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.     

In vivo Antimalarial Activity of α‐Mangostin and the New Xanthone δ‐Mangostin

Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α‐mangostin and a new compound, δ‐mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α‐Mangostin was more active against the resistant Plasmodium falciparum chloroquine‐resistant (FCR3) strain (IC₅₀ = 0.2 ± 0.01 μM) than δ‐mangostin (IC₅₀ = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances. Copyright © 2015 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.     

Extracts from Epilobium sp. Herbs,Their Components and Gut Microbiota Metabolites of Epilobium Ellagitannins,Urolithins, Inhibit Hormone‐Dependent Prostate Cancer Cells‐(LNCaP) Proliferation and PSA Secretion

Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate‐associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC₅₀ values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin‐3‐O‐glucuronide, myricetin‐3‐O‐rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC₅₀ = 7.8 ± 0.8 μM), PSA secretion (IC₅₀ = 21.9 ± 3.2 μM) and arginase activity (IC50 = 19.2 ± 2.0 μM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC₅₀ = 35.2 ± 3.7 μM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases. Copyright © 2013 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.     

Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human Liver Cytochrome P450 Activities

When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb–drug interactions. This work was conducted to evaluate the herb–drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC₅₀, Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 μM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 μM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 μM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC₅₀ > 100 μM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 μM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 μM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols. Copyright © 2014 John Wiley & Sons, Ltd.     

Labdane‐type diterpenes from Hedychium gardnerianum with potent cytotoxicity against human small cell lung cancer cells

Seven labdane‐type diterpenes, coronarin E, coronarin A, yunnancoronarin A, yunnancoronarin B, hedyforrestin B, villosin, and hedyforrestin C were isolated from the rhizome of Hedychium gardnerianum and evaluated for cytotoxic activity against human small cell lung cancer (NCI‐H187) and non‐cancerous Vero cells. The results showed that villosin exhibited potent cytotoxic activity with IC₅₀ of 0.40 μM, which was higher than that of the drug ellipticine (IC₅₀ 1.79 μM). Moreover, ellipticine was very toxic to Vero cells (IC₅₀ 7.47 μM) whereas the toxicity of villosin was undetectable at concentration lower than 166.42 μM. The results have indicated that the lactone ring is essential for high cytotoxic activity and that the presence of a hydroxyl group at the 6 or 7 position causes decrease in activity. The very high cytotoxicity against the NCI‐H187 cells and the exceptionally high selectivity index (>416) of villosin suggested that this compound may be used as a potential lead molecule for antitumor therapeutic development. Copyright © 2009 John Wiley & Sons, Ltd.     

Evaluation of the antiprotozoal activity of neo‐clerodane type diterpenes from Salvia polystachya against Entamoeba histolytica and Giardia lamblia

Chia (Salvia polystachya Ort., Lamiaceae) is frequently used in Mexican traditional medicine to treat dysentery. In this study the main neo‐clerodane diterpenes (polystachynes A, B and D, as well as linearolactone) were isolated from the aerial parts of chia, and their antiprotozoal activities toward Entamoeba histolytica and Giardia lamblia trophozoites were evaluated in vitro. Linearolactone was the most potent antiamoebic and antigiardial compound with IC₅₀ values of 22.9 μM for E. histolytica and 28.2 μM for G. lamblia. Polystachynes A, B and D, showed moderate antiprotozoal activity against both protozoans with IC₅₀ values ranging from 117.0 to 160.6 μM for E. histolytica and from 107.5 to 134.7 μM for G. lamblia. These data suggest that linearolactone may play an important role in the antidiarrhoeal activity of S. polystachya. Copyright © 2009 John Wiley & Sons, Ltd.     

Inhibitory Effects of Isolated Compounds from Black Coloured Rice Bran on the Complement Classical Pathway

The present study evaluated the anticomplement effects of isolated compounds from black coloured rice bran in the classical pathway of the complement system. Using column chromatography, three compounds: oryzafuran, quercetin and protocatechuic acid, were isolated and evaluated for in vitro anticomplement activity. Oryzafuran showed the most potent inhibitory activity against the complement system, with 50% inhibitory concentration (IC₅₀) values of 126.2 µg/mL. This is the first report of anticomplement activity of isolated compounds from black coloured rice bran. Copyright © 2011 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.     

Inhibition of phospholipase C activity by auriculatin and 8-prenylluteone isolated from Erythrina senegalensis

Auriculatin and 8-prenylluteone were isolated from Erythrina senegalensis (Leguminosae) as inhibitors of phospholipase C (PLC) and phosphoinositides (PI)-turnover in PLC-γ1 overexpressing NIH3T3 fibroblasts (NIH3T3γ1). Auriculatin (1) and 8-prenylluteone (2) showed inhibitory activity with an IC₅₀ value of 20 μm on PLC in vitro as well as the formation of inositol phosphates in platelet-derived growth factor (PDGF)-stimulated NIH3T3γ1 cells. They also showed a moderate cytotoxicity against several human tumour cell lines with an IC₅₀ of 9.0–20 μm , i.e. PC-3 (prostate), NCI-H226 (lung), CRL1579 (melanoma) in vitro. © 1998 John Wiley & Sons, Ltd.     

Antimalarial Activity of Cryptolepine and Isocryptolepine,Alkaloids Isolated from Cryptolepis sanguinolenta

Cryptolepis sanguinolenta extracts are currently used by African herbalists to cure malaria but the compounds involved in its antimalarial activity have not been identified. Two alkaloids, cryptolepine and isocryptolepine, have been isolated from the roots of C. sanguinolenta and their antimalarial activity evaluated. Both alkaloids possess intrinsic inhibitory activity against the human malaria parasite, Plasmodium falciparum in vitro , whatever the chloroquine-resistance status of the strains used. Cryptolepine was slightly more efficient for parasite killing with an IC₅₀ in the range of 0.2 to 0.6 μMSC compared with an IC₅₀ of about 0.8 μMSC for isocryptolepine. The antimalarial activity of cryptolepine was confirmed in vivo on the rodent malarial parasites Plasmodium vinckei petteri and Plasmodium berghei ANKA.     

Antiprotozoal,antimycobacterial and cytotoxic potential of some british green algae

In the continuation of our search for natural sources for antiprotozoal and antitubercular molecules, we have screened the crude extracts of four green marine algae (Cladophora rupestris, Codium fragile ssp. tomentosoides, Ulva intestinalis and Ulva lactuca) collected from the Dorset area of England. Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Mycobacterium tuberculosis were used as test organisms in the in vitro assays. The selective toxicity of the extracts was also determined toward mammalian skeletal myoblast (L6) cells. The crude seaweed extracts had no activity against M. tuberculosis, but showed antiprotozoal activity against at least two protozoan species. All algal extracts were active against T. brucei rhodesiense, with C. rupestris being the most potent one (IC₅₀ value 3.7 μg/ml), whilst only C. rupestris and U. lactuca had moderate trypanocidal activity against T. cruzi (IC₅₀ values 80.8 and 34.9 μg/ml). Again, all four extracts showed leishmanicidal activity with IC₅₀ values ranging between 12.0 and 20.2 μg/ml. None of the extracts showed cytotoxicity toward L6 cells, indicating that their antiprotozoal activity is specific. This is the first study reporting antiprotozoal and antimycobacterial activity of British marine algae. Copyright © 2009 John Wiley & Sons, Ltd.     

Antiinflammatory Constituents from Eclipta prostrata using RAW264.7 Macrophage Cells

The whole plant extract of Eclipta prostrata and its isolated compounds were tested for their antiinflammatory effects against lipopolysaccharide (LPS)‐induced nitric oxide (NO), prostaglandin E₂ (PGE₂) and tumor necrosis factor‐alpha (TNF‐α) release in RAW264.7 cells, as well as for the antiinflammatory mechanism of the active compound on mRNA expression. Among the isolated compounds, orobol (5) exhibited the highest activity against NO release with an IC₅₀ value of 4.6 μm , followed by compounds 1, 2 and 4 with IC₅₀ values of 12.7, 14.9 and 19.1 μm , respectively. The IC₅₀ value of compound 5 against PGE₂ release was found to be 49.6 μm , whereas it was inactive towards TNF‐α (IC₅₀ > 100 μm ). The mechanism of orobol (5) was found to down‐regulate iNOS and COX‐2 mRNA expression in a concentration‐dependent manner. The present study may support the traditional use of Eclipta prostrata for the treatment of inflammatory‐related diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

Inhibition of oncogene product enzyme activity as an approach to cancer chemoprevention. Tyrosine-specific protein kinase inhibition by daphnoretin from Thymelaea hirsuta root

Inhibitors of oncogene product enzyme activity were sought as a prescreen for potential cancer chemopreventive agents. Daphnoretin, a dicoumaryl ether from Thymelaea hirsuta root, inhibited the erb-b oncogene product, the tyrosine-specific protein kinase of human epidermal growth factor receptor (IC₅₀ = 97.5 μM ). Daphnoretin was moderately cytotoxic (IC₅₀ = 21–114 μM ) only in rapidly proliferating cultured mammalian cells. © 1998 John Wiley & Sons, Ltd.     

Extracts of Bolivian plants,Copaifera reticulata and Heisteria pallida inhibit in vitro free radical-mediated DNA damage

The presence of different extracts of antiinflammatory plants Copaifera reticulata and Heisteria pallida in a reaction medium containing calf thymus DNA in a free radical generating system protected DNA against oxidative damage in terms of deoxyribose oxidation. The highest antioxidant activity was obtained using the methanol extract of C. reticulata (IC₅₀=3 μg/mL), followed by the aqueous extracts of H. pallida (IC₅₀=257 μg/mL) and C. reticulata (IC₅₀=380 μg/mL). Both dichloromethane extracts and the methanol extract of H. pallida showed a decreased antioxidant activity at higher concentrations. These results suggest that these extracts are capable of suppressing the in vitro oxidative degradation of DNA. © 1997 John Wiley & Sons, Ltd.     

In vitro and in vivo antimalarial activity of cryptolepine,a plant-derived indoloquinoline

Cryptolepine is an indoloquinoline, high yields of which may be extracted from the roots of the West African shrub Cryptolepis sanguinolenta. The use of this plant as a traditional treatment for malaria is widespread in Ghana and is reported to be clinically effective. We have tested cryptolepine for in vitro antiplasmodial activity against the multidrug resistant (K1) strain of Plasmodium falciparum and found it to be highly active with an IC₅₀ value of 0.031±0.0085 (SE) μg/mL, equivalent to 0.134±0.037 μM (n = 3). In a 4-day suppression test there was, however, no significant reduction in parasitaemia in P. berghei-infected mice treated subcutaneously with cryptolepine (7–113 mg/kg/d×4), when compared with untreated controls. Like 9-aminoacridine, this compound appears to intercalate with DNA and this may explain the high degree of antimalarial activity demonstrated in vitro.     

A Novel Diterpene Skeleton: Identification of a Highly Aromatic,Cytotoxic and Antioxidant 5‐Methyl‐10‐demethyl‐abietane‐type Diterpene from Premna serratifolia

Premna serratifolia Linn. (syn: . P. corymbosa (Burm. f.) Merr., P. integrifolia L. and P. obtusifolia R. Br.) is a member of the Verbenaceae family that is extensively used in the Ayurvedic system of medicine in India. As part of our continuous pharmacological and phytochemical studies on medicinal plants, we have screened the methanolic extracts of leaves, root bark (RB) and root wood of P. serratifolia for cytotoxic activity against two cancer cell lines: SHSY‐5Y neuroblastoma and B16 melanoma cells. The RB extract that showed promising activity was fractionated using solvents of increasing polarity followed by a combination of Sephadex LH‐20 column and Combiflash chromatography as well as HPLC to afford the active principle. Comprehensive spectroscopic analysis including 1D and 2D NMR (COSY, HMQC, HMBC, NOESY) and MS analysis revealed the identity of the isolated compound as 11,12,16‐trihydroxy‐2‐oxo‐5‐methyl‐10‐demethyl‐abieta‐1[10],6,8,11,13‐pentene that appears to be a novel compound based on a new diterpene skeleton. The cytotoxic activity of the isolated compound was 21 and 23 times higher than the crude extract against the SHSY‐5Y and B16 cells, respectively. The novel compound also possesses in vitro antioxidant effects as evidenced by the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging effect where an IC₅₀ value of 20.4 ± 1.3 μM was obtained. In comparison, the positive control, caffeic acid, showed an IC₅₀ value of 14.4 ± 1.6 μM. Copyright © 2014 John Wiley & Sons, Ltd.