Potential Of Luteolin Research Articles

Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression

Abstract Diabetes patients are more prone to acute kidney injury (AKI). Endopeptidases known as matrix metalloproteinases (MMPs) cause extracellular matrix destruction and are responsible for ischemic organ damage. Diabetic nephropathy (DN) affects almost one third of all diabetic patients. MMP-2 and MMP-9 lead to the breakdown of the basement membrane of the glomeruli and thereby the advancement of ischemic injury in diabetes. In addition, histone deacetylase-2 (HDAC-2) is the primary regulator of important signalling processes in the diabetic kidney. A possible treatment approach for diabetic kidney preservation is the flavonoid luteolin (LT), which has anti-inflammatory and antioxidant effects. Our aim was to investigate the renoprotective potential of LT in diabetes by modulating MMP-2, MMP-9 and HDAC-2 activity. The expression of MMP-2, MMP-9 and HDAC-2 were statistically higher in streptozotocin-induced diabetic rat renal homogenate after renal ischemic reperfusion injury. These changes were reversed with 2 weeks of pre-treatment with LT (50 mg/kg po). In diabetic rats, pre-treatment with LT significantly reduced oxidative stress, inflammation and fibrosis compared to control animals. Preventive LT prior to renal ischemia showed improvement in body weight, kidney weight/body weight ratio, reversal of renal injury and biochemical changes with lower activity of malondialdehyde (MDA), myeloperoxidase (MPO), hydroxyproline (HP), pathological damage and fibrosis in renal tissue. Our data imply that LT prevents DN in rats by inhibiting MMP-2, MMP-9 and HDAC-2 expression, as well as by lowering the indices of oxidative stress, pro-inflammatory factors and fibrosis.

Luteolin-Rich Extract of Thespesia garckeana F. Hoffm. (Snot Apple) Contains Potential Drug-Like Candidates and Modulates Glycemic and Oxidoinflammatory Aberrations in Experimental Animals.

The present study evaluated the polyphenolic contents and hypoglycemic, antioxidant, and anti-inflammatory effects of the diethyl ether fraction of Thespesia garckeana using various in vitro and in vivo models. Total phenol and flavonoid contents of the extract were 613.65 ± 2.38 and 152.83 ± 1.56 mg/100 g dry weight, respectively. The extract exhibited in vitro antioxidant activities against DPPH, FRAP, LPO, and ABTS with respective half-maximal inhibitory concentration (IC50) values of 30.91 ± 0.23, 16.81 ± 0.51, 41.29 ± 1.82, and 42.39 ± 2.24 μg/mL. In vitro anti-inflammatory studies using membrane stabilization, protein denaturation, and proteinase activities revealed the effectiveness of the extract with respective IC50 values of 54.45 ± 2.89, 93.62 ± 3.04, and 56.60 ± 2.34 μg/mL, while in vitro hypoglycemic analysis of the extract revealed inhibition of α-amylase (IC5064.59 ± 3.29 μg/mL) and enhancement of glucose uptake by yeast cells. Interestingly, the extract demonstrated in vivo hypoglycemic and anti-inflammatory effects in streptozotocin- (STZ-) induced diabetic and xylene-induced ear swelling models, respectively. In addition, the extract improved insulin secretion, attenuated pancreatic tissue distortion and oxidative stress, and increased the activities of superoxide dismutase (SOD), catalase, and reduced glutathione (GSH), while reducing the concentration of LPO in the diabetic rats. A high-performance liquid chromatography (HPLC) analysis identified the presence of catechin (6.81e − 1 ppm), rutin (8.46 e − 1 ppm), myricetin, apigenin (4.019 e − 1 ppm), and luteolin (15.09 ppm) with respective retention times (RTs) of 13.64, 24.269, 27.781, 29.58, and 32.23 min, and these were subjected to a pharmacoinformatics analysis, which revealed their drug-likeness and good pharmacokinetic properties. A docking analysis hinted at the potential of luteolin, the most abundant compound in the extract, for targeting glucose-metabolizing enzymes. Thus, the present study provides preclinical insights into the bioactive constituents of T. garckeana, its antioxidant and anti-inflammatory effects, and its potential for the treatment of diabetes.

The PPARγ-dependent effect of flavonoid luteolin against damage induced by the chemotherapeutic irinotecan in human intestinal cells

Irinotecan (CPT-11) is one of the main agents used to treat colorectal cancer; unfortunately, it is associated with increased intestinal mucositis developing. Luteolin has been shown to prevent damage induced by this chemotherapeutic in mice; thus, in this research, we have investigated luteolin's action mechanism in human intestinal epithelial cells. The potential of luteolin in reducing inflammation and oxidative stress induced by irinotecan in Caco-2 cells was evaluated by PCR through mRNA expression of inflammatory and oxidative genes and by ELISA at the protein level. To assess whether luteolin's ability to control irinotecan-induced damage occurs in a PPARγ dependent manner, experiments were performed on PPARγ downregulated cells. Irinotecan downregulated PPARγ expression and upregulated inflammatory and oxidative genes, while luteolin upregulated PPARγ, HO-1, SOD and decreased expression of IL-1β and iNOS. Interestingly, when the cells were co-stimulated with luteolin and irinotecan, the flavonoid reversed the inflammation and oxidative imbalance evoked by the chemotherapeutic. However, when these experiments were performed in cells downregulated for PPARγ, luteolin lost the capacity to increase PPARγ and reverse the effect of irinotecan in all tested genes, except by IL-1β. The present study showed that the protective effect of luteolin against irinotecan is PPARγ dependent.

Antibiofilm Efficacy of Luteolin Against Single and Dual Species of Candida albicans and Enterococcus faecalis.

Candida albicans and Enterococcus faecalis biofilm-associated infections have been a huge challenge to the medical community. However, the efficacy of natural products against mixed biofilms of C. albicans and E. faecalis still remains largely unexploited. The aim of this study was to evaluate the efficacy of luteolin against planktonic cell growth, adhesion, and biofilm formation of C. albicans and E. faecalis in single and mixed cultures in vitro. The results showed that the minimum inhibitory concentrations of luteolin against planktonic cells of C. albicans, E. faecalis, and mixed cultures were 32 and 64 μg ml–1, respectively. The results displayed that a remarkable variation in biofilm biomass, viability, structure, and composition of single and dual-species biofilms formed by mono- and dual-species biofilms of C. albicans and E. faecalis in the presence of luteolin was confirmed by mainly crystal violet staining assay (CVSA), optical microscope, field emission scanning electron microscope (FESEM), and confocal laser scanning microscope (CLSM). The tolerance of luteolin-treated single- and dual-species biofilms to antibiotics was found to obviously decrease, and the loss of biofilm matrix components (mainly polysaccharides and proteins) was revealed by CLSM. Moreover, luteolin was effective at inactivating biofilm cells, as well as destructing preformed biofilm structures by single and dual species by CVSA, FESEM, and CLSM. Collectively, these data indicate the potential of luteolin as a promising antibiofilm agent for the therapeutic management of biofilm-related infections induced by single and dual species of C. albicans and E. faecalis.

Effects of luteolin on treatment of psoriasis by repressing HSP90

AimsThis study was conducted to further clarify the efficacy and potential of luteolin in treating psoriasis and to explore its inner mechanisms. MethodsA pharmacology network displayed the construction of a drug disease target prediction method. The prediction technique was validated via cell experiments in vitro and animal experiments in vivo, respectively. The effects of IFN-γ and luteolin were detected in HaCaT cells. The secretion of exosome and expression of mRNA and protein were detected to explain the relationship between luteolin's regulation of HSP90 (HSP90α and HSP90β) activity in vitro. An in vivo psoriasis mouse model was established to further explore the efficacy of luteolin. Morphological and histological changes in skin lesions were observed, and the CD63, calnexin, Hsp90α, and Hsp90β protein expression was analyzed. Peripheral blood mononuclear cells (PBMCs) were separated and detected via flow pattern analysis to determine how luteolin effects the immune cells in a psoriasis model. ResultsLuteolin as a candidate compound is predicted to have a molecular-target correspondence with HSP90 according to a pharmacology network analysis. Cell experiments indicated that the pathogenesis of psoriasis was significantly related to the increase in IFN-γ, which promoted the transcriptional expression and exosome secretion of HSP90 in HaCaT cells; conversely, luteolin inhibited those and alleviated the promotion of IFN-γ. The effect of luteolin on HSP90 was slightly weaker than that of INF-γ. Animal experiments indicated that the efficacy of luteolin was similar to that of 17-AAG, which both alleviated skin tissue lesions and symptoms, improved the expression of Hsp90 mRNA and protein in skin tissue, and promoted exosome secretion of Hsp90 in plasma. For immune cells in mice with psoriasis, luteolin reduced the proportion of Th1/Th2 and Th17/Treg and inhibited the increase in Th1 and Th17 in the peripheral blood. ConclusionLuteolin can relieve the lesions and symptoms of psoriasis through reversing the effects of IFN-γ, inhibiting the expression and exosome secretion of HSP90, and regulating the proportion of immunocytes. Therefore, this study provides the possible mechanisms and potential utilization of luteolin as a novel treatment for psoriasis.

Bioavailability and Pharmaco-therapeutic Potential of Luteolin in Overcoming Alzheimer's Disease.

Luteolin is a naturally occurring, yellow crystalline flavonoid found in numerous dietary supplements we frequently have in our meals. Studies in the last 2 decades have revealed its therapeutic potential to reduce the Alzheimer's disease (AD) symptoms in various in vitro and in vivo models. The anti-Alzheimer's potential of luteolin is attributed to its ability to suppress Aβ as well as tau aggregation or promote their disaggregation, down-regulate the expression of COX-2, NOS, MMP-9, TNF-α, interleukins and chemokines, reduce oxidative stress by scavenging ROS, modulate the activities of transcription factors CREB, cJun, Nrf-1, NF-κB, p38, p53, AP-1 and β-catenine and inhibiting the activities of various protein kinases. In several systems, luteolin has been described as a potent antioxidant and anti-inflammatory agent. In addition, we have also discussed about the bio-availability of the luteolin in the plasma. After being metabolized luteolin persists in plasma as glucuronides and sulphate-conjugates. Human clinical trials indicated no dose limiting toxicity when administered at a dose of 100 mg/day. Improvements in the formulations and drug delivery systems may further enhance the bioavailability and potency of luteolin. The current review describes in detail the data supporting these studies.

Assessment of in vitro antitumor potential of luteolin loaded polymeric nanofromulations

Assessment of in vitro antitumor potential of luteolin loaded polymeric nanofromulations

Inhibitory effects of delphinidin and luteolin on genotoxicity induced by K2B3O3F4OH) in human lymphocytes in vitro

AbstractThe genotoxicity of halogenated boroxine [K