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  1. Antiangiogenic properties of nanoparticles: a systematic review
    Saeed BA, Lim V, Yusof NA, Khor KZ, Rahman HS, Abdul Samad N
    Int J Nanomedicine, 2019;14:5135-5146.
    PMID: 31371952 DOI: 10.2147/IJN.S199974
    Nanoparticles appear to be one of the most promising agents that offer efficacy in angiogenesis-related disease therapy. The objective of this research is to systematically review studies that have probed into the effect of nanoparticles on angiogenesis. Selected inclusion criteria were used to extract articles, references that were cited in the initial search were sought to identify more potential articles, and articles that did not meet the inclusion criteria and duplicates were discarded. The spherical shape was shown to be the most common shape employed to investigate the role of nanoparticles in angiogenesis therapy. The size of nanoparticles appears to play a crucial role for efficacy on angiogenesis, in which 20 nm emerged as the preferred size. Gold nanoparticles exhibit the most promise as an antiangiogenesis agent, and the toxicity was adjustable based on the dosages applied.
    Matched MeSH terms: Angiogenesis Inhibitors
  2. Fulltext The Adjunctive Use of Anti-vascular Endothelial Growth Factor Agents in the Management of Iris Neovascularisation in Malaysia
    Bastion ML, Then KY, Faridah HA, Mushawiahti M, Othmaliza O, Wong HS
    Med J Malaysia, 2011 Mar;66(1):10-4.
    PMID: 23765135 MyJurnal
    This retrospective study investigated the role of antivascular endothelial growth factor agents (VEGF), ranibizumab, bevacizumab and pegaptanib sodium in patients with iris neovascularisation (INV), in which 9 eyes received intraocular injections for various ischaemic ocular conditions. Ocular sequelae included recurrence of rubeosis (n=2) and hyphaema (n=2). Systemic complication included one case of cerebrovascular accident. INV regressed in all cases from day one. INV recurrence occurred in 2 cases. The mean intraocular pressure of the study eyes decreased from 25.3 mmHg to 18.3 mmHg at one month. Five eyes are medication free. Visual acuity improved in 5 eyes. Four eyes achieved a Snellen visual acuity of 6/24 or better. We conclude that the use of intraocular anti-VEGF agents are safe and effective for inducing the regression of INV. Patients with multiple systemic risk factors should be counseled on stroke risk.
    Matched MeSH terms: Angiogenesis Inhibitors*
  3. Fulltext Visual Parameters and Retinal Morphology for Polypoidal Choroidal Vasculopathy Pre- and Post-Intravitreal Ranibizumab with or without Photodynamic Therapy: A Short-Term Prospective Study
    Ghoshal R, Sharanjeet-Kaur S, Fadzil NM, Ghosh S, Ngah NF, Aziz RABA
    Int J Environ Res Public Health, 2021 03 04;18(5).
    PMID: 33806713 DOI: 10.3390/ijerph18052581
    The objective of this study was to compare visual parameters and retinal layers' morphology pre-treatment (baseline) and 6 months post-treatment in polypoidal choroidal vasculopathy (PCV) eyes. A single centre, longitudinal, prospective study was conducted at a public tertiary hospital of Malaysia. Visual parameters including distance and near visual acuity (DVA and NVA), contrast sensitivity (CS), reading speed (RS), and different qualitative and quantitative optical coherence tomography (OCT) parameters were evaluated pre- and 6 months post-treatment. Thirty-three naïve PCV eyes of 32 patients (mean age of 67.62 years) were evaluated pre- and post-treatment of intravitreal ranibizumab with and without photodynamic therapy. After treatment, sub retinal fluid decreased from 27 eyes (84.35%) at baseline to 7 eyes (21.88%) at 6 months while pigment epithelium detachment decreased from 32 eyes (100%) at base line to 15 eyes (46.87%) at 6 months. Mean pre-treatment quantitative morphological OCT retinal parameters including thickness and volume of central sub field, center thickness, center minimum, and maximum thickness reduced significantly. Similarly, all visual parameters including DVA, NVA, CS, and RS showed statistically significant improvement. While 89% of the eyes showed improvement in CS, 78%, 71%, and 65% of the eyes showed improvement in NVA, RS, and DVA, respectively. Thus, CS was the most treatment responsive visual parameter.
    Matched MeSH terms: Angiogenesis Inhibitors/therapeutic use
  4. Intravitreal bevacizumab: a viable treatment for bilateral central retinal vein occlusion with serous macular detachment secondary to Waldenström macroglobulinaemia
    Ratanam M, Ngim YS, Khalidin N, Subrayan V
    Br J Haematol, 2015 Aug;170(3):431-4.
    PMID: 25640801 DOI: 10.1111/bjh.13307
    Matched MeSH terms: Angiogenesis Inhibitors/administration & dosage*
  5. The role of pazopanib on tumour angiogenesis and in the management of cancers: A review
    Chellappan DK, Chellian J, Ng ZY, Sim YJ, Theng CW, Ling J, et al.
    Biomed Pharmacother, 2017 Dec;96:768-781.
    PMID: 29054093 DOI: 10.1016/j.biopha.2017.10.058
    Pazopanib is a relatively new compound to be introduced into the chemotherapy field. It is thought to have decent anti-angiogenic properties, which gives an additional hope for the treatment of certain types of cancers. A systematic review solely discussing about pazopanib and its anti-angiogenic effect is yet to be published to date, despite several relevant clinical trials being conducted over the recent years. In this review, we aim to investigate the mechanism of pazopanib's anti-angiogenic effect and its effectiveness in treating several cancers. We have included, in this study, findings from electronically searchable data from randomized clinical trials, clinical studies, cohort studies and other relevant articles. A total of 352 studies were included in this review. From the studies, the effect of pazopanib in various cancers or models was observed and recorded. Study quality is indefinite, with a few decent quality articles. The most elaborately studied cancers include renal cell carcinoma, solid tumors, advanced solid tumors, soft tissue sarcoma, breast cancer and gynecological cancers. In addition, several less commonly studied cancers are included in the studies as well. Pazopanib had demonstrated its anti-angiogenic effect based on favorable results observed in cancers, which are caused by angiogenesis-related mechanisms, such as renal cell carcinoma, solid tumors, advanced solid tumors and soft tissue sarcoma. This review was conducted to study, analyze and review the anti-angiogenic properties of pazopanib in various cancers. The results obtained can provide a decent reference when considering treatment options for angiogenesis-related malignancies. Furthermore, the definite observations of the anti-angiogenic effects of pazopanib could provide newer insights leading to the future development of drugs of the same mechanism with increased efficiency and reduced adverse effects.
    Matched MeSH terms: Angiogenesis Inhibitors/therapeutic use
  6. Fulltext The role of intravitreal anti-vascular endothelial growth factor injection in peripheral exudative hemorrhagic chorioretinopathy: A systematic review
    Gowda A, Bahrami B, Jie WWJ, Casson R, Chan WO
    Surv Ophthalmol, 2024;69(2):173-178.
    PMID: 37806565 DOI: 10.1016/j.survophthal.2023.10.004
    Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionized the field of ophthalmology, and their use in a variety of retinal diseases is growing. One target disease is peripheral exudative hemorrhagic chorioretinopathy, a disease that is uncommon and poorly understood. Despite this, there are numerous studies and case reports outlining the potential role of intravitreal injection of anti-VEGF medicines to treat it. As such, an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of anti-VEGF injections in peripheral exudative hemorrhagic chorioretinopathy. Anti-VEGF was first used in 2010 to aid in the management of peripheral exudative hemorrhagic chorioretinopathy. Since then, it has been increasingly used to manage this disease. Other potential management strategies, including laser photocoagulation, cryotherapy, photodynamic therapy, and vitrectomy are explored and compared with anti-VEGF where possible. Anti-VEGF appears to be an effective therapy in managing peripheral exudative hemorrhagic chorioretinopathy, especially when there is an exudative threat to the macula.
    Matched MeSH terms: Angiogenesis Inhibitors/therapeutic use
  7. Anti-angiogenic activity of Morinda citrifolia extracts and its chemical constituents
    Beh HK, Seow LJ, Asmawi MZ, Abdul Majid AM, Murugaiyah V, Ismail N, et al.
    Nat Prod Res, 2012;26(16):1492-7.
    PMID: 22292423 DOI: 10.1080/14786419.2011.562208
    Morinda citrifolia L. has been used for the treatment of a wide variety of diseases, including cancer. This study was undertaken to evaluate the anti-angiogenic effect of M. citrifolia fruits and leaves. Anti-angiogenic activity was evaluated in vivo using the chick chorioallantoic membrane assay. Bioactivity-guided fractionation and isolation were performed to identify the active constituent, and high-performance liquid chromatography analysis was then used to quantify the amount of this active constituent in the active extracts and fraction. The methanol extracts of fruits and leaves of M. citrifolia and the subsequent chloroform fraction of the fruit methanolic extract were found to have potential anti-angiogenic activity and were more potent compared to suramin. Scopoletin was identified as one of the chemical constituents that may be partly responsible for the anti-angiogenic activity of M. citrifolia fruits. The present findings further support the use of M. citrifolia in cancer or other pathological conditions related to angiogenesis.
    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/chemistry*
  8. Anti-angiogenic activity of Gynura segetum leaf extracts and its fractions
    Seow LJ, Beh HK, Majid AM, Murugaiyah V, Ismail N, Asmawi MZ
    J Ethnopharmacol, 2011 Mar 24;134(2):221-7.
    PMID: 21167271 DOI: 10.1016/j.jep.2010.12.007
    Gynura segetum is a popular medicinal plant in Indonesia and Malaysia, known to possess various medicinal properties especially for treatment of cancer, diabetes and hypertension.
    Matched MeSH terms: Angiogenesis Inhibitors/analysis; Angiogenesis Inhibitors/pharmacology*
  9. Fulltext Intravitreal ranibizumab in the management of stage 2B Coats disease in a young adult Malay man
    Teh SS, Ahem A, Bastion ML
    BMJ Case Rep, 2013;2013.
    PMID: 23774706 DOI: 10.1136/bcr-2013-009697
    This paper describes a rare case of Coats disease with late presentation in a young adult. The condition improved with a combination of focal photocoagulation, cryotherapy and intravitreal ranibizumab.
    Matched MeSH terms: Angiogenesis Inhibitors/administration & dosage; Angiogenesis Inhibitors/therapeutic use*
  10. Anti-angiogenic and cytotoxicity studies of some medicinal plants
    Ng KW, Salhimi SM, Majid AM, Chan KL
    Planta Med, 2010 Jun;76(9):935-40.
    PMID: 20112179 DOI: 10.1055/s-0029-1240813
    Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation.
    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/therapeutic use
  11. Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer
    Wang S, Yang J, Kuang X, Li H, Du H, Wu Y, et al.
    J Ethnopharmacol, 2024 May 23;326:117913.
    PMID: 38360380 DOI: 10.1016/j.jep.2024.117913
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated.

    AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.

    MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.

    RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.

    CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology; Angiogenesis Inhibitors/therapeutic use
  12. Fulltext Green synthesis of silver nanoparticles using Achillea biebersteinii flower extract and its anti-angiogenic properties in the rat aortic ring model
    Baharara J, Namvar F, Ramezani T, Hosseini N, Mohamad R
    Molecules, 2014 Apr 15;19(4):4624-34.
    PMID: 24739926 DOI: 10.3390/molecules19044624
    Silver nanoparticles display unique physical and biological properties which have attracted intensive research interest because of their important medical applications. In this study silver nanoparticles (Ab.Ag-NPs) were synthesized for biomedical applications using a completely green biosynthetic method using Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs were investigated using UV-visible spectroscopic techniques, transmission electron microscopy (TEM), zeta potential and energy dispersive X-ray spectrometers (EDS). The UV-visible spectroscopic analysis showed the absorbance peak at 460 nm, which indicates the synthesis of silver nanoparticles. The average particle diameter as determined by TEM was found to be 12±2 nm. The zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis also exhibits presentation of silver element. As angiogenesis is an important phenomenon and as growth factors imbalance in this process causes the acceleration of several diseases including cancer, the anti-angiogenic properties of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed that Ab.Ag-NPs (200 μg/mL) lead to a 50% reduction in the length and number of vessel-like structures. The synthesized silver nanoparticles from the Achillea biebersteinii flowers extract, which do not involve any harmful chemicals were well-dispersed and stabilized through this green method and showed potential therapeutic benefits against angiogenesis.
    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology; Angiogenesis Inhibitors/chemistry*
  13. A novel caryophyllene type sesquiterpene lactone from Asparagus falcatus (Linn.); structure elucidation and anti-angiogenic activity on HUVECs
    Ghalib RM, Hashim R, Sulaiman O, Mehdi SH, Valkonen A, Rissanen K, et al.
    Eur J Med Chem, 2012 Jan;47(1):601-7.
    PMID: 22074984 DOI: 10.1016/j.ejmech.2011.10.037
    In this study the novel caryophyllene type sesquiterpene lactone (aspfalcolide) has been isolated from the leaves of Asparagus falcatus (Linn.) and characterized by IR, 1D NMR, 2D NMR, EI-MS, HR-ESI-MS and X-ray single crystal diffraction analysis. The aspfalcolide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 6.37360(10), b = 7.6890(2), c = 27.3281(6) Å, α = β = γ = 90(°) and Z = 4. One intermolecular O-H⋯O hydrogen bond enforces these natural molecules to form infinite chains through the crystal. Aspfalcolide was screened for its anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs) and the result showed the remarkable inhibitory effect of aspfalcolide on the proliferation (IC(50) 1.82 μM), migration and tube formation of HUVECs.
    Matched MeSH terms: Angiogenesis Inhibitors/isolation & purification; Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/chemistry*
  14. Synthesis, thymidine phosphorylase, angiogenic inhibition and molecular docking study of isoquinoline derivatives
    Zaman K, Rahim F, Taha M, Wadood A, Adnan Ali Shah S, Gollapalli M, et al.
    Bioorg Chem, 2019 08;89:102999.
    PMID: 31151055 DOI: 10.1016/j.bioorg.2019.102999
    Isoquinoline analogues (KA-1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11, all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1-9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12, 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues.
    Matched MeSH terms: Angiogenesis Inhibitors/chemical synthesis; Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/chemistry
  15. Development and investigation of thiazolidinedione and pyrazoline compounds as antiangiogenic weapons targeting VEGFR-2
    Upadhyay N, Tilekar K, Safuan S, Kumar AP, Schweipert M, Meyer-Almes FJ, et al.
    Future Med Chem, 2021 11;13(22):1963-1986.
    PMID: 34581188 DOI: 10.4155/fmc-2021-0139
    Background: Angiogenesis deregulation is often linked to cancer and is thus an essential target. Materials & methods: Twenty-nine compounds were developed as VEGFR-2 inhibitors. Compounds were evaluated to determine their antiangiogenic activity. Results: B1, PB11 and PB16 showed HUVEC's IC50 scores in the submicromolar range. B1, B2 and PB16 reduced cellular migration and capillary tube formation of HUVECs. VEGFR-2 inhibitory activity was found in the nanomolar range: 200 nM of B1, 500 nM of B2 and 600 nM of PB16. B1 and PB16 suppressed the formation of new capillaries on growing CAMs. B1 and PB16 occupied the ATP site and allosteric pocket of VEGFR-2 in docking studies. Conclusion: These compounds can target VEGFR-2 and are endowed with in vitro and in vivo antiangiogenic activity.
    Matched MeSH terms: Angiogenesis Inhibitors/chemical synthesis; Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/chemistry
  16. Therapeutic uses of epicatechin in diabetes and cancer
    Abdulkhaleq LA, Assi MA, Noor MHM, Abdullah R, Saad MZ, Taufiq-Yap YH
    Vet World, 2017 Aug;10(8):869-872.
    PMID: 28919675 DOI: 10.14202/vetworld.2017.869-872
    Epicatechin is a natural flavonoid found in green tea. It has been reported to possess an immense antioxidant effect which contributes to its therapeutic effect against a handful of ailments. In this review, we discuss its therapeutic role in the management of two of the most important human diseases; diabetes and cancer. The consumption of epicatechin has been shown to reduce blood glucose levels in diabetic patients, while is anticancer effect was attributed to its antioxidant properties, antiangiogenic and direct cytotoxicity to cancer cells. Although the exact mechanism of action of epicatechin is still being explored, there is no doubt that it is a promising candidate as an alternative. The significance of this review is to highlight the importance of the usage of natural products (in this case, epicatechin) as an alternative for the treatment of two potentially fatal diseases which is diabetes and cancer. The aim of this review is to educate the scientific community on the role of epicatechin in ameliorating the effects of diabetes and cancers on human while understanding the potential mechanisms of these aforementioned effects.
    Matched MeSH terms: Angiogenesis Inhibitors
  17. Fulltext Anti-angiogenesis effect of biogenic silver nanoparticles synthesized Using Saliva officinalis on chick chorioalantoic membrane (CAM)
    Baharara J, Namvar F, Mousavi M, Ramezani T, Mohamad R
    Molecules, 2014;19(9):13498-508.
    PMID: 25255752 DOI: 10.3390/molecules190913498
    Angiogenesis, which is required for physiological events, plays a crucial role in several pathological conditions, such as tumor growth and metastasis. The use of plant extracts is a cost effective and eco-friendly way to synthesize nanoparticles. In the present study, we investigated the anti-angiogenesis properties of silver nanoparticles synthesized using Saliva officinalis extract on chick chorioalantoic membrane. The production of nanoparticles was confirmed by the color change from yellow to brown observed after approximately 3 h at 37 °C. Then, the nanoparticles were characterized by UV-visible spectroscopy, FTIR, and TEM. The UV-visible spectroscopy results showed that the surface plasmon resonance band for AgNPs was around 430 nm. The intensity of the AgNP-specific absorption peak improved with an increase of 0.5 mL of extract into 10 mL of AgNO3 (2.5 mM). The FTIR results showed good interaction between the plant extracts and AgNPs. The TEM images of the samples revealed that the NPs varied in morphology and size from 1 to 40 nm; the average was recorded at 16.5 ± 1.2 nm. Forty Ross fertilized eggs were divided into four groups; the control and three experimental groups. On the 8th day, gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of NPs. On the 12th day, all the cases were photographed using a photostereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. Then the hemoglobin content was measured using Drabkin's reagent kit for quantification of the blood vessel formation. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation. The hemoglobin content in the treated samples with AgNPs decreased, which showed its inhibitory effect on angiogenesis.
    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology*
  18. Fulltext Antioxidant and antiangiogenic activities of the essential oils of Myristica fragrans and Morinda citrifolia
    Piaru SP, Mahmud R, Abdul Majid AM, Mahmoud Nassar ZD
    Asian Pac J Trop Med, 2012 Apr;5(4):294-8.
    PMID: 22449521 DOI: 10.1016/S1995-7645(12)60042-X
    OBJECTIVE: Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans (M. fragrans) (nutmeg) and Morinda citrifolia (M. citrifolia)(mengkudu) oils.

    METHODS: The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essential oils were determined by beta-carotene/linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations.

    RESULTS: The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil. The nutmeg oil effectively inhibited the oxidation of linoleic acid with (88.68±0.1)% while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is (69.44±0.4)%. The nutmeg oil and mengkudu oil showed reducing power with an EC(50) value of 181.4 μg/mL and 3 043.0 μg/mL, respectively. The antiangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC(50) of 77.64 μg/mL comparing to mengkudu oil which exhibits IC(50) of 109.30 μg/mL.

    CONCLUSIONS: Bioactive compound(s) will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.

    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology*
  19. Utilizing Zebrafish to Identify Anti-(Lymph)Angiogenic Compounds for Cancer Treatment: Promise and Future Challenges
    Okuda KS, Lee HM, Velaithan V, Ng MF, Patel V
    Microcirculation, 2016 08;23(6):389-405.
    PMID: 27177346 DOI: 10.1111/micc.12289
    Cancer metastasis which predominantly occurs through blood and lymphatic vessels, is the leading cause of death in cancer patients. Consequently, several anti-angiogenic agents have been approved as therapeutic agents for human cancers such as metastatic renal cell carcinoma. Also, anti-lymphangiogenic drugs such as monoclonal antibodies VGX-100 and IMC-3C5 have undergone phase I clinical trials for advanced and metastatic solid tumors. Although anti-tumor-associated angiogenesis has proven to be a promising therapeutic strategy for human cancers, this approach is fraught with toxicities and development of drug resistance. This emphasizes the need for alternative anti-(lymph)angiogenic drugs. The use of zebrafish has become accepted as an established model for high-throughput screening, vascular biology, and cancer research. Importantly, various zebrafish transgenic lines have now been generated that can readily discriminate different vascular compartments. This now enables detailed in vivo studies that are relevant to both human physiological and tumor (lymph)angiogenesis to be conducted in zebrafish. This review highlights recent advancements in the zebrafish anti-vascular screening platform and showcases promising new anti-(lymph)angiogenic compounds that have been derived from this model. In addition, this review discusses the promises and challenges of the zebrafish model in the context of anti-(lymph)angiogenic compound discovery for cancer treatment.
    Matched MeSH terms: Angiogenesis Inhibitors/chemistry*
  20. Interference Potential of Tannins and Chlorophylls in Zebrafish Phenotypic-Based Assays
    Samat N, Ng MF, Ruslan NF, Okuda KS, Tan PJ, Patel V
    Assay Drug Dev Technol, 2018 10;16(7):408-419.
    PMID: 29985634 DOI: 10.1089/adt.2017.833
    Natural products are prolific producers of diverse chemical scaffolds, which have yielded several clinically useful drugs. However, the complex features of natural products present challenges for identifying bioactive molecules using high-throughput screens. For most assays, measured endpoints are either colorimetric or luminescence based. Thus, the presence of the major metabolites, tannins, and chlorophylls, in natural products could potentially interfere with these measurements to give either false-positive or false-negative hits. In this context, zebrafish phenotypic assays provide an alternative approach to bioprospect naturally occurring bioactive compounds. Whether tannins and/or chlorophylls interfere in zebrafish phenotypic assays, is unclear. In this study, we evaluated the interference potential of tannins and chlorophylls against efficacy of known small-molecule inhibitors that are known to cause phenotypic abnormalities in developing zebrafish embryos. First, we fractionated tannin-enriched fraction (TEF) and chlorophyll-enriched fraction (CEF) from Camellia sinensis and cotreated them with PD0325901 [mitogen-activated protein kinase-kinase (MEK) inhibitor] and sunitinib malate (SM; anti-[lymph]angiogenic drug). While TEF and CEF did not interfere with phenotypic or molecular endpoints of PD0325901, TEF at 100 μg/mL partially masked the antiangiogenic effect of SM. On the other hand, CEF (100 μg/mL) was toxic when treated up to 6 dpf. Furthermore, CEF at 100 μg/mL potentially enhanced the activity of γ-secretase inhibitors, resulting in toxicity of treated embryos. Our study provides evidence that the presence of tannin and/or chlorophyll in natural products do interfere with zebrafish phenotype assays used for identifying potential hits. However, this may be target/assay dependent and thus requiring additional optimization steps to assess interference potential of tannins and chlorophylls before performing any screening assay.
    Matched MeSH terms: Angiogenesis Inhibitors/pharmacology*
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