Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese Göttingen Minipigs.

BACKGROUND: Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs. METHODS: Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design. RESULTS: Bitter gourd fruit from the cultivars "Palee" and "Good healthy" reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 µmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars "Palee" (>3.9-fold) and "Good healthy" (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar "Bilai" increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs. CONCLUSIONS: Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.

Comparison of extraction methods in vitro Plasmodium falciparum: A 1H NMR and LC-MS joined approach.

Malaria is a parasitic disease that remains a global concern and the subject of many studies. Metabolomics has emerged as an approach to better comprehend complex pathogens and discover possible drug targets, thus giving new insights that can aid in the development of antimalarial therapies. However, there is no standardized method to extract metabolites from in vitro Plasmodium falciparum intraerythrocytic parasites, the stage that causes malaria. Additionally, most methods are developed with either LC-MS or NMR analysis in mind, and have rarely been evaluated with both tools. In this work, three extraction methods frequently found in the literature were reproduced and samples were analyzed through both LC-MS and 1H NMR, and evaluated in order to reveal which is the most repeatable and consistent through an array of different tools, including chemometrics, peak detection and annotation. The most reliable method in this study proved to be a double extraction with methanol and methanol/water (80:20, v/v). Metabolomic studies in the field should move towards standardization of methodologies and the use of both LC-MS and 1H NMR in order to make data more comparable between studies and facilitate the achievement of biologically interpretable information.

Cytotoxic Metabolites from Calophyllum tacamahaca Willd.: Isolation and Detection through Feature-Based Molecular Networking.

Isocaloteysmannic acid (1), a new chromanone, was isolated from the leaf extract of the medicinal species Calophyllum tacamahaca Willd. along with 13 known metabolites belonging to the families of biflavonoids (2), xanthones (3-5, 10), coumarins (6-8) and triterpenes (9, 11-14). The structure of the new compound was characterized based on nuclear magnetic resonance (NMR), high-resolution electrospray mass spectrometry (HRESIMS), ultraviolet (UV) and infrared (IR) data. Its absolute configuration was assigned through electronic circular dichroism (ECD) measurements. Compound (1) showed a moderate cytotoxicity against HepG2 and HT29 cell lines, with IC50 values of 19.65 and 25.68 µg/mL, respectively, according to the Red Dye method. Compounds 7, 8 and 10-13 exhibited a potent cytotoxic activity, with IC50 values ranging from 2.44 to 15.38 µg/mL, against one or both cell lines. A feature-based molecular networking (FBMN) approach led to the detection of a large amount of xanthones in the leaves extract, and particularly analogues of the cytotoxic isolated xanthone pyranojacareubin (10).

Secondary Metabolites Isolated from Artemisia afra and Artemisia annua and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties-Pharmacokinetics and Pharmacodynamics: A Review.

There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.

Prioritization of Microorganisms Isolated from the Indian Ocean Sponge Scopalina hapalia Based on Metabolomic Diversity and Biological Activity for the Discovery of Natural Products.

Despite considerable advances in medicine and technology, humanity still faces many deadly diseases such as cancer and malaria. In order to find appropriate treatments, the discovery of new bioactive substances is essential. Therefore, research is now turning to less frequently explored habitats with exceptional biodiversity such as the marine environment. Many studies have demonstrated the therapeutic potential of bioactive compounds from marine macro- and microorganisms. In this study, nine microbial strains isolated from an Indian Ocean sponge, Scopalina hapalia, were screened for their chemical potential. The isolates belong to different phyla, some of which are already known for their production of secondary metabolites, such as the actinobacteria. This article aims at describing the selection method used to identify the most promising microorganisms in the field of active metabolites production. The method is based on the combination of their biological and chemical screening, coupled with the use of bioinformatic tools. The dereplication of microbial extracts and the creation of a molecular network revealed the presence of known bioactive molecules such as staurosporin, erythromycin and chaetoglobosins. Molecular network exploration indicated the possible presence of novel compounds in clusters of interest. The biological activities targeted in the study were cytotoxicity against the HCT-116 and MDA-MB-231 cell lines and antiplasmodial activity against Plasmodium falciparum 3D7. Chaetomium globosum SH-123 and Salinispora arenicola SH-78 strains actually showed remarkable cytotoxic and antiplasmodial activities, while Micromonospora fluostatini SH-82 demonstrated promising antiplasmodial effects. The ranking of the microorganisms as a result of the different screening steps allowed the selection of a promising strain, Micromonospora fluostatini SH-82, as a premium candidate for the discovery of new drugs.

Bioactive Clerodane Diterpenoids from the Leaves of Casearia coriacea Vent.

Casearia coriacea Vent., an endemic plant from the Mascarene Islands, was investigated following its antiplasmodial potentialities highlighted during a previous screening. Three clerodane diterpene compounds were isolated and identified as being responsible for the antiplasmodial activity of the leaves of the plant: caseamembrin T (1), corybulosin I (2), and isocaseamembrin E (3), which exhibited half maximal inhibitory concentrations (IC50) of 0.25 to 0.51 µg/mL. These compounds were tested on two other parasites, Leishmania mexicana mexicana and Trypanosoma brucei brucei, to identify possible selectivity in one of them. Although these products possess both antileishmanial and antitrypanosomal properties, they displayed selectivity for the malaria parasite, with a selectivity index between 6 and 12 regarding antitrypanosomal activity and between 25 and 100 regarding antileishmanial activity. These compounds were tested on three cell lines, breast cancer cells MDA-MB-231, pulmonary adenocarcinoma cells A549, and pancreatic carcinoma cells PANC-1, to evaluate their selectivity towards Plasmodium. This has not enabled us to establish selectivity for Plasmodium, but has revealed the promising activity of compounds 1-3 (IC50 < 2 µg/mL), particularly against pancreatic carcinoma cells (IC50 < 1 µg/mL). The toxicity of the main compound, caseamembrin T (1), was then evaluated on zebrafish embryos to extend our cytotoxicity study to normal, non-cancerous cells. This highlighted the non-negligible toxicity of caseamembrin T (1).

OSMAC Method to Assess Impact of Culture Parameters on Metabolomic Diversity and Biological Activity of Marine-Derived Actinobacteria.

Actinobacteria are known for their production of bioactive specialized metabolites, but they are still under-exploited. This study uses the "One Strain Many Compounds" (OSMAC) method to explore the potential of three preselected marine-derived actinobacteria: Salinispora arenicola (SH-78) and two Micromonospora sp. strains (SH-82 and SH-57). Various parameters, including the duration of the culture and the nature of the growth medium, were modified to assess their impact on the production of specialized metabolites. This approach involved a characterization based on chemical analysis completed with the construction of molecular networks and biological testing to evaluate cytotoxic and antiplasmodial activities. The results indicated that the influence of culture parameters depended on the studied species and also varied in relation with the microbial metabolites targeted. However, common favorable parameters could be observed for all strains such as an increase in the duration of the culture or the use of the A1 medium. For Micromonospora sp. SH-82, the solid A1 medium culture over 21 days favored a greater chemical diversity. A rise in the antiplasmodial activity was observed with this culture duration, with a IC50 twice as low as for the 14-day culture. Micromonospora sp. SH-57 produced more diverse natural products in liquid culture, with approximately 54% of nodes from the molecular network specifically linked to the type of culture support. Enhanced biological activities were also observed with specific sets of parameters. Finally, for Salinispora arenicola SH-78, liquid culture allowed a greater diversity of metabolites, but intensity variations were specifically observed for some metabolites under other conditions. Notably, compounds related to staurosporine were more abundant in solid culture. Consequently, in the range of the chosen parameters, optimal conditions to enhance metabolic diversity and biological activities in these three marine-derived actinobacteria were identified, paving the way for future isolation works.

Recent metabolomic developments for antimalarial drug discovery.

Malaria is a parasitic disease that remains a global health issue, responsible for a significant death and morbidity toll. Various factors have impacted the use and delayed the development of antimalarial therapies, such as the associated financial cost and parasitic resistance. In order to discover new drugs and validate parasitic targets, a powerful omics tool, metabolomics, emerged as a reliable approach. However, as a fairly recent method in malaria, new findings are timely and original practices emerge frequently. This review aims to discuss recent research towards the development of new metabolomic methods in the context of uncovering antiplasmodial mechanisms of action in vitro and to point out innovative metabolic pathways that can revitalize the antimalarial pipeline.

Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks.

Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.

Exploration by molecular networking of Strychnos alkaloids reveals the unexpected occurrence of strychnine in seven Strychnos species.

INTRODUCTION: Plants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. OBJECTIVE: Investigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. MATERIAL AND METHODS: Twenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. RESULTS: Further analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. CONCLUSION: This work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.

Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.

BACKGROUND: Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (also known as sleeping sickness), a disease causing serious neurological disorders and fatal if left untreated. Due to its lethal pathogenicity, a variety of treatments have been developed over the years, but which have some important limitations such as acute toxicity and parasite resistance. Metabolomics is an innovative tool used to better understand the parasite's cellular metabolism, and identify new potential targets, modes of action and resistance mechanisms. The metabolomic approach is mainly associated with robust analytical techniques, such as NMR and Mass Spectrometry. Applying these tools to the trypanosome parasite is, thus, useful for providing new insights into the sleeping sickness pathology and guidance towards innovative treatments. AIM OF REVIEW: The present review aims to comprehensively describe the T. brucei biology and identify targets for new or commercialized antitrypanosomal drugs. Recent metabolomic applications to provide a deeper knowledge about the mechanisms of action of drugs or potential drugs against T. brucei are highlighted. Additionally, the advantages of metabolomics, alone or combined with other methods, are discussed. KEY SCIENTIFIC CONCEPTS OF REVIEW: Compared to other parasites, only few studies employing metabolomics have to date been reported on Trypanosoma brucei. Published metabolic studies, treatments and modes of action are discussed. The main interest is to evaluate the metabolomics contribution to the understanding of T. brucei's metabolism.

Bioassay-guided isolation of vilasinin-type limonoids and phenyl alkene from the leaves of Trichilia gilgiana and their antiplasmodial activities.

Bioassay-guided fractionation of the CH2Cl2-MeOH (1:1) leaves extract of Trichilia gilgiana, yielded two new vilasinin-type limonoids named gilgianin A (1) and gilgianin B (2), one new phenyl alkene derivative designated as gilgialkene A (3), along with six known compounds: rubescin H (4), TS3 (5), trichirubine A (6), sitosteryl-6'-O-undecanoate-ß-D-glucoside (7), scopoletin (8), and octadecane-2-one (9). Their structures were elucidated based on spectroscopic analysis and comparison with literature data. Compounds 5 and 6 exhibited the highest antiplasmodial activity with IC50 values of 1.14 and 1.32 µM respectively. Moreover, compound 5 was very cytotoxic with CC50 value of 0.88 µM, compared to compound 6, which was not cytotoxic (CC50 > 10 µg/mL). Compounds 1 (IC50 = 9.84 µM), 2 (IC50 = 11.04 µM) and 4 (IC50 = 10.71 µM) presented good antiplasmodial activity while also exhibiting significant cytotoxicity, with CC50 values ranging from of 14.45 to 29.7 µM.[Formula: see text].

Cytotoxicity of Poupartone B, an Alkyl Cyclohexenone Derivative from Poupartia borbonica, against Human Cancer Cell Lines.

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A - C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp., high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 - 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed.

Pentas longiflora Oliv. (Rubiaceae), a plant used in the treatment of Pityriasis Versicolor in Rwanda: Chemical composition and standardization of leaves and roots.

In Rwanda, the roots of Pentas longiflora Oliv. (Rubiaceae) have been used for a long time to treat Pityriasis versicolor. However, many people reported the use of leaves instead of roots. This research was conducted to compare the phytochemical composition and establish chromatographic methods for the standardization of roots and leaves extracts of P. longiflora. During this process, three new pentalongin glycosides (pentalonginoside A, pentalonginoside B, and pentalonginoside C) and two known glycosides of the same type (harounoside and clarinoside), as well as rutin, luteolin-7-rutinoside were isolated from methanol extract of leaves. In addition, pentalongin and psychorubrin, previously isolated from ethylacetate roots extract, were also identified in Pentas longiflora ethylacetate leaves extract. The presence of the antifungal compound pentalongin in leaves may explain the traditional use of leaves in the treatment of Pytiriasis versicolor. Furthermore, harounoside, psychorubrin, and pentalongin were selected as markers for HPLC fingerprints of MeOH extract. The accuracy and risk profile demonstrated the reliability of the validated method. In general, considerable variations of concentration in plant metabolites, including pentalongin, were observed between samples from different sites. The content in pentalongin (expressed as juglone) in collected samples ranged between 1.7 and 70.0 mg/100 g. The highest concentration (70.0 ± 17 mg/100 g) was registered in the cultivated samples from Mukoni. This important variation of pentalongin concentrations according to sampling sites, shows that in order to guarantee equivalent efficacy, finished products with P. longiflora should be standardized based on their pentalongin content.

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae).

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.

Phytochemical Investigation and Biological Activities of Lantana rhodesiensis.

Lantana rhodesiensis Moldenke is a plant widely used to treat diseases, such as rheumatism, diabetes, and malaria in traditional medicine. To better understand the traditional uses of this plant, a phytochemical study was undertaken, revealing a higher proportion of polyphenols, including flavonoids in L. rhodesiensis leaf extract and moderate proportion in stem and root extracts. The antioxidant activity of the extracts was also determined using three different assays: the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, the FRAP method (Ferric-reducing antioxidant power) and the ß-carotene bleaching test. The anti-malarial activity of each extract was also evaluated using asexual erythrocyte stages of Plasmodium falciparum, chloroquine-sensitive strain 3D7. The results showed that the leaf extract exhibited higher antioxidant and anti-malarial activities in comparison with the stem and root extracts, probably due to the presence of higher quantities of polyphenols including flavonoids in the leaves. A positive linear correlation was established between the phenolic compound content (total polyphenols including flavonoids and tannins; and total flavonoids) and the antioxidant activity of all extracts. Furthermore, four flavones were isolated from leaf dichloromethane and ethyl acetate fractions: a new flavone named rhodescine (5,6,3',5'-tetrahydroxy-7,4'-dimethoxyflavone) (1), 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (2), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (3), and 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (4). Their structures were elucidated by 1H, 13CNMR, COSY, HSQC, HMBC, and MS-EI spectral methods. Aside from compound 2, all other molecules were described for the first time in this plant species.

The Inhibition of NLRP3 Inflammasome and IL-6 Production by Hibiscus noldeae Baker f. Derived Constituents Provides a Link to Its Anti-Inflammatory Therapeutic Potentials.

The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1ß (IL-1ß) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1ß and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1ß and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.

Seasonal Effect on the Chemical Composition, Insecticidal Properties and Other Biological Activities of Zanthoxylum leprieurii Guill. & Perr. Essential oils.

This study focused, for the first time, on the evaluation of the seasonal effect on the chemical composition and biological activities of essential oils hydrodistillated from leaves, trunk bark and fruits of Zanthoxylum leprieurii (Z. leprieurii), a traditional medicinal wild plant growing in Côte d'Ivoire. The essential oils were obtained by hydrodistillation from fresh organs of Z. leprieurii growing on the same site over several months using a Clevenger-type apparatus and analyzed by gas chromatography-mass spectrometry (GC/MS). Leaf essential oils were dominated by tridecan-2-one (9.00 ± 0.02-36.80 ± 0.06%), (E)-ß-ocimene (1.30 ± 0.50-23.57 ± 0.47%), ß-caryophyllene (7.00 ± 1.02-19.85 ± 0.48%), dendrolasin (1.79 ± 0.08-16.40 ± 0.85%) and undecan-2-one (1.20 ± 0.03-8.51 ± 0.35%). Fruit essential oils were rich in ß-myrcene (16.40 ± 0.91-48.27 ± 0.26%), citronellol (1.90 ± 0.02-28.24 ± 0.10%) and geranial (5.30 ± 0.53-12.50 ± 0.47%). Tridecan-2-one (45.26 ± 0.96-78.80 ± 0.55%), ß-caryophyllene (1.80 ± 0.23-13.20 ± 0.33%), ?-humulene (4.30 ±1.09-12.73 ± 1.41%) and tridecan-2-ol (2.23 ± 0.17-10.10 ± 0.61%) were identified as major components of trunk bark oils. Statistical analyses of essential oil compositions showed that the variability mainly comes from the organs. Indeed, principal component analysis (PCA) and hierarchical cluster analysis (HCA) allowed us to cluster the samples into three groups, each one consisting of one different Z. leprieurii organ, showing that essential oils hydrodistillated from the different organs do not display the same chemical composition. However, significant differences in essential oil compositions for the same organ were highlighted during the studied period, showing the impact of the seasonal effect on essential oil compositions. Biological activities of the produced essential oils were also investigated. Essential oils exhibited high insecticidal activities against Sitophilus granarius, as well as antioxidant, anti-inflammatory and moderate anti-plasmodial properties.