Current Pharmaceutical Situation (Services) in Yemen and Future Challenges

This article deals with Yemen’s current pharmaceutical scenario and possible future challenges that it may face. The manuscript provides an overview of health services particularly pharmaceutical services and the critical health challenges facing the people of the country. Details included are statistical data with regard to the health of the Yemeni population and their demographic backgrounds following administrative issues, policy for the medicinal trade and production, the regulation and financing. The manuscript also deals with the government’s action about medicines, their procurement, and distribution in the public sector, and the public perception of medicines. Rational use of medicines is determined by the knowledge and attitude of the consumers. Future challenges are also anticipated. World health systems have been facing an incredible transformation to address new challenges with regard to the demographics, disease trends, the emergence and the re-emergence of diseases along with higher costs of health care delivery. This has led to a comprehensive review of health systems and how they function to serve the masses. Some health systems do not seem to adequately provide services that really matter to the people and some deteriorate, following governments’ lack of efficiency in supporting and extending the services. Other issues can also affect the ability of the health systems to deliver including health administration, healthcare financing, the lack of balance of the human resources, inaccessible and poor quality services and the impact of modifications and reform prevalent in other economic areas

Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague–Dawley Rats

Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC–HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited �-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis

Anti-tumor Activity of NuvastaticTM (C5OSEW5050ESA) of Orthosiphon stamineus and Rosmarinic Acid in An Athymic Nude Mice Model of Breast Cancer

The current treatment strategies for metastatic breast cancer depend on the cancer subtype by palliating symptoms and prolonging life. However, triple-negative breast cancers have no targeted treatment available. Orthosiphon stamineus (O.s) is a traditional folk medicine plant used in South East Asia to treat many diseases. The aim of this study is to evaluate the anti-tumor activity of O.s extract formulation (ID: C5EOSEW5050ESA trademarked as NuvastaticTM) and its major component, rosmarinic acid in a breast in vivo tumor xenograft model. Human triple-negative breast cancer cells were transplanted into the mammary fat pad of 20 athymic nude mice. Fourteen days post-injection, mice were randomly assigned to four groups. C5EOSEW5050ESA (200 and 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally. The body weight and tumor size were measured twice a week. Histopathological analyses of tumor tissues were conducted. Tumor necrosis and tumor growth were determined by hematoxylin and eosin staining. A significant reduction in tumor size and growth was found in all treatment groups. No significant difference between C5EOSEW5050ESA at 200 mg/kg and rosmarinic acid in the reduction of tumor size and necrosis. However, a more significant reduction was found in tumor growth and necrosis with 400 mg/kg of C5EOSEW5050ESA treatment as compared to other treatments. These results highlighted the anti-tumor activity of C5EOSEW5050ESA in reducing breast tumor growth in mice compared to the lower dose of C5EOSEW5050ESA and rosmarinic acid. This study provides valuable insights into using C5EOSEW5050ESA as a treatment to target triple-negative breast cancers in vivo

Serum leptin correlates in fertile and idiopathic infertile Yemeni males: a comparative cross-sectional study

This comparative cross-sectional study aimed to evaluate the relationship between serum leptin and testosterone, FSH, LH, PRL and semen quality in fertile and idiopathic infertile Yemeni men. A total of 30 infertile males with unknown causes and 30 age-matched healthy fertile males were enrolled in this study. The body mass index (BMI) and waist circumference (WC) were measured. Semen samples were analyzed according to the WHO manual for semen analysis. Serum samples were tested for hormones. Subjects were then divided into subgroups and compared based on their main seminal findings. The WC, serum leptin, PRL, FSH and LH levels were significantly higher (p < 0.05) in the infertile subjects than in the fertile group. Serum leptin demonstrated a significant positive correlation (p < 0.01) with body weight, BMI and WC in fertile males and a significant negative correlation (p < 0.01) with testosterone in fertile and infertile males. Similarly, a significant positive correlation was found between serum leptin and FSH (p < 0.01) and LH (p < 0.05) levels in the infertile subjects. The findings showed that non-obstructive azoospermic (NOA) patients have significant (p < 0.05) high levels of serum leptin, FSH, and LH. These findings may support the possibility of a direct peripheral negative effect of leptin on testicular steroidogenesis independent of the suggested indirect effect, and it could directly impact spermatogenesis without inhibiting testosterone production. This effect was accompanied by increasing serum PRL levels. Furthermore, serum leptin and gonadotropins were found to be increased in the idiopathic NOA group. The present study provided valuable insights into the fertile and idiopathic infertile Yemeni males and could establish an important foundation for future andrological-related studies such as investigating the relationship between leptin and other hormones; and infertility-related genetic and epigenetic factors

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged

Comparative proteomic analysis of different stages of breast cancer tissues using ultra high performance liquid chromatography tandem mass spectrometer.

BACKGROUND:Breast cancer is the fifth most prevalent cause of death among women worldwide. It is also one of the most common types of cancer among Malaysian women. This study aimed to characterize and differentiate the proteomics profiles of different stages of breast cancer and its matched adjacent normal tissues in Malaysian breast cancer patients. Also, this study aimed to construct a pertinent protein pathway involved in each stage of cancer. METHODS:In total, 80 samples of tumor and matched adjacent normal tissues were collected from breast cancer patients at Seberang Jaya Hospital (SJH) and Kepala Batas Hospital (KBH), both in Penang, Malaysia. The protein expression profiles of breast cancer and normal tissues were mapped by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The Gel-Eluted Liquid Fractionation Entrapment Electrophoresis (GELFREE) Technology System was used for the separation and fractionation of extracted proteins, which also were analyzed to maximize protein detection. The protein fractions were then analyzed by tandem mass spectrometry (LC-MS/MS) analysis using LC/MS LTQ-Orbitrap Fusion and Elite. This study identified the proteins contained within the tissue samples using de novo sequencing and database matching via PEAKS software. We performed two different pathway analyses, DAVID and STRING, in the sets of proteins from stage 2 and stage 3 breast cancer samples. The lists of molecules were generated by the REACTOME-FI plugin, part of the CYTOSCAPE tool, and linker nodes were added in order to generate a connected network. Then, pathway enrichment was obtained, and a graphical model was created to depict the participation of the input proteins as well as the linker nodes. RESULTS:This study identified 12 proteins that were detected in stage 2 tumor tissues, and 17 proteins that were detected in stage 3 tumor tissues, related to their normal counterparts. It also identified some proteins that were present in stage 2 but not stage 3 and vice versa. Based on these results, this study clarified unique proteins pathways involved in carcinogenesis within stage 2 and stage 3 breast cancers. CONCLUSIONS:This study provided some useful insights about the proteins associated with breast cancer carcinogenesis and could establish an important foundation for future cancer-related discoveries using differential proteomics profiling. Beyond protein identification, this study considered the interaction, function, network, signaling pathway, and protein pathway involved in each profile. These results suggest that knowledge of protein expression, especially in stage 2 and stage 3 breast cancer, can provide important clues that may enable the discovery of novel biomarkers in carcinogenesis

Proapoptotic and Antiangiogenic Activities of Arctium Lappa L. on Breast Cancer Cell Lines

In this study, the bioactivity-guided fractionation was conducted on the aerial parts of Arctium lappa L. and then the extracts were tested in vitro on breast cancer (MCF-7), colorectal cancer (HCT-116), and normal cells (EA.hy926). The n-hexane fraction (EHX) of the ethanolic extract showed strong activity against both MCF-7 and EA.hy926 cell lines (IC50 values: 14.08 ± 3.64 and 27.25 ± 3.45 μg/mL, respectively). The proapoptotic activity of EHX was assessed using MCF-7. Morphological alterations were visualized using Hoechst staining and a transmission electron microscope. Cancer cell signal transduction pathways were investigated, and EHX significantly upregulated p53, TGF-β, and NF-κB. Furthermore, EHX was found to disrupt the metastatic cascade of breast cancer cells by the inhibition of cell proliferation, migration, invasion, and colonization. The antiangiogenic activity of EHX fraction showed potent inhibition of rat aorta microvessels with IC50 value: 4.34 ± 1.64 μg/mL. This result was supported by the downregulation of VEGF-A expression up to 54%. Over 20 compounds were identified in EHX using GC-MS, of which stigmasterol, ß-sitosterol, and 3-O-acetyllupeol are the major active compounds. Phytochemical analysis of EHX showed higher phenolic and flavonoid contents with a substantial antioxidant activity. In conclusion, this work demonstrated that A. lappa has valuable anticancer activity and antiangiogenic properties that might be useful in breast cancer therapy

Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague–Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes

Chemical composition, antiproliferative and antioxidant attributes of ethanolic extract of resinous sediment from Etlingera elatior (Jack.) inflorescence

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 μg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 μg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro