Characterization, quantification and a multi-computational in silico toxicity assessment of impurity (feruloyl methane) in synthetic curcumin using RP-HPLC-UV technique.

Feruloyl Methane (FM) is a common impurity in Synthetic Curcumin (SC) that affects its purity and potency. The identification and quantification of FM is crucial to ensure the quality and safety of SC based drugs. The current study aims to develop and validate a simple, rapid and cost-effective analytical technique for the precise and accurate quantification of FM in SC using RP-HPLC with a UV-Vis detector (Ultraviolet/Visible) and assessment of its toxicity by multi-computational methods. The developed HPLC method with a UV-Vis detector enabled accurate identification and quantification of FM in SC. The optimized method was validated in accordance with ICH guidelines Q2(R1) and all parameters were found to be within the standard acceptance range. The ideal run time was determined to be 10 min and the impurity eluting at a retention time of 2.65 min was characterized using spectral techniques viz., mass spectrometry, FTIR and 1 H NMR, confirming the presence of FM. The amount of FM in SC was estimated to be 8.26 µg/kg. In addition, toxicity assessments using in silico tools such as ProTox- II, ADMETlab 2.0 and PASS Online indicated that the presence of FM in SC is not safe for human consumption. In conclusion, the developed method is not only capable of quantifying FM but also aids in distinguishing Natural Curcumin (NC) adulterated with SC and can be applied to a wide range of fields such as natural drug analysis, food analysis and toxicity prediction.

Safety assessment of a solid lipid curcumin particle preparation: In vitro and in vivo genotoxicity studies.

Curcumin, one of the three principal curcuminoids found within turmeric rhizomes, has long been associated with numerous physiologically beneficial effects; however, its efficacy is limited by its inherently low bioavailability. Several novel formulations of curcumin extracts have been prepared in recent years to increase the systemic availability of curcumin; Longvida®, a solid lipid curcumin particle preparation, is one such formulation that has shown enhanced bioavailability compared with standard curcuminoid extracts. As part of a safety assessment of Longvida® for use as a food ingredient, a bacterial reverse mutation test (OECD TG 471) and mammalian cell erythrocyte micronucleus test (OECD TG 474) were conducted to assess its genotoxic potential. In the bacterial reverse mutation test, Longvida® did not induce base-pair or frame-shift mutations at the histidine locus in the genome of Salmonella typhimurium strains TA98, TA100, TA102, TA1535, and TA1537, in the presence or absence of exogenous metabolic activation. Additionally, two gavage doses (24 h apart) of Longvida® to Swiss albino mice at 500, 1000, or 2000-mg/kg body weight/day did not cause structural or numerical chromosomal damage in somatic cells in the mammalian erythrocyte micronucleus test. It was therefore concluded that Longvida® is non-genotoxic.

Toxicity and biodistribution assessment of curcumin-coated iron oxide nanoparticles: Multidose administration.

AIM: Iron oxide nanoparticles (IONPs) have been widely used in diagnosis, drug delivery, and therapy. However, the biodistribution and toxicity profile of IONPs remain debatable and incomplete, thus limiting their further use. We predict that coating iron oxide nanoparticles using curcumin (Cur-IONPs) will provide an advantage for their safety profile. MATERIALS AND METHODS: In this study, an evaluation of the multidose effect (6 doses of 5 mg/kg Cur-IONPs to male BALB/c mice, on alternating days for two weeks) on the toxicity and biodistribution of Cur-IONPs was conducted. KEY FINDINGS: Serum biochemical analysis demonstrated no significant difference in enzyme levels in the liver and kidney between the Cur-IONP-treated and control groups. Blood glucose level measurements showed a nonsignificant change between groups. However, the serum iron concentration was found to initially increase significantly but then decreased at 10 days after the final injection. Histopathological examination of the liver, spleen, kidneys, and brain showed no abnormalities or differences between the Cur-IONP-treated and control groups. There were no abnormal changes in mouse body weight. The biodistribution results showed that Cur-IONPs accumulated mainly in the liver, spleen, and brain, while almost no Cur-IONPs were found in the kidney. The iron content in the liver remained high even 10 days after the final injection, while the iron content in the spleen and brain had returned to normal levels by this time point, indicating their complete clearance. SIGNIFICANCE: These results are significant and promising for the further application of Cur-IONPs as theragnostic nanoparticles.

Toxicity and Selective Biochemical Assessment of Quercetin, Gallic Acid, and Curcumin in Zebrafish.

In recent years, numerous research outcomes were established on various naturally occurring compounds that have been shown to have beneficial antioxidant and other biological activities. Antioxidant defence mechanism plays a vital role in combating various diseases mainly due to oxidative stress. However, various models have been utilized to identify their bioactivities using these compounds (quercetin, gallic acid and curcumin). Their toxicity level also has to be explored to determine the threshold levels on the usage of these compounds. In this study, we investigated the lethal concentration of these compounds and abnormalities, biochemical and morphological changes in zebrafish embryo (Danio rerio). Toxicity level was evaluated by calculating the LD50 on the embryonic stages at 24, 48 and 72 h. Antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and biological assays such as lipid peroxidation, protein estimation were performed. Microscopic evaluations were also observed to find out morphological abnormalities. However, these naturally derived compounds are reported to have their protective and curative role in many health complications. From the above assays, we are studying the effect of the drugs in both biochemical and molecular way in the zebrafish model organism.

Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies.

Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD50 of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested.

Pharmacokinetics prediction and drugability assessment of diphenylheptanoids from turmeric (Curcuma longa L).

Cheminformatics approaches are currently not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which do not have toxic effects but at the same time have desired pharmacokinetic profile. In the present study of the class 'diphenylheptanoids' from turmeric, cheminformatics methods were employed to predict properties such as physicochemical properties, Absorption, Distribution, Metabolism, Toxicity (mutagenicity, rodent carcinogenicity and human hepatotoxicity). These studies confirmed that curcumin and its derivatives cause dose-dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric such as compounds (8) and (9) [refer text], exhibit better activities and are drugable and do not have any side-effects.