Journal of Dental Anesthesia and Pain Medicine

The Korean Dental Society of Anesthsiology (대한치과마취과학회)
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Evaluation of phytochemical components, cytotoxicity, and molecular docking of Anacyclus pyrethrum and Commiphora myrrha for formulating a herbal topical anaesthetic gel development

  • Parthipann J (Department of Pediatric and Preventive Dentistry, K.S.R. Institute of Dental Science and Research) ;
  • Geetha Priya PR (Department of Pediatric and Preventive Dentistry, K.S.R. Institute of Dental Science and Research) ;
  • Sharath Asokan (Department of Pediatric and Preventive Dentistry, K.S.R. Institute of Dental Science and Research) ;
  • Yogesh Kumar Thoppe Dhamodharan (Department of Pediatric and Preventive Dentistry, K.S.R. Institute of Dental Science and Research) ;
  • Sudhandra Viswanath (Department of Pediatric and Preventive Dentistry, K.S.R. Institute of Dental Science and Research)
  • Received : 2026.01.10
  • Accepted : 2026.03.13
  • Published : 2026.06.01
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Abstract

Background: Synthetic intraoral topical anesthetics, such as lignocaine and benzocaine can cause adverse effects in pediatric dentistry, creating a need for safer plant-based alternatives. Anacyclus pyrethrum (A. pyrethrum) and Commiphora myrrha (C. myrrha) have traditionally demonstrated anesthetic and analgesic properties. Therefore, we aimed to evaluate the phytochemical composition, cytotoxicity, and molecular docking interactions of A. pyrethrum and C. myrrha extracts for potential use as novel herbal topical anesthetic gels. Methods: Ethanolic extracts of A. pyrethrum roots and C. myrrha resin were prepared by Soxhlet extraction and maceration, respectively. Phytochemical profiling was performed using High-Performance Liquid Chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and Fourier-Transform Infrared Spectroscopy (FTIR). Cytotoxicity was assessed in L929 fibroblasts and neural cells using the MTT assay. Molecular docking and codocking of pyrethrin and furanoeudesma-1,3-diene with neuronal sodium, potassium, and GABA-A receptors were performed. Results: HPLC and GC-MS confirmed the presence of bioactive compounds, including pyrethrin and furanoeudesma-1,3-diene, and the functional groups were validated by FTIR. Cytotoxicity assays revealed high biocompatibility, with half-maximal Inhibitory Concentration (IC50) values of 53 ± 0.21 ㎍/mL for A. pyrethrum and 54 ㎍/mL for C. myrrha. Molecular Docking studies showed strong binding affinities (-6.1 to -8.2 kcal/mol) across target receptors, and co-docking demonstrated synergistic ligand-receptor interactions. Conclusion: Phytochemical, cytotoxic, and molecular docking analyses confirmed the anesthetic potentials of A. pyrethrum and C. myrrha. These findings support their further development as safe plant-based topical anesthetic gels.

Keywords

References

  1. Sruthi MA, Ramakrishnan M. Transpapillary injection technique as a substitute for palatal infiltration: a split-mouth randomised clinical trial. Int J Clin Pediatr Dent 2021; 14: 640-3. https://doi.org/10.5005/jp-journals-10005-2026
  2. Jälevik B, Klingberg GA. Dental treatment, dental fear and behaviour management problems in children with severe enamel hypomineralization of their permanent first molars. Int J Paediatr Dent 2002; 12: 24-32. https://doi.org/10.1046/j.0960-7439.2001.00318.x
  3. Milgrom P, Coldwell SE, Getz T, Weinstein P, Ramsay DS. Four dimensions of fear of dental injections. J Am Dent Assoc 1997; 128: 756-66. https://doi.org/10.14219/jada.archive.1997.0301
  4. Askitopoulou H, Ramoutsaki IA, Konsolaki E. Analgesia and anaesthesia: etymology and literary history of related Greek words. Anesth Analg 2000; 91: 486-91.
  5. Kumar M, Chawla R, Goyal M. Topical anaesthesia. J Anaesthesiol Clin Pharmacol 2015; 31: 450-6. https://doi.org/10.4103/0970-9185.169049
  6. Nair M, Gurunathan D. Comparative evaluation of the efficacy of two anesthetic gels (2% lignocaine and 20% benzocaine) in reducing pain during administration of local anesthesia - a randomized controlled trial. J Anaesthesiol Clin Pharmacol 2019; 35: 65-9. https://doi.org/10.4103/joacp.JOACP_73_18
  7. Hindocha N, Manhem F, Bäckryd E, Bågesund M. Ice versus lidocaine 5% gel for topical anaesthesia of oral mucosa - a randomised cross-over study. BMC Anesthesiol 2019; 19: 227. https://doi.org/10.1186/s12871-019-0902-8
  8. FDA. FDA takes action against use of OTC benzocaine teething products due to serious safety risk, lack of benefit [Internet]. Silver Spring, MD, FDA. 2018. Available from https://www.fda.gov/news-events/press-announcements/fda-takes-action-against-use-otc-benzocaine-teething-products-due-serious-safety-risk-lack-benefit.
  9. World Health Organization. Integrating traditional medicine into healthcare [Internet]. Geneva, World Health Organization. 2023. Available from https://www.who.int/southeastasia/news/feature-stories/detail/integrating-traditional-medicine.
  10. Tsuchiya H. Anesthetic agents of plant origin: a review of phytochemicals with anesthetic activity. Molecules 2017; 22: 1369. https://doi.org/10.3390/molecules22081369
  11. Youssef ER, Barakat IF, Abbas AN. A comparative evaluation of pain perception following application of eutectic mixture of local anesthetic (EMLA) and clove gel before intraoral injection in children. Al-Azhar J Dent Sci 2023; 26: 547-53. https://doi.org/10.21608/ajdsm.2022.154820.1355
  12. Havale R, Rao DG, S P S, M Tuppadmath K, Tharay N, Mathew I, et al. Comparative evaluation of pain perception following topical application of clove oil, betel leaf extract, lignocaine gel, and ice prior to intraoral injection in children aged 6-10 years: a randomized control study. J Dent Anesth Pain Med 2021; 21: 329-36. https://doi.org/10.17245/jdapm.2021.21.4.329
  13. Jawhari FZ, El Moussaoui A, Bourhia M, Imtara H, Saghrouchni H, Amine A, et al. Anacyclus pyrethrum (L): chemical composition, analgesic, anti-inflammatory, and wound healing properties. Molecules 2020; 25: 5469. https://doi.org/10.3390/molecules25225469
  14. Mohite VA, Baliga S, Thosar N, Rathi N, Khobragade P, Srivastava R. Comparative evaluation of a novel herbal anaesthetic gel and 2% lignocaine gel as an intraoral topical anaesthetic agent in children: bilateral split-mouth, single-blind, crossover in vivo study. J Indian Soc Pedod Prev Dent 2020; 38: 177-83. https://doi.org/10.4103/JISPPD.JISPPD_226_20
  15. Shen T, Lou HX. Bioactive constituents of myrrh and frankincense, two simultaneously prescribed gum resins in Chinese traditional medicine. Chem Biodivers 2008; 5: 540-53. https://doi.org/10.1002/cbdv.v5:4
  16. Dolara P, Corte B, Ghelardini C, Pugliese AM, Cerbai E, Menichetti S, et al. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med 2000; 66: 356-8. https://doi.org/10.1055/s-2000-8532
  17. Mujeeburrahman R, Kasar SA, Gangurde AB, Khadabadi SS. Review on Indian medicinal plant Anacyclus pyrethrum as local anaesthetic and other medicinal value. IJBPAS 2023; 12: 1010-20.
  18. Hassanzadeh-Taheri M, Salimi M, Vazifeshenas-Darmiyan K, Mohammadifard M, Hosseini M. Investigating the effect of ethanolic extract of Commiphora myrrha (Nees) Engl. gum-resin against hepatorenal injury in diabetic rats. J Diabetes Metab Disord 2021; 20: 1573-81. https://doi.org/10.1007/s40200-021-00904-1
  19. Baslam A, Aitbaba A, Aboufatima R, Habbadi K, Attar A, El Abidine AL, et al. Phytochemistry, antioxidant potential, and antibacterial activities of Anacyclus pyrethrum: promising bioactive compounds. Horticulturae 2023; 9: 1196.
  20. Alqahtani AS, Herqash RN, Noman OM, Mothana RA, Al-Rehaily AJ, Al-Musayeib NM, et al. Impact of different extraction methods on furanosesquiterpenoids content and antibacterial activity of Commiphora myrrha resin. J Anal Methods Chem 2021; 2021: 5525173. https://doi.org/10.1155/2021/5525173
  21. Anand SP, Nagalakshmi R, Karthick S, Vanathi S. FT-IR and GC-MS characterisation of bioactive compounds from the root extract of Anacyclus pyrethrum Linn. IJAEB 2024; 9: 208-17.
  22. Meneses J, Silva JC, Fernandes SR, Pinto AM. A multimodal stimulation cell culture bioreactor for tissue engineering: a numerical modelling approach. Polymers 2020; 12: 940. https://doi.org/10.3390/polym12040940
  23. Agu PC, Afiukwa CA, Orji OU, Ezeh EM, Ofoke IH, Ogbu NW, et al. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in disease management. Sci Rep 2023; 13: 13398.
  24. Huang J, MacKerell AD Jr. CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J Comput Chem 2013; 34: 2135-45. https://doi.org/10.1002/jcc.23354
  25. Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 2015; 1: 19-25. https://doi.org/10.1016/j.softx.2015.06.001
  26. Boroujeni MB, Dastjerdeh MS, Shokrgozar M, Rahimi H, Omidinia E. Computational driven molecular dynamics simulation of keratinocyte growth factor behaviour at different pH conditions. Inform Med Unlocked 2021; 23: 100514. https://doi.org/10.1016/j.imu.2021.100514
  27. Muralikrishnan K, Asokan S, Geetha Priya PR, Zameer Ahmed KS, Ayyappadasan G. Comparative evaluation of the local anaesthetic activity of root extract of Anacyclus pyrethrum and its interaction at the site of injection in guinea pigs. Anesth Essays Res 2017; 11: 444-8. https://doi.org/10.4103/0259-1162.194568
  28. Patel VK, Patel RV, Venkatakrishna-Bhatt H, Gopalakrishna G, Devasankariah G. A clinical appraisal of Anacyclus pyrethrum root extract in dental patients. Phytother Res 1992; 6: 158-9. https://doi.org/10.1002/ptr.v6:3
  29. El Ashry ES, Rashed N, Salama OM, Saleh A. Components, therapeutic value and uses of myrrh. Pharmazie 2003; 58: 163-8.
  30. Bahri H, El Idrissi A, Rotando S, Tazi B. Antioxidant and anti-cancer activities of Anacyclus pyrethrum root extracts. Acad J Med Plants 2019; 7: 269-77.
  31. Su S, Wang T, Chen T, Duan JA, Yu L, Tang Y. Cytotoxicity activity of extracts and compounds from Commiphora myrrha resin against human gynecologic cancer cells. J Med Plants Res 2011; 5: 1382-9.
  32. Zhorov BS, Dong K. Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel. Neurotoxicology 2017; 60: 171-7. https://doi.org/10.1016/j.neuro.2016.08.013
  33. Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, et al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev 2012; 64: 16-28. https://doi.org/10.1016/j.addr.2011.02.008
  34. Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1: 337-41. https://doi.org/10.1016/j.ddtec.2004.11.007
  35. Sankar V, Hearnden V, Hull K, Juras DV, Greenberg MS, Kerr AR, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis 2011; 17: 73-84. https://doi.org/10.1111/odi.2011.17.issue-s1