Flavonoid Constituents Research Articles

Kaempferol, the melanogenic component of Sanguisorba officinalis, enhances dendricity and melanosome maturation/transport in melanocytes

Kaempferol, a representative flavonoid constituent of Sanguisorba officinalis, promotes melanogenesis, but the underlying mechanisms remain unknown. Here, we evaluated the effects of kaempferol on melanocytes morphology and behavior and determined the mechanisms regulating kaempferol-induced pigmentation. We observed that kaempferol increased melanin contents and dendritic length and stimulated melanocyte migration both in vitro and vivo. It significantly enhanced the expression of microphthalmia-associated transcription factor (MITF) and downstream enzymes of melanin biosynthesis—tyrosinase (TYR), tyrosinase-related protein (TRP-1), and dopachrome tautomerase (DCT). It also induced melanosome maturation (increased stage III and IV melanosomes) and melanin transfer to dendritic tips; this was evidenced as follows: kaempferol-treated melanocytes exhibited the perimembranous accumulation of HMB45-positive melanosomes and increased the expression of Rab27A, RhoA, and Cdc42, which improved melanosome transport to perimembranous actin filaments. These results jointly indicated that kaempferol promotes melanogenesis and melanocyte growth. Additionally, kaempferol stimulated the phosphorylation of P38/ERK MAPK and downregulated p-PI3K, p-AKT, and p-P70s6K expression. Pre-incubation with P38 (SB203580) and ERK (PD98059) signaling inhibitors reversed the melanogenic and dendritic effects and MITF expression. PI3K/AKT inhibitor augmented kaempferol-induced melanin content and dendrite length. In summary, kaempferol regulated melanocytes’ dendritic growth and melanosome quantity, maturation, and transport via P38/ERK MAPK and PI3K/AKT signaling pathways.

Anti-diabetic potential of Plectranthus lanuginosus in streptozotocin-induced diabetic rats

Purpose: To determine the antidiabetic effect of methanol extract of Plectranthus lanuginosus leaves in streptozotocin-induced hyperglycemic (HGD) rats.
 Methods: P. lanuginosus leaves were collected from Saad Medhas, Al Baha, Kingdom of Saudi Arabia. After defatting with n-hexane, they were extracted in vacuo at 40 oC with 75 % methanol. Streptozotocin (50 mgkg−1, i.p.) was used to induce hyperglycemia (diabetes) in the rats. The HGD rats received either standard drug (glibenclamide, 10 mgkg−1, p.o.) or Plectranthus lanuginosus leaf methanol leaf extract (PLLM) at doses of 200 and 400 mgkg−1/day, p.o. for 21 consecutive days. Blood samples were taken from the rat tails 2 h after dosing, and at 7-day intervals (i.e., 0, 7th, 14th and 21st days). The blood samples were used for measurement of fasting blood glucose (FBS), using a glucometer. On the 21st day, the rats were sacrificed via cardiac puncture. The activities of liver marker enzymes (SGPT and SGOT), and serum lipid profile (cholesterol, triglycerides, HDL and LDL) were determined using a hemolyzer.
 Results: Streptozotocin treatment produced significant hyperglycemia in the rats (348.9 ± 5.6) when compared to control (79.2 ± 1.3). However, PLLM (200 and 400 mg kg−1) produced significant and dose-dependent anti-diabetic (166.4 ± 5.6 and 123.86 ± 6.8 respectively) and antihyperlipidemic effects in HGD rats, at levels similar to those produced by the standard drug, glibenclamide (120.6 ± 6.4).
 Conclusion: P. lanuginosus leaf extract possesses pronounced anti-diabetic and anti-hyperlipidemic properties which may be due to the presence of phenolic and flavonoid constituents in the plant. Therefore, the plant extract can be further developed for the management of diabetes

A comprehensive phytochemical, biological, toxicological and molecular docking evaluation of Suaeda fruticosa (L.) Forssk.: An edible halophyte medicinal plant

Suaeda fruticosa is an edible medicinal halophyte known for its traditional uses. In this study, methanol and dichloromethane extracts of S. fruticosa were explored for phytochemical, biological and toxicological parameters. Total phenolic and flavonoid constituents were determined by using standard aluminum chloride and Folin-Ciocalteu methods, and UHPLC-MS analysis of methanol extract was performed for tentative identification of secondary metabolites. Different standard methods like DPPH, ABTS, FRAP, CUPRAC, total antioxidant capacity (TAC), and metal chelation assays were utilized to find out the antioxidant potential of extracts. Enzyme inhibition studies of extracts against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase and, α-glucosidase enzymes were also studied. Likewise, the cytotoxicity was also assessed against MCF-7, MDA-MB-231, and DU-145 cell lines. The higher phenolic and flavonoids contents were observed in methanol extracts which can be correlated to its higher radical scavenging potential. Similarly, 11 different secondary metabolites were tentatively identified by UHPLC profiling. Both the extract showed significant inhibition against all the enzymes except for α-glucosidase. Moreover, docking studies were also performed against the tested enzymes. In the case of cytotoxicity, both the samples were found moderately toxic against the tested cell lines. This plant can be explored further for its potential therapeutic and edible uses.

UPLC-MS/MS profiling and antitumor activity of Silene succulenta Forssk. Growing in Egypt

Abstract The present study aims to detect the phenolics and flavonoids constituents of Silene succulenta Forssk. belonging to Caryophyllaceae family, also screening of their antioxidant and cytotoxic activities. GC-MS analysis is one of our goals in this study. The phenolic and flavonoid profiles were carried out using Micro plate assay. In addition, in vitro antioxidant activity was performed using DPPH assay while the Cytotoxicity was summarized by SRB test. GC-MS analysis for n-hexane was carried out using gas chromatography-mass spectrometry. Also ultra-performance liquid chromatography coupled with hybrid triple time-of-flight mass spectrometry (UPLC-Triple TOF-MS/MS) was carried out to determine the different phytochemicals in total alcoholic extract. Total phenolic and flavonoids content in aerial parts of S. succulenta were found 20.86 mg/g and 8.06 mg/g respectively. Cytotoxicity of n-hexane fraction showed a high activity against Breast (MCF7) and Lung Carcinoma (A549) cell lines with IC50 15.5 and 22.6 µg /ml respectively. Total alcoholic extract and ethyl acetate fraction showed antioxidant activities with IC50 799.8 ± 45.45 and 749.9 ± 29.73 (ug/ ml) respectively. Finally, ninety six compounds were detected in n-hexane using GC-MS and comparison with standards. UPLC-Triple TOF-MS/MS showed the presence of different classes of secondary metabolites (flavonoids, coumarins, amino acids, anthocyanidines and alkaloids)

Qualitative and Quantitative Analysis on Flavonoid Distribution in Different Floral Parts of 42 Hemerocallis Accessions

The Hemerocallis accessions is widely consumed as nutritious vegetable and traditional medicine in eastern Asia and used as an ornamental flower worldwide. Compared with most other horticultural products, its flower is richer in polyphenols, flavonoids, carotenoids, and anthocyanins. Therefore, the flower has strong antioxidant activity that inhibits cancer cell proliferation, which could used for health and pharmaceutical purposes. The flavonoids composition and distribution in the flowers, and the content varied between different accssions is still unclear. In this context, eight flavonols, two flavones, and two anthocyanins were determined in Hemerocallis flower by high-performance liquid chromatography (HPLC) coupled with photodiode array and mass spectrometric detectors. Rutin was the most abundant flavonols and cyanidin 3,5-glucoside and cyanidin 3-rutinoside were the major anthocyanins in Hemerocallis tepals, resulting in flower petal coloration, and their content in the petal was higher than that of the sepal. Hierarchical cluster analysis grouped the 42 accessions into four groups, and they were significantly different (p < 0.05) from each other in the ten significant compounds by One-way ANOVA. Overall, the qualitative and quantitative analysis of flavonoid constituents in six floral parts of 42 Hemerocallis accessions were elucidated, which could be helpful for the food and pharmaceutical industries, and lay the foundation for the Hemerocallis flower color research.

Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress, inflammatory and fibrotic markers.

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

Didymin switches M1-like toward M2-like macrophage to ameliorate ulcerative colitis via fatty acid oxidation

Inflammatory response by different polarized macrophages has a critical role in a variety of immunological pathophysiology, such as ulcerative colitis (UC). Herein, targeting the paradigm of macrophage phenotypes by small molecular modulators may influence the disease status. In the present study, we firstly demonstrated that didymin, one of the most abundant flavonoid constituents present in the citrus fruits such as oranges and lemons, remarkably attenuated the clinical symptoms of acute and chronic colitis in mice. Mechanistic studies showed that didymin converted pro-inflammatory M1-like to anti-inflammatory M2-like macrophage phenotype, but did not alter the polarization of M2-like macrophages. Metabolic tracing studies revealed that didymin strengthened fatty acid oxidation rather than glycolysis by inducing Hadhb expression. More importantly, in vivo studies verified that promotion of Hadhb expression resulted in the conversion of M1- toward M2-like macrophages and eventually alleviated colitis. Our data highlights the potential of macrophage paradigm in UC inflammation and put forth the stage for considering didymin as a metabolism regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated disorders.

Toxicological, histological and biochemical effects of Lepidium sativum seeds extract on Galleria mellonella L. (Lepidoptera: Pyralidae) larvae

The greater wax moth Galleria mellonella L. is a serious destructive pest of honeybee colonies in the beekeeping industry all over the world. The larvae feed on almost all of the honeybee products and have the ability to completely destroy the bee colony, especially the weakened ones. The toxicity and biochemical effect of garden cress, Lepidium sativum seed methanolic extract as natural product against greater wax moth was evaluated under laboratory conditions. The defatted seeds (250g) of garden cress were refluxed in 500 ml methanol, filtered and then dry in a rotary evaporator. Results revealed that the toxic effect of the garden cress extract against 5th instar larvae of G. mellonella was 1.15%, (LC50) after 24h. which induced more histopathological alterations on cuticle layers, fat bodies and muscle. Moreover, it causes highly significant inhibition in α, β esterase and phenol oxidase activities as well as possesses a significant reduction in protein content. On other hand, it causes an elevation in total lipid content and acid phosphatase activity. Also, apoptotic activity with DNA fragmentation was occurred at concentrations of 3, 2 and 1%. GC-MS analysis illustrated the toxic effect of methanol extract of L. sativum seeds related to a high ratio of phenolic, flavonoid and fatty acids constituents.

Characterization of Flavonoid Constituents in Stems of Lithocarpus litseifolius (Hance) Chun by UHPLC-Q-Exactive Orbitrap MS

Background: Lithocarpus litseifolius (Hance) Chun (L. litseifolius) has been used for treating diabetes, allergic and inflammatory diseases, and hyperlipidemia in folk medicine. Previous studies have shown that the main active ingredients of its leaves are flavonoids. However, to the best of our knowledge, the stem of L. litseifolius has not been investigated for its constituents yet. The stems of the decaying plants fall every year. It is considered as a waste due to limited knowledge of the benefits of these stems, which is a sheer waste of the plant resource. Therefore, it is necessary to investigate the chemical constituents of the stem, which will be beneficial for the treatment of many diseases and help utilize the stem in a better way instead of wasting the plant resource. Methods: In this study, the dry twigs of L. litseifolius were collected, powdered, and extracted. Then, the extracted sample was subjected to UHPLC-Q-Exactive Orbitrap MS in negative mode combined with Parallel reaction monitoring scanning to gain the high-resolution mass spectrum, which was processed by the Compound Discover version 3.0 using high resolution extracted ion chromatography to predict the constituent compounds. Results: A total of 35 flavonoids including flavone, flavonol, dihydroflavone, isoflavone, and dihydrochalcone were putatively identified based on their accurate mass measurement, chromatographic retention, MSn spectra, and bibliography data. Conclusion: In this study, a total of 35 flavonoids were identified in the stem of L. litseifolius, among which 5 flavonoids were the first to be reported from this plant, which will be very helpful for the development of medicines for the treatment of many diseases and utilization of the stem of L. litseifolius.

Evaluation of in vitro antioxidant, anticancer activities and molecular docking studies of Capparis zeylanica Linn. leaves

BackgroundCapparis zeylanica Linn. leaf extract was subjected to phytochemical screening for the determination of antioxidant and anticancer activity on (MCF-7) human breast cancer cells. The phytoconstituents previously determined were subjected to molecular docking studies against human epidermal growth factor receptor 2 (HER2) protein as a target receptor to support antioxidant and anticancer activities.ResultsPowdered plant leaves were extracted by maceration method using ethyl acetate, chloroform, methanol, ethanol and distilled water. Preliminary phytochemical evaluation and total phenolic and flavonoid content of the extract were evaluated using biochemical tests. Total antioxidant capacity of the extract was evaluated using different assays. Anticancer potential of methanolic and ethanolic extracts was studied on human breast cancer cells. Molecular docking studies were performed to evaluate the binding interactions of phytoconstituents on HER2 protein using AutoDock Vina.Phytochemical evaluation confirmed the presence of saponins, flavonoids, tannins, phenols, carbohydrates and proteins. Ethanolic extract showed a maximum total phenolic and flavonoid content in support with antioxidant and anticancer activities. The ethanolic leaf extract showed 66.63% cell growth inhibition against MCF-7 cells. Molecular docking studies revealed the highest binding affinity (− 8.4 Kcal/mol) of α-amyrin followed by quercetin and β-carotene. Glucocapparin, syringic acid, vanillic acid and p-coumaric acid showed almost a similar binding affinity to the amino acid residues of HER2 protein as compared to 5-FU.ConclusionC. zeylanica leaf extract showed the presence of phenolic and flavonoid constituents responsible for antioxidant and in vitro anticancer activities. Molecular docking studies showed the binding affinity of phytoconstituents on targeted HER2 protein.

Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways.

Chrysin, one of the main active constituents of flavonoids, is known for demonstrating protective effects against various types of cancer including cervical cancer. The aim of this study was to determine apoptosis induction and antiproliferative action of chrysin on human cervical cancer cells. In this study, attempts have been made to establish anticancer role of chrysin on HeLa cells. MTT, mitochondrial potential, DNA fragmentation, annexin V/propidium iodide assays, qPCR and protein profiling were performed. Chrysin treated HeLa cells showed time and dose dependent decrease in cell viability and demonstrated profound effects on nuclear morphology and DNA fragmentation. Chrysin treatment increased the expression of proapoptotic genes BAD, BAX, BID, BOK and APAF1, TNF, FASL, FAS, FADD and caspases (like caspase 3, caspase 7, caspase 8 and caspase 9), whereas it decreased the expression level of antiapoptotic genes MCL-1, NAIP, XIAP and Bcl-2 and cell cycle regulatory genes CCNB1, CCNB2, CCND1, CCND2, CCND3, CCNE2, CDK4 and CDK2 at transcript level. Furthermore, chrysin significantly upregulated pro-apoptotic proteins, like TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95, phosphoP53(S15), BAD, BAX, cleaved caspase 3, procaspase 3, HTRA2/Omi and SMAC/Diablo, while downregulated anti-apoptotic proteins like BCL-X, BCL2, XIAP and CIAPs that support chrysin mediated apoptosis in HeLa cells. Remarkably, chrysin downregulated the phosphorylated AKT pathway proteins, (p-473) AKT, (p-Ser 2448) mTOR, (p-Ser241) PDK1, (p-Ser112) BAD, and upregulated (p-Ser21) GSK3b, (p-Thr172) AMPKa, P27 (p-Thr198) and (p-Ser15) P53, which endorses chrysin mediated apoptosis. Chrysin significantly inhibited proliferation and induced apoptosis by modulation of various apoptotic genes and AKT/MAPK pathway genes.

Phytochemicals in Chinese Chive (Allium tuberosum) Induce the Skeletal Muscle Cell Proliferation via PI3K/Akt/mTOR and Smad Pathways in C2C12 Cells.

Chinese chive (Allium tuberosum) is a medicinal food that is cultivated and consumed mainly in Asian countries. Its various phytochemicals and physiological effects have been reported, but only a few phytochemicals are available for skeletal muscle cell proliferation. Herein, we isolated a new compound, kaempferol-3-O-(6″-feruloyl)-sophoroside (1), along with one known flavonoid glycoside (2) and six amino acid (3–8) compounds from the water-soluble fraction of the shoot of the Chinese chive. The isolated compounds were identified using extensive spectroscopic methods, including 1D and 2D NMR, and evaluated for their proliferation activity on skeletal muscle cells. Among the tested compounds, newly isolated flavonoid (1) and 5-aminouridine (7) up-regulated PI3K/Akt/mTOR pathways, which implies a positive effect on skeletal muscle growth and differentiation. In particular, compound 1 down-regulated the Smad pathways, which are negative regulators of skeletal muscle growth. Collectively, we suggest that major constituents of Chinese chive, flavonoids and amino acids, might be used in dietary supplements that aid skeletal muscle growth.

Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance

BackgroundOtostegia integrifolia Benth. (Lamiaceae) leaves are used to treat hypertension in Ethiopian folk medicine. However, the claim has so far not been investigated scientifically. Thus, the objective of this study was to evaluate the antihypertensive activity of 80% methanol leaf extract of O. integrifolia in animal model of hypertension and possible underlying mechanisms in isolated rat aorta.MethodsAntihypertensive effect of various oral doses of the extract (250, 500 and 1000 mg/kg) was determined in fructose-induced hypertensive rats using the non-invasive tail-cuff method. Thoracic aortic strips of rats were isolated and suspended in organ bath, and the vasodepressor effect as well as the possible mechanism (s) of action were studied by means of isometric tension recording experiments ex vivo. Phytochemical analysis was also performed to suggest possible constituents related to the activity.ResultsBlood pressure was significantly lowered in a dose-dependent manner following extract administration, suggesting that the extract possesses antihypertensive activity. The extract also caused a dose-dependent relaxation of aortic strip precontracted with KCl at a concentration of 6.25–125 μg/L, with a maximum relaxation (100%) achieved at a cumulative concentration of 318.75 μg/ml. The relaxation mechanism was found to be independent of muscarinic receptors, prostanoids, histamine receptors, ATP dependent K+ channels, sarcoplasmic reticulum stored Ca2+ and the endothelium system. The extract shifted the Ca2+ concentration-response curve to the right similar to that caused by nifedipine, suggesting that vasorelaxation could possibly be mediated via calcium channel blockade. The extract was found to contain phenolic compounds (164.3 mg/g, expressed as gallic acid equivalents) and flavonoids (125.7 mg/g, expressed as quercetin equivalents).ConclusionThe findings revealed that the plant is endowed with antihypertensive activity, providing evidence for its traditional use. The effect maybe, at least in part, due to dilation of blood vessels through blockade of Ca+ 2 channels mediated by phenolic and flavonoid constituents.

Review of Medicinal Uses, Phytochemistry, Pharmacological Properties, Extraction Methods and Toxicology of Lannea microcarpa (African Grapes)

Ethnopharmacological Relevance: Lannea microcarpa is an African herbal medicinal plant by pan-African distribution and has huge native medicinal and non-medicinal applications. The plant is being used traditionally as a medicine for many diseases such as mouth blisters, rheumatism, dysentery, sore throat, as a dressing on boils, as a cathartic, livestock feed, diarrhoea, gastroenteritis, malaria, dysentery, infection from bacteria, toothaches, gastroenteritis, female infertility, in blood pressure, oedema, coughing, cathartic, poisoning, and burns. It is also used in the manufacture of the cloths termed ‘basilan fini’ widely related to the concept of healing (medicine applied on cloth). Aim of the Review: This review aims to assemble an up-to-date review of the advancement made in the continuous pharmacological and phytochemical study of Lannea microcarpa and the consistent commercial and therapeutic application of it. These findings provide guide to the upcoming research on this plant. Methods: The assessment is systematically directed by searching the database of MEDLINE, PubMed, Springer, BMC, the Web of Knowledge, Google Scholar, ChemSpider and Science Direct for original research articles and books using related search terms. Result: Pharmacological studies verified the capability of this plant as it showed antioxidant, anti-inflammatory, and antibacterial activities. Bioactive constituents are found to be present in all parts of the plant. So far, this plant having high antioxidant capabilities, Lannea microcarpa is composed of many chemical compounds such as vitexin, lipids, proteins &amp; amino acids, epi-catechin, gallic acid, myricetin, iso-Vitexin, fatty acid, carbohydrates, and tannins. This plant possesses antioxidant and antimicrobial properties owing to the presence of polyphenolics &amp; flavonoids constituents. Novel compounds with the potent antiinflammatory effects such as 4’-methoxy-myricetin 3-O-α-L-rhamnopyranoside, myricetin 3-O-α-L-rhamnopyranoside, and myricetin 3-O-β-D-glucopyranoside among others, have been identified. Microparticles formulation of Lannea microcarpa was also prepared and further studies are still going on.

African mistletoe (Tapinanthus bangwensis Lor.) infestation improves the phenolic constituents, antioxidative and antidiabetic effects of almond (Terminalia catappa Linn.) host leaf in sucrose‐rich diet‐induced diabetic‐like phenotypes in fruit fly (Drosophila melanogaster Meigen)

AbstractAlmond is a medicinal plant commonly infested with mistletoe, and its leaves are consumed as food and/or medicine due to their health‐promoting benefits. Mistletoe infestation may interfere with the chemical composition and biological activities of host plants. Therefore, we investigated the influence of mistletoe infestation on polyphenol constituents, antioxidative and hypoglycemic activities of almond leaves in sucrose‐rich diet (SRD)‐induced diabetic‐like phenotypes in the Drosophila melanogaster model. Infested almond leaf (IAL) had higher polyphenol constituents; ellagic acid and isorhamnetin were the most abundant phenolic acid and flavonoid constituents in the almond leaves. However, this study revealed significant (P &lt; 0.05) infestation‐induced increase in some phenolic acids (p‐hydroxybenzoic, protocatechuic, gallic, and chlorogenic acids) and flavonoids (apigenin and catechin) with known antioxidative, antidiabetic, and neuroprotective properties. Moreover, IAL had higher in vitro antioxidant and inhibition of α‐amylase, α‐glucosidase, and acetylcholinesterase (AChE) activities. The SRD‐fed flies had significant (P &lt; 0.05) decrease in percentage survival and locomotion and increase in weight. In addition, elevated levels of glucose, trehalose, insulin‐like peptides and triglycerides coupled with increased oxidative and AChE activities were obtained. However, treatment with the leaves significantly (P &lt; 0.05) lessened the negative alterations caused by SRD with IAL having higher hypoglycemic activities. Hence, we suggest that improved antidiabetic activities of IAL could be related to its higher phenolic constituents.

Rapid identification of isoprenylated flavonoids constituents with inhibitory activity on bacterial neuraminidase from root barks of paper mulberry (Broussonetia papyrifera)

This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis to identify potent bacterial neuraminidase (bNA) inhibitors from the Broussonetia papyrifera roots extract. To isolate unbound compounds from the enzyme-binding complex, the root bark extracts were either incubated in the absence of bNA, in the presence of bNA, or with the time-dependent bNA before the ultrafiltration was performed. Thirteen flavonoids were separated from the target extract, and their inhibitory activities were tested against bNA. The isolated flavonoids exhibited potent inhibition against NA (IC50 = 0.7–54.0 μM). Our kinetic analysis of representative active flavonoids (1, 2, and 6) showed slow and time-dependent reversible inhibition. Additionally, chalcones exhibited noncompetitive inhibition characteristics, whereas flavonols and flavans showed mixed-type behavior. The computational results supported the experimental behaviors of flavonoids 2, 6, 10, and 12, indicating that bounded to the active site, but flavonoids 6 and 10 binds near but not accurately at the active site. Although this is mixed-type inhibition, their binding can be considered competitive.

Pharmacological activity and flavonoids constituents of Artemisia judaica L aerial parts

Ethno-pharmacological relevanceArtemisia judaica L is an aromatic medicinal plant growing widely in Saint Katherine, Sinai, Egypt, and used in traditional medicine as a herbal remedy for antibacterial, anthelmintic, antidiabetic, analgesic and anti-inflammatory activities. Additionally, other Arabic regions commonly used it in their folk medicines for the treatment of fungal infections, atherosclerosis, cancer, diabetes, arthritis, and inflammatory-related diseases. Aim of the studyBased on the traditional medicinal uses of A. judaica, the present study was designed to validate some of the traditional uses as the analgesic, anti-inflammatory, antipyretic, hepatoprotective, antidiabetic, and antioxidant activities of 80% aqueous methanol extract (AME) of A. judaica aerial parts as well as isolation and identification of its flavonoid content. Materials and methodsAME of A. judaica aerial parts was fractionated using column chromatography and the structures of the isolated compounds were established using different spectroscopic data. Analgesic activity was evaluated using acetic acid-induced writhing in mice; antipyretic activity was assessed using yeast suspension-induced hyperthermia in rats; anti-inflammatory activity was evaluated using carrageenan-induced paw edema; the hepatoprotective effect was studied by measuring liver enzymes in carbon tetrachloride(CCl4)-induced hepatotoxicity rats while antidiabetic activity was estimated in alloxan hyperglycemia. ResultsEight flavone compounds namely luteolin 4′ methyl ether 7-O-β-D-4C1-glucopyranoside (1), 8-methoxyapigenin 7-O-β-D-4C1-galactopyranoside (2), isovitexin (3), 8-methoxyluteolin 7-O-β-D-4C1-glucopyranoside (4), diosmetin (5), cirsimaritin (6), luteolin (7), and apigenin (8) were identified from AME of A. judaica. The AME was found to be non-toxic to mice up to 5 g/kg b.w. Moreover, it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities in a dose-dependent manner. ConclusionThe AME was nontoxic; it exhibits significant analgesic, antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities. Moreover, the isolated flavone was identified from AME for the first time.

Determination of bioactive phytochemicals, antioxidant and anti-inflammatory activity of Colchicum autumnale L. (Suranjanshireen)

In Unani System of Medicine Suranjanshireen (Colchicum autumnale L.) is primarily used for the treatment of arthritis, and it belongs to the family of Liliaceae. The current investigation was conducted to evaluate the phytochemical constituents, anti-oxidant, and anti-inflammatory activity of C. autumnale L. Anti-oxidant activity was done using 2, 2'-azinobis (3-ethyl benzothiazoline-6-sulfonic acid), and 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging test. The bioactive compounds of the extracts of C. autumnale were identified by GC-MS and UHPLC-QExactiveOrbitrap. Docking studies were carried out for anti-inflammatory activity.The subjective phytochemicals examination demonstrated the existence of phenols, flavonoids, glycosides, and terpenoids. Whereas the quantitative investigation indicated dichloromethane extract contains the maximum number of phenolic and flavonoids constituents and demonstrated the highest antioxidant activity. GC-MS, and UHPLC- QExactiveOrbitrap investigation of the extracts confirmed the existence of bioactive compounds. Docking analysis revealed that colchicoside (3 demethyl colchicine glucoside) inhibits IL-6 having binding energy -7.1 kcal/mol with an RMSD value of 0.00. Phytochemicals, antioxidant, GC-MS, UHPLC- QExactiveOrbitrap analysis and molecular docking results revealed that the compounds presented in C. autumnale L extracts were accountable for numerous therapeutic uses, for instance, antioxidant, and anti-inflammatory activities.

UPLC-PDA-ESI-QTOF-MS/MS fingerprint of purified flavonoid enriched fraction of Bryophyllum pinnatum; antioxidant properties, anticholinesterase activity and in silico studies

Context Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is used traditionally to treat many ailments. Objectives This study characterizes the constituents of B. pinnatum flavonoid-rich fraction (BPFRF) and investigates their antioxidant and anticholinesterase activity using in vitro and in silico approaches. Materials and methods Methanol extract of B. pinnatum leaves was partitioned to yield the ethyl acetate fraction. BPFRF was isolated from the ethyl acetate fraction and purified. The constituent flavonoids were structurally characterized using UPLC-PDA-MS2. Antioxidant activity (DPPH), Fe2+-induced lipid peroxidation (LP) and anticholinesterase activity (Ellman’s method) of the BPFRF and standards (ascorbic acid and rivastigmine) across a concentration range of 3.125–100 μg/mL were evaluated in vitro for 4 months. Molecular docking was performed to give insight into the binding potentials of BPFRF constituents against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Results UPLC-PDA-MS2 analysis of BPFRF identified carlinoside, quercetin (most dominant), luteolin, isorhamnetin, luteolin-7-glucoside. Carlinoside was first reported in this plant. BPFRF significantly inhibited DPPH radical (IC50 = 7.382 ± 0.79 µg/mL) and LP (IC50 = 7.182 ± 0.60 µg/mL) better than quercetin and ascorbic acid. Also, BPFRF exhibited potent inhibition against AChE and BuChE with IC50 values of 22.283 ± 0.27 µg/mL and 33.437 ± 1.46 µg/mL, respectively compared to quercetin and rivastigmine. Docking studies revealed that luteolin-7-glucoside, carlinoside and quercetin interact effectively with crucial amino acid residues of AChE and BuChE through hydrogen bonds. Discussion and conclusions BPFRF possesses an excellent natural source of cholinesterase inhibitor and antioxidant. The material could be further explored for the potential treatment of oxidative damage and cholinergic dysfunction in Alzheimer’s disease.

Protective role of Allium cepa Linn (onion) juice on maternal dexamethasone induced alterations in reproductive functions of female offspring of Wistar rats

Maternal treatment with dexamethasone induces oxidative stress in the reproductive structures of offspring. Consumption of Allium cepa Linn improves antioxidant status. This study was designed to evaluate the protective role of Allium cepa Linn juice on maternal dexamethasone induced alterations in reproductive functions of the female offspring of Wistar rats.Twenty lactating dams (180–200 ​g) were randomly assigned into four groups (n ​= ​5) on the day of parturition and treated as follows during lactation for 21 days: Control (5 ​ml/kg BW distilled water); Dexamethasone (60 ​μg/kg BW); Allium cepa (5 ​ml/kg BW); Dexamethasone ​+ ​Allium cepa (60 ​μg/kg BW ​+ ​5 ​ml/kg BW). The female offspring were separated at birth. Days of vaginal opening and first oestrus cycle, length and frequency of estrous cycle as well as serum hormonal profiles were assessed as measure of reproductive functions. Ovarian superoxide dismutase (SOD) activity, catalase activity and malondialdehyde (MDA) level were measured as indices of oxidative stress.Oestrous cycle length, frequencies of diestrus as well as the Ovarian MDA were significantly increased (p ​< ​0.05) in dexamethasone (DEX) group relative to control group. Serum 17β-oestradiol and corticosterone level in addition to SOD and catalase activities were significantly reduced (p ​< ​0.05) in DEX group relative to control. Co-administration of Dex with Allium cepa Linn juice reduced the oestrous length, frequency of diestrous as well as ovarian MDA. There was also a significant increase in serum 17β-oestradiol, ovarian SOD and catalase activity.The results suggest that Allium cepa could protect against alterations in reproductive functions of offspring induced by maternal treatment with dexamethasone during lactation in Wistar rats. The flavonoid constituent of onion may also help in reducing oxidative stress in the offspring.