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.

Mushroom mediated selective bioreduction of S-(+)-carvone to cis-(-)-dihydrocarvone: approach towards a safer biocatalysis.

Dihydrocarvone, possessing four stereoisomers is an important flavour and chiral building block in chemical synthesis. Ascomycetes are well known for the selective bioreduction of carvone to dihydrocarvone. Often, these fungi produce mycotoxins which may contaminate the biocatalytic product. Herein, Ganoderma sessile, a polypore mushroom, selectively reduced S-(+)-carvone to cis-(-)-dihydrocarvone (DHC) in its submerged culture. In an optimised condition (0.75 g/L, 18 h, pH 3-5, 30 °C and 150 rpm), 82.7% cis-(-)-DHC was obtained in gas chromatography-mass spectrometry profile of the fermented product. The absolute titre of cis-(-)-DHC in fermentation medium was 0.35 ± 0.01 g/L. However, substrate toxicity (IC50 0.15 g/L) drastically reduced the transformation at higher carvone concentration (≥1.0 g/L). On the other hand, R-(-)-carvone was less selective and efficient in producing the desired isomer i.e. trans-(+)-DHC. G. sessile is the member of a group of non-toxic medicinal mushrooms and may be a safer yet efficient option for producing cis-(-)-DHC biocatalytically.

Chavibetol: major and potent phytotoxin in betel (Piper betle L.) leaf essential oil.

BACKGROUND: Many essential oils and their constituent volatile organic compounds are known to be phytotoxic and potential bioherbicides. This study aims to investigate the phytotoxicity of propenylbenzene-rich essential oils and identify active molecule(s) therein. RESULTS: Five commercially available propenylbenzene-rich oils were screened, of which betel (Piper betle L.) oil was identified as a potent natural phytotoxin. It dose-dependently inhibited wheatgrass (Triticum aestivum) seed germination and growth in water and agar medium with half maximal inhibitory concentration (IC50 ) in the range 23.2-122.7 µg mL-1 . Phytotoxicity-guided fractionation and purification revealed chavibetol as the major and most potent phytotoxic constituent of betel oil, followed by chavibetol acetate. A structure-activity relationship study involving 12 propenylbenzenes indicated the structural and positional importance of aromatic substitutions for the activity. Furthermore, the phytotoxic efficacy of chavibetol was established against wheatgrass germination and growth in water (IC50 15.8-53.4 µg mL-1 ), agar (IC50 34.4-53.6 µg mL-1 ) and aerial (IC50 1.7-4.5 mg L-1 ) media with a more pronounced effect on the radicle. Also, in open phytojars, chavibetol efficiently inhibited the growth of 3-7-day-old bermudagrass (Cynodon dactylon) seedlings when sprayed directly (IC50 2.3-3.4 mg jar-1 ) or supplemented in agar (IC50 116.6-139.1 µg mL-1 ). The growth of pre-germinated green amaranth (Amaranthus viridis) was inhibited more effectively in both application modes (1.2-1.4 mg jar-1 and IC50 26.8-31.4 µg mL-1 respectively). CONCLUSION: The study concluded betel oil as a potent phytotoxic herbal extract and its major constituent chavibetol as a promising volatile phytotoxin for the future management of weeds in their early phase of emergence. © 2023 Society of Chemical Industry.

Thermolabile essential oils, aromas and flavours: Degradation pathways, effect of thermal processing and alteration of sensory quality.

Plant-based aroma chemicals, constituting the essential oils play a great role as the natural flavours and preservatives in the food industries. Many of these metabolites are susceptible to degradation under heat (i.e. thermolabile aroma chemicals) which may influence the organoleptic properties of the end-products e.g. essential oil, oleoresin, dry herb, tea and packaged juice. The current review identified in total 42 thermolabile aroma and/or flavour molecules belonging to monoterpenoids, sesquiterpenoids and phenolics. The probable pathway of their degradation and its promoting conditions were also described. Degradation pathways were categorized into five major classes including oxidation, C-C bond cleavage, elimination, hydrolysis and rearrangement. Numerous evidences were cited in support of the thermosensitivity of these phytochemicals under pyrolytic, thermal heating or gas chromatographic conditions. Various post-harvest processes involved in the manufacturing such as drying and distillation of the crops or thermal treatment of the food-products for storage were highlighted as the root cause of degradation. The influence of thermolabile aroma chemicals to maintain the sensory quality of the end-products such as citrus juices, floral oils and thermally cooked foods was discussed in detail. In the present article, detailed insight into the chemical and sensory aspects of thermosensitive aromas and flavours was provided, covering the period from 1990 up to 2020.

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.

Evaluation of Postharvest Drying, Key Odorants, and Phytotoxins in Plai (Zingiber montanum) Essential Oil.

Plai or cassumunar ginger (Zingiber montanum), mainly distributed in tropical Asia, is an essential oil-bearing rhizomatous crop belonging to the Zingiberaceae family. Rhizomes and essential oil of this herb are used in culinary as flavoring agents, traditional medicines, and aromatherapy. In this study, the effect of different postharvest drying methods (air-, oven-drying at 40 and 60 °C, sun-, microwave-, and freeze-drying) of its sliced rhizome on the essential oil yield, composition, and sensory quality was investigated. The major key odorants and phytotoxins in its essential oil were identified for the first time through sensory- or bioassay-guided fractionation. Although the drying methods did not alter the oil composition significantly, oven-drying at 40 °C and freeze-drying produced the highest oil yield (81.0% of fresh rhizome) while maintaining the sensory quality. 4-Terpineol was found to be the majorly abundant key odorant in its oil through detailed sensory analysis. This oxygenated monoterpene was also demonstrated to be the major phytotoxin negatively affecting seed germination and shoot and root growth of wheatgrass seeds with IC50 values of 0.67, 0.10, and 0.17 mM, respectively. The current study is beneficial for further value addition of this crop in food industries and the agricultural sector.

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.

A 1H NMR spectroscopic method for the quantification of propenylbenzenes in the essential oils: Evaluation of key odorants, antioxidants and post-harvest drying techniques for Piper betle L.

1H quantitative Nuclear Magnetic Resonance (qNMR) spectroscopy technique has certain advantages such as low-temperature operation, authentic structural prediction and short data acquisition time. In this study, a 1H qNMR method was developed for the analysis of propenylbenzenes (eugenol and seven analogues) in the essential oils, a broadly distributed class of natural flavours. It was validated in terms of specificity (methoxy/acetate signal), linearity (range 0.05-5.00 mg per assay), sensitivity (limit of detection and quantification 4.4 and 14.9 µg/mL respectively), accuracy and precision. The qNMR technique was utilized during the sensory or activity-guided identification of chavibetol as the key odorant and antioxidant in the betel (Piper betle L., Bangla cultivar) oil, a widely consumed chewing stimulant and valuable flavouring agent. The method was also applied for the evaluation of six different post-harvest drying techniques for betel leaves through the quantitative analysis of unambiguously identified propenylbenzene markers (chavibetol, chavibetol acetate and 4-allyl-1,2-phenylene diacetate).

A 1 H-NMR spectroscopic method for the analysis of thermolabile chemical markers from the essential oil of black turmeric (Curcuma caesia) rhizome: application in post-harvest analysis.

INTRODUCTION: Curcuma caesia (black turmeric), an essential oil-bearing rhizomatous herb has been a part of ethnomedicinal practices in India and southeast Asian countries since ancient time. Oleochemical profile of black turmeric has been investigated previously by gas chromatography coupled to mass spectrometry (GC-MS) technique from different geographical regions showing a large variation in the identity as well as abundance of the constituents. OBJECTIVES: To develop an analytical method for the reliable analysis of essential oil from black turmeric rhizome through identified chemical markers and to show the credibility of the developed method on real samples. METHODS: The essential oil of black turmeric was analysed through proton nuclear magnetic resonance (1 H-NMR) based method using an internal standard. RESULTS: Four thermolabile sesquiterpene markers were unambiguously identified from the essential oil of black turmeric rhizome. GC-MS based analysis produced an erroneous identification of the constituents. A standardised 1 H-NMR spectroscopy based method was developed for the qualitative and quantitative analysis of the identified chemical markers. The developed method was further utilised for analysing the variation in oleochemical profile across multiple batches of harvest and the rhizomes subjected to different post-harvest storage or drying conditions. CONCLUSION: The identified marker molecules and developed 1 H -NMR spectroscopic method might prove to be a useful tool for the analysis of essential oil and quality control of this endangered crop material. Also, the present study provided information on the preferred drying and storage condition of black turmeric rhizome prior to the extraction of essential oil.