Cetilistat

Cafeteria diet (CD) model for in-vivo studies mimics the western diet having imbalanced nutritional value, high caloric-density and palatability. Uncontrolled eating leads to the development of childhood obesity, poor self-esteem and depression due to its effects on brain development. Herbal supplements are novel inclusion in the management of obesity and mental well-being. Pterostilbene (PTE) found in blueberries and Pterocarpus marsupium heartwood, is known to prevent obesity in invivo models. Adolescent Swiss albino male mice were fed on CD for 70 days and the development of obesity was assessed by gain in body weight, abdominal circumference. Forced swim and tail suspension test confirmed depression in CD fed mice. Obesity induced depressed (OID) mice were treated with PTE (10, 20, 40 mg/kg), standard antiobesity drug cetilistat (10 mg/kg), antidepressant fluoxetine (10 mg/kg) for 28 days. Post treatment, PTE-treated mice showed reduction in BW and depression-like behavior analysed using paradigms such as sucrose preference, open field, marble burying, and resident intruder test in comparison to the CD group. Insulin resistance, lipid profile, antioxidant enzyme, inflammatory cytokines (NF-κB, IL-6, TNF α) and cortisol levels were mitigated by PTE. It also restored normal cellular architecture of the brain and adipose tissue and increased the Silent mating type information regulation 2 homolog1 (SIRT1), leptin and ghrelin receptors gene expression in the brain. Thus, it can be concluded that PTE might have inhibited OID like behavior in mice via inhibition of IR, modulating neuroinflammation and hypothalamic-pituitary-adrenal axis dysfunction and upregulating SIRT1 mediated leptin-ghrelin signaling.

Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC₅₀ values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC₅₀ value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α-glucosidase inhibitory activity displaying IC₅₀ values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC₅₀ value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC₅₀ values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC₅₀ value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.