The ethnopharmacological study of plant drugs used traditionally in Djibouti for malaria treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Djibouti was a country where malaria has been endemic for centuries. The local population use the plants as repellents or first aid for uncomplicated malaria. AIM OF THE STUDY: The aim was, for the first time, to collect and identify plants used by the local population to treat malaria and select the most interesting plants (those that are more commontly used, more available, and have fewer studies). These plants were evaluated for their antiplasmodial activity as well as their cytotoxicity on human cell lines for the most active ones. MATERIALS AND METHODS: A semi-structured questionnaire was developed for this study to collect information about the use and identity of botanical drugs used to treat malaria. The use-reports (percentage) of each plant were recorded to determine their use importance. Also, the availability status of the plants was assessed; and those in critical condition were discarded excluded from further study. Fifteen plants, out of the 41 listed, were extracted with hydro alcohol, ethyl acetate, and dichloromethane for biological testing. Chloroquine-resistant strain FcB-1 of P. falciparum and a human diploid embryonic lung cell line were used for the antiplasmodial test, and to assess the cytotoxicity for human cells respectively. Preliminary analysis of extract constituents was carried out using thin layer chromatography (TLC). RESULTS: This study identifies 41 plant taxa belonging to 32 families and records their use against malaria. Balanites rodunfolia, belonging to the Zygophyllaceae family, was the most commonly used plant, representing 44 % of use-reports. It was followed by Cadaba rodunfolia (15 %) from the Capparaceae family, and then the three species of Aloe: Aloe djiboutiensis (8.2 %), Aloe ericahenriettae (3.4 %), and Aloe rigens (3.4 %) from the Asphodelaceae family. The leaves are the most commonly used part of the plants to treat malaria, accounting for 76 % of usage. The preparation methods were decoction (52 %), maceration (29 %), and boiling (19 %). The administration routes were by oral (80 %), inhalation 19 %), and bathing (1 %). The best antiplasmodial activities were observed in the dichloromethane extracts of Cymbopogon commutatus and the ethyl acetate extracts of Aloe rigens and Terminalia brownii, with IC50 values of 9.8, 5, and 7.5 µg/mL, respectively. Their toxicity/activity levels were very favorable with selectivity indices of 5.6, 8.1, and 11.8 for C. commutatus, A. rigens, and T. Brownii, respectively. CONCLUSION: Forty-one species of botanical drugs were listed as being used to treat malaria in Djibouti. All fifteen selected species showed antiplasmodial activity (IC50 < 50 µg/mL). This work will help guide the valorization of botanical drugs used to treat malaria in Djibouti.

Role of MicroRNAs in Inflammatory Joint Diseases: A Review.

Inflammatory arthritis commonly initiates in the soft tissues lining the joint. This lining swells, as do the cells in it and inside the joint fluid, producing chemicals that induce inflammation signs such as heat, redness, and swelling. MicroRNA (miRNA), a subset of non-coding small RNA molecules, post-transcriptionally controls gene expression by targeting their messenger RNA. MiRNAs modulate approximately 1/3 of the human genome with their multiple targets. Recently, they have been extensively studied as key modulators of the innate and adaptive immune systems in diseases such as allergic disorders, types of cancer, and cardiovascular diseases. However, research on the different inflammatory joint diseases, such as rheumatoid arthritis, gout, Lyme disease, ankylosing spondylitis, and psoriatic arthritis, remains in its infancy. This review presents a deeper understanding of miRNA biogenesis and the functions of miRNAs in modulating the immune and inflammatory responses in the above-mentioned inflammatory joint diseases. According to the literature, it has been demonstrated that the development of inflammatory joint disorders is closely related to different miRNAs and their specific regulatory mechanisms. Furthermore, they may present as possible prognostic and diagnostic biomarkers for all diseases and may help in developing a therapeutic response. However, further studies are needed to determine whether manipulating miRNAs can influence the development and progression of inflammatory joint disorders.

In vitro and in silico analysis for elucidation of antioxidant potential of Djiboutian Avicennia Marina (Forsk.) Vierh. phytochemicals.

The present work aims to study the phytochemical composition, the antioxidant capacity of the crude extracts, and the fraction of extract giving the best antioxidant activity of Avicennia marina. The leaves contain high TFC compared to other parts of the plant, whereas fruits have the highest amount of TPC. Fat-soluble pigments are strongly present in the leaves of Avicennia marina i.e. ß-carotene, lycopene, chlorophyll a, and chlorophyll b. The crude methanolic flower extracts showed strong DPPH and ABTS radical scavenging activity with IC50 values of 0.30 and 0.33 mg/mL respectively compared to the leaf and stem methanolic extracts for the DPPH and ABTS models with a value IC50 greater than 1 mg/mL. The crude fruit extract shows good activity with the ABTS model, unlike the DPPH model whose IC50 values are 0.95 and 0.38 mg/mL, respectively. Fractionation improved the antioxidant effect of crude flower extract. The ethyl acetate fraction exhibits the best antioxidant activity for both DPPH and ABTS methods with IC50 values of 0.125 and 0.16 mg/mL. The HR-LCMS/MS led to the identification of 13 compounds: 6 flavonoids and 7 iridoid glycoside compounds in the different parts of the plant. A bioinformatics study was performed to evaluate the antioxidant activity of the three major Iridoid glycosides towards the target protein Catalase compound II through free binding energy. Out of these three iridoid glycosides, compound C10 does not represent any toxicity, unlike C8 and C9 which showed an irritancy effect. Furthermore, molecular dynamics shows good stability of the C10-2CAG complex. HighlightsExtraction and fractionation of different part (leaf, stem, flower and fruit) of Avicennia marina.Botanical description and phytochemical analysis of crude extract methanolic. Investigation by HR-LCMS characterization of polyphenols and iridoid glycosides.Evaluation the antioxidant activity of crudes extracts methanolics by two methods in vitro DPPH and ABTS.Antioxidant activity of the fraction of the crude flower extracts presenting the best biological response.Evaluate the contribution of three major compounds 2'-Cinnamoylmussaenosidic acid, 10-O-[E-Cinnamoyl]-geniposidic acid and 10-O-[(E)-p-Coumaroyl]-geniposidic acid in the ethyl acetate fraction on the antioxidant activity through docking and dynamic molecular.Communicated by Ramaswamy H. Sarma.

Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach.

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.

Aloe djiboutiensis: Antioxidant Activity, Molecular Networking-Based Approach and In Vivo Toxicity of This Endemic Species in Djibouti.

For the first time, the study of the antioxidant activity, the characterization of the phytoconstituants, and the evaluation of in vitro and in vivo toxicity of A. djiboutiensis leave and latex are performed. The antioxidant activity of both latex (ADL) and the methanolic extract of leaves (ADM) is determined using 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging radical methods and ferric reducing/antioxidant power (FRAP) assay. The phytochemical study of latex is done using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and a molecular networking-based approach. The evaluation of in vivo toxicity is performed on mice by oral gavage with a suspension of ADL. Our results show that weak antioxidant activity of ADL and ADM in opposition to their high polyphenol, 83.01 mg and 46.4 mg expressed in gallic acid equivalent (GAE)/g of dry weight (DW), respectively, and flavonoid contents 13.12 mg and 4.25 mg expressed in quercetin equivalent (QE)/g dry weight (DW), respectively. Using the Global Natural Products Social Molecular Networking (GNPS) website, nine (9) anthraquinones derivatives, ten (10) chromones derivatives, two (2) flavonols/ chromones isomers are annotated in the molecular network. The treated mice do not display abnormalities in their general physical appearance and biochemistry parameters, compared to the controls. Only glucose and calcium levels are slightly higher in male treated mice compared to the vehicles.

Evaluation of Antioxidant and Antibacterial Activities, Cytotoxicity of Acacia seyal Del Bark Extracts and Isolated Compounds.

Water extract of Acacia seyal bark is used traditionally by the population in Djibouti for its anti-infectious activity. The evaluation of in vitro antibacterial, antioxidant activities and cytotoxicity as well as chemical characterization of Acacia seyal bark water and methanolic extracts were presented. The water extract has a toxicity against the MRC-5 cells at 256 µg/mL while the methanolic extract has a weak toxicity at the same concentration. The methanolic extract has a strong antioxidant activity with half maximal inhibitory concentration (IC50) of 150 ± 2.2 µg/mL using 1-diphenyl-2-picrylhydrazyl (DPPH) and IC50 of 27 ± 1.3 µg/mL using 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical methods. For ferric reducing/antioxidant power (FRAP) assay, the result is 45.74 ± 5.96 µg Vitamin C Equivalent (VCE)/g of dry weight (DW). The precipitation of tannins from methanol crude extract decreases the MIC from 64 µg/mL to 32 µg/mL against Staphylococcus aureus and Corynebacterium urealyticum. However, the antioxidant activity is higher before tannins precipitation than after (IC50 = 150 µg/mL for methanolic crude extract and 250 µg/mL after tannins precipitation determined by DPPH method). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, the results showed that the condensed tannins consist of two types of catechin and gallocatechin-based oligomers. The fractionation led to the identification of three pure compounds: two flavanols catechin and epicatechin; one triterpene as lupeol; and a mixture of three steroids and one fatty acid: campesterol, stigmasterol, clionasterol, and oleamide.