Aim: To study acute and chronic toxicity profile of Commiphora opobalsamum (CO) in rats. Methods: Acute oral lethal effect and single oral dose toxicity of CO was determined in rats by comparison with standard control. In contrast repeated dose oral toxicity in rats were performed in four groups of rats, CO was orally administered to three groups of rats in graded doses (250, 500 and 1000 mg/kg/day) once daily for 14 daysVs standard control. The sub-acute toxicity of CO was observed on hematological, coagulation and biochemical parameters. Results: Acute oral lethal dose of CO in rats was demonstrated to be safe and higher than the tested dose i.e., 2000 mg/kg, moreover, single oral dose toxicity revealed no symptoms of toxicity. Furthermore, sub-acute toxicological effect on hematological analysis of CO rats groups treated withgraded dosed after 14 days treatment revealed insignificant decrease in complete blood count (CBC)in contrast with the control group (p>0.05) additionally the biochemical parameters includedanalysis of urea, creatinine, glucose; lipid profile and thyroid function markers fairly demonstrated insignificant differences utilizing the same methodology. Conclusion: Our current explorative study strongly substantiates that the CO extract have no significantoral toxicity in rats and even the results of 14 days oral treatment indicated that there were no obvious toxic effects at the dosage of 1000 mg/kg/day. The comprehensive sub-acute toxicological effect of CO extracts on hematological and coagulation parameters and biochemical parameters included analysis of urea, creatinine, glucose; lipid profile and thyroid function markers fairly demonstrated no significant harmful outcome even after 14 days treatment with CO.

This study aims to investigate the analgesic and anti-inflammatory effects of Commiphora opobalsamum in rodents in comparison with diclofenac, and its ability to enhance the activity of diclofenac in reduced doses. Wister rats or Swiss mice (5 groups/ 6 each) were administered methalonic extract of C. opobalsamum, saline and diclofenac 30 min before the test initiation by i.p. route. The analgesic activities were examined utilizing the acetic acid, hot plate and formalin paw lick techniques. The anti-inflammatory efficacy was examined by utilizing the granuloma induced by cotton pelletand paw edema induced by carrageenan C. opobalsamum demonstrated a stronger inhibition of writhing compared to diclofenac, and the 500 mg/kg dose completely inhibited the writhing response. In hot plate, C. opobalsamum co-administrated with diclofenac exhibited significant prolongation of reaction time compared to diclofenac alone. Furthermore, C. opobalsamum (500 mg/kg) significantly shortens the licking time compared to diclofenac at both phases. In addition, the suppression of paw edema induced by carrageenan was significant in comparison to diclofenac at first hour. Interestingly, significant weight reduction of granuloma tissue was perceived at all doses of C. opobalsamum in contrast to control group. This study provides a strong evidence of the analgesic and anti-inflammatory activity of extract of C. opobalsamum, additionally it has revealed significant anti-inflammatory effect, equivalent to non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the combination of reduced doses of C. opobalsamum and diclofenac with resultant synergistic potentiation of both analgesic and anti-inflammatory effect, necessitates a cautious approach to elucidate its mechanism with the concomitant meticulous study of its safety profile.

Background: Our recent past studies accomplished the target to investigate the anti-inflammatory effect as well as toxicological profile of Commiphora opobalsamum (CO), with almost identical potency in comparison to the contemporary anti-inflammatory drugs. This inspired us to explore its mechanism of action to further strengthen its efficacy. Aim: To investigate the mechanism of anti-inflammatory action of CO by exploration of its correlation to its antioxidant activity as well as inhibitory effect on inflammatory mediators by interaction with MDA, NO, PGE2 and TNF-α. Methods: 10 weeks old male Swiss albino mice (30 to 40 g) were used. Carrageenan–induced paw edema method was used, pretreatment with CO alone in different doses and in combination with diclofenac was done prior to carrageenan administration, subsequently homogenate of the paw was used to quantify the levels of MDA, NO, PGE2 and TNF-α by using their specific assays. In addition, Histological examination of edema paw was performed to evaluate the anti-inflammatory effect of CO extract versus diclofenac and control investigating their impact on the inflammatory cell migration and edema formation. Results: CO extract in the dose of 500mg/kg demonstrated maximum reduction of MDA level; hence antioxidant activity of CO could be contributed to its anti-inflammatory effect. Furthermore, notable observation indicated that CO administration significantly suppress increment in NO level in response to carrageenan, unequivocally significant inhibition of PGE2 accumulation at the site of inflammation by the pretreatment of CO extract was observed in the dose of 500mg/kg (0.001). Finally in contrast, the CO extract in the dose of 500mg/kg significantly accomplished the reduction of TNF-α in the paw in comparison to the control group (p<0.05). Conclusion: In this study we have illustrated a pioneering perspective to elucidate the mechanism of anti- inflammatory and antioxidant action of methanolic extract of CO, attributed through suppression of MDA. NO, PGE2 and TNF-α at the site of inflammation.