(±)-Naringenin

6-Hydroxydopamine (6-OHDA) is a neurotoxin that inhibits the mitochondrial complex I causing mitochondrial impairment, aetiology of Parkinson's. Naringenin is a flavanone predominantly present in citrus fruits. Due to its high antioxidant and anti-inflammatory potential, it has been widely studied against various disorders. In this study, the neuroprotective effect of naringenin was determined against 6-OHDA induced toxicity with Levodopa (l-DOPA) as the standard. Naringenin reduced 6-OHDA induced oxidative stress biomarker levels such as CAT, GSH, SOD, and ROS. Naringenin rescued 6-OHDA induced reduction of the mitochondrial membrane potential. Treatment with naringenin improved the locomotion of the 6-OHDA treated zebrafish larvae which showed stagnant swimming patterns. Naringenin was also found to downregulate the expression of some Parkinsonian genes such as casp9, lrrk2, and polg and upregulate pink1. These studies attribute to naringenin as a viable molecule to study further for its neuroprotective effects against 6-OHDA induced neurotoxicity and neurodegeneration.

Phenolic compounds constitute one of the important classes of secondary metabolites in the plants. Flavonoids are primary phenolic compounds found in natural drugs. Naringenin is a flavanone, aglycone of Naringin, predominantly found in citrus fruits with various pharmacological activities. Large number of scientific papers has been published on Naringenin describing its structure, physicochemical properties and its therapeutic use in different diseases. This review provides highlights of Naringenin with respect to its distribution, pharmacokinetic and its use in conditions like oxidative stress, inflammation, cancer, diabetes, cardiovascular diseases and neurological disorders. Furthermore, the review also focuses on molecular level mechanisms of Naringenin for its therapeutic effect. Various attempts have been made to formulate advanced dosage forms to address issue of solubility of Naringenin. Systematic review of data published on formulation aspects of Naringenin has also been presented in the article.

Introduction:Naringenin, a dihydro-flavonoid compound that shows chemotactic activity, may have a good application prospect in repairing bone tissue, but its specific mechanism in bone regeneration, especially the osteogenic differentiation of stem cells, needs for a further study. The aim of this study was to investigate the effect of naringenin on the osteogenic differentiation and its roles in the C-X-C chemokine receptor type 4/stromal cell-derived factor 1 (SDF-1/CXCR4) signal pathway of bone marrow-derived mesenchymal stem cells (BMSCs).Material and methods:BMSCs were harvested from the femurs and tibias of 4-to-6-week-old male Sprague-Dawley rats. Cell Counting kit-8 assay was used to determine cytotoxicity of naringenin. Alkaline phosphatase (ALP) activity was measured in cell's precipitates and alizarin-red staining was performed to determine the osteogenic differentiation capacity of the BMSCs. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting were adopted to determine the expression of genes and proteins.Results:The cellular morphology was spindle-shaped, and arranged in radial and whorled patterns. The flow cytometric analysis have confirmed the presence of characteristic surface proteins in the harvested BMSCs. Different concentrations (0-200 μg/ml) of naringenin have no influence on the viability and proliferation rate of the BMSCs. The highest ALP activity was found at culture day 7 and 9 when the concentration of naringenin was 75 and 100 μg/ml. Positive red or dark red stained cells with mineralized nodules can be observed on day 14. The expression of ALP, Runt-related transcription factor 2, CXCR4 and SDF-1a at the gene and protein levels in naringenin-treated cells were significantly higher than those in the control cells. Moreover, AMD3100, an inhibitor of CXCR4, suppressed the expression of the studied genes and proteins.Conclusions:Naringenin does not show toxic effect on BMSCs. Naringenin promotes the expression of the SDF-1a gene and protein via the SDF-1/CXCR4 signaling pathway. A better understanding of the mechanisms of naringenin action would be helpful for developing specific therapeutic strategies to improve bone regeneration after injuries.

Cardiovascular disease is an important cause for morbidity and mortality worldwide. Flavonoids, such as naringin, and naringenin are important natural phytochemicals in the treatment or prevention of various disorders such as obesity, cardiac diseases, diabetes, and metabolic syndrome. Naringin and naringenin have significant therapeutic potential in several diseases through anti-oxidative, anti-inflammatory, and anti-apoptotic actions; these flavonoids play a protective role in human pathophysiology. In this review, based on the latest evidence, we present a summary of the impact of naringin, and naringenin on cardiovascular disease, and analyze and discuss the basic roles of naringin and naringenin and their mechanisms of actions in cardiovascular disease and other vascular dysfunction. The data collected in this review may serve as a comprehensive reference for the effects of naringin, and naringenin in cardiovascular disease, which may be beneficial for further research and for the design of naringin and naringenin analogs as new therapeutic options for cardiovascular diseases.