Subjective biosafety assessment of bisdemethoxycurcumin from the rhizomes of Curcuma longa.

Introduction/Background: Curcuma longa, a plant native to the Indian subcontinent has a variety of biological activities. Curcumin is the most abundant and biologically active compound with many therapeutic properties. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) - the two other bioactive components present in Curcuma longa, besides curcumin, are collectively termed curcuminoids. Apart from the well-known curcumin, BDMC also has been reported to possess promising biological and pharmacological effects, but very little scientific evidence on its safety assessment has been published.Objective: The present study was undertaken to determine the safety of pure BDMC from Curcuma longa extract in rodents which comprises of general toxicity (both four weeks and three months duration), reproductive/developmental toxicity and genotoxicity studies.Methods: The Good Laboratory Practice studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development.Results: No treatment-related adverse findings were seen in general toxicity testing and a no observed adverse effect level (NOAEL) of 1000 mg/kg/day was established after four weeks (sub-acute) and three-months (sub-chronic) dosing. Evaluation of fertility, embryo-fetal, and post-natal reproductive and developmental parameters also showed no adverse findings with a NOAEL of 1000 mg/kg/day established. The results of genotoxicity as evaluated by in vitro reverse mutation assay, and in vivo micronucleus test in mice indicate that BDMC did not induce any genotoxic effects.Conclusion: Oral administration of BDMC is safe in rodents and non-mutagenic, with no adverse effects under experimental conditions.

Inhibition of proinflammatory cytokines and mediators by euphol.

The anti-inflammatory properties of Euphol (EU) a diterpene, isolated from the rhizomes of the plant Euphorbia acaulis, were evaluated. This study was designed to examine the effects of EU on inflammation in a rat model of pleurisy compared with a steroidal anti-inflammatory drug (DEX, dexamethasone). The rat model of pleurisy was used to evaluate the effectiveness of EU on leukocyte migration, exudation volume, proinflammatory cytokines i.e. Tumor Necrosis factor α (TNFα), Interleukin-1 (IL-1β) and Interleukin-6 (IL-6) as well as on proinflammatory mediators PGE2, nitrite/nitrate levels, and LTB4. Pleurisy was induced by carrageenan (cg ), administered by intra pleural route (i.pl.) and the leukocyte infiltration and inflammatory parameters analyzed 4 h after pleurisy induction. EU (8mg/kg-1, p.o.) treated groups caused significant decrease in the infiltration of neutrophils and exudate volume . There was an observed marked reduction in TNFα, IL-1β and IL-6 levels. Flow cytometric analysis of intracellular TNFα by leukocytes present in pleural exudates showed a significant decrease relative to the total extracellular TNFα inhibition in the pleural fluid. The proinflammatory mediators PGE2, LTB4 release and the nitrite/nitrate levels were remarkably deregulated which are interrelated to TNFα and IL-1β levels.

Amelioration of inflammatory responses by Chlorogenic acid via suppression of pro-inflammatory mediators.

The premise of the present investigation was to evaluate the detailed anti-inflammatory properties of chlorogenic acid (CGA) and to delineate the possible mode of action. To explore the anti-inflammatory profile, we evaluated the effect of CGA on TNF-alpha expression (in vitro); carrageenan induced rat paw edema and carrageenan induce pleurisy (in vivo). In our studies, CGA significantly inhibited the TNF-alpha expression, paw edema and antioxidant enzymes in livers of rats in pre-treatment schedule but failed to exert any effect when administered 1 h after carrageenan injection. CGA was also found to be safe, as confirmed by the results of acute toxicity studies and MTT assay. CGA also caused reduction in total leucocytes count most probably by inhibiting neutrophils, but could not alter mononuclear cells count in carrageenan induced pleurisy. Inhibition of exudation was evidenced by the less exudate formation in CGA treated animals, which may be due to decrease in vascular permeability which was further confirmed in acetic acid induced vascular permeability model in mice where significant decrease in vascular permeability was observed. CGA was highly effective in reducing the arachidonic acid metabolites, nitric oxide and pro-inflammatory cytokines production in a dose dependent manner and in some conditions effect observed was almost comparable to ibuprofen. Result of the present investigation shows the anti-inflammatory effects of CGS in different models.