Systematic and comprehensive investigation of the toxicity of curcuminoid-essential oil complex: A bioavailable turmeric formulation

Abstract

Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti-inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid-essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non-mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non-toxic pharmacological formulation.

Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review

“…Curcumin at the single dose of 5,000 mg/kg body weight that was given orally to Swiss albino mice did not show any toxic effects during 14 days. In the same way, no toxicity was observed during 14 days in rats at the single dose of 5,000 mg/kg and no pathological effects were observed in both rats and mice and no death occurred (Aggarwal, Chacko, & Kuruvilla, ).…”

“…No toxic effects were observed in 90‐day study on Wistar albino rats at the doses of 100, 500, and 1,000 mg/kg body weight of curcuminoid essential oil given via oral route once a day. Also, no signs of abnormality and toxicity were seen compared with control groups (Aggarwal et al, ). In another research, oral administration of 5% turmeric to Swiss mice through diet for 90 days demonstrated a significant decrease in body weight and focal necrosis in liver were observed (Deshpande et al, ).…”

Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms

“…In mice, 0.2% dietary curcumin (approximately 300 mg/kg BW) exhibited no toxicity [40]. Furthermore, curcumin at the single dose of 5000 mg/kg body weight that was given orally to Swiss albino mice did not show any toxic effects during 14 days with no pathological effects observed and no deaths occurred [41]. In addition, 500 mg/kg BW, 1000 mg/kg BW, and 2000 mg/kg BW of oral curcumin showed no significant genotoxicity in mice [42].…”

Safety and efficacy of Curcumin versus Diclofenac in Knee Osteoarthritis: a randomized open label parallel arm study

“…Availability of curcumin in blood plasma was seven folds higher after consuming curcuminoids and essential oil of turmeric than normal curcumin. Significant level of curcumin was retained even at 8 hours post administration and found to be non-toxic and safe [29][30][31]. Studies has been conducted on curcuminoid-essential oil complex showing therapeutic efficacy in numerous diseases like major depressive disorders, alzhiemer's disease, rheumatoid arthritis and has potential for widespread application and radioprotective effect in different kinds of cancer [32][33][34][35][36][37][38].…”