63 research outputs found
Antiangiogenic activity and cytotoxicity of triterpenoids and homoisoflavonoids from 'Massonia pustulata' and 'Massonia bifolia'
The Hyacinthaceae family (sensu APGII) with approximately 900 species in around 70 genera, plays a significant role in traditional medicine in Africa as well as across Europe and the Middle and Far East. The dichloromethane extract of the bulbs of Massonia pustulata (Hyacinthaceae sensu APGII) yielded two known homoisoflavonoids, (R)-5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromanone 1 and 5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromone 2 and four spirocyclic nortriterpenoids, eucosterol 3, 28-hydroxyeucosterol 4 and two previously unreported triterpenoid derivatives, (17S,23S)-17Ī±,23-epoxy-3Ī²,22Ī²,29-trihydroxylanost-8-en-27,23-olide 5 and (17S, 23S)-17Ī±,23-epoxy-28,29-dihydroxylanost-8-en-3-on-27,23-olide 6. Compounds 1, 2, 3, and 5 were assessed for cytotoxicity against CaCo-2 cells using a neutral red uptake assay. Compounds 1, 2 and 5 reduced cell viability by 70% at concentrations of 30, 100 and 100 Ī¼M respectively. Massonia bifolia yielded three known homoisoflavonoids, (R)-(4ā-hydroxy)-5-hydroxy-7-methoxy-4-chromanone 1, (R)-(4ā-hydroxy)-5,7-dihydroxy-4-chromanone 7 and (R)-(3ā-hydroxy-4ā-methoxy)-5,7-dihydroxy-4-chromanone 9, two previously unreported homoisoflavonoids, (E)-3-benzylidene-(3ā,4ā-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 8 and (R)-(3ā,4ā-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 10, and a spirocyclic nortriterpenoid, 15-deoxoeucosterol 11. Compounds 1, 1Ac, 7, 8, 9 and 10 were screened for antiangiogenic activity against human retinal microvascular endothelial cells. Some compounds showed dose-dependent antiproliferative activity and blocked endothelial tube formation, suggestive of antiangiogenic activity
Phytochemical investigations of three Rhodocodon (Hyacinthaceae Sensu APG II) species
The genus Rhodocodon (Hyacinthaceae sensu APG II) is endemic to Madagascar and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3 and 6-8) have been isolated and identified. Compounds 1-3 and 6-8 have not been described previously. The COX-2 inhibitory activity of compound 6 and compound 7 acetate (compound 7A) were investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 M compared to 12% for 1 mM aspirin (the positive control)
Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by 'Annona muricata' L. bark extract and phytochemical, annonacin
Background: Annona muricata L. was identified as a popular medicinal plant in treatment regimens among cancer patients in Jamaica by a previously conducted structured questionnaire. Ethnomedically used plant parts, were examined in this study against human prostate cancer cells for the first time and mechanisms of action elucidated for the most potent of them, along with the active phytochemical, annonacin.
Methods: Nine extracts of varying polarity from the leaves and bark of A. muricata were assessed initially for cytotoxicity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on PC-3 prostate cancer cells and the ethyl acetate bark (EAB) extract was identified as the most potent. EAB extract was then standardized for annonacin content using High-performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) and shown to be effective against a second prostate cancer cell line (DU-145) also. The mode of cell death in DU-145 cells were assessed via several apoptotic assays including induction of increased reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, activation of caspases and annexin V externalization combined with morphological observations using confocal microscopy. In addition, the potential to prevent metastasis was examined via inhibition of cell migration, vascular endothelial growth factor (VEGF) and angiogenesis using the chorioallantoic membrane assay (CAM).
Results: Annonacin and EAB extract displayed selective and potent cytotoxicity against the DU-145 prostate carcinoma cells with IC50 values of 0.1 Ā± 0.07 Ī¼M and 55.501 Ā± 0.55 Ī¼g/mL respectively, without impacting RWPE-1 normal prostate cells, in stark contrast to chemotherapeutic docetaxel which lacked such selectivity. Docetaxelās impact on the cancerous DU-145 was improved by 50% when used in combination with EAB extract. Insignificant levels of intracellular ROS content, depolarization of mitochondrial membrane, Caspase 3/7 activation, annexin V content, along with stained morphological evaluations, pointed to a non-apoptotic mode of cell death. The extract at 50 Ī¼g/mL deterred cell migration in the wound-healing assay, while inhibition of angiogenesis was displayed in the CAM and VEGF inhibition assays for both EAB (100 Ī¼g /mL) and annonacin (0.5 Ī¼M).
Conclusions: Taken together, the standardized EAB extract and annonacin appear to induce selective and potent cell death via a necrotic pathway in DU-145 cells, while also preventing cell migration and angiogenesis, which warrant further examinations for mechanistic insights and validity in-vivo
Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of 'Artocarpus heterophyllus' Lam
Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLCāMSāDAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 Ī¼g/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-Ī³) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent
The antiangiogenic activity of naturally occurring and synthetic homoisoflavonoids from the Hyacinthaceae (sensu APGII)
Excessive blood vessel formation in the eye is implicated in wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes of blindness. Small molecule antiangiogenic drugs are strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown to have potent antiproliferative activities in endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Here, we tested the antiangiogenic activity of a group of naturally occurring homoisoflavonoids isolated from the family Hyacinthaceae and related synthetic compounds, chosen for synthesis based on structureāactivity relationship observations. Several compounds showed interesting antiproliferative and antiangiogenic activities in vitro on retinal microvascular endothelial cells, a disease-relevant cell type, with the synthetic chromane, 46, showing the best activity (GI50 of 2.3 Ć 10ā4 Ī¼M)
In vitro cytotoxic effects of chemical constituents of Euphorbia grandicornis Blanc against breast cancer cells
Euphorbia grandicornis Blanc is widely utilized in traditional medicine for a variety of ailments including body pains associated with skin irritations, inflammation, and snake or scorpion bites. Compounds from E. grandicornis were characterized using spectroscopic techniques, NMR, IR, MS, and melting points and alongside the extracts were evaluated for in vitro anticancer activity against several cancer cell lines. The root extract afforded known, Ī²-glutinol (1), Ī²-amyrin (2), 24-methylenetirucalla-8-en-3Ī²-ol (3), tirucalla-8,25-diene-3Ī²,24R-diol (4), stigmasterol (5), sitosterol (6), and hexyl (E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate (7) based on their NMR spectroscopic data for the first report in E. grandicornis. The extracts and isolated compounds were evaluated for anticancer activities against hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. The CH2Cl2 extract exhibited potent, cytotoxicity against MCF-7, HCC70, and MCF-12A cells. The aerial extract exhibited IC50 values of 1.03, 0.301, and 1.68 Āµg/mL, and root extract displayed IC50 values of 0.83, 0.83 and 3.98 Āµg/mL against MCF-7, HCC70, and MCF-12A cells respectively. The root extract thus showed selectivity for the cancer cell lines over the non-cancerous control cell line (SIāÆ=āÆ4.80). Hexyl (E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate (7) showed significant activity with IC50 values of 23.41, 29.45 and 27.01 ĀµM against MCF-7, HCC70 and MCF-12A cells respectively, suggesting non-specific cytotoxicity
Melanin production inhibitors from the West African 'Cassipourea congoensis'
Cassipourea congoensis (syn. Cassipourea malosana) is used in African countries as a skin-lightening agent. Two previously unreported cycloartane triterpenoids, 26-hydroxy-3-keto-24-methy lenecycloartan-30-oic acid 1 and 24-methylene-cycloartan-3Ī²,26,30-triol 2 along with the known mahuannin B 3, 7-methoxymahuannin B 4, 7-methoxygeranin A 5, methyl-3-(4-hydroxy-3-methoxyphenyl)-2E-propenoate, glycerol-1-alkanoate, (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enal 6, (-)-syringaresinol 7, and stigmast-5-en-3-O-Ī²-D-glucoside, were isolated from the roots of C. congoensis. The crude extract and compounds 1 and 5 were found to inhibit the production of melanin at 10 Ī¼M with low cytotoxicity validating the ethno-medicinal use of this plan
Plant Power:Opportunities and challenges for meeting sustainable energy needs from the plant and fungal kingdoms
Societal Impact Statement
Bioenergy is a major component of the global transition to renewable energy technologies. The plant and fungal kingdoms offer great potential but remain mostly untapped. Their increased use could contribute to the renewable energy transition and addressing the United Nations Sustainable Development Goal 7 āEnsure access to affordable, reliable, sustainable and modern energy for all.ā Current research focuses on species cultivated at scale in temperate regions, overlooking the wealth of potential new sources of smallāscale energy where they are most urgently needed. A shift towards diversified, accessible bioenergy technologies will help to mitigate and adapt to the threats of climate change, decrease energy poverty, improve human health by reducing indoor pollution, increase energy resilience of communities, and decrease greenhouse gas emissions from fossil fuels.
Summary
Bioenergy derived from plants and fungi is a major component of the global transition to renewable energy technologies. There is rich untapped diversity in the plant and fungal kingdoms that offers potential to contribute to the shift away from fossil fuels and to address the United Nations Sustainable Development Goal 7 (SDG7) āEnsure access to affordable, reliable, sustainable and modern energy for all.ā Energy povertyāthe lack of access to modern energy servicesāis most acute in the Global South where biodiversity is greatest and least investigated. Our systematic review of the literature over the last 5 years (2015ā2020) indicates that research efforts have targeted a very small number of plant species cultivated at scale, mostly in temperate regions. The wealth of potential new sources of bioenergy in biodiverse regions, where the implementation of SDG7 is most urgently needed, has been largely overlooked. We recommend next steps for bioenergy stakeholdersāresearch, industry, and governmentāto seize opportunities for innovation to alleviate energy poverty while protecting biodiversity. Smallāscale energy production using native plant species in bioenergy landscapes overcomes many pitfalls associated with bioenergy crop monocultures, such as biodiversity loss and conflict with food production. Targeted traitābased screening of plant species and biological screening of fungi are required to characterize the potential of this resource. The benefits of diversified, accessible bioenergy go beyond the immediate urgency of energy poverty as more diverse agricultural landscapes are more resilient, store more carbon, and could also reduce the drivers of the climate and environmental emergencies
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