Records of Natural Products Articles

A new cyclic tetrapeptide (1) named aspergilpeptide A, together with a known cyclic tetrapeptide penicopeptide A (2) and chaetominine (3) were obtained from the endophytic fungus Aspergillus versicolor E-2 isolated from the medicinal plant Euphorbia royleana. The structures of compounds (1-3) were elucidated using NMR and MS methods.

A new coumarin, angedahurin A (1), and seven known analogues (2−8), were isolated from the roots of Angelica dahurica. Their structures were identified by extensive NMR, IR, and HR-ESIMS spectroscopic analyses. The cytotoxicities of coumarins 1−8 against MG-63 human osteosarcoma cell lines were screened. Compound 1 showed significant cytotoxic effects against MG-63 with an IC50 value of 7.2 uM，for comparison, the positive control, 5-FU, had an IC50 value of 32.4 uM. Morphological features of apoptosis activities were evaluated in 1-induced MG-63 cells and the results confirmed MG-63 cell apoptosis in a dose-dependent manner.

A phytochemical investigation of the methanolic extract of Endiandra kingiana (bark) led to the isolation of four major compounds which are kingianic acid A (1), tsangibeilin B (2), kingianin A (3) and kingianin F (4). The structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The compounds were screened for their in vitro α-glucosidase inhibition activity. Among them, compounds 3-4 showed potent α-glucosidase inhibition activity with IC50 value at 11.9 ± 2.0 µM and 19.7 ± 1.5 µM, respectively. The molecular docking study found that both compounds were bound into the active site of the N-terminal of MGAM, and thus agreed with the in vitro α-glucosidase enzyme inhibition activity results.

Radix Angelica sinensis (RAS) is a famous Chinese medicine with hematinic effects and has been applied for the treatment of blood deficiency syndrome for many years. Previous studies have indicated that RAS has beneficial effects in the treatment of hemolytic anemia. The hemolytic anemia/blood deficiency syndrome is a common syndrome that is often presented in most traditional Chinese medicine (TCM) clinics. Based on routine blood indicators, metabolomics analysis was conducted to investigate the mechanism of RAS in the treatment of hemolytic anemia. Multivariate and univariate statistical analysis were used to identify potential biomarkers in the serum. On administering RAS to the haemololitic anaemic rat, the levels of WBC, RBC, HGB, and PLT in AG tended to shift toward that of the control group. Additionally, all the 26 metabolites such as cholic acid, succinic acid and orotate which are regulated by blood deficiency appeared normal through the five metabolic pathways, such as linoleic acid metabolism, alanine, aspartic acid and glutamate metabolism, pyrimidine metabolism, arginine and proline metabolism. Thus, three metabolic pathways predicted by the network pharmacology were consistent with the metabolism pathway of Angelica sinensis: linoleic acid metabolism, arginine and proline metabolism, tryptophan metabolism. The integrated metabolomics and network pharmacology comprehensively improved the understanding of the physiological and metabolic state of an organism. The possible hematopoietic effects and underlying mechanism of action on hemolytic anemia rats after lavage with RAS water extracts, could potentially be elucidated by combining pharmacology with untargeted metabolomics. These pointed out the significance of metabolomics as a valuable tool for studying the essence of Chinese medicine’s syndrome theory and the mechanism of RAS under anti-blood deficiency syndrome.

Several applications of natural products around the world arise from traditional knowledge or evident organoleptic properties, and essential oils from Salvia species are a current example. The genus is integrated by native and endemic species from Africa, the Americas, Asia, and Europe. In the present work, essential oil compositions of Salvia dugesii and S. gesneriiflora were experimentally determined and statistically correlated with ten described Salvia species from four continents by using multivariate methods complemented with univariate analysis and PCA protocols, to establish metabolic approaches. Essential oils data from S. angulata, S. miltiorrhiza, S. plebeia, S. sclarea, S. argentea, S. viridis, S. lavandulifolia, S. africana-lutea, S. chamelaeagnea, and S. officinalis were included in the study. By the above, 146 essential oil components, classified into 29 structural skeletons, according to its biogenesis, were analyzed. The results provided metabolic similarities between American and Asian Salvia species due to a higher active sesquiterpene metabolism; and African and European species revealed chemical similarities, since monoterpene pathways dominate. Such correlations are in concordance with genetic knowledge about genus, thereby, approaches on metabolism of Salvia can be easily visualized using statistical tools, consequently, practical method to analyze Salvias for scientific proposes.

Different species of the genus Selaginella are exploited for various ethnomedicinal purposes around the globe; mainly to cure fever, jaundice, hepatic disorders, cardiac diseases, cirrhosis, diarrhea, cholecystitis, sore throat, cough of lungs, promotes blood circulation, removes blood stasis and stops external bleeding after trauma and separation of the umbilical cord. Though, high content of various phytochemicals has been isolated from Selaginella species, flavonoids have been recognized as the most active component in the genus. Crude extract and different bioactive compounds of this plant have revealed various in vitro bioactivities such as, antimicrobial, antiviral, anti-diabetic, anti-mutagenic, anti-inflammatory, anti-nociceptive, anti-spasmodic, anticancer and anti-Alzheimer. However, more studies into the pharmacological activities are needed, since none of the professed bioactivity of this plant have ever been fully evaluated. Therefore, this review aims to discuss the evidence-based ethnomedicinal and ethnopharmacological uses, phytochemicals and bioactive potential of Selaginella species. It will provide an updated knowledge for ethnobotanists, ethnopharmacologists and other scientific communities to rethink over the possible usage of Selaginella in medicine. Moreover, further explorations are needed to formulate a novel medicinal product from Selaginella extracts for the improvement of human health, together with toxicity evaluations, necessary to ensure about the safety of these medicinal lycophytes.

A new eudesmane sesquiterpene (1), named sapleudesone, together with four known analogs (25) were isolated from the aerial parts of Salvia plebeia. The structure of compound 1 was established by NMR and HRESIMS data, and the absolute configuration of 1 was determined by comparing the experimental ECD spectrum with the calculated ECD spectra. The known compounds were identified to be salplebeone A (2), linderolide I (3), chlorantene D (4), and chlomultin B (5) by comparing the NMR data and specific rotations with reported data. All five compounds were tested for the inhibitory effects against NO production in LPS-activated RAW 264.7 macrophages, As a result, compound 2 exhibited weak inhibitory effects with an IC50 value of 42.3  1.4 uM.

Abstract: Abstract: The hydrodistilled volatile constituents of Cistanche tubulosa (commonly known as Desert Ginseng) have been chemically and biologically investigated. Based on the retention times and mass fragmentation of the obtained GC-MS chromatogram, 106 individual components which representing ≈ 99.29 % of the total volatile constituents have been identified. The major compounds (66.57% of the total composition) were identified as hexanal (15.98%), trans-sabinyl acetate (12.22%), allo-aromadendrene (9.30%), nonanoic acid (6.66%), 3Z- hexeny-2-methyl butanoate (6.09%), valeranone (5.25%), (E, E)-α-Farnesene (3.18%), a-pinene (3.06%), linalool isovalerate (3.03%) and a-humulene (1.8%). Estimation of the antioxidant activity of EO showed promising effect at 80 mg/mL concentration, it exerted 62.40, 863.29 and 62.72 % inhibition compared to TBHQ that showed 78.62, 77.56 and 79.23 % inhibition using DPPH, ABTS and β-carotene/Linoleic acid, respectively. The antioxidant activity was pronounced at 80 mg/mL than other concentrations. The volatile constituents showed inhibitory activity against gram positive bacteria ranged from 2.23 mg/100 mL ( for staphylococcus aureus ), and  15.68 mg/100 mL (for Bacillus cereus) compared to ciprofloxacin which showed inhibitory activity 0.185, and 0.182 mg/100 mL, respectively. Moreover, the MIC of volatiles towards gram negative bacteria are ranged from 18.35 (Escherichia coli) to 31.61 mg/100 mL (Klebsiella pneumonia) compared to ciprofloxacin with 0.184 to 0.188 mg/mL respectively. Additionally, the antifungal activity against candida albicans was rather promising (4.36 mg/mL).

The use of Silybum marianum L. for therapeutic purposes has been known since ancient times. Its phytocomplex reduces transaminases and other biohumoral indices in the course of liver disease and also in hepato-renal syndrome. In particular, the flavonolignan component has shown properties that would partially explain the ability of the phytocomplex to induce a certain regeneration of liver cells, stimulate the cellular elimination of toxins and reduce the inflammatory component, present in fatty, alcoholic and hormonal therapies with steroids. S. marianum is also successfully used in the treatment of patients with symptomatic chronic hepatitis, with complete disappearance of clinical symptoms, such as asthenia, loss of appetite, severe meteorism, dyspepsia, and with normalization of transaminases. The same results can be obtained in patients undergoing heavy chemotherapy cycles. Modern herbal medicine uses it in decoction or infusion, however with some caution in patients suffering from hypertension, due to the presence of tyramine. In addition, the extracts of the roots have antioxidant, diuretic and febrifugal properties and those of the leaves have aperitif properties. It is therefore interesting to provide a picture of the different non-flavonolignanic components (terpenes, steroids and essential oils) of the plant and their properties, which have perhaps been wrongly neglected over the past few years.

The essential oil (EO) of aerial parts of Mallotus repandus (Willd.) Muell. Arg. was extracted by hydrodistillation and characterized by GC/FID and GC/MS. Fifty-one compounds comprising 97.1% of the EO were identified, of which α-humulene  (18.7%), β-selinene (12.8%), aciphyllene (10.7%), (E)-caryophyllene (8.4%), α-copaene (5.5%), humulene epoxide II (4.9%) and caryophyllene oxide (4.3%) were the major compounds. The EO was evaluated for antibacterial properties using broth microdilution method and crystal-violet static biofilm formation assay. The M. repandus EO possessed a bactericidal effect against tested gram-positive bacteria strains (MIC = MBC: 0.05-0.10 mg/mL). Further, the EO showed the ability to inhibit the biofilm formation of Staphylococcus aureus. In addition, the potential synergistic effect was assessed by checkerboard method. Combination of the M. repandus EO with Streptomycin showed synergistic effects against the tested bacterial strains. This study demonstrates that M. repandus EO could be further explored as good alternative for potential pharmaceuticals.

Phytochemical investigation of the chloroform fraction obtained from Saudi collection of Tephrosia purpurea L. (Pers.) resulted in the isolation of four new and two known flavonoid derivatives. Three of the new compounds were 5-deoxyflavonoid derivatives identified as tephropurpugazanin (1), 4’’-hydroxyapollinin (4), epi-tephroapollin E (5) as well as (-)-tephropurpulin A (2). The known compounds were identified as 3,7-dihydroxy-8-methoxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one (3) and tephroapollin E (6). Structures were elucidated utilizing different spectroscopic tools including UV, optical rotation, 1D- and 2D-NMR as well as HRESIMS.

Biotransformation of bis-bibenzyl perrottetin F (1), isolated from the liverwort Lunularia cruciata by Aspergillus niger, has been investigated. New metabolites (2-4) have been isolated using reversed phase semipreparative HPLC and their structures were established to be 8-hydroxyperrottetin F, C-7-C-8 cleaved product, and perrottetin F 6’-sulfate using 1D and 2D NMR, HR-ESI-MS, IR and UV spectroscopy. The antimicrobial and cytotoxic properties of these compounds were also evaluated. Given the suggested cytotoxic properties of the parent compound, antiproliferative activity against healthy human lung fibroblasts (MRC5) and human lung carcinoma (A549) of three metabolites were evaluated revealing their lower cytotoxic properties in comparison to the starting compound - perrottetin F. The antimicrobial properties of these compounds were also evaluated, with the inhibitory activity against the Pseudomonas aeruginosa PAO1 and Staphylococcus aureus determined between 100 µM and 450 µM. The metabolites showed remarkable ability to inhibit synthesis of bacterial quorum-sensing signal molecules such as short chain acyl homoserine lactones (AHLs). Therefore, biotransformation method represents fast and effective tool for obtaining new bioactive structures.

Fifteen phenylpropanoids were isolated from the ethanol extract of the roots of Solanum melongena L., including a new compound, melongenapanoid A (1), together with fourteen known compounds (2-15). Their chemical structures were elucidated by 1D and 2D NMR and HR-MS data according to those values of the literatures. The fourteen known compounds (2-15) were all firstly isolated from this plant. While, the isolates were evaluated for the inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 cell line. Compounds 2, 4 and 5 showed moderate inhibition of NO production with IC50 values of 28.7, 24.4 and 32.6 μM, respectively.

A phytochemical study on the flowers of Cercis glabra ‘Spring-1’ led to the isolation and identification of twelve compounds, including one new compound named as 1-O-α-l-rhamnosyl-(E)-phytol (1) and eleven known compounds. Their structures were elucidated based on physical data analysis, including HR-ESI-MS, NMR, UV, IR, and acid hydrolysis. All compounds were screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl method. Compounds 4 and 5 exhibited obvious DPPH radical scavenging activities. All the isolates were tested for their inhibitory effects on mushroom tyrosinase, and compounds 6, 7, 10 and 11 showed moderate tyrosinase inhibitory activities. 

The goal of the work is to determine the bioactive pharmaceutical metabolites produced by the Fusarium oxysporum YP9B isolate. Ten new natural compounds were isolated from the ethyl acetate extract of the F. oxysporum YP9B strain.  Their structures were elucidated by spectroscopic methods using 1D and 2D NMR, UV, FT-IR, and mass spectra (LC-QTOF MS and GC-FID/MS). Identified compounds were named as; (1-benzyl-2-methoxy-2-oxoethyl)-2-hydroxy-3-methylbutanoate (1), 2-oxo-8-azatricyclo[9.3.1.13,7]-hexadeca-1(15),3(16),4,6,11,13-hexaen-10-one (2), 2,3-dihydroxypropanoic, hexadecanoic anhydride (3a), 2,3-dihydroxypropanoic (9Z)-octadecenoic anhydride (3b), 2,3-dihydroxy-propanoic (9Z,12Z)-octadecadienoic anhydride (3c), 2,3-dihydroxypropanoic (11Z)-octadecenoic anhydride (4a), 2,3-dihydroxypropanoic, (9E,12E)-octadecadienoic anhydride (4b), 3-hydroxy-1,2,6,10-tetramethylundecyl hexzadecanoate (5a), 3-hydroxy-1,2,6,10-tetramethylundecyl (9E)-octadecaenoate (5b),  and 3-hydroxy-1,2,6,10-tetramethylundecyl octadecanoate (5c). Antimicrobial activities of the isolates obtained from the YP9B strain were determined. Cytotoxic and antiviral activities were tested for the isolates against VERO, MCF-7, PC-3, and A549. Compounds 5a-c, 1, and 3a-c showed bacteriostatic activity at low concentrations, and 4a-b and 2 were found to be bactericides. MIC and MBC values against Mycobacterium smegmatis for the compounds 5a-c and 1 were determined to be ​​ <0.5 µg/mL and 0.46 µg/mL, respectively. The experimental result showed that compounds 2, 5a-c and 1 have strong cytotoxic (7.51±1.38 and 19.13± 0.68 (µM) IC50) activity. The antiviral activity against HSV type-1 was determined to be 1.25 µM for compounds 4a-c and 0.312 µM for compound 1.

Plants of the genus Melaleuca which belong to family Myrtaceae, commonly named "tea trees”, are economically important plants. When talking about tea trees, the essential oils are the center of attention, leaving all other phytoconstituents in their shade. Many reviews addressed the composition and pharmacological activities of Melaleuca alternifolia L. essential oil as the most common one. To date, there are no detailed reviews summarizing the phytochemical and pharmacological properties of the non-volatile components of members of the genus Melaleuca. After distillation of the volatile oil, large amounts of these plants’ waste remain untapped. This review indicates that this genus is a rich source of diverse groups of bioactive phytochemicals, including flavonoids, triterpenoids, benzylic phloroglucinol-terpene derivatives, polyphenols, hydrolysable tannins, and other compounds. It also discusses the diverse pharmacological activities reported for plants of this genus.

7-methoxy-8-hydroxy cycloanthranilylproline (2), a new natural product with pyrrolobenzodiazepine (PBD) framework, was isolated from marine-derived actinobacterium Streptomyces cacaoi 14CM034, together with cycloanthranilylproline (1). Structural elucidation of the compounds was based on FTIR, 1D- (1H and 13C NMR), 2D-NMR (COSY, HMBC and NOESY) and HR-MS analyses. Compounds 1 and 2 exhibited notable antimicrobial activity. The presence of PBD derivatives in S. cacaoi was first demonstrated with this study.