Down‐regulatory effect of usnic acid on nuclear factor‐κB‐dependent tumor necrosis factor‐α and inducible nitric oxide synthase expression in lipopolysaccharide‐stimulated macrophages RAW 264.7

The purpose of this study was to investigate the molecular mechanisms that are responsible for the antiinflammatory effect of usnic acid (UA). UA is one of the most common and abundant lichen metabolites. The present study examined the effects of UA on the tumor necrosis factor‐α (TNF‐α) and nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and the underlying molecular mechanisms. UA decreased the TNF‐α level in LPS‐stimulated RAW264.7 macrophages in dose‐dependent manner, the IC₅₀ value was 12.8 µM. RT‐PCR analysis indicated that it inhibited TNF‐α mRNA expression. Furthermore, it inhibited NO production in LPS‐activated RAW264.7 macrophages, the IC₅₀ value was 4.7 µM. Western blot analysis showed that UA attenuated LPS‐induced synthesis of iNOS protein and nuclear translocation of NF‐κB p65 in the macrophages, in parallel. UA also inhibited LPS‐mediated I‐κBα degradation. Taken together, this suggests that UA has an antiinflammatory effect by inhibiting TNF‐α and iNOS expression, possibly through suppression of nuclear translocation of NF‐κB p65 and I‐κBα degradation. Copyright © 2008 John Wiley & Sons, Ltd.     

Biological activities of xanthatin from Xanthium strumarium leaves

The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL‐60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC₅₀ value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE₂ synthesis (24% inhibition) and 5‐lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC₅₀ values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa‐2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE₂ synthesis and 5‐lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. Copyright © 2011 John Wiley & Sons, Ltd.     

Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb.

Epilobium parviflorum Schreb. (Onagraceae) is used for the treatment of benign prostatic hyperplasia (BPH), but its biological action is not entirely identified. This paper aims to report data on E. parviflorum with respect to its antioxidant and antiinflammatory effects. The aqueous acetone extract of E. parviflorum showed higher antioxidant effect in the DPPH assay than well known antioxidants and inhibited the lipid peroxidation determined by the TBA assay (IC₅₀ = 2.37 ± 0.12 mg/mL). In concentrations of 0.2–15.0 µg/mL the extract possessed a protective effect, comparable to catalase (250 IU/mL), against oxidative damage, generated in fibroblast cells. In the COX inhibition assay E. parviflorum decreased the PGE₂ release, so showing inhibition of the COX‐enzyme (IC₅₀ = 1.4 ± 0.1 µg/mL). Copyright © 2008 John Wiley & Sons, Ltd.     

Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Expression by Phenolic Compounds from Roots of Rhododendron mucronulatum

The roots of Rhododendron mucronulatum Turzaninov have been used in Oriental traditional medicine for the treatment of dysuria, fever, increase of digestive activity and tonics in China and Korea. Activity guided isolation of the roots of Rhododendron mucronulatum Turzaninov has led to the isolation of three flavonoids, one flavan 3‐ol and one proanthocyanidin. Chemical investigation of the 80% Me₂CO extract from the roots of Rhododendron mucronulatum led to the isolation and identification of five compounds: taxifolin (1), taxifolin 3‐O‐β‐d ‐glucopyranoside (2), quercetin 3‐O‐α‐l ‐arabinofuranoside (3), (‐)‐epicatechin (4), procyanidin B‐3 (5). To investigate the antioxidative and antiinflammatory effects of these compounds, their 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activities and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in LPS‐stimulated HaCaT cells were also quantified by western blotting and their end products, nitric oxide (NO) and prostaglandin E₂ (PGE₂), respectively. Compounds (1–5) showed potent DPPH radical scavenging compared with positive controls (l ‐ascorbic acid). Also, compounds 1 and 2 dose‐dependently inhibited the expressions of inflammatory mediators, NO and PGE₂, suggesting they are promising candidates as antiinflammatory agents. Copyright © 2011 John Wiley & Sons, Ltd.     

Multifunctional Activity of Polyphenolic Compounds Associated with a Potential for Alzheimer's Disease Therapy from Ecklonia cava

Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC₅₀ from 16.0 to 96.3 μM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol‐A (PFF‐A), showed a particularly potent inhibitory activity (IC₅₀ 0.95 μM), which is over 100‐fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aβ. Bieckol and PFF‐A inhibited amyloid precursor protein biosynthesis. PFF‐A also showed very strong β‐secretase inhibitory activity with IC₅₀ of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease. Copyright © 2015 John Wiley & Sons, Ltd.     

Phytochemical and Pharmacological Investigations on Nymphoides indica Leaf Extracts

Nymphoides indica (L.) Kuntze (Menyanthaceae) is traditionally used in the Indian subcontinent. However, scientific data reporting its constituents are poor. This study aimed at evaluating its phytochemical constituents and various biological activities. Phytochemical investigations of the extracts and fractions resulted in the isolation of 5 lipophilic compounds, i.e. azelaic (nonanedioic) acid (1) and 4‐methyl‐heptanedioic acid (3), hexadecanoic (2) and stearic acid (5) and the fatty alcohol hexadecanol (4); 3 seco‐iridoids, i.e. 7‐epiexaltoside (6), 6″,7″‐dihydro‐7‐epiexaltoside (7) and menthiafolin (8); 3 flavonoids, i.e. 3,7‐di‐O‐methylquercetin‐4′‐O‐β‐glucoside (9), 3‐O‐methylquercetin‐7‐O‐β‐glucoside (10) and 3,7‐di‐O‐methylquercetin (11); scopoletin (12) and ferulic acid (13); and the monoterpenoids foliamenthoic acid (14) and 6,7‐dihydrofoliamenthoic acid methyl ester (15). Compounds 1–5 showed moderate antimicrobial activities, whereas compound 9 presented mild antiprotozoal activities against Trypanosoma brucei (IC₅₀ 8 μM), Leishmania infantum (IC₅₀ 32 μM) and Trypanosoma cruzi (IC₅₀ 30 μM). Antiglycation activity was shown by compounds 7 (IC₅₀ 0.36 mM), 10 (IC₅₀ 0.42 mM) and 15 (IC₅₀ 0.61 mM). Finally α‐glucosidase inhibition was shown by compounds 7, 9, 11 and 13–15. It could be concluded that N. indica leaf extracts possess mild to moderate antimicrobial, antiprotozoal, antioxidant and antidiabetic activities. Copyright © 2016 John Wiley & Sons, Ltd.     

Antiplasmodial and cytotoxic activity of phloroglucinol derivatives from Hypericum erectum thunb

The chloroform extracts of whole plants of Hypericum erectum were investigated for antiplasmodial activity against chloroquine‐sensitive strains of Plasmodium falciparum. Five phloroglucinol derivatives, otogirin (1), otogirone (2), erectquione A (3), erectquione B (4), and erectquione C (5) were isolated from the whole plants of H. erectum. Also, five compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK‐OV‐3 cancer cell line cells. Compounds 2, 4 showed notable growth inhibitory activity against chloroquine‐sensitive strains of Plasmodium falciparum with IC₅₀ values from 5.6 and 7.2 μM. This compound showed no significant cytotoxicity (IC₅₀ > 150 μM) evaluated using SK‐OV‐3 cancer cell line cells. Copyright © 2010 John Wiley & Sons, Ltd.     

Antiparasitic activity of C-geranyl flavonoids from Mimulus bigelovii

Bioactivity‐directed fractionation of the MeOH fraction of the extract of Mimulus bigelovii by means of an axenic Leishmania amastigote assay and chromatographic techniques resulted in the isolation of four C‐geranyl flavanones, diplacone (1), 3′‐O‐methyldiplacone (2), 4′‐O‐methyldiplacone (3), 3′‐O‐methyldiplacol (4), together with a geranylated flavone, cannflavin A (5). These compounds were separated from M. bigelovii for the first time. All compounds showed moderate antileishmanial activity against axenic Leishmania donovani amastigotes with IC₅₀ values ranging from 4.8 to 14.6 μg/mL. The compounds were also tested against the related kinetoplastid parasite Trypanosoma brucei brucei and they showed activity with IC₅₀ values ranging from 1.4 to 7.2 μg/mL. Copyright © 2011 John Wiley & Sons, Ltd.     

Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor‐kappa‐B,cyclooxygenase and tumor cell proliferation

Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S‐linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase‐2 (COX‐2) enzyme by 60% at 100 µm with no activity against COX‐1 enzyme. The IC₅₀ values of compound 1 against human gastric (AGS), breast (MCF‐7), central nervous system (SF‐268) and colon (HCT‐116) cancer cell lines were in the range 0.74–3.63 µm. Both S‐containing dimeric withanolides, 1 and 2, completely suppressed TNF‐induced NF‐κB activation when tested at 100 µm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX‐2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF‐induced NF‐κB activation for compounds 1 and 2. Copyright © 2009 John Wiley & Sons, Ltd.     

Antiplasmodial and cytotoxic activity of khellactone derivatives from Angelica purpuraefolia chung

The methanolic extract of the rhizomes parts of Agelica purpuraefolia was investigated for its activity against chloroquine‐sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two natural khellactone, (+)‐4′‐Decanoyl‐cis‐khellactone (1) and (+)‐3′‐Decanoyl‐cis‐khellactone (2) were isolated from the rhizomes parts of A. purpuraefolia. Two compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK‐OV‐3 cancer cell line cells. Compounds 1, 2 showed notable growth inhibitory activity against chloroquine‐sensitive strains of Plasmodium falciparum with IC₅₀ values from 1.5 and 2.4 μM. This compound showed no significant cytotoxicity (IC₅₀ > 100 μM) evaluated using SK‐OV‐3 cancer cell line cells. This is the first report on the antiplasmodial activity of the compounds from A. purpuraefolia. Copyright © 2009 John Wiley & Sons, Ltd.     

Compounds with tyrosinase inhibition, elastase inhibition and DPPH radical scavenging activities from the branches of Distylium racemosum Sieb. et Zucc

Twenty compounds were isolated from the ethanol extract of Distylium racemosum branches and their inhibitory activities on tyrosinase, elastase and free radicals evaluated. The isolated compounds were identified as dibenzofurans (1–4), abscisic acid (5), 6′‐O‐galloylsalidroside (6), catechin derivatives (7–11), gallic acid derivatives (12–14), tyrosol (15), flavonoids (16–18), lupeol (19) and 1,2,3,6‐tetragalloylglucose (20). For study of tyrosinase inhibition activities, when compared with arbutin (IC₅₀ 48.8 μg/mL), four compounds (8, 11, 13, 17) showed higher activities, with IC₅₀ values of 4.8, 30.2, 40.5 and 37.7 μg/mL, respectively. For the elastase inhibition test, dibenzofuran 1 showed greater activity than the positive control, oleanolic acid (IC₅₀ 9.7 μg/mL), with an IC₅₀ of 7.7 μg/mL. In the studies on DPPH radical scavenging activities, five compounds (11, 12, 13, 14, 15) showed higher activities than ascorbic acid (IC₅₀ 5.0 μg/mL), with IC₅₀ values of 4.6, 3.9, 2.9, 3.8 and 4.7 μg/mL, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Inhibition of Proinflammatory Biomarkers in THP1 Macrophages by Polyphenols Derived From Chamomile,Meadowsweet and Willow bark

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0–100 μM) were incubated with THP1 macrophages, and interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐alpha (TNF‐α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL‐6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF‐α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL‐6 and TNF‐α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts. Copyright © 2012 John Wiley & Sons, Ltd.     

In Vitro activities of plant extracts from Saudi Arabia against malaria,leishmaniasis, sleeping sickness and Chagas disease

The in vitro activity of the methanol extracts of 51 plants randomly collected from the Kingdom of Saudi Arabia and some of their fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were evaluated against Plasmodium falciparum, Trypanosoma brucei brucei, T. cruzi and Leishmania infantum, as well as toxicity against MRC‐5 fibroblast cells. Ten crude methanolic extracts that demonstrated potent and adequately selective antiprotozoal activity were subjected to solvent fractionation using petroleum ether, ethyl acetate and chloroform. Only three samples showed promising antiprotozoal activity. Argemone ochroleuca (CHCl₃ fraction) showed pronounced activity against P. falciparum_GHA (IC₅₀ 0.32 μg/mL) and T. cruzi (IC₅₀ 0.30 μg/mL) with low cytotoxicity against MRC‐5 cells (CC₅₀ 11.6 μg/mL). Capparis spinosa (EtOAc fraction) showed pronounced activity against P. falciparum_GHA with an IC₅₀ 0.50 μg/mL in the absence of toxicity against MRC‐5 cell line (CC₅₀ > 30 μg/mL). Heliotropium curassavicum (CHCl₃ fraction) showed similar activity against P. falciparum (IC₅₀ 0.65 μg/mL; MRC‐5 CC₅₀ > 30 μg /mL). These three extracts will be subjected for further extensive studies to isolate and identify their active constituents. Copyright © 2010 John Wiley & Sons, Ltd.     

Antihyperlipidemic Components of Cassia auriculata Aerial Parts: Identification Through In Vitro Studies

Cassia auriculata (Caesalpiniaceae) is a common Asian beverage and medicinal plant widely used in tradition medicine for diabetes, hyperlipidemia and various other disease conditions. Previous studies on crude extracts of C. auriculata have documented the scientific basis for some of its traditional medicinal uses. The present study investigates the antilipase activity of the ethanol extract of the aerial parts along with the previously isolated compounds (kaempferol‐3‐O‐rutinoside, rutin, kaempferol, quercetin and luteolin). The crude extract displayed inhibitory activity against pancreatic lipase with IC₅₀ of 6.0 ± 1.0 µg/mL. The most active antilipase compound was kaempferol‐3‐O‐rutinoside with IC₅₀ value (2.9 ± 0.50 μM) only about twice weaker than the standard antilipase drug, orlistat (IC₅₀ = 1.45 ± 0.26 μM). Luteolin, quercetin and rutin were found to be weak pancreatic lipase inhibitors (IC₅₀ over 100 μM), whereas kaempferol showed no activity up to 250 μM. The antihyperlipidemic effect of C. auriculata could be attributed to direct lipase inhibitory effect of the plant constituents. Copyright © 2012 John Wiley & Sons, Ltd.     

Anti‐complement activity of isolated compounds from the roots of Clerodendrum bungei Steud.

To determine the anti‐complement activity of natural diterpenes, chromatographic separation of the acetone‐soluble fraction from the roots of Clerodendrum bungei (Verbenaceae) led to the isolation of five diterpenoids. An acetone‐soluble extract of the roots of C. bungei exhibited significant anti‐complement activity on the classical pathway complement system, which was expressed as total hemolytic activity. Five compounds isolated from the roots of C. bungei, namely 12‐O‐β‐d ‐glucopyranosyl‐3,11,16‐trihydroxyabieta‐8,11,13‐triene (1), 3,12‐O‐β‐d ‐diglucopyranosyl‐11,16‐dihydroxyabieta‐8,11,13‐triene (2), ajugaside A (3), uncinatone (4) and 19‐hydroxyteuvincenone F (5). Compounds 1, 2, 3, 4 and 5 showed inhibitory activity against complement system with 50% inhibitory concentrations (IC₅₀) values of 24 µm , 138 µm , 116 µm , 87 µm and 232 µm . Among the compounds tested, 1 showed the most potent anti‐complement activity (IC₅₀, 24 µm ). Copyright © 2010 John Wiley & Sons, Ltd.