luteolin

Eclipta alba (Bhringraj) in ayurveda has been widely used as a traditional medicine for its multi-therapeutic properties for ages. Luteolin (LTL), wedelolactone (WDL) and apigenin (APG) are the three main bioactive phytochemicals present in Eclipta alba extract. However there was a lack of sensitive bioanalytical method for the pharmacokinetics of these free compounds in plasma which majorly contributes for their activities after oral administration of Eclipta alba. The present study aims to develop a sensitive, rapid and reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous estimation of mice plasma concentrations of LTL, WDL and APG using quercetin as an internal standard for the pharmacokinetic analysis. Analytes were separated on Phenomenex Luna C18 (150 x 4.6 mm, 3.0 µm) column with mobile phase containing methanol: acetonitrile (90: 10, v/v) and 0.1% formic acid in 10 mM ammonium formate buffer in the ratio of 70: 30 (v/v) in isocratic mode. Liquid-liquid extraction was optimized using Hansen solubility parameters and diethyl ether finalized as an extraction solvent for the recovery ranging from 61-76% for all analytes in mice plasma. The validated method has an accuracy and precision over the linearity range of 0.1 – 200 ng/mL with a correlation coefficient (r2) of ≥0.997. The intra and inter-day assay accuracy was between 98.17-107% and 95.83-107.89% respectively and the intra and inter day assay precision ranged from 0.37-6.05% and 1.85-10.76%, respectively for all the analytes. This validated method can be used for future clinical investigation studies of Eclipta alba extracts.

Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels.

Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE.

Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.

Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia.

Trial Registration: UMIN-CTR: UMIN000042327

Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd.

Keywords: Chrysanthemum, luteolin, uric acid, purine base

Schistosomiasis and trichuriasis affects millions of people worldwide and are caused by blood flukes and whipworms, respectively. Only a handful of anthelmintic drugs exist to treat these infections and the pipeline for the next generation of anthelmintic drugs is sparse, precipitating the need for new drug development. In this context, medicinal plants present a viable source of novel anthelmintic compounds. This inspired us to study the selected naturally occurring compounds derived from a Bhutanese daisy medicinal plant,
Ajania nubigena for their anthelmintic activities. Here, using the xWORM motility assay, we demonstrate that two compounds, luteolin (3) and (3R,6R)-linalool oxide acetate (1), display significant broad-spectrum anthelmintic activity against two of the most important genera of human helminth parasites, the nematode whipworm and the platyhelminth blood fluke. Luteolin exhibited the best activities with IC50
values of 5.8μg/mL against schistosomes and 9.7μg/mL against whipworms. Using scanning electron microscopy we showed that luteolin damages the tegument of blood flukes and induces abnormalities in the bacillary bands/glands and cuticles of whipworms. Intriguingly, our previous study showed that luteolin (3) was effective against multi-drug resistant Plasmodium falciparum malaria. Due to its broad-spectrum anti-parasitic activities, luteolin (3) is a desirable drug
lead scaffold, which could be used for developing effective compounds to control and treat numerous tropical diseases.

A highly invasive Du145-III subline was isolated by three successive passages of the parental Du145 prostate tumor cell line (Du145-P) through a Boyden chamber with matrigel-coated membrane support. Du145-III cells showed great invasion potential based on their increased ability to spread/migrate and enhanced expression/secretion of the matrix metalloproteinase 9 (MMP9). Du145-III cells exerted vasculogenic mimicry (VM) properties, reminiscent of endothelial cell characteristics and expressed elevated levels of cancer stem cell (CSC) markers, including Nanog, Sox2, CD44 and ABCG2 and ability to self-renew. Of prominence, MMP9 was required for the induction of VM and for increased stemness in Du145-III cells. Using Du145-III as a model, the effects of dietary flavonoids, luteolin and quercetin, were evaluated on stemness and invasion capacity of Du145-III cells in relation to JNK signaling pathway activation. These flavonoids depressed the malignancy of highly invasive Du145-III cell...

SIDERITIS SCARDICA Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in ext...

Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importan...

The major flavonoids present in the leaves and flowers of the cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) cultivars Felina and Futura are orientin (1), vitexin (2), luteolin-7-O-beta-D-glucuronide (3), and apigenin-7-O-beta-D-glucuronide (4), while prenylated flavonoids, to which the potent estrogenicity of hops (Humilus lupulus L.) is associated, are absent. The different composition of flavonoids has chemotaxonomic value.

Pedilanthus tithymaloides (PT), a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2). Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 μg/ml, respectively), with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/ml, respectively. The inhibitory effect was significant (p<0.001) when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-...

Chemical investigation of the leaves of Struchium sparganophora by the application of VLC, CL and PTLC resulted in isolation of three compounds. The cytotoxicity activity of these compounds on malignant human cultured cells was examined. Vernodalin showed a significant cytotoxic activity on the melanoma and ovarian cancer cell lines (P<0.05) while the conjugated 3 methyl, 2, 6 hexacosedienol and luteolin caused cell death after 48h reculture without them. These compounds portend an effective remedy if subjected to structural modification to enhance its' efficacy and the dietary importance of this plant as a culinary herb in west Africa countries is evidence by the presence of these antitumour compounds in this plant.

Chemical investigation of the leaves of Struchium sparganophora by the application of VLC, CL and PTLC resulted in isolation of three compounds. The cytotoxicity activity of these compounds on malignant human cultured cells was examined. Vernodalin showed a significant cytotoxic activity on the melanoma and ovarian cancer cell lines (P<0.05) while the conjugated 3 methyl, 2, 6 hexacosedienol and luteolin caused cell death after 48h reculture without them. These compounds portend an effective remedy if subjected to structural modification to enhance its' efficacy and the dietary importance of this plant as a culinary herb in west Africa countries is evidence by the presence of these antitumour compounds in this plant.

In this paper we present results on the vacuolar uptake mechanism for two flavone glucuronides present in rye mesophyll vacuoles. In contrast to barley flavone glucosides ( Klein et al. (1996 ) J. Biol. Chem. 271, 29666–29671), the flavones luteolin 7-O-diglucuronyl-4′-O-glucuronide (R1) and luteolin 7-O-diglucuronide (R2) were taken up into vacuoles isolated from rye via a directly energised mechanism. Kinetic studies suggested that the vacuolar glucuronide transport system is constitutively expressed throughout rye primary leaf development. Competition experiments argued for the existence of a plant MRP-like transporter for plant-specific and non-plant glucuronides such as β-estradiol 17-(β- d-glucuronide) (E217G). The interaction of ATP-dependent vacuolar glucuronide uptake with glutathione and its conjugates turned out to be complex: R1 transport was stimulated by dinitrobenzene-GS and reduced glutathione but was inhibited by oxidized glutathione in a concentration-dependent manner. In contrast, R2 uptake was not increased in the presence of reduced glutathione. Thus, the transport system for plant-derived glucuronides differed from the characteristic stimulation of vacuolar E217G uptake by glutathione conjugates but not by reduced glutathione ( Klein et al. (1998 ) J. Biol. Chem. 273, 262–270). Using tonoplast vesicles isolated with an artificial K+ gradient, we demonstrate for the first time for plant MRPs that the ATP-dependent uptake of R1 is membrane-potential dependent. We discuss the kinetic capacity of the ABC-type glucuronide transporter to explain net vacuolar flavone glucuronide accumulation in planta during rye primary leaf development and the possibility of an interaction of potential substrates at both the substrate binding and allosteric sites of the MRP transporter regulating the activity towards a certain substrate.

Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down-regulation o...

Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 μM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species.

Abstract: The present study was designed to investigate the bioactive compounds in extracts of Rumex vesicarius L.(Polygonaceae), a wild edible herb growing in Egypt. Ethyl acetate and n-butanol fractions of leaves of R. vesicarius were conducted by HPLC-PDA-MS/MS-...

A number of pre-Columbian textiles, most discovered in northern Peru and dating to the Late Intermediate Period (ca. 1050-1200 AD), were analyzed by high-performance liquid chromatography with diode array and mass spectrometric detection (LC-DAD-MS), after extraction of the dyes with formic acid and methanol. The focus of this work was yellow dyes, most of which are present as glycosides of flavonoids and related compounds, with the objective of identifying the plants originally used for dyeing. Two major types of dyes were found in this set of specimens. The first type is characterized by the presence of flavonol 3-O-sulfates (never before reported as being present in dyes) and 3-O-glycosides; this type was probably derived from the plant Flaveria haumanii or a close relative. The second type is characterized by the presence of both chalcone (heretofore not reported in pre-Columbian textiles) and luteolin glycosides, though a specific plant source could not be identified. Two other...