Identification of Potential Anti-Inflammatory Phytochemicals from Leucas Aspera Using A Computer-Aided Drug Design Approach

Inflammation is a protective biological response to tissue injury, infection, and other harmful stimuli^10,11. Chronic inflammation contributes to numerous diseases including arthritis, cardiovascular disorders, and autoimmune diseases^12,13. Although several anti-inflammatory drugs are available, long-term use may result in adverse effects. Medicinal plants represent an important source of bioactive compounds with therapeutic potential^4,5. Leucas aspera (Willd.) Link, belonging to the family Lamiaceae, has been traditionally used for the treatment of inflammation, fever, skin disorders, and other ailments^7,9. Previous phytochemical investigations have reported the presence of flavonoids, terpenoids, sterols, and phenolic compounds in the plant^5,8,9. Computer-aided drug design (CADD) techniques, particularly molecular docking, provide an efficient approach for identifying potential drug candidates by predicting ligand–protein interactions^20,22,29. Therefore, the present study was undertaken to evaluate selected phytochemicals from Leucas aspera against an anti-inflammatory target protein using molecular docking and pharmacokinetic analysis. Microsomal prostaglandin E synthase-1 (mPGES-1) is a terminal enzyme involved in prostaglandin E2 biosynthesis and plays a crucial role in inflammatory responses^26,28. Selective inhibition of mPGES-1 has emerged as a promising strategy for development safer anti-inflammatory agents. Recent advances in computer-aided drug design (CADD) have accelerated the identification of bioactive compounds through virtual screening molecular docking, and pharmacokinetics prediction.

MATERIALS AND METHODS

1. Selection of Phytochemicals

Eight phytochemicals reported from Leucas aspera were selected:

1. Ursolic acid
2. Oleanolic acid
3. Apigenin
4. Chrysoeriol
5. Catechin
6. β-Sitosterol
7. Acacetin
8. β-Caryophyllene

Figure 1. Workflow of the computer-aided drug design (CADD) approach employed for the identification of potential anti-inflammatory phytochemicals from Leucas aspera targeting mPGES-1 (PDB ID: 5IKR).

Figure 2. Comparison of molecular docking binding affinities of selected phytochemicals from Leucas aspera against mPGES-1 (PDB ID: 5IKR).

Figure 3. Molecular docking interaction of ursolic acid with 5IKR. (A) Three-dimensional binding pose of Ursolic acid within the active site of microsomal prostaglandin E synthase-1(mPGES-1; PDB ID: 5IKR). (B) Two-dimensional protein-ligand interaction diagram showing the binding interaction of ursolic acid with residue in the active site.

Figure 4. Molecular docking interaction of Oleanolic acid with 5IKR. (A) Three-dimensional binding pose of Oleanolic acid within the active site of microsomal prostaglandin E synthesis-1 (mPGES-1; PDB ID: 5IKR), illustrating its accommodation within the receptor binding pocket. (B)  2D protein-ligand interaction diagram of oleanolic acid docking with 5IKR showing interactions with ARG456 and LEU171 residues.

Figure 5. Molecular docking interaction of apigenin with 5IKR. (A) Three-dimensional binding pose of apigenin within the active site of microsomal prostaglandin E synthesis-1 (mPGES-1; PDB ID: 5IKR), illustrating its accommodation within the receptor binding pocket. (B) 2D protein-ligand interaction diagram of apigenin docking with 5IKR showing hydrogen bond interaction with CYS47 residue.

DISCUSSION

The observed docking scores indicate that triterpenoids such as ursolic acid and oleanolic acid possess strong binding affinity toward the selected anti-inflammatory target. Previous studies have reported significant anti-inflammatory effects of these compounds through inhibition of inflammatory mediators and signaling pathways. Apigenin, a well-known flavonoid, has also demonstrated anti-inflammatory activity through modulation of NF-kB and cytokine production^18,19,34,37. The present findings are consistent with previous reports and further support the therapeutic potential of phytochemicals present in Leucas aspera^7,9,40. Ursolic acid exhibited the highest binding affinity (−9.4 kcal/mol), suggesting stronger interaction with the active site of mPGES-1 compared with the other phytochemicals investigated. The interaction analysis revealed hydrogen bond formation with SER143 and ASN144 residues, which may contribute to stabilization of the protein–ligand complex. Oleanolic acid and apigenin also demonstrated favorable binding energies and interaction profiles, indicating their potential as promising anti-inflammatory lead compounds.

LIMITATIONS

The present investigation is limited to computational predictions and does not include experimental validation. Therefore, in vitro and in vivo studies are required to confirm the anti-inflammatory activity of the identified lead compounds.

FUTURE PERSPECTIVES

Although molecular docking provides valuable insights into protein-ligand interactions, molecular dynamics (MD) simulations are recommended to further evaluate the stability and conformational behaviour of protein-ligand complexes under physiological conditions. Furthermore, in vitro and in vivo studies are necessary to validate the anti-inflammatory efficacy and safety of the identified lead compounds^20,21,30.

CONCLUSION

The present study employed molecular docking and pharmacokinetic analysis to evaluate the anti-inflammatory potential of phytochemicals from Leucas aspera against Microsomal Prostaglandin E Synthase-1 (mPGES-1; PDB ID: 5IKR). Among the screened compounds, ursolic acid (-9.4 kcal/mol), oleanolic acid (-9.0 kcal/mol), and apigenin (-9.0 kcal/mol) demonstrated the most favourable binding affinities toward the target protein. SwissADME analysis further revealed promising pharmacokinetic characteristics and drug-likeness profiles for these compounds. Among all the compounds investigated, ursolic acid exhibited the highest binding affinity and may represent the most promising lead candidate for further development. These findings suggest that phytochemicals from Leucas aspera may serve as potential anti-inflammatory lead molecules for future drug development. However, further molecular dynamics simulations and experimental validation through in vitro and in vivo studies are required to confirm their therapeutic efficacy and safety.

Conflict of Interest

The authors declare no conflict of interest.

ACKNOWLEDGEMENTS

The authors acknowledge Shantha College of Pharmacy for providing the facilities required for conducting this study.

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