Hypothetical biosynthetic pathways of pharmaceutically potential hallucinogenic metabolites in Myristicaceae, mechanistic convergence and co-evolutionary trends in plants and humans.

The family Myristicaceae harbour mind-altering phenylpropanoids like myristicin, elemicin, safrole, tryptamine derivatives such as N,N-dimethyltryptamine (DMT) and 5-methoxy N,N-dimethyltryptamine (5-MeO-DMT) and ß-carbolines such as 1-methyl-6-methoxy-dihydro-ß-carboline and 2-methyl-6-methoxy-1,2,3,4-tetrahydro-ß-carboline. This study aimed to systematically review and propose the hypothetical biosynthetic pathways of hallucinogenic metabolites of Myristicaceae which have the potential to be used pharmaceutically. Relevant publications were retrieved from online databases, including Google Scholar, PubMed Central, Science Direct and the distribution of the hallucinogens among the family was compiled. The review revealed that the biosynthesis of serotonin in plants was catalysed by tryptamine 5-hydroxylase (T5H) and tryptophan 5-hydroxylase (TPH), whereas in invertebrates and vertebrates only by tryptophan 5-hydroxylase (TPH). Indolethylamine-N-methyltransferase catalyses the biosynthesis of DMT in plants and the brains of humans and other mammals. Caffeic acid 3-O-methyltransferase catalyses the biosynthesis of both phenylpropanoids and tryptamines in plants. All the hallucinogenic markers exhibited neuropsychiatric effects in humans as mechanistic convergence. The review noted that DMT, 5-MeO-DMT, and ß-carbolines were natural protectants against both plant stress and neurodegenerative human ailments. The protein sequence data of tryptophan 5-hydroxylase and tryptamine 5-hydroxylase retrieved from NCBI showed a co-evolutionary relationship in between animals and plants on the phylogenetic framework of a Maximum Parsimony tree. The review also demonstrates that the biosynthesis of serotonin, DMT, 5-MeO-DMT, 5-hydroxy dimethyltryptamine, and ß-carbolines in plants, as well as endogenous secretion of these compounds in the brain and blood of humans and rodents, reflects co-evolutionary mutualism in plants and humans.

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.

A sensitive 1 H NMR spectroscopic method for the quantification of capsaicin and capsaicinoid: morpho-chemical characterisation of chili land races from northeast India.

INTRODUCTION: Proton (1 H) nuclear magnetic resonance (NMR) spectroscopy based analytical method for the quantification of capsaicin (major pungent principle of chili) has certain advantages including short data acquisition time and better structural authentication. Earlier NMR methods are associated with either of the bottlenecks such as low or lack of information on the sensitivity and scope for the quantification of total capsaicinoid. OBJECTIVE: To develop a sensitive 1 H quantitative NMR (qNMR) technique for capsaicin and total capsaicinoid in dry chili and chili oleoresin and to demonstrate its applicability in a real sample set. METHOD: A 1 H qNMR method was developed using benzene as the internal standard for the quantification of capsaicin (terminal methyl signal) as well as total capsaicinoid (benzyl methylene signal) in dry chili and oleoresin and validated in terms of specificity, linearity, sensitivity, accuracy and precision. RESULTS: The developed 1 H qNMR method was specific, sensitive (limit of detection 4.4 µg/mL and limit of quantitation 14.8 µg/mL), linear in the range 0.083-8.33 mg/mL of capsaicin, accurate and precise. The credibility of the developed method was showcased in the morpho-chemical characterisation of commercially available 15 chili land races from northeast India. The analysis identified the land races with a wide range of capsaicin (trace to 1.49% in the dry fruit and trace to 6.21% in the oleoresin w/w) and oleoresin content (3.35-26.78% w/w). CONCLUSION: The standardized 1 H qNMR method facilitated the findings of chemical basis for the selection of chili land races from this region, capable of producing high-yielding oleoresin with intended degree of pungency.