment, the viability and reproductive health indices were comparable between the treated and control groups over the two generations. Similarly, histopathology of the testis and ovary also revealed an intact architecture. Genotoxic evaluation also showed comparable erythrocyte scoring (micronucleus count and ratios) between the treated and control groups. HPLC measurements revealed undetectable salicin, while trace levels of glycyrrhizin (4.99 mg) and vasicine (5.75 mg) were found per sachet. In conclusion, the present study is the first to extensively investigate and advocate for the safer nature of the widely used Insty, suggesting its continued consumption in humans.
Keywords: acute toxicity; repeated dose toxicity; reproductive toxicity; genotoxicity
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SALMERÓN-MANZANO E., GARRIDO-CARDENAS J.A., & MANZANO-AGUGLIARO F. Worldwide research trends on medicinal plants. International Journal of Environmental Research and Public Health, 2020, 17(10): 3376. https://doi.org/10.3390/ijerph17103376
LALANI N.S. Beliefs and perceptions regarding the use of herbal remedies among the users and sellers in Karachi, Pakistan. Pakistan Journal of Public Health, 2012, 2(1): 36-39.
KANWAL H., & SHERAZI B.A. Herbal medicine: Trend of practice, perspective, and limitations in Pakistan. Asian Pacific Journal of Health Sciences, 2017, 4(4): 6-8. http://doi.org/10.21276/apjhs.2017.4.4.2
JAN H.A., JAN S., BUSSMANN R.W., WALI S., SISTO F., & AHMAD L. Complementary and alternative medicine research, prospects and limitations in Pakistan: a literature review. Acta Ecologica Sinica, 2020, 40(6): 451-463. https://doi.org/10.1016/j.chnaes.2019.12.005
BHUSNURE O.G., SHINDE M.C., VIJAYENDRA S.S., GHOLVE S.B., GIRAM P.S., & BIRAJDAR M.J. Phytopharmaceuticals: An emerging platform for innovation and development of new drugs from botanicals. Journal of Drug Delivery & Therapeutics, 2019, 9(3-s): 1046-1057. https://doi.org/10.22270/jddt.v9i3-s.2940
NOOREEN Z., RAI V.K., & YADAV N.P. Phytopharmaceuticals: A new class of drug in India. Annals of Phytomedicine, 2018, 7(1): 27-37.
WU C., LEE S.-L., TAYLOR C., LI J., CHAN Y.-M., AGARWAL R., TEMPLE R., THROCKMORTON D., & TYNER K. Scientific and regulatory approach to botanical drug development: A US FDA perspective. Journal of Natural Products, 2020, 83(2): 552-562. https://doi.org/10.1021/acs.jnatprod.9b00949
FDA. Guidance for industry: Botanical drug products. 2004.
OECD. OECD guideline for testing of chemicals. 2001.
FAROOQA A.D., BANOB S., HAQUEB S., ZAHOORB A., & ALIB R. Genotoxic Evaluation of Linkus Polyherbal Cough Preparation in Bone Marrow of Wistar Rats. Hamdard Medicus, 2016, 59(3): 5-17.
SHEIKH Z.A., ZAHOOR A., KHAN S.S., & USMANGHANI K. Design, development and phytochemical evaluation of a poly herbal formulation linkus syrup. Chinese Medicine, 2014, 5(02): 104.
HURST W.J., MCKIM J.M., & MARTIN Jr R.A. High-performance liquid chromatographic determination of glycyrrhizin in licorice products. Journal of Agricultural and Food Chemistry, 1983, 31(2): 387-389.
SEWELL F., CORVARO M., ANDRUS A., BURKE J., DASTON G., DELANEY B., DOMORADZKI J., FORLINI C., GREEN M.L., HOFMANN T., JÄCKEL S., LEE M.S., TEMEROWSKI M., WHALLEY P., & LEWIS R. Recommendations on dose level selection for repeat dose toxicity studies. Archives of Toxicology, 2022, 96(7): 1921-1934. https://doi.org/10.1007/s00204-022-03293-3
JANER G., HAKKERT B.C., SLOB W., VERMEIRE T., & PIERSMA A.H. A retrospective analysis of the two-generation study: what is the added value of the second generation? Reproductive Toxicology, 2007, 24(1): 97-102.
SCHULZ F., BATKE M., MANGELSDORF I., POHLENZ-MICHEL C., SIMETSKA N., & LEWIN G. Sensitivity of different generations and developmental stages in studies on reproductive toxicity. Toxicology Letters, 2014, 226(2): 245-255.
HAYASHI M. The micronucleus test—most widely used in vivo genotoxicity test. Genes and Environment, 2016, 38(1): 18.
EMA. European Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex. European Medicines Agency London; 2017.
KARKANIS A., MARTINS N., PETROPOULOS S., & FERREIRA I.C. Phytochemical composition, health effects, and crop management of liquorice (Glycyrrhiza glabra L.): Α medicinal plant. Food Reviews International, 2018, 34(2): 182-203. https://doi.org/10.1080/87559129.2016.1261300
KUMARI N., AKHTAR J., AHMAD M., BADRUDDEEN, & KHAN M.I. An outline on vasicine, its ethnomedical and nanoformulation approach. Journal of Biologically Active Products from Nature, 2021, 11(1): 42-59. https://doi.org/10.1080/22311866.2021.1886990
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