Hemn Hassan Othman

Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect

Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostructured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68 ± 0.1 nm and a polydispersity index of 0.29 ± 0.004 μm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was −25.03 ± 1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64 ± 0.38 μg/mL, and for free zerumbone was 5.39 ± 0.43 μg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia.

Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line.

This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.

Biomedical properties of a natural dietary plant metabolite, zerumbone, in cancer therapy and chemoprevention trials

Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

Comparison of Tamoxifen with Edible Seaweed (Eucheuma cottonii L.) Extract in Suppressing Breast Tumor

The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 106 cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Effects of Brown Seaweed (Sargassum polycystum) Extracts on Kidney, Liver, and Pancreas of Type 2 Diabetic Rat Model.

The edible seaweed Sargassum polycystum (SP) is traditionally used against several human diseases. This investigation evaluated the effects of two dietary doses of SP ethanolic and aqueous extracts on the pancreatic, hepatic, and renal morphology of type 2 diabetic rats (T2DM). T2DM was induced by feeding rats on high calorie diet followed by a low dose streptozotocin. Changes in the diabetic rat organs in SP treated groups with different doses of extracts were compared with normal rats, diabetic control rats, and metformin treated rats. After 22 days of treatment, the pathological lesions of the livers and kidneys in the diabetic rats were quantitatively and qualitatively alleviated (P < 0.05) by both the SP extracts at 150 mg/kg body weight and by metformin. All the treated diabetic groups revealed marked improvement in the histopathology of the pancreas compared with the control diabetic group. Oral administration of 300 mg/kg body weight of aqueous and ethanolic extracts of SP and metformin revealed pancreas protective or restorative effects. The seaweed extracts at 150 mg/kg body weight reduced the liver and kidney damages in the diabetic rats and may exert tissue repair or restoration of the pancreatic islets in experimentally induced diabetes to produce the beneficial homeostatic effects.

Antileukemic effect of zerumbone-loaded nanostructured lipid carrier in WEHI-3B cell-induced murine leukemia model

Cancer nanotherapy is progressing rapidly with the introduction of many innovative drug delivery systems to replace conventional therapy. Although the antitumor activity of zerumbone (ZER) has been reported, there has been no information available on the effect of ZER-loaded nanostructured lipid carrier (NLC) (ZER-NLC) on murine leukemia cells. In this study, the in vitro and in vivo effects of ZER-NLC on murine leukemia induced with WEHI-3B cells were investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase activity assays showed that the growth of leukemia cells in vitro was inhibited by ZER-NLC. In addition, outcomes of histopathology, transmission electron microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the number of leukemia cells in the spleen of BALB/c leukemia mice significantly decreased after 4 weeks of oral treatment with various doses of ZER-NLC. Western blotting and reverse-transcription quantitative polymerase chain reaction assays confirmed the antileukemia effects of ZER-NLC. In conclusion, ZER-NLC was shown to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading of ZER in NLC did not compromise the anticancer effect of the compound, suggesting ZER-NLC as a promising and effective delivery system for treatment of cancers.

Comparison of apoptotic inducing effect of zerumbone and zerumbone-loaded nanostructured lipid carrier on human mammary adenocarcinoma MDA-MB-231 cell line

This study investigated the anticancer effect of zerumbone (ZER) and zerumbone-loaded nanostructured lipid carrier (ZER-NLC) on the human mammary gland adenocarcinoma (MDA-MB-231) cell line. The effect of ZER and ZER-NLC on MDA-MB-231 cells was determined via electron and fluorescent microscopy and flow cytometry using the Annexin V, cell cycle, and Tdt-mediated dUTP nick-end labeling assays. We demonstrated that ZER and ZER-NLC significantly suppressed the proliferation of MDA-MB- 231 cells with an IC50 of 5.96 ± 0.13 and 6.01 ± 0.11 µg/mL, respectively. ZER and ZER-NLC arrested MDA-MB-231 cell cycle at the G2/M phase. The induction of apoptosis by ZER and ZER-NLC was via the intrinsic pathway through the release of cytochrome c and activation of caspase-3 and caspase-9. The treatments also caused the downregulation of antiapoptotic Bcl-2, Bcl-xL proteins, and proliferating cell nuclear protein and upregulation of proapoptotic Bax protein. Therefore, loading of ZER into NLC did not compromise the anticancer effects of ZER on MDA-MB-231 cells. In conclusion, ZER-NLC, which increased the bioavailability of ZER, is an effective agent in the treatment of cancers.

Zerumbone, a Natural Dietary Sesquiterpene from Zingiber Zerumbet for Leukaemia Therapy In Vitro

Zerumbone (ZER) is a natural crystalline phytochemical compound that isolated from Zingiber zerumbet (L.) Smith in 1956. In this investigation, the anticancer properties of ZER were evaluated for the first time on cancer cells of T-acute lymphoblastic leukemia, Jurkat cells; using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and microscopic investigation (fluorescent microscope and scanning electron microscope). The results showed that ZER has cytotoxic effect against Jurkat cells in time dependent manner (24, 48 and 72 h) with an IC50 of 11.87±0.17 μg/mL, 8.59±0.48 μg/mL and 5.39±0.43 μg/mL respectively. Comparatively, doxorubicin (positive control) imposed an inhibitory effect on Jurkat cells with an IC50 of 1.51±0.07 μg/mL after 72 h incubation. Simultaneously, we revealed that the inhibitory effect of ZER on leukaemic cells growth was due to induction of apoptosis as evidenced by microscopic investigation. The current finding suggested that ZER with its unique chemical structure and versatile pharmacological activities might be helpful for improving the usefulness of anticancer agents in the therapy of leukemia.

Advancements in the Therapy of Ebola Virus Disease

Ebola virus disease is an infection of human and nonhuman primates with fatality rates of up to 90%. Since 2014, the largest outbreak of Ebola virus in recorded history spread into several adjacent West African nations. The infection especially propagated into highly populated areas and where there was inadequate healthcare infrastructure and public sanitation. Such deficiencies permitted the widespread of the virus and caused more than 10,000 casualties to-date. Currently, no specific therapy is available and treatment of Ebola patients depends mainly on supportive care and symptomatic treatment. A worldwide effort has been made to develop new therapeutic strategies, several of which were potential vaccines where promising results were demonstrated in non-human primates. High throughput screening of FDA-approved drugs has revealed several compounds with potential anti-Ebola activity in vitro, which raises the idea of reconsidering the previously approved drugs as possible candidates against the virus. This article reviews the current drug candidates and prospects towards the development of potential EVD therapy.