Pharmacological and molecular insights into linalool-rich Coriandrum sativum essential oil: Anticonvulsant, analgesic, anti-inflammatory, and antioxidant potential in rodent models

Abstract

Background and Aim: Coriandrum sativum L. (coriander) has long been valued for its culinary and medicinal uses. C. sativum essential oil (CsEO), particularly linalool-rich chemotypes, exhibits diverse biological activities; however, integrated evaluations encompassing neurological, inflammatory, and molecular targets remain limited. This study aimed to chemically characterize Peruvian CsEO and assess its anticonvulsant, analgesic, anti-inflammatory, and antioxidant effects, alongside those of pure linalool, while elucidating potential mechanisms through cytokine modulation and molecular docking of cyclooxygenase (COX) enzymes. Materials and Methods: CsEO was extracted from Peruvian coriander seeds through steam distillation and analyzed using gas chromatography-mass spectrometry (GC-MS). Antioxidant activity was quantified using the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assay. Anticonvulsant effects were tested in BALB/c mice using the pentylenetetrazole-induced seizure model, analgesic activity through the acetic acid-induced writhing test, and anti-inflammatory effects in Holtzman rats using the carrageenan-induced paw edema model. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Molecular docking evaluated linalool’s binding affinity to COX-1 and COX-2 relative to standard non-steroidal anti-inflammatory drugs. Results: GC-MS identified linalool as the major constituent (59.80%), alongside α-pinene (8.65%), camphor (8.48%), and γ-terpinene (7.09%). CsEO demonstrated potent antioxidant activity (half-maximal inhibitory concentration [IC50] = 32.04 µg/mL), exceeding that of linalool alone (IC50 = 152.29 µg/mL). Significant anticonvulsant effects occurred at 200 mg/kg for both CsEO and linalool, increasing seizure latency by up to 87.20% and reducing seizure frequency by ~43%. In analgesic assays, linalool (200 mg/kg) achieved a 93.80% writhing reduction, comparable to tramadol, while CsEO showed strong but slightly lower efficacy. CsEO (200 mg/kg) inhibited carrageenan-induced edema by 51.35% at 4 h, reduced IL-1β by 49.8%, and IL-6 by 26.5%, effects comparable to ibuprofen. Docking revealed moderate linalool affinity for COX-1 (-5.70 kcal/mol) and COX-2 (-6.10 kcal/mol), sharing key hydrophobic interactions with reference drugs. Conclusion: Peruvian CsEO, characterized by a distinctive linalool-rich chemotype, exhibits significant multi-target pharmacological activities, with synergistic contributions from minor constituents enhancing antioxidant and anti-inflammatory effects. Its integrated efficacy profile and favorable safety indicators highlight CsEO as a promising phytotherapeutic candidate for managing seizures, pain, and inflammation. Further studies should explore chronic models, pharmacokinetics, and formulation strategies to optimize clinical applicability.