Gut Microbiota and Inflammation Modulation in a Rat Model for Ulcerative Colitis after the Intraperitoneal Administration of Apigenin, Luteolin, and Xanthohumol.

Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colon, with symptomatology influenced by factors including environmental, genomic, microbial, and immunological interactions. Gut microbiota dysbiosis, characterized by bacterial population alterations, contributes to intestinal homeostasis disruption and aberrant immune system activation, thereby exacerbating the inflammatory state. This study assesses the therapeutic efficacy of intraperitoneal (IP) injected flavonoids (apigenin, luteolin, and xanthohumol) in the reduction of inflammatory parameters and the modulation of the gut microbiota in a murine model of ulcerative colitis. Flavonoids interact with gut microbiota by modulating their composition and serving as substrates for the fermentation into other anti-inflammatory bioactive compounds. Our results demonstrate the effectiveness of luteolin and xanthohumol treatment in enhancing the relative abundance of anti-inflammatory microorganisms, thereby attenuating pro-inflammatory species. Moreover, all three flavonoids exhibit efficacy in the reduction of pro-inflammatory cytokine levels, with luteolin strongly demonstrating utility in alleviating associated physical UC symptoms. This suggests that this molecule is a potential alternative or co-therapy to conventional pharmacological interventions, potentially mitigating their adverse effects. A limited impact on microbiota is observed with apigenin, and this is attributed to its solubility constraints via the chosen administration route, resulting in its accumulation in the mesentery.

Synergistic effect of paeoniflorin combined with luteolin in alleviating Lipopolysaccharides-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is an acute multifactorial infectious disease caused by trauma, pneumonia, shock and sepsis. Paeoniae Radix Rubra (Paeonia lactiflora Pall. or Paeonia veitchii Lynch, Chishao in Chinese, CS) and Salviae Miltiorrhizae Radix et Rhizoma (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese, DS) are common traditional Chinese medicines (TCMs). CS-DS herb pair has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, appearing in a variety of prescriptions. However, it is still unclear for the effect and active ingredients of the herb pair on ALI. AIM OF THE STUDY: The study investigated the effect and active ingredients of CS-DS herb pair and demonstrated the synergistic effect and mechanisms of the active ingredients. MATERIALS AND METHODS: Lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage cells and BALB/c mice were used to establish an ALI model to investigate the effect of CS-DS herb pair on ALI. Network pharmacology and molecular docking were used to analyze the active ingredients and potential mechanisms of the herb pair. The synergistic effects and mechanisms of active ingredients on ALI were validated by in vitro and in vivo experiments. RESULTS: CS-DS herb pair had a synergistic effect on LPS-induced ALI. Based on the network pharmacology, the compounds paeoniflorin and luteolin were screened. Both paeoniflorin and luteolin had good affinity for NF-κB and MAPK by molecular docking. LPS stimulation of RAW264.7 cells resulted in a significant increase in ROS, NO, TNF-α, IL-6 and IL-1ß, while the paeoniflorin combined with luteolin significantly reduced their expressions. In the LPS-induced ALI model, the combination also reduced the expression of inflammatory factors and oxidative stress levels. Furthermore, LPS activated the NF-κB and MAPK signaling pathways, whereas the combination decreased the expression of proteins in both pathways. CONCLUSION: CS-DS herb pair alleviated LPS-induced ALI with the active ingredients paeoniflorin and luteolin, which suppressed inflammation and oxidative stress via regulation of NF-κB and MAPK signaling pathways.

Unraveling the pharmacodynamic substances and possible mechanism of Trichosanthis Pericarpium in the treatment of coronary heart disease based on plasma pharmacochemistry, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.

In silico anti-alzheimer study of phytochemicals from Lamiaceae family through GSK3-ß inhibition.

Glycogen synthase kinase 3-beta (GSK3-ß) is a serine-threonine protease expressed in the brain, and its hyperactivity is considered the underlying cause of Alzheimer's disease. This enzyme requires an ATP molecule in its N-terminal lobe to phosphorylate its substrates, with the most important substrate being the Tau protein. This study focuses on the inhibitory mechanism of four naturally occurring compounds-apigenin, luteolin, rosmarinic acid, and salvianolic acid-from the Laminaceae family against GSK3-ß. The orientation of the ligands within the ATP-binding pocket of GSK3-ß and their binding energy were determined through molecular docking. Additionally, molecular dynamics simulations was conducted to study the conformational changes induced by the ligands in the protein structure. The results showed that apigenin and salvianolic acid achieved deeper parts of the cavity compared to luteolin and rosmarinic acid and formed stable complexes with the enzyme. In the rosmarinic acid complex, the enzyme exhibited the most exposed conformation. On the other hand, luteolin binding caused a small closure of the opening, suggesting a potentially ATP-competitive role. Our results suggest these compounds as lead candidates for the design of GSK3-ß inhibitors.

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

Luteolin: Nature's promising warrior against Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDs) are defined as the slow loss of a group of neurons that are particularly sensitive. Due to the intricate pathophysiological processes underlying neurodegeneration, no cure exists for these conditions despite the extensive research and advances in our knowledge of the onset and course of NDs. Hence, there is a medical need for the creation of a novel therapeutic approach for NDs. By focusing on numerous signaling pathways, some natural substances derived from medicinal herbs and foods have demonstrated potent activity in treating various NDs. In this context, flavonoids have recently attracted increased popularity and research attention because of their alleged beneficial effects on health. By acting as antioxidant substances, nutritional supplements made up of flavonoids have been found to lessen the extent of NDs like Alzheimer's disease (AD) and Parkinson's disease (PD). Luteolin is a flavone that possesses potent antioxidant and anti-inflammatory properties. As a consequence, luteolin has emerged as an option for treatment with therapeutic effects on many brain disorders. More research has focused on luteolin's diverse biological targets as well as diverse signaling pathways, implying its potential medicinal properties in several NDs. This review emphasizes the possible use of luteolin as a drug of choice for the treatment as well as the management of AD and PD. In addition, this review recommends that further research should be carried out on luteolin as a potential treatment for AD and PD alongside a focus on mechanisms and clinical studies.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Preparation of luteolin loaded nanostructured lipid carrier based gel and effect on psoriasis of mice.

This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 µg/cm2) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 µg/cm2). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases.

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

BACKGROUND: Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies. AIMS: In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective. RESULTS: The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions. CONCLUSIONS: Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.

Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation.

BACKGROUND: The prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear. PURPOSE: To investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex). STUDY DESIGN AND METHODS: The components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia-reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments. RESULTS: The HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway. CONCLUSION: This work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.

Preparation and evaluation of luteolin-loaded PLA-based shape memory gastroretentive drug delivery systems.

Luteolin, a natural flavonoid, is gaining growing attention for its potential in the treatment of gastric cancer. However, its clinical application is limited by factors such as poor aqueous solubility. This study aimed to develop a novel gastroretentive drug delivery system (GRDDS) to both enhance the oral bioavailability of luteolin and prolong its release and in vivo circulation time. Out of 10 luteolin-loaded PLA-based shape memory films prepared in this study, the LPC-PLA/PEG(7/3) formulation incorporated with PEG, HPMC, and NaHCO3 exhibited optimal properties in terms of drug release and inhibitory activity against SGC-7901 cells. Moreover, small-animal imaging revealed that LPC-PLA/PEG(7/3) exhibited a prolonged gastric retention time of approximately 8 h. Furthermore, the pharmacokinetic studies indicated a 354 % increase in the oral bioavailability of LPC-PLA/PEG(7/3) in rats compared to luteolin. In sum, a novel GRDDS was developed to enhance the relative bioavailability of luteolin, offering a potential strategy for practical oral administration.

Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions.

BACKGROUND: Postoperative abdominal adhesion (PAA) is a common postoperative complication. Clinically, various methods have been used to prevent the occurrence of PAA, such as drugs and physiotherapy; however, no satisfactory results have been obtained. Luteolin (LUT) is a natural flavonoid that reduces inflammation and acts as an antioxidant. This research aimed to examine the impact and mechanism of LUT in reducing PAA. METHODS: C57/BL6 mice were used in vivo experiments. PAA model was established using a brush friction method. Visual scoring and hematoxylin and eosin staining were used to score the severity of adhesions. Network pharmacology was used to infer potential targets and core pathways of LUT. Hydrogen peroxide (H2O2) was used to induce oxidative stress in vitro, while the reactive oxygen species (ROS) assay kit was used to evaluate oxidative stress levels. Western blotting, cell immunofluorescence, and multiple immunofluorescence assays were used to detect α-SMA, vimentin, E-cadherin, collagen I, or AKT phosphorylation level. Scratch assay was used to detect cell migration. RESULTS: LUT reduced the degree of PAA in mice. It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells. Network pharmacology analysis showed that LUT likely exerted anti-adhesion activity by regulating the PI3K-Akt signaling pathway. Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells. LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression. CONCLUSION: LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA. To this end, LUT has potential in PAA therapy.

Luteolin suppresses oral carcinoma 3 (OC3) cell growth and migration via modulating polo-like kinase 1 (PLK1) expression and cellular energy metabolism. / æœ¨çŠ€è‰ç´ é€šè¿‡è°ƒèŠ‚PLK1è¡¨è¾¾å’Œç»†èƒžèƒ½é‡ä»£è°¢æŠ‘åˆ¶å£è ”ç™Œç»†èƒžOC3的生长和迁移.

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).

Luteolin Pretreatment Ameliorates Myocardial Ischemia/Reperfusion Injury by lncRNA-JPX/miR-146b Axis.

Background: In the present study, we aimed to find out whether luteolin (Lut) pretreatment could ameliorate myocardial ischemia/reperfusion (I/R) injury by regulating the lncRNA just proximal to XIST (JPX)/microRNA-146b (miR-146b) axis. Methods: We established the models in vitro (HL-1 cells) and in vivo (C57BL/6J mice) to certify the protection mechanism of Lut pretreatment on myocardial I/R injury. Dual luciferase reporter gene assay was utilized for validating that JPX could bind to miR-146b. JPX and miR-146b expression levels were determined by RT-qPCR. Western blot was utilized to examine apoptosis-related protein expression levels, including cleaved caspase-9, caspase-9, cleaved caspase-3, caspase-3, Bcl-2, Bax, and BAG-1. Apoptosis was analyzed by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, as well as flow cytometry. Animal echocardiography was used to measure cardiac function (ejection fraction (EF) and fractional shortening (FS) indicators). Results: miR-146b was demonstrated to bind and recognize the JPX sequence site by dual luciferase reporter gene assay. The expression level of miR-146b was corroborated to be enhanced by H/R using RT-qPCR (P < 0.001 vs. Con). Moreover, JPX could reduce the expression of miR-146b, whereas inhibiting JPX could reverse the alteration (P < 0.001 vs. H/R, respectively). Western blot analysis demonstrated that Lut pretreatment increased BAG-1 expression level and Bcl-2/Bax ratio, but diminished the ratio of cleaved caspase 9/caspase 9 and cleaved caspase 3/caspase 3 (P < 0.001 vs. H/R, respectively). Moreover, the cell apoptosis change trend, measured by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, along with flow cytometry, was consistent with that of apoptosis-related proteins. Furthermore, pretreatment with Lut improved cardiac function (EF and FS) (P < 0.001 vs. I/R, respectively), as indicated in animal echocardiography. Conclusion: Our results demonstrated that in vitro and in vivo, Lut pretreatment inhibited apoptosis via the JPX/miR-146b axis, ultimately improving myocardial I/R injury.

Occurrence of Luteolin in the Greek Flora, Isolation of Luteolin and Its Action for the Treatment of Periodontal Diseases.

Higher plants possess the ability to synthesize a great number of compounds with many different functions, known as secondary metabolites. Polyphenols, a class of flavonoids, are secondary metabolites that play a crucial role in plant adaptation to both biotic and abiotic environments, including UV radiation, high light intensity, low/high temperatures, and attacks from pathogens, among others. One of the compounds that has received great attention over the last few years is luteolin. The objective of the current paper is to review the extraction and detection methods of luteolin in plants of the Greek flora, as well as their luteolin content. Furthermore, plant species, crop management and environmental factors can affect luteolin content and/or its derivatives. Luteolin exhibits various biological activities, such as cytotoxic, anti-inflammatory, antioxidant and antibacterial ones. As a result, luteolin has been employed as a bioactive molecule in numerous applications within the food industry and the biomedical field. Among the different available options for managing periodontitis, dental care products containing herbal compounds have been in the spotlight owing to the beneficial pharmacological properties of the bioactive ingredients. In this context, luteolin's anti-inflammatory activity has been harnessed to combat periodontal disease and promote the restoration of damaged bone tissue.

Exploration of the effect and mechanism of Scutellaria barbata D. Don in the treatment of ovarian cancer based on network pharmacology and in vitro experimental verification.

The mortality rate of ovarian cancer is the highest among gynecological cancers, posing a serious threat to women health and life. Scutellaria barbata D. Don (SBD) can effectively treat ovarian cancer. However, its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of SBD in the treatment of ovarian cancer using network pharmacology, and to verify the experimental results using human ovarian cancer SKOV3 cells. The Herb and Disease Gene databases were searched to identify common targets of SBD and ovarian cancer. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind SBD. Finally, the molecular docking and main possible pathways were verified by experimental studies. Cell proliferation, the mRNA expression level of key genes and signaling pathway were all investigated and evaluated in vitro. A total of 29 bioactive ingredients and 137 common targets in SBD were found to inhibit ovarian cancer development. The active ingredients identified include quercetin, luteolin, and wogonin. Analysis of the PPI network showed that AKT1, VEGFA, JUN, TNF, and Caspase-3 shared centrality among all target genes. The results of the KEGG pathway analysis indicated that the cancer pathway, PI3K-Akt signaling pathway, and MAPK signaling pathways mediated the effects of SBD against ovarian cancer progression. Cell experiments showed that quercetin, luteolin, and wogonin inhibited the proliferation and clone formation of SKOV3 cells and regulated mRNA expression of 5 key genes by inhibiting PI3K/Akt signaling pathway. Our results demonstrate that SBD exerted anti-ovarian cancer effects through its key components quercetin, luteolin and wogonin. Mechanistically, its anti-cancer effects were mediated by inhibition of the PI3K/Akt signaling pathways. Therefore, SBD might be a candidate drug for ovarian cancer treatment.

Application of Luteolin in Neoplasms and Nonneoplastic Diseases.

Researchers are amazed at the multitude of biological effects of 3',4',5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and pro-oxidant, as well as antimicrobial, anti-inflammatory, and cancer-preventive, properties. The anticancer properties of luteolin constitute a mosaic of pathways due to which this flavonoid influences cancer cells. Not only is it able to induce apoptosis and inhibit cancer cell proliferation, but it also suppresses angiogenesis and metastasis. Moreover, luteolin succeeds in cancer cell sensitization to therapeutically induced cytotoxicity. Nevertheless, apart from its promising role in chemoprevention, luteolin exhibits numerous potential utilizations in patients with conditions other than neoplasms, which include inflammatory skin diseases, diabetes mellitus, and COVID-19. This review aims to present the multidimensionality of the luteolin's impact on both neoplastic and nonneoplastic diseases. When it comes to neoplasms, we intend to describe the complexity of the molecular mechanisms that underlay luteolin's anticancer effectiveness, as well as to prove the usefulness of integrating this flavonoid in cancer therapy via the analysis of recent research on breast, colon, and lung cancer. Regarding nonneoplastic diseases, this review aims to emphasize the importance of researching the potential of luteolin in areas such as diabetology, virology, and dermatology as it summarizes the most important discoveries in those fields regarding its application.

Mechanisms of action underlying Shentong Zhuyu decoction based treatment of rheumatoid arthritis using systems biology and computer-aided drug design.

Rheumatoid arthritis is an autoimmune disease characterized by chronic polyarticular pain, for which no cure currently exists. In Chinese medicine, rheumatoid arthritis (RA) is believed to be caused by phlegm and blood stagnation. Shentong Zhuyu decoction can be used to treat RA, as it promotes blood circulation, resolves blood stasis, and relieves pain. In our study, we used network pharmacology and computer-aided drug design to evaluate the components, active compounds, and targets of Shentong Zhuyu decoction (STZY). Our results suggest that STZY contains active compounds such as quercetin, luteolin, and formononetin that regulate immune network targets. RA associated genes are enriched in pathways including those associated with nuclear factor kappa B, phosphatidylinositol-3-kinase/AKT, and hypoxia inducible factor 1 signaling. The main active compounds in STZY (quercetin and luteolin) were derived from Achyranthis Bidentatae Radix, Carthami Flos, licorice, Cyperi Rhizoma, and Myrrha and targeted the pro-inflammatory cytokines interleukin 2, interleukin 1 alpha, interleukin 1 beta, and interleukin 6. In addition, the compounds quercetin, luteolin, and formononetin in these herbs can target the anti-inflammatory cytokines interleukin 4 and interleukin 10. Our results suggest that STZY can balance the immune network, promote an anti-inflammatory environment, and reduce the clinical symptoms of RA. Based on the close relationship between inflammatory response and osteoclast formation, we hypothesized that STZY may inhibit inflammation and alleviate bone destruction in RA. Our findings indicate that STZY can treat RA through multiple components, targets, and pathways. This study may provide a reference for the clinical application of STZY in RA treatment.

Luteolin is a potential inhibitor of COVID-19: An in silico analysis.

The severe respiratory syndrome 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread explosively, raising global health concerns. Luteolin shows antiviral properties, but its effect on SARS-CoV-2 and the associated mechanisms are not elucidated. We used network pharmacology, molecular docking and molecular dynamics to provide potential molecular support of luteolin (3,4,5,7-tetrahydroxyflavone) (LUT) against COVID-19. We employed network pharmacology, molecular docking, and molecular dynamics techniques to investigate how LUT affected COVID-19. Several databases were queried to determine potential target proteins related to LUT and COVID-19. Protein-protein interaction network was constructed, and core targets were filtered by degree value. Following that, functional enrichment was conducted. Molecular docking was utilized to ensure LUT was compatible with core target proteins. Finally, molecular dynamics was used to analyze the effects of the LUT on the optimal hub target. A total of 64 potential target genes for treating COVID-19 were identified, of which albumin, RAC-alpha serine/threonine-protein kinase, caspase-3, epidermal growth factor receptor, heat shock protein HSP 90-alpha, and mitogen-activated protein kinase 1 might be the most promising. In addition, molecular docking results showed that LUT could interact with SARS-CoV-2 major protease 3CL. LUT can bind to the active sites of 3CL protease and mitogen-activated protein kinase 1, showing an anti-SARS-CoV-2 potential.

Luteolin inhibits Porphyromonas gingivalis growth and alleviates alveolar bone destruction in experimental murine periodontitis.

Periodontal disease is a major oral infectious disease that destroys alveolar bones and causes tooth loss. Porphyromonas gingivalis is a key pathogen that plays a crucial role in periodontitis. In our previous study on the anti-P. gingivalis activity of flavonoid, luteolin, a major flavonoid in edible plants, inhibited the proteolytic activity of gingipains, the major virulence factor in P. gingivalis. This study demonstrated luteolin in vitro and in vivo anti-bacterial activities. Thus, luteolin inhibits planktonic growth and biofilm formation in P. gingivalis. Furthermore, oral administration of luteolin alleviated maxillary alveolar bone resorption (ABR) in murine periodontitis induced by P. gingivalis infection. These results indicate that luteolin may be a potential therapeutic compound that targets P. gingivalis by hindering its growth, biofilm formation, and ABR in the oral cavity.