Anticancer effect of spices used in Mediterranean diet: preventive and therapeutic potentials
Authors : Wamidh H. Talib1*, Mallak J. AlHur 2 , Sumaiah Al.Naimat 2 , Rawand E. Ahmad1, Arkan Hadi Al-Yasari 3, Anfal Al-Dalaeen4, Samar Thiab5 and Asma Ismail Mahmod1
Abstract : Cancer is one of the leading causes of death worldwide, with almost 10 million cancer-related deaths worldwide in 2020, so any investigation to prevent or cure this disease is very important. Spices have been studied widely in several countries to treat different diseases. However, studies that summarize the potential anticancer effect of spices used in Mediterranean diet are very limited. This review highlighted chemo-therapeutic and chemo-preventive effect of ginger, pepper, rosemary, turmeric, black cumin and clove. Moreover, the mechanisms of action for each one of them were figured out such as anti-angiogenesis, antioxidant, altering signaling pathways, induction of cell apoptosis, and cell cycle arrest, for several types of cancer. The most widely used spice in Mediterranean diet is black pepper (Piper nigrum L). Ginger and black cumin have the highest anticancer activity by targeting multiple cancer hallmarks. Apoptosis induction is the most common pathway activated by different spices in Mediterranean diet to inhibit cancer. Studies discussed in this review may help researchers to design and test new anticancer diets enriched with selected spices that have high activities.
Keywords : spices, cell apoptosis, chemo-prevention, anti-angiogenesis, ginger
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Daily Consumption of Lemon and Ginger Herbal Infusion Caused Tumor Regression and Activation of the Immune System in a Mouse Model of Breast Cancer
Authors : Israa A. AL-ataby and Wamidh H. Talib*
Abstract : The Mediterranean diet includes the consumption of various fruits and vegetables. Lemon and ginger are highly popular in Mediterranean cuisine. The current study aims to evaluate both anticancer and immunomodulatory activities of lemon and ginger combination. The antiproliferative activities of the combination were tested against different cancer cell lines using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The degree of apoptosis induction and vascular endothelial growth factor expression were detected using ELISA. Balb/C mice were inoculated with the EMT6/P breast cancer cells and received combination water extract orally for 14 days. The effect of the water extract on splenocytes proliferation was measured using the mitogen proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay and pinocytosis was assessed using the neutral red method. Gas chromatography coupled to the tandem mass spectrometry was used to determine the composition of the combination. The lemon and ginger combination showed significant apoptosis induction and angiogenesis suppression effects. Fifty percent of the mice taking this combination did not develop tumors with a percentage of tumor reduction of 32.8%. This combination showed a potent effect in stimulating pinocytosis. Alphapinene and α-terpineol were detected in high percentages in the combination water extract. The lemon and ginger combination represents promising options to develop anticancer infusions for augmenting conventional anticancer therapies. Further testing is required to understand the exact molecular mechanisms of this combination.
Keywords : ginger, lemon, pinocytosis, apoptosis induction, angiogenesis, immunomodulatory activities
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Immunomodulatory and Anticancer Activities of Barley Bran Grown in Jordan: An in vitro and in vivo Study
Authors : Sara Feras Abuarab and Wamidh H. Talib*
Abstract : The Mediterranean diet is regarded as one of the most healthful dietary patterns in the world, owing to a combination of foods high in antioxidants and anticancer constituents. Barley bran is one of the components of the Mediterranean diet. It has nutritional and beneficial effects in different pathological conditions. Many studies were achieved to assess the nutritious values of barley bran, but there is no research indicating immunomodulatory and anticancer activities of barley bran grown in Jordan. The present study aims to examine and assess the potential immunomodulatory and antitumor activities of ethanol, n-hexane, aqueous/methanol, and water extracts obtained from barley bran. The Maceration method was utilized to prepare ethanol, n-hexane, aqueous/methanol, and water extracts. Various phytochemical groups were determined by using qualitative phytochemical tests. The antiproliferative activity of extracts was determined against MCF-7, HCT-116, A549, and EMT6/p by the MTT assay. The FolinCiocalteu reagent was used to detect the total phenolic content in extracts. Furthermore, immunomodulatory activity was assessed by determining the effect of extracts on splenocytes proliferation in the presence and absence of mitogens. The nitro blue tetrazolium assay and the neutral red method were used to assess the effect of each extract on the phagocytic activity of macrophages and pinocytosis, respectively. For the in vivo part, three different concentrations (10, 20, and 30% w/v) of barley bran were used to test the prophylactic effect in four Balb/C mice groups inoculated with EMT6/p cell-line subcutaneously. Also, serum samples were collected to assess the effect on cytokines (IFN-gamma, IL-2, IL-4, and IL-10). Barley bran extracts inhibited cancer cell proliferation. According to immunoassays, n-hexane and aqueous/methanol extracts could significantly rise lymphocyte proliferation and pinocytosis activity of macrophages. The activity of phagocytosis was increased by n-hexane and ethanol extracts. For the in vivo part, the average tumor size and weight of mice given the 30% barley bran group was significantly reduced (p < 0.05) compared with the control group. During our study, higher levels of TH1 cytokines (IFN- γ, IL-2) and lower levels of TH2 cytokine (IL-4) and T regulatory cytokine (IL-10) were obtained due to consumption of barley bran in food. Barley bran can be used as a prophylactic agent because it has anti-cancer and immunomodulatory activities.
Keywords : anticancer nutrition, immunomodulatory effect, natural products, tumors, animal model
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Gaz alafi: A Traditional Dessert in the Middle East with Anticancer, Immunomodulatory, and Antimicrobial Activities
Authors : Wamidh H. Talib1*, Meena A. Al Safi1, Hasan M. Rashid1 and Fatma U. Afifi1
Abstract : Background: From the earliest times, manna has been widely used as a tasty local sweet or folk medicine. The type of manna being investigated in the present study is called Gaz-alafi, a mixture of insect and Quercus brantii leaves secretions from oak forests in the north of Iraq and west of Iran. Methods: Water and ethanol extracts were made. The phytochemical examination included total phenolic contents using the Folin-Ciocalteu method and LC-MS to analyze the composition. Gallic acid and catechin were detected in both extracts, and tiliroside added more value to the ethanol extract phenolic content. Cytotoxic activities of Gaz alafi were evaluated against breast cancer cell lines and compared to normal cell lines and doxorubicin using the MTT assay method. Antimicrobial properties were assessed against E. coli, P. aeruginosa, S. aureus, B. subtilis, and C. albicans using the dilution method of the micro-titer plate. Serum levels of interferon-gamma, interleukin IL-2, IL-4, and IL-10 of tumor implanted, and normal mice were measured using ELISA. The effect on splenocyte proliferation was evaluated using the MTT assay. Macrophage function was assessed using nitro blue tetrazolium assay, whereas pinocytosis was evaluated using the neutral red method. Ten days after inoculation, changes in tumor size, survival rates, levels of AST, ALT, and creatinine were quantified. Results: The growth of cancer cells was inhibited by Gaz alafi ethanol extract. An alteration in IFN- γ, IL-2, IL-4 levels towards antiproliferation immune response were noted for both extracts. The aqueous extract efficiently stimulated lymphocyte proliferation, phagocytosis, and pinocytosis, followed by the ethanol extracts with moderate activity. After treating the mice with ethanol extracts, a significant reduction in tumor size and several undetected tumors was recorded. Conclusions: Studied extracts exhibited promising anticancer and immunostimulatory effects strongly related to the active components of Gaz alafi.
Keywords : Antiproliferation, antimicrobial, immunomodulatory, Functional Food, in-vivo
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Wild Thyme Herbal Infusion Consumption Suppresses Tumor Growth in a Murine Model of Breast Cancer
Authors : Israa A. AL-ataby1 and Wamidh H. Talib1,*
Abstract : Abstract: Background: Wild thyme (Thymus serpyllum) belongs to the Lamiaceae family. They were used traditionally to treat different sorts of diseases, including cancer. Aims: The current study aims to evaluate both anticancer and immunomodulatory activities of wild thyme water extract. Methods: The antiproliferative activities of the extract were tested against different cancer cell lines using MTT assay, while the degree of apoptosis induction and VEGF expression were detected using ELISA. The lymphocyte proliferation assay was used to evaluate the acquired immunity, whereas both: the nitro blue tetrazolium assay and the neutral red method were used to assess the innate activity; phagocytosis and pinocytosis, respectively. Balb/C mice were inoculated with the EMT6/P breast cancer cells and received the extract orally for 14 days. GC-MS and LC-MS were used to determine the composition of the wild thyme water extract. Results: Results showed that wild thyme had significant apoptosis induction and angiogenesis suppression effects. The extract stimulated lymphocyte proliferation, phagocytosis and pinocytosis strongly. Seventy percent (70%) of the mice taking this extract did not develop tumors, with a percentage of tumor reduction (49.4%). Rosmarinic acid was the highest in the wild thyme water extract in GC-MS and LC-MS. Conclusion: Wild thyme herbal infusion is rich in phytochemicals that have the potential to activate the immune system and inhibit tumor progression. Further testing is required to understand the exact molecular mechanisms of this extract. Further studies are also needed to test the wild thyme infusion against tumors established in mice
Keywords : herbal infusions, breast cancer, functional food, mouse model, Wild thyme, Lamiaceae family
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The first detection of Pneumocystis jirovecii in asthmatic patients post COVID-19 in Jordan
Authors : Ahmad Riyad Alsayed, Wamidh Talib, Abdullah Al-Dulaimi, Safa Daoud, Mohammed Al Maqbali
Abstract : Pneumocystis jirovecii pneumonia (PCP), caused by fungal species named Pneumocystis jirovecii, is a frequent opportunistic infection in those with human immunodeficiency virus (HIV) infection. However, PCP has been documented in immunocompetent patients. This study aims to determine if P. jirovecii detection occurs in asthma patients following coronavirus disease 2019 (COVID-19) in a Jordanian cohort. Also, to evaluate a method of TaqMan quantitative polymerase chain reaction (qPCR) assay to detect P. jirovecii, from sputum samples. The nasopharyngeal swabs were used to detect SARS-CoV-2 and sputum samples were tested for P. jirovecii using real time qPCR assay. Beta-tubulin (BT) and Dihydrofolate reductase (DHFR) genes were the directed targets of P. jirovecii. The results showed that the mean qPCR efficiencies of BT and DHFR were 96.37% and 100.13%, respectively. Three out of 31 included patients (9.7%) had a positive P. jirovecii. All of the three patients had used oral corticosteroids (OCS) in the last two months due asthma exacerbation and were treated with OCS for COVID-19. This is the first study based in Jordan to demonstrate that P. jirovecii and COVID-19 can co-exist and that it is important to maintain a broad differential diagnosis, especially in immunocompromised patients. Chronic lung disease can be a risk factor for the P. jirovecii colonization possibly due to corticosteroid's immunosuppression
Keywords : Asthma; COVID-19; developing country; Pneumocystis jirovecii; polymerase chain reaction
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New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation
Authors : Dima A Sabbah, BARA’A A AL-AZAIDEH, Wamidh H Talib, Rima Hajjo, Kamal Sweidan, Aya M Al-Zuheiri, Ghassan Abu Sheikha, Sawsan Shraim
Abstract : Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’- (diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1 H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue
Keywords : sulfonylhydrazones, antitumor, HCT-116, PI3Kα- -inhibitors, cheminformatics, docking
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Anticancer activity of Mandragora autumnalis: an in vitro and in vivo study
Authors : Asma Ismail Mahmod, Wamidh H Talib
Abstract : Abstract Ethanol crude extract and four solvent fractions were extracted from M. autumnalis leave to evaluate their anticancer effect in both models: in vitro and in vivo. The in vitro assessments were conducted using the MTT method in five cancer cell lines and one normal cell line. Ethanol extract and n-hexane fraction showed antitumor activity against MCF-7 breast cancer cells with ICââ values of 0.1 and 0.4 mg/ml, respectively, and low cytotoxicity against normal VERO cell line (ICââ value 4 mg/ml). Furthermore, expression levels of VEGF were tested in MCF-7 cells treated with M. autumnalis using Human VEGF Simple Step ELISA Kit. The results indicated downregulation of VEGF expression in the treated cells compared to the control group. Additionally, the LDââ of M. autumnalis ethanol extract was calculated by applying an acute toxicity assay. Balb/C mice were inoculated with EMT6/p breast cancer cells and then treated with (137 mg/kg/day intraperitoneal injection) of ethanol extract for ten days. Interestingly, a significant (p M. autumnalis extract showed normal serum level of AST, ALT, and creatinine. The results indicate that M. autumnalis has antitumor properties in both models in vitro and in vivo. However, further molecular investigation is required to understand the molecular bearings of M. autumnalis ' activity.
Keywords : anticancer activity, M. autumnalis , VEGF, MTT assay, LD50
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Targeting drug chemo-resistance in cancer using natural products
Authors : Wamidh H Talib, Ahmad Riyad Alsayed, Muna Barakat, May Ibrahim Abu-Taha, Asma Ismail Mahmod
Abstract : Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.
Keywords : anticancer natural products; drug efflux; drug detoxification; plants derived natural products
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Ketogenic diet in cancer prevention and therapy: molecular targets and therapeutic opportunities
Authors : Wamidh H Talib, Asma Ismail Mahmod, Ayah Kamal, Hasan M Rashid, Aya Alashqar, Samar Khater, Duaa Jamal, Mostafa Waly
Abstract : Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies
Keywords : alternative cancer therapies; anticancer diet; targeting cancer metabolism; calories restriction
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Immunomodulatory and Anticancer Activities of Hyacinthus orientalis L.: An In Vitro and In Vivo Study
Authors : Lina T Al Kury, Zainab Taha, Wamidh H Talib
Abstract : : Hyacinthus orientalis L. (family Hyacinthaceae) is traditionally used to treat different diseases including cancer. In this study, the anticancer and immunomodulatory effects of this plant were evaluated. Hydroalcoholic extract was prepared, and different solvent fractions were obtained using solvent–solvent extraction. In the anticancer part, MTT assay and caspase-3 ELISA kits were used to measure the antiproliferative and apoptosis induction ability for each extract, respectively. In the immunomodulatory part, lymphocyte proliferation assay and cytokines detection kit were used to measure the effect of extracts of acquired immunity. Phagocytosis and pinocytosis induction were used to evaluate the effect of extracts on the innate immunity. GC–MS, LC–MS, and Foline–Ciocalteu assays were used to identify the chemical composition of the plant. Balb/C mice were inoculated with breast cancer and treated with hydroalcoholic extract of H. orientalis L. Results showed that hydroalcoholic extract and n-hexane fraction were highly effective in apoptosisinduction. Both extract and fraction were also effective in stimulating lymphocytes proliferation and phagocytosis. Significant reduction in tumor size was achieved after treating tumor-bearing mice with hydroalcoholic extract. Additionally, high cure percentages (50%) were obtained in treated mice. Results of this study showed that H. orientalis L. has promising anticancer and immunomodulatory activities. However, further studies are needed to explore more details of apoptosis induction abilityand other mechanisms of action and to measure different signaling pathways responsible for the anticancer and immunomodulatory response.
Keywords :
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Evaluation of the Single and Combined Antibacterial Efficiency of the Leaf Essential Oils of Four Common Culinary herbs: Dill, Celery, Coriander and Fennel Grown in Jordan
Authors : Al-Hasan Alsalman, Nour Aboalhaija, Wamidh Talib, Ismail Abaza, Fatma Afifi
Abstract : This study aimed to determine the volatile oil composition of the fresh leaves of dill, celery, coriander, and fennel, grown in Jordan, and to evaluate the antimicrobial activity of the essential oils individually and in binary (50:50) and quaternary (25:25:25:25) mixtures. The volatile oils, obtained by hydrodistillation, were analysed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). In vitro antimicrobial activities of the essential oils were evaluated against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans. Using the microtiter plate dilution method minimal inhibitory concentrations (MICs) of the essential oils were determined and the checkerboard method was then used to investigate the antimicrobial efficacy of the essential oil combinations by means of the fractional inhibitory concentration index (FICI). Dill and celery samples were rich in monoterpene hydrocarbons, while the oils of fennel and coriander were dominated by non-terpenoid compounds. In antimicrobial experiments, the essential oil of dill yielded the best activity against all tested microorganisms. In binary combination of the essential oils, best results were detected in a combination of dill with coriander against B. subtilis and P. aeruginosa, and fennel with coriander against E. coli and P. aeruginosa. The present study is the first evaluation of the volatile oil composition and determination of the antimicrobial activities of the fresh leaves of dill, celery, coriander, and fennel in binary and quaternary combinations. Additive or synergistic effects were detected in certain binary oil combinations while indifferent and antagonist effects were noticed in other mixtures.
Keywords : Culinary herbs, hydrodistillation, GC-MS, antimicrobial activity, FICI.
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Aroma Profile, Chemical Composition and Antiproliferative Activity of the Hydrodistilled Essential Oil of a Rare Salvia Species (Salvia greggii)
Authors : Ismail Abaza, Nour Aboalhaija, Alhasan Alsalman, Wamidh Talib, Fatma Afifi
Abstract : The present study deals with the gas chromatography/mass spectrometry (GC/ MS) analysis of the aroma profile of different aerial organs obtained by solid-phase microextraction (SPME) and that of the hydro distilled essential oil of the fresh leaves and flowers of Salvia greggii A. Gray grown in Jordan. Oxygenated sesquiterpenes dominated the hydrodistilled oils of the leaves and flowers with guaiol (35.60 % and 31.92 %, respectively) and patchouli alcohol (16.30 % and 16.88 %, respectively) as the main constituents. Alpha-pinene, camphene, limonene, and γ-terpinene were detected as the major hydrocarbon monoterpenes and 1,8-cineol, camphor, and isobornyl acetate as the major oxygenated monoterpenes. The antiproliferative activity of the leaf essential oil was screened on MCF-7 and HCT116 cell lines. The essential oil exhibited a promising dosedependent inhibition of cell growth with low IC50’s (MCF-7: 35.35 μg/mL; HCT116: 23.57 μg/mL) with a high safety profile against the normal Vero cell line compared to the positive control Doxorubicin.
Keywords : GC-MS, HCT116, Lamiaceae, MCF-7, Salvia greggii A. Gray
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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
Authors : Wamidh H Talib, Ahmad Riyad Alsayed, Alaa Abuawad, Safa Daoud, Asma Ismail Mahmod
Abstract : Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.
Keywords : pineal gland; anticancer; cancer therapy; hormonal therapy; phytomelatonin
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Diabetes and Cancer: metabolic association, therapeutic challenges, and the role of natural products
Authors : Wamidh H Talib, Asma Ismail Mahmod, Sara Feras Abuarab, Eliza Hasen, Amer A Munaim, Shatha Khaled Haif, Amani Marwan Ayyash, Samar Khater, Intisar Hadi Al-Yasari, Lina T Al Kury
Abstract : Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base for researchers and physicians to test natural products as adjuvant alternative therapies to treat cancer in diabetic patients.
Keywords : hyperglycemia; cancer; Warburg effect; alternative therapies; obesity; metabolic syndrome; hyperinsulinemia; cancer metabolism; oxidative stress; natural products
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Hyperhomocysteinemia and Cancer: The Role of Natural Products and Nutritional Interventions
Authors : Wamidh H Talib, Muna Barakat, Lina T Al Kury
Abstract : Hyperhomocysteinemia is a defect in the metabolism of sulfur-containing amino acids characterized by elevated levels of homocysteine (Hcy) in the blood [1]. The main cause of this defect is mutations in cystathionine beta synthase which is an essential enzyme in Hcy metabolism. Other environmental and genetic factors were also described as a cause of hyperhomocysteinemia [2]. The normal level of Hcy in healthy individuals is 5–15 μM. It increases to 50 μM in mild cases and may reach 500 μM in severe cases [3]. Elevated serum Hcy is associated with different pathological disorders including cardiovascular, neurodegenerative, osteoporosis, diabetes, megaloblastic anemia, and cancer [4]. Hyperhomocysteinemia was observed to be associated with cancers of various histologic origins and was also suggested as a potential biomarker for tumors [5]. The mechanistic bases that link between hyperhomocysteinemia and cancer involves folate depletion in cancer patients and polymorphisms in enzymes involved in the Hcy detoxifcation [4]. Thus, one important strategy to control hyperhomocysteinemia is dietary interventions using vitamins and plant derived natural products. Several studies were conducted to show the effect of vitamins supplementation and the use of natural product to control hyperhomocysteinemia. This chapter will focus on hyperhomocysteinemia induction, its link with cancer, and the role of natural products and nutritional interventions to reduce tumor associated hyperhomocysteinemia.
Keywords : Hyperhomocysteinemia; Cancer; Natural Products
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Synthesis, computational, anticancerous and antiproliferative effects of some copper, manganese and zinc complexes with ligands derived from symmetrical 2,2’-diamino-4,4’-dimethyl-1,1’-biphenyl-salicylaldehyde
Authors : Taher S. Ababneh1*, Mohammad El-Khateeb2 , Aissar K. Tanash1 , Tareq M.A. AL-Shboul3, Mohammad Jamal A. Shammout4, Taghreed M.A. Jazzazi1, Mohammad Alomari5, Safa Daoud6, Wamidh H. Talib7
Abstract : Four new symmetrical Schiff bases derived from 2,2’-diamino-4,4’-dimethyl-1,1’-biphenyl-salicylaldehyde have been synthesized and characterized by elemental analysis and different spectroscopic techniques. The reaction of 2,2’-diamino-4,4’-dimethyl-1,1’-biphenyl with two equivalents of 5-tert-butyl-, 3,5-dinitro-, 3,5-dibromo- and 3-tertbutyl-salicylaldehyde yielded 2,2’-bis(5-tert-butyl-salicylideneamino)-4,4’-dimethyl-1,1’-biphenyl (A1) as well as the 3,5-dinitro- (A2), 3,5-dibromo- (A3) and 3-tert-butyl- (A4) substituted derivatives. The tetradentate ligands were then reacted with copper-, manganese- and zinc-acetate producing the tetra-coordinate metal complexes which were characterized by FTIR, UV-Visible spectroscopy, magnetic susceptibility and elemental analysis. Zinc complexes were characterized by 1H-NMR spectroscopy. Density functional theory (DFT) calculations at the B3LYP/6-31G(d) level of theory were carried out to fully optimize and examine the molecular geometries of complexes. Subsequently, IR vibrational and UV-Vis absorption spectra were computed and correlated with the observed values and the results are in good agreement with the experimental data. The anticancerous and antiproliferative activity of the A3 ligand and its metal complexes were determined
Keywords : Tetradentate Schiff base, Symmetrical metal complexes, DFT calculation, Spectroscopy, Anticancerous, Antiproliferative.
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Middle East medicinal plants in the treatment of diabetes: a review
Authors : Alaa M Abu-Odeh, Wamidh H Talib
Abstract : Diabetes is a global health problem, and the number of diabetic patients is in continuous rise. Conventional antidiabetic therapies are associated with high costs and limited efficiency. The use of traditional medicine and plant extracts to treat diabetes is gaining high popularity in many countries. Countries in the Middle East region have a long history of using herbal medicine to treat different diseases, including diabetes. In this review, we compiled and summarized all the in vivo and in vitro studies conducted for plants with potential antidiabetic activity in the Middle East region. Plants of the Asteraceae and Lamiaceae families are the most investigated. It is hoped that this review will contribute scientifically to evidence the ethnobotanical use of medicinal plants as antidiabetic agents. Work has to be done to define tagetes, mechanism of action and the compound responsible for activity. In addition, safety and pharmacokinetic parameters should be investigated.
Keywords : antidiabetic plants; natural products; hyperglycemia; plant extracts
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In vitro evaluation of the antioxidant, anti-Propioni bacterium acne and antityrosinase effects of Equisetum ramosissimum (Jordanian horsetail)
Authors : Noor Sabah Abed Savaya, Reem Adnan Issa, Wamidh Hadi Talib
Abstract : Purpose: The investigation of Equisetum ramosissimum Desf. (Equisetaceae) extracts for total phenolic content, potential antioxidant properties, and antibacterial activity against Propioni bacterium acne and antityrosinase effects. Methods: The aerial parts of the E. ramosissimum from Jordan were extracted by maceration and Soxhlet methods, using solvents of different polarities. The composition of the extracts were qualitatively screened using standard phytochemical tests. Quantitatively, total phenolic content (mg/mL, equivalent to gallic acid), ABTS free radical scavenging activity (IC50), anti-P. acne (MIC and MBC), and tyrosinase inhibitory effects (IC50) were also determined. Results: The aqueous-methanol Soxhlet extract contained the highest total phenolic content (0.675 mg/mL gallic acid equivalents). Besides, phytochemical screening tests revealed the presence of phenols, flavonoids, tannins, alkaloids and saponins in the aqueous methanol Soxhlet extract, contributing to the antioxidant (IC50 = 0.125) and antityrosinase (IC50 = 1.125) effects. This extract also showed potent antimicrobial effects against P. acne (MIC = 6.250 mg/mL; MBC = 12.500 mg/mL). Other extracts, including ethanol, water and ethyl acetate, showed lower total phenolic content with moderate and weak biological activity. Conclusion: E. ramosissimum is a promising plant species to be considered for antioxidant, antiacne, and antityrosinase effects. However, further testing (including invivo, histological examination, and highperformance liquid chromatography (HPLC) analysis) is necessary to understand more about its mechanisms of action.
Keywords : Antioxidant, Anti-Propioni bacterium acne, Antityrosinase, Equisetum ramosissimum, Total phenolic content, Jordanian horsetail
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Investigations on the spontaneous emitted and hydrodistilled volatiles of Platycladus orientalis (L.) Franco grown in four different biogeographic zones of Jordan
Authors : Osama A Al-Mahmood, Nour H Aboalhaija, Ismail F Abaza, Wamidh H Talib, Fatma U Afifi
Abstract : The essential oil of the fresh leaves of Platycladus orientalis (L.), grown in four different biogeographic zones of Jordan,- (the Mediterranean, Irano-Turanian, Saharo-Arabian, and Sudanian penetration) -, were obtained by hydrodistillation and analysed by gas chromatography (GC) and gas chromatography-mass-spectrometry (GC/MS). The actual composition of the spontaneous emitted volatiles was obtained using the solid-phase-micro-extraction (SPME) method and investigated using the same chromatographic and spectroscopic methods. Hydrocarbon monoterpenes dominated the hydrodistilled oils and emissions of all regions. Bicyclic monoterpenes (sabinene, α-pinene, and α-thujene) and monocyclic α-terpinene were detected as the major constituents of the oils and emissions. Additionally, hierarchical cluster analysis (HCA) revealed that the clustering is based on the region of collection rather than the applied methodology. Differences were observed in the quantity of the obtained oils (P-values <0.01); the highest amount of volatile oil was obtained from samples grown in the Irano-Turanian biogeographic zone.
Keywords : SPMEHierarchical cluster analysisVolatile organic compoundsGC/MSLeaves
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New maleimide 1,2,3-triazole hybrids: design, synthesis, anticancer, and antimicrobial activities
Authors : Bader A. Salameh, Kayed A. Abu-Safieh, Eman H. Al-Hushki, Wamidh H. Talib, Israa A. Al-ataby & Raed A. Al-Qawasmeh
Abstract : A new series of maleimide triazole hybrid compounds namely 3-chloro-1-[(1-aryl-1H-1,2,3-triazol-4-yl)methyl]-4-(arylamino)-1H-pyrrole-2,5-dione have been prepared. Our synthetic strategy starts via the reaction of 2,3-dichloromaleic anhydride with propargyl amine followed by chlorine displacement with arylamine and subsequent formation of a triazole utilizing copper(I) catalyzed azide-alkyne cycloaddition reaction, that generates the designed triazole nucleus. The produced hybrid compounds were identified using various physicochemical properties of the pure compounds. The synthesized compounds were screened for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, and Bacillus spizizenii. While selected compounds were tested for their anticancer activities against T47D, HCT 116, and VERO cell lines.
Keywords : Alkynes; Antitumor agents; Heterocycles; Triazole; Maleimide
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Terfezia boudieri: A desert truffle with anticancer and immunomodulatory activities
Authors : Maha Farid Al Obaydi, Wafaa M Hamed, Lina T Al Kury, Wamidh H Talib
Abstract : Desert truffles have high nutritional value and grow wild in the Mediterranean basin and Western Asia. Although, many studies were performed to evaluate truffles nutritious values and phytochemical composition, studies are limited to evaluate their anticancer and/ or immunomodulatory effects. Our study was conducted to evaluate the anticancer and immunomodulatory effects of Terfezia boudieri (desert truffle). Different solvent extracts were prepared from the truffle and MTT assay was used to measure their anticancer activity against cancer cell lines (T47D, MCF-7, MDA-MB231, HCT-116, and Hela). Total phenolic content in each extract was determined by using Folin-Ciocalteu reagent and qualitative phytochemical screening was performed using standard methods. The degree of apoptosis induction (using caspase 3 assay) and vascular endothelial growth factor expression were detected using standard kits. Also, ELISA was used to measure levels of IFN-γ, IL-2, IL-4, and IL-10 secreted by splenocytes after treatment with the extracts. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay and pinocytosis function was evaluated using neutral red method. Terpenoids, phytosterols, and carbohydrates were present in all the solvent extracts, while tannins, alkaloids and flavonoids were detected only in aqueous/methanol and aqueous extracts. The highest total phenolic content was observed in aqueous and aqueous methanol extracts. The growth of cancer cell lines was inhibited by T. boudieri extracts in a dose dependent manner. N-hexane extract was the most potent against most cell lines. Aqueous/methanol extract showed high apoptosis induction andangiogenesis suppression effects. An increase in TH1 cytokines (IFN-γ, IL-2) level and a decrease in TH2 cytokine (IL-4) level were evident after lymphocytes stimulation by aqueous/methanol, n-hexane and ethyl acetate extracts of T. boudieri. Ethyl acetate extract of T. boudieri were the most potent extracts to stimulate lymphocytes proliferation while all other extracts showed moderate stimulation. Aqueous/methanol extract was the most active extract to stimulate phagocytosis. Ethyl acetate extract was the most active extract to stimulate pinocytosis. The use of T. boudieri provides variable health benefits. N-hexane, ethyl acetate, and aqueous/methanol extracts exhibited anticancer activities and are potent stimulators of innate and acquired immunity. Further testing is needed to identify the biologically active compounds and detect them quantitatively using GC-MS analysis.
Keywords : truffles, fungi, anticancer, functional food, immunomodulatory
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A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft
Authors : Wamidh H Talib
Abstract : Objectives Chemotherapy is one of the major treatments of cancer. However, the emergence of resistance to chemotherapeutic agents is still a major obstacle in the successful management of resistant tumors. Therefore, development of new mechanisms to overcome drug resistance is essential and may be further developed into effective therapies that can flip the switch from drug resistance to susceptibility. The aim of this study was to evaluate a combination consisting of a ketogenic diet and melatonin to determine whether it would inhibit cisplatin- and vincristine-resistant breast cancer. Methods In the in vitro part of the study, drug-resistant cell lines were treated with melatonin and real-time polymerase chain reaction was used to measure levels of gene expression involved in apoptosis and resistance. On the protein level, the activity of caspase-3 and the level of vascular endothelin growth factor protein were determined. In the in vivo part, tumor-bearing mice received one of the following treatments: ketogenic diet, melatonin, combination of melatonin and ketogenic diet, vehicle, or chemotherapy. Results Successful inhibition of resistant cell lines was achieved by melatonin. This inhibition was mediated by induction of apoptosis, inhibition of angiogenesis, and downregulation of resistance genes. A synergistic anticancer effect was observed between melatonin and the ketogenic diet against resistant breast tumors inoculated in mice with a cure rate of 70%. Conclusions The combination of melatonin and a ketogenic diet represents a promising option to overcome drug resistance in cancer chemotherapy. However, further testing on the protein level using flow cytometry is important to better understand the mechanisms of action.
Keywords : Drug resistance, Breast cancer, Chemotherapy Combination, therapy
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Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation
Authors : Wamidh H Talib, Izzeddin Alsalahat, Safa Daoud, Reem Fawaz Abutayeh, Asma Ismail Mahmod
Abstract : Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.
Keywords : alternative anticancer therapies; natural products; plant extracts; curcumin; thymoquinon
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Resveratrol and tumor microenvironment: mechanistic basis and therapeutic targets
Authors : Wamidh H Talib, Ahmad Riyad Alsayed, Faten Farhan, Lina T Al Kury
Abstract : Resveratrol (3,4′,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tumor microenvironment. These players include blood and lymphatic vessels, infiltrating immune cells, stromal fibroblasts and the extracellular matrix. Targeting tumor microenvironment components is a promising strategy in cancer therapy. Resveratrol with its diverse biological activities has the capacity to target tumor microenvironment by manipulating the function of many components surrounding cancer cells. This review summarizes the targets of resveratrol in tumor microenvironment and the mechanisms involved in this targeting. Studies discussed in this review will participate in building a solid ground for researchers to have more insight into the mechanism of action of resveratrol in tumor microenvironment
Keywords : resveratrol; tumor microenvironment; natural products; anti-cancer; phytotherapy
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The impact of herbal infusion consumption on oxidative stress and cancer: the good, the bad, the misunderstood
Authors : Wamidh H Talib, Israa A Al-Ataby, Asma Ismail Mahmod, Sajidah Jawarneh, Lina T Al Kury, Intisar Hadi Al-Yasari
Abstract : The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated for their antioxidant capacities, anticancer potential and possible toxicity. These herbal infusions are highly popular and consumed as daily drinks in different countries. Studies discussed in this review will provide a solid ground for researchers to have better understanding of the use of herbal infusions to reduce oxidative stress and as protective supplements against cancer development.
Keywords : antioxidant; natural products; anti-tumor; dietary agents
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