As more serotonergic drugs are developed and used for psychiatric disorders, frequently in combination or close temporal proximity, clinicians must be aware of and consider the factors that may increase the risk of patients experiencing serotonin syndrome.

In the present investigation, the supercritical carbon dioxide (SC-CO2) extracts of small cardamom (SC) and yellow mustard (YM) seeds have been investigated for their efficacies in combating type 2 diabetes in streptozotocin-induced Wistar albino rats. Fasting blood glucose (FBG) levels in the rats were monitored on days 8, 15, and 21. On day 15, FBG level reduced appreciably by 31.49% in rats treated with SC seed extract and by 32.28% in rats treated with YM seed extract, comparable to metformin (30.70%) and BGR-34 (a commercial polyherbal drug) (31.81%) administered rats. Either extract exhibited desirable effects on hepatic glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and catalase activities in controlling diabetes. A molecular docking exercise was conducted to identify specific compounds in the extracts which possessed augmenting effect on glucose-6-phosphate dehydrogenase. The results revealed that all the bioactive compounds in the extracts have binding affinities with the enzyme and contributed to the antidiabetic efficacies of the extracts as glucose-6-phosphate dehydrogenase augmenters. The effects of the extracts on insulin sensitivity and glucose uptake were investigated using non-invasive modeling by iHOMA2 software. This in vitro approach indicated that extract administration resulted in increased both insulin sensitivity of the liver and glucose uptake in the gut. The findings of this study attest these SC-CO2 extracts of the spices as safe alternatives of metformin and BGR-34 in combating type 2 diabetes and could be safely subjected to clinical studies. These extracts could also be employed in designing proactive food supplements in mitigating the metabolic disorder.

Melatonin-rich and 1,8-cineole-rich extracts have been successfully obtained from yellow mustard (YM) and small cardamom (SC) seeds, respectively, employing green technology of supercritical CO2 (SC-CO2) extraction. Chemical profiling confirmed the presence of melatonin and 1,8-cineole and co-extractants in the respective extracts. Electron paramagnetic resonance spectroscopy attested strong antioxidant activities of the extracts foregoing pan-assay interference compounds involved in spectroscopic analysis. These extracts also exhibited synergistic efficacies greater than unity confirming antioxidant synergy among the co-extracted bioactives therein. To ascertain hypocholesterolaemic efficacies, these extracts were co-administered orally with Triton X (at the pre-optimised dose of 175 mg/kg body weight (BW)) to Wistar albino rats at doses of 550, 175 and 55 mg/kg BW. Serum total cholesterol levels in the rats were monitored on days 3, 7, 15 and 21. On day 21, total cholesterol level reduced appreciably by 49·44 % in rats treated with YM seed extract and by 48·95 % in rats treated with SC seed extract, comparable with atorvastatin-administered rats (51·09 %). Either extract demonstrated inhibitory effects on hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase activity. A molecular docking exercise identified specific compounds in the extracts which possessed binding affinities comparable with therapeutically used HMG-CoA reductase inhibitors. In silico and in vivo studies concertedly concluded that the consortium of bioactive components in the extracts cannot be considered as invalid metabolic panaceas and therefore these ‘green’ extracts could be safely subjected to clinical studies as preventive biotherapeutics for hypercholesterolaemia. These extracts could be consumed per se as hypocholesterolaemic supplements or could be ingredients of new spice-based therapeutic foods.

Background & Objectives: In our previous investigation, oral administration of 1,8- cineole-rich supercritical carbon dioxide extract of small cardamom seeds in Wistar albino rats resulted in achieving normal fasting blood glucose (FBG) and serum cholesterol levels. The objective of this study was to further protect the aforesaid extract and to enhance its in vivo therapeutic efficacies in redressing type 2 diabetes and hypercholesterolemia, by encapsulating it as nanoliposomes. Patents related to nanoliposomes have been revised thoroughly. Methods: PEGylated nanoliposomes of the aforesaid extract were formulated using soya phosphatidylcholine and Tween 80 by probe-sonication. These nanoliposomes were subjected to in vitro characterizations and were orally administered to Wistar albino rats at three different doses viz. 550, 175 and 55 mg/kg b.w. for detailed investigation of their antidiabetic and hypocholesterolemic efficacies. Results: FT-IR, DSC and XRD analyses, HLB value (16), entrapment efficiency (84%) and release kinetics (obeying Higuchi model) revealed that the nanoliposomes were o/w type and were hydrophilic. They exhibited appreciable in vitro antioxidant potency (59% DPPH scavenging activity) owing to a synergistic consortium of antioxidants present therein. Oral administration of the liposomes in rats at 550 mg/kg b.w. could restore their normal FBG levels and serum lipid profiles on day 35, with desirable up-down regulations of related key enzymes. The iHOMA2 model could successfully predict the effects of nanoliposomes on insulin sensitivity and glucose uptake in rat liver and brain, respectively. Conclusion: Nanoliposome of 1,8-cineole rich extract of small cardamom seeds is a new biotherapeutic in redressing type 2 diabetes and hypercholesterolemia.