Therapeutic Effect Of Luteolin Research Articles

Luteolin targets the AGE-RAGE signaling to mitigate inflammation and ferroptosis in chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and precancerous lesion in stomach cancer. Abnormal activation cellular ferroptosis further damages gastric tissue, which is susceptible to inflammation. Luteolin has powerful anti-inflammatory and regulatory potential for cellular ferroptosis. We aimed to clarify the involvement of luteolin in inflammation and ferroptosis during CAG. Luteolin targets were searched to identify intersecting genes in the chronic atrophic gastritis disease database. The AGE-RAGE pathway is a potential target of luteolin for the treatment of chronic atrophic gastritis and a binding site between luteolin and RAGE was predicted through a computer simulation of molecular docking. We established a CAG rat model using N-methyl-N-nitro-N-nitroguanidine. The therapeutic effect of luteolin on CAG was detected using western blotting, qPCR, hematoxylin and eosin staining, lipid oxidation (MDA), and Fe2+ assays. Luteolin inhibited the AGE-RAGE signaling pathway and reduced the inflammatory response in gastric tissues. Additionally, luteolin downregulated the concentration of (MDA) and Fe2+, and CAG downregulated the expression levels of ACSL4 and NOX1 and upregulated the expression levels of FIH1 and GPX4 ferroptosis-related proteins, thus inhibiting the ferroptosis of gastric tissue cells, which had a therapeutic effect on CAG.

Therapeutic administration of Luteolin protects against Escherichia coli-derived Lipopolysaccharide-triggered inflammatory response and oxidative injury

Endometritis reduces reproductive effectiveness and leads to significant financial losses in the dairy sector. Luteolin is a natural phyto-flavonoid compound with many biological activities. However, the therapeutic effect of Luteolin against lipopolysaccharides (LPS)-induced endometritis has not yet been explored. A total of eighty female Kunming mice were randomly assigned into four treatment groups (n = 20). Following a successful initiation of the endometritis model by LPS, Luteolin was intraperitoneally administered three times, at six-hour intervals between each injection in the Luteolin groups. The histopathological findings revealed that Luteolin significantly alleviated uterine injury induced by LPS. Moreover, Luteolin suppressed the synthesis of pro-inflammatory mediators [interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α] while promoting the synthesis of an anti-inflammatory mediator (IL-10) altered by LPS. Furthermore, Luteolin significantly mitigated the LPS-induced oxidative stress by scavenging malondialdehyde (MDA) and reactive oxygen species (ROS), accumulation and boosting the capacity of antioxidant enzyme activities such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (Gpx1) in the uterine tissue of mice. Additionally, injection of Luteolin markedly increased the expression of Toll-like receptors (TLR) 4 both at mRNA and protein levels under LPS stimulation. Western blotting and ELISA findings demonstrated that Luteolin suppressed the activation of the NF-κB pathway in response to LPS exposure in the uterine tissue of mice. Notably, Luteolin enhanced the anti-oxidant defense system by activating the Nrf2 signaling pathway under LPS exposure in the uterine tissue of mice. Conclusively, our findings demonstrated that Luteolin effectively alleviated LPS-induced endometritis via modulation of TLR4-associated Nrf2 and NF-κB signaling pathways.

Protective effect of luteolin on acute lung injury in sepsis mice

Objective To investigate the potential therapeutic effect of luteolin on sepsis-induced ALI and the underlying mechanisms. Methods Total of 50 mice were randomly(random number) divided into five groups: a sham control group, a sepsis-induced ALI group, and three sepsis groups pre-treated with 20, 40, and 80 mg/kg body weight luteolin. Mice in the treatment groups were pre-treated with luteolin at the respective oral dose two days before ALI induction. The lungs were isolated for histopathological examinations, and the bronchoalveolar lavage fluid (BALF) was collected for biochemical analyses. Results Luteolin significantly attenuated sepsis-induced ALI. Additionally, luteolin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice. Pulmonary myeloperoxidase (MPO) activity was lower in the luteolin-pre-treated sepsis groups than in the sepsis group. The mechanism underlying the protective effect of luteolin on sepsis is related to the up-regulation of certain antioxidation genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutases (SODs), and heme oxygenase 1 (HO-1), and the reduction of inflammatory responses through blockage of the activation of the nuclear factor (NF)-κB pathway. Conclusions Luteolin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity, suggesting that luteolin may be a potential therapeutic agent for sepsis-induced ALI. Key words: Luteolin; Sepsis; COX-2; SODs; iNOS

Luteolin attenuates high glucose-induced podocyte injury via suppressing NLRP3 inflammasome pathway

AimsDiabetic nephropathy is a growing health concern, which is reported to be associated with inflammation. Luteolin has been explored for the treatment of some diabetic complications. Although several studies have verified the effect of luteolin on diabetic nephropathy, the mechanism by which the therapeutic effects of luteolin on diabetic nephropathy has not been established. Therefore, we aimed to investigate the effect of luteolin on diabetic nephropathy and its underlying mechanism. Main methodsWe used western blot, Real-time PCR, immunofluorescence and flow cytometry to analyze the effects of luteolin on podocyte injury and NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in high glucose (HG) condition. Reactive oxygen species (ROS) generation was measured by flow cytometry and malondialdehyde (MDA) level. To investigate the potential mechanism, we examined cell apoptosis upon transfection of siNLRP3. Key findingsWe showed that luteolin treatment could protect podocyte against HG-induced cell apoptotic and mitochondrial membrane potential collapse. In addition, luteolin significantly reduced NLRP3 inflammasome formation and subsequent interleukin-1β (IL-1β) secretion in HG-induced MPC-5 cells. Interestingly, siNLRP3 abolished the effect of luteolin on cell apoptosis, suggesting that the anti-apoptotic effect was found to be mostly related to NLRP3 inflammasome. SignificanceIn summary, our data demonstrated the abilities of luteolin to inhibit podocyte injury and NLRP3 inflammasome activation, which could be used in the treatment of diabetic nephropathy.

Ameliorative effects of luteolin against endometriosis progression in vitro and in vivo

Endometriosis is a common gynecological disease in reproductive-aged women. Generally, accumulation of backflow and debris of endometrial tissue develops into a lesion outside of the endometrium, inducing severe pelvic pain and infertility in some patients. Hormone therapy and surgery are the main treatments available, but various therapeutic phytochemicals are being reviewed in animal studies or clinical trials for endometriosis patients nowadays. However, the therapeutic effects of luteolin in human endometriosis have not been studied well. Here, we demonstrate that luteolin exerts antiproliferative and apoptotic effects in human VK2/E6E7 and End1/E6E7 and in an animal endometriosis model. Luteolin inhibits cell proliferation through cell cycle arrest and induces apoptosis through DNA fragmentation in VK2/E6E7 and End1/E6E7 cells. Cytosolic calcium levels, ROS production and lipid peroxidation also increased dose-dependently (0, 5, 10 and 20 μM) in the treatment with luteolin. In VK2/E6E7 and End1/E6E7 cells, luteolin decreased ERK1/2, JNK and PI3K/AKT signal proteins while activating P38. In addition, intraperitoneal injection of luteolin in the endometriosis mouse model reduced lesion size compared to vehicle-injected mice. Ccne1, Cdk2 and Cdk4 were significantly down-regulated in the autoimplanted endometriosis lesions of mice intraperitoneally injected with luteolin. Knockdown of CCNE1 mRNA in VK2/E6E7 and End1/E6E7 cells decreased cell viability through inhibition of G0/G1 phase progression and increased apoptosis. Together, our results imply that luteolin suppresses endometriosis development by regulation of the PI3K/AKT and MAPK signal proteins as well as the expression of CCNE1 in vitro and in vivo.

Abstract 4159: Therapeutic effects of luteolin against progestin-dependent breast cancer involves induction of apoptosis, and suppression of both stem-cell-like cells and angiogenesis

Abstract Clinical and epidemiological evidence show that combined estrogen (E) and progestin (P) hormone replacement therapy (HRT) increases the risk of breast cancer in postmenopausal women. Tumor progression is dependent on cell survival and angiogenesis, which provides nutrients vital to the developing cancer. We have shown that physiological levels of P (10 nM), including medroxyprogesterone acetate (MPA), which is widely used in HRT, increases the production of the potently angiogenic vascular endothelial growth factor (VEGF), in human breast cancer cells both in vitro and in vivo. The anti-progestin RU-486 blocks this effect, suggesting the involvement of progesterone receptors in the process (Int J Cancer, 2001, 92:469). Evidence from our laboratory using in vivo breast cancer models suggests that P accelerates the development of tumors from latent tumorigenic cells, leading to the development of palpable tumors (Cancer Res., 2007, 67:9929; Clin Can Res, 2006, 12:4062), a process that may be attributed to increased production of VEGF. RU-486 blocks P-dependent VEGF production and thereby reduces tumor growth; however, the anti-progestin has severe side-effects and therefore cannot be used in the long-term. Recently, we have been studying less toxic naturally-occurring compounds for their ability to block P-dependent tumor progression. We tested the effects of the flavonoid luteolin, which is commonly found in fruits and vegetables, on proliferation of BT-474 and T47-D breast cancer cells and their production of VEGF. Luteolin treatment (10-100 μM) for 24 h reduced tumor cell viability, induced apoptosis, blocked P-dependent increases in CD44 high stem-cell-like cells, and blocked production of P-dependent VEGF induction in vitro. Interestingly, luteolin also reduced the ability of cells to form mammospheres, a characteristic of self-renewable cells. Furthermore, luteolin (20 mg/kg, i.p.) suppressed the growth of MPA-dependent BT-474 human xenograft tumors in nude mice. Immunohistochemical analysis showed that luteolin significantly reduced P-induced VEGF production in vitro (p<0.05). Our findings strongly suggest that luteolin disrupts tumor progression by blocking several processes that are vital to P-dependent tumor development. We contend therefore that luteolin is a compound with valuable therapeutic properties against P-dependent human breast cancer. Supported by a COR award from the College of Veterinary Medicine. Citation Format: Matthew Thomas Cook, Yayun Liang, Sandy Goyette, Benford Mafuvadze, Cynthia Besch-Williford, Salman Hyder. Therapeutic effects of luteolin against progestin-dependent breast cancer involves induction of apoptosis, and suppression of both stem-cell-like cells and angiogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4159. doi:10.1158/1538-7445.AM2015-4159

The comparative study of the medical action of lyuteolin, rosmarinic acid and echinochrom A at experimental stress-induced cardiopathology

The method of the physical load in condition of the coronary circulation of the blood disturbance, caused mesaton injection, induced development rat cardiopathology, bring about of the heart function decompensation and 40% death of experimenthal animals. Under electronic-microscopic study of rat cardiomyocytes are discovered signs to disorganizations of mitochondrial apparatus of these cells. Administration to therapeutic mode of luteolin and echinochrome A preparations has provided to 100% animal probability of survival. At the same time, mitochondrial apparatus of cardiomyocytes was characterized by the normal parameter i.e. given preparations have provided of defensive adative effect at cardiomyocytes level. Similar activities for rosmarinic acid have not shown. Study some metabolic parameter and endocrine status animal has also allowed revealing of therapeutic effect of luteolin and echinochrome A. Findings be evidence of that echinochrome A and luteolin capable to play the important positive role in metabolism of cardiomyocytes by stimulating of mitochondrial biogenesis and by changing of adaptative mechanisms of the organism cardiovascular system protection.