Plants as a Source of Anticancer Agents: From Bench to Bedside
Authors : Wamidh H. Talib, Safa Daoud, Asma Ismail Mahmod, Reem Ali Hamed, Dima Awajan, Sara Feras Abuarab, Lena Hisham Odeh, Samar Khater, and Lina T. Al Kury
Abstract : Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.
Keywords : plant-derived natural products; alternative cancer therapies; anticancer; apoptosis
induction; plants
Visit
Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities
Authors : Wamidh H Talib 1, Asma Ismail Mahmod 1, Ayah Kamal 1, Hasan M Rashid 1, Aya M D Alashqar 1, Samar Khater 1, Duaa Jamal 1, Mostafa Waly 2
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; calories restriction; targeting cancer metabolism.
Visit
Diabetes and Cancer: Metabolic Association, Therapeutic Challenges, and the Role of Natural Products
Authors : Wamidh H Talib 1, Asma Ismail Mahmod 1, Sara Feras Abuarab 1, Eliza Hasen 1, Amer A Munaim 1, Shatha Khaled Haif 1, Amani Marwan Ayyash 1, Samar Khater 1, Intisar Hadi Al-Yasari 2, Lina T Al Kury 3
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 : Warburg effect; alternative therapies; cancer; cancer metabolism; hyperglycemia; hyperinsulinemia; metabolic syndrome; natural products; obesity; oxidative stress.
Visit
User error with Diskus and Turbuhaler by asthma patients and pharmacists in Jordan and Australia
Authors : Iman A Basheti 1, Eyad Qunaibi, Sinthia Z Bosnic-Anticevich, Carol L Armour, Samar Khater, Muthana Omar, Helen K Reddel
Abstract : Background: Use of inhalers requires accurate completion of multiple steps to ensure effective medication delivery. Objective: To evaluate the most problematic steps in the use of Diskus and Turbuhaler for pharmacists and patients in Jordon and Australia. Methods: With standardized inhaler-technique checklists, we asked community pharmacists to demonstrate the use of Diskus and Turbuhaler. We asked patients with asthma to demonstrate the inhaler (Diskus or Turbuhaler) they were currently using. Results: Forty-two community pharmacists in Jordan, and 31 in Australia, participated. In Jordan, 51 asthma patients demonstrated use of Diskus, and 40 demonstrated use of Turbuhaler. In Australia, 53 asthma patients demonstrated use of Diskus, and 42 demonstrated use of Turbuhaler. Results: The pharmacists in Australia had received inhaler-technique education more recently than those in Jordan (P = .03). With Diskus, few pharmacists in either country demonstrated correct technique for step 3 (exhale to residual volume) or step 4 (exhale away from the device), although there were somewhat fewer errors in Australia than Jordan (16% vs 0% in step 3, P = .007, and 20% vs 0% in step 4, P = .003 via chi-square test). With Turbuhaler there were significant differences between the pharmacists from Australia and Jordan, mainly in step 2 (hold the device upright while loading, 45% vs 2% correct, P < .001). Few of the patients had received inhaler-technique education in the previous year. The patients made errors similar to those of the pharmacists in individual steps with Diskus and Turbuhaler. The essential steps with Diskus were performed correctly more often by the Jordanian patients, and with Turbuhaler by the Australian patients. Conclusions: Despite differences in Jordan's and Australia's health systems, pharmacists from both Australia and Jordan had difficulty with the same Diskus and Turbuhaler steps. In both countries, the errors made by the asthma patients were similar to those made by the pharmacists.
Keywords : inhaler technique, asthma management, pharmacists, asthma education
Visit
Acute effects of thymoquinone on the pregnant rat and embryo-fetal development
Authors : Majed M AbuKhader 1, Samar H Khater, Hisham Y Al-Matubsi
Abstract : The effect of a single intraperitoneal (i.p.) injection of thymoquinone (TQ) on the pregnant rat and embryo-fetal development was investigated. Pregnant female Wistar rats received 15, 35, and 50 mg/kg body weight of TQ i.p. on day 11 or 14 of gestation, and on day 18 of gestation they were sacrificed and laparotomized. Results showed that TQ induces maternal and embryonic toxicities in a dose- and time-dependent manner. With a dose of 50 mg/kg, treated rats experienced a significant decrease in maternal body weight and complete fetal resorption when the dose was given on day 11 of gestation. On the other hand, 46.2% of implants were resorbed and the viable fetuses showed no TQ-related malformations when the dose was given on day 14 of gestation. At a lower TQ dose of 35 mg/kg, maternal and embryonic toxicities were observed only when it was given on day 11 of gestation. The dose of 15 mg/kg was considered to be a dose with no observed adverse effect level for maternal and embryo-fetal toxicities when it was given day 11 or 14 of gestation. Based on the results of this study, TQ, at doses of 50 and 35 mg/kg, has a potentially disruptive effect on embryonic development during the second trimester of rat pregnancy.
Keywords : Thymoquinone, resorption, pregnancy, placental lactogen
Visit
A Comparative Evaluation of Microwave and Conventional Soxhlet Extraction Methods for the Antioxidant, Hypoglycemic and Hypolipidemic Potentials of Jordanian Psidium guajava Raw Fruit Peel Extracts
Authors : Reem Issa, Samar Khater, Mahmoud Abu-Samak
Abstract: Background: Psidium guajava L. (Myrtaceae) is one of the medicinal plants in Jordan that have been reported in the folk medicine for different indications and few of them have been experimentally and/or clinically determined. Objective: The current study aims to explores the aqueous extracts obtained from Jordanian premature P. guajava fruit peel ( PGFP) , using t wo different methods of extraction .Also to assess these extracts different pharmacological activities as well as their phytochemistry. Materials and Methods: Two different methods for extraction were used, Microwave-Integrated Soxhlet (MIS) and Conventional Soxhlet (CS) extraction methods. The TLC analysis was used to optimize each extraction method and for the preliminary phytochemical screening. The HPLC-MS/MS analysis allowed the identification and quantification of the phenol compounds in the PGFP two extracts. For each extract type, the antioxidant activity was evaluated using the ABTS method. In addition, the hypoglycemic and hypolipidemic potentials for each extract were also evaluated on normoglycemic and streptozotocin-treated diabetic rats. Statistical analysis was performed using the one-way analysis of variance (ANOVA) in order to reveal significant (p<0.05) differences between the tested animal groups. Results: The CS extract showed ellagic acid as the major constituent, followed by gallic, P-coumaric, furelic acids, quercetin and ascorbic acid in order of their percentage content (total phenol content). Regarding the MIS extract, ascorbic acid was detected as the major compound followed by gallic, P-coumaric acids and quercetin. Moreover, MIS extract showed to contain higher level of total phenol compounds. Comparison of pharmacological studies showed more potent effects of CS as antioxidant and hypolipidemic extract, where the MIS extract showed higher hypoglycemic effect. Conclusion: The presented data suggest that PGFP can be used for their antioxidant, hypolipidemic and hypoglycemic effects, if the extraction methods were optimized for the required pharmacological effect. In this study, it was correlated that, significant hypolipidemic effect of unripe guava to high content of ellagic acid in its fruit peels and antioxidant action of the active extract. This effect for ellagic acid seems to be mediated by metabolic pathway by which it acts as antilypolytic agent to reduce the consequences of diabetes mellitus, such as atherosclerosis rather than antidiabetic effect.
Keywords : Psidium guajava, fruit peel, hypoglycemic, hypolipidaemic, microwave, extraction, phenol
Visit
Education on Correct Inhaler Technique in Pharmacy Schools: Barriers and Needs
Authors : Basheti I, Natsheh AI, Ammari WG, Khater S, Qunaibi EQ, Bosnic-Anticevich SZ.
Abstract : Purpose: To investigate the effectiveness of a standard educational module on pharmacy students 'inhaler technique demonstration skills. Methods: This investigational study was conducted during the Clinical Pharmacy and Therapeutics tutorial classes in 2011. All fifth-year students were given placebo inhaler devices and information leaflets explaining the use of these devices. Students were then shown, by demonstration, the correct technique for each of the inhalers. All the students were assessed on the use of each of the inhalers two weeks following the tutorial. A validated questionnaire regarding the students’ barriers to demonstrate the correct inhaler technique was completed by all the students. The inhaler techniques demonstrated were Accuhaler (ACC), Turbuhaler (TH) and metered-dose inhaler (MDI). Results: Students scored significantly better with ACC with a score of 4.38 ± 1.81 (out of 9.00) than with TH (3.96 ± 1.75 out of 9.00); p = 0.004, and MDI (2.69 ± 1.76 out of 8.00); p < 0.001, based on Friedman test 2 weeks following training. The majority of students (78 %) believed that lack of practice with the devices was the primary barrier to correct inhaler use. Conclusion: Standard educational training may not be the most appropriate method of teaching students the correct use of inhalers. Clearly, there is a practice element missing which needs to be addressed in a feasible way.
Keywords : Inhaler technique, Pharmacy education, Hands-on training, Training barrier
Visit
Collagen toxicity in rabbits
Authors : Sarita A.Gomes, Martha Thomson, Muslim Ali, 1MajedAlnaqeeb, Samar H.Khater
Abstract : Different preparations of soluble collagen, from rabbit skin, rat skin, rat tail tendon and guinea-pig skin, produced respiratory distress, agitation, convulsions and finally death when infused intravenously in lethal doses. Analysis of plasma enzyme levels indicated significant increases in total, cardiac and hepatic lactate dehydrogenase, suggesting that damage to the liver occurred as a result of collagen infusion. Histopathological examination of lungs, livers and hearts of collagen-treated rabbits confirmed that damage had occurred to the lungs and livers of these animals, while heart tissues appeared to be normal. The source of collagen did not appear to influence its toxicity at the tissue level
Keywords : Collagen, Lactate dehydrogenase, Liver, Lung, Histopathology
Visit
Antithrombotic activity of garlic: its inhibition of the synthesis of thromboxane-B2 during infusion of arachidonic acid and collagen in rabbits
Authors : M Ali, M Thomson, MA Alnaqeeb, JM Al-Hassan, SH Khater, SA Gomes
Abstract : Rabbits were given collagen and arachidonic acid intravenously. Blood pressure, platelet counts, plasma thromboxane-B2 (TXB2) and plasma 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined. Both thrombogenic agents, upon infusion of a lethal dose, caused thrombocytopenia, indicative of in vivo platelet aggregation and hypotension. These changes were associated with an increase in plasma levels of TXB2 and 6-keto-PGF1α measured by radioimmunoassay (RIA). Pretreatment of rabbits with an aqueous extract of garlic (500 mgkg) provided protection from thrombocytopenia and hypotension. Thromboxane-B2 synthesis was significantly reduced in animals pretreated with garlic and then injected with a lethal dose of either collagen or arachidonic acid. The amount of TXB2 synthesized in these animals was not sufficient to induce thrombocytopenia or hypotension. All animals pretreated with garlic were well protected against the effects of collagen or arachidonate infusion, and no apparent symptoms were observed in these animals. These observations indicate that garlic may be beneficial in the prevention of thrombosis.
Keywords : Collagen, garlic, Arachidonic acid, thromboxane
Visit
Histopathological evidence of protective action of garlic against collagen and arachidonic acid toxicity in rabbits
Authors : MA Alnaqeeb, M Ali, M Thomson, SH Khater, SA Gomes, JM Al-Hassan
Abstract : Soluble rat tail tendon collagen produced respiratory distress, agitation, convulsions and finally death in rabbits when infused intravenously (i.v.) in lethal doses. Similar observations were noted when a lethal dose of arachidonic acid (unsaturated essential fatty acid) was infused. These agents caused thrombocytopenia, indicative of in vivo platelet aggregation, hypotension and increased levels of thromboxane (TX) B2 (a stable metabolite of TXA2) in the plasma. Histopathological examination of lung, heart and liver tissue indicated that the lungs and livers of treated animals were adversely affected, while heart tissues appeared to be normal. Histopathological examination of lung and liver tissues of animals pretreated with garlic, then treated with a lethal dose of collagen or arachidonic acid showed a significant reduction in the damage observed compared to animals not pretreated with garlic.
Keywords : Garlic, collagen toxicity, arachidonic acid
Visit
The effect of indomethacin and metamizole on ureteral motility and urine flow in sheep
Authors : Samar Khater, Maria Khattar, O Thulesius
Abstract : The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1-2 mg/kg) and metamizole (60-120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.
Keywords : Indomethacin, Dipyrone, prostaglandins, anti-inflammatory agents, ureteral obstruction, ureters
Visit