Antiviral Rotenoids and Isoflavones Isolated from Millettia oblata ssp. teitensis.

Three new (1-3) and six known rotenoids (5-10), along with three known isoflavones (11-13), were isolated from the leaves of Millettia oblata ssp. teitensis. A new glycosylated isoflavone (4), four known isoflavones (14-18), and one known chalcone (19) were isolated from the root wood extract of the same plant. The structures were elucidated by NMR and mass spectrometric analyses. The absolute configuration of the chiral compounds was established by a comparison of experimental ECD and VCD data with those calculated for the possible stereoisomers. This is the first report on the use of VCD to assign the absolute configuration of rotenoids. The crude leaves and root wood extracts displayed anti-RSV (human respiratory syncytial virus) activity with IC50 values of 0.7 and 3.4 µg/mL, respectively. Compounds 6, 8, 10, 11, and 14 showed anti-RSV activity with IC50 values of 0.4-10 µM, while compound 3 exhibited anti-HRV-2 (human rhinovirus 2) activity with an IC50 of 4.2 µM. Most of the compounds showed low cytotoxicity for laryngeal carcinoma (HEp-2) cells; however compounds 3, 11, and 14 exhibited low cytotoxicity also in primary lung fibroblasts. This is the first report on rotenoids showing antiviral activity against RSV and HRV viruses.

Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia. AIM: Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats. MATERIALS AND METHODS: The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD50) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus. RESULTS: No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD50 was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract. CONCLUSION: M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

Purification, structural elucidation and biological activities of exopolysaccharide produced by the endophytic Penicillium javanicum from Millettia speciosa Champ.

An acid polysaccharide, named HP, was produced by endophytic Penicillium javanicum MSC-R1 isolated from southern medicine Millettia speciosa Champ. The molecular weight of HP was 37.8 kDa and consisted of Ara f, Galр, Glcр, Manр, and GlcрA with a molar ratio of 1.09: 3.47: 68.48: 16.59: 8.85. The glycosidic linkage of HP was proven to be →3, 4)-α-D-Glcр-(1→6)-α-D-Manр-(1→, →3, 4)-α-D-Glcр-(1→4)-α-D-Glcр-(1→, →3), →6)-α-D-Manр-(1→4)-α-D-Glcр-(1→, →3), ß-D-Galр-(1→3)-α-D-Glcр-(1→, →4), →5)-α-L-Ara f -(1→3)-α-D-Glcр-(1→, →4), →6)-α-D-Manр-(1→4)-α-D-GlcAр-(1→ and →4)-α-D-GlcAр-(1→4)-α-D-Glcр-(1→, →3). Additionally, 250 µg/mL of HP possessed nontoxicity to RAW 264.7 cells and exhibited anti-inflammation activity. HP could significantly restrain the amount of tumor necrosis factor-α, interleukin-6 and NO release in RAW264.7, which property is possibly associated with its abundant glucosidic linkage. These results indicated that HP could be regarded as a ponderable ingredient for the health-beneficial functional foods.

Cytotoxic effect and antioxidant activity of pterocarpans from Millettia aboensis root.

Chemical analysis of the methanol extract of the root bark of Millettia aboensis led to the isolation of homopterocarpin (1), secundiflorol I (2), and maackain (3). The structures of these compounds were elucidated based on their MS and NMR spectra. The crude methanol root extract was screened for its cytotoxic activity on mouse lymphoma cell line (L5178Y), and the isolated compounds were tested for their antioxidant activity using a 2, 2-diphenylhydrazyl (DPPH) radical scavenging model. The crude methanol root extract gave a percentage growth inhibition of 87.5% on the mouse lymphoma cell line (L5178Y). Compound 3 gave the highest antioxidant activity with an IC50 of 83 µg/ml. These compounds can serve as leads for anticancer agents.

Hepatoprotective Effect of Millettia dielsiana: In Vitro and In Silico Study.

In silico docking studies of 50 selected compounds from Millettia dielsiana Harms ex Diels (family Leguminosae) were docked into the binding pocket of the PI3K/mTOR protein. In there, compounds trans-3-O-p-hydroxycinnamoyl ursolic acid (1) and 5,7,4'-trihydroxyisoflavone 7-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (2) are predicted to be very promising inhibitors against PI3K/mTOR. They direct their cytotoxic activity against Hepatocellular carcinoma with binding affinity (BA) values, the pulling work spent to the co-crystallized ligand from the binding site of PI3K/mTOR (W and Fmax), and the non-equilibrium binding free energy (∆GneqJar) as BA values = -9.237 and -9.083 kcal/mol, W = 83.5 ± 10.6 kcal/mol with Fmax = 336.2 ± 45.3 pN and 126.6 ± 21.7 kcal/mol with Fmax = 430.3 ± 84.0 pN, and ∆GneqJar = -69.86074 and -101.2317 kcal/mol, respectively. In molecular dynamic simulation, the RMSD value of the PI3K/mTOR complex with compounds (1 and 2) was in the range of 0.3 nm to the end of the simulation. Therefore, the compounds (1 and 2) are predicted to be very promising inhibitors against PI3K/mTOR. The crude extract, ethyl acetate fraction and compounds (1 and 2) from Millettia dielsiana exhibited moderate to potent in vitro cytotoxicity on Hepatocellular carcinoma cell line with IC50 values of 81.2 µg/mL, 60.4 µg/mL, 23.1 µM, and 16.3 µM, respectively, and showed relatively potent to potent in vitro antioxidant activity on mouse hepatocytes with ED50 values of 24.4 µg/mL, 19.3 µg/mL, 30.7 µM, and 20.5 µM, respectively. In conclusion, Millettia dielsiana and compounds (1 and 2) are predicted to have very promising cytotoxic activity against Hepatocellular carcinoma and have a hepatoprotective effect.

Brandisianones F and G from Millettia brandisiana Kurz and their cytotoxicity.

A new flavanone and a new chalcone, brandisianones F and G, were purified from the roots of Millettia brandisiana Kurz, moreover, sixteen known compounds were found. The chemical structures of all isolated compounds were identified using spectroscopic methods including 1D-NMR, 2D-NMR, MS, IR and CD data. Chalcone 15 exhibited the most cytotoxic activity against liver cancer, HepG2, and cholangiocarcinoma, KKU-M156, cell lines with IC50 values of 1.74 ± 0.91 and 1.95 ± 0.95 µg/mL, respectively. Chalcones 2, 14, 16 and 18 as well as flavones 5, 6 and 12 showed moderate cytotoxicity with IC50 values ranging from 5.39 to 14.00 µg/mL.[Formula: see text].

Health promoting benefits of pongamol: An overview.

Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization, these novel chemicals have led to the discovery of new pharmacological active agents. Research on herbal medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities. Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer, anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity, and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pongamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers information related to the toxicological assessment and safety of this phytochemical, and highlights the medicinal and folk values of this compound against various diseases and ailments.

A comparative appraisal of three important oil yielding plants for their biodiesel potential.

In the present scenario, alternative energy sources are required to achieve the future economic prosperity where shortage of fossil fuels will be a limiting factor and hamper the global economic growth. Therefore, interest in biofuel is increasing continuously. The best way of sustainable development is fossil fuel supplementation with biodiesel to reduce the fossil fuel demand. Biodiesel is a clean burning, ester-based, oxygenated fuel derived from natural and renewable sources. Till now, majority of the people have worked on the biodiesel derived from edible oil. Instead of using edible oil, non-edible oil needs to be explored as feedstock for biofuel because half of the world's population is unable to afford the food oil as feedstock for fuel production. Looking at the significance of biodiesel and the resources of biofuel, in this paper, a comparative exhaustive study has been reported with for three important plants, namely Jatropha curcas, Pongemia pinnata and Balanites aegyptiaca. These plants were selected based on their biodiesel potential, availability, cultivation practices and general information available. The present study involves scientometric publications, comparison of fatty acid composition and biodiesel parameters. We have also compared climatic conditions for the growth of the plants, economic feasibility of biodiesel production and other ecological services. The study paves a way for sustainable solution to policy makers and foresters looking for selection of plant species as bioenergy resource.

Cytotoxicity of isoflavones from Millettia dura.

The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 µM. Durmillone was the most active with IC50 values of 6.6 µM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 µM), LO2 hepatocytes (IC50 78.7 µM) and CCD19Lu fibroblasts (IC50 >100 µM).

Derrischalcone suppresses cholangiocarcinoma cells through targeting ROS-mediated mitochondrial cell death, Akt/mTOR, and FAK pathways.

Chemotherapy is a palliative treatment for unresectable patients with cholangiocarcinoma (CCA). However, drug resistance is a major cause of the failure of this treatment. Derrischalcone (DC), a novel chalcone isolated from Derris indica fruit, has been shown pharmacologically active; though, the effect of DC on CCA is unknown. The present study investigated the cytotoxic, antiproliferative, anti-migration, and anti-invasion effects and underlying mechanisms of DC on CCA KKU-M156 and KKU-100 cells. Cytotoxicity and apoptosis were evaluated by acridine orange and ethidium bromide fluorescent staining. Reactive oxygen species (ROS) was measured by dihydroethidium assay. Cell proliferation and reproductive cell death were assessed by sulforhodamine B staining and colony-forming assay. Migration and invasion were determined by wound healing and transwell chamber assays. Protein expressions associated with cell death, proliferation, migration, and invasion were analyzed by western immunoblotting. We found that DC induced cytotoxicity and apoptosis in association with ROS formation and oxidative stress. Treatment with N-acetylcysteine suppressed ROS formation and attenuated DC-induced cytotoxic and apoptotic effects. DC increased the expression of p53, p21, Bax, and cytochrome c proteins in association with cell death. DC-induced antiproliferation, colony formation, anti-migration, and anti-invasion were associated with the suppression of Akt/mTOR/cyclin D1 and FAK signaling pathways. These findings suggest that the multi-targeting strategies with DC may be a novel treatment for cancer therapy.

Antimicrobial, antibiofilm, antioxidant, anticancer, and phytochemical composition of the seed extract of Pongamia pinnata.

Ethyl acetate seed extract of Pongamia pinnata displayed the highest antimicrobial potential against all test pathogens and Staphylococcus epidermidis was reported as the most sensitive strain with MIC/MBC 1.56/3.12 mg ml-1. It inhibited S. epidermidis biofilm 97.43% at MIC and LM as well as FE-SEM micrographs displayed extensive disintegration in biofilm. It showed the highest TPC (1.23 ± 0.04 g GAE g-1), TFC (0.95 ± 0.05 g CE g-1), and antioxidant activity with IC50 18.47 ± 0.33 µg ml-1. MTT assay displayed concentration-dependent strong cytotoxicity on K562 cells on the treatment of ethyl acetate extract with an IC50 value of 84.41 µg ml-1. On the other hand, it showed minute cytotoxicity on normal PBMCs with an IC50 value of 410.14 µg ml-1. GC-MS analysis revealed that Hexadecanoic acid (35.97%); 2-(1,3-Benzodioxol-5-yl)furo[2,3-h]chromen-4-one (Pongaglabrone) (22.82%); 2,2-Dimethylindane-1,3-dione- (13.05%) were the three major components in ethyl acetate extract. The present investigation showcases ethyl acetate extract as a potent antimicrobial, antibiofilm, antioxidant, and anticancer agent that opens a new avenue for its phytochemicals as a therapeutic agent.

Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition.

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. METHODS: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. RESULTS: Ovalitenone was used at concentrations of 0-200 µM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. CONCLUSIONS: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

Curcumin-Chitosan Nanocomposite Formulation Containing Pongamia pinnata-Mediated Silver Nanoparticles, Wound Pathogen Control, and Anti-Inflammatory Potential.

BACKGROUND: Because of its diverse range of use in several ethics of diagnosis and care of multiple diseases, nanotechnology has seen remarkable growth and has become a key component of medical sciences. In recent years, there has been rapid advancement in medicine and biomaterials. Nanomedicine aids in illness prevention, diagnosis, monitoring, and treatment. AIM: The purpose of this work is to evaluate the antibacterial, anti-inflammatory, and cytotoxic capabilities of green produced silver nanoparticle with the addition of curcumin-assisted chitosan nanocomposite (SCCN) against wound pathogenic as reducing agents. MATERIALS AND METHODS: The plant extract of Pongamia pinnata, silver nanoparticles, and its based curcumin nanoformulations was studied in this study utilizing UV visible spectrophotometer, selected area electron diffraction (SAED), and TEM. Anti-inflammatory, antimicrobial, and cytotoxic tests were performed on silver nanoparticles with the addition of curcumin-assisted chitosan nanocomposite (SCCN). Furthermore, these produced nanocomposites were coated on clinical silk and tested for antibacterial activity. RESULTS: The produced silver nanoparticle with the addition of curcumin-assisted chitosan nanocomposite (SCCN) has significant antibacterial activities against Pseudomonas aeruginosa and staphylococcus aureus. They are as well as possess anti-inflammatory activity and furthermore prove to be biocompatible. CONCLUSION: This advancement in the field of biomaterials, which means nanocomposite, not only helps to reduce the harmful effects of pathogenic organisms while representing an environmentally benign material but it also shows to be a material with zero danger to humans and the environment.

Modulation of LPS-induced inflammation in RAW264.7 murine cells by novel isoflavonoids from Millettia pulchra.

Millettia pulchra is a renowned anti-inflammatory herbal medicine in southeast provinces of China. However, the underlying anti-inflammation mechanism remained incompletely understood. Herein, four new isoflavones, pulvones A-D and eleven reported constituents were isolated from the stems of Millettia pulchra with their structures being elucidated by HRMS and NMR analysis. The anti-inflammatory activities of pulvones A and C were further evaluated due to the better inhibitory activity on nitric oxide production in LPS-stimulated RAW264.7 cells and no obvious cytotoxicity to RAW264.7 cells. Western blot showed that pulvones A significantly decreased the levels of iNOS and COX-2 proteins and pulvones C only decreased the level of iNOS protein. ELISA analysis demonstrated that pulvones A inhibited the production of both interleukin-6 (IL-6) and IL-1ß while pulvones C showed better suppression effect on IL-1ß production in LPS-stimulated RAW264.7 cells. Then, their potential inhibitory effects on NF-κB pathway were tested in LPS-stimulated RAW264.7 cells. Immunofluorescence and western blot assay showed that pulvones A and C reduced the nuclear translocation of NF-κB(p65) and interrupted IκB phosphorylation. The ADP-Glo™ kinase assay showed pulvones A and C could directedly inhibit the IKKß kinase activity with the inhibitory rate of 40%, which were also verified by docking study. Collectively, these results suggested that pulvones A and C's anti-inflammatory effects were relevant to the interruption of NF-κB activation by inhibiting IKKß kinase.

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells.

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3',4'-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

A new isoflavone with anti-inflammatory effect from the seeds of Millettia pachycarpa.

A new isoflavone, milletenol A (1), along with four known flavonoids (2-5) were isolated from the seeds of Millettia pachycarpa. The structure of 1 was established by extensive spectroscopic methods while known compounds were identified by comparisons with literature data. Compound 1 and 2 showed significant anti-inflammatory activities against nitric oxide production in LPS-induced RAW264.7 macrophages. The state of CuSO4-stimulated inflammation was effectively alleviated by compound 1 in zebrafish. However, no significant cytotoxicity against human breast cancer cells was observed among all isolates.

Method development for optimised green synthesis of gold nanoparticles from Millettia pinnata and their activity in non-small cell lung cancer cell lines.

Green synthesis of gold nanoparticles (GNPs) has received substantial attention, because nanoparticles are produced in an eco-friendly way using biomolecules present in plant extracts in a single step reaction. This research article highlights GNPs obtained using shade-dried leaf extracts of Millettia pinnata (L.) with aqueous auric chloride (HAuCl4) at ambient temperature. In the present study, GNPs with average particle size 37 nm in size were fabricated. Furthermore, the synthesis method to obtain stable and monodispersed GNPs was advanced by optimising enzyme concentration 100 µg/ml, pH 5.4, substrate concentration 0.45 mM and 12 h time of reaction. The confirmation of GNPs formation and characterisation was followed by UV-vis-absorption spectroscopy, dynamic light scattering (DLS), and zeta potential (ZP) for the analysis of shape, size, and stability, respectively. TEM images and powder XRD revealed the GNPs synthesis of spherical-shaped nanoparticles in the face-centred cubic arrangement. Cytotoxicity of GNPs was studied against A549 lung cancer cells with IC50 14.76 µg/ml and found lower as compared to doxorubicin IC50 11.23 µg/ml but significant enough to be used as a vehicle GNPs produced using green source can be used as significant therapeutic agents and drug delivery carriers.

Identification of profilin 1 as the primary target for the anti-cancer activities of Furowanin A in colorectal cancer.

BACKGROUND: Furowanin A (Fur A) is a flavonoid compound isolated from medicinal plant Millettia pachycarpa Benth. This study aims to explore the effect of Fur A on Colorectal cancer (CRC) and its molecular mechanisms. METHODS: Cell proliferative capacity of CRC cells was assessed by CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell migration and invasion were detected by wound healing and Transwell assay, respectively. EMT markers, apoptosis and profilin 1(Pfn1) expression were detected by immunohistochemistry (IHC). The protein expression levels were examined by western blotting. i-TRAQ analyses were conducted to identify the differentially expressed genes in CRC cells. CRC xenograft model was also used to validate the in vivo anti-cancer activity of Fur A. RESULTS: Fur A exhibited anti-prolifertive, blocked cell cycle progression and promoted apoptotic cell death in CRC cells. Fur A suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro, and tumor growth and pulmonary metastasis in vivo, without causing obvious toxicity. iTRAQ analysis identified Pfn1 as a gene up-regulated by Fur A. In xenograft tumor tissue, the expression of Pfn1 was also elevated by Fur A treatment. In clinical CRC samples, high expression of Pfn1 was correlated with lower stage and longer survival. Knockdown of Pfn1 significantly dampened the pro-apoptotic and anti-metastatic activities of Fur A in CRC cells. Ectopic Pfn1 expression augmented the anti-neoplastic activities of Fur A. CONCLUSION: Fur A exhibited anti-cancer activities in vitro and in vivo in CRC by up-regulating Pfn1.

Diverse flavonoids from the roots of Millettia brandisiana.

The phytochemical investigation for the constituents of the roots of Millettia brandisiana, using bioassay guided fractionation, resulted in the isolation of five previously undescribed (namely brandisianones A-E) and twenty-six known flavonoids. Their chemical structures were determined using a combination of NMR, MS, IR, optical rotation and CD analysis, as well as comparison with the literature data. The crude extract as well as the isolated compounds were evaluated in various biological assays for their cytotoxicity against a panel of human cancer cell lines, potential inhibitory activity against aromatase, and antioxidant property using the oxygen radical absorbance capacity (ORAC) with an aim to search for leads and develop them to drug candidates in our drug discovery effort, we identified three bioactive flavonoids from M. brandisiana which could be further developed into a potential chemopreventive (antiaromatase) agent against breast cancer.

Pongapin and Karanjin, furanoflavanoids of Pongamia pinnata, induce G2/M arrest and apoptosis in cervical cancer cells by differential reactive oxygen species modulation, DNA damage, and nuclear factor kappa-light-chain-enhancer of activated B cell signaling.

In this study, the antitumor activity of two furanoflavanoid derivatives, Pongapin and Karanjin, was evaluated in comparison with Plumbagin, a plant-derived polyphenol with proven antitumor activity. The compounds differentially inhibit the growth of different cancer cell lines (most effective on HeLa cells), with very low inhibitory effect on the growth of normal mouse embryonic fibroblast cell line. Pongapin like Plumbagin could significantly increase the intracellular reactive oxygen species (ROS) in the HeLa cells by stabilization of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (I-κB) expression and reduction of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression. In contrast, Karanjin could decrease ROS level by inhibition of I-κB degradation resulting restriction of NF-κB nuclear translocation. Pongapin and Plumbagin significantly increased DNA damage-induced p53 expression and p21 nuclear expression. However, Karanjin treatment showed low DNA damage with increased p53 expression. The compounds induced G2/M arrest and increase in SubG1 population, indicating induction of apoptosis. Apoptosis was further validated by acridine orange/ethidium bromide dual staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay in HeLa cells after treatment with the compounds. The compounds induced caspase-dependent apoptosis through induction of Bax/Bcl-2 ratio either through increased expression of Bax by Pongapin and Plumbagin or low expression of Bcl-2 by Karanjin. Thus, Pongapin and Karanjin may be potential natural anticancer agents in the future, like Plumbagin.