New Phenolic Lipids from the Leaves of Clausena harmandiana Inhibit SARS-CoV-2 Entry into Host Cells.

Induced by the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic underlined the clear need for antivirals against coronaviruses. In an effort to identify new inhibitors of SARS-CoV-2, a screening of 824 extracts prepared from various parts of 400 plant species belonging to the Rutaceae and Annonaceae families was conducted using a cell-based HCoV-229E inhibition assay. Due to its significant activity, the ethyl acetate extract of the leaves of Clausena harmandiana was selected for further chemical and biological investigations. Mass spectrometry-guided fractionation afforded three undescribed phenolic lipids (1-3), whose structures were determined via spectroscopic analysis. The absolute configurations of 1 and 2 were determined by analyzing Mosher ester derivatives. The antiviral activity against SARS-CoV-2 was subsequently shown, with IC50 values of 0.20 and 0.05 µM for 2 and 3, respectively. The mechanism of action was further assessed, showing that both 2 and 3 are inhibitors of coronavirus entry by acting directly on the viral particle. Phenolic lipids from Clausena harmandiana might be a source of new antiviral agents against human coronaviruses.

Ginkgols and bilobols in Ginkgo biloba L. A review of their extraction and bioactivities.

Ginkgo biloba (GB) has enormous bioactives with anti-bacterial, anti-oxidant, anti-cancer, and immune-stimulating properties, with global sales exceeding $10 billion. The terpene trilactones (ginkgolides A, B, and C) and flavonoids (mostly quercetin, isorhamnetin, and kaempferol) have received the most significant focus in GB research to date, whereas other bioactive compounds such as ginkgols and bilobols with various bioactivities such as anti-viral, anti-oxidant, and anti-tumor actions have received less attention. Therefore, for the first time, this review focused on GB ginkgols, bilobols extraction, and bioactivities. This review showed that petroleum ether and acetone extraction had successfully extracted ginkgols and bilobols. Furthermore, bioactivities such as anti-tumor activity and so on have been demonstrated for ginkgols, and bilobols, providing theoretical justification for ginkgols and bilobol as raw material for nutraceuticals, functional foods, pharmaceuticals, and cosmeceuticals. Future research could look into other biological applications (such as anti-oxidant, antitoxins, anti-radiation, anti-microbial, and antiparasite) and their applications in the pharmaceutical, cosmetic, and nutraceutical industries. Besides, the primary research should be on developing green and effective methods for preparing ginkgols and bilobols and fully utilizing their pharmacological activity. This will also provide a new avenue for efficiently utilizing these bioactive compounds.

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.

The effect of Spondias mombin L. against Strongyloides venezuelensis: An in vitro approach.

Strongyloidiasis is a neglected tropical disease mainly caused by the nematode parasite Strongyloides stercoralis. Current treatment consists in the administration of ivermectin or, alternatively, albendazole (or analogues). Concerns regarding these drugs' irregular cure rates and side effects, raise a need for therapeutic alternatives. In this study, we tested the in vitro effect of Spondias mombin L. ethanolic extract against the laboratory model for strongyloidiasis, Strongyloides venezuelensis. The ethanolic extract was further fractionated and each fraction was also tested. Tested fractions were analyzed through thin layer chromatography and gas chromatography (GC/MS). Our results showed that S. mombin extract and fractions had a better in vitro effect than ivermectin, particularly fraction 4 which showed the better results causing 100% mortality in 4 h after exposure to an extract concentration of 400 µg/mL of RPMI medium and caused 100% mortality 12 h after exposure to an extract concentration of 50 µg/mL. Scanning electron microscopy showed that this fraction caused both wrinkling and peeling of the parasites cuticle, whilst ivermectin only caused wrinkling. GC/MS showed a high percentage of monoaromatic phenolic lipids (3-R phenol and 3-R1 phenol), which were likely responsible for the anti-Strongyloides effect. The use of polyvinylpyrrolidone reduced the efficiency, thus raising a need for alertness when using this excipient. Our results suggest that S. mombin is a potential source of compounds that could be used for stongyloidiasis treatment.

Bioactive lipids from the fruits of Solanum xanthocarpum and their anti-inflammatory activities.

Bioactive lipids widely found in daily consumed plants and animals are essential or beneficial to health and some of them are important physiological regulators in the human body. In our current investigation, 18 bioactive lipids (1-18), including 8 sphingolipids (1-8), 7 oxylipins (9-15), 3 phenolic lipids (16-18) were isolated from the fruits of Solanum xanthocarpum. And compounds 1, 9, 15, 16, and 18 were new lipids. In this study, homologues (4-8, 16, and 17) and configuration isomers (2 and 3) of bioactive lipids were separated, and NMR combined with MS/MS2 was an effective method to identify these compounds. These findings provided the reference for the separation and structural identification of bioactive lipids. The anti-inflammatory activities of all isolated lipids were evaluated by their inhibition of the NO release of LPS-induced RAW 264.7 cells. Aglycone components of sphingolipids, oxylipids with free carboxylic acid groups, phenylpropionic acid-fatty acid glyceride polymer exhibited significant anti-inflammatory activities. Further analysis by molecular docking revealed the interactions of bioactive compounds with the iNOS protein.

Chemical profile and allelopathic potential of Anacardium humile St. Hill. (cajuzinho-do-cerrado) leaf aqueous extract in the seed germination and seedling growth of lettuce, tomato and sicklepod / Perfil químico e potencial alelopático do extrato aquoso de Anacardium humile St. Hill. (cajuzinho-do-cerrado) na germinação e formação de plântulas de alface, tomate e fedegoso

Anacardium genus, Anacardiaceae, stands out for the presence of phenolic compounds. One of its species, investigated for its different potential uses, is Anacardium humile; however, little is known about its allelopathic effects. Therefore, the present study aimed to determine the chemical profile and evaluate the herbicide potential of your leaves in the germination of seeds and growth of seedlings of Lactuca sativa(lettuce), Lycopersicon esculentum (tomato) and Senna obtusifolia (sicklepod), both in vitro and in greenhouse. Leaves of A. humile were obtained from 20 matrices of Cerrado fragments in the municipality of Campo Grande, Mato Grosso do Sul state, Brazil. A voucher specimen was deposited at the herbarium (no. 8448). The aqueous extract was obtained from dried and crushed leaves using the extraction method of ultrasonic bath (30 min) with subsequent static maceration. After solvent evaporation, 12.78 g of extract were obtained. The chemical profile of the aqueous extract included determination of total phenolic and flavonoid contents, pH, electrical conductivity, and soluble solids concentration. For the in vitro bioassays, the extract was used at different concentrations, namely, 25, 50, 100, 150, and 200 mg mL-1. In greenhouse, the substrates were prepared using 950 g of vermiculite and 50 g of A. humile leaf powder at the following ratios: (950/50) (5%), 900/100 (10%), 800/200 (20%), and a control (100% vermiculite), under a completely randomized experimental design. Phenolic compounds and anthraquinones were predominant in the chemical profile of the extract, which presented different levels of allelopathic effect on seed germination and seedling growth of plants both ingermination chamber and in greenhouse, indicating strong allelopathic activity associated with the different compounds found in the leaves. Therefore, the results showed germination and growth inhibition at different levels, indicating that the substances contained in the leaves of Anacardium humile may be a promising alternative for the control of invasive species.

O gênero Anacardium, Anacardiaceae, destaca-se pela presença de compostos fenólicos. Uma de suas espécies, investigada pelos diferentes potenciais de uso, é Anacardium humile. No entanto, pouco se sabe sobre seus efeitos alelopáticos. Portanto, o presente trabalho objetivou determinar o perfil químico e avaliar o potencial herbicida de suas folhas sobre a germinação e crescimento de Lactuca sativa (alface), Lycopersicon esculentum (tomate) e Senna obtusifolia (fedegoso) in vitro e em casa de vegetação. Folhas de A. humile foram obtidas de 20 matrizes de Cerrado, município de Campo Grande/MS, Brasil. Uma espécime foi depositada no herbário (N. 8448). O extrato aquoso foi obtido das folhas secas e trituradas e o método de extração foi banho de ultrassom (30 minutos) seguido de maceração estática, sendo o solvente evaporado e 12,78 g de extrato obtido. O extrato foi submetido ao perfil químico e determinado: teor de fenóis totais e flavonóides, pH, condutividade elétrica e concentração de sólidos solúveis. Para os bioensaios in vitro, o extrato foi utilizado em diferentes concentrações (25, 50, 100, 150 e 200 mg mL-1). Em casa de vegetação, os substratos foram preparados com 950 g do substrato vermiculita e 50 g do pó das folhas de A. humile (950/50) (5%); 900/100 (10%); 800/200 (20%), além do controle, 100% vermiculita, com delineamento experimental inteiramente casualizado. O extrato apresentou como perfil químico predominante os compostos fenólicos e antraquinonas, com efeito alelopático sobre a germinação e crescimento em câmara de germinação e estufa, em diferentes graus, indicando que há uma forte atividade alelopática associada aos diferentes compostos encontrados nas folhas. Portanto, os resultados indicaram germinação e inibição do crescimento, em diferentes níveis, demonstrando que as substâncias contidas nas folhas de A. humile podem ser uma alternativa promissora para o controle de espécies invasoras.

High-Performance Thin-Layer Chromatography Hyphenated with Microchemical and Biochemical Derivatizations in Bioactivity Profiling of Marine Species.

Marine organisms produce an array of biologically active natural products, many of which have unique structures that have not been found in terrestrial organisms. Hence, marine algae provide a unique source of bioactive compounds. The present study investigated 19 marine algae and one seagrass collected from Torquay beach, Victoria, Australia. High-performance thin-layer chromatography (HPTLC) hyphenated with microchemical (DPPH•, p-anisaldehyde, and Fast Blue B) and biochemical (α-amylase and acetylcholine esterase (AChE) enzymatic) derivatizations was used to evaluate antioxidant activity, presence of phytosterols and phenolic lipids, α-amylase and AChE inhibitory activities of extract components. Significant α-amylase and AChE inhibitory activities were observed in samples 2, 6, 8 and 10. Antioxidant activities in the samples were found to be correlated to phytosterol content (R² = 0.78), but was not found to be related to either α-amylase or AChE inhibitory activities. α-Amylase inhibitory activities were correlated to AChE inhibition (R² = 0.77) and attributed to the phytosterol content, based on the similar peak position in the chromatograms with the ß-sitosterol chromatogram. Samples 1, 8, and especially sample 20, were found to contain phenolic lipids (alkyl resorcinol derivatives) with significant antioxidant activities. The results suggest that these marine species have a significant number of bioactive compounds that warrant further investigation.

Interrogation of spatial metabolome of Ginkgo biloba with high-resolution matrix-assisted laser desorption/ionization and laser desorption/ionization mass spectrometry imaging.

Ginkgo biloba is one of the oldest extant seed plants and has a number of unique properties and uses. Numerous efforts have characterized metabolites within the ginkgo plant and their corresponding biosynthesis pathways, but spatio-chemical information on ginkgo metabolites is lacking. Mass spectrometry (MS) imaging was used to interrogate the spatio-chemical localization of metabolites with matrix-assisted laser desorption/ionization and laser desorption/ionization Fourier-transform ion cyclotron resonance MS across the ginkgo leaf. Flavonoids, particularly unexpected and rare flavonoid cyclodimers, were detected predominately from leaf epidermis; ginkgolic acids and cardanols were observed exclusively in the secretory cavities. A non-uniform distribution of flavonoids observed between the upper and lower leaf epidermis was verified by liquid chromatography-MS analyses. Other metabolites, such as saccharides, phospholipids, and chlorophylls, occurred mainly in mesophyll cells. Furthermore, organ- and tissue-specific distributions of ginkgolides were revealed in the ginkgo root, young stem, and leaf. The acquired ion images provide important information regarding biosynthesis, transportation, and accumulation of metabolites throughout the ginkgo plant and should help us to understand the physiological roles of several plant secondary metabolites.

Microencapsulation of esterified krill oil, using complex coacervation.

The microencapsulation of the esterified krill oil (EKO), obtained from the transesterification of krill oil (KO) with 3,4-dihydroxyphenylacetic acid (DHPA), via complex coacervation and was investigated. The experimental findings showed that the DHPA and phenolic lipids (PLs) in the EKO affected the stability of the gelatine (GE)-EKO emulsion. To improve its stability, the effects of varying the pH of GE and the use of two emulsification devices, including the homogeniser and ultrasonic liquid processor were investigated, where the ultrasonic liquid processor was found to be a relatively more appropriate emulsification device. In addition, the capsules prepared using a pH of GE of 8.0 showed superior storage and had significantly (p <0.05) lower peroxide value as compared to those prepared with a pH of GE of 6.5. The microencapsulation of the EKO was effective in delaying the development of oxidation products during a period of 25 d of storage, at 25 °C.

A potent larvicidal agent against Aedes aegypti mosquito from cardanol

ABSTRACT Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids.

The synthesis of five novel methyl 10-undecenoate-based lipoconjugates of phenolic acids from undecenoic acid was carried out. Undecenoic acid was methylated to methyl 10-undecenoate which was subjected to a thiol-ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their structures were confirmed by spectral data. The anti-oxidant activity of the synthesized lipoconjugates of phenolic acids was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and also by the inhibition of linoleic acid oxidation in micellar medium by differential scanning calorimetry (DSC). The prepared compounds were also screened for their cytotoxic activity against five cell lines. It was observed that the lipoconjugates of caffeic acid, sinapic acid, ferulic acid, and coumaric acid displayed anticancer and anti-oxidant properties. The anticancer properties of these derivatives have been assessed by their IC50 inhibitory values in the proliferation of MDA-MB231, SKOV3, MCF7, DU 145 and HepG2 cancer cell lines.

Antimicrobial activity of the synthesized non-allergenic urushiol derivatives.

Synthesized urushiol derivatives possessing different carbon atomic length in the alkyl side chain inhibited the growth of food spoilage and pathogenic microorganisms. Particularly, non-allergenic 3-pentylcatechol showed a broad antimicrobial spectrum on an agar plate. Most food spoilage and pathogenic microorganisms were sensitive to urushiol derivatives in the liquid culture. The morphologies of the microorganisms were changed after treatment of 3-pentylcatechol.

Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis.

Chemical investigation of a sample of propolis originating from North-Western Cameroon led to the isolation of thirteen alk(en)ylphenols (1-13) (inseparable mixture) along with α-amyrin (14), ß-amyrin (15), lupeol (16), cycloartenol (17), mangiferonic acid (18), ambonic acid (19), mangiferolic acid (20), ambolic acid (21), isomangiferolic acid (22) and nine alk(en)ylresorcinols (23-31) (inseparable mixture). All compounds were identified following analysis of their spectroscopic data and comparison with previously published reports. Compounds (8), (12), (13) and (30) are new natural products. GC-MS analysis carried out on the alk(en)ylphenol and alk(en)ylresorcinol mixtures (dimethyl disulphide trimethylsilyl derivatives) revealed the presence of saturated and mono-unsaturated compounds with side chain lengths ranging from C11 to C19 and C15 to C19, respectively. The position of the double bond in mono-unsaturated derivatives was established from the characteristic fragments resulting from the cleavage of the bond between the two methylthio-substituted carbons. The most abundant compound in each mixture was 3-(12'Z-heptadecenyl)-phenol (10) and 5-(12'Z-heptadecenyl)-resorcinol (29). This study is the first to report the presence of triterpenes (except for lupeol) and phenolic lipids, including eighteen compounds previously unreported in bee glue, in an African sample.

Assessment of the antioxidant capacity and oxidative stability of esterified phenolic lipids in selected edible oils.

The research work was aimed at the determination of the antioxidant capacity (AOC) and the oxidative stability of phenolic lipids (PLs), obtained by lipase-catalyzed transesterification of phenolic acids (PAs) with selected edible oils (EOs), including flaxseed (FSO), fish liver (FO), and krill (KO) oils. The statistical analyses (Tukey's test at P < 0.05) revealed that the difference in AOC between that of the esterified FSO (EFSO) and the esterified krill oil (EKO) containing PLs and their control trials of EOs was significant (P < 0.05). To evaluate the storage stability, the EOs and their esterified products were subjected to 2 oxidation treatments. The experimental findings showed that the esterified EOs had higher oxidative stability when they were subjected to light, oxygen, and agitation at 50 °C as compared to that of the EOs; however, only the esterified fish oil (EFO) showed a significant difference in its peroxide value, when the esterified EOs were placed in the dark at 25 °C. Overall, the phenolic mono- and diacyglycerols present in the EOs have shown to be potential antioxidants in improving the oxidative stability of the oil and enhancing its AOC.

Inhibitory effect of some natural and semisynthetic phenolic lipids upon acetylcholinesterase activity.

The effect of phenolic lipids isolated from rye grains and cashew nut shell liquid (CNSL) from Anacardium occidentale and their semisynthetic derivatives on erythrocyte ghost's acetylcholinesterase activity was studied. It has been shown that all tested compounds decreased the enzymatic activity of acetylcholinesterase. This effect depends on the type of studied compounds. Three of them completely inhibit acetylcholinesterase activity at the micromolar concentration.