X-Linked Familial Hypophosphatemia: A Case Report of 27-Year Old Male and Review of Literature.

X-linked hypophosphatemia (XLH) associated with short stature during childhood are mostly referred to the hospital and diagnosed as vitamin D deficiency rickets and received vitamin D before adulthood. A case is presented with clinical features of hypophosphatemia from childhood who did not seek medical care for diagnosis and treatment, nor did his mother or two brothers, who have short statures, bone pain, and fractures. The patient was assessed for sociodemographic, hematological, and biochemical parameters together with a genetic assessment. A DEXA scan and X-ray were done to determine the abnormalities and deformities of joints and bones despite clinical examination by an expert physician. All imaging, laboratory parameters, and the genetic study confirmed the diagnosis of XLH. A detailed follow-up of his condition was performed after the use of phosphate tablets and other treatments. X-linked hypophosphatemia needs a good assessment, care, and follow up through a complementary medical team including several specialties. Phosphate tablets in adulthood significantly affects clinical and physical improvement and prevention of further skeletal abnormality and burden on daily activity. The patients should be maintained with an adequate dose of phosphate for better patient compliance. More awareness is needed in society and for health professionals when conducting medical checkups during the presence of stress fractures, frequent dental and gum problems, rickets, short stature, or abnormality in the skeleton or walking to think of secondary causes such as hypophosphatemia. Further investigations including a visit to a specialist is imperative to check for the primary cause of these disturbances.

The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.

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.

Beneficial and toxicological aspects of zinc oxide nanoparticles in animals.

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.

Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol.

BACKGROUND: Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu. METHODS: Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model. RESULTS: As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of - 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 µg/mL and 17.70 ± 0.57 µg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents. CONCLUSIONS: This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.

COVID-19 severity in relation to sociodemographics and vitamin D use.

Most COVID-19 cases are treated as outpatients, while the majority of studies on COVID-19 focus on inpatients. Little is known about the self-reporting and self-rating of the disease's symptoms, and the associations of prophylactic use of dietary supplements with COVID-19 severity have not been addressed. The aims of this study are to evaluate COVID-19 severity and to relate them to sociodemographic characteristics and prophylactic dietary supplements. An observational patient-based study conducted through an online questionnaire on recovered COVID-19 patients. The patients were assessed for several severity parameters, sociodemographic parameters, and prophylactic dietary supplement use. A total of 428 patients were evaluated. Age and presence of comorbidities had positive associations with the severity parameters. The severe infection group had the highest proportion of patients stressed about COVID-19 (P < 0.05). Cigarette, but not hookah, smoking was significantly associated with less severe symptoms. Vitamin D negatively predicted disease severity (P < 0.05). In conclusion, stress, age, and presence of comorbidities were the most important positive predictors of COVID-19 severity, while prophylactic vitamin D use and smoking were significant negative predictors. The use of protective measures and other prophylactic dietary supplements was not significantly associated with symptom severity.

Preclinical Drug Discovery in Colorectal Cancer: A Focus on Natural Compounds.

BACKGROUND: Colorectal cancer (CRC) is considered one of the most predominant and deadly cancer globally. Nowadays, the main clinical management for this cancer includes chemotherapy and surgery; however, these treatments result in the occurrence of drug resistance and severe side effects, and thus it is a crucial requirement to discover an alternative and potential therapy for CRC treatment. Numerous therapeutic cancers were initially recognized from natural metabolites utilized in traditional medicine, and several recent types of research have shown that many natural products own potential effects against CRC and may assist the action of chemotherapy for the treatment of CRC. It has been indicated that most patients are well tolerated by natural compounds without showing any toxicity signs even at high doses. Conventional chemotherapeutics interaction with natural medicinal compounds presents a new feature in cancer exploration and treatment. Most of the natural compounds overwhelm malignant cell propagation by apoptosis initiation of CRC cells and arresting of the cell cycle (especially at G, S, and G2/M phase) that result in inhibition of tumor growth. OBJECTIVE: This mini-review aimed to focus on natural compounds (alkaloids, flavonoids, polysaccharides, polyphenols, terpenoids, lactones, quinones, etc.) that were identified to have anti- CRC activity in vitro on CRC cell lines and/or in vivo experiments on animal models. CONCLUSION: Most of the studied active natural compounds possess anti-CRC activity via different mechanisms and pathways in vitro and in vivo that might be used as assistance by clinicians to support chemotherapy therapeutic strategy and treatment doses for cancer patients.

Novel Drug Delivery Systems for Loading of Natural Plant Extracts and Their Biomedical Applications.

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.

The strategy for controlling COVID-19 in Kurdistan Regional Government (KRG)/Iraq: Identification, epidemiology, transmission, treatment, and recovery.

This study has carried out a mini-review on first wave of COVID-19 infection and its control by the Kurdistan Regional Government (KRG)/Iraq. COVID-19 infection, which was named by the International Committee of Taxonomy of Viruses (ICTV) as SARS-CoV-2, is a newly identified coronavirus. The last century has seen the outbreak of numerous life-threatening human pathogens including Nipah, Ebola, Zika, Chikungunya, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and more recently a novel coronavirus has been observed. COVID-19 infection has so far spread to more than 186 countries around the world and KRG/Iraq has not been free from this virus. In this survey, the control of COVID-19 infection in KRG as a part of Iraq is discussed in detail. The methods of identification as well as the drugs that are currently in common use to reduce the wide distribution of COVID-19 infection and their effects in countries around the world are considered. So far, 714 positive cases have been reported by the ministry of health in Kurdistan Region Government-Iraq (KRG), among which there have been only 8 deaths, and 420 cases have recovered. Those who died had a previous history of a chronic disease such as diabetes, hypertension, heart disease, and hypercholesteremia. Alternative medicine based on natural green methods has been widely used by Kurdish people in past years for treatment of strong coughs. In the present study, some natural products which are cost free and effective in enhancing the body's resistance against the virus are considered. A surprising finding is that the patients in KRG have not in general had a severe cough, flu, or fever. The possible explanation may relate to the patients' strong immune systems, since none of them had a history of using alcohol and drugs, or of chronic disease. The epidemiology and transmission of the virus are discussed as well.

The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double-blind, randomized, placebo-controlled trial.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is one of the major diseases confronting the health care systems. In diabetes mellitus (DM), combined use of oral hypoglycemic medications has been shown to be more effective than metformin (Met) alone in glycemic control. This study determined the effects of Ginkgo biloba (GKB) extract as an adjuvant to Met in patients with uncontrolled T2DM. SUBJECTS AND METHODS: Sixty T2DM patients were recruited in a randomized, placebo-controlled, double-blinded, and multicenter trial. The patients, currently using Met, were randomly grouped into those treated with either GKB extract (120 mg/day) or placebo (starch, 120 mg/day) for 90 days. Blood glycated hemoglobin (HbA1c), fasting serum glucose, serum insulin, body mass index (BMI), waist circumference (WC), insulin resistance, and visceral adiposity index (VAI) were determined before (baseline) and after 90 days of GKB extract treatment. RESULTS: GKB extract significantly decreased blood HbA1c (7.7%±1.2% vs baseline 8.6%±1.6%, P<0.001), fasting serum glucose (154.7±36.1 mg/dL vs baseline 194.4±66.1 mg/dL, P<0.001) and insulin (13.4±7.8 µU/mL vs baseline 18.5±8.9 µU/mL, P=0.006) levels, BMI (31.6±5.1 kg/m2 vs baseline 34.0±6.0 kg/m2, P<0.001), waist WC (102.6±10.5 cm vs baseline 106.0±10.9 cm, P<0.001), and VAI (158.9±67.2 vs baseline 192.0±86.2, P=0.007). GKB extract did not negatively impact the liver, kidney, or hematopoietic functions. CONCLUSION: GKB extract as an adjuvant was effective in improving Met treatment outcomes in T2DM patients. Thus, it is suggested that GKB extract is an effective dietary supplement for the control of DM in humans.

Green synthesis palladium nanoparticles mediated by white tea (Camellia sinensis) extract with antioxidant, antibacterial, and antiproliferative activities toward the human leukemia (MOLT-4) cell line.

Among nanoparticles used for medical applications, palladium nanoparticles (PdNPs) are among the least investigated. This study was undertaken to develop PdNPs by green synthesis using white tea (W.tea; Camellia sinensis) extract to produce the Pd@W.tea NPs. The Pd@W.tea NPs were characterized by UV-vis spectroscopy and X-ray diffractometry, and evaluated with transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The Pd@W.tea NPs were spherical (size 6-18 nm) and contained phenols and flavonoids acquired from the W.tea extract. Pd@W.tea NPs has good 1-diphenyl-2-picrylhydrazyl (DPPH), OH, and NO-scavenging properties as well as antibacterial effects toward Staphylococcus epidermidis and Escherichia coli. MTT assay showed that Pd@W.tea NPs (IC50 =0.006 µM) were more antiproliferative toward the human leukemia (MOLT-4) cells than the W.tea extract (IC50 =0.894 µM), doxorubicin (IC50 =2.133 µM), or cisplatin (IC50 =0.013 µM), whereas they were relatively innocuous for normal human fibroblast (HDF-a) cells. The anticancer cell effects of Pd@W.tea NPs are mediated through the induction of apoptosis and G2/M cell-cycle arrest.

Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits.

Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions.

Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling.

Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an IC50 value of 12.0 µg/mL, without affecting human normal liver cells, WRL-68 (IC50>50 µg/mL) causing G0/G1 cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of NF-κB that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.

Cytotoxic effects of biosynthesized zinc oxide nanoparticles on murine cell lines.

The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 µg/mL (4T1), 17.45 ± 1.1 µg/mL (CRL-1451), 11.75 ± 0.8 µg/mL (CT-26), and 5.6 ± 0.55 µg/mL (WEHI-3B), respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 µg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

Brewers' rice induces apoptosis in azoxymethane-induced colon carcinogenesis in rats via suppression of cell proliferation and the Wnt signaling pathway.

BACKGROUND: Brewers' rice is locally known as temukut, is a byproduct of the rice milling process, and consists of broken rice, rice bran, and rice germ. Unlike rice bran, the health benefit of brewers' rice has yet to be fully studied. Our present study aimed to identify the chemopreventive potential of brewers' rice with colonic tumor formation and to examine further the mechanistic action of brewers' rice during colon carcinogenesis. METHODS: Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) azoxymethane (AOM) alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. Rats in group 2 to 5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. Colon tumor incidence and multiplicity was assessed by hematoxylin and eosin (H&E) staining. The expression of ß-catenin, cyclooxygenase-2 (COX-2), and Ki-67 was evaluated by immunohistochemical staining. The apoptosis-inducing activity was analyzed using a TUNEL assay. The data were analyzed using a one-way analysis of variance (ANOVA) with P-value<0.05 was considered significant. RESULTS: Overall analyses revealed that brewers' rice reduced colon tumor incidence and multiplicity. The results from immunohistochemistry analysis also showed that brewers' rice decreased the expression of ß-catenin, COX-2, and Ki-67 in a dose-dependent manner. Furthermore, TUNEL analysis demonstrated that administration of brewers' rice in AOM-induced rat colorectal cancer resulted in a dose-dependent increase in cell apoptosis. CONCLUSIONS: Taken together, our data suggested that brewers' rice can inhibit cell proliferation, induce apoptosis, and suppress COX-2 and ß-catenin expression via the Wnt signaling pathway and holds great promise in the field of chemoprevention as a dietary agent.

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.

Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract.

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 µg/mL (HepG2), 18.75±2.1 µg/mL (MCF-7), 12.5±1.7 µg/mL (HeLa), and 6.4±2.3 µg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.

Hypocholesterolemic activity of monascus fermented product in the absence of monacolins with partial purification for functional food applications.

Hypercholesterolemia is one of the most common chronic diseases in human. Along with chemical therapy traditional medication is used as hypocholesterolemic remedy, however, with unfavorable side effects. Recently, Monascus fermented product (MFP) has become a popular hypocholesterolemic natural supplement. In the present study, the hypocholesterolemic activity of Monascus purpureus FTC5391 fermented product ethanolic extract (MFPe) was investigated in hypercholesterolemic rats. Results showed that MFPe not only reduced the serum total cholesterol (TC), LDL-C, TG concentration, and TC/HDL-C ratio but also increased the HDL-C. Further, solid phase extraction (SPE) was carried out to obtain the hypocholesterolemic bioactive fraction. The high polar fraction of SPE increased the HDL-C (42%) and decreased the TC (53.3%), LDL-C (47%), and TG (50.7%) levels as well as TC/HDL-C ratio (69.1%) in serum. The GC-MS results of the active fraction revealed two main compounds, isosorbide and erythritol, which act as coronary vasodilator compounds.

Zerumbone induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in Jurkat cell line.

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.

Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum).

In the present study, we evaluated the effect of brown seaweeds Sargassum muticum methanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines proliferation. This algae extract was also evaluated for reducing activity and total polyphenol content. The MTT assay results indicated that the extracts were cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50 of 22 µg/ml for MCF-7 and 55 µg/ml for MDA-MB-231 cell lines. The percentages of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the concentration of the SMME. The antiproliferative efficacy of this algal extract was positively correlated with the total polyphenol contents, suggesting a causal link related to extract content of phenolic acids. Cell cycle analysis showed a significant increase in the accumulation of SMME-treated cells at sub-G1 phase, indicating the induction of apoptosis by SMME. Further apoptosis induction was confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into fertilized chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). Our results imply a new insight on the novel function of Sargassum muticum polyphenol-rich seaweed in cancer research by induction of apoptosis, antioxidant, and antiangiogenesis effects.

Inclusion Complex of Zerumbone with Hydroxypropyl- ß -Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio.

Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl- ß -cyclodextrin (HP ß CD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HP ß CD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HP ß CD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HP ß CD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.