Lignans, amides, and saponins from Haplophyllum tuberculatum and their antiprotozoal activity

A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract of; Haplophyllum tuberculatum; exhibited appreciable bioactivity against; Leishmania donovani; . The antileishmanial activity was tracked by HPLC-based activity profiling, and eight compounds were isolated from the chloroform fraction. These included lignans tetrahydrofuroguaiacin B (; 1; ), nectandrin B (; 2; ), furoguaiaoxidin (; 7; ), and 3,3'-dimethoxy-4,4'-dihydroxylignan-9-ol (; 10; ), and four cinnamoylphenethyl amides, namely dihydro-feruloyltyramine (; 5; ), (; E; )-; N; -feruloyltyramine (; 6; ),; N; ,; N; '-diferuloylputrescine (; 8; ), and 7'-ethoxy-feruloyltyramine (; 9; ). The water fraction yielded steroid saponins; 11; -; 13; . Compounds; 1; ,; 2; , and; 5; -; 13; are reported for the first time from; Haplophyllum; species and the family Rutaceae. The antiprotozoal activity of the compounds plus two stereoisomeric tetrahydrofuran lignans-fragransin B; 2; (; 3; ) and fragransin B; 1; (; 4; )-was determined against; Leishmania donovani; amastigotes,; Plasmodium falciparum,; and; Trypanosoma brucei rhodesiense; bloodstream forms, along with their cytotoxicity to rat myoblast L6 cells. Nectandrin B (; 2; ) exhibited the highest activity against; L. donovani; (IC; 50; 4.5 µM) and the highest selectivity index (25.5)

Clerodane diterpenes from casearia corymbosa as allosteric GABAA receptor modulators

An EtOAc extract of Casearia corymbosa leaves led to an allosteric potentiation of the GABA signal in a fluorometric imaging plate reader (FLIPR) assay on Chinese hamster ovary (CHO) cells stably expressing GABAA receptors with an α1β2γ2 subunit composition. The activity was tracked by HPLC-based activity profiling, and four known (2, 3, 4, and 8) and five new clerodane-type diterpenoids (1, 5−7, and 9) were isolated. Compounds 1−8 were obtained from the active time window. The absolute configuration of all compounds was established by ECD. Compounds 3, 7, and 8 exhibited EC50 values of 0.5, 4.6, and 1.4 μM, respectively. To explore possible binding sites at the receptor, the most abundant diterpenoid 8 was tested in combination with diazepam, etazolate, and allopregnanolone. An additive potentiation of the GABA signal was observed with these compounds, while the effect of 8 was not inhibited by flumazenil, a negative allosteric modulator at the benzodiazepine binding site. Finally, the activity was validated in voltage clamp studies on Xenopus laevis oocytes transiently expressing GABAA receptors of the α1β2γ2S and α1β2 subtypes. Compound 8 potentiated GABA-induced currents with both receptor subunit compositions [EC50 (α1β2γ2S) = 43.6 μM; Emax = 809% and EC50 (α1β2) = 57.6 μM; Emax = 534%]. The positive modulation of GABA-induced currents was not inhibited by flumazenil, thereby confirming an allosteric modulation independent of the benzodiazepine binding site

Ingadosides A-C, acacic acid-type saponins from Inga sapindoides with potent inhibitory activity against grapevine downy mildew as potential alternatives to copper fungicides

The reduction of copper-based fungicides has a high priority in European policy as well as in organic agriculture. To successfully reduce copper use, preventive strategies have to be fully implemented, and several substitution products need to be brought to the market. Plantderived plant protection products could provide sustainable and environmentally friendly alternatives. As part of a project aiming at the discovery of such new products, we screened a library of more than 3000 plant extracts against important plant pathogens. One of the extracts with promising activity against grapevine downy mildew (Plasmopara viticola) was an 96% ethanolic extract from the leaves of Inga sapindoides (in vitro MIC100 25 μg/mL). On grapevine plantlets under controlled conditions, compared to non-treated plants, the I.sapindoides ethanolic extract reduced grapevine downy mildew by 96%-97% at 0.5 mg/mL, and its efficacy was comparable to a standard copper treatment (two independent experiments). Targeted isolation of the active constituents resulted in the characterization of three acacic acid-type bidesmosidic saponins with high antifungal activity (in vitro MIC100 values of 3 - 6 μg/mL). I. sapindoides, a tree which is often cultivated for shading coffee plantations in Central America, may represent a sustainable source of fungicidal products to be used in the replacement of copper

Extraction of natural analgesic compounds from plants used in traditional medicine in Mali

Le travail présenté dans ce manuscrit porte sur l’isolation de métabolites secondaires de plantes utilisées en médecine traditionnelle au Mali. Après avoir réalisé une enquête ethnopharmacologique, mis en parallèle avec la littérature, trois plantes ont été sélectionnées pour être étudiées : Cassia sieberiana DC., Vitex madiensis Oliv. et Pericopsis laxiflora (Benth.) Meeuwen. L’activité analgésique des extraits aqueux et méthanoliques de ces plantes ont été évaluées. Les résultats nous ont mené à conduire un fractionnement bio-guidé des extraits méthanoliques de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen. Huit composés ont été isolés à partir de fractions de l’extrait méthanolique de Cassia sieberiana DC., parmi lesquels quatre nouvelles molécules et trois nouveaux stéréoisomères ont été identifiés. Onze composés ont été isolés à partir de fractions de l’extrait méthanolique de Pericopsis laxiflora (Benth.) Meeuwen. Ce travail de recherche a permis d’approfondir nos connaissances sur la composition chimique de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen et leur potentielle activité antalgique.The present work deals with the isolation of analgesic secondary metabolites from plants used in traditional medicine in Mali. After conducting an ethnopharmacological study and comparing it with the literature, three plants were selected to be studied: Cassia sieberiana DC., Vitex madiensis Oliv. And Pericopsis laxiflora (Benth.) Meeuwen. The analgesic activity of their aqueous and methanolic extracts were screened. Results lead us to realise a bioguided partitionning on the methanolic extracts of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen. Eight coumpounds were isolated from analgesic fractions of methanolic extract of Cassia sieberiana DC., among which four new compounds and three new stereoisomers were identified. Eleven coumpounds were isolated from analgesic fractions of methanolic extract of Pericopsis laxiflora (Benth.) Meeuwen. This research work allowed us to deepen our knowledge about the chemical composition of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen and their potential analgesic activity

Extraction de substances naturelles antalgiques à partir de plantes utilisées dans la pharmacopée traditionnelle au Mali

The present work deals with the isolation of analgesic secondary metabolites from plants used in traditional medicine in Mali. After conducting an ethnopharmacological study and comparing it with the literature, three plants were selected to be studied: Cassia sieberiana DC., Vitex madiensis Oliv. And Pericopsis laxiflora (Benth.) Meeuwen. The analgesic activity of their aqueous and methanolic extracts were screened. Results lead us to realise a bioguided partitionning on the methanolic extracts of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen. Eight coumpounds were isolated from analgesic fractions of methanolic extract of Cassia sieberiana DC., among which four new compounds and three new stereoisomers were identified. Eleven coumpounds were isolated from analgesic fractions of methanolic extract of Pericopsis laxiflora (Benth.) Meeuwen. This research work allowed us to deepen our knowledge about the chemical composition of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen and their potential analgesic activity.Le travail présenté dans ce manuscrit porte sur l’isolation de métabolites secondaires de plantes utilisées en médecine traditionnelle au Mali. Après avoir réalisé une enquête ethnopharmacologique, mis en parallèle avec la littérature, trois plantes ont été sélectionnées pour être étudiées : Cassia sieberiana DC., Vitex madiensis Oliv. et Pericopsis laxiflora (Benth.) Meeuwen. L’activité analgésique des extraits aqueux et méthanoliques de ces plantes ont été évaluées. Les résultats nous ont mené à conduire un fractionnement bio-guidé des extraits méthanoliques de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen. Huit composés ont été isolés à partir de fractions de l’extrait méthanolique de Cassia sieberiana DC., parmi lesquels quatre nouvelles molécules et trois nouveaux stéréoisomères ont été identifiés. Onze composés ont été isolés à partir de fractions de l’extrait méthanolique de Pericopsis laxiflora (Benth.) Meeuwen. Ce travail de recherche a permis d’approfondir nos connaissances sur la composition chimique de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen et leur potentielle activité antalgique

Extraction of natural analgesic compounds from plants used in traditional medicine in Mali

Le travail présenté dans ce manuscrit porte sur l’isolation de métabolites secondaires de plantes utilisées en médecine traditionnelle au Mali. Après avoir réalisé une enquête ethnopharmacologique, mis en parallèle avec la littérature, trois plantes ont été sélectionnées pour être étudiées : Cassia sieberiana DC., Vitex madiensis Oliv. et Pericopsis laxiflora (Benth.) Meeuwen. L’activité analgésique des extraits aqueux et méthanoliques de ces plantes ont été évaluées. Les résultats nous ont mené à conduire un fractionnement bio-guidé des extraits méthanoliques de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen. Huit composés ont été isolés à partir de fractions de l’extrait méthanolique de Cassia sieberiana DC., parmi lesquels quatre nouvelles molécules et trois nouveaux stéréoisomères ont été identifiés. Onze composés ont été isolés à partir de fractions de l’extrait méthanolique de Pericopsis laxiflora (Benth.) Meeuwen. Ce travail de recherche a permis d’approfondir nos connaissances sur la composition chimique de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen et leur potentielle activité antalgique.The present work deals with the isolation of analgesic secondary metabolites from plants used in traditional medicine in Mali. After conducting an ethnopharmacological study and comparing it with the literature, three plants were selected to be studied: Cassia sieberiana DC., Vitex madiensis Oliv. And Pericopsis laxiflora (Benth.) Meeuwen. The analgesic activity of their aqueous and methanolic extracts were screened. Results lead us to realise a bioguided partitionning on the methanolic extracts of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen. Eight coumpounds were isolated from analgesic fractions of methanolic extract of Cassia sieberiana DC., among which four new compounds and three new stereoisomers were identified. Eleven coumpounds were isolated from analgesic fractions of methanolic extract of Pericopsis laxiflora (Benth.) Meeuwen. This research work allowed us to deepen our knowledge about the chemical composition of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen and their potential analgesic activity

Machine Learning-Based Analysis Reveals Triterpene Saponins and Their Aglycones in Cimicifuga racemosa as Critical Mediators of AMPK Activation.

Cimicifuga racemosa (CR) extracts contain diverse constituents such as saponins. These saponins, which act as a defense against herbivores and pathogens also show promise in treating human conditions such as heart failure, pain, hypercholesterolemia, cancer, and inflammation. Some of these effects are mediated by activating AMP-dependent protein kinase (AMPK). Therefore, comprehensive screening for activating constituents in a CR extract is highly desirable. Employing machine learning (ML) techniques such as Deep Neural Networks (DNN), Logistic Regression Classification (LRC), and Random Forest Classification (RFC) with molecular fingerprint MACCS descriptors, 95 CR constituents were classified. Calibration involved 50 randomly chosen positive and negative controls. LRC achieved the highest overall test accuracy (90.2%), but DNN and RFC surpassed it in precision, sensitivity, specificity, and ROC AUC. All CR constituents were predicted as activators, except for three non-triterpene compounds. The validity of these classifications was supported by good calibration, with misclassifications ranging from 3% to 17% across the various models. High sensitivity (84.5-87.2%) and specificity (84.1-91.4%) suggest suitability for screening. The results demonstrate the potential of triterpene saponins and aglycones in activating AMP-dependent protein kinase (AMPK), providing the rationale for further clinical exploration of CR extracts in metabolic pathway-related conditions

Phylobioactive hotspots in plant resources used to treat Chagas disease.

Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses

Bitter taste impact and thermal conversion of a naringenin glycoside isolated from Cyclopia genistoides

A naringenin derivative, isolated from Cyclopia genistoides, a bitter tasting herbal tea, especially when in green (unoxidized) form, was identified as (2S)-5-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyloxy]naringenin (1). The compound partially epimerizes to (2R)-5-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyloxy]naringenin (2) when heated at different temperatures (80, 90, 100, 110, and 120 °C) for a prolonged period in a phosphate buffer at pH 5. The fractional conversion model predicted the decrease in the concentration of compound 1 the best. The activation energy of the conversion reaction was calculated as 99.16 kJ mol–1. Prolonged heating resulted not only in formation of compound 2 but eventually a decrease in its concentration and the formation of another conversion product, (E)-2′-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyloxy]-4′,6′,4-trihydroxychalcone (3). In contrast, naringin, glycosylated at C-7, remained stable when heated under the same conditions (100 °C for 6 h at pH 5). The bitter intensity of compound 1 was substantially less than that of naringin, both tested at 0.04 mM, a concentration typical of compound 1 in an herbal tea infusion of green C. genistoides. This comparison indicates that the position of the sugar moiety plays an important role in determining both bitter intensity and heat stability of naringenin glycosides

HPLC-based activity profiling for antiprotozoal compounds in Croton zambesicus and Cuscuta hyalina

In a screening of Sudanese medicinal plants for antiprotozoal activity, the chloroform fractions obtained by liquid-liquid partitioning from ethanolic extracts of fruits of; Croton gratissimus; var.; gratissimus; and stems of; Cuscuta hyalina; Roth ex Schult. exhibited; in vitro; activity against axenically grown; Leishmania donovani; amastigotes. This antileishmanial activity was localized by HPLC-based activity profiling. Targeted preparative isolation afforded flavonoids; 1; -; 6; , 3-methoxy-4-hydroxybenzoic acid (; 7; ), and benzyltetrahydroisoquinoline alkaloids laudanine (; 8; ) and laudanosine (; 9; ) from; C. gratissimus; , and pinoresinol (; 10; ), isorhamnetin (; 11; ), (-)-pseudosemiglabrin (; 12; ), and kaempferol (; 13; ) from; C. hyalina.; The antiprotozoal activity of; 1; -; 13; against; L. donovani; (axenic and intracellular amastigotes),; Trypanosoma brucei rhodesiense; (bloodstream forms), and; Plasmodium falciparum; (erythrocytic stages), and the cytotoxicity in L6 murine myoblast cells were determined; in vitro; . Quercetin-3,7-dimethylether (; 6; ) showed the highest activity against axenic; L. donovani; (IC; 50,; 4.5 µM; selectivity index [SI], 12.3),; P. falciparum; (IC; 50,; 7.3 µM; SI, 7.6), and; T. b. rhodesiense; (IC; 50; , 2.4 µM; SI, 23.2). The congener ayanin (; 2; ) exhibited moderate antileishmanial (IC; 50; , 8.2 µM; SI, 12.2), antiplasmodial (IC; 50; , 7.8 µM; SI, 12.9), and antitrypanosomal activity (IC; 50; , 11.2 µM; SI, 8.9). None of the compounds showed notable activity against the intramacrophage form of; L. donovani;