Advances in functional lipid nanoparticles: from drug delivery platforms to clinical applications.

Since Doxil's first clinical approval in 1995, lipid nanoparticles have garnered great interest and shown exceptional therapeutic efficacy. It is clear from the licensure of two RNA treatments and the mRNA-COVID-19 vaccination that lipid nanoparticles have immense potential for delivering nucleic acids. The review begins with a list of lipid nanoparticle types, such as liposomes and solid lipid nanoparticles. Then it moves on to the earliest lipid nanoparticle forms, outlining how lipid is used in a variety of industries and how it is used as a versatile nanocarrier platform. Lipid nanoparticles must then be functionally modified. Various approaches have been proposed for the synthesis of lipid nanoparticles, such as High-Pressure Homogenization (HPH), microemulsion methods, solvent-based emulsification techniques, solvent injection, phase reversal, and membrane contractors. High-pressure homogenization is the most commonly used method. All of the methods listed above follow four basic steps, as depicted in the flowchart below. Out of these four steps, the process of dispersing lipids in an aqueous medium to produce liposomes is the most unpredictable step. A short outline of the characterization of lipid nanoparticles follows discussions of applications for the trapping and transporting of various small molecules. It highlights the use of rapamycin-coated lipid nanoparticles in glioblastoma and how lipid nanoparticles function as a conjugator in the delivery of anticancer-targeting nucleic acids. High biocompatibility, ease of production, scalability, non-toxicity, and tailored distribution are just a meager of the enticing allowances of using lipid nanoparticles as drug delivery vehicles. Due to the present constraints in drug delivery, more research is required to utterly realize the potential of lipid nanoparticles for possible clinical and therapeutic purposes.

Antidiabetic with antilipidemic and antioxidant effects of flindersine by enhanced glucose uptake through GLUT4 translocation and PPARγ agonism in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by the people of developing countries to treat various diseases. WHO also recommends the use of medicines from plants source. In that, diabetes also one of the diseases that have been treated traditionally by several people all over the world. In India, Toddalia asiatica (L.) Lam. (Rutaceae) is also a medicinal plant used traditionally for the treatment of diabetes in Ayurveda. Moreover, T. asiatica is also used in a polyherbal formulation to treat diabetes. AIM OF THE STUDY: This study examined the antidiabetic with antilipidemic and antioxidant effects of flindersine isolated from T. asiatica leaves. MATERIALS AND METHODS: Diabetes was induced in Wistar rats by feeding a high-fat diet (HFD) for 15 days and injecting a single dose of 40 mg/kg b. wt. of Streptozotocin (STZ). Five days post-injection, the grouped diabetic rats were treated with 20 and 40 mg/kg of flindersine. RESULTS: Flindersine resulted in a clear decline of blood glucose levels during 28 days of treatment in two different doses. Flindersine also significantly (P ≤ 0.05; P ≤ 0.005) reduced the body weight gain, plasma insulin concentration, urea, creatinine, total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) levels and significantly increased (P ≤ 0.05; P ≤ 0.005) the total protein level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared to the standard drug, pioglitazone. Additionally, flindersine restored the glucose transporter protein 4 (GLUT4), adenosine monophosphate protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) expressions in adipose tissues and skeletal muscles. CONCLUSION: It has been found that flindersine has potent antilipidemic and antidiabetic activities by improving insulin sensitivity by enhancing the phosphorylation of AMPK, GLUT4 translocation, and PPARγ agonism on adipose tissue and skeletal muscles of diabetic rats.

Friedelin exhibits antidiabetic effect in diabetic rats via modulation of glucose metabolism in liver and muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: Demand for plant-based medications and therapeutics is increasing worldwide as of its potential effects and no toxic. Traditionally, so many medicinal plants are used to treat diabetes. Subsequently, investigation on medicinal plants was enduring to discover potential antidiabetic drugs. A. tetracantha is used traditionally to cure diabetes mellitus, cough, dropsy, chronic diarrhea, rheumatism, phthisis and smallpox. Scientifically, A. tetracantha has been reported as an antidiabetic agent. Friedelin, the isolated compound has been reported as hypolipidemic, antioxidant, scavenging of free radicals, antiulcer, anti-inflammatory, analgesic and antipyretic agent. AIM OF THE STUDY: To scrutinize the mechanism of antidiabetic activity of friedelin isolated from the leaves of A. tetracantha. MATERIALS AND METHODS: A. tetracantha leaves powder (5 kg) was soaked in hexane (15 L) to obtain hexane extract. Using column chromatography, the hexane extract was fractionated using a combination of solvents like hexane and ethyl acetate. 25 fractions were obtained and the fractions 13 and 14 yielded the compound, friedelin. Friedelin at the doses of 20 and 40 mg/kg was used to treated STZ -induced diabetic rats for 28 days. Later 28 days of treatment, the bodyweight changes, levels of blood glucose, insulin, SGOT, SGPT, SALP, liver glycogen and total protein were assessed. RESULTS: Friedelin significantly brought these altered levels to near normal. Moreover, friedelin also enhanced the translocation as well as activation of GLUT2 and GLUT4 through PI3K/p-Akt signaling cascade in skeletal muscles and liver on diabetic rats. CONCLUSION: This finding proved that friedelin has an anti-diabetic effect through insulin-dependent signaling cascade mechanism, thus it may lead to establishing a drug to treat type 2 diabetes mellitus.

Antioxidant, antilipidemic and antidiabetic effects of ficusin with their effects on GLUT4 translocation and PPARγ expression in type 2 diabetic rats.

In this study, the antioxidant, antilipidemic and antidiabetic effects of ficusin isolated from Ficus carica leaves and their effects on GLUT4 translocation and PPARγ expression were evaluated in HFD-STZ induced type 2 diabetic rats. Ficusin (20 and 40 mg/kg b. wt.) lowered the levels of fasting blood glucose, plasma insulin and body weight gain, in HFD-STZ induced diabetic rats. Ficusin also significantly lowered the serum antioxidant enzymes (SOD, CAT and GPx) and lipids (TC, TG and FFA) levels to near normal. Ficusin significantly enhanced the PPARγ expression and improved the translocation and activation of GLUT4 in the adipose tissue. Molecular docking analysis exhibited promising interactions of GLUT4 and PPARγ into their active sites. This study suggests that ficusin improved the insulin sensitivity on adipose tissue and it can be used for the treatment of obesity related type 2 diabetes mellitus.

Hypoglycemic activity of 6-bromoembelin and vilangin in high-fat diet fed-streptozotocin-induced type 2 diabetic rats and molecular docking studies.

AIMS: This paper investigates the hypoglycemic activity of two derivatives of embelin (1) viz. 6-bromoembelin (2) and vilangin (3), in high-fat diet - STZ induced diabetic rats. MAIN METHODS: The effects of 6-bromoembelin (2) and vilangin (3) on insulin resistance, ß-cell dysfunction and glucose transport in high-fat diet (HFD) fed-streptozotocin (STZ) (40mg/kg) induced type 2 diabetic rats were evaluated. The binding modes of 6-bromoembelin (2) and vilangin (3) into PPARγ, PI3K, Akt, and GLUT4 were also studied using Autodock 4.2 and ADT 1.5.6 programs. KEY FINDINGS: At the dose of 30mg/kg, the plasma glucose, plasma insulin and body weight were reduced by both embelin derivatives in diabetic rats. Additionally the altered lipid profiles and hexokinase, glucose-6-phosphatase and fructose-1,6-bisphosphatase levels were brought to normal. Compared to diabetic control group, there was a significant increase in the expression of PPARγ in epididymal adipose tissue. Inhibition of adipogenic activity and mild activation of PPARγ levels in the skeletal muscle and liver were observed. In epididymal adipose tissue, the compounds increased the insulin-mediated glucose uptake through the activation and translocation of GLUT4 in PI3K/p-Akt signaling cascade. SIGNIFICANCE: The derivatives of embelin such as 6-bromoembelin (2) and vilangin (3) may be useful in the prevention and treatment of obesity-linked type 2 diabetes mellitus.

Hypolipidemic activity of friedelin isolated from Azima tetracantha in hyperlipidemic rats

Abstract The hypolipidemic activity of friedelin isolated from Azima tetracantha Lam., Salvadoraceae, was studied in Triton WR-1339 and high-fat diet-induced hyperlipidemic rats. In Triton WR-1339 induced hyperlipidemic rats, treatment with friedelin (50 and 70 mg/kg) showed a significant (p < 0.01) lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol (TC), triacylglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). In high-fat diet fed hyperlipidemic rats, treatment with friedelin (50 and 70 mg/kg) caused lowering of lipid levels in plasma and liver. The hypolipidemic activity of friedelin was compared with fenofibrate, a known lipid-lowering drug, in both models.

Polyphenols-rich Cyamopsis tetragonoloba (L.) Taub. beans show hypoglycemic and ß-cells protective effects in type 2 diabetic rats.

The aim of this study was to evaluate the antidiabetic activity of Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans in high-fat diet (HFD) fed-streptozotocin (STZ)-induced type 2 diabetic rats. Dose dependent response of oral treatment of C. tetragonoloba beans' methanol extract (CTme) (200 and 400mg/kg b wt.) was assessed by measuring fasting blood glucose, changes in body weight, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, oral glucose tolerance, intraperitoneal insulin tolerance, hepatic glycogen, marker enzymes of carbohydrate metabolism in HFD fed-STZ-induced type 2 diabetic rats. Histology and immunohistochemical analysis of pancreatic islets were also performed. High-performance liquid chromatography (HPLC) analysis of CTme showed the presence of polyphenols such as gallic acid and caffeic acid in the concentrations of 2.46% (W/W) and 0.32% (W/W). CTme significantly reverted the altered biochemical parameters to near normal levels in diabetic rats. Furthermore CTme showed the protective effect on the ß-cells of pancreatic tissues in diabetic rats. These findings indicate that C. tetragonoloba beans have therapeutic potential in HFD fed-STZ-induced hyperglycemia; therefore this can be used in the management of type 2 diabetes.

In vitro antioxidant and antihyperlipidemic activities of Toddalia asiatica (L) Lam. leaves in Triton WR-1339 and high fat diet induced hyperlipidemic rats.

The present study was undertaken to evaluate the in vitro antioxidant and antihyperlipidemic activity of Toddalia asiatica (L) Lam. leaves in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. In in vitro studies T. asiatica leaves ethyl acetate extract showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC50 605.34±2.62 µg/ml), hydroxyl (IC50 694.37±2.12 µg/ml) and nitric oxide (IC50 897.83±1.48 µg/ml) radicals, as well as high reducing power. In Triton WR-1339 induced hyperlipidemic rats, oral treatment with T. asiatica leaves ethyl acetate extract produced a significant (P≤0.005) decrease in the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and significant increase in high-density lipoprotein cholesterol (HDL-C) in comparison with hexane and methanol extracts. In high fat diet-fed hyperlipidemic rats, the ethyl acetate extract (200 and 400 mg/kg) significantly altered the plasma and liver lipids levels to near normal.