Intermedianin, a new furofuran lignan from the leaves of Knema intermedia Warb.

Phytochemical investigation of the leaves of Knema intermedia has led to the isolation of a new furofuran lignan, intermedianin 1 together with five known lignans, α-cubebin 2, ß-cubebin 3, bicubebin A 4, bicubebin B 5, and bicubebin C 6. The characterisation and structural elucidation of the isolated compounds were established by extensive spectroscopic data analysis and comparison with literature data. The antifungal activity was tested using the broth microdilution assay, whereas the microbial biofilms were determined using a semi-quantitative static biofilm. Compound 1 exhibited activity against C. albicans, C. lusitanae, and C. auris, (each with MIC/MFC value 250 µg/mL) and increased the biofilm of C. auris (64.07 ± 3.83%) and Candida lusitanae (62.90 ± 3.41%) when treated with 500 µg/mL.

Two New Benzoquinone Derivatives from Vietnamese Knema globularia Stems.

The chemical investigation of the stems of Knema globularia led to the isolation of two new benzoquinones derivatives, embenones A and B (1 and 2), along with three known compounds (3-5). The structures of the isolated compounds were determined using spectroscopic techniques, including HRESIMS, 1D and 2D NMR, in conjunction with comparison to existing literature data. Compounds 1 and 2 represent new carbon skeletons in nature. Furthermore, all isolated compounds were evaluated for their α-glucosidase inhibitory activity, with compounds 1-3 exhibiting superior potency relative to the positive control (acarbose, IC50 331 µM). Their IC50 values ranged from 1.40 to 96.1 µM.

Globunoids A-D, undescribed bichalconoid and biflavanoids with α-glucosidase and α-amylase inhibitory activities from Knema globularia stems.

A bichalconoid, globunoid A (1) and three biflavanones, globunoids B-D (2-4), previously undescribed, were isolated from the stems of Knema globularia, along with fourteen known analogues 5-18. The chemical structures of 1-4 were elucidated by the comprehensive spectroscopic analysis including UV, IR, HRESIMS, and NMR; the absolute configurations were determined based on their NOESY data, DP4+ statistical analysis, and ECD calculation. Up to now, compounds 2 and 3 represent the first 3,3″-linked biflavanone structures. Among the isolated compounds, 2, 3, and 2,3-dihydrocalodenin B (6) potently inhibited α-glucosidase and α-amylase activities, with IC50 values in the range 1.1-7.5 µM. Furthermore, the most active compound 6 was found to be a non-competitive inhibitor against these two enzymes.

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.

Acylphenols and Dimeric Acylphenols from the Genus Myristica: A Review of Their Phytochemistry and Pharmacology.

The genus Myristica is a medicinally important genus belonging to the Myristicaceae. Traditional medicinal systems in Asia have employed plants from the genus Myristica to treat a variety of ailments. Acylphenols and dimeric acylphenols are a rare group of secondary metabolites, which, to date, have only been identified in the Myristicaceae, in particular, in the genus Myristica. The aim of the review would be to provide scientific evidence that the medicinal properties of the genus Myristica could be attributed to the acylphenols and dimeric acylphenols present in the various parts of its plants and highlight the potential in the development of the acylphenols and dimeric acylphenols as pharmaceutical products. SciFinder-n, Web of Science, Scopus, ScienceDirect, and PubMed were used to conduct the literature search between 2013-2022 on the phytochemistry and the pharmacology of acylphenols and dimeric acylphenols from the genus Myristica. The review discusses the distribution of the 25 acylphenols and dimeric acylphenols within the genus Myristica, their extraction, isolation, and characterization from the respective Myristica species, the structural similarities and differences within each group and between the different groups of the acylphenols and dimeric acylphenols, and their in vitro pharmacological activities.

Chemical composition, acetylcholinesterase inhibition and molecular docking studies of essential oil from Knema hookeriana Warb. (Myristicaceae).

The genus Knema Lour. is distributed mainly in Southeast Asian and widely used in folk medicine for treating diseases such as jaundice, chronic fever, and inflammation. The chemical composition, acetylcholinesterase inhibition, and molecular docking studies of essential oil from Knema hookeriana Warb. were investigated in this study. The essential oil was achieved through hydrodistillation and was characterised using gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The acetylcholinesterase inhibitory activity was evaluated using Ellman method while molecular docking studies were carried out using Autodock v.4.3.2. The results revealed that the essential oil examined consisted mainly of ß-caryophyllene (26.2%), germacrene D (12.5%), δ-cadinene (9.2%), germacrene B (8.8%) and bicyclogermacrene (5.5%). The essential oil showed acetylcholinesterase activity with IC50 value of 70.5 µg/mL. The enzyme-ligand molecular docking study showed that ß-caryophyllene and δ-cadinene exhibited good binding affinities towards AChE with docking scores -8.1 kcal/mol and -8.3 kcal/mol, respectively.

Essential oil composition, anti-tyrosinase activity, and molecular docking studies of Knema intermedia Warb. (Myristicaceae).

Knema is one of the genera in the Myristicaceae family. The genus includes 60 species in Southeast Asia and is traditionally used for treating skin disorders. Here, for the first time, the essential oil, anti-tyrosinase, and molecular docking studies of Knema intermedia were evaluated. The essential oil was obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Anti-tyrosinase activity was evaluated against mushroom tyrosinase, whereas molecular docking studies were performed using Autodock vina embedded in PyRx to evaluate the binding interactions of major components. A total of 37 components (97.3%) were successfully identified in the essential oil, which was characterized by high amounts of t-muurolol (20.1%), α-copaene (14.4%), δ-cadinene (13.9%), germacrene B (9.5%), and δ-selinene (7.0%). The essential oil displayed moderate inhibitory activity towards tyrosinase with an IC50 value of 70.2 µg/mL. The best docking energy was observed with δ-selinene (-7.8 kcal/mol), and it also forms interactions with His85, His263, and His244 which are important amino acid residues of the tyrosinase receptor. Hence, this study provides valuable scientific data on K. intermedia as potential candidate for the development of natural antiaging formulations.

Genus Knema: An Extensive Review on Traditional Uses, Phytochemistry, and Pharmacology.

BACKGROUND: Knema (the Myristicaceae family) is a large genus of small-medium trees found in Southeast Asia, Africa, and Australia. Historical records dealt with the uses of Knema species as medicinal plants against various diseases, especially cancer remedies, or their application as tonic agents in Asian communities Objective: The aim of this review is to provide the most current knowledge on the traditional uses, chemical profiles, as well as pharmacological values of Knema plants. METHODS: Through electronic search, the literature materials on Knema plants were acquired from scholarly journals, books, and internationally recognized scientific databases, such as PubMed, ScienceDirect, Sci-Finder, Web of Science, and Google Scholar. All full-text articles and abstracts on Knema were screened. Genus Knema, traditional use, phytochemistry, and pharmacology were the first selective keywords to search for references. RESULTS: Since the 1970s, more than 185 metabolites have been isolated from Knema plants and structurally elucidated. Among them, phenolic lipids, flavonoids, and lignans are the principal metabolites. Crude extracts, fractions, and isolated compounds of Knema species possess a wide variety of pharmacological properties, such as antioxidative, antidiabetic, antimicrobial, antiinflammatory, antimalarial, neuroprotective, and hepatoprotective activities, but cytotoxicity is the most striking feature. Phenolic lipids containing long alkyl side chains and polar hydroxyl or acyl groups are found as the most active molecules in cytotoxic assays. CONCLUSION: Further studies on phytochemistry and pharmacological activities, toxicological assessments, pharmacological mechanisms, and pharmacokinetics are urgently needed.

Chemical composition of essential oil and antioxidant activity of the essential oil and methanol extracts of Knema globularia (Lam.) Warb. from Vietnam.

This study is the first to investigate the chemical composition of essential oil and antioxidant activity of the essential oil and methanol extracts from the leaves of Knema globularia (Lam.) Warb. from Vietnam. According to gas chromatography and gas chromatography-mass spectrometry analysis, the major constituents of K. globularia essential oil were ß-elemene (25.48%), α-copaene (17.05%), ß-caryophyllene (9.37%), and α-humulene (8.42%). The antioxidant activity of the samples was determined using DPPH and ABTS methods. In both assays, the polar subfraction of the methanolic extract showed better antioxidative capacity than the nonpolar subfraction and the essential oil. In addition, the amounts of total phenol value in the polar subfraction and the nonpolar subfraction were determined to be 113.84 µg/mg and 47.52 µg/mg, respectively. The findings demonstrate that the essential oil and methanol extracts of K. globularia possess significant antioxidant activities and may be a new potential source of natural antioxidants.

New antimicrobial cyclolignan and others constituents from the leaves of Scyphocephalium mannii (Benth. & Hook.f.) Warb.

Chemical investigation of the MeOH extract of the leaves of Scyphocephalium mannii (Benth. & Hook.f.) Warb. (Myristicaceae) led to the isolation and characterization of one new metabolite (+)-(7'S, 8S, 8'S)-4,4'-dihydroxy-3,3',5,5'-tetramethoxy-2,7'-cyclolignan (1) along with five known compounds. Their structures were elucidated by spectroscopic means, including 1 D and 2 D NMR, HRESI-MS and by comparison with published data. The absolute configuration of compound 1 was determined by single-crystal X-RAY diffraction. Compound 1 showed moderate antifungal activity against Cryptococcus neoformans with respective MIC and MMC values of 64 and 256 µg/mL.

Neolignans from Myristica fragrans seeds, revision of their absolute configurations, reduction products and biological activities.

Chromatographic purification of the CH2Cl2 extract of Myristica fragrans seeds provided 19 known compounds, four dihydrofuran neolignans, licarines A, B and maceneolignans A, B were among the isolates. Prior to hydrogenation, in order to obtain their di- and tetrahydrogenated products, the absolute configuration of these compounds was thoroughly investigated based on their optical rotations and ECD spectra. This report provides evidences concerning the disagreement between the use of an aromatic quadrant rule and time-dependent density function theory calculation for the prediction of the absolute configurations at C-7 and C-8 in these dihydrobenzofuran neolignans. The absolute configurations of licarines A, B and maceneolignans A, B were subsequently redefined. The antimicrobial and cytotoxic activities of the isolates and reduction products of licarines A, B and maceneolignans A, B were also investigated.

Chemical composition of three Malaysian Horsfieldia essential oils.

This study aims to assess the chemical compositions of the essential oils from three Horsfieldia species namely H. fulva Warb., H. sucosa Warb. and H. superba Warb., which are found in Malaysia. The essential oils were derived from the samples through hydrodistillation which were then characterised by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Based on the findings, the H. fulva, H. sucosa and H. superba essential oils represented 98.2%, 98.7% and 98.5% of the total oils, respectively. The major component of H. fulva oil was identified to be germacrene D (20.8%), H. sucosa oil mainly contained α-cadinol (17.5%), whereas H. superba oil was rich in δ-cadinene (18.2%). To the best of our knowledge, this is the first study of the composition of the essential oils from these selected Horsfieldia species.

Metabolitos secundarios aislados de especies de la familia Myristicaceae que producen inhibición enzimática / Secondary metabolites of species of the Myristicaceae family that produce enzymatic inhibition / Metabólitos secundários isolados de espécies da família Myristicaceae que produzem inibição enzimática

RESUMEN Introducción: Diferentes especies de la familia Myristicaceae han sido utilizadas con fines medicinales, nutricionales e industriales, mostrando así la importancia y potencial de la familia en diversos campos. El uso medicinal ha sido primordial por diferentes comunidades indígenas y ha venido en aumento como alternativa al tratamiento de enfermedades, por lo cual la investigación se está concentrando en la medicina herbaria y plantas medicinales, siendo este el primer paso para el desarrollo e innovación de fármacos. Entre los tipos de fármacos se destacan los inhibidores enzimáticos, que actúan regulando procesos metabólicos o atacando patógenos. Objetivos: Recopilar información de la herboristería de la familia Myristicaceae que incluya aspectos de fitoquímica, etnobotánica, usos industriales, actividad biológica y determinar posibles metabolitos secundarios que producen inhibición enzimática y actividad biológica. Metodología: La búsqueda de información se realizó con artículos científicos, libros especializados y tesis de grado. Resultados y conclusiones: Se encontró que compuestos fenólicos de tipo: acilfenol, lignano, neolignano, flavonoide, alquenil-fenol, tocotrienol y ácido fenólico producen inhibición enzimática. Los compuestos fenólicos identificados en especies de la familia Myristicaceae son una fuente promisoria de metabolitos que producen inhibición enzimática. Siendo los metabolitos de tipo lignanos los que presentaron mayor número de estudios de inhibición enzimática. La información analizada puede servir de base para el desarrollo de investigaciones de relación estructura actividad y/o acoplamiento molecular entre metabolitos secundarios y enzimas inhibidas, con especies de la familia Myristicaceae.

SUMMARY Introduction: Different species of the Myristicaceae family have been used for medicinal, nutritional and industrial purposes, showing the importance and potential of the family in various fields. Medicinal use has been primordial for different indigenous communities and has been increasing as an alternative for the treatment of diseases, for which research is concentrating on herbal medicine and medicinal plants, being this the first step for the development and innovation of pharmaceuticals. Among the types of drugs, enzymatic inhibitors, which act by regulating metabolic processes or attacking pathogens, stand out. Objectives: To gather information on the herbalism of the Myristicaceae family including aspects of phytochemistry, ethnobotany, industrial uses, biological activity and to determine possible secondary metabolites that produce enzymatic inhibition and biological activity. Methodology: The search for information was carried out using scientific articles, specialized books and degree theses. Results and conclusions: Phenolic compounds of type: acylphenol, lignan, neolignan, flavonoid, alkenylphenol, tocotrienol and phenolic acid were found to produce enzymatic inhibition. Phenolic compounds identified in species of the Myristicaceae family are a promising source of metabolites that produce enzymatic inhibition. Lignan-type metabolites were the ones that presented the greatest number of enzymatic inhibition studies. The information analyzed can serve as a basis for the development of research on the structure-activity relationship andlor molecular coupling between secondary metabolites and inhibited enzymes, with species of the Myristicaceae family.

RESUMO Introdução: Diferentes espécies da família Myristicaceae têm sido utilizadas para fins medicinais, nutricionais e industriais, mostrando a importância e o potencial da família em vários campos. O uso medicinal tem sido de suma importância para diferentes comunidades indígenas e tem aumentado como alternativa para o tratamento de doenças, razão pela qual a pesquisa está se concentrando na medicina herbal e plantas medicinais, sendo este o primeiro passo para o desenvolvimento e inovação de produtos farmacêuticos. Entre os tipos de drogas estão os inibidores enzimáticos, que atuam regulando processos metabólicos ou atacando patógenos. Objetivos: Compilar informações sobre o herbalismo da família Myristicaceae, incluindo aspectos de fitoquímica, etnobotànica, usos industriais, atividade biológica e determinar possíveis metabolitos secundários que produzem inibição enzimática e atividade biológica. Metodologia: A busca de informações foi realizada utilizando artigos científicos, livros especializados e teses de graduação. Resultados e conclusões: Foram encontrados compostos fenólicos como: acylphenol, lignan, neolignan, flavonoid, alkenylphenol, tocotrienol e ácido fenólico para produzir inibição enzimática. Os compostos fenólicos identificados em espécies da família Myristicaceae são uma fonte promissora de meta-bólitos que produzem inibição enzimática. Os metabólitos do tipo lignano mostraram o maior número de estudos de inibição enzimática. As informações analisadas podem servir como base para o desenvolvimento de pesquisas sobre a relação estrutura-ativi-dade eIou acoplamento molecular entre metabolitos secundários e enzimas inibidas, com espécies da família Myristicaceae.

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.

Pharmacological Extracts and Molecules from Virola Species: Traditional Uses, Phytochemistry, and Biological Activity.

Virola is the largest genus of Myristicaceae in America, comprising about 60 species of medium-sized trees geographically spread from Mexico to southern Brazil. The plant species of this genus have been widely used in folk medicine for the treatment of several ailments, such as rheumatic pain, bronchial asthma, tumors in the joints, intestinal worms, halitosis, ulcers, and multiple infections, due to their pharmacological activity. This review presents an updated and comprehensive summary of Virola species, particularly their ethnomedicinal uses, phytochemistry, and biological activity, to support the safe medicinal use of plant extracts and provide guidance for future research. The Virola spp.'s ethnopharmacology, including in the treatment of stomach pain and gastric ulcers, as well as antimicrobial and tryponosomicidal activities, is attributable to the presence of a myriad of phytoconstituents, such as flavonoids, tannins, phenolic acids, lignans, arylalkanones, and sitosterol. Hence, such species yield potential leads or molecular scaffolds for the development of new pharmaceutical formulations, encouraging the elucidation of not-yet-understood action mechanisms and ascertaining their safety for humans.

Chemical investigation and biological activities of the essential oil of Knema kunstleri Warb. from Malaysia.

The chemical composition of the essential oil of Knema kunstleri Warb. (Myristicaceae) was investigated for the first time. The essential oil was obtained by hydrodistillation and fully characterized by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). In total, 36 components were identified in the essential oil, which made up 91.7% of the total oil. The essential oil is composed mainly of ß-caryophyllene (23.2%), bicyclogermacrene (9.6%), δ-cadinene (7.3%), α-humulene (5.7%), and germacrene D (4.3%). The essential oil showed moderate activity towards DPPH free-radical scavenging and lipoxygenase inhibition. To the best of our knowledge, this is the first study of the composition and bioactivities of the essential oil report concerning the genus Knema.

The complete chloroplast genome sequence of Knema elegans (Myristicaceae).

Knema elegans is a member of Myristicaceae. The K. elegans chloroplast genome is found to be 155,691 bp in length and has a base composition of A (30.02%), G (19.31%), C (19.89%), and T (30.78%). The genome contained two short inverted repeat (IRa and IRb) regions (48,122 bp) which were separated by a large single-copy (LSC) region (86,883 bp) and a small single-copy (SSC) region (20,686 bp). The chloroplast genome has 85 protein-coding genes, 27 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Further, complete chloroplast sequence of K. elegans was aligned together with two species of Myristicaceae and five basal angiosperms species for which the complete chloroplast sequence have been reported. This complete chloroplast genome will provide valuable information for the development of DNA markers for future species resource development and phylogenetic analysis of K. elegans.

The complete chloroplast genome sequence of Knema conferta (Myristicaceae).

Knema conferta is a member of Myristicaceae. The K. conferta chloroplast genome is found to be 155,744 bp in length and has a base composition of A (30.02%), G (19.30%), C (19.90%), and T (30.78%). The genome contained two short inverted repeat (IRa and IRb) regions (48,052 bp) which were separated by a large single copy (LSC) region (86,926 bp) and a small single copy (SSC) region (20,770 bp). The genome encoded a total of 128 unigenes, including 89 protein-coding genes, 31 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Further, complete chloroplast sequence of K. conferta was aligned together with 2 species of Knema and 5 basal angiosperms species which have reported the complete chloroplast sequence. This complete chloroplast genome will provide valuable information for the development of DNA markers for future species resource development and phylogenetic analysis of K. conferta.

Phytochemical and pharmacological properties of Myristica fragrans Houtt.: an updated review.

Myristica fragrans Houtt. (Myristicaceae), an aromatic evergreen tree, is well known as a commercial source of mace (aril) and nutmeg (seed), which have long been widely used as spices in the culinary field. In addition, various parts of M. fragrans have been used in folk medicine for treating several diseases. Since its extensive uses in the culinary sector and folk medicine, M. fragrans has long attracted a great deal of attention from pharmacologists and chemists. Numerous studies have indicated that M. fragrans contains diverse phytochemicals such as lignans, neolignans, diphenylalkanes, phenylpropanoids, and terpenoids, which exhibit many of pharmacological activities. Among them, macelignan (1), meso-dihydroguaiaretic acid (2), myristicin (111), and malabaricone C (Mal C, 104) are the most active compounds. The aim of this review is to comprehensively summarize the phytochemical and pharmacological properties of M. fragrans that have reported to date.

A new genus and species of Neotropical gregarious braconine parasitoid (Hymenoptera: Braconidae) of a caterpillar (Lepidoptera: Hesperiidae).

A new genus of braconine parasitoid wasp, Acgorium Sharkey Quicke gen. nov., based on a new species from Costa Rica, Acgorium felipechavarriai Sharkey sp. nov., is described and illustrated, based on specimens reared from wild-caught hesperiid caterpillars of Dyscophellus phraxanor (Hewitson). Acgorium felipechavarriai is the first known braconine gregarious ectoparasitoid of a butterfly caterpillar.