The effects of methanolic extract of clinacanthus nutans L. (belalai gajah) on atherogenic risk markers in a type 2 diabetic rat model

Diabetes mellitus is associated with endothelial dysfunction (ED); causing progressive vascular damage. Clinacanthus nutans has been documented to have antioxidant, hypoglycemic, hypolipidemic and anti-inflammatory properties; properties with the potential to improve endothelial function and prevent atherosclerosis development. Firstly, this study aims to evaluate endothelial function, early vascular structural changes, vascular oxidative stress and inflammation in a model of type 2 diabetes (T2DM) rat induced by high-fat diet (HFD) and low-dose streptozotocin (STZ). Secondly, to determine the effects of C. nutans methanolic leaves extract (CNME) on the above parameters on the same model. First part of study: Male Sprague-Dawley rats were divided into non-diabetic and diabetic groups (n=12 per group). Diabetic groups were fed 4 weeks of HFD before intraperitoneal injection of STZ; and sacrificed at week 15. Fasting blood glucose (FBG) and lipid profile were measured prior to sacrifice. Upon sacrifice, the aorta was isolated; endothelial-dependent and -independent relaxations and contractions were determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS) expression was assessed via Western blotting. Aortic superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), histopathological changes and aortic intima-media thickness (IMT) were also measured. Second part of study: Male Sprague-Dawley rats were divided into non-diabetic and diabetic groups. After seven week of diabetes induction, rats were divided into five groups (n=12 per group): non-diabetic control (C), non-diabetic treated with 4 weeks of CNME (500 mg/kg/daily)(C+CNME), untreated diabetic rats (DM), diabetic treated with metformin (300 mg/kg/daily)(DM+Met) and diabetic treated with CNME (500 mg/kg/daily)(DM+CNME). Rats were sacrificed after 4 weeks of treatment and experimental parameters similar to part 1 of study were performed. Results; First part: Diabetic rats have higher FBG, total cholesterol (TC), triglycerides (TG), lowdensity lipoprotein cholesterol (LDL-C) and atherogenic index (AI) compared to non-diabetic rats. Endothelium-dependent relaxation was decreased while endothelial-dependent and -independent contractions were increased in diabetic rats. eNOS expression was lower in diabetic rats. IMT, MDA and TNF-a levels were increased while SOD activity lower in diabetic rats. Second part: Both DM+CNME and DM+Met groups reduced FBG levels compared to the DM group. Treatment with CNME and metformin in diabetic rats showed lower TC, TG, LDL-C and AI compared to untreated diabetic rats. Both diabetic-treated with CNME and metformin groups significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of eNOS. Treatment with CNME and metformin also reduced endothelium-dependent and -independent contractions in diabetics. Aortic IMT, MDA and TNF-α levels were reduced while SOD activity was higher in both CMNE and metformin treated diabetic rats. These results demonstrated that the T2DM model induced by HFD and low-dose STZ has ED associated with early vascular structural changes, and increased vascular oxidative stress and inflammation. Treatment with C. nutans extract improved endothelial-dependent vasodilatation, reduced endothelial-dependent and - independent contractions, increased eNOS expression and SOD levels, lower AI, MDA, TNF-a levels, and reduced IMT in aorta of T2DM rats; all these effects were comparable with metformin-treated diabetic rats. Thus, the methanolic extract of C. nutans leaves has the potential to be further explored as an adjunct in the treatment of T2DM to prevent or reduce severity of diabetes induced atherosclerosis

Antiulcer activity of methanol-chloroform extract of Channa striatus fillet

Channa striatus (Haruan) is Malaysian freshwater fish that is traditionally used to treat ailments related to wound and also ulcers. The aimed of the present study was to determine the mechanisms of anti-ulcer activity of chloroform: methanol extract of C. striatus fillet (CMCS) in rats. The antiulcer profile of CMCS, given orally in the doses of 50, 250 and 500mg/kg, was assessed using the ethanol- and indomethacin-induced gastric ulcer models. The mechanisms of antiulcer of CMCS were determined as follows; i) the antisecretory activity of CMCS was measured using the pyloric ligation rat model, and; ii) the role of nitric oxide (NO) and sulfhydryl compounds in the modulation of CMCS antiulcer activity were determined by pre-treating the rats with L-NAME or NEM, respectively, followed by the pre-treatment of rats with CMCS before subjecting the animals to the ethanol-induced gastric ulcer model. From the results obtained, CMCS exerted significant (P<0.05) antiulcer activity in both models of gastric ulcer wherein the macroscopic and microscopic analysis of the stomach supported the antiulcer claim. With regard to its antisecretory effect, CMCS did not change the volume and pH, but reduce the total acidity only at the lower doses of the gastric juice. Moreover, CMCS demonstrated antiulcer activity was reversed by NEM, but not affected by L-NAME. In conclusion, CMCS shows antiulcer activity that is modulated via its cytoprotective, but not antisecretory effect, and in the presence of sulfhysryl compounds, but not NO

Peptide-Based Vaccine against Breast Cancer: Recent Advances and Prospects

Breast cancer is considered the second-leading cancer after lung cancer and is the most prevalent cancer among women globally. Currently, cancer immunotherapy via vaccine has gained great attention due to specific and targeted immune cell activity that creates a potent immune response, thus providing long-lasting protection against the disease. Despite peptides being very susceptible to enzymatic degradation and poor immunogenicity, they can be easily customized with selected epitopes to induce a specific immune response and particulate with carriers to improve their delivery and thus overcome their weaknesses. With advances in nanotechnology, the peptide-based vaccine could incorporate other components, thereby modulating the immune system response against breast cancer. Considering that peptide-based vaccines seem to show remarkably promising outcomes against cancer, this review focuses on and provides a specific view of peptide-based vaccines used against breast cancer. Here, we discuss the benefits associated with a peptide-based vaccine, which can be a mainstay in the prevention and recurrence of breast cancer. Additionally, we also report the results of recent trials as well as plausible prospects for nanotechnology against breast cancer

Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, accounting for almost one-third of all deaths. The risk factors for developing this disease include high levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), alongside low levels of high-density lipoprotein (HDL). Dietary linoleic acid has been suggested to reduce these risk factors. This study aims to determine the effects of linoleic acid on cholesterol levels, liver function tests, and structural changes in liver tissue in comparison with fenofibrate in a hypercholesterolemic rat model. Thirty-six male Sprague Dawley rats (150–180 g) were divided into non-hypercholesterolemic and hypercholesterolemic groups. Hypercholesterolemia was induced in the rats by feeding them with a high-fat diet for two weeks. After two weeks, the non-hypercholesterolemic and hypercholesterolemic rats were equally divided into six groups (n = 6): control non-hypercholesterolemic rats, non-hypercholesterolemic rats treated with fenofibrate (60 mg/kg), non-hypercholesterolemic rats treated with linoleic acid (5 mg/kg), control hypercholesterolemic rats, hypercholesterolemic rats treated with fenofibrate (60 mg/kg), and hypercholesterolemic rats treated with linoleic acid (5 mg/kg). The changes in the rats’ body weight, serum lipid profiles, atherogenic indices, and liver function test results were obtained. The rats’ liver tissues were stained for histopathological analysis. The linoleic acid-treated hypercholesterolemic rats exhibited significantly reduced serum TC, TG, LDL, aspartate aminotransferase, and alanine aminotransferase levels, as well as increased HDL levels compared with the control hypercholesterolemic rats. These linoleic acid effects were comparable to those in the fenofibrate-treated hypercholesterolemic rats. In conclusion, linoleic acid possesses early anti-hypercholesterolemic properties, which may be due to the reductions in serum cholesterol levels and mild early structural changes in the liver tissues of hypercholesterolemic rats. Therefore, continued studies on linoleic acid in atherosclerotic and/or obese animal models are suggested

<i>Xestospongia muta</i> Fraction-7 and Linoleic Acid: Effects on <i>SR-BI</i> Gene Expression and HDL Cholesterol Uptake

Xestospongia muta is a marine sponge belonging to the family Petrosiidae. It is an important source of biologically active marine natural products, with different kinds of essential fatty acids. Scavenger receptor class B type I (SR-BI) is the main receptor for high-density lipoprotein (HDL) cholesterol, which plays a pivotal role in preventing atherosclerosis. It removes cholesterol from HDL cholesterol, returning lipid-poor lipoprotein into blood circulation. The present study investigated the effects of X. muta Fraction-7 and linoleic acid on SR-BI gene expression and HDL cholesterol uptake. In vitro studies of the activity of X. muta and linoleic acid against the therapeutic target for hypercholesterolemia were conducted using the HDL receptor SR-BI via luciferase assay and HepG2 cells. In the present study, Fraction-7 of X. muta showed the highest expression level of the SR-BI gene via luciferase assay. Profiling of Fraction-7 of X. muta by GC-MS revealed 58 compounds, comprising various fatty acids, particularly linoleic acid. The in vitro study in HepG2 cells showed that the Fraction-7 of X. muta and linoleic acid (an active compound in X. muta) increased SR-BI mRNA expression by 129% and 85%, respectively, compared to the negative control. Linoleic acid increased HDL uptake by 3.21-fold compared to the negative control. Thus, the Fraction-7 of X. muta and linoleic acid have the potential to be explored as adjuncts in the treatment of hypercholesterolemia to prevent or reduce the severity of atherosclerosis development

Time-Restricted Feeding Improved Vascular Endothelial Function in a High-Fat Diet-Induced Obesity Rat Model

Obesity, where there is enhancement of stored body fat in adipose tissues, is associated with cardiovascular complications that are mainly related to atherosclerosis. Time-restricted feeding (TRF) is a form of restricted eating aimed at reducing weight in obese subjects. The present study aims to investigate changes in vascular endothelial function, endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt) protein expressions with TRF in obese and normal rats. Male Sprague Dawley rats were divided into two normal and three obese groups; obesity was induced in the obese groups by feeding with a high-fat diet (HFD) for six weeks. After six weeks, rats were equally divided into five groups (n = 7 per group): Normal group (NR) which continued on a standard diet for six more weeks, normal group switched to TRF with a standard diet for six weeks (NR + TRFSD), obese group (OR) which continued on HFD for six more weeks, obese group switched to TRF of HFD (OR + TRFHFD), and obese group switched to TRF of a standard diet (OR + TRFSD). TRF was practiced for six weeks, after which the rats were sacrificed. Aortic endothelium-dependent and endothelium-independent relaxations and contractions were assessed using the organ bath. Aortic eNOS and Akt protein expressions were determined using immunoblotting. Fasting blood glucose, body weight, body mass index (BMI), serum lipid profile, Lee&rsquo;s index, serum insulin levels, and sensitivity (HOMA-IR) were also measured. Endothelium-dependent relaxation was significantly impaired, while endothelium-dependent contraction increased in obese rats compared to that in normal rats. Both obese groups which underwent TRF with a HFD and standard diet improved their impairments in endothelium-dependent relaxation and reduced endothelium-dependent contraction; these were associated with increased expressions of aortic eNOS and Akt protein. Both obese groups with TRF reduced body weight, BMI, Lee&rsquo;s index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and improved insulin sensitivity. TRF improved endothelium-dependent relaxation and reduced endothelium-dependent contraction, thus attenuating endothelial dysfunction in obese rats. These were associated with increased aortic eNOS and Akt protein expressions

Haruan (Channastriatus) extract as halal innovation productsfor healing of gastric ulcer: preliminary investigation

Channastriatus (Haruan), a freshwater and snakehead fish, is traditionally used by the Malay to heal wound and lessens post-operative pain and discomfort. The objective of the present study is to elucidate the gastroprotective activity of chloroform:metanol extract of C. striatus fillet. The fillets were extracted using the methanol: chloroform (2:1; v/v) solvent system. The extract (labeled as MCECS), prepared in the doses of 50, 250, and 500 mg/kg, was orally administered into rats for 7 continuous days and then the animals were subjected to the ethanol- and indomethacin-induced gastric ulcer models. Following the euthanization of treated rats, the stomach was callected for macroscopic and microscopic analysis. The results showed that oral administration of MCECS exhibited significant (p<0.05) and dose-dependent antiulcer activity when assessed using both models of gastric ulcer. In addition, the macroscopic findings were supported by the microscopic observations. In conclusion, C. striatus extract exerted remarkable antiulcer activity that warranted in-depth studies in an attempt to develop its extract as a halal-based product

Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity

The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory cytokines, and free fatty acids (FFAs) found in diabesity (a pathophysiological link between obesity and diabetes) could lead to ER stress. However, limited data exist regarding ER stress and its association with diabesity, particularly the implicated proteins and molecular mechanisms. Thus, this review highlights the role of ER stress in relation to some proteins involved in diabesity pathogenesis and provides insight into possible pathways that could serve as novel targets for therapeutic intervention