Diversity and Population Sizes of Wintering Waterbirds in the Wetlands of the Saïss-Middle Atlas Region (North-Central Morocco): Main Survival Factors and Evaluation of Habitat Loss.

Moroccan wetlands host up to half a million wintering birds and provide a stopover for tens of thousands of migrants, while they are inhabited by few nesting species. Most of this avifauna prefers to use the large coastal wetlands or reservoirs, while many species are dispersed across hundreds of small inland wetlands of various types. In this study, we monitored the wintering avifauna of 11 wetlands of the Saïss plain and its adjacent Atlas Mountains (north-center of Morocco), during six wintering seasons (2017-2018 to 2022-2023), with the objective of assessing the importance of this region as a waterbird wintering area. Using the richness of the species, we determine the bird population changes during this pentad and between the different types of wetlands (natural, human-made, and natural wetlands). During this study, we recorded 51 species, belonging to 17 families, among which exist four remarkable birds: the endangered Oxyura leucocephala, the vulnerable Aythya ferina and the near-threatened Aythya nyroca and Limosa limosa. Bird diversity is higher in human-made ecosystems than in peri-urban and natural ecosystems, while the populations' size is similar in urban and non-urban wetlands. With regard to bird conservation, these inland wetlands, mainly the small ones, are threatened by recurrent droughts and various anthropic stressors, which we describe using our observations of the two last decades (2003-2023). The loss of habitat is significant, reaching 348.5 hectares, while the impacts of reduced precipitation and temperature increase are particularly evident in the mountainous natural lakes.

UHPLC-MS characterisation of principal triterpene glycosides and biological activities of different solvent extracts of Allochrusa gypsophiloides (Caryophyllaceae).

A crude methanol extract of the roots of Allochrusa gypsophiloides (syn. Acanthophyllum gypsophiloides) (collected from the Tashkent region of Uzbekistan) was chemically characterised by UHPLC-ESI-QTOF-MS/MS analysis. The results indicate the presence of six major bisdesmosidic saponins derived from gypsogenin, gypsogenic and quillaic acids, including five compounds reported for the first time for this species. The chloroform, methanol and water extracts of A. gypsophiloides showed weak antioxidant and anthelmintic activities. Among the tested extracts, the water extract exhibited the highest level of cytotoxicity in CCRF-CEM and CEM/ADR5000 cell lines with IC50 values of 23.6 and 31.9 µg/mL, respectively.

A fruit extract of Styphnolobium japonicum (L.) counteracts oxidative stress and mediates neuroprotection in Caenorhabditis elegans.

BACKGROUND: Despite its widespread uses in Chinese and European medicine, Styphnolobium japonicum (Chinese scholar tree, formerly Sophora japonicum) has not been extensively investigated for its potential to protect against neurodegenerative processes and to promote resistance to oxidative stress. In this study, we evaluated the neuroprotective activities of a hydroalcoholic extract from Chinese scholar tree fruits that could be possibly linked to its antioxidant properties using Caenorhabditis elegans as a well-established in vivo model. METHODS: Survival rate in mutant daf-16 and skn-1 worms, stressed by the pro-oxidant juglone and treated with the extract, was tested. Localization of the transcription factors SKN-1 and DAF-16, and expression of gst-4 were measured. For evaluation of neuroprotective effects, formation of polyglutamine (polyQ40) clusters, α-synuclein aggregates, loss of amphid sensilla (ASH) neuronal function, and amyloid ß (Aß) accumulation (as markers for Huntington's, Parkinson's, and Alzheimer's) was examined. RESULTS: The extract, which contains substantial amounts of phenolic phytochemicals, showed an increase in the survival rate of worms challenged with juglone in daf-16 mutants but not in skn-1 mutants. The transcription factor SKN-1 was activated by the extract, while DAF-16 was not affected. Upon application of the extract, a significant decline in GST-4 levels, polyQ40 cluster formation, number of lost ASH sensory neurons, α-synuclein aggregation, and paralysis resulting from Aß accumulation was observed. CONCLUSIONS: Styphnolobium japonicum fruit extract activated the SKN-1/Nrf2 pathway, resulting in oxidative stress resistance. It revealed promising pharmacological activities towards treatment of Huntington's, Parkinson's, and Alzheimer's diseases. Polyphenolics from Styphnolobium japonicum may be a promising route towards treatment of CNS disorders, but need to be tested in other in vivo systems.

Lycorine suppresses the malignancy of breast carcinoma by modulating epithelial mesenchymal transition and ß-catenin signaling.

Lycorine, an isoquinoline alkaloid can exhibit significant anti-cancer effects. The present study was conducted to illustrate the underlying mechanisms of action of lycorine on breast carcinoma under in vitro and in vivo settings Tandem Mass Tag assay and Kyoto Encyclopedia of Genes and Genomes analysis revealed that 20 signaling pathways were closely related to tumorigenesis, especially Wnt signaling pathway and tight junctions. The results demonstrated that lycorine evidently inhibited the proliferation of MDA-MB-231 and MCF-7 cells with IC50 values of 1.84 ± 0.21 µM and 7.76 ± 1.16 µM, respectively. It also blocked cell cycle in G2/M phase, caused a decrease in mitochondrial membrane potential, and induced apoptosis pathways through regulating caspase-3, caspase-8, caspase-9, and PARP expression. Moreover, lycorine effectively repressed the ß-catenin signaling and reversed epithelial-mesenchymal transition (EMT) process. Furthermore, 4T1/Luc homograft tumor model was used to further demonstrate that lycorine significantly inhibited the growth and metastasis of breast tumor. These findings highlight the significance of lycorine as potential anti-neoplastic agent to combat breast cancer.

Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites.

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35 µM, 26.53 ± 3.12 µM and 11.62 ± 1.44 µM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.

Fucoxanthin Potentiates the Bactericidal Activity of Cefotaxime Against Staphylococcus aureus.

The increasing prevalence of antimicrobial resistance (AMR) in Staphylococcus aureus against commonly used antibiotics is a major global health issue. To prevent the emergence of AMR and maintain the desired therapeutic effect, the use of drug combinations in the therapeutic management of infections can be contemplated. This approach allows for the administration of lower antibiotic dosages without compromising the desired therapeutic outcome. Despite the documented antimicrobial activity of fucoxanthin, a widely recognized marine carotenoid, there are a lack of previous reports exploring its potential to enhance the therapeutic effect of antibiotics. The current study aimed to investigate whether fucoxanthin can inhibit S. aureus including the strains resistant to methicillin and to investigate whether fucoxanthin can enhance the therapeutic effect of cefotaxime, a widely prescribed 3rd-generation cephalosporin ß-lactam antibiotic known to exhibit resistance in certain cases. Synergism or additive interactions were determined using checkerboard dilution and isobologram analysis, while bactericidal activity was carried out using the time-kill kinetic assay. It is important to highlight that a synergistic bactericidal effect was observed in all strains of S. aureus when fucoxanthin was combined with cefotaxime at a specific concentration ratio. These findings suggest that fucoxanthin holds promise in enhancing the therapeutic efficacy of cefotaxime.

Modulation of Cellular Senescence in HEK293 and HepG2 Cells by Ultrafiltrates UPla and ULu Is Partly Mediated by Modulation of Mitochondrial Homeostasis under Oxidative Stress.

Protein probes, including ultrafiltrates from the placenta (UPla) and lung (ULu) of postnatal rabbits, were investigated in premature senescent HEK293 and HepG2 cells to explore whether they could modulate cellular senescence. Tris-Tricine-PAGE, gene ontology (GO), and LC-MS/MS analysis were applied to describe the characteristics of the ultrafiltrates. HEK293 and HepG2 cells (both under 25 passages) exposed to a sub-toxic concentration of hydrogen peroxide (H2O2, 300 µM) became senescent; UPla (10 µg/mL), ULu (10 µg/mL), as well as positive controls lipoic acid (10 µg/mL) and transferrin (10 µg/mL) were added along with H2O2 to the cells. Cell morphology; cellular proliferation; senescence-associated beta-galactosidase (SA-ß-X-gal) activity; expression of senescence biomarkers including p16 INK4A (p16), p21 Waf1/Cip1 (p21), HMGB1, MMP-3, TNF-α, IL-6, lamin B1, and phospho-histone H2A.X (γ-H2AX); senescence-related gene expression; reactive oxygen species (ROS) levels; and mitochondrial fission were examined. Tris-Tricine-PAGE revealed prominent detectable bands between 10 and 100 kDa. LC-MS/MS identified 150-180 proteins and peptides in the protein probes, and GO analysis demonstrated a distinct enrichment of proteins associated with "extracellular space" and "proteasome core complex". UPla and ULu modulated senescent cell morphology, improved cell proliferation, and decreased beta-galactosidase activity, intracellular and mitochondrial ROS production, and mitochondrial fission caused by H2O2. The results from this study demonstrated that UPla and Ulu, as well as lipoic acid and transferrin, could protect HEK293 and HepG2 cells from H2O2-induced oxidative damage via protecting mitochondrial homeostasis and thus have the potential to be explored in anti-aging therapies.

BAAE-AgNPs Improve Symptoms of Diabetes in STZ-induced Diabetic Rats.

OBJECTIVES: Nanoparticles can be employed to improve the therapeutic activity of natural products. Type 2 diabetes mellitus is a serious health condition that has spread like a "modern pandemic" worldwide. In the present study, we developed silver nanoparticles, Ag-NPs, with an aqueous extract from Balanites aegyptiaca to investigate their antioxidant and anti-inflammatory activity in STZ-induced diabetic rats. METHODS: Aqueous extracts of Balanites aegyptiaca seeds (BAAE) were used in the synthesis of BAAE-AgNPs, which were characterized using FTIR and TEM. Different doses of BAAE-AgNP (1/50 LD50; 29.4 mg/kg b.w. and 1/20 LD50: 73.5 mg/kg b.w.) were administered to STZ-induced diabetic rats to evaluate their potential antidiabetic activity. RESULTS: FTIR spectral data indicated the presence of flavonoids and polyphenols in BAAEAgNPs. The size of the BAAE-AgNPs, determined by TEM examination, was 49.33 ± 7.59 nm, with a zeta potential of +25.37. BAAE-AgNPs were characterized by an LD50 value of 1470 mg/kg b.w. In diabetic rats, the daily oral administration of both doses of BAAE-AgNPs (29.4 and 73.5 mg/kg b.w.) for 12 weeks resulted in a significant improvement in body weight, insulin homeostasis, HbA1c, HDL-C, MDA, and pancreatic SOD, CAT, and GSH. They reduced plasma glucose, cholesterol, and triglycerides. This treatment also resulted in a significant decrease in pancreatic IL-6, p53, and TNF-α in diabetic rats. Furthermore, BAAE-AgNPs down-regulated pancreatic TGF-ß1 and Akt gene expression in diabetic rats and resulted in a significant decrease in the regulation of hepatic GLUT-2, as well as an increase in the regulation of hepatic GK and pancreatic B-cl2 gene expression. The histopathological results obtained indicated that BAAEAgNPs improved pancreatic tissue metabolism by enhancing antioxidant enzymes, suppressing inflammatory cytokines, and scavenging free radicals. CONCLUSION: The findings implied that similar to the glibenclamide-treated groups, in the BAAEAgNPs treated group, the compromised antioxidant status normalized in STZ-induced diabetes. By scavenging free radicals, BAAE-Ag-NPs protected against lipid peroxidation while reducing the risk of complications from diabetes. Compared to the daily dose of 29.4 mg, the impact was more prominent at 73.5 mg.

Comparative metabolic profiling of olive leaf extracts from twelve different cultivars collected in both fruiting and flowering seasons.

Olea europaea is an economically significant crop native to Mediterranean countries. Its leaves exhibit several biological properties associated to their chemical composition. The aqueous ethanolic extracts of olive leaves from twelve different cultivars were analyzed by high performance liquid chromatography coupled to photodiode array and electrospray ionization mass spectrometry (HPLC/PDA/ESI-MS/MS). A total of 49 phytochemicals were identified in both positive and negative ionization modes. The identified compounds belonged to four classes of secondary metabolites including secoiridoids, flavonoids, pentacyclic triterpenoids and various phenolic compounds. Seasonal variation in chemical composition among the studied cultivars was apparent in autumn and spring. Secologanoside, oleuropein, hydroxy-oleuropein, demethyl oleuropein, gallocatechin, luteolin-O-hexoside, diosmetin, oleanolic acid and maslinic acid were detected in all cultivars in both seasons. Oleuropein-O-deoxyhexoside was tentatively identified for the first time in olive leaf extracts; detected only in the Spanish cultivar Picual (PIC) collected in spring. Also, dihydroxy-oxooleanenoic acid and hydroxy-oxooleanenoic acid, two bioactive pentacyclic triterpenes, were identified. Principle component analysis (PCA) showed good discrimination among the studied cultivars in terms of their botanical origin. This study is considered the first study for non-targeted metabolic profiling of different olive leaf cultivars cultivated in Egypt.

Combined Gamma Conglutin and Lupanine Treatment Exhibits In Vivo an Enhanced Antidiabetic Effect by Modulating the Liver Gene Expression Profile.

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combining both compounds and the effective dose of the combination have not been assessed. Moreover, the resulting gene expression profile from this novel combination remains to be explored. Therefore, we aimed to evaluate different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the higher antidiabetic effect on a T2D rat model. Later, we administered the selected dose combination during a week. Lastly, we evaluated biochemical parameters and liver gene expression profile using DNA microarrays and bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine significantly reduced glycemia and lipid levels. Moreover, this treatment positively influenced the expression of Pdk4, G6pc, Foxo1, Foxo3, Ppargc1a, Serpine1, Myc, Slc37a4, Irs2, and Igfbp1 genes. The biological processes associated with these genes are oxidative stress, apoptosis regulation, and glucose and fatty-acid homeostasis. For the first time, we report the beneficial in vivo effect of the combination of two functional lupin compounds. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combined treatment.

Vanin 1 Gene Role in Modulation of iNOS/MCP-1/TGF-ß1 Signaling Pathway in Obese Diabetic Patients.

Introduction: Cysteamine, a powerful endogenous antioxidant, is produced mostly by the vanin-1 with pantetheinase activity. With regard to glycemic, inflammatory, and redox factors, the current study sought to evaluate the association between the expression of the vanin-1 gene, oxidative stress, and inflammatory and iNOS signaling pathway in obese diabetic patients. Methods: We enrolled 67 male subjects with an average age of 53.5 ± 5.0 years, divided into 4 groups according to the WHO guideline. We determined their plasma levels of glucose, insulin, IRI, HbA1c, TC, TG, HDL-C, TNF- α, MCP-1, TGF-ß1, SOD, CAT, and TBARs, as well as expression of the iNOS and Vanin1 genes. Results: Overweight and obese class I and II diabetics had significantly higher levels of plasma glucose, insulin, HbA1c, TNF-α, MCP-1, TGF-ß1, CAT, and TBAR as well as iNOS and vanin-1 gene expression compared to healthy control individuals. In addition, as compared to healthy control individuals, overweight obese class I and II diabetics' plasma HDL-C levels and blood SOD activity were significantly lower. In addition, ultrasound and computed tomography showed that the presence of a mild obscuring fatty liver with mild hepatic echogenicity appeared in overweight, class I and II obese diabetic patients. Conclusion: These findings provide important information for understanding the correlation between Vanin 1 and glycemic, inflammatory, and redox factors in obese patients. Furthermore, US and CT analysis were performed to visualize the observed images of fatty liver due to obesity.

Salix subserrata Bark Extract-Loaded Chitosan Nanoparticles Attenuate Neurotoxicity Induced by Sodium Arsenate in Rats in Relation with HPLC-PDA-ESI-MS/MS Profile.

Pollution is a worldwide environmental risk. Arsenic (As) is an environmental pollutant with a major health concern due to its toxic effects on multiple body organs, including the brain. Humans are exposed to As through eating contaminated food and water or via skin contact. Salix species (willow) are plants with medicinal efficacy. Salix subserrata Willd bark extract-loaded chitosan nanoparticles (SBE.CNPs) was formulated, characterized, and evaluated against As-induced neurotoxicity. The stem bark was selected for nanoparticle formulation based on HPLC-PDA-ESI-MS/MS profiling and in vitro antioxidant assessment using free radical scavenging activity. SBE.CNPs demonstrated an average un-hydrated diameter of 193.4 ± 24.5 nm and zeta potential of + 39.6 ± 0.4 mV with an encapsulation efficiency of 83.7 ± 4.3%. Compared to As-intoxicated rats, SBE.CNP-treated rats exhibited anxiolytic activity and memory-boosting as evidenced in open field test, light-dark activity box, and Y-maze. Also, it increased the antioxidant biomarkers, including superoxide dismutase and glutathione peroxidase associated with reducing the malondialdehyde levels and apoptotic activity. Besides this, SBE.CNPs maintained the brain architecture and downregulated both nuclear factor-kappa B and heme oxygenase-1 expression. These results suggest that SBE.CNP administration showed promising potent neuroprotective and antioxidative efficiencies against arsenic-induced oxidative threats.

High density and successful breeding of Turtle doves Streptopelia turtur in Moroccan olive groves.

Background: The turtle dove is a migratory species that has suffered a rapid decline principally across its Northern ranges, despite pronounced conservation measures. Consequently, it has been categorized as 'Near Threatened' in Europe. Degradation of breeding habitats and a decrease in food resources are listed as principal causes of this decline. Despite its importance, the productivity of the North African population is widely unknown. Here we present the first estimation of the density of the breeding population and the superior reproductively of Streptopelia turtur arenicola in Morocco and entire North Africa. Methods: This study was carried out for two seasons 2018-2019 in the Saïss plain, central Morocco. Based on previous data, doves were monitored weekly, from early March to late August, in aquatic ecosystems (two dams and one river) and farmlands (cereals and orchards). The breeding population was censused using the "point-count" method, following a walked transect of 5 km in orchards, 7 km in cereal fields, and 3 km along the river. Equally, nests were searched in natural habitats counting riparian trees, forests, and ornamental trees, and in orchards based on the Common Birds Census (CBC) methodology, in which the singing doves, mating pairs, nesting, and/or feeding behavior were the most monitored signs to discover nests. In orchards, nests were searched line-by-line based on the rows of fruit trees. For each recorded nest, we note the breeding chronology, clutch size and incubation period, success and failure factors, dimensions, and vertical placement on trees. To evaluate the predictors of doves' occurrence, we noted at each site the presence of cereals, water, human disturbance, presence of nesting trees, and predators. Results and Discussion: In total, 3,580 turtle doves (22.37 birds/ha), including 240 breeding pairs, were documented. Nesting occurred mainly in olive groves, cereals were used for forage, and aquatic ecosystems for water sources. The nesting period lasted from late April to July (last fledglings). All nests were located on olive trees at a height of 225.30 ± 48.87 cm. The clutch size was 1.98 ± 0.13 (laid eggs/built nests), the incubation period lasted 14.16 ± 1.32 days, and the rearing period lasted 16.54 ± 1.76 days. The breeding success among the 240 monitored nests accounted for 73.84% during the nesting phase and 87.42% during the incubation phase; 71.5%% of nestlings have fledged, which is the highest success rate for turtle doves in Europe and Northwest Africa. Clutches were aborted mostly due to predation from snakes (7.5% of nests, 16.12% of eggs, and 5.63% of chicks), nest desertion (9.16% of nests and 5.37% of eggs), and marginally by the destruction of nests through farming activities. These findings are important for conservation plans, to restore turtle doves' habitats in Europe, where the species is widely declining.

Euclea divinorum Hiern: Chemical Profiling of the Leaf Extract and Its Antioxidant Activity In Silico, In Vitro and in Caenorhabditis elegans Model.

Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin-Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant's antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract's ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract's metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites' residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders.

Molecular design, synthesis and biological evaluation of novel 1,2,5-trisubstituted benzimidazole derivatives as cytotoxic agents endowed with ABCB1 inhibitory action to overcome multidrug resistance in cancer cells.

Multidrug resistance (MDR) is a leading cause for treatment failure in cancer patients. One of the reasons of MDR is drug efflux by ATP-binding cassette (ABC) transporters in eukaryotic cells especially ABCB1 (P-glycoprotein). In this study, certain novel 1,2,5-trisubstituted benzimidazole derivatives were designed utilising ligand based pharmacophore approach. The designed benzimidazoles were synthesised and evaluated for their cytotoxic activity towards doxorubicin-sensitive cell lines (CCRF/CEM and MCF7), as well as against doxorubicin-resistant cancer cells (CEM/ADR 5000 and Caco-2). In particular, compound VIII showed a substantial cytotoxic effect in all previously mentioned cell lines especially in doxorubicin-resistant CEM/ADR5000 cells (IC50 = 8.13 µM). Furthermore, the most promising derivatives VII, VIII and XI were tested for their ABCB1 inhibitory action in the doxorubicin-resistant CEM/ADR 5000 subline which is known for overexpression of ABCB1 transporters. The results showed that compound VII exhibited the best ABCB1 inhibitory activity at three tested concentrations (22.02 µM (IC50), 50 µM and 100 µM) in comparison to verapamil as a reference ABCB1 inhibitor. Such inhibition resulted in a synergistic effect and a massive decrease in the IC50 of doxorubicin (34.5 µM) when compound VII was used in a non-toxic dose in combination with doxorubicin in doxorubicin-resistant cells CEM/ADR 5000 (IC50(Dox+VII) = 3.81 µM). Molecular modelling studies were also carried out to explain the key interactions of the target benzimidazoles at the ABCB1 binding site. Overall the obtained results from this study suggest that 1,2,5-trisubstituted benzimidazoles possibly are promising candidates for further optimisation and development of potential anticancer agents with ABCB1 inhibitory activity and therefore overcome MDR in cancer cells.

Oolonghomobisflavans exert neuroprotective activities in cultured neuronal cells and anti-aging effects in Caenorhabditis elegans.

Potential health benefits of tea has attracted significant scientific and public attention worldwide. Tea polyphenols are considered as natural promising complementary therapeutical agents for neurodegenerative diseases. However, the anti-neurodegeneration or anti-aging activities of oolong tea polyphenols have not been investigated. The current study aims to document beneficial effects of oolong tea polyphenols [dimers of epigallocatechin gallate (EGCG), oolonghomobisflavan A (OFA), and oolonghomobisflavan B (OFB)] with neuroprotective and neuritogenesis properties in cultured neuronal (Neuro-2a and HT22) cells and Caenorhabditis elegans models. In vitro, we found that the compounds (EGCG, OFA, and OFB) protect against glutamate-induced neurotoxicity via scavenging radical activity, suppression intracellular ROS and up-regulation of antioxidant enzymes. Moreover, the compounds induce neurite outgrowth via up-regulate Ten-4 gene expression. Interestingly, OFA and OFB exert stronger neuroprotective and neurite outgrowth properties than EGCG known as an excellent antioxidant agent in tea. In vivo, we found that the compounds protect against C. elegans Aß-induced paralysis, chemotaxis deficiency and α-synuclein aggregation. Moreover, the compounds are capable of extending the lifespan of C. elegans. OFA and OFB possess both anti-neurodegeneration and anti-aging activities, supporting its therapeutic potential for the treatment of age-related neurodegenerative diseases which need to be studied in more detail in intervention studies.

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being.

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review.

Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management.

The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.

Phytochemical Profiling of the Leaf Extract of Ximenia americana var. caffra and Its Antioxidant, Antibacterial, and Antiaging Activities In Vitro and in Caenorhabditis elegans: A Cosmeceutical and Dermatological Approach.

We previously annotated the phytochemical constituents of a root extract from Ximenia americana var. caffra and highlighted its hepatoprotective and hypoglycemic properties. We here extended our study on the leaf extract and identified its phytoconstituents using HPLC-PDA-ESI-MS/MS. In addition, we explored its antioxidant, antibacterial, and antiaging activities in vitro and in an animal model, Caenorhabditis elegans. Results from HPLC-PDA-ESI-MS/MS confirmed that the leaves contain 23 secondary metabolites consisting of condensed tannins, flavonol glycosides, flavone glycosides, and flavonol diglycosides. The leaf extract demonstrated significant antioxidant activity in vitro with IC50 value of 5 µg/mL in the DPPH assay and 18.32 µg/mL in the FRAP assay. It also inhibited four enzymes (collagenase, elastase, hyaluronidase, and tyrosinase) crucially involved in skin remodeling and aging processes with comparable activities to reference drugs along with four pure secondary metabolites identified from the extract. In accordance with the in vitro result, in vivo tests using two transgenic strains of C. elegans demonstrated its ability to reverse oxidative stress. Evidence included an increased survival rate in nematodes treated with the prooxidant juglone to 68.9% compared to the 24.8% in untreated worms and a reduced accumulation of intracellular reactive oxygen species (ROS) in a dose-dependent manner to 77.8%. The leaf extract also reduced levels of the expression of HSP 16.2 in a dose-dependent manner to 86.4%. Nuclear localization of the transcription factor DAF-16 was up to 10 times higher in worms treated with the leaf extract than in the untreated worms. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa (a pathogen in skin infections) and reduced the swimming and swarming mobilities in a dose-dependent fashion. In conclusion, leaves of X. americana are a promising candidate for preventing oxidative stress-induced conditions, including skin aging.