Natural polymers have received a great deal of interest for their potential use in the encapsulation and transportation of pharmaceuticals and other bioactive compounds for disease treatment. In this perspective, the drug delivery systems (DDS) constructed by representative natural polymers from animals (gelatin and hyaluronic acid), plants (pectin and starch), and microbes (Xanthan gum and Dextran) are provided. In order to enhance the efficiency of polymers in DDS by delivering the medicine to the right location, reducing the medication’s adverse effects on neighboring organs or tissues, and controlling the medication’s release to stop the cycle of over- and under-dosing, the incorporation of Fe₃O₄ magnetic nanoparticles with the polymers has engaged the most consideration due to their rare characteristics, such as easy separation, superparamagnetism, and high surface area. This review is designed to report the recent progress of natural polymeric Fe₃O₄ magnetic nanoparticles in drug delivery applications, based on different polymers’ origins.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Muntingia calabura L. (family Muntingiaceae), commonly known as Jamaican cherry or kerukup siam in Malaysia, is used traditionally to treat various ailments. The aim of this study is to elucidate the possible underlying gastroprotective mechanisms of ethyl acetate fraction (EAF) of Muntingia calabura methanolic leaves extract (MEMC). MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined. HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p < 0.01 and p < 0.05, respectively), while free and total acidity reduced in the doses of 250 and 500 mg/kg (p <0.001 and p <0.05, respectively). EAF also augmented the mucus content significantly (p < 0.001). Pre-treatment with N-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) reversed the gastroprotective activity of EAF. EAF treatment markedly ameliorated the SOD, GSH and CAT activity and PGE2 and NO level while attenuating MDA level, relative to the vehicle group. In conclusion, the underlying gastroprotective mechanisms of EAF could be associated with the antisecretory, participation of mucus, antiperoxidative, improvement of antioxidant status, modulation of NO and SH compounds, stimulation of PGE2 as well as presence of quercetin and gallic acid.

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.

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’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’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.

We used a type 2 diabetes rat model produced by a high fat diet (HFD) followed by low dose streptozotocin (STZ) to study diabetic vasculopathy. Animals were evaluated for early vascular structural changes, endothelial function, inflammation, lipid profile and oxidative stress. We used 20 male Sprague-Dawley rats divided equally into control and diabetic groups. Diabetic rats were fed an HFD for 4 weeks, injected intraperitoneally with STZ, then sacrificed at week 15. Aortic endothelial nitric oxide synthase (eNOS), aortic superoxide dismutase (SOD), endothelial-dependent and independent relaxation and contraction, intima-media thickness (IMT), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were measured. Histopathological characteristics also were assessed. Diabetic rats exhibited higher fasting blood glucose (FBG), low density lipoprotein, total cholesterol and triglycerides compared to the control group. Aortic endothelium-dependent relaxation due to acetylcholine (ACh) was lower, while aortic endothelium-dependent contraction due to calcium ionophore and endothelium-independent contraction due to phenylephrine (PE) were higher for the diabetic group. eNOS expression was lower in the diabetic group compared to controls. IMT and MDA levels were increased, while SOD activity was decreased in the diabetic group compared to controls. TNF-α was higher in the diabetic group than for controls. Our type 2 diabetes model exhibited endothelial dysfunction associated with early vascular structural changes, dyslipidemia, increased vascular oxidative stress, and inflammation. Therefore, the model is suitable for studying diabetic atherosclerosis.