In Vitro Evaluation of Amritabhallataka Paka on Cell Viability and Apoptosis in U87MG Glioblastoma Cells and Cytocompatibility in L929 Fibroblasts

Authors

  • Akansha G Puppalwar
  • Prashant G Jadar
  • Vijay M Kumbar
  • Shahana Shahpuri
  • Reeshma Nambiar 3rd year Post Graduate Scholar, Department of Agada Tantra, KLE Academy of Higher Education and Research, Deemed to be University, Shri BMK Ayurveda Mahavidyalaya, Shahpur, Belagavi, Karnataka, India- 590003
  • VS Aarathy

DOI:

https://doi.org/10.70066/jahm.v14i9.2873

Keywords:

Amritabhallataka Paka, Apoptosis, Glioblastoma, In Vitro Techniques, L929, MTT Assay, Semecarpus anacardium L.f., U87MG.

Abstract

Background: Glioblastoma is an aggressive primary brain tumour with poor prognosis due to recurrence and treatment resistance. Amritabhallataka Paka (AP), an Ayurvedic formulation containing Semecarpus anacardium L.f. (Bhallataka), has limited experimental evidence in glioblastoma models. Objective: To evaluate the effects of AP on U87MG glioblastoma cell viability and apoptosis, assess its cytocompatibility in L929 mouse fibroblasts, and compare its effects with temozolomide (TMZ) and their combination. Methods: U87MG cells were treated with AP, TMZ and AP+TMZ, while L929 fibroblasts received AP and TMZ. Cell viability was assessed using the MTT assay at six concentrations in three independent experiments with technical replicates. IC₅₀ values were estimated using nonlinear dose-response regression. Apoptosis in U87MG cells was evaluated using Annexin V-FITC/propidium iodide flow cytometry in three independent experiments. Cellular morphology was examined using phase-contrast microscopy. Results: AP produced a concentration-dependent reduction in U87MG cell viability. The IC₅₀ values were 334.85 µg/mL for AP, 249.42 µg/mL for TMZ and 327.20 µg/mL for AP+TMZ. In L929 fibroblasts, AP maintained 71–87% viability across tested concentrations. TMZ-treated L929 cells showed 99.5% viability at 15.6 µg/mL, with reduced viability at concentrations ≥31.25 µg/mL. Total apoptosis in U87MG cells was highest with AP+TMZ (25.15 ± 1.80%), followed by TMZ (14.71 ± 1.20%), AP (11.85 ± 1.75%) and untreated controls (3.26 ± 0.50%). Conclusion: AP reduced U87MG cell viability while maintaining comparatively high L929 fibroblast viability under the tested conditions. AP+TMZ produced higher total apoptosis than either treatment alone. However, synergistic or enhanced combination efficacy cannot be established without formal drug-interaction analysis.

Author Biographies

Akansha G Puppalwar

Final Year Post Graduate Scholar, Department of Rasashastra and Bhaishajya Kalpana, KLE Academy of Higher Education and Research, Deemed to be University, Shri BMK Ayurveda Mahavidyalaya, Shahpur, Belagavi, Karnataka, India- 590003

Prashant G Jadar

Professor, Department of Rasashastra and Bhaishajya Kalpana, KLE Academy of Higher Education and Research, Deemed to be University, Shri BMK Ayurveda Mahavidyalaya, Shahpur, Belagavi, Karnataka, India- 590003

Vijay M Kumbar

Assistant Professor/Scientist KAHER’s Dr. Prabhakar Kore Basic Science Research Centre, KLE Academy of Higher Education (KLE University), and Jawaharlal Nehru Medical College Nehru Nagar, Belagavi, Karnataka, India- 001059

Shahana Shahpuri

Laboratory assistant (Cell Culture) Dr. Prabhakar Kore Basic Science Research Centre, Nehru Nagar, Belagavi, Karnataka, India-001059

VS Aarathy

Final year Post Graduate Scholar, Department of Agada Tantra, KLE Academy of Higher Education and Research, Deemed to be University, Shri BMK Ayurveda Mahavidyalaya, Shahpur, Belagavi, Karnataka, India- 590003

References

Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: Result from National Cancer Registry Programme, India. Indian Journal of Medical Research. 2022 Oct-Nov;156(4-5):598-607. Available from: https://doi.org/10.4103/ijmr.ijmr_1821_22

Barkade GD, Bhosale PS, Shirsath SK. Overview of brain cancer, its symptoms, diagnosis and treatment. IP International Journal of Comprehensive Advances in Pharmacology. 2023;8(3):159-164. Available from: https://doi.org/10.18231/j.ijcaap.2023.027

Chen L, Yang F, Yang J, Ren B, Tu Q, Wang M, et al. Epidemiological trends of burden of brain and CNS cancer at global, regional, and national level: A trend analysis study from 1990 to 2021. European Journal of Medical Research. 2025;30(1):1268. Available from: https://doi.org/10.1186/s40001-025-03511-5

Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee ShU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pacific Journal of Cancer Prevention. 2017;18(1):3-9. Available from: https://pubmed.ncbi.nlm.nih.gov/28239999/

Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: Good news and bad news. Science Translational Medicine. 2016;8(354):354re3. Available from: https://pubmed.ncbi.nlm.nih.gov/27582061/

Jezierzański M, Nafalska N, Stopyra M, Furgoł T, Miciak M, Kabut J, et al. Temozolomide (TMZ) in the treatment of glioblastoma multiforme-A literature review and clinical outcomes. Current Oncology. 2024;31(7):3994-4002. Available from: https://doi.org/10.3390/curroncol31070296

Rathiya K. A conceptual study on Arbuda (Cancer) and its management: A review. International Journal of Ayurveda and Pharma Research. 2018;6(6). Available from: https://ijapr.in/index.php/ijapr/article/view/947

Vijay MK, Tiwari S, Kahar L, Malviya D, Aharwar M, Singh N. A comprehensive review of nutritional, phytochemical and pharmacological properties of Semecarpus anacardium L.: A significant wild edible fruit species of central India. International Journal of Advanced Biochemistry Research. 2025;9(4):350-361. Available from: https://doi.org/10.33545/26174693.2025.v9.i4e.4116

Semalty M, Semalty A, Badola A, Joshi GP, Rawat MS. Semecarpus anacardium Linn.: A review. Pharmacognosy Reviews. 2010;4(7):88-94. Available from: https://pubmed.ncbi.nlm.nih.gov/22228947/

Sharma S, Yadav PR, Galib R, Prajapati PK. Cytotoxic potential of Bhallataka Rasayana in MCF-7 and HT-29 cancer cell lines. Annals of Ayurvedic Medicine. 2026;15(Suppl 1):153-161. Available from: http://dx.doi.org/10.5455/AAM.59654

Joseph JP, Raval SK, Sadariya KA, Jhala M, Kumar P. Anti-cancerous efficacy of Ayurvedic milk extract of Semecarpus anacardium nuts on hepatocellular carcinoma in Wistar rats. African Journal of Traditional, Complementary and Alternative Medicines. 2013;10(5):299-304. Available from: https://journals.athmsi.org/index.php/ajtcam/article/view/1946

Mallick M, Khan W, Singh M, Najm M, Kashif M, Ahmad S, et al. In vitro anticancer potential of Semecarpus anacardium Linn. Drug Development and Therapeutics. 2016;7:55-58. Available from: https://doi.org/10.4103/2394-6555.180167

Singh RK, Mallik B, Ranjan A, Tripathi R, Verma SS, Sharma V, et al. Semecarpus anacardium L.f. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor-bearing mice. Natural Product Research. 2024;38(6):1080-1084. Available from: https://pubmed.ncbi.nlm.nih.gov/37157823/

Adams M, Jewell AP. The use of complementary and alternative medicine by cancer patients. International Seminars in Surgical Oncology. 2007;4:10. Available from: https://doi.org/10.1186/1477-7800-4-10

Malik V. Drug and Cosmetic Act 1940 with Drug and Cosmetic Rules. 18th edition. Lucknow; Eastern Book Company;2005;282.

Shastri K (editor). Sharma S. Rasatarangini. Vishoupavishadi Vignaneeyam, chapter 24, verse no.473. 11th edition. New Delhi; Motilal Banarsidass;2014;734.

Gupta KA (editor). Ashtanga Hridaya of Vagbhata, Chikitsa Sthana, chapter 4, verse no.72. Varanasi; Chaukhambha Krishnadas Academy;2016;401.

Yadunandana Upadhyaya (editor). Commentary: Vidyotini Hindi Commentary of Atrideva Gupta on Ashtanga Hridaya of Vagbhata, Uttarasthana, chapter 39, verse no.75-78, Reprint edition, Varanasi; Chaukhambha Sanskrit Sansthan;2005; 600.

Freshney RI. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications. 6th edition. Oxford; Wiley-Blackwell;2010.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods. 1983 Dec 16;65(1-2):55-63. Available from: https://doi.org/10.1016/0022-1759(83)90303-4

van Meerloo J, Kaspers GJL, Cloos J. Cell sensitivity assays: The MTT assay. Methods in Molecular Biology. 2011;731:237-245. Available from: https://doi.org/10.1007/978-1-61779-080-5_20

Saunshimath NM, Karoshi SS, Bhat K, Kumbhar V. Cardioprotective activity of Dashanga Agada in doxorubicin-induced cardiotoxicity in mice cardiomyoblasts (H9c2). International Journal of Ayurvedic Medicine. 2024;15(2):513-521. Available from: https://doi.org/10.47552/ijam.v15i2.4417

Rajaratnam V, Islam MM, Yang M, Slaby R, Ramirez HM, Mirza SP. Glioblastoma: Pathogenesis and current status of chemotherapy and other novel treatments. Cancers. 2020;12(4):937. Available from: https://doi.org/10.3390/cancers12040937

Kumbar VM, Muddapur U, Bin Muhsinah A, Alshehri SA, Alshahrani MM, Kugaji MS, et al. Curcumin-encapsulated nanomicelles improve cellular uptake and cytotoxicity in cisplatin-resistant human oral cancer cells. Journal of Functional Biomaterials. 2022;13(4):158. Available from: https://doi.org/10.3390/jfb13040158

Kumar AD, Bevara GB, Kaja LK, Badana AK, Malla RR. Protective effect of 3-O-methyl quercetin and kaempferol from Semecarpus anacardium against H2O2 induced cytotoxicity in lung and liver cells. BMC Complementary and Alternative Medicine. 2016;16(1):376. Available from: https://doi.org/10.1186/s12906-016-1354-z

Paradakara HS (editor). Astangahrdayam of Vagbhata, Chikitsasthana, chapter 15, verse no.70. 9th edition. Varanasi; Chaukhamba Orientalia;2005;697.

Ruhila A, Srivastava A, Yadav P, Galib R, Prajapati PK. Preliminary GC-MS profiling of Bhallataka oil. Asian Journal of Research in Chemistry. 2021;14(2):108-110. Available from: https://www.proquest.com/scholarly-journals/preliminary-gc-ms-profiling-bhallataka-oil/docview/2532695073/se-2

Nagabhushana KS, Umamaheshwari S, Tocoli FE, Prabhu SK, Green IR, Ramadoss CS. Inhibition of soybean and potato lipoxygenases by bhilawanols from bhilawan (Semecarpus anacardium) nut shell liquid and some synthetic salicylic acid analogues. Journal of Enzyme Inhibition and Medicinal Chemistry. 2002 Aug;17(4):255-259. Available from: https://doi.org/10.1080/1475636021000006243

Schultz DJ, Wickramasinghe N, Klinge CM. Anacardic acid biosynthesis and bioactivity. Recent Advances in Phytochemistry. 2006;40:131-156. Available from: https://doi.org/10.1016/S0079-9920(06)80040-7

Huang H, Peng J, Gao Z, Huang Y, Song W, Wu W, et al. Targeted delivery of PTX by lactoferrin-modified nanoemulsions for the treatment of glioblastoma. International Journal of Pharmaceutics: X. 2025;10:100460. Available from: https://doi.org/10.1016/j.ijpx.2025.100460

Additional Files

Published

2026-10-23

How to Cite

Puppalwar, A. G. ., Jadar, P. G. ., Kumbar, V. M., Shahpuri, S., Nambiar, R., & Aarathy, V. (2026). In Vitro Evaluation of Amritabhallataka Paka on Cell Viability and Apoptosis in U87MG Glioblastoma Cells and Cytocompatibility in L929 Fibroblasts. Journal Title: Journal of Ayurveda and Holistic Medicine, 14(9), 15-27. https://doi.org/10.70066/jahm.v14i9.2873

Issue

Section

Original Research Article- Experimental Research