Role of CaMKII in the regulation of fatty acids and lipid metabolism.

BACKGROUND & AIMS: Previous studies have reported the beneficial roles of the activation of calmodulin-dependent protein kinase (CaMK)II to many cellular functions associated with human health. This review aims at discussing its activation by exercise as well as its roles in the regulation of unsaturated, saturated, omega 3 fatty acids, and lipid metabolism. METHODS: A wide literature search was conducted using online database such as 'PubMed', 'Google Scholar', 'Researcher', 'Scopus' and the website of World Health Organization (WHO) as well as Control Disease and Prevention (CDC). The criteria for the search were mainly lipid and fatty acid metabolism, diabetes, and metabolic syndrome (MetS). A total of ninety-seven articles were included in the review. RESULTS: Calmodulin-dependent protein kinase activation by exercise is helpful in controlling membrane lipids related with type 2 diabetes and obesity. CaMKII regulates many health beneficial cellular functions in individuals who exercise compared with those who do not exercise. Regulation of lipid metabolism and fatty acids are crucial in the improvement of metabolic syndrome. CONCLUSIONS: Approaches that involve CaMKII could be a new avenue for designing novel and effective therapeutic modalities in the treatment or better management of metabolic diseases such as type 2 diabetes and obesity.

Exploration of Modern Chromatographic Methods Coupled to Mass Spectrometric Techniques for Trace Element and Chemical Composition Analyses in the Leaf Extracts of Kigelia africana.

The use of Kigelia africana (Lam.) Benth. plant dates back to last century. The different parts of the plant exhibited various pharmacological activities. But literature search revealed scanty use of the leaf extract owing to few information regarding the various phytochemical constituents. The aim of this study is, therefore, to profile the chemical compounds through the use of omics-based approach. Ultrahigh-pressure liquid chromatography quadrupole-time-of-flight tandem mass spectrometry (qTOF-UPLC/MS) alongside gas chromatography quadrupole time-of-flight tandem mass spectrometry (qTOF-GC/MS) were used to profile these chemical compounds. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to determine the concentration of trace elements as well as limit of detection (LOD) and quantification (LOQ). For broader metabolite determination, a modified sample preparation was employed and to ascertain the cytoprotective potential of the leaf extract, MTT assay on A375 human melanoma cell lines was carried out. Sixty-eight peaks were characterized with the identification of 275 metabolites where 8 of these were confirmed. Of importance is the identification of eugenol; a polyphenolic compound at m/z 165.09 on fragments 119.09, 147.08, 109.10, 137.10, and 137.06. for qTOF-GC/MS analysis, 232 metabolites were identified consisting of terpenes, fatty acids, furans, amines, amides, and alkanes. The concentration of trace elements in the leaf extract ranged from 0.08 for Zn to 0.28 mg/kg for Fe with low concentrations of Cd according to the recommendation of European Legislation. The leaf showed higher inhibition of growth against A375 human melanoma cell lines in a dose-dependent manner. The results showed that K. africana leaf contained various pharmaceuticals, nutraceuticals, designer drugs, and phytochemicals, and these chemicals have minimal cytotoxic side effects. To the best of our knowledge, this is the first study providing information on the various secondary metabolites in the leaf extract through the use of omics-based approach. Therefore, the leaves of K. africana plant can be used as antiinflammatory, antimicrobial, antibacterial, antifungal, and antiproliferative agents for industrial, therapeutic, and medicinal applications. Graphical Abstract.

Evaluation of Phytochemicals, Antioxidants, Trace Elements in Kigelia africana Fruit Extracts and Chemical Profiling Analysis Using UHPLC-qTOF-MS2 Spectrometry.

The study aimed at evaluating the phytochemical composition, antioxidant potentials and the levels of trace elements in the fruit extract of Kigelia africana obtained by different extraction solvents in order to ascertain its numerous pharmacological activities and identify the different chemical compounds responsible for these activities. The crude extract in ethanol and four other solvent fractions (hexane, ethylacetate, butanol and aqueous) were obtained for phytochemical screening. Antioxidant potentials of K. africana fruit were investigated spectrophotometrically using hydroxyl ion scavenging (OH-) activity, metal ion chelating activity, anti-lipid peroxidation activity as well as total antioxidant capacity assays. Trace element (Mn, Zn, Cd, Ni, Cu, Pb, Cr, Co and Fe) levels were measured using a plasma-emission spectrometer that has an auto sampler AS 93-plus and coupled with Nebulizer CETAC U-6000AT+ after microwave acid digestion of the fruit extracts. Chemical identification was performed using ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS2). Kigelia africana fruit extracts obtained showed a variety of bioactive phytochemical compounds including phenolic acids, flavonoids, saponins, tannins and glycosides. The total antioxidant capacity activities of the aqueous, butanol, ethanol, hexane and ethylacetate extracts are 15.04, 52.11, 44.95, 79.27 and 175.20 mg AAE/g. Metal ion chelating activity showed significant correlation with lipid peroxidation inhibition activity at p ≤ 0.01 and with OH- scavenging activity at p ≤ 0.05. PCA analysis revealed that all the extract/fractions have higher total antioxidant activities compared to aqueous extract with hexane extract exhibiting the highest radical scavenging potential. HCA showed similarities with three well-defined clusters and PLS regression was used to predict total antioxidant activity. High sensitivity by low values of limits of detection and quantification was observed ranging from 0.021 to 0.085 mg/ml and 0.063 to 0.258 mg/ml for Zn and Fe respectively. Ethylacetate extract had high concentration of Fe (0.5656 mg/kg). For the standardization of the K. africana fruit extract, 244 chemical compounds were identified by measuring m/z values with threshold override of 100,000 and analysing mass spectrometer fragmentation behaviour while 16 of these were confirmed. Kigelia africana fruit extract is a good source of antioxidant and possess maximum accepted concentration of trace elements according to European legislation (1881/2006/EC). The metabolites identified exhibited numerous pharmacological activities. The method and results suggest the applicability for commercial use of this K. africana fruit in the treatment of oxidative-related diseases. Graphical abstract The phytochemical, antioxidant and trace element composition of crude ethanol extract, hexane, butanol, aqueous and ethylacetate extracts of Kigelia africana fruit were determined. The fruit extracts were found to possess good antioxidant activity, maximum acceptable amount of essential trace elements as well as the presence of bioactive phytochemicals. K. africana fruit would be an ideal candidate in improving human health and thus the management of oxidative-related diseases such as diabetes, by involving in the antioxidant defense system against free radical generation.