Is Baikiain in Tara Flour a Causative Agent for the Adverse Events Associated with the Recalled Frozen French Lentil & Leek Crumbles Food Product? - A Working Hypothesis.

The French Lentil & Leek Crumbles frozen food product was recently recalled due to reports of gastrointestinal issues. So far, 393 adverse illness complaints and 133 hospitalizations have been reported from consumption of this food, and the tara (Tara spinosa) protein flour ingredient is hypothesized to be responsible. A multipronged approach resulted in identification of (S)-(-)-baikiain in tara as a compound of interest due to its abundance, possible metabolic fate, and close resemblance to irreversible inhibitors of L-pipecolate oxidase. Oral administration of baikiain in ND4 mice showed a statistically significant increase in blood ALT levels and a reduction in liver GSH.

Benzoylcyclopropane Derivatives from Hypoxis hemerocallidea Corms.

Two monobenzoylcyclopropane (hypoxhemerol A (1: ) and hypoxhemeroloside G (2: )) and three dibenzoylcyclopropane (hypoxhemerol B (3: ), hypoxhemeroloside H (4: ), and hypoxhemeroloside I (5: )) derivatives were isolated from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. This is the first instance where benzoylcyclopropane analogs were isolated from any natural source. Structure elucidation was mainly based on 1D- and 2D-NMR and HRESIMS data. The absolute configuration (2R, 4R) of 1: was determined via NOESY NMR and experimental and calculated ECD data analyses. Compounds 1: -5: and 11 recently reported metabolites (hypoxoside, obtuside A, interjectin, acuminoside, curcapicycloside, and hypoxhemerolosides A - F) were screened for in vitro antimicrobial activity against various bacterial and fungal strains. Curcapicycloside and acuminoside exhibited antibacterial activity against Escherichia coli with 78 and 79% inhibition at 20 µg/mL, respectively. Hypoxhemeroloside A showed mild antifungal activity against Cryptococcus neoformans with 63% inhibition at 20 µg/mL.

Undescribed C-Glycosylflavones from Corn Silk and Potential Anti-inflammatory Activity Evaluation of Isolates.

Phytochemical investigation of corn silk resulted in isolation and characterization of four flavone C-glycosides, chrysoeriol 6-C-ß-oliopyranosyl-7-O-ß-D-glucopyranoside (1: ), 3'-methoxycassiaoccidentalin A (2: ), chrysoeriol 6-C-ß-boivinopyranosyl-7-O-ß-D-glucopyranoside (3: ), and ax-4″-OH-3'-methoxymaysin (4: ), a triterpenoid, friedelin (5: ), two sterols, (22E)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol (6: ) and 6ß-hydroxystigmasta-4,22-diene-3-one (7: ), and a mixture of ß-sitosterol and stigmasterol. Compounds 1: and 2: were previously undescribed. Structure elucidation of the isolated compounds was attained using spectral data including 1D and 2D NMR and HRESIMS. Compounds1, 2, 5: , and 6: inhibited iNOS activity in LPS-induced macrophages and decreased nitrite levels by 68.64 ± 4.46, 65.67 ± 6.47, 88.50 ± 0.50, and 94.00 ± 4.00%, respectively, at 50 µM. Compound 5: also showed inhibition of NF-κB (51.00 ± 1.50%). Compounds 1: and 2: induced NAG-1 activity in chondrocytes by 1.80 ± 0.05 and 2.00 ± 0.13 fold, respectively. The extract of corn silk, however, did not exhibit inhibition of iNOS or NF-κB but induced NAG-1 by 1.80 ± 0.51 fold.

Bioassay-Guided Isolation of Iridoid Glucosides from Stenaria nigricans, Their Biting Deterrence against Aedes aegypti (Diptera: Culicidae), and Repellency Assessment against Imported Fire Ants (Hymenoptera: Formicidae).

In our natural product screening program, we screened natural products for their repellency and toxicity against insect vectors. Methanolic extract of aerial parts of Stenaria nigricans (Lam.), with no published chemistry, was tested for repellency against mosquitoes and imported hybrid fire ants. Methanolic extracts showed biting deterrence similar to DEET (N,N-diethyl-3-methylbenzamide) against Aedes aegypti L. Based on this activity, the crude extract was fractionated into chloroform, ethyl acetate, and methanol subfractions. The active methanolic subfraction was further fractionated into 13 subfractions. These fractions were tested for their biting deterrence against Ae. Aegypti. Active subfractions were further characterized to identify the compounds responsible for this activity. Four undescribed iridoid glucosides (1-4) and three previously reported compounds (5-7) were isolated from active subfractions and tested for their biting deterrent activity. Based on BDI values, compounds 2, 3, 6, and 7, with biting deterrence similar to DEET, showed the potential to be used as repellents against mosquitoes. In an in vitro digging bioassay, none of these compounds showed any repellency against hybrid imported fire ants at a dose of 125 µg/g. This is the first report of biting deterrence and repellency of S. nigricans extract and its pure compounds, iridoid glucosides against mosquitoes and imported fire ants. Further studies will be conducted to explore the repellent potential of these compounds in different formulations under field conditions.

Phytochemical study of Piliostigma thonningii, a medicinal plant grown in Nigeria.

Piliostigma thonningii (Schumach.) Milne-Redhead. (Leguminosae) is used for various medicinal purposes in African countries. Phytochemical investigation of P. thonningii yielded two compounds newly isolated from natural sources, 2ß-methoxyclovan-9α-ol (1), and methyl-ent-3ß-hydroxylabd-8(17)-en-15-oate (2), along with 14 known compounds (3-16). Compounds 1 and 4 (alepterolic acid) showed potential selectivity towards Trypanosoma brucei brucei with IC50 7.89 and 3.42 µM, respectively. Compound 2 showed activity towards T. brucei and Leishmania donovani Amastigote with IC50 3.84 and 7.82 µM, respectively. The structure activity relationship (SAR) of the isolated metabolites suggested that hydroxylation at C-2 enhances the antiprotozoal activity towards T. brucei in sesquiterpenes 1 and 3. Similarly hydroxylation at C-3 in labdane diterpenes elevates the antiprotozoal activity towards T. brucei.

Phytochemical analysis of Cichorium bottae root and anti-inflammatory potential assessment of isolates.

The Cichorium plants are particularly notable due to their remarkable therapeutic and medicinal properties, besides being used as food and conventional medication. Although Cichorium plants have been studied for their phytoconstituents and biological activities, there is limited knowledge about the constituents of the roots of C. bottae. A phytochemical study of the 90% MeOH extract of C. bottae roots resulted in the isolation of twelve compounds belonging to guaianolide sesquiterpene lactones, sesquiterpene lactone glucosides, and phenolic derivatives, of which two compounds designated as 9α-hydroxycrepediaside B (1) and cichobotinal (2) were previously undescribed. The isolated compounds were assessed for their anti-inflammatory potential through the inhibition of inducible nitric oxide synthase (iNOS) and resultant decrease in nitric oxide generation in LPS-induced macrophages. Among the isolates, compounds 2 and 11 (8-deoxylactucin) inhibited iNOS activity with IC50 values of 21.0 ± 4 and 6.8 ± 0.1 µM, respectively. The methanolic extract of C. bottae inhibited iNOS with an IC50 of 10.5 ± 0.5 µg/mL.

Phytochemical study of Seriphidium khorassanicum (syn. Artemisia khorassanica) aerial parts: sesquiterpene lactones with anti-protozoal activity.

Two new eudesmane-type sesquiterpene lactones, 1ß,3α,8α-trihydroxy-11ß,13-dihydroeudesma-4(15)-en-12,6α-olide (1) and 1ß,4α,8α-trihydroxy-11ß,13-dihydroeudesma-12,6α-olide (2), and an unprecedented elemane-type sesquiterpene lactone, 1ß,2ß,8α-trihydroxy-11ß,13-dihydroelema-12,6α-olide (3) along with a known eudesmanolide artapshin (4) were isolated from Seriphidium khorassanicum. Structures were elucidated by NMR, HR-ESI-MS, and ECD spectral data analysis. The anti-protozoal activity was evaluated against Leishmania major promastigotes and amastigote-infected macrophages. They showed dose- and time-dependent activity against L. major amastigotes with IC50 values in the range of 4.9 to 25.3 µM being favourably far below their toxicity against normal murine macrophages with CC50 values ranging from 432.5 to 620.7 µM after 48 h of treatment. Compound 3 exhibited the strongest activity and the highest selectivity index (SI) with IC50 of 4.9 ± 0.6 µM and SI of 88.2 comparable with the standard drug, meglumine antimoniate (Glucantime), with IC50 and SI values of 15.5 ± 2.1 µM and 40.0, respectively.

Phytochemical profiling of Striga asiatica; characterisation and anti-microbial assessment of the isolates.

One undescribed compound, striasinol (1), and twelve previously described compounds were isolated from the aerial parts of Striga asiatica. Structure elucidation of isolated compounds was achieved by the interpretation of 1D and 2D NMR and HRESIMS data. The absolute configuration (1S,5S) of 1 was ascertained based on GIAO NMR calculations, DP4+ probability analysis, and a comparison of the experimental and calculated specific rotation values. The isolated compounds were evaluated for their antimalarial action, and none was found to be effective against the chloroquine-sensitive (D6) or chloroquine-resistant (W2) strains of Plasmodium falciparum. The isolates were found non-toxic to the Vero cell line as well. Subsequent testing of these metabolites for antimicrobial activities against various bacterial and fungal strains (up to 20 µg/mL), revealed that compounds 6 (chryseriol) and 7 (apigenin) showed a reasonable activity towards methicillin-resistant Staphylococcus aureus ATCC 1708 (MRSA), with IC50 values of 5.81 and 3.60 µg/mL, respectively.

A novel nor-megastigmane from the leaves of Rhaphiostylis beninensis.

A novel nor-megastigmane, normegastigmane-5α,9-epoxy-3ß,8-diol (1), together with 10 known compounds of diverse classes including megastigmanes, sesquiterpenoids, and triterpenoids were isolated from the leaves of Rhaphiostylis beninensis. The structure of 1 was established by 1D and 2D NMR and HRESIMS data analysis. The known compounds were identified as 5,11-epoxy-3,9-megastigmanediol (2), 7-megastigmene-3,6,9-triol (3), 1,3-dihydroxypropan-2-yl stearate (4), (1E,5E)-1,5-dimethyl-8-(propan-2-ylidene)cyclodeca-1,5-diene germacrene (5) 3,5-dihyroxy-6,7-megastigmadien-9-one (6), squalene (7), ß-amyrin (8), ß-amyrone (9), ß-amyrin eicosanoate (10), and ß-sitosterol (11). Compounds 2, 3, and 6 displayed inhibitory effects on acetylcholinesterase enzyme. This is the first report of these compounds from the plant and their anticholinesterase activity.

Fatimanols Y and Z: two neo-clerodane diterpenoids from Teucrium yemense.

Teucrium yemense (Defl.), a medicinal plant, grows in Yemen and Saudi Arabia and is also referred to as Reehal Fatima. The plant has a long history of use in these regions for the treatment of diabetes, rheumatism, and renal conditions. Phytochemical investigation of the aerial parts of T. yemense yielded two previously undescribed neo-clerodane diterpenoids, namely fatimanols Y and Z (1 and 2) along with the known teulepicephin (3), 8-acetylharpagide (4) and teucardosid (5). Structure elucidation was accomplished from their 1D and 2D NMR, ECD, and MS characteristics as well as by comparing them to related reported compounds. The new molecules expand understanding of secondary metabolites of this genus. Compounds 1-5 did not show antimicrobial activity against various bacterial and fungal strains.

Flavonoid glycosides and ellagic acid cognates from defatted African mango (Irvingia gabonensis) seed kernel.

Seventeen compounds of diverse classes including four flavonoid glycosides, five ellagic acid derivatives, and eight other metabolites were isolated from the methanolic extract of the defatted seed kernel of Irvingia gabonensis. Among the isolates, quercetin 3-O-methyl-4'-[α-L-rhamnopyranosyl-(1→3)]-O-α-L-rhamnopyranoside (1) and 3,3'-di-O-methyl-4'-O-α-L-rhamnopyranosylellagic acid 4-sulfate ester (5) were found to be previously undescribed. Structure elucidation was mainly achieved by the interpretation of 1D and 2D NMR and HRESIMS spectral data. Though compound 6 was previously reported, its 13C NMR data is being reported herein for the first time. To the best of our literature search knowledge, this is the first phytochemical report on I. gabonensis seed kernels.

A combined experimental and computational chiroptical approach to establish the biosynthesis and absolute configuration of licochalcone L.

Often, chiral natural products exist as single stereoisomers; however, simultaneous occurrences of both enantiomers can exist in nature, resulting in scalemic or racemic mixtures. Ascertaining theabsolute configuration (AC) of natural products is pivotal for attributing their specific biological signature. Specific rotation data commonly characterize chiral non-racemic natural products; however, measurement conditions, viz., solvent and concentration, can influence the sign of specific rotation values, especially when characterizing natural products possessing small values. For example, licochalcone L, a minor constituent of Glycyrrhiza inflata, was reported with a specific rotation of [α]D22= +13 (c 0.1, CHCl3); however, not establishing the AC and the reported zero specific rotation for an identical compound, licochalcone AF1, resulted in debatable chirality and its biogenesis. In this study, a combined experimental and computational chiroptical approach involving specific rotation and electronic circular dichroism (ECD) data, supported by time-dependent density functional theory (TDDFT), were effectively utilized to establish the AC of licochalcone L as the (E, 2″S)-isomer. Establishing the 2″S absolute configuration permitted the conception of a reasonable biosynthetic pathway involving intramolecular '5-exo-tet' ring opening of a chiral oxirane to form chiral licochalcone L in G. inflata.

Cannabisol, a novel Δ9-THC dimer possessing a unique methylene bridge, isolated from Cannabis sativa.

Cannabisol (1), a unique dimer of Δ9-tetrahydrocannabinol (Δ9-THC) with a methylene bridge, was isolated from Cannabis sativa. This is the first example of a C-bridged dimeric cannabinoid. The structure of 1 was unambiguously deduced by HRESIMS, GCMS, and NMR spectroscopy. A plausible biogenesis of 1 is described.

Phytochemical analysis of Artemisia kopetdaghensis: Sesquiterpene lactones with proapoptotic activity against prostate cancer cells.

Phytochemical investigation of the aerial parts of Artemisia kopetdaghensis resulted in the isolation and characterization of three undescribed eudesmane-type sesquiterpene lactones, persianolide A, 4-epi-persianolide A, and 3α,4-epoxypersianolide A, together with three previously described eudesmane-type sesquiterpene lactones, 11-epi-artapshin, 1ß,8α-dihydroxy-11α,13-dihydrobalchanin, and 1ß-hydroxy-11-epi-colartin. The abundantly obtained 11-epi-artapshin was oxidized to undescribed 11α,13-dihydroeudesma-12,6α-olide-1,8-dione and 8ß-hydroxy-11α,13-dihydroeudesma-12,6α-olide-1-one and acetylated to the undescribed 1,8-O-diacetyl-11α,13-dihydroeudesma-12,6α-olide. Structures were elucidated based on extensive spectral data analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration was determined using calculated and experimental ECD spectral data. Compounds were subsequently subjected to the MTT assay to evaluate their cytotoxicity against prostate cancer cells (DU-145 and LNCaP). Related factors associated with the sequence of apoptosis were tested by ELISA, western blotting, and biochemical assay. Results suggested that 11-epi-artapshin hinders the growth of DU-145 cells through mitochondria-mediated apoptosis initiated by stimulation of ROS build-up, ΔΨm depletion, regulation of the Bax/Bcl-2 ratio, and activation of caspase 3, respectively.

Two undescribed paradol-related specialized metabolites from Aframomum melegueta.

Aframomum melegueta seeds are widely used as a spice in Africa. Two undescribed paradol-related compounds, (S)-9-hydroxy-[6]-paradol (1) and (9S)-3,9-dihydroxydihydro-[6]-paradol (2) together with eight reported constituents (3-10) were isolated and characterised from the methanol extract of A. melegueta seeds. Structure elucidation of these metabolites was achieved by means of NMR and mass spectroscopic data analyses. The absolute configuration of undescribed compounds (1 and 2) was determined using the modified Mosher's method.

In silico and in vitro studies of isolated constituents from Callistemon citrinus leaves: Anti-microbial potential and inhibition of iNOS activity.

Phytochemical investigation of Callistemon citrinus (Curtis) Skeels (syn. Callistemon lanceolatus (Sm.) Sweet and Melaleuca citrina (Curtis) Dum.Cours.) leaves resulted in the isolation of five undescribed compounds, including one acylphloroglucinol derivative and four monoterpene galloylglucosides, in addition to 29 known diverse secondary metabolites. Interestingly, this study reports chemosystematically significant isolation of the monoterpene galloylglucosides from the genus for the first time. Furthermore, exploration of the isolated compounds as inhibitors of inflammation-related molecular targets, molecular docking studies targeting human adipocyte lipid-binding protein FABP4 (3P6H) and human nitric oxide synthase (3E7G) were carried out in order with the in vitro evaluation of the isolated compounds for their anti-microbial and inhibitory of inducible nitric oxide synthase (iNOS) activities. Molecular docking studies revealed that eighteen compounds showed lower docking scores than ibuprofen, the native ligand in the crystal structure 3P6H, and nine compounds showed lower docking scores than AR-C95791, the native ligand in the binding site of 3E7G. Additionally, in vitro studies revealed that seven compounds showed moderate iNOS inhibitory activity. They also were moderately cytotoxic to HepG2, LLC-PK1 and Vero cells. Pulverulentone A showed moderate antibacterial activity against MRSA (IC50 22.2 µM) and antifungal activity against C. neoformans, while corosolic acid showed strong antibacterial activity against VRE (IC50 15.9 µM).Thus, the in silico and in vitro studies indicated that some isolated compounds hold potentials as inhibitors of iNOS activity and anti-microbial agents.

Norlignan glucosides from Hypoxis hemerocallidea and their potential in vitro anti-inflammatory activity via inhibition of iNOS and NF-κB.

Eleven diarylpentanoid/norlignan glucosides, along with five other specialized metabolites, were isolated and characterized from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. Hypoxhemerolosides A-F were found to be undescribed compounds. Curcapicycloside was isolated and identified for the first time in its original form, previously it was reported as a methylated derivative. In addition, (1S,2R)-1-(3,4-dihydroxyphenyl)-5-(4-ß-D-glucopyranoxy-3-hydroxyphenyl)-1-methoxypent-4-yn-2-ol and (1S,2R)-1-(3,4-dihydroxyphenyl)-1-ethoxy-5-(4-ß-D-glucopyranoxy-3-hydroxyphenyl)pent-4-yn-2-ol were isolated and characterized as artifacts, generated during extraction/isolation procedures from possible 1-(3,4-dihydroxyphenyl)-5-(4-ß-D-glucopyranoxy-3-hydroxyphenyl)pent-4-yne-1,2-diol. Structure elucidation was mainly achieved by the interpretation of 1D and 2D NMR and HRESIMS data. The isolated compounds were screened for anti-inflammatory activity in terms of iNOS and NF-κB inhibition as well as for cytotoxicity. Hypoxhemerolosides C-E and obtuside A moderately inhibited nitric oxide production in LPS-stimulated mouse macrophages (RAW 264.7).

Salvia ceratophylla L. from South of Jordan: new insights on chemical composition and biological activities.

In Jordan, Salvia ceratophylla L. is traditionally used in the treatment of cancer, microbial infections, and urinary disorders. This study aimed: (1) to chemically characterize S. ceratophylla essential oil (EO) from South Jordan, by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS); and (2) to evaluate in vitro the cytotoxic, anti-inflammatory, and antiprotozoal activities of the EO, it's predominant components, and the hexane (A), ethyl acetate (B), methanol (C) and crude-methanol extracts (D). The analysis revealed that the EO has 71 compounds, with linalool (54.8%) as main constituent. Only the hexane extract (A) showed some cytotoxic activity against SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells lines with IC50 between 60 and > 100 µg/mL. The EO inhibited NO production (IC50 90 µg/mL) and NF-κB activity (IC50 38 µg/mL). The extracts A, B, and D inhibited NO production and NF- κB activity with IC50 between 32 and 150 µg/mL. Linalool considerably inhibited NO production (IC50 18 µg/mL). The extracts tested did not exhibit antileishmanial activity. Regarding antitrypanosomal activity, the EO exhibited significant results with IC50 2.65 µg/mL. In conclusion, Jordan S. ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.

Analysis of prenylflavonoids from aerial parts of Epimedium grandiflorum and dietary supplements using HPTLC, UHPLC-PDA and UHPLC-QToF along with chemometric tools to differentiate Epimedium species.

An UHPLC method was developed for the determination of 15 prenylflavonoids from aerial parts of Epimedium grandiflorum and related species (Berberidaceae). The separation was achieved using a reverse phased column and water/acetonitrile gradient as a mobile phase at a temperature of 40°C. The developed analytical method was validated for linearity, limits of detection (LOD) and limits of quantification (LOQ), stability and repeatability. The LOD and LOQ were found to be in the range from 0.1-0.5 µg/mL and 0.3-1 µg/mL, respectively. The wavelength used for quantification with the photodiode array detector was 269 nm. The total content of 15 prenylflavonoids was 9.1-20.6 mg/g for E. grandiflorum (except for sample #2899 and #20862), 5.6-35.4 mg/g for E. brevicornu and 10.8-30.5 mg/g for E. sagittatum. Twenty dietary supplements contained in the range from 0.1 to 81.7 mg/day. The developed method is simple, rapid and especially suitable for quality assessment of E. grandiflorum and dietary supplements containing E. grandiflorum. Liquid chromatography quadrupole time-of-flight-mass spectrometry (LC-QToF) is described for the identification and confirmation of compounds in plant samples and dietary supplements. This technique is also used for chemical profiling of Epimedium samples. This method involved the use of protonated ions in the positive ion mode and deprotonated ions in the negative ion mode with extracted ion chromatogram (EIC). Chemometric analytical tools for visualizing the plant and commercial samples quality were used for discriminating between Epimedium species and dietary supplements with regards to the relative content or presence of components. A HPTLC method was also developed for the fast chemical fingerprint analysis of Epimedium species.

Isoquinoline alkaloids from Asimina triloba.

A new aporphine glycoside, (-)-anolobine-9-O-ß-D-glucopyranoside was isolated from the twigs of pawpaw (Asimina triloba) along with 7 known alkaloids including five aporphine alkaloids (anolobine, nornuciferine, norushinsunine, liriodenine, and lysicamine), a proaporhine alkaloid (stepharine), and a tetrahydrobenzylisoquinoline alkaloid (coclaurine). Among these compounds, nornuciferine, lysicamine, stepharine, and coclaurine are reported for the first time from this plant. The structure of the new compound was elucidated by spectroscopic methods, including 1 D, 2 D NMR, and HRESI-MS. The absolute configuration of compounds 1, 2, 7 and 8 was determined by CD experiment.