Analgesic and Anti-inflammatory Activities of Trayodashang Guggulu, an Ayurvedic Formulation

Abstract

• Analgesic and anti-inflammatory activity of trayodashang guggulu . • Analgesic activity by Eddy's hot plate, tail immersion and formalin-induced pain models • Anti-inflammatory activity by carrageenan and formalin-induced inflammation models. • TG did not reduced centrally acting pain models i.e. Eddy's hot plate and tail immersion. • In formalin-induced pain model, TG significantly decreased both flinching and licking pain responses in early and late phase. • TG showed significant reduction in formalin and carrageenan-induced inflammation • Study substantiates the traditional use of TG in various painful inflammatory conditions. Background: Trayodashang guggulu (TG) is a compound Ayurvedic formulation used in Indian traditional system of medicine for the treatment of various inflammatory conditions like arthritis and associated pain. Purpose: To study the analgesic and anti-inflammatory effects of trayodashang guggulu . Methods: Trayodashang guggulu (TG) was standardized as per standard procedures and TLC profile was carried as per Ayurvedic Pharmacopoeia of India and LC-MS analysis was done to identify its bioactive constituents. Trayodashang guggulu was suspended in water and administered orally at 270 and 540 mg/kg dose for evaluating pain and inflammation in rats. Analgesic activity was assessed by Eddy's hot plate, tail immersion and formalin-induced pain models while anti-inflammatory activity was assessed by carrageenan and formalin-induced inflammation models. Further, the mechanism of anti-inflammatory action is predicted through various in silico methods like molecular docking and dynamics studies using AutodockVina and AMBER, respectively. Results: TG was found compliant as per pharmacopoeial standards. TG (270 and 540 mg/kg, orally) did not cause significant reduction in pain in centrally acting pain models i.e. Eddy's hot plate and tail immersion tests as like Pentazocin (10 mg/kg). In formalin-induced pain model, TG (270 and 540 mg/kg, orally) significantly decreased both flinching and licking pain responses in early and late phase while indomethacin (10 mg/kg) only affected late phase flinching and licking. Further, TG showed significant time-dependent reduction in formalin and carrageenan-induced inflammation as compared to vehicle control. Indomethacin (10 mg/kg), standard drug also showed significant reduction in pain and inflammation. LC-MS analysis revealed the presence of 17 phytoconstituents in TG. Further, in silico studies revealed that some of the identified phytochemicals may have inhibitory activity against COX-2 enzyme and the synergistic effects due to multi components may be responsible for the anti-inflammatory properties of TG. Conclusion: In conclusion, trayodashang guggulu inhibited the inflammatory pain as well as showed anti-inflammatory activity in rats. The effect may be attributed to the presence of anti-inflammatory phytoconstituents through the inhibition of anti-inflammatory enzymes like COX-2. The study further validates its traditional use in various painful inflammatory conditions.