Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities.

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography-mass spectrometry (GC-MS), and their antiproliferative and antimicrobial activities were evaluated. GC-MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3-88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg-1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg-1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg-1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL-1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL-1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.

HRMS Characterization, Antioxidant and Cytotoxic Activities of Polyphenols in Malus domestica Cultivars from Costa Rica.

There is increasing interest in research into fruits as sources of secondary metabolites because of their potential bioactivities. In this study, the phenolic profiles of Malus domestica Anna and Jonagold cultivars from Costa Rica were determined by Ultra Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry (HRMS) using a quadrupole-time-of-flight analyzer (UPLC-QTOF-ESI MS), on enriched-phenolic extracts from skins and flesh, obtained through Pressurized Liquid Extraction (PLE). In total, 48 different phenolic compounds were identified in the skin and flesh extracts, comprising 17 flavan-3-ols, 12 flavonoids, 4 chalcones, 1 glycosylated isoprenoid and 14 hydroxycinnamic acids and derivatives. Among extracts, the flesh of Jonagold exhibits a larger number of polyphenols and is especially rich in procyanidin trimers, tetramers and pentamers. Evaluating total phenolic content (TPC) and antioxidant activities using ORAC and DPPH procedures yields higher values for this extract (608.8 mg GAE/g extract; 14.80 mmol TE/g extract and IC50 = 3.96 µg/mL, respectively). In addition, cytotoxicity evaluated against SW620 colon cancer cell lines and AGS gastric cancer cell lines also delivered better effects for Jonagold flesh (IC50 = 62.4 and 60.0 µg/mL, respectively). In addition, a significant negative correlation (p < 0.05) was found between TPC and cytotoxicity values against SW620 and AGS adenocarcinoma (r = -0.908, and -0.902, respectively). Furthermore, a significant negative correlation (p < 0.05) was also found between the number of procyanidins and both antioxidant activities and cytotoxicity towards SW620 (r = -0.978) and AGS (r = -0.894) cell lines. These results align with Jonagold flesh exhibiting the highest abundance in procyanidin oligomers and yielding better cytotoxic and antioxidant results. In sum, our findings suggest the need for further studies on these Costa Rican apple extracts-and particularly on the extracts from Jonagold flesh-to increase the knowledge on their potential benefits for health.

Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

Phytochemical investigation and effective therapeutic potential of plants extracts against breast and ovarian cancer cell lines: compounds from zizyphus mauritiana and triticum aestivum.

ancer is the leading cause of death, accounting for approximately one out of six people dying with this disease worldwide. Among all, the breast and ovarian cancers are top-ranked causes of women mortalities compared to other disorders. Although, there is advancement in technologies, but still, there are unresolved concerns to overcome the global disease burden. Currently, plants are being explored as a natural remedy to cure disorders. This research was planned to explore phytochemicals in methanolic extracts of Zizyphus mauritiana and Triticum aestivum, and their pharmacological activities were studied through Agrobacterium tumefaciens bacteria, in vitro breast cancer cell line and ovarian cancer cell line to find out novel candidates in disease control and prevention. Eleven different types of bioactive compounds were analysed in the tested extracts. The highest crude extracts percentage (75±0.02) was observed with Z. mauritiana. The extracts showed promising cell growth inhibition and tumor initiation inhibition in potato disc assay. MTT assay and Incucytes imaging analysis revealed that Z. mauritiana extract had a higher anticancer potential with 40 ± 0.92 cell viability against breast cancer cells (SKBR3) and 45 ±0.29 against ovarian cancer cells (SKOV3). In conclusion, these extracts could be used as chemotherapeutics owing to their cheapness, and easy availability. While detailed study is required for further purification and characterization of bioactives/target compounds and in-vivo activity confirmations.

In-silico HMG-CoA reductase-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.

OBJECTIVES: Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin. METHODS: Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects. KEY FINDINGS: Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-ß-ß-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs. CONCLUSION: Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.

Comparative Quantitative Study of Ardisiacrispin A in Extracts from Ardisia crenata Sims Varieties and Their Cytotoxic Activities.

Ardisia crenata Sims (Primulaceae) occurs in natural habitats in two varieties, bearing red or white fruits. While roots of the red-berried ardisia are valued as a medicinal product, the pharmacological activity of which is attributed to triterpene saponins, including ardisiacrispin A, data on the white-berried variety are scarce. A TLC-densitometric method was developed and validated to estimate the levels of saponins, calculated as ardisiacrispin A, in different plant parts in both varieties. Their content amounted to 22.17±4.75 and 25.72±1.46 mg/g d.w. in roots, and 2.64±0.74 and 3.43±0.70 mg/g d.w. in fruits of red-berried and white-berried ardisia, respectively. Assessment of cytotoxicity of ardisiacrispin A and A. crenata extracts on a panel of human cancer cell lines revealed a similar effect of root extracts from both varieties, with the highest potency against melanoma WM793 and colon cancer Caco2. Thus, roots of the white-berried variety may be treated as a substitute for red-berried ardisia and serve as an alternative source for the acquisition of plant material rich in bioactive saponins.

Bioactive benzoquinones content variability in red-berry and white-berry varieties of Ardisia crenata Sims. and assessment of cytotoxic activity.

Ardisia crenata Sims (Myrsinaceae) occurs in two varieties differing in the fruit color, the red berries being common while the white ones are rare. The roots of red-berried A. crenata are a valued TCM product which contains bioactive benzoquinones such as embelin and rapanone. In this study we compared their profiles in different organs of the plant to provide an insight in the pattern of their accumulation within the two varieties. Moreover, cytotoxic activity against human melanoma and prostate cancer cells was evaluated. Quantitative HPLC revealed that the white-berried variety differs profoundly in the content of rapanone, with its total level of 606.5 mg/100 g d.w., as compared to 16.2 mg/100 g d.w. in A. crenata 'red'. Embelin was less distributed and found in minor amounts in both varieties. This is the first report on rapanone content in various parts of Ardisia crenata and on benzoquinones in the white-berried variety.

Effect of cold plasma and elicitors on bioactive contents, antioxidant activity and cytotoxicity of Thai rat-tailed radish microgreens.

BACKGROUND: Raphanus sativus var. caudatus or Thai rat-tailed radish (RTR) contains glucosinolates and isothiocyanates with chemopreventive effects; however, only mature plants have been investigated to date. Thus, the present study aimed to determine isothiocyanates, phenolic compounds and flavonoid compounds, antioxidant activity, cytotoxicity, and antiproliferative activity of RTR microgreens grown from seeds treated with cold plasma (21 kV for 5 min), organic elicitor (160 mmol L-1 NaCl, 10 mmol L-1 CaCl2 or 176 mmol L-1 sucrose) or both in combination. Seeds were germinated on vermiculite and sprayed with deionized water or elicitor for 7 days before harvest. RESULTS: Cold plasma had insignificant effect on growth, whereas NaCl and CaCl2 increased fresh weight. Plasma with CaCl2 led to the highest total isothiocyanate (ITC) content [1.99 g kg-1 dry weight (DW)] in RTR microgreens containing raphasatin as the only ITC detected. Plasma treatment gave the highest total phenolic content (7.56 mg gallic acid equivalents g-1 DW), antioxidant activity from a 2,2-diphenyl-1-picrylhydrazyl assay (7.70 mg trolox equivalents g-1 DW) and ferric reducing antioxidant power assay (21.72 mg Fe2+ g-1 DW). Microgreen extracts from plasma showed an IC50 value of 29.28 and 13.83 µg mL-1 towards MCF-7 and HepG2, respectively, with inhibitory properties on matrix metalloproteinase (MMP)-2 and MMP-9 proteins. Plasma enhanced Bax and Caspase-3 gene expression but reduced Bcl-2 and MMP-9 expression, indicating activation of apoptosis. CONCLUSION: Cold plasma shows promise as an innovative tool to enhance bioactive compounds with chemopreventive benefits in microgreens. © 2020 Society of Chemical Industry.

Interactions of the major effective components in Shengmai formula with breast cancer resistance protein at the cellular and vesicular levels.

Shengmai Formula (SMF) is one of the traditional Chinese medicine representative formulas and is widely used for the treatment of cardio- and cerebrovascular disease. Previous studies demonstrated that the major effective ingredients in SMF can interact with each other based on some uptake transporters. However, the role of the efflux transporter breast cancer resistance protein (BCRP) in these interactions involving SMF remains unclear. The purpose of this study was to investigate the interactions of the major active components of SMF with BCRP and the compatibility mechanism of these complex components in SMF based on BCRP. We selected 4 main fractions, including ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), and fructus schisandrae total lignans (STL), and 12 bioactive components, including ginsenosides Re, Rd, Rb1, and Rg1, ophiopogonins D and D', methylophiopogonanones A and B, schizandrins A and B, and schizandrols A and B to explore the interactions of SMF with BCRP in LLC-PK1 and LLC-PK1/BCRP cells and BCRP membrane vesicles. The results showed that ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A can be transported by BCRP into LLC-PK1/BCRP cells. Schisandrol B exhibited a markedly inhibitory effect on the transport function of BCRP and can significantly inhibit the uptake of methylophiopogonanone B and schizandrin A into LLC-PK1/BCRP cells. In "Inside-Out" BCRP membrane vesicles, BCRP mediated the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A, with Km values of 111.9 ±â€¯31.26 µM, 82.01 ±â€¯16.72 µM, 57.06 ±â€¯8.789 µM, and 37.19 ±â€¯6.512 µM, respectively. GTS, STL, ginsenosides Rd and Rb1, and schisandrol B were potent inhibitors of BCRP and showed different degrees of inhibition on the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A via BCRP. In conclusion, GTS, STL, ginsenosides Rd and Rb1, and schizandrol B are potential inhibitors of BCRP. Ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A are potential substrates of BCRP, and their transport, which is mediated by BCRP, may be inhibited by potential inhibitors in SMF. There are potential interactions of these main effective components of SMF at the cellular and vesicular levels that are mediated by BCRP. The interplay of these bioactive components based on BCRP may be an important compatibility mechanism in SMF.

Chemical profiling and cytotoxic activity of 150-year old original sample of Jerusalem Balsam.

Herbal formulations have been used in ethnomedicine and pharmacy around the world for thousands of years. One of them is Jerusalem Balsam (JB), which came into use in the seventeenth century. Today, people still produce and use it regularly as prophylactic supplement. JB has been widely used in Europe since the nineteenth century, as a remedy possessing antibacterial, antifungal and anti-inflammatory activities. The composition of the product was not known, although possible formulations were reported. In this study the original sample, which dated back to 1870, was investigated for chemical composition and cytotoxic activity. The obtained results were compared with results from more recently produced samples. Several tests were carried out, namely GC-MS, UPLC-PDA-Q-TOF-MS and MTT. Only the 150-year old sample showed a significant cytotoxic activity on cancer cell lines. At a concentration of 125 µg/mL after 72 h of incubation, the original sample inhibited almost 90% of cell metabolic activity, while contemporary samples showed none or little activity. None of the tested samples showed a significant impact on normal cells. These results may be attributed to the activities of benzoic acid and its derivatives, cinnamic acid derivatives, vanillin, group of sesquiterpenes and cembrene.

Comparative study of salicylic acid contents in young wheat and rice plants and their anticancer activities in HepG2 and Caco-2 cells.

Some recent results reported that aspirin (acetylsalicylic acid) had a positive effect on the treatment of certain types of cancer. However, the results cannot be generalized and it is not always clear whether it is a direct anticancer effect or a general health effect. Since plants produce different amounts of salicylic acid, we have sought a relationship between the salicylic acid content of some plant extracts and their anticancer activity. Growing of wheat and rice plants were carried out under controlled conditions. The salicylic acid content was determined by high-performance liquid chromatography. The viability and cell cycle assays were performed on HepG2 and Caco-2 cell lines. Despite the high content of salicylic acid, the extracts from rice plants did not show significant anticancer activity. In spite of the low salicylic acid content, the positive effect of wheat germ was confirmed in both tests. There is no direct relationship between the salicylic acid content of the plant extracts and their anticancer activity. However, it has been proven that young wheat germ is more effective than mature leaf.

Herb-Drug Interaction Potential of Licorice Extract and Paclitaxel: A Pharmacokinetic Study in Rats.

BACKGROUND AND OBJECTIVES: Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb-drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. METHODS: A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). RESULTS: The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC0-t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC0-t (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05). CONCLUSIONS: The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.

Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells.

For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-α, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-α, IL-1ß, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids >30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC50) ≤ 7.0 µg/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, ß-ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC50 = 5.9 µM, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokines. Its content in nutraceuticals correlated strongly with TNF-, IL-6, and IL-8 release inhibition.

Essential oil extracted from erythrina corallodendron L. leaves inhibits the proliferation, migration, and invasion of breast cancer cells.

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.

Separation and determination of amygdalin and unnatural neoamygdalin in natural food supplements by HPLC-DAD.

This work is focused on separation and determination of amygdalin and its unnatural form neoamygdalin in natural food supplements. Reversed-phase high-performance liquid chromatography with a high-stability silica-based column with C18 functional group has been used for solving this problem. The effect of the mobile phase composition as well as the column temperature on the separation of the amygdalin epimers has been investigated. Isocratic elution using a mobile phase composed of 0.05% aqueous formic acid and acetonitrile achieved the required separation within 17 min. Under optimum chromatographic conditions, the developed method was validated and was applied for the determination of amygdalin epimers in natural food supplements containing apricot or peach kernels. A simple extraction method using methanol as an extractant supported by an ultrasonic bath was used with recovery in the range of 94.8% to 104.3%. The limit of detection and limit of quantification values for R-amygdalin were 0.13 mg/L and 0.40 mg/L, respectively. The developed method proved to be precise with the intra-day and inter-day relative standard deviation values less than 2.23%.

The Nutritional Value and Biological Activity of Concentrated Protein Fraction of Potato Juice.

Potato protein is recognized as one of the most valuable nonanimal proteins due to the high content of essential amino acids. So far, it has not been used in human nutrition on a large scale due to technological limitations regarding its acquisition. In this study, the protein fraction of potato juice was concentrated with the use of membrane separation. The obtained potato juice protein concentrate (PJPC) was characterized in terms of nutritional value and biological activity, and the amino acid composition, mineral content, and antioxidant properties were determined. Moreover, in vitro cytotoxic activity against cancer cells of the gastrointestinal tract was investigated. The results of the present study indicate that PJPC is an excellent source of lysine and threonine, while leucine is its limiting amino acid, with an amino acid score (AAS) of 65%. Moreover, PJPC contains substantial amounts of Fe, Mn, K, and Cu. As demonstrated experimentally, PJPC is also characterized by higher antioxidant potential than potato itself. Biological activity, however, is not limited to antioxidant activity alone. Cytotoxicity studies using a gastric cancer cell line (Hs 746T), a colon cancer cell line (HT-29), and human colon normal cells (CCD 841 CoN) proved that PJPC is characterized by selective activity against cancer cells. It can thus be concluded that the developed method of producing protein concentrate from potato juice affords a product with moderate nutritional value and interesting biological activity.

Anti-cervical carcinoma effect of Portulaca oleracea L. polysaccharides by oral administration on intestinal dendritic cells.

BACKGROUND: Cervical cancer is the second most prevalent cancer worldwide. Portulaca oleracea L. polysaccharide (POL-P3b) has been found to have enhancing immune and anti-cervical cancer activity by oral administration. Dendritic cells (DC) play a key roles in regulating intestinal immune homeostasis. In this study, we analyzed the inhibition apoptosis effects of POL-P3b on intestinal DC and relevant mechanisms. METHODS: Intestinal DC was isolated from U14-bearing mice treated with POL-P3b (50 mg/kg, 100 mg/kg and 200 mg/kg, respectively). The effects of POL-P3b on proliferation and inhibiting apoptosis in intestinal DC were evaluated by MTT assay, Hoechst 33342 and Annexin V-FITC/PI staining. Mitochondrial Ca2+ was analyzed using flow cytometry instrument. The potential mechanisms underlying POL-P3b-induced protection of intestinal DC from cervical cancer-induced apoptosis were detected with Western blotting evaluation of expression levels of TLR4 and relevant proteins for apoptotic signaling pathway. RESULTS: We found that a large number of intestinal DC were apoptosis in U14-bearing mice. Treatment with POL-P3b in U14-bearing mice at different doses for 12 d resulted in a significant increase in intestinal DC survival, and the mechanisms were related to inhibiting DC apoptosis. CONCLUSION: Our results suggested that POL-P3b-induced protection against tumor-induced intestinal DC apoptosis through stimulating the TLR4-PI3K/AKT-NF-κB signaling pathway. This study enhanced understanding of the oral administration with POL-P3b exerted on anti-tumor activity and its action mechanism.

Biological and toxicological evaluation of Rhus trilobata Nutt. (Anacardiaceae) used traditionally in mexico against cancer.

BACKGROUND: Rhus trilobata Nutt. (Anacardiaceae) (RHTR) is a plant of Mexico that is traditionally used as an alternative treatment for several types of cancer. However, the phytochemical composition and potential toxicity of this plant have not been evaluated to support its therapeutic use. Therefore, this study aimed to evaluate the biological activity of RHTR against colorectal adenocarcinoma cells, determine its possible acute toxicity, and analyze its phytochemical composition. METHODS: The traditional preparation was performed by decoction of stems in distilled water (aqueous extract, AE), and flavonoids were concentrated with C18-cartridges and ethyl acetate (flavonoid fraction, FF). The biological activity was evaluated by MTT viability curves and the TUNEL assay in colorectal adenocarcinoma (CACO-2), ovarian epithelium (CHO-K1) and lung/bronchus epithelium (BEAS-2B) cells. The toxicological effect was determined in female BALB/c mice after 24 h and 14 days of intraperitoneal administration of 200 mg/kg AE and FF, respectively. Later, the animals were sacrificed for histopathological observation of organs and sera obtained by retro-orbital bleeding for biochemical marker analysis. Finally, the phytochemical characterization of AE and FF was conducted by UPLC-MSE. RESULTS: In the MTT assays, AE and FF at 5 and 18 µg/mL decreased the viability of CACO-2 cells compared with cells treated with vehicle or normal cells (p ≤ 0.05, ANOVA), with changes in cell morphology and the induction of apoptosis. Anatomical and histological analysis of organs did not reveal important pathological lesions at the time of assessment. Additionally, biochemical markers remained normal and showed no differences from those of the control group after 24 h and 14 days of treatment (p ≤ 0.05, ANOVA). Finally, UPLC-MSE analysis revealed 173 compounds in AE-RHTR, primarily flavonoids, fatty acids and phenolic acids. The most abundant compounds in AE and FF were quercetin and myricetin derivates (glycosides), methyl gallate, epigallocatechin-3-cinnamate, ß-PGG, fisetin and margaric acid, which might be related to the anticancer properties of RHTR. CONCLUSION: RHTR exhibits biological activity against cancer cells and does not present adverse toxicological effects during its in vivo administration, supporting its traditional use.

Comparative Analysis of Pentacyclic Triterpenic Acid Compositions in Oleogum Resins of Different Boswellia Species and Their In Vitro Cytotoxicity against Treatment-Resistant Human Breast Cancer Cells.

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC50 of 8.3 ± 0.6 µg/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts.

Potent antitumor property of Allium bakhtiaricum extracts.

BACKGROUND: Allium species are magnificently nutritious and are commonly used as a part of the diet in Iran. They have health enhancing benefits including anticancer properties due to the presence of numerous bioactive compounds. Herein, we investigated in vitro and in vivo anticancer properties of Allium bakhtiaricum extracts. METHODS: Anti-growth activity of different fractions was explored in vitro on different cancerous cells using MTT assay, Annexin V/PI and SA-ß-gal staining, Western blotting, flowcytometric and immunofluorescence microscopic evaluations. In vivo antitumor activity was investigated in BALB/c mice bearing 4 T1 mammary carcinoma cells. RESULTS: We demonstrated that chloroformic and ethyl acetate fractions exert cytotoxic activity toward MDA-MB-231 cells, the most sensitive cell line, after 72 h of treatment with IC50 values of 0.005 and 0.006 mg/ml, respectively. Incubation of MDA-MB-231 cells with » and ½ IC50-72h concentrations of each fraction resulted in a significant G2/M cell cycle arrest. » IC50-72h concentration of the chloroform fraction led to the disruption of polymerization in mitotic microtubules. Exposure of human breast cancer cells to different concentrations of the extracts at different incubation times did not induce apoptosis, autophagy or senescence. Our in vivo study revealed that administration of the chloroform extract at a dose of 1 mg/kg/day strongly suppressed mammary tumor progression and decreased the number of proliferative cells in the lung tissues indicating its anti-metastatic effect. CONCLUSION: Our findings imply that the chloroform fraction of Allium bakhtiaricum possesses the suppressive action on breast cancer through mitotic cell cycle arrest suggesting a mechanism associated with disturbing microtubule polymerization.