Therapeutic potential and bioactive phenolics of locally grown Pakistani and Chinese varieties of ginger in relation to extraction solvents

Abstract Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

Cancer is the most dreadful disease and the second main cause of death worldwide. The continuous developments havebeen going on in order to design potent molecules such that this leading cause of death can be dealt with. In order todecrease the level of toxicity and to improve the selectivity of drugs toward cancer targets, the development of hybridmolecules has become the center of research, and scientists are doing timeless efforts to generate such a hybrid whichhas got no comparison with the previous developments. The heterocyclic moiety Uracil and many of its derivativeswere already exposed as promising anticancer agents. Moreover, coupling of Uracil and 5-Fluorouracil (5-FU) withdifferent pharmacophores has been proven to be an excellent strategy against cancer. Hence, the present review is aneffort to collectively represent all the earlier and recent developments of Uracil and 5-FU hybrids reported to have asignificant anticancer profile. Expectantly, we can assure that this article can serve as the basis for further developmentsin Uracil and 5-FU hybrids and will surely motivate the medicinal chemists for producing unique anticancer drug

Antiangiogenic potential of Jatropha curcas latex in the chick chorioallantoic membrane model / Potencial antiangiogênico do látex de Jatropha curcas em modelo de membrana corioalantoica de embrião de galinha

AIMS: To perform a physicochemical and phytochemical characterization of Jatropha curcas latex and to investigate its antiangiogenic potential. METHODS: We performed an initial physicochemical characterization of J. curcas latex using thermal gravimetric analyses and Fourier Transform Infrared spectroscopy. After that, phenols, tannins and flavonoids were quantified. Finally, the potential of J. curcas latex to inhibit angiogenesis was evaluated using the chick chorioallantoic membrane model. Five groups of 20 fertilized chicken eggs each had the chorioallantoic membrane exposed to the following solutions: (1) water, negative control; (2) dexamethasone, angiogenesis inhibitor; (3) Regederm®, positive control; (4) 25% J. curcas latex diluted in water; (5) 50% J. curcas latex diluted in water; and (6) J. curcas crude latex. Analysis of the newly-formed vascular net was made through captured images and quantification of the number of pixels. Histological analyses were performed to evaluate the inflammation, neovascularization, and hyperemia parameters. The results were statically analyzed with a significance level set at p<0.05. RESULTS: Physicochemical characterization showed that J. curcas latex presented a low amount of cis-1.4-polyisoprene, which reduced its elasticity and thermal stability. Phytochemical analyses of J. curcas latex identified a substantial amount of phenols, tannins, and flavonoids (51.9%, 11.8%, and 0.07% respectively). Using a chick chorioallantoic membrane assay, we demonstrated the antiangiogenic potential of J. curcas latex. The latex induced a decrease in the vascularization of the membranes when compared with neutral and positive controls (water and Regederm®). However, when compared with the negative control (dexamethasone), higher J. curcas latex concentrations showed no significant differences. CONCLUSIONS: J. curcas latex showed low thermal stability, and consisted of phenols, tannins, and flavonoids, but little or no rubber. Moreover, this latex demonstrated a significant antiangiogenic activity on a chick chorioallantoic membrane model. The combination of antimutagenic, cytotoxic, antioxidant and antiangiogenic properties makes J. curcas latex a potential target for the development of new drugs.

OBJETIVOS: Realizar uma caracterização físico-química e fitoquímica do látex de Jatropha curcas e investigar o seu potencial antiangiogênico. MÉTODOS: foi realizada uma caracterização físico-química inicial do látex de J. curcas utilizando as análises termogravimétricas e a espectroscopia com a Transformada de Fourier. Depois disso, fenóis, taninos e flavonoides foram quantificados. Finalmente, o potencial do látex de J. curcas em inibir a angiogênese foi avaliado através do uso de modelo de membrana corioalantoica de embrião de galinha. Cinco grupos, cada um com 20 ovos de galinha fertilizados, tiveram a membrana corioalantoica exposta às seguintes soluções: (1) água, controle negativo; (2) dexametasona, inibidor da angiogênese; (3) Regederm®, controle positivo; (4) 25% de látex de J. curcas diluído em água; (5) 50% de látex de J. curcas diluído em água; e (6) látex bruto de J. curcas. A análise da rede vascular recém-formada foi feita por meio de imagens capturadas e quantificação do número de pixels. Análises histológicas foram realizadas para avaliar os parâmetros de inflamação, neovascularização e hiperemia. Os resultados foram analisados estaticamente com nível de significância estabelecido em p<0,05. RESULTADOS: A caracterização físico-química mostrou que o látex de J. curcas apresenta uma baixa quantidade de cis-1,4-poliisopreno, o que reduz sua elasticidade e estabilidade térmica. Análises fitoquímicas do látex de J. curcas identificaram uma quantidade significativa de fenóis, taninos e flavonoides (51,9%, 11,8% e 0,07% respectivamente). Usando o modelo de membrana corioalantoica de ovo de galinha embrionado, demonstrou-se o potencial antiangiogênico do látex de J. curcas. O látex induziu a diminuição da vascularização das membranas, em comparação aos grupos controle neutro e positivo (água e Regederm®). CONCLUSÕES: O látex de J. curcas apresentou baixa estabilidade térmica, ausência ou pouca quantidade de borracha e presença de fenóis, taninos e flavonoides em sua composição. Além disso, apresentou alta atividade antiangiogênica no modelo de membrana corioalantoica de embrião de galinha. A combinação de propriedades antimutagênicas, citotóxicas, anti-inflamatórias, antioxidantes e antiangiogênicas faz com que o látex de J. curcas seja um alvo potencial para o desenvolvimento de novos medicamentos.

Antitumor profiles and cardiac electrophysiological effects of aurora kinase inhibitor ZM447439

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with IC₅₀ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect I(Na), I(Ks) or I(K1), but decreased I(hERG) in a dose-dependent manner (IC₅₀: 6.53 µM). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to 3 µM, but it at 10 µM induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

In vitro cytotoxicity and antimicrobial activity of Talaromyces flavus SP5 inhabited in the marine sediment of Southern Coast of India / 中国天然药物

Marine sediment samples were collected from the coastal areas of Southern India, particularly in Kanyakumari District. Twenty-eight different fungal strains were isolated. The screening of fungi from marine sediment was done to isolate a potent fungus that can produce bioactive compounds for biomedical applications. Only three strains viz Trichoderma gamsii SP4, Talaromyces flavus SP5 and Aspergillus oryzae SP6 were screened for further studies. The intracellular bioactive compounds were extracted using solvent extraction method. The crude extracts were tested for its anti-microbial and anti-cancer properties and analytically characterized using Gas Chromatography Mass Spectrometry (GC-MS). All the three extracts were active, but the extract from T. flavus SP5 was found to be more active against various human pathogens, viz., Pseudomonas aeruginosa ATCC 27853 (17.8 ± 0.1), Escherichia coli ATCC 52922 (18.3 ± 0.3), and Candida tropicalis ATCC 750 (17.7 ± 0.4). It also exhibited cytotoxic activity against HEp2 carcinoma cell line with the LC value of 25.7 μg·L. The GC-MS data revealed the presence of effective bioactive compounds. These results revealed that the extract from isolated fungus T. flavus SP5 acted as a potent antimicrobial, antifungal, and anticancer agent, providing basic information on the potency of marine fungi towards biomedical applications; further investigation may lead to the development of novel anticancer drugs.

A systematic review of anticancer effects of radix astragali / 中国结合医学杂志

<p><b>OBJECTIVE</b>To review the anticancer effects of Radix astragali (RA), one of the most commonly used herbs to manage cancer in East Asia, and its constituents and to provide evidence of clinical usage through previously performed clinical studies.</p><p><b>METHODS</b>Preclinical and clinical studies related to the anticancer effects of RA were searched from inception to November 2013 in electronic databases. Two reviewers independently investigated 92 eligible studies, extracted all the data of studies and appraised methodological quality of clinical trials. The studies were categorized into in vitro and in vivo experimental studies and clinical studies, and analyzed by saponins, polysaccharides, and flavonoids of RA constituents, RA fraction, and whole extract.</p><p><b>RESULTS</b>In preclinical studies, RA was reported to have tumor growth inhibitory effects, immunomodulatory effects, and attenuating adverse effects by cytotoxic agents as well as chemopreventive effects. Saponins seemed to be the main constituents, which directly contributed to suppression of tumor growth through the activation of both intrinsic and extrinsic apoptotic pathway, modulation of intracellular signaling pathway, and inhibition of invasion and angiogenesis. Flavonoids suppressed tumor growth through the similar mechanisms with saponins. Polysaccharides showed immunomodulatory effects, contributing tumor shrinkages in animal models, despite the low cytotoxicity to cancer cells. Most of the clinical studies were performed with low evidence level of study designs because of various limitations. RA whole extracts and polysaccharides of RA were reported to improve the quality of life and ameliorate myelosuppression and other adverse events induced by cytotoxic therapies.</p><p><b>CONCLUSION</b>The polysaccharides, saponins, and flavonoids of RA, and the whole extract of RA have been widely reported with their anticancer effects in preclinical studies and showed a potential application as a adjunctive cancer therapeutics with the activities of immunomodulation, anti-proliferation and attenuation of adverse effects induced by cytotoxic therapy.</p>

Nano-mechanical Phenotype as a Promising Biomarker to Evaluate Cancer Development, Progression, and Anti-cancer Drug Efficacy

Since various bio-mechanical assays have been introduced for studying mechanical properties of biological samples, much progress has been made in cancer biology. It has been noted that enhanced mechanical deformability can be used as a marker for cancer diagnosis. The relation between mechanical compliances and the metastatic potential of cancer cells has been suggested to be a promising prognostic marker. Although it is yet to be conclusive about its clinical application due to the complexity in the tissue integrity, the nano-mechanical compliance of human cell samples has been evaluated by several groups as a promising marker in diagnosing cancer development and anticipating its progression. In this review, we address the mechanical properties of diverse cancer cells obtained by atomic force microscopy-based indentation experiments and reiterate prognostic relations between the nano-mechanical compliance and cancer progression. We also review the nano-mechanical responses of cancer cells to the anti-cancer drug treatment in order to interrogate a possible use of nano-mechanical compliance as a means to evaluate the effectiveness of anti-cancer drugs.

Exploring the Anticancer Activity of Grape Seed Extract on Skin Cancer Cell Lines A431

In this study, grape seeds were extracted using ethyl acetate and petroleum ether by solvent-solvent extraction method. The phytochemical tests were performed to identify different phytochemical compounds present in the grape seed extract (GSE). Antibacterial activity of the GSE was determined using agar diffusion method against Gram- positive and Gram-negative bacteria. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FTIR) analysis was done to identify the presence of bioactive compounds and their functional groups. The GC-MS results revealed a total of four compounds, known to have potent activity against cancer cells, viz, squalene, the most potent compound found in ethyl acetate extract and diethyl phthalate, ethyl-9- cis -11- trans octadecadienoate and (R)-(-)-14,-methyl-8-Hexadecyn-1-ol in petroleum ether extract. Cytotoxic activity of the GSE was observed against skin cancer cell lines A4321 using 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide) MTT assay. The IC50 value of the GSE against A431 skin cancer cell line was 480 µg/mL. This is first such report against A4321 cell lines. The study gives the overall perception about importance of GSE in medicine and nutraceuticals purposes.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Screening of North African Medicinal Plant Extracts for Cytotoxic Activity Against Tumor Cell Lines.

Aims: The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of organic extracts and fractions of four plants; Inula viscosa, Ormenis eiriolepis (Asteraceae), Retama monosperma (Fabaceae) and Marrubium vulgare (Lamiaceae), all of them used in Moroccan traditional medicine. Methodology: The four plants were extracted using organic solvents and screened on a panel of human cancer cell lines including cell types from both solid and haematological cancer origin as well as non-transformed murine fibroblasts. Cell viability assays were performed with sixteen plant extracts. Sensitive cell lines were then exposed to increasing concentrations of the most efficient extracts in order to calculate IC50 values. Microscopy, flow cytometry and caspase activity assays were then performed in LN229, SW620 and PC-3 cell lines upon treatment to investigate the cell morphology, cell cycle distribution and cell death. Results: cell viability assays reveals that at least one extract from each plant was able to exert cytotoxic activity against the majority of cell lines tested, the IC50 values of the active extracts were in most cases ≤ 30 μg/ml. the study of the cellular effects of the most active extracts on LN229, SW620 and PC-3 cell lines shows their ability to promote cell cycle arrest and cell death. The data obtained herein support strongly the use of these plants by traditional healers for the treatment of cancer patients and could have some scientific support indicating the presence of bioactive compounds. Conclusion: The reported biological activity of these four medicinal plants used in traditional Moroccan medicine provides a starting point for forthcoming studies to determine the molecular basis of their activity and to identify the chemical compounds within the most active extracts responsible for their antitumoral effects.

Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

Background : The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results : Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions : Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines.(AU)

Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

Background : The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results : Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions : Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines.

Therapeutic potential of snake venom in cancer therapy：current perspectives

Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.

Therapeutic potential of snake venom in cancer therapy: current perspectives

Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.

Important Herbs in Treatment of Cancer.

Cancer is a major public health burden in bath developed and developing countries. Plant derived agents are being used for the treatment of cancer. Reservoir of bioactive compounds exists in many species of plants of Earth, only a small percentage of which have been examined and continued to be an important source of anticancer agents. Worldwide effects are ongoing to identify new anticancer compounds from plants. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines. In recent years owing to the fear of side effects people prefer more and more use of natural plant products for cancer. This article reveals a detailed review of important herbs in cancer from Indian medicinal plants which will be useful to treat various types of cancer. It will be helpful to explore the medicinal value of the plants and for the new drug discovery from them for the researchers and scientists around the globe.

Recent advances in pharmacologic study of natural anticancer agents in China

In this paper a number of anticancer agents of natural origin will be presented. Hydroxycamtothecin (HCPT) was found to produce a strong inhibitory action on a variety of animal tumors. It is also effective for treatment of patients with gastric carcinoma, liver carcinoma, tumor of head and neck or leukemia. Pharmacologic studies showed that it could depress S phase of tumor cells significantly and cause formation of cellular chromatid breaks. By means of alkaline elution and nick translation methods it has been proved that HCPT induced DNA singlo strand breaks remarkably. Homoharringyonine (hhrt) was shown to be effective against acute leukemia. Recent experiments in tumor-bearing mice inidcated that (HHRT) could diminish tumor metastasis. Using molecular hybridization technique it was demonstrated that (HHRT) decreased the content of c-myc RNA in the cytoplasm but not in the nuclei. Lycobetaine (LBT) poddrddrf dytnh inhibitory effects on a number of ascites tumors. In clinical trials it was against ovarian and gastric carcinomas. It is able to intercalate into DNA. Oxalysine (OXL) is a new antibiotic and shown to be effective against tumor metastatis. When used in combination with 5-FU, its anticancer action could be enhanced. Other natural compounds such as indirubin, ß-elemene, irisquinone, oridonine, norcantharidin and PSP have been also found to possess antitumor action.