Nutmegs and wild nutmegs: An update on ethnomedicines, phytochemicals, pharmacology, and toxicity of the Myristicaceae species.

Prized medicinal spice true nutmeg is obtained from Myristica fragrans Houtt. Rest species of the family Myristicaceae are known as wild nutmegs. Nutmegs and wild nutmegs are a rich reservoir of bioactive molecules and used in traditional medicines of Europe, Asia, Africa, America against madness, convulsion, cancer, skin infection, malaria, diarrhea, rheumatism, asthma, cough, cold, as stimulant, tonics, and psychotomimetic agents. Nutmegs are cultivated around the tropics for high-value commercial spice, used in global cuisine. A thorough literature survey of peer-reviewed publications, scientific online databases, authentic webpages, and regulatory guidelines found major phytochemicals namely, terpenes, fatty acids, phenylpropanoids, alkanes, lignans, flavonoids, coumarins, and indole alkaloids. Scientific names, synonyms were verified with www.theplantlist.org. Pharmacological evaluation of extracts and isolated biomarkers showed cholinesterase inhibitory, anxiolytic, neuroprotective, anti-inflammatory, immunomodulatory, antinociceptive, anticancer, antimicrobial, antiprotozoal, antidiabetic, antidiarrhoeal activities, and toxicity through in-vitro, in-vivo studies. Human clinical trials were very few. Most of the pharmacological studies were not conducted as per current guidelines of natural products to ensure repeatability, safety, and translational use in human therapeutics. Rigorous pharmacological evaluation and randomized double-blind clinical trials are recommended to analyze the efficacy and therapeutic potential of nutmeg and wild nutmegs in anxiety, Alzheimer's disease, autism, schizophrenia, stroke, cancer, and others.

Elaeocarpus floribundus Bl. seeds as a new source of bioactive compounds with promising antioxidant and antimicrobial properties.

The fruits of Elaeocarpus floribundus Bl. (Elaeocarpaceae) are edible and are normally prescribed for treatment of diseases. The medicinal uses of the fruit create considerable quantities of seeds as wastes. In an attempt to valorise this biomass, we studied the antimicrobial and antioxidant activities of the ethanolic seed extract. The extract inhibited the growth of the tested pathogens and was also a very strong scavenger of DPPH free radicals. Consequently, the extract was phytochemically investigated and this study reports the initial isolation of five phenolic compounds from this source. The structures of the isolated compounds were elucidated by spectra analyses including HR-ESI-MS, 1D and 2D NMR experiments. The isolated compounds exhibited a wide range of antimicrobial activities against the tested pathogens. Gallic acid (4) showed the most activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 30 µg/mL, while the MIC values of the antimicrobial standards range between 10 and 35 µg/mL. Compound 4, crude ethanolic extract, and the ethyl acetate fraction were more a potent free radical scavenger of DPPH compared to ascorbic acid. Hence, the seeds of E. floribundus could be considered as a new source of bioactive compounds for pharmaceutical and food-related industries.

Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents.

Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic α-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for α-amylase inhibition, azadiradione and exhibited potential inhibition with an IC50 value of 74.17 and 68.38 µM, respectively against HPA under in vitro conditions. Further screening on AR42J α-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC50 of 11.1 and 13.4µM. Maximal secreted α-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3µM, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (Ki 42.2, 18.6 µM) and starch (Ki' 75.8, 37.4 µM) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ΔG° of -21.25 kJ mol-1 and -21.16 kJ mol-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.