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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 β-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 IC 50 value of 70.5 µg/mL. The enzyme-ligand molecular docking study showed that β-caryophyllene and δ-cadinene exhibited good binding affinities towards AChE with docking scores -8.1 kcal/mol and -8.3 kcal/mol, respectively.

This study isolated pure compounds from Canna edulis aerial parts and assessed their antiplatelet and anticoagulant potential. Structural elucidation resulted in the identification of two new compounds: caneduloside A (1) and caneduloside B (2), and eleven known compounds: 6'-acetyl-3,6,2'-tri-p-coumaroyl sucrose (3), 6'-acetyl-3,6,2'-triferuloyl sucrose (4), tiliroside (5), afzelin (6), quercitrin (7), 2-hydroxycinnamaldehyde (8), cinnamic acid (9), 3,4-dimethoxycinnamic acid (10), dehydrovomifoliol (11), 4-hydroxy-3,5-dimethoxybenzaldehyde (12), and (S)-(-)-rosmarinic acid (13). Compounds 3, 4, 6-9, 13 were previously reported for antithrombotic properties. Hence, antithrombotic tests were conducted for 1, 2, 5, 10-12. All tested compounds demonstrated a dose-dependent antiaggregatory effect, and 10 and 12 were the most potent for both ADP and collagen activators. Additionally, 10 and 12 showed anticoagulant effects, with prolonged prothrombin time and activated partial thromboplastin time. The new compound 1 displayed antiplatelet and anticoagulant activity, while 2 mildly inhibited platelet aggregation. C. edulis is a potential source for developing antithrombotic agents., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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, IC 50 331 μM). Their IC 50 values ranged from 1.40 to 96.1 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Myristicaceae was widly distributed from tropical Asia to Oceania, Africa, and tropical America. There are 3 genera and 10 species of Myristicaceae present in China, mainly distributed in the south of Yunnan Province. Most research on this family focuses on fatty acids, medicine, and morphology. Based on the morphology, fatty acid chemotaxonomy, and a few of molecular data, the phylogenetic position of Horsfieldia pandurifolia Hu was controversial., Results: In this study, the chloroplast genomes of two Knema species, Knema globularia (Lam.) Warb. and Knema cinerea (Poir.) Warb., were characterized. Comparing the genome structure of these two species with those of other eight published species, including three Horsfieldia species, four Knema species, and one Myristica species, it was found that the chloroplast genomes of these species were relatively conserved, retaining the same gene order. Through sequence divergence analysis, there were 11 genes and 18 intergenic spacers were subject to positive selection, which can be used to analyze the population genetic structure of this family. Phylogenetic analysis showed that all Knema species were clustered in the same group and formed a sister clade with Myristica species support by both high maximum likelihood bootstrap values and Bayesian posterior probabilities; among Horsfieldia species, Horsfieldia amygdalina (Wall.) Warb., Horsfieldia kingii (Hook.f.) Warb., Horsfieldia hainanensis Merr. and Horsfieldia tetratepala C.Y.Wu. were grouped together, but H. pandurifolia formed a single group and formed a sister clade with genus Myristica and Knema. Through the phylogenetic analysis, we support de Wilde' view that the H. pandurifolia should be separated from Horsfieldia and placed in the genus Endocomia, namely Endocomia macrocoma subsp. prainii (King) W.J.de Wilde., Conclusion: The findings of this study provide a novel genetic resources for future research in Myristicaceae and provide a molecular evidence for the taxonomic classification of Myristicaceae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

A new diarylhexane, kneglobularone B ( 1 ) and two new diarylpropanols, kneglobularols A - B ( 2 - 3 ) along with seven known compounds ( 4 - 10 ) were isolated and characterized from the roots of Knema globularia. It is the first time to find arylpropyl quinone ( 4 ) and isoflavone ( 8 ) in Myristicaceae family. In addition, 5 was found for the first time in Knema genus. Their structures were elucidated by UV, IR, MS, 1 D and 2 D NMR techniques. Compound 4 exhibited strong cytotoxicity against the NCI - H187 and MCF - 7 cell lines with IC 50 values of 3.08 and 6.68 µg/mL, respectively.

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., (© 2021 John Wiley & Sons Ltd.)

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 β-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 .

Ethnopharmacological Relevance: Virola oleifera (Schott) A.C. Smith, Myristicaceae, has been widely used in traditional medicine in Brazil to treat rheumatic pain, joint tumours, skin diseases, halitosis, bronchial asthma, haemorrhoids, and intestinal worms. Recently, research data showed the antioxidant properties in several oxidative stress-related models. However, there is no experimental evidence supporting its potential use in managing rheumatic diseases and bone malignancies., Aims of the Study: To evaluate the therapeutic potential of the resin from Virola oleifera in joint and bone diseases, namely arthritis, osteosarcoma, chondrosarcoma, and multiple myeloma., Materials and Methods: To determine Virola oleifera resin (VO) effects on arthritis-associated inflammation and cartilage degradation, the LPS-induced NO production, and mRNA and protein expression of ADAMTS5, MMP13, COL2, and ACAN, were evaluated in chondrocytes (ATDC5 and TC28 cell lines). The cytotoxic effects of VO (0.05-50 μg/ml) on multiple myeloma (ARH-77), osteosarcoma (SAOS-2), and chondrosarcoma (SW-1353) cell lines were analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The VO effects, combined with dexamethasone or bortezomib, were evaluated in a multiple myeloma cell line. The mechanisms of VO, alone or in combination with bortezomib, were determined by cell cycle analysis through flow cytometry, while expression levels of p-Akt/Akt, p-ERK/ERK, p-p38/p38 MAPK, Bax, Bcl-2, and cleaved-caspase-3/caspase-3 proteins by Western blot., Results: VO had no significant effect on LPS-induced NO production in chondrocytes at non-cytotoxic concentrations. VO treatment diminished the mRNA levels of metalloproteinases and ECM components; however, any significant effect was observed on the protein expression levels. The cell viability of a multiple myeloma cell line was strongly reduced by VO treatment in a dose- and time-dependent manner, while osteosarcoma and chondrosarcoma cell lines viability was significantly affected only by the highest dose assessed. In multiple myeloma cells, VO leads to G2/M cell cycle arrest. Furthermore, it synergizes with dexamethasone by increasing cell toxicity. Finally, VO reverts bortezomib activity by counteracting ERK1/2, Bax, and caspase-3 activation., Conclusions: The current work supports the ethnopharmacological use of Virola oleifera (Schott) A.C. Smith in bone and joint diseases, but there is no evidence for the amelioration of arthritis-associated inflammatory or catabolic processes. Our data also supports the potential use of Virola oleifera as adjuvant therapy to optimize the pharmacologic effects of current chemotherapeutic drugs. However, possible herb-drug interactions should be considered before clinical application., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Three new diarylpropanes ( 1 - 3 ), including two diarylpropane glycosides, and three known ones, were isolated from 70% aqueous acetone extract of the twigs and leaves of Horsfieldia kingii . Their structures were elucidated by spectroscopic analysis. Bioactive evaluation of inhibition on DDC enzyme assay showed that the new compounds were inactive.

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.

The n -hexane extract of Knema pachycarpa fruits (Myristicaceae family), exhibiting strong anti-acetylcholinesterase activity, was investigated by gas chromatography/mass spectrometry and then purified by column chromatography. Guided by GC/MS profiling and bioassay, chromatographic separations led to the isolation of five new compounds: two anacardic acid derivatives 1 - 2 , two cardanol derivatives 3 - 4 and a cardol derivative 5 , along with mixtures of known phenolic lipids 6 - 9 . The chemical structures were determined by various spectroscopic methods. New isolated compounds 1 - 5 were evaluated for their cytotoxicity and anti-acetylcholinesterase activity. Cardanol 3 and cardol 5 were the most active compounds in the acetylcholinesterase inhibitory assay with IC 50 values of 2.60 ± 0.24 µM and 2.46 ± 0.23 µM, respectively. Cardanol 4 and cardol 5 showed moderate cytotoxicity against Hela and MCF-7 cancer cell lines with IC 50 values ranging from 31.36 ± 0.41 µM to 41.30 ± 2.49 µM.

Seeds of Monodora myristica and M. tenuifolia were extracted with hexane and the extracts were subjected to column chromatography, LC-MS and NMR analysis. In addition to masses of previously isolated compounds, other masses corresponding to unidentified compounds from the plants were detected. Using 2 D NMR techniques, one of the fractions from M. tenuifolia was characterised as a novel 13-(2-butylcyclopropyl)-6,9-dodecadienoic acid. However, none of the compounds detected in LC-MS corresponded to the ones previously identified by GC-MS.

Twenty-seven compounds, including a new diarypropane and two new lignans were isolated from the twigs and leaves of Endocomia macrocoma . Their structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of the new compounds against five human tumor lines showed no inhibitory effects.[Formula: see text].

Pycnanthus angolensis (Welw) Warb., Myristicaceae, is used extensively in ethnomedicine. Numerous health benefits have been ascribed to the use of different parts of P. angolensis including its role in cognitive function and inflammatory conditions. Hence, this study was undertaken to investigate the effect of stem bark of the plant on memory function in mice.The plant material was pulverized into powder and extracted by maceration with 80% methanol at room temperature for 48 h. This was subsequently fractionated using N-hexane, Dichloromethane (DCM) and Ethyl acetate. The Dichloromethane fraction which is the most potent fraction (25, 50 and 100 mg/kg) was evaluated for memory enhancing activity using the Y-maze (YMT), morris water maze (MWM) and the elevated plus maze (EPM) on D-galactose plus scopolamine and ketamine induced amnesia. The antioxidant markers and acetylcholinesterase (AChE) inhibiting effect of DCM were also investigated.The results obtained from the behavioural study indicates that the DCM fraction significantly (p<0.05) increased alternation behaviour of mice in the YMT, decreased the escape latency in the MWM paradigm and decreased the transfer latency in the EPM. Biochemically, DCM increased glutathione, and superoxide dismutase, but decreased malondialdehyde and AChE activity in the brain.The findings therefore suggests that the DCM possesses significant memory enhancing activity, which may be due to enhancement of antioxidant activity and cholinergic transmission. The attenuation of the effect of ketamine by the DCM may possibly result from an increase in NMDA receptor mediated neurotransmission and attenuation of oxidative stress., Competing Interests: The authors declare no conflict of interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

The essential oils (EOs) obtained from the leaves of Iryanthera polyneura Ducke trees was chemically Assessed and tested for the ability of inhibiting the growth of Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans and S. sanguinis. The oil was also tested against breast (MCF-7) and prostate (PC-3) cancer cell lines. Minimum bactericidal concentrations (MBCs) and 50 % inhibition concentrations (IC 50 ) values were obtained. EOs were active against Gram-positive bacteria. Spathulenol, α-cadinol and τ-muurolol were major components of EOs. The oils showed a higher cytotoxicity against PC-3 than MCF-7 cells, although the oils were active against both cell types. Oils obtained from leaves collected in the dry season were more active against E. faecalis, S. aureus and PC-3, while the oils obtained from leaves collected in the rainy season were more active against S. mutans, S. sanguinis and MCF-7. The antibacterial and cytotoxic activities of the essential oils from the leaves of I. polyneura are related to the seasonal climate variation and are influenced by compounds that are minor components of the oils., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Virola elongata is a tree species belonging to the Myristicaceae family, distributed in the North and Midwest regions of Brazil, in the phytogeographic domain of the Amazon. The aqueous infusion or the hydroethanolic macerate of the stem bark of V. elongata are used in Brazilian and Ecuadorian indigenous folk medicine for several ethnopharmacological purposes, principally, in the treatment of stomach pain, indigestions, and gastric ulcers. This study was aimed to investigate the gastroprotective activity of this plant in order to support its popular use with scientific evidence., Materials and Methods: The stem bark hydroethanolic extract of the plant (HEVe) was prepared by maceration. Its qualitative and quantitative phytochemical constituents were investigated by classical colorimetric techniques, HPLC, and electrospray ionization-multiple stage fragmentation (ESI-MS n ). The gastroprotective and antiulcer activity of HEVe at doses of 100, 300 and 900 mg/kg p.o. were tested using three acute (acidified ethanol, piroxicam, and in-water-restrain stress), and one chronic (acetic acid) animal ulcer models. The probable mode of action of the HEVe was evaluated by analyzing gastric acid secretion, mucus content, nitric oxide effect, and its antioxidant properties (on catalase, myeloperoxidase, and GSH content) in experimental rodents. The direct extract's activity on the growth of Helicobacter pylori was also investigated., Results: Total phenolic content in the HEVe was of 146.20 ± 1.07 mg, being flavonoids about 50% (71.79 ± 0.70 mg) of it. Comparative HPLC fingerprint analysis revealed the presence of known phenolic antiulcer compounds, such as gallic acid, catechin, and rutin. Also, methanol/water fractionation and ESI-MS n analysis of the HEVe reveals the presence of quinic acid, 3,3',4-trihydroxystilbene, juruenolid D, one catechin dimer, one C-glycosyl flavonoid, one polyketide and two neolignans as the major components of the extract. The HEVe attenuated gastric ulceration in all the different models of acute gastric ulcer, by enhancing gastroprotection through its antioxidant properties in vivo, and reducing also considerably the gastric secretion and total acidity. The HEVe also presented healing properties against the induced chronic ulceration process. On the other hand, the HEVe did not exhibit direct activity against H. pylori., Conclusion: The HEVe exhibited significant gastroprotective/antiulcer effects and contain a relative high proportion of phenolic compounds, especially flavonoids, that could likely account, at least in part, for its pharmacological properties. The results justify its traditional usage and provided scientific evidence for its potential as a new herbal medicine to treat gastric ulcers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Two new dibenzylbutyrolactol lignans and three known dibenzylbutyrolactone lignans were isolated from the twigs and leaves of Horsfieldia kingii. Their structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of these compounds against five human tumour lines showed no inhibitory effects.

Samento (extract from Uncaria tomentosa ) and Banderol (extract from Otoba parvifolia ) have been demonstrated to have anti-inflammatory and antimicrobial properties, e.g., against different morphological forms of Borrelia burgdorferi . However, there is hardly any data on the pharmacological safety of these two herbal medicines. This in vitro study aimed at scrutinizing their possible characteristics as perpetrators in pharmacokinetic herbal⁻drug interactions. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits and inhibition of drug transporters by use of fluorescent probe substrates. Induction was quantified by real-time RT-PCR and activation of pregnane x receptor (PXR) and aryl hydrocarbon receptor (AhR) by reporter gene assays. Organic anion transporting polypeptide 1B1 (OATP1B1) (IC 50 = 0.49 ± 0.28%) and OATP1B3 (IC 50 = 0.65 ± 0.29%) were potently inhibited by Banderol, but only weakly by Samento. CYP3A4 was inhibited about 40% at a Samento concentration of 1%. Samento significantly induced mRNA expression of CYP2J2 , UGT1A3 , UGT1A9 , ABCB1 , and SLCO1B1 and strongly activated PXR, but hardly AhR. In conclusion, the perpetrator profiles of Samento and Banderol for herb⁻drug interactions completely differ. Clinical studies are strongly recommended to clarify whether the effects observed in vitro are of clinical relevance.

The first synthesis of myristicyclin A, which was isolated from the Papua New Guinean plant Horsfieldia spicata, is described. The synthesis features acid-mediated hydroarylation reaction to form a dihydrocoumarin moiety, construction of the 2,8-dioxabicyclo[3.3.1]nonane skeleton under acidic conditions, and regioselective Friedel-Crafts acylation at a later stage.

In search for effective antidiabetic agents that simultaneously inhibit α-glucosidase and scavenge free radicals, Horsfieldia motleyi showed promising bioactivity according to the proposed criteria. Bioassay-guided isolation of pericarp extract yielded a new 4-arylflavan named myristinin G (6), whose gross structure and absolute configuration were verified by 2D NMR and electronic circular dichorism (ECD). Myristinin G (6) concomitantly inhibited α-glucosidases (IC 50 107.0 and 126.9 μM) and free radicals (SC 50 54.3 and 279.9 μM). Of interest, 6 inhibited sucrase through an uncompetitive manner, which is rare in nature.

The development of effective nanoparticle therapeutics has been hindered by their surface characteristics, such as hydrophobicity and charge. Therefore, the success of biomedical applications with nanoparticles is governed by the control of these characteristics. In this article, we report an efficient green capping method for gold nanoparticles (AuNPs) by a reduction with sodium citrate and capping with Virola oleifera (Vo), which is a green exudate rich in polyphenols and flavonoids. The Vo-capped AuNPs were characterized by UV, DLS, FTIR, Raman, TEM, DPPH, FRAP and their cytotoxicity was evaluated on the viability of Murine macrophage cell. The AuNPs had an average particle size of 15 nm and were stable over a long time, as indicated by their unchanged SPR and zeta potential values. These nanoparticles were assessed for their antioxidant potential using DPPH and FRAP and demonstrated the highest antioxidant activities and low cytotoxicity. We propose that the Virola oleifera-capped AuNPs have potential biomedical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC 50 values of 63.70 ± 0.546, and 43.61 ± 0.620 µM respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Five compounds, including a new dimeric diarylpropane, were isolated from the petroleum ether extract of the twigs and leaves of Horsfieldia tetratepala. The structures of these compounds were elucidated by spectroscopic analysis. Moreover, the antiproliferative activities of these compounds were tested on cancer cell lines, but none is active.

Context: The resin from the trunk wood of Virola oleifera (Schott) A. C. Smith (Myristicaceae) is used in folk medicine to hasten wound repair and to treat pain and inflammatory conditions, and our previous report indicated the anti-oxidative properties in other oxidative stress model., Objective: To investigate the protective effects of resin from V. oleifera in two experimental models of gastric ulcer oxidative-stress dependent., Materials and Methods: Plant material was collected and the resin was subjected to partitioning with organic solvents. The buthanol fraction was subjected to chromatographic and spectrometric methods for isolation and structural elucidation. The resin was quantified for polyphenols and flavonoids by colorimetric methods. Furthermore, the antioxidant activity of resin was determined by three different methods. The ulcers were induced acutely in Swiss male mice with ethanol/HCl and indomethacin using single-doses of 10 and 100 mg/kg. The gastroprotection of the experimental groups was comparable to reference control lansoprazole (3 mg/kg)., Results: The high content of polyphenols (∼82%) and the presence of epicatechin and eriodictyol were determined. The LD 50 was estimated at 2500 mg/kg. At minimum (10 mg/kg) and maximum (100 mg/kg) dosage of resin, both in ethanol/HCl as indomethacin ulcer induction models demonstrate reduction of lesions (minimum: ∼97% and ∼66%; maximum: ∼95% and ∼59%)., Discussion: The gastroprotection might be related to tannins, phenolic acids and flavonoids present in the resin by antioxidant properties., Conclusions: The results indicate that this resin has gastroprotective activity probably associated with the presence of phenolic antioxidant substances.

Ethnopharmacological Relevance: Virola oleifera (Schott) A. C. Smith, Myristicaceae has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and our previous data indicated the antioxidant properties in other oxidative stress-related models. However, its effects on atherosclerosis (AT) are not yet investigated., Aims of the Study: To evaluate the influence of resin from Virola oleifera (RV) on progression of AT in LDLr -/- mice., Materials and Methods: LDLr -/- mice were divided into 4 groups: 1) The ND group received a normal diet without treatment. 2) The HD group received a high-fat diet without treatment. 3) The HD-V50 received a high-fat diet and was orally treated with RV at 50mg/Kg. 4) The HD-V300 received a high-fat diet and was orally treated with RV at 300mg/Kg. After 4 weeks, blood was collected to quantify biochemical parameters and ROS total and the aorta was removed to measure the lipid deposition by en face analysis. The liver was also collected to determine total lipids and lipid and protein oxidation. In order to investigate in more detail the contributions of RV in the vascular structure, we carried out the in vitro tests using four cellular types: macrophages, fibroblasts, vascular smooth muscle and endothelial cells., Results: We showed that the chronic treatment of RV at both doses reduced vascular lipid accumulation (~50%, p<0.05), probably through systemic and hepatic antioxidant effects, independent of dyslipidemia. Moreover, the in vitro assay results demonstrated that RV develops antioxidant properties on the vascular smooth muscle and endothelial cells, reinforcing the protective role of RV in progression of AT. LPS-stimulated macrophages treated with RV resulted in a significant reduction of NO production in a concentration-dependent manner., Conclusions: Chronic treatment with RV diminishes lipid deposition in atherosclerotic mice, which may be justified, at least in part, by antioxidant systemic and local mechanisms, reinforcing the protective role this resin in the setting of vascular lipid deposition, independent of hypercholesterolemia., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.

The malabaricones A-D belong to the class of diarylnonanoids isolated from the Myristicaceae family of plants. Although malabaricone C displayed various interesting biological activities, its isolation remains tedious due to its close chemical similarity to malabaricones A, B, and D. Therefore, development of an efficient synthesis route has become essential to cater to the need of large amounts of malabaricone C for its pharmacological profiling. So far there is only one report of the synthesis of malabaricone C through a lengthy sequence of reactions. We have developed an efficient and short route for the syntheses of malabaricones B and C, which will also provide a convenient access to all other members of the malabaricone family. Synthesis of an important building block, ω-aryl heptyl bromide, employed in the synthesis was realized by adopting a cross-metathesis reaction as the key step.

Virola species have been used in traditional medicine as healing in skin infections. From V. surinanensis oil were isolated several sesquiterpene as the nerolidol which showed activity against species of Leishmania. The current study aimed to evaluate the leishmanicide activity and toxicity of extracts, fractions and surinamesin obtained from leaves of Virola surinamensis. Hexane, Ethyl Acetate, and Methanol extracts were obtained from powder of dry leaves of V. surinamensis. The hexane and ethyl acetate extracts were fractionated by silica gel column chromatography and increasingly polar gradient. The viability of L. chagasi and L. amazonensis promastigotes was assessed by tetrazolium salt assay (MTT). Peritoneal macrophages were exposed to L. amazonensis promastigotes. The treatment was performed with the extracts for 24 h. Then, the coverslips were stained and the infection index was determined. Cytotoxicity was determined in macrophage cells by peritoneum viability assay (MTT). The selectivity index was calculated as the product of cytotoxic concentration 50% and inhibitory concentration 50%. The hexane extract showed leishmanicide activity in promastigotes. The ethyl acetate, methanol extracts and fractions (C1-C6), were inactive against promastigote form of L. chagasi and L. amzazonensis. None extract showed effect on L. amazonensis amastigotes. All samples tested showed low cytotoxicity (CC 50  > 500 μg/mL). The selectivity index of the hexane extract was greater than 5. The hexane extract of V. surinamensis was active against L. chagasi and L. amazonensis promastigotes. The extract fractionation did not increase significantly its antipromastigote activity. The surinamensin is probably not responsible for the activity. The extracts were inactive against amastigotes of L. amazonensis., (Copyright © 2017. Published by Elsevier Inc.)

Two new flavans, (2R, 4R)-4'-hydroxy-3',5'-methyl-6,7-methylenedioxy-4-O-2'-cycloflavan (1), and (2R, 4R)-4'-hydroxy-3'-methyl-6,7-methylenedioxy-4-O-2'-cycloflavan (2), along with six known compounds were isolated from the trunk and leaves of Horsfieldia glabra. Their structures were elucidated by means of extensive spectroscopic analysis. Compounds 1 and 2, together with 4-7 were assessed for their cytotoxicity against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that they had no activity.

A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84±0.19 and 1.76±0.21μM, respectively) and 4 (1.94±0.27 and 2.80±0.49μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver-Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity., (Copyright © 2016. Published by Elsevier B.V.)

Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti- and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of Knema hookeriana for further phytochemical investigations. The ethyl acetate extract from the stem bark led to the isolation of six new compounds, three acetophenone derivatives (1-3) and three anacardic acid derivatives (4-6), along with four known anacardic acids (7-10) and two cardanols (11, 12). Their structures were elucidated by 1D and 2D NMR analysis in combination with HRMS experiments. The ability of these compounds to antagonize Bcl-xL/Bak and Mcl-1/Bid association was determined, using a protein-protein interaction assay, but only anacardic acid derivatives (4-10) exhibited significant binding properties, with Ki values ranging from 0.2 to 18 μM. Protein-ligand NMR experiments further revealed that anacardic acid 9, the most active compound, does not interact with the anti-apoptotic proteins Bcl-xL and Mcl-1 but instead interacts with pro-apoptotic protein Bid.

Malabaricones A-C (1-3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated.

A dimeric acylphenol and a potent α-glucosidase inhibitor, giganteone D (IC50 5.05μM), was isolated and characterized from the bark of Myristica cinnamomea King. The bark also yielded an acylphenol with an unprecedented skeleton for which the name cinnamomeone A (IC50 358.80μM) was proposed. Their structures were established by means of NMR and MS spectrometric analyses. The Lineweaver-Burk plot of giganteone D indicated that it was a mixed-type inhibitor. This is the first report on the α-glucosidase inhibiting potential of acylphenols., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A new isoflavanone, 2,2'-epoxy-4'-methoxy-3,7-dihydroxyisoflavanone (1), and a new natural coumaranone, 2-hyroxy-2-(4'-methoxybenzyl)-6-methoxy-3-coumaranone (2), along with 26 known compounds, were first isolated from the trunk of Horsfieldia pandurifolia. Their structures were elucidated by the means of spectroscopic analysis. Compound 1 was assessed for its cytotoxicity against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that it has no activity.

An efficient approach towards the first racemic total synthesis of dactyloidin (2) and demethyldactyloidin (3) is described. Their oxygen-bridged tricyclic ketal systems were rapidly constructed by using a remarkable biomimetic Knoevenagel condensation/[4 + 2] cycloaddition cascade as the critical strategy and the 1,5-dicarbonyl segment was assembled by Grignard addition.

In search of effective antidiabetic agents having therapeutic effect by inhibiting α-glucosidase and preventive effect by scavenging free radicals, Horsfieldia macrobotrys showed promising bioactivity required for the proposed criteria. Bioassay-guided isolation of the stem bark extract resulted in two new arylalkanones named horsfieldone A (1) and maingayone D (2), together with a new flavanone C-glucoside named 8-C-β-d-glucopyranosylpinocembrin (3). Their structures and stereochemistry were determined by spectroscopic techniques as well as Mosher's method. Of isolated compounds, maingayone D (2) was the most potent inhibitors against both α-glucosidases and free radicals. The presence of additional phenolic moieties in 2 clearly indicated their critical roles in inhibitory effects. Further investigation on mechanism underlying α-glucosidase inhibition indicated that maingayone D (2) could retard the enzyme function by both competitive and noncompetitive manners., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To study the simultaneous determination method of daodi Psoraleae Fructus-Myristicae Semen Chinese drug pair for the seven ingredients, and Psoraleae Fructus-Myristicae Semen Chinese drug pair on the chemical composition of initial ownership and identification., Methods: UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 µm) was used in the determination. The flow rate was kept at 0.25 mL/min, and 2 µL of standard and sample solution were injected in each run. The mobile phase was consisted of acetonitrile and water using a gradient elution. The UPLC/Q-TOF MS condition: Waters HSS T3 (100 mm x 2.1 mm,1.7 µm); capillary voltage 3.0 kV (positive ion mode) and 2.5 kV (negative ion mode); Mass spectrometric detection was carried out on a Waters Xevo G2 Q/ TOF mass spectrometer equipped with an ESI source operating in both positive and negative ion modes. The parameters of the mass spectrometer under the ESI mode were as follows: ion source temperature 110 °C, cone gas flow 50 L/h, desolvation gas temperature 450 °C, desolvation gas flow 800 L/h., Results: The seven chemical markers in the selected linear range had good linearity. The recoveries were in the range of 95.07%-98.16% and RSDs were between 1.23%-1.97%., Conclusion: It is suitable for the quality control and further studies of the herb in vivo of daodi Psoraleae Fructus-Myristicae Semen Chinese drug pair.

Purpose: The 'two-faced' character of reactive oxygen species (ROS) plays an important role in cancer biology by acting as secondary messengers in intracellular signaling cascades, enhancing cell proliferation and survival, thereby sustaining the oncogenic phenotype. Conversely, enhanced generation of ROS can trigger an oxidative assault leading to a redox imbalance translating into an apoptotic cell death. Intrinsically, cancer cells have higher basal levels of ROS which if supplemented by additional oxidative insult by pro-oxidants can be cytotoxic, an example being Malabaricone-A (MAL-A). MAL-A is a plant derived diarylnonanoid, purified from fruit rind of the plant Myristica malabarica whose anti-cancer activity has been demonstrated in leukemic cell lines, the modality of cell death being apoptosis. This study aimed to compare the degree of effectiveness of MAL-A in leukemic vs. solid tumor cell lines., Methods: The cytotoxicity of MAL-A was evaluated by the MTS-PMS cell viability assay in leukemic cell lines (MOLT3, K562 and HL-60) and compared with solid tumor cell lines (MCF7, A549 and HepG2); further studies then proceeded with MOLT3 vs. MCF7 and A549. The contribution of redox imbalance in MAL-A induced cytotoxicity was confirmed by pre-incubating cells with an antioxidant, N-acetyl-L-cysteine (NAC) or a thiol depletor, buthionine sulfoximine (BSO). MAL-A induced redox imbalance was quantitated by flow cytometry, by measuring the generation of ROS and levels of non protein thiols using dichlorofluorescein diacetate (CM-H2DCFDA) and 5-chloromethylfluorescein diacetate (CMFDA) respectively. The activities of glutathione peroxidase (GPx), superoxide dismutase, catalase (CAT), NAD(P)H dehydrogenase (quinone 1) NQO1 and glutathione-S-transferase GST were measured spectrophotometrically. The mitochondrial involvement of MAL-A induced cell death was measured by evaluation of cardiolipin peroxidation using 10-N-nonyl acridine orange (NAO), transition pore activity with calcein-AM, while the mitochondrial transmembrane electrochemical gradient (∆ψ(m)) was measured by JC-1, fluorescence being acquired in a flow cytometer. The apoptotic mode of cell death was evaluated by double staining with annexin V-FITC and propidium iodide (PI), cell cycle analysis by flow cytometry and caspase-3 activity spectrophotometrically. The expression of Nrf2 and HO-1 was examined by western blotting., Results: MAL-A demonstrated a higher degree of cytotoxicity in three leukemic cell lines whose IC50 ranged from 12.70 ± 0.10 to 18.10 ± 0.95 µg/ml, whereas in three solid tumor cell lines, the IC50 ranged from 28.10 ± 0.58 to 55.26 ± 5.90 µg/ml. This higher degree of cytotoxicity in MOLT3, a leukemic cell line was due to a higher induction of redox imbalance, evident by both an increased generation of ROS and concomitant depletion of thiols. This was confirmed by pre-incubation with NAC and BSO, wherein NAC decreased MAL-A induced cytotoxicity by 2.04 fold while BSO enhanced MAL-A cytotoxicity and decreased the IC50 by 5.60 fold. However, in solid tumor cell lines (MCF7 and A549), NAC minimally decreased MAL-A induced cytotoxicity, and BSO increased the IC50 by 1.96 and 2.39 fold respectively. Furthermore, the generation of ROS by MAL-A increased maximally in MOLT3 as the fluorescence increased from 44.28 ± 7.85 to 273.99 ± 32.78, and to a lesser degree in solid tumor cell lines, MCF7 (44.28 ± 14.89 to 207.97 ± 70.64) and A549 (37.87 ± 3.24 to 147.12 ± 38.53). In all three cell lines there was a concomitant depletion of thiols as in MOLT3, the GMFC decreased from 340.65 ± 60.39 to 62.67 ± 11.32, in MCF7 (277.82 ± 50.32 to 100.39 ± 31.93) and in A549 (274.05 ± 59.13 to 83.15 ± 21.43). In MOLT3 as compared to MCF7 and A549, decrease in the activities of GPx, CAT, NQO1 and GST was substantially greater. In all cell lines, the MAL-A induced redox imbalance translated into triggering of initial mitochondrial apoptotic events. Here again, MAL-A induced a higher degree of cardiolipin peroxidation in MOLT3 (67.01%) than MCF7 and A549 (29.15% and 44.30%), as also down regulated the mitochondrial transition pore activity from baseline to a higher extent, GMFC being 48.05 ± 2.37 to 10.70 ± 3.97 (MOLT3), 43.55 ± 3.36 to 15.36 ± 0.60 (MCF7) and 39.58 ± 0.4 to 12.65 ± 1.56 (A549). Perturbation of mitochondrial membrane potential evident by a decrease in the ratio of red/green (J-aggregates/monomers) was 134 fold (14.73/0.11) in MOLT3, 45 fold in MCF7 (20.72/0.46) and 34 fold in A549 (22.01/0.64). The extent of apoptosis using a similar concentration of MAL-A was maximal in MOLT3, wherein a 105 fold increase in annexin V binding was evident (0.83 ± 0.51 to 87.08 ± 9.85%) whereas it increased by 43.11 fold in MCF7 (0.69 ± 0.30 to 29.75 ± 11.79%) and 47.52 fold in A549 (0.61 ± 0.31 to 28.99 ± 17.21%). MAL-A induced apoptosis was also associated with a higher degree of caspase-3 activity in MOLT3 vs. MCF7 or A549 which translated into halting of cell cycle progression, evident by an increment in the sub-G0/G1 population [19.26 fold in MOLT3 (0.95 ± 0.45 vs. 18.30 ± 1.90%), 11.01 fold in MCF7 (0.97 ± 0.37 vs. 10.68 ± 0.69%) and 8.58 fold in A549 (1.06 ± 0.45 vs. 9.10 ± 1.05%)]. MAL-A effectively inhibited Nrf2 and HO-1, more prominently in MOLT3. Furthermore, the decreased expression of Nrf2 in MOLT3 correlated with the decreased activities of NQO1 and GST, suggesting that targeting of the Nrf2 anti-oxidant pathway could be considered., Conclusion: Taken together, MAL-A a pro-oxidant compound is likely to be more effective in leukemias, meriting further pharmacological consideration., (Copyright © 2015. Published by Elsevier GmbH.)

The metabonomics method was used to study the intervention effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on the changes in serum endogenous metabolites in spleen-kidney Yang deficiency diarrhea rats before and after processing, screen out differentiated metabolites related to spleen-kidney Yang deficiency diarrhea and explore the metabolic patterns related to spleen-kidney Yang deficiency diarrhea and the processing synergy mechanism of Psoraleae Fructus and Myristicae Semen in "Ershen pill". Efforts were made to detect SOD and MDA of each group, test rat serum metabolic fingerprints in different stages by using GC-MS, analyze by PCA and PLS-DA methods and screen out potential biomarks through VIP and t test. The results revealed that "Ershen pill" could enhance the level of SOD and decrease the level of MDA and identified 10 differentiated metabolites related to spleen-kidney Yang deficiency diarrhea. Compared with the model group, all of metabolites recovered to varying levels after being intervened with "Ershen pill", with the best effect shown in the "Ershen pill" IV group (salt-processed Psoraleae Fructus + bran-roasted Myristicae Semen). It is speculated that that Psoraleae Fructus and Semen Myristicae in "Ershen pill" show a synergistic effect by inhibiting peroxide, improving aglucolipid, amino acids and energy metabolism, with multiple target sites.

Horsfieldia macrobotrys Merr has long been used by Dayak people in East Kalimantan of Indonesia, for diabetes therapy. Inspired by ethnopharmacological use and promising α-glucosidase and radical scavenging activities, an attempt to identify the active components was carried out. Bioassay-guided isolation yielded two related arylalkanones named 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one (1) and malabaricone A (2). Arylalkanone 1 showed potent radical scavenging comparable with that of the standard antioxidant, ascorbic acid, and promising inhibition against α-glucosidases. Noticeably, arylalkanone 1 was 3-30 times more potent than malabaricone A (2) in all bioassays examined, thus suggesting the critical role in exerting bioactivities of the hydroxy group on the aryl moiety. This hypothesis was also supported by reduction in inhibitory effects of the methyl ether analogues la and 2a. Arylalkanone 1 inhibited yeast α-glucosidase in a mixed-type manner in which the noncompetitive pathway was dominant over competitive inhibition. This study is the first report of α-glucosidase inhibition of arylalkenone-type compounds and the first phytochemicals from H. macrobotrys.