Tetraenone A: A New ß-Ionone Derivative from Tetraena aegyptia.

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-ß-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-ß-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3ß,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1-7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with Mpro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with Mpro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of Mpro of SARS-CoV-2.

Inhibition of Pseudomonas aeruginosa quorum sensing by methyl gallate from Mangifera indica.

Antipathogenic drugs are a potential source of therapeutics, particularly following the emergence of multiple drug-resistant pathogenic microorganisms in the last decade. The inhibition of quorum sensing (QS) is an advanced antipathogenic approach for suppression of bacterial virulence and dissemination. This study aimed to investigate the inhibitory effect of some Egyptian medicinal plants on the QS signaling system of Pseudomonas aeruginosa. Among the tested plants, Mangifera indica exhibited the highest quorum sensing inhibition (QSI) activity against Chromobacterium violaceum ATCC 12472. Four pure compounds were extracted and identified; of these, methyl gallate (MG) showed the most potent QSI. MG had a minimum inhibitory concentration (MIC) of 512 g/mL against P. aeruginosa strains PAO1, PA14, Pa21, Pa22, Pa23, Pa24, and PAO-JP2. The virulence factors of PAO1, PA14, Pa21, Pa22, Pa23, and Pa24 were significantly inhibited by MG at 1/4 and 1/2 sub-MICs without affecting bacterial viability. Computational insights were performed by docking the MG compound on the LasR receptor, and the QSI behavior of MG was found to be mediated by three hydrogen bonds: Trp60, Arg61, and Thr75. This study indicates the importance of M. indica and MG in the inhibition and modulation of QS and QS-related virulence factors in P. aeruginosa.

Genistin modulates high-mobility group box protein 1 (HMGB1) and nuclear factor kappa-B (NF-κB) in Ehrlich-ascites-carcinoma-bearing mice.

Cancer is the world's second-largest cause of death. Although there are numerous cancer treatment options, they are typically uncomfortable owing to side effects and ineffectual due to increased resistance to traditional anti-cancer medications or radiation therapy. A key method in cancer treatment is to target delayed/inhibited inflammation and apoptosis, which are very active areas of research. Natural chemicals originating from plants are of particular interest because of their high bioavailability, safety, few side effects, and, most importantly, cost-effectiveness. Flavonoids have become incredibly common as anti-cancer medications, with promising findings as cytotoxic anti-cancer agents that cause cancer cell death. Isolated compound (genistin) was evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7 and MDA-MB-231). The compound exhibited good cytotoxic activities against both cell lines. In vivo antiproliferative efficacy was also investigated in Ehrlich's ascites carcinoma (EAC). Compared to the control group, genistin revealed a significant decrease in tumor weight, volume, high-mobility group box1 (HMGB1), and nuclear factor-kappa B (NF-κB) contents. On the other hand, B-cell lymphoma 2 (Bcl-2) contents increase suggesting an anti-inflammatory and anti-apoptotic activity through inhibition of HMGB1 signaling and activating the Bcl-2 pathway.

Two new cytotoxic tetralin derivatives from Panicum turgidum.

Two new tetralin compounds were isolated from the aerial parts of Panicum turgidum Forssk. Their structures were elucidated by comprehensive 1 D and 2 D NMR experiments as well as high resolution ESI mass spectrometry. In addition, these two compounds have been tested for in vitro cytotoxicity against SKOV3 (Ovarian Carcinoma) and BT-549 (Breast Carcinoma). Compound 1 showed good cytotoxic activities against SKOV3 and BT 549 with IC50 value of 5.65 ± 0.31 and 10.3 ± 0.56 µg/mL, respectively.

In Vitro Antidiabetic, Antioxidant, and Prebiotic Activities of the Chemical Compounds Isolated from Guizotia abyssinica.

India and Ethiopia employ Guizotia abyssinica (niger plant) as a source of edible vegetable oil. Previous studies have documented the niger plant's antioxidant properties and dietary benefits. Here, G. abyssinica extract was obtained and ten known bioactive components (1-10) were isolated. The antioxidant, antidiabetic, and prebiotic properties of whole extract and isolated components of niger and the plant's ability to cooperate symbiotically with probiotic strains were examined. Compound 10, myricetin-3-O-L-rhamnoside, had the highest antioxidant capacity measured in the 2,2-diphenylpicrylhydrazyl (DPPH, 4629.76 ± 6.02 µmol Trolox equivalent/g compound) and ferric-reducing antioxidant power (FRAP, 2667.62 ± 7.5 mol Trolox equivalent/g compound) assays. The lowest α-amylase and glycogen phosphorylase activities and glucose diffusion were obtained with whole G. abyssinica extracts, whereas compounds 8-10 had moderate inhibitory effects. G. abyssinica extract also induced the highest glucose absorption by yeast cells in the presence of 5 mM of glucose. Moreover, Lactobacillus plantarum and L. rhamnosus incubated with ß-sitosterol 3-O-D-glucoside (compound 7) showed the highest prebiotic activity score. The levels of L-(+)-lactic acid isomer in the probiotic strains were the highest in presence of the whole extract and decreased progressively in the presence of flavonoid glycosides (compounds 8-10) and ß-sitosterol 3-O-D-glucoside. The enzymatic profile of the probiotic strains was unaffected by the niger extract and compounds 7-10. The findings revealed that the biological activities of G. abyssinica extract are mediated by the compounds 1-10, and it may be considered as a promising plant for the treatment of diabetes mellitus.

Mosquitocidal Activity of the Methanolic Extract of Annickiachlorantha and Its Isolated Compounds against Culex pipiens, and Their Impact on the Non-Target Organism Zebrafish, Danio rerio.

In this study, the crude extract and its isolated compounds from the stem bark of Annickia chlorantha were tested for their larvicidal, developmental, and repellent activity against the mosquito vector, Culex pipiens, besides their toxicity to the non-target aquatic organism, the zebrafish (Danio rerio). The acute larvicidal activity of isolated compounds; namely, palmatine, jatrorrhizine, columbamine, ß-sitosterol, and Annickia chlorantha methanolic extract (AC), was observed. Developmentally, the larval duration was significantly prolonged when palmatine and ß-sitosterol were applied, whereas the pupal duration was significantly prolonged for almost all treatments except palmatine and jatrorrhizine, where it shortened from those in the control. Acetylcholinesterase (AChE) enzyme showed different activity patterns, where it significantly increased in columbamine and ß-sitosterol, and decreased in (AC), palmatine, and jatrorrhizine treatments, whereas glutathione S-transferase (GST) enzyme was significantly increased when AC methanolic extract/isolated compounds were applied, compared to the control. The adult emergence percentages were significantly decreased in all treatments, whereas tested compounds revealed non-significant (p > 0.05) changes in the sex ratio percentages, with a slight female-to-male preference presented in the AC-treated group. Additionally, the tested materials revealed repellence action; interestingly, palmatine and jatrorrhizine recorded higher levels of protection, followed by AC, columbamine, and ß-sitosterol for 7 consecutive hours compared to the negative and positive control groups. The non-target assay confirms that the tested materials have very low toxic activity compared to the reported toxicity against mosquito larvae. A docking simulation was employed to better understand the interaction of the isolated compounds with the enzymes, AChE and GST. Additionally, DFT calculations revealed that the reported larvicidal activity may be due to the differing electron distributions among tested compounds. Overall, this study highlights the potential of A. chlorantha extract and its isolated compounds as effective mosquitocidal agents with a very low toxic effect on non-target organisms.

Methoxyisoflavan derivative from Trigonella stellata inhibited quorum sensing and virulence factors of Pseudomonas aeruginosa.

The number of deaths caused by multidrug-resistant Pseudomonas aeruginosa has risen in the recent decade. The development of quorum sensing inhibition (QSI) is a promising approach for controlling Pseudomonas infection. Therefore, this study mainly aimed to investigate how a plant-source material inhibits QSI to produce an antipathogenic effect for fighting microbial infections. The QSI effect of Trigonella stellata was assessed by using Chromobacterium violaceum ATCC 12472 reporter strain. Trigonella stellata exhibited high QSI activity, and an ethanolic extract of T. stellata was prepared for phytochemical isolation of the most active QSI compound. Nine pure compounds were isolated and identified as kaempferitrin (1), soyasaponin I (2), ß-sitosterol-3-O-glucoside (3), dihydromelilotoside (4), astrasikokioside I (5), methyl dihydromelilotoside (6), (3R, 4S)-4, 2', 4'-trihydroxy-7-methoxy-4'-O-ß-D-glucopyranosylisoflavan (7), (3S, 4R)-4, 2', 4'-trihydroxy-7-methoxyisoflavan (8, TMF), and (+)-D-pinitol (9). These compounds were screened against C. violaceum ATCC 12472, and TMF exhibited a potent QSI. The effect of TMF at sub-minimum inhibitory concentrations (MICs) was assessed against P. aeruginosa virulence factors, including biofilm, pyocyanin formation protease and hemolysin activity. TMF induced significant elimination of QS-associated virulence behavior. In addition, TMF at sub-MICs significantly reduced the relative expression of lasI, lasR, rhlI, and rhlR compared with that in untreated cells. Furthermore, molecular docking was performed to predict structural basis of the QSI activity of TMF. The study demonstrated the importance of T. stellata as a signal modulator and inhibitor of P. aeruginosa pathogenesis.

Isolation and biological activities of compounds from Rumex vesicarius L. and their use as a component of a synbiotic preparation.

The study evaluated prebiotic potential and the enzyme inhibition of extracts and isolated compounds of Rumex vesicarius (ruby dock), family Polygonaceae. Eight known compounds were identified in the roots of R. vesicarius. Extracts and compounds (1-8) increased the growth rate of Escherichia coli Nissle 1917 differentially compared to controls. The highest prebiotic index (PI) and activity score was recorded for EcN in the presence of compound 4, followed by, in descending order, petroleum ether, ethyl acetate, and total methanol extracts. The compounds and extracts reduced protease, α-amylase, and angiotensin-converting enzyme activities. This inhibitory activity was positively correlated with PI, Pscore, µu, and Ymax. These findings suggest that R. vesicarius is a good source of potential prebiotic and can boost beneficial bacteria. It may also be considered promising for treatment of diabetes mellitus, controlling weight, and regulating blood pressure.

Unravelling the antifungal and antiprotozoal activities and LC-MS/MS quantification of steroidal saponins isolated from Panicum turgidum.

Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1-7). They were evaluated for their in vitro antifungal, antileishmanial, and antitrypanosomal activities. Turgidosterone 6 was the most active antifungal against Candida albicans and Candida neoformans (IC50 values of 2.84 and 1.08 µg mL-1, respectively). Turgidosterones 4-7 displayed antileishmanial activity against Leishmania donovani promastigotes with IC50 values ranging from 4.95 to 8.03 µg mL-1 and against Leishmania donovani amastigote/THP with IC50 values range of 4.50-9.29 µg mL-1. Activity against Trypanosoma brucei was also observed for Turgidosterones 4-7 with an IC50 values range of 1.26-3.77 µg mL-1. Turgidosterones 1-3 did not display any activity against the tested pathogens. The study of structure-activity relationships of the isolated saponins indicated that the antifungal, antileishmanial, and antitrypanosomal activities are markedly affected by the presence of spirostane-type saponins and the elongation of the sugar residue at C-3. To quantitatively determine the most abundant active ingredient in Panicum turgidum extract, a single run, sensitive, and highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been applied under positive and negative modes. The obtained results showed that compound 5 was the most abundant (95.93 ± 1.10 mg per gram of dry Panicum turgidum extract), followed by 6 (52.51 ± 1.05 mg gm-1), 4 (32.71 ± 0.48 mg gm-1), and 7 (13.19 ± 0.50 mg gm-1). Docking of these saponins against the Candida albicans oxidoreductases and Leishmania infantum trypanothione reductase active sites revealed their potential to effectively bind with a number of key residues in both receptor targets.

A new antiprotozoal compound from Calendula officinalis.

A new phytoconstituent; (6Z,9Z)-heptadeca-6,9-diene-5,11-dione (1) was isolated from Calendula officinalis methanol extract. The structure of 1 was determined based on the analysis of NMR spectra and HRESIMS. It was tested for antimicrobial and antiprotozoal activities. Compound 1 showed leishmanicidal activity against L. donovani amastigote with an IC50 of 16.4394 µM and IC90 of 28.9015 µM and a weak antitrypanosomal activity with an IC50 of 37.6136 µM. The cytotoxicity of 1 was evaluated using standard experimental procedures against THP1 cells and no cytotoxicity was observed indicating its selectivity and safety.Supplemental data for this article can be accessed here.

Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies.

BACKGROUND AND AIM: The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, natural products can provide therapeutic alternatives that could be employed as an effective safe treatment for COVID-19. EXPERIMENTAL PROCEDURE: Twelve compounds were isolated from the aerial parts of C. officinalis L. and investigated for their inhibitory activities against SARS-CoV-2 Mpro compared to its co-crystallized N3 inhibitor using molecular docking studies. Furthermore, a 100 ns MD simulation was performed for the most active two promising compounds, Calendulaglycoside A (SAP5) and Osteosaponin-I (SAP8). RESULTS AND CONCLUSION: At first, molecular docking studies showed interesting binding scores as compared to the N3 inhibitor. Calendulaglycoside A (SAP5) achieved a superior binding than the co-crystallized inhibitor indicating promising affinity and intrinsic activity towards the Mpro of SARS-CoV-2 as well. Moreover, findings illustrated preferential stability for SAP5 within the Mpro pocket over that of N3 beyond the 40 ns MD simulation course. Structural preferentiality for triterpene-Mpro binding highlights the significant role of 17ß-glucosyl and carboxylic 3α-galactosyl I moieties through high electrostatic interactions across the MD simulation trajectories. Furthermore, this study clarified a promising SAR responsible for the antiviral activity against the SARS-CoV-2 Mpro and the design of new drug candidates targeting it as well. The above findings could be promising for fast examining the previously isolated triterpenes both pre-clinically and clinically for the treatment of COVID-19.

New sesquiterpene glycoside ester with antiprotozoal activity from the flowers of Calendula officinalis L.

Continued chromatographic investigation of Calendula officinalis flowers led to the isolation of two sesquiterpenes, including one new, viridiflorol-10-O-ß-quinovopyranoside-2`-O-(3``-methyl-2``-pentenoate) (1), along with a previously reported compound viridiflorol-10-O-ß-fucopyranoside-2`-O-(3``-methyl-2``-pentenoate) (2). The new compound 1 was tested for antiprotozoal activity against Leishmania donovani Amastigote/THP1 and Trypanosoma brucei and it showed IC50 values of 3.57 and 7.84 µg/mL, respectively, while compound 2 exhibited no activity at the highest concentration tested 10 µg/mL.

A new anti-inflammatory flavonoid glycoside from tetraena aegyptia.

The chromatographic reinvestigation the methanol extract of Tetraena aegyptia led to the separation of a new flavonoid glycoside, isorhamnetin-3-O-[2```,3```-O-isopropylidene-α-L-rhamnopyranosyl]-(1```→6``)-O-ß-D-glucopyranoside (1), together with two known flavonoids, isorhamnetin (2) and isorhamnetin-3-O-glucoside (3), isolated for the first time from the plant. The new compound was evaluated for the anti-inflammatory activity by using LPS-induce RAW 264.7 cells model. Compound 1 showed significant inhibitory effect on NO release. ELISA assay showed a pronounced effect of 1 on the secretion of cytokines IL-6 and TNF-α, in a dose-dependent manner. Consistent results were obtained by qRT-PCR which revealed that compound 1 markedly reduced the mRNA expression of IL-6 and TNF-α. Together these data, we demonstrated the anti-inflammatory activity of compound 1.

Chemical characterization of Cassia fistula polysaccharide (CFP) and its potential application as a prebiotic in synbiotic preparation.

Prebiotics are non-digestible food ingredients that are selectively fermented by probiotics. The aim of this study was to investigate the chemical properties of a polysaccharide extracted from Cassia fistula mature fruit pulp and to evaluate its effects on probiotic strains: L. casei, L. rhamnosus, E. coli Nissle 1917 (EcN), and E. faecalis. These strains were compared for their growth behavior in culture media supplemented with different Cassia fistula polysaccharide (CFP) concentrations. The molecular weight of CFP was approximately 8.707 × 105 Da. The recovered polysaccharide contained a low percentage of crude protein (4.4%). Aspartic acid, glutamic acid, and proline were the most abundant amino acids. Glucose and mannose were the predominant sugars followed by arabinose and rhamnose. L. casei grew faster at high CFP concentrations (2%) compared with the lower concentrations of CFP. The highest values for the prebiotic index and prebiotic activity score were observed for L. casei treated with 2% CFP, and it may be considered a prebiotic due to its high resistance against α-amylase and acidic conditions. CFP provides two ways to adjust nitric oxide (NO) synthesis in macrophages. Finally, the use of 1.5 and 2% CFP for cultured milk production significantly shortened the fermentation period from 210 min to 180 min and 150 min, respectively.

Machaerinic acid 3-O-ß-D-glucuronopyranoside from Calendula officinalis.

Machaerinic acid 3-O-ß-D-glucuronopyranoside (1), along with ten known compounds (2-11) were isolated from the methanol extract of Calendula officinalis L. aerial parts. Their structures were confirmed by 1D and 2D NMR analysis and HRESIMS. Compound 1 was evaluated for the anti-proliferative activity against 95D and HT29 cancer cell lines and showed no cytotoxicity at the concentration of 100 µM.

Anthraquinone-Based Specialized Metabolites from Rhizomes of Bulbine natalensis.

The rhizomes of Bulbine natalensis furnished six previously unreported anthraquinone derivatives (1-6), together with eight known specialized metabolites. Their structures were determined by interpretation of 1D and 2D NMR and HRESIMS data. The absolute configurations of compounds 1-6 were determined by specific rotation and circular dichroism experiments. The isolated compounds were evaluated for antimicrobial activities, and compound 1 was found to be a moderate inhibitor (IC50 0.02 µM) against methicillin-resistant Staphylococcus aureus (MRSA).

PPARα and γ Activation Effects of New Nor-triterpenoidal Saponins from the Aerial Parts of Anabasis articulata.

Anabasis articulata, traditionally used to treat diabetes, is rich in saponin content. This study was performed to investigate the agonistic effect of its saponins on peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in human hepatoma (HepG2) cells to explore the possibility of the involvement of these nuclear receptors in the mechanism of the antidiabetic effect of the plant. Chemical investigation of the n-butanol fraction resulted in the isolation of three new and one known 30-noroleanane triterpenoid saponins. The structures of the new compounds were elucidated as 3ß-hydroxy,23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-ß-D-glucopyranosyl ester (1: ), 3ß-O-D-galactopyranosyl-23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-ß-D-glucopyranosyl ester (2: ), and 3ß-O-D-xylopyranosyl-30-norolean-12,20(29)-dien-28-oic acid 28-O-ß-D-glucopyranosyl ester (3: ), while the known 30-nortriterpenoidal saponin was identified as boussingoside E (4: ). Although, the isolated saponins (1:  - 4: ) did not show > 1.5-fold activation of peroxisome proliferator-activated receptor-γ, but two of them (1: and 3: ) activated peroxisome proliferator-activated receptor-α to the higher extents of 2.25- and 1.86-fold, respectively. These results suggest that the reported antidiabetic action of the isolated saponins may not solely involve the activation of peroxisome proliferator-activated receptor-γ. However, the agonistic activity of the n-butanol fraction of A. articulata (1.71-fold induction) and two of its saponins (1: and 3: ) towards peroxisome proliferator-activated receptor-α may be beneficial in the cardiovascular condition that is closely associated with diabetes and other metabolic disorders.

Cytotoxic steroidal saponins from Panicum turgidum Forssk.

Three new bidesmosidic cholestane-type steroidal glycosides, 16-O-ß-d-glucopyranosyl-cholest-5-en-3ß,16ß-diol-22-one-3-O-α-l-rhamnopyranosyl-(1→2)-O-[(ß-d-glucopyranosyl(1→4)]-O-ß-d-glucopyranoside (1), 16-O-ß-d-glucopyranosylcholest-5-en-3ß,16ß-diol-22-one-3-O-α-l-rhamnopyranosyl-(1→2)-O-ß-d-glucopyranoside (2), and 16-O-ß-d-glucopyranosylcholestan-3ß,16ß-diol-6,22-dione-3-O-α-l-rhamnopyranosyl-(1→2)-O-ß-d-glucopyranoside (3) were isolated from a methanolic extract of Panicum turgidum. In addition four known compounds, pennogenin 3ß-O-α-l-rhamnopyranosyl-(1→2)-O-[α-l-rhamnopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→4)]-O-ß-d-glucopyranoside (4), yamogenin 3ß-O-α-l-rhamnopyranosyl-(1→2)-O-[α-l-rhamnopyranosyl-(1→4)]-O-ß-d-glucopyranoside (5), yamogenin 3ß-O-α-l-rhamnopyranosyl-(1→2)-O-[α-l-rhamnopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→4)]-O-ß-d-glucopyranoside (6), and pennogenin 3ß-O-α-l-rhamnopyranosyl-(1→2)-O-[α-l-rhamnopyranosyl-(1→4)]-O-ß-d-glucopyranoside (7) were also isolated and characterized. Their structures were established using extensive spectroscopic methods including 1D and 2D NMR and HRESIMS. The isolated compounds were screened for cytotoxicity towards a panel of mammalian cell lines and 4-7 were found to be cytotoxic.

A New Neolignan from Panicum turgidum.

A new neolignan, paniculignan (1), and a known lignan, tetracentronside B (2), were isolated from Panicum turgidum. The structure of 1 was elucidated by extensive spectroscopic methods including ID and 2D NMR and HR-ESI-MS. The relative configuration of 1 was determined on the basis of circular dichroism spetroscopy, optical rotation, and NOESY correlations.