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Heshu Sulaiman Rahman,1,2 Darya Saeed Abdulateef,1 Narmin Hamaamin Hussen,3 Aso Faiq Salih,4 Hemn Hassan Othman,5 Trifa Mahmood Abdulla,1 Shirwan Hama Salih Omer,1 Talar Hamaali Mohammed,1 Mohammed Omar Mohammed,6 Masrur Sleman Aziz,7 Rasedee Abdullah8 1Department of Physiology, College of Medicine, University of Sulaimani, Sulaimaniyah, Republic of Iraq; 2Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Republic of Iraq; 3Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Republic of Iraq; 4Department of Pediatrics, College of Medicine, University of Sulaimani, Sulaimaniyah, Republic of Iraq; 5Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Republic of Iraq; 6Department of Medicine, College of Medicine, University of Sulaimani, Sulaimaniyah, Republic of Iraq; 7Department of Biology, College of Education, Salahaddin University, Erbil, Republic of Iraq; 8Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM, Serdang, Selangor, 43400, MalaysiaCorrespondence: Heshu Sulaiman RahmanDepartment of Physiology, College of Medicine, University of Sulaimani, Sulaimaniyah, 46001, Republic of IraqTel +964 7726159598Email heshu.rhaman@univsul.edu.iqAso Faiq SalihDepartment of Pediatrics, College of Medicine, University of Sulaimani, Sulaimaniyah, Republic of IraqEmail aso.salih@univsul.edu.iqAbstract: Over the last few decades, there have been several global outbreaks of severe respiratory infections. The causes of these outbreaks were coronaviruses that had infected birds, mammals and humans. The outbreaks predominantly caused respiratory tract and gastrointestinal tract symptoms and other mild to very severe clinical signs. The current coronavirus disease-2019 (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly spreading illness affecting millions of people worldwide. Among the countries most affected by the disease are the United States of America (USA), India, Brazil, and Russia, with France recording the highest infection, morbidity, and mortality rates. Since early January 2021, thousands of articles have been published on COVID-19. Most of these articles were consistent with the reports on the mode of transmission, spread, duration, and severity of the sickness. Thus, this review comprehensively discusses the most critical aspects of COVID-19, including etiology, epidemiology, pathogenesis, clinical signs, transmission, pathological changes, diagnosis, treatment, prevention and control, and vaccination.Keywords: recent advancements, COVID-19, pandemic infection, global outbreak, a comprehensive review

Tavga Ahmed Aziz, Ahmed Azad Kareem, Hemn Hassan Othman, Zheen Aorahman Ahmed Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, Kurdistan Region, IraqCorrespondence: Tavga Ahmed AzizDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, IraqTel +9647701523544Email tavga.aziz@univsul.edu.iqObjective: The present study was designed to evaluate the anti-inflammatory effects of different doses of aliskiren in two animal models of inflammation.Methodology: Sixty-six Wistar rats were allocated into five groups: the first group (six rats) was treated with the vehicle only, without induction of paw edema and granulomatous inflammation, and served as a negative control; the second group (12 rats) was allocated into two subgroups and treated with the vehicle only, with induction of paw edema and granulomatous inflammation, and served as a positive control; the third group (36 rats) was allocated into six subgroups and treated with different doses of aliskiren (15, 30, and 60 mg/kg) in both models; the fourth group (12 rats) was treated with dexamethasone (1 mg/kg) in both models of inflammation. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and high sensitivity C-reactive protein (hs-CRP) were measured. Skin samples were also sent for histopathological examination.Results: Aliskiren, in a dose-dependent pattern, significantly decreased inflammation in rat models of inflammation, by attenuating the percentage of exudate, granuloma, and paw edema. Furthermore, it significantly reduced serum concentrations of TNF-α, VCAM-1, and hs-CRP and restored the serum concentration of IL-10. Additionally, significant improvement was seen in the histopathological findings.Conclusion: In the current study, aliskiren was successful in decreasing inflammation in both models. These findings suggest that aliskiren is a good candidate for the treatment of inflammatory diseases.Keywords: aliskiren, inflammation, granuloma, paw edema, inflammatory markers

Heshu Sulaiman Rahman,1,2 Hemn Hassan Othman,3 Nahidah Ibrahim Hammadi,4 Swee Keong Yeap,5 Kawa Mohammad Amin,6 Nozlena Abdul Samad,7 Noorjahan Banu Alitheen8 1Department of Physiology, College of Medicine, University of Sulaimani, Sulaymaniyah 46001, Republic of Iraq; 2Department of Medical Laboratory Sciences, College of Health Sciences, Komar University of Science and Technology, Sulaymaniyah, Republic of Iraq; 3Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaymaniyah 46001, Republic of Iraq; 4Department of Histology, College of Veterinary Medicine, University of Al-Anbar, Ramadi, Republic of Iraq; 5China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang, Malaysia; 6Department of Microbiology, College of Medicine, University of Sulaimani, Sulaymaniyah 46001, Republic of Iraq; 7Integrative Medicine Cluster, Institut Perubatan dan Pergigian Termaju (IPPT), Sains@BERTAM, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia; 8Department of Cell and Molecular Biology, Faculty of Biotechnology and Bio-Molecular Sciences, Universiti Putra Malaysia, Selangor, MalaysiaCorrespondence: Noorjahan Banu AlitheenDepartment of Cell and Molecular Biology, Faculty of Biotechnology and Bio-Molecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaTel +60 126866947Email noorjahan@upm.edu.myHeshu Sulaiman RahmanDepartment of Physiology, College of Medicine, University of Sulaimani, Sulaymaniyah 46001, Republic of IraqTel +964 7726159598Email heshu.rhaman@univsul.edu.iqAbstract: Many types of research have distinctly addressed the efficacy of natural plant metabolites used for human consumption both in cell culture and preclinical animal model systems. However, these in vitro and in vivo effects have not been able to be translated for clinical use because of several factors such as inefficient systemic delivery and bioavailability of promising agents that significantly contribute to this disconnection. Over the past decades, extraordinary advances have been made successfully on the development of novel drug delivery systems for encapsulation of plant active metabolites including organic, inorganic and hybrid nanoparticles. The advanced formulas are confirmed to have extraordinary benefits over conventional and previously used systems in the manner of solubility, bioavailability, toxicity, pharmacological activity, stability, distribution, sustained delivery, and both physical and chemical degradation. The current review highlights the development of novel nanocarrier for plant active compounds, their method of preparation, type of active ingredients, and their biomedical applications.Keywords: nanomedicine, natural plant metabolite, biomedical application, carrier formulation, drug delivery

Rahman H, Rasedee A, How CW, et al. Int J Nanomedicine. 2015;10(1):1649-1666. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged manipulation of transmission electron microscopy (TEM) images in Figure 8. The authors responded to our queries and were able to provide the original TEM images. The authors explained that the images had intentionally been modified to clear away artefacts created during sample processing. While the journal accepted the original TEM images were available, they were considerably different to those in the published article, and this raised doubts over the validity of the reported results. The decision was made to retract the article and the authors do not agree with this ruling. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Zheen Aorahman Ahmed,1 Aso Nihad Abtar,1 Hemn Hassan Othman,2 Tavga Ahmed Aziz1 1Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq; 2Department of Anatomy and Pathology, College of Veterinary Medicine, University of Sulaimani, Sulaimani, Kurdistan Region, IraqCorrespondence: Zheen Aorahman Ahmed; Tavga Ahmed AzizDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, Kurdistan Region, IraqTel +964 770 972 4959; +964 770 152 3455Email zheen.ahmed@univsul.edu.iq; tavga.aziz@univsul.edu.iqObjective: This study aimed to evaluate the effect of quercetin and/or sitagliptin on testicular damage induced by doxorubicin (DOX).Methodology: Twenty-five male Wistar rats, weighing 240±20 g, were randomly divided into five groups as follows: a negative control group; that was treated with 1 mL of 0.9% sodium chloride; a DOX-treated group received Intraperitoneal (I.P.) DOX injection (3 mg/kg); a group treated with quercetin 80 mg/kg + sitagliptin 10 mg/kg + DOX; a group treated with quercetin 80 mg/kg + DOX; and a group treated with sitagliptin 10 mg/kg+ DOX. All treatment were given orally daily for 21 days with I.P. DOX 3 mg/kg injection for the treatment groups at days 8, 10, 12, 15, 17, and 19. On day 22, blood was collected for analysis of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutathione peroxidase (GPx), and total antioxidant capacity (TAOC). The testes were also removed and sent for histopathological examination.Results: The study revealed that the combination of quercetin with sitagliptin produced a significant increase in testosterone and FSH levels with a non-significant increase in LH level. This combination also non-significantly decreased the level of ALP and LDH and restored the GPx level with enhancing TAOC.Conclusion: The results suggest quercetin/sitagliptin combination as a promising therapeutic modality for attenuation of DOX-induced testicular toxicity in rats, and the main mechanism involved in such effect could be due to the antioxidant and anti-inflammatory properties of both agents.Keywords: doxorubicin, quercetin, sitagliptin, testicular damage

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Chee Wun How,2 Nazariah Allaudin Zeenathul,1,2 Max Stanley Chartrand,4 Swee Keong Yeap,2 Ahmad Bustamam Abdul,2,5 Sheau Wei Tan,2 Hemn Hassan Othman,1,3 Zahra Ajdari,6 Farideh Namvar,7 Palanisamy Arulselvan,2 Sharida Fakurazi,2,5 Parvaneh Mehrbod,2 Nasibeh Daneshvar,2 Hasina Begum2 1Faculty of Veterinary Medicine, 2Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 3Faculty of Veterinary Medicine, University of Sulaimany, Sulaimany City, Northern Iraq; 4DigiCare Behavioral Research, Casa Grande, AZ, USA; 5Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; 6Faculty of Science and Technology, University Kebangsaan Malaysia, Selangor, Malaysia; 7Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, Selangor, Malaysia Abstract: 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. Keywords: zerumbone-loaded nanostructured lipid carrier, leukemia, WEHI-3B cells, BALB/c mice, apoptosis, mitochondrial pathway

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Ahmad Bustamam Abdul,2,4 Nazariah Allaudin Zeenathul,1,2 Hemn Hassan Othman,1,3 Swee Keong Yeap,2 Chee Wun How,2 Wan Abd Ghani Wan Nor Hafiza4,51Faculty of Veterinary Medicine, 2Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 3Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq; 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; 5College of Medical Laboratory Technology, Institute for Medical Research, Kuala Lumpur, MalaysiaAbstract: 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.Keywords: zerumbone-loaded nanostructured lipid carrier, cell cycle arrest, apoptosis, mitochondrial pathway

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Chee Wun How,2 Ahmad Bustamam Abdul,2 Nazariah Allaudin Zeenathul,1,2 Hemn Hassan Othman,1 Mohamed Ibrahim Saeed,2 Swee Keong Yeap21Department of Microbiology and Pathology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia; 2Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Microbiology, Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern IraqAbstract: 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.Keywords: zerumbone, nanostructured lipid carrier, leukemia

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

Nanotechnology is a far-reaching technology with tremendous applications in various aspects, including general medicine, veterinary medicine, agriculture, aquaculture, and food production. Nanomaterials have exceptional physicochemical characteristics, including increased intestinal absorption, biodistribution, bioavailability, and improved antimicrobial and catalytic properties. Although nanotechnology is gaining ground in animal management, husbandry, and production, its wide use is still hampered by occasional toxicity and side effects. Zinc oxide nanoparticles (ZnO-NPs) have long been utilized in animal production, aquaculture, and pet animal medicine. However, the use ZnO-NPs in animals has been associated with reports of toxicity and side effects. ZnO-NPs may have shown numerous beneficial effects in animals; its use must be regulated with care to avoid unwanted consequences. Thus, this review emphasizes the usage of ZnO-NPs in animal production and laboratory animals and the potential side effects associated with the use of nanoparticles as a feed supplement and therapeutic compound., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

In the present paper, a sensitive and selective inner filter effect sensing platform was designed to detect nitrofurantoin (NIT) in pharmaceutical dosage form. Nitrogen and phosphorus co-doped carbon nanodots (CNDs) prepared via solvothermal treatment of folic acid and phosphoric acid. The prepared CNDs exhibit greenish fluorescence at 470 nm when excited at 340 nm with fluorescence quantum yield up to 40%. The CNDs exhibit high stability in various pH, temperature, and ionic strength which adds valuable merits to its pharmaceutical applications. The emission is quenched in the presence of absorber (here NIT) while the fluorophores were not quench by the presence of common pharmaceutical excipients. A fluorometric assay was fabricated to determine NIT in capsules by quenching of the CNDs. The linear response for the proposed method was from 5.0 μM to 90 μM with the detection limit being 1.4 μM. To validate the method, the recovery of NIT in spiked sample was measured which was 96.6% -103.3%. The method was applied to the determination of NIT in pharmaceutical capsule samples, with comparable results of a reference method stated by the British Pharmacopeia (BP). Furthermore, the sub-acute toxicity studies of CNDs were investigated using normal male Balb/c mice forcefully drunk with 3 different dosages of CNDs. Animals did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 28 days observation period. Additionally, no significant (P > 0.05) changes in the body weight, haematological and biochemical parameters compared with the control group were not revealed. Similarly, histopathological examination of the internal vital organs did not show any morphological alterations., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest with this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro , in vivo , and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field., Competing Interests: No conflict of interest is recorded for this review article., (Copyright © 2020 Heshu Sulaiman Rahman et al.)

The current rampant coronavirus infection in humans, commonly known as COVID-19, a pandemic that may cause mortality in humans, has been declared a global emergency by the World Health Organization (WHO). The morbidity and mortality rates due to the pandemic are increasing rapidly worldwide, with the USA most affected by the disease. The source COVID-19 is not absolutely clear; however, the disease may be transmitted by either by COVID-19-positive individuals or from a contaminated environment. In this review, we focused on how the COVID-19 virus is transmitted in the community. An extensive literature search was conducted using specific keywords and criteria. Based on the published report, it is concluded that COVID-19 is primarily transmitted human-to-human via oral and respiratory aerosols and droplets with the virus-contaminated environment play a lesser role in the propagation of disease. Healthcare providers and the elderly with comorbidities are especially susceptible to the infection., (© 2020 The Author(s).)

Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.

This investigation determined the anticancer properties of zerumbone (ZER) on the human T-cell (Jurkat) line using the MTT assay, microscopic evaluations, flow cytometric analyses, and caspase activity estimations. The results showed that ZER is selectively cytotoxic to Jurkat cells in a dose and time-dependent manner with IC50 of 11.9 ± 0.2, 8.6 ± 0.5 and 5.4 ± 0.4 μg/mL at 24, 48 and 72 hours of treatment, respectively. ZER did not produce an adverse effect on normal human peripheral blood mononuclear cells (PBMC). ZER is not as cytotoxic as doxorubicin, which imposed an inhibitory effect on Jurkat cells with IC50 of 2.1 ± 0.2, 1.8 ± 0.15, 1.5 ± 0.07 μg/mL after 24, 48 and 72 hours treatment, respectively. ZER significantly (P < 0.05) arrested Jurkat cells at the G2/M phase of the cell cycle. The antiproliferative effect of ZER on Jurkat cells was through the apoptotic intrinsic pathway via the activation of caspase-3 and -9. The results showed that ZER can be further developed into a safe chemotherapeutic compound for the treatment of cancers, especially leukemia.

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.

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.

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.

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 × 10(6) 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.