Cytotoxicity of an Innovative Pressurised Cyclic Solid-Liquid (PCSL) Extract from Artemisia annua.

Therapeutic treatments with Artemisia annua have a long-established tradition in various diseases due to its antibacterial, antioxidant, antiviral, anti-malaria and anti-cancer effects. However, in relation to the latter, virtually all reports focused on toxic effects of A. annua extracts were obtained mostly through conventional maceration methods. In the present study, an innovative extraction procedure from A. annua, based on pressurised cyclic solid-liquid (PCSL) extraction, resulted in the production of a new phytocomplex with enhanced anti-cancer properties. This extraction procedure generated a pressure gradient due to compressions and following decompressions, allowing to directly perform the extraction without any maceration. The toxic effects of A. annua PCSL extract were tested on different cells, including three cancer cell lines. The results of this study clearly indicate that the exposure of human, murine and canine cancer cells to serial dilutions of PCSL extract resulted in higher toxicity and stronger propensity to induce apoptosis than that detected by subjecting the same cells to Artemisia extracts obtained through canonical extraction by maceration. Collected data suggest that PCSL extract of A. annua could be a promising and economic new therapeutic tool to treat human and animal tumours.

Antidiabetic profiling, cytotoxicity and acute toxicity evaluation of aerial parts of Phragmites karka (Retz.).

ETHNOPHARMACOLOGICAL RELEVANCE: Phragmites karka (Retz.) of family Poaceae is a pristine tropical plant that is well known to the local healers for ailments of diabetes, fever, diarrhea and CNS depression but lacks the scientific evidence behind its traditional usage. Hence, we explicated this plant to find the scientific basis of its traditional utilization. AIM OF THE STUDY: The current study aims to find out the antidiabetic potential, toxicity after oral administration and in vitro cytotoxic activity of aerial parts of the plant on HeLa cells. METHODS: The plant was extracted with methanol by maceration and the crude extract was then subjected to solvent partitioning with modified Kupchan method for preparing several fractions. Phytochemical screening and total phenolic content of the plant was first determined through established procedures. Acute toxicity of the plant was studied by orally administering a single high dose (5000 mg/kg) of drug. Cytotoxicity of the methanolic plant extract was determined by measuring the percentage of cell viability on human cervical cancer cell lines, HeLa. In vitro antidiabetic activity was determined through iodine starch and DNSA (3,5-dinitrosalicylic acid) method of α-amylase inhibition. Finally, in vivo oral glucose tolerance test and alloxan induced antidiabetic activity test was performed at 150 and 300 mg/kg body weight doses of plant extract to confirm the in vivo antidiabetic activity. RESULTS: No mortality was demonstrated by Phragmites karka in the acute toxicity test. However, signs of cellular toxicity was observed and histopathological studies on major organs exhibited necrosis in liver and kidney. In vitro cytotoxicity assay revealed the death of HeLa cells by DCM (dichloromethane) and n-hexane fractions of plant extract at 100 and 10 µg/mL concentrations. The IC50 value of the fractions were later evaluated by MTT assay (316.1 and 96.7 µg/mL for n-hexane and DCM fractions, respectively). In the iodine starch and DNSA method of α-amylase enzyme inhibitory activity test, substantial inhibition of enzyme was observed with the IC50 values of 2.05 and 2.08 mg/mL, respectively. In the in vivo antidiabetic activity test, considerable reduction in blood glucose level of diabetic mice was detected in both oral glucose tolerance test and alloxan induced antidiabetic activity test. In addition, the microscopic examination of pancreas showed noticeable recovery of pancreatic ß cells and the blood lipid profile analysis represented a significant (p < 0.05) reduction of total cholesterol, LDL (low density lipoprotein) and triglyceride level in plant extract treated mice. CONCLUSION: Results of this study reveals that the Phragmites karka extract is toxic at cellular level after oral administration and cytotoxic when tested on HeLa cells. The plant also evidenced hypoglycemic property, possibly through the inhibition of α-amylase enzyme and recovered the pancreatic beta cells along with the improvement of lipid profile of diabetic mice. However, robust studies on this plant is required to isolate the bioactive compounds, elucidate structures and evaluate their mechanism of actions in support of our findings. CLASSIFICATION: Toxicology and Safety, Quality Traditional Medicine.

Potential Nutraceutical Properties of Leaves from Several Commonly Cultivated Plants.

Chronic dietary ingestion of suitable phytochemicals may assist with limiting or negating neurodegenerative decline. Current therapeutics used to treat Alzheimer disease elicit broad adverse drug reactions, and alternative sources of cholinesterase inhibitors (ChEIs) are required. Herein, we screened methanolic extracts from seven commonly cultivated plants for their nutraceutical potential; ability to inhibit acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), and provision of antioxidant activity through their 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging capabilities. Potential neurotoxicity of plant extracts was examined via application to SHSY-5Y neuroblastoma cells and quantitation of cell viability. Methanolic extracts of Citrus limon (Lemon), Bombax ceiba (Red silk-cotton), Lawsonia inermis (Henna), Eucalyptus globulus (Eucalyptus), Ocimum basilicum (Basil), Citrus reticulata (Mandarin orange), and Mentha spicata (Spearmint) all displayed concentration-dependent inhibition of AChE and BuChE. The majority of extracts inhibited AChE and BuChE to near equipotency, with Henna and Eucalyptus extracts the two most potent ChEIs. All plant extracts were able to scavenge free radicals in a concentration-dependent manner, with Eucalyptus the most potent antioxidant. Toxicity of plant extracts to neuronal cells was concentration dependent, with Eucalyptus also the most toxic extract. Fractionation of plant extracts and analysis by mass spectrometry identified a number of plant polyphenols that might have contributed to the cholinesterase inhibition: 3-caffeoylquinic acid, methyl 4-caffeoylquinate, kaempferol-acetyl-glycoside, quercetin 3-rutinoside, quercetin-acetyl-glycoside, kaempferol 3-O-glucoside, and quercetin 3-O-glucoside. In silico molecular modeling of these polyphenols demonstrated their improved AChE and BuChE binding affinities compared to the current FDA-approved dual ChEI, galantamine. Collectively, all the plant extracts contained nutraceutical agents as antioxidants and ChEIs and, therefore, their chronic consumption may prove beneficial to combat the pathological deficits that accrue in Alzheimer disease.

Arabinoxylan-Based Particles: In Vitro Antioxidant Capacity and Cytotoxicity on a Human Colon Cell Line.

Background and objectives: Arabinoxylans (AX) can gel and exhibit antioxidant capacity. Previous studies have demonstrated the potential application of AX microspheres as colon-targeted drug carriers. However, the cytotoxicity of AX gels has not been investigated so far. Therefore, the aim of the present study was to prepare AX-based particles (AXM) by coaxial electrospraying method and to investigate their antioxidant potential and cytotoxicity on human colon cells. Materials and Methods: The gelation of AX was studied by monitoring the storage (G') and loss (G'') moduli. The morphology of AXM was evaluated using optical and scanning electron microscopy (SEM). The in vitro antioxidant activity of AX before and after gelation was measured using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. In addition, the effect of AX and AXM on the proliferation of human colon cells (CCD 841 CoN) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The final G' and G'' values for AX gels were 293 and 0.31 Pa, respectively. AXM presented spherical shape and rough surface with a three-dimensional and porous network. The swelling ratio and mesh size of AXM were 35 g water/g AX and 27 nm, respectively. Gelation decreased the antioxidant activity of AX by 61-64 %. AX and AXM did not affect proliferation or show any toxic effect on the normal human colon cell line CCD 841 CoN. Conclusion: The results indicate that AXM could be promising biocompatible materials with antioxidant activity.

Emerging senolytic agents derived from natural products.

Cellular senescence is a hallmark of aging, it is a permanent state of cell cycle arrest induced by cellular stresses. During the aging process, senescent cells (SCs) increasingly accumulate in tissues, causing a loss of tissue-repair capacity because of cell cycle arrest in progenitor cells and produce proinflammatory and matrix-degrading molecules which are known as the senescence-associated secretory phenotype (SASP), and thereby contribute to the development of various age-related diseases. Genetic evidence has demonstrated that clearance of SCs can delay aging and extend healthspan. Senolytics, small molecules that can selectively kill SCs, have been developed to treat various age-related diseases. In recent years, emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog. Some of the compounds have been validated in animal models and have great potential to be pushed to clinical applications. In this review, we will discuss cellular senescence and its potential as a target for treating age-related diseases, and summarize the known natural compounds as senolytic agents and their applications.

Cynaropicrin and inhibition of NF-κB activation: A structure activity relationship study.

Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. This natural product has various biological activities including anti-inflammatory properties and antitrypanosomal activity. It was also found to suppress photoaging of the skin by inhibiting the transcription activity of nuclear factor-kappa B (NF-κB). In this paper, nine chemical derivatives of cynaropicrin were prepared, and the structure activity relationship (SAR) study for NF-κB inhibition by measuring relative light units (RLU) was conducted.

Structure of constituents isolated from the bark of Cassipourea malosana and their cytotoxicity against a human ovarian cell line.

Three aromatic compounds, 2α,3α-epoxyflavan-5,7,4'-triol-(4ß â†’ 8)-afzelechin (1), 2ß,3ß-epoxyflavan-5,7,4'-triol-(4α → 8)-epiafzelechin (2), and methyl 4-ethoxy-2-hydroxy-6-propylbenzoate (3), as well as eight known compounds (4-11) were isolated from the bark of Cassipourea malosana (Rhizophoraceae). Their structures were determined on the basis of an analysis of spectroscopic data. The in vitro cytotoxic activities of these compounds against human ovarian cancer cell line TOV21G were evaluated. Most compounds showed little activity; however, the methyl derivatives of flavan dimers (1a and 2a) showed higher activity (IC50 value of 30.3 and 75.4 µM) than parent compounds 1 and 2.

Pregnane glycosides from the bark of Marsdenia cundurango and their cytotoxic activity.

Seven new pregnane glycosides (1-7) and eight known compounds (8-15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1-7 were determined by spectroscopic analysis, including two-dimension NMR spectroscopy, chemical transformations, and chromatographic analysis of the hydrolyzed products. The isolated compounds 1-15 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human lung cells, including apoptosis-inducing activity of a representative pregnane glycoside in HL-60 cells.

Cytotoxicity and selectiveness of Brazilian Piper species towards oral carcinoma cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the ten most common types of cancer worldwide. Plants of the genusPiper are used in traditional medicine to treat cancer, and they have a vast diversity of phytochemicals with cytotoxic potential. Purpose and Study Design: In this work, we analyzed the cytotoxic and selective potential of extracts and semipurified fractions of Piper mollicomum (PM), Piper truncatum (PT), Piper cernuum (PC), Piper arboreum (PA), and Piper cabralanum (PCa) using three different OSCC cell lines (SCC4, SCC9 and SCC25), and we measured their in vivo toxicities and conducted chemical analyses of their active fractions. RESULTS: The dichloromethane fractions of the crude methanolic extracts of the leaves of PM(-L-D), PC(-L-D) and PCa(-L-D) exhibited notable IC50 values of 94.2, 47.2 and 47.5 µg/mL, respectively, and all three of these extracts were more active than carboplatin (172.3 µg/mL). The most selective fraction was PC-L-D, which exhibited SI > 4.5; less than 5% hemolysis; and no significant alterations in in vivo acute toxicology. The major constituents in active fractions were lignans (PC-L-D and PCa-L-D) and chromenes (PM-L-D). CONCLUSION: PC-L-D demonstrated great potential for further development as an anticancer drug and could be the key to developing more effective and less toxic therapies against oral cancer.

New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines.

Three new limonoids, limonophyllines A-C (1, 4 and 5), along with two known limonoids (2 and 3) and 11 acridone alkaloids (6-16) were isolated from the stems of Atalantia monophylla. All isolates were evaluated against cholangiocarcinoma, KKU-M156, and HepG2 cancer cell lines. Compounds 12, 14 and 16 displayed cytotoxicity against KKU-M156 cell line with IC50 ranging from 3.39 to 4.1 µg/mL while cytotoxicity against HepG2 cell line with IC50 ranging from 1.43 to 8.4 µg/mL. The structures of all isolated compounds were established by spectroscopic methods including 1D and 2D NMR, IR and mass spectrometry.

Chaga ( Inonotus obliquus), a Future Potential Medicinal Fungus in Oncology? A Chemical Study and a Comparison of the Cytotoxicity Against Human Lung Adenocarcinoma Cells (A549) and Human Bronchial Epithelial Cells (BEAS-2B).

BACKGROUND: Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. METHODS: A quantification method by HPLC-MS-MS (high-performance liquid chromatography-tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). RESULTS: French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga's aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B ( P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).

Eulophia macrobulbon - an orchid with significant anti-inflammatory and antioxidant effect and anticancerogenic potential exerted by its root extract.

BACKGROUND: The Orchidaceae family is one of the largest families of flowering plants. Orchids are widely used for the traditional herbal medicine, acting as aphrodisiac, antisepic, antimicrobial, anti-cancer agent, etc. PURPOSE: This study was designed to elucidate the anti-inflammatory, antioxidant and cytotoxic potential of a 50% ethanolic extract of Eulophia macrobulbon roots (EME) in vitro, an orchid growing in Southern Asia. Furthermore, the main active compounds were isolated, and the bioactivity of the single constituents was determined. METHODS: The anti-inflammatory activity of EME and its compounds was evaluated by the secretion of pro- and anti-inflammatory cytokines and by the expression of inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated macrophage model, as determined by an enzyme linked immunosorbent assay (ELISA) and Western blot. Antioxidant activity was assessed using a DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) photometric assay. Cytotoxic effects were determined using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. RESULTS: EME and its compounds significantly reduced the production of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), the expression of iNOS and subsequently increased the production of the anti-inflammatory cytokine interleukin 10 (IL-10) in LPS-stimulated macrophages. Additionally it could be demonstrated that EME is rich in radical scavengers. Furthermore, EME and its components showed notable cytotoxic effects on the human cervical adenocarcinoma cell line HeLa, the human colorectal adenocarcinoma cell line CaCo-2 and the human breast adenocarcinoma cell line MCF-7. The most active constituents were identified as 4-methoxy-9,10-dihydro-2,7-phenanthrenediol (8), 4-methoxy-2,7-phenanthrenediol (9), 1,5-dimethoxy-2,7-phenanthrenediol (10), 1,5,7-trimethoxy-2,6-phenanthrenediol (11), 1-(4-hydroxybenzyl)-4,8-dimethoxy-2,7-phenanthrenediol (15). CONCLUSION: Based on this data, EME provides various beneficial anti-inflammatory, antioxidant and cytotoxic attributes and may be used as herbal remedy in the pharmaceutical or food industries.

Glaucarubulone glucoside from Castela macrophylla suppresses MCF-7 breast cancer cell growth and attenuates benzo[a]pyrene-mediated CYP1A gene induction.

Quassinoids often exhibit antioxidant and antiproliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons into carcinogenic metabolites. Gg reduced the viability of MCF-7 breast adenocarcinoma cells (IC50 = 121 nm) to a greater extent than standard of care anticancer agents 5-fluorouracil, tamoxifen (IC50 >10 µm) and the tamoxifen metabolite 4-hydroxytamoxifen (IC50 = 2.6 µm), yet was not cytotoxic to non-tumorigenic MCF-10A breast epithelial cells. Additionally, Gg induced MCF-7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF-10A cells mediated by the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) metabolite B[a]P 1,6-quinone, yet downregulated the expression of genes that promote antioxidant activity in MCF-7 cells. This implies that Gg exhibits antioxidant and cytoprotective actions in non-tumorigenic breast epithelial cells and pro-oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non-competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF-7 cells. These data indicate that Gg selectively suppresses MCF-7 breast cancer cell growth without impacting non-tumorigenic breast epithelial cells and blocks B[a]P-mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-inflammatory, anti-diarrheal, thrombolytic and cytotoxic activities of an ornamental medicinal plant: Persicaria orientalis.

BACKGROUND: Persicaria orientalis, an ornamental medicinal plant, has been used in traditional medicine for the treatment of various diseases. Although the plant is reported to have some important pharmacological effects, many medicinal values remain unidentified. Our objective was to evaluate the anti-inflammatory, anti-diarrheal, thrombolytic, and cytotoxic properties of the methanol extract of P. orientalis leaves (Po-MeOH). METHODS: Anti-inflammatory activity was measured by the inhibition of hypotonicity-induced human red blood cell hemolysis and albumin denaturation technique in vitro of Po-MeOH. Diarrheal episodes were examined in mice with castor oil-induced diarrhea. The clot lysis and brine shrimp lethality bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities of the plant extract, respectively. RESULTS: Using in vitro anti-inflammatory models, the results demonstrated that Po-MeOH at the five different dose ranges from 31.25 to 500 µg/mL significantly (p<0.05) protected (0.98%-50.71%) the erythrocyte membrane against lysis induced by hypotonic medium solution and protein denaturation (38.27%-79.22%) of bovine albumin, respectively. The extract exhibited a significant reduction of severity (75.17%) of castor oil-induced diarrhea in mice at the highest dose of 400 mg/kg compared to loperamide (82.06%) at 5 mg/kg. Po-MeOH also showed 33.14% clot lytic activity in the thrombolytic test and cytotoxicity with LC50 value 58.91 µg/mL in the brine shrimp bioassay. CONCLUSIONS: These findings suggest that Po-MeOH has significant anti-inflammatory and anti-diarrheal effects along with moderate thrombolytic and lower cytotoxic properties that may warrant the further exploration.

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells.

CONTEXT: Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment. OBJECTIVE: The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. MATERIALS AND METHODS: NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. RESULTS: Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. DISCUSSION AND CONCLUSION: Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.

Erythrina excelsa exhibits estrogenic effects in vivo and in vitro and is cytotoxic on breast and colon cancer cell lines.

CONTEXT: Eythrina excelsa Baker (Fabaceae) is a medicinal plant used to treat various ailments including those of the female genital tract. OBJECTIVE: The objective of this study is to investigate the estrogenic and cytotoxic effects of the ethanol extract of the stem bark of E. excelsa. MATERIALS AND METHODS: Erythrina excelsa was evaluated in vitro using the yeast estrogen screen (YES). The extract was then tested in a 3-day uterotrophic assay on ovariectomised Wistar rats at doses of 50 and 100 mg/kg BW/d. Cytotoxic effects were assessed on breast (MCF-7) and colon (HT-29) cancer cell lines using the MTT cell viability assay. Additionally, a LC-PDA-ESI (+)-HRMS and HRMS/MS method was developed and applied for the identification of representative secondary metabolites scaffolds in the extract. RESULTS: In the YES, the extract stimulated the transactivation of the estrogen receptor in a dose-dependent manner with an EC50 value of 1.8 µg/mL. In rats, E. excelsa increased uterine wet weight, uterine epithelial height, and the mRNA expression of estrogen-responsive genes in the uterus and liver at 50 whereas at 100 mg/kg BW/d anti-estrogenic effects were observed. In the MTT-assay, a dose-dependent decrease of the viability of both cell lines was observed with EC50 values of 13.6 µg/mL (MCF-7) and 27.7 µg/mL (HT-29). The phytochemical analysis revealed that the extract is rich in isoflavonoids, mainly prenylated and pyran-derivatives thereof. CONCLUSION: Erythrina excelsa is rich in prenylated and pyran-substituted isoflavonoids, exhibits estrogenic/anti-estrogenic and cytotoxic effects and warrant sufficient interest for deeper investigations.

Leishmanicidal and cytotoxic activities of Nigella sativa and its active principle, thymoquinone.

CONTEXT: Leishmaniasis is a complex disease with a broad spectrum of clinical presentations. OBJECTIVE: We evaluated the anti-leishmanial effects of Nigella sativa L. (Ranunculaceae) against Leishmania tropica and Leishmania infantum with an in vitro model. MATERIALS AND METHODS: Antileishmanial effects of essential oil and methanolic extract of N. sativa (0-200 µg/mL) and thymoquinone (0-25 µg/mL) on promastigotes of both species and their cytotoxicity activities against murine macrophages were evaluated using the MTT assay at 24, 48, and 72 h. Moreover, their leishmanicidal effects against amastigotes were investigated in a macrophage model, for 48 and 72 h. RESULTS: The findings showed that essential oil (L. tropica IC50 9.3 µg/mL and L. infantum IC50 11.7 µg/mL) and methanolic extract (L. tropica IC50 14.8 µg/mL and L. infantum IC50 15.7 µg/mL) of N. sativa, particularly thymoquinone (L. tropica IC50 1.16 µg/mL and L. infantum IC50 1.47 µg/mL), had potent antileishmanial activity on promastigotes of both species after 72 h. In addition, essential oil (L. tropica IC50 21.4 µg/mL and L. infantum IC50 26.3 µg/mL), methanolic extract (L. tropica IC50 30.8 µg/mL and L. infantum IC50 34.6 µg/mL), and thymoquinone (L. tropica IC50 2.1 µg/mL and L. infantum IC50 2.6 µg/mL) mediated a significant decrease in the growth rate of amastigote forms of both species. Thymoquinone (CC50 38.8 µg/mL) exhibited higher cytotoxic effects against murine macrophages than the other extracts. CONCLUSION: N. sativa, especially its active principle, thymoquinone, showed a potent leishmanicidal activity against L. tropica and L.infantum with an in vitro model.

Inula sesquiterpenoids: structural diversity, cytotoxicity and anti-tumor activity.

INTRODUCTION: The plants of the genus Inula (Asteraceae) are widely distributed throughout Europe, Africa and Asia, and many of these plants have long been used in folk medicine. This genus is a rich source of sesquiterpenoids, which exhibit a wide range of biological activities. Recently, a series of bioactive sesquiterpenoid dimers, with unusual carbon skeletons, have been reported and these have gathered considerable interest. AREAS COVERED: This article systematically reviews sesquiterpenoids isolated from the genus Inula that have appeared in literature up to August 2013, critically highlighting their anti-tumoral activities and relevant mechanistic insights. The authors also discuss the initial structure-activity relationships for the cytotoxic and anti-tumoral activities of the Inula sesquiterpenoids. Finally, the authors discuss the challenges and potential applications of these sesquiterpenoids in the future. EXPERT OPINION: Cytotoxic and anti-tumor activities of Inula sesquiterpenoids have been extensively studied since the 1970s. One promising compound, Japonicone A, a dimeric sesquiterpene lactone from traditional herb Inula japonica, has displayed potent in vitro and in vivo anti-tumor activity against Burkitt's lymphoma. Additionally, acetylbritannilactone is thought to be capable of suppressing the abnormal vascular smooth muscle cell proliferation, with the induction of apoptosis in vivo and in vitro. In this regard, it may be worthwhile further investigating acetylbritannilactone in patients with vascular restenosis. Furthermore, given the anti-inflammatory property of britanin, clinical studies on chronic bronchitis and asthma, using the ethanol extract of I. japonica, are currently underway in South Korea. However, despite demonstrating good therapeutic effects, additional pharmacological and toxicological studies are still needed.

Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines.

Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and (+)-3-hydroxy-anhydrolycorine N-oxide (4). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (¹H-¹H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3). Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC50 of 9.2-11.3 µM and 10.4-12.2 µM respectively.

Cytotoxic activity evaluation and QSAR study of chromene-based chalcones.

Chalcone and chromene motifs are synthetic or naturally occurring scaffolds with significant cytotoxic profile. Two types of novel regioisomeric chromene-chalcone hybrids, namely 1-(6-chloro or 6-methoxy-2H-chromen-3-yl)-3-phenylprop-2-en-1-one (Type A) and 3-(6-chloro or 6-methoxy-2H-chromen-3-yl)-1-phenylprop-2-en-1-one (Type B), both with different substituents on the phenyl ring attached to propenone linkage, have been evaluated for their cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231). The results indicate that type A of chromene-chalcones demonstrated better cytotoxic profile than type B especially in MDA-MB-231 cell line. In addition, the growth inhibitory activity of most of the target compounds is higher than Etoposide as a reference drug. QSAR analysis of these novel compounds demonstrated that topological and geometrical parameters are among the important descriptors that influence the cytotoxic activity profile of compounds.