Current Drug Metabolism - Volume 22, Issue 6, 2021

Obesity is a common nutritional disorder associated with a variety of chronic diseases, among them, type 2 diabetes (T2DM) has emerged as a serious worldwide health problem. Insulin resistance and β cell dysfunction are the main pathological characteristics of T2DM, and obesity and hyperlipidemia are the critical causal factors. It is commonly accepted that dietary factors are of paramount importance in the management of obesity and T2DM. Particularly, many botanic products and their extracts are endowed with a wide spectrum of biological activities, making them extensively reviewed as anti-obesity and anti-diabetes dietary supplements or new drug candidates. In this review, we aimed to summarize the effects, related mechanisms, and safety issues of dietary continents on obesity and T2DM, to provide theoretical support for better research and development of dietary therapy strategy for the treatment of obesity and T2DM. Based on many clinical investigations, specific carbohydrates and fatty acids, such as dietary fibers, polysaccharides, unsaturated fatty acids, have hypoglycemic and hypolipidemic effects. Vitamin D plays an important role in metabolism and immunity modulation. Apart from them, natural bioactive ingredients from plants, such as flavonoids, polyphenols, alkaloids, terpenoids, polysaccharides, and quinones are efficient in helping weight loss and improving insulin sensitivity and glycemic control. They can protect β cell function by antiinflammation, anti-oxidation, and anti-apoptosis properties, as well as regulating lipid metabolism. Therefore, promoting the consumption of diverse natural bioactive ingredients-rich products could be an effective nutritional strategy to benefit patients with obesity and type 2 diabetes.

Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form, derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three-dimensional honeycombs like structure provided with two internal aqueous channels for the incorporation of many s biologically active ingredients. In contrast to liposomes, they provide a large surface area for the incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as a method of choice in the sustained release, controlled release, and targeted release dosage forms as new drug delivery system for the better release of the drugs. As a lot of advancement in the new form of dosage form brought the novel avenues in drug delivery mechanisms, so it was a matter of worth to compile the latest updates on the various aspects of the mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health-related benefits.

Obesity is a major disorder characterized by excessive fat in the body. Various factors responsible for obesity are dietary, lifestyle, genetic, and environmental factors. The last two decades witnessed an enormous increase in obesity and its comorbidities among people worldwide, thus making it the fifth major cause of human death. As per the recent report of WHO, a total of 38 million children (age < 5 years) were overweight or obese in 2019, and according to the Organization for Economic Cooperation and Development (OECD) report, almost 1 in 4 people are obese. For the treatment of obesity, various synthetic drugs are available but on the other side, these are associated with severe adverse effects. To overcome this problem and in the view of the current situation, researchers emphasize more on the development of natural products for the management of obesity. Primary and secondary metabolites like polyphenols, alkaloids, saponins, and flavonoids derived from various plants worldwide are used to develop a formulation for the management of obesity. The phytoconstituents exert their action by suppressing the proliferation of adipocytes, inducing apoptosis of adipocytes, inhibiting lipogenesis, activating lipases, stimulating fatty acid β-oxidation, diminishing inflammatory responses, or conquering oxidative stress. This review also highlights the importance of the nanoencapsulation technique which enhances the efficacy of phytoconstituents by improving solubility, stability, and bioavailability to fight against obesity and comorbidity.

Background: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction of pantoprazole and atorvastatin is worthy of being investigated. Objective: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification of pantoprazole and atorvastatin in rat plasma. Methods: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin, respectively. Simple protein precipitation was used to extract analytes from 50.0 μL plasma samples. Results: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was 3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple- reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼ 5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity, specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per FDA guidelines. Conclusion: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.

Background: Caesalpinia sappan L. is a traditional medicinal plant that is used to promote blood circulation and treat stroke in China. Protosappanin B (PTB) is a unique homoisoflavone compound isolated from Sappan Lignum (the heartwood of Caesalpinia sappan L). In a previous study, the metabolic fate of PTB remained unknown. Objective: To explore whether PTB is extensively metabolized, the metabolites of PTB in bile, plasma, urine, feces, and intestinal bacteria samples in rats were investigated. Methods: The biosamples were investigated by ultraperformance liquid chromatography combined with time-offlight mass spectrometry (UPLC-TOF-MS/MS) with MetabolitePilot software. Results: 28 metabolites were identified in the biosamples: 18 metabolites in rat bile, 8 in plasma, 20 in feces, 7 in urine and 2 in intestinal bacteria samples. Both phase I and phase II metabolites were observed. Metabolite conversion occurred via 9 proposed pathways: sulfate conjugation, glucuronide conjugation, bis-glucuronide conjugation, glucose conjugation, dehydration, oxidation, hydrolysis, methylation and hydroxymethylene loss. The metabolic pathways differed among biosamples and exhibited different distributions. Among these pathways, the most important was sulfate and glucuronide conjugation. Conclusion: The results showed that the small intestinal and biliary routes play an important role in the clearance and excretion of PTB. The main sites of metabolism in the PTB chemical structure were the phenolic hydroxyl and the side-chains on the eight-element ring.