Canna x generalis L.H. Bailey rhizome extract ameliorates dextran sulfate sodium-induced colitis via modulating intestinal mucosal dysfunction, oxidative stress, inflammation, and TLR4/ NF-Ò¡B and NLRP3 inflammasome pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Genus Canna is used in folk medicine as demulcent, diaphoretic, antipyretic, mild laxative and in gastrointestinal upsets therapy. Canna x generalis (CG) L.H. Bailey is traditionally used as anti-inflammatory, analgesic and antipyretic. Besides, CG is used in Ayurvedic medicines' preparations and in the treatment of boils, wounds, and abscess. Nevertheless, its anti-inflammatory effects against ulcerative colitis (UC) are not yet investigated. AIM: This study aimed to investigate the phytoconstituents of CG rhizome ethanol extract (CGE). Additionally, we aimed to comparatively evaluate its therapeutic effects and underlying mechanisms against the reference drug "sulphasalazine (SAS)" in dextran sodium sulfate (DSS)-induced UC in mice. MATERIAL AND METHODS: Metabolic profiling of CG rhizomes was performed via UHPLC/qTOF-HRMS; the total phenolic, flavonoid and steroid contents were determined, and the main phytoconstituents were isolated and identified. Next, DSS-induced (4%) acute UC was established in C57BL/6 mice. DSS-induced mice were administered either CGE (100 and 200 mg/kg) or SAS (200 mg/kg) for 7 days. Body weight, colon length, disease activity index (DAI) and histopathological alterations in colon tissues were examined. Colon levels of oxidative stress (GSH, MDA, SOD and catalase) and pro-inflammatory [Myeloperoxidase (MPO), nitric oxide (NO), IL-1ß, IL-12, TNF-α, and INF-γ] markers were colourimetrically determined. Serum levels of lipopolysaccharide (LPS) and relative mRNA expressions of occludin, TLR4 and ASC (Apoptosis-Associated Speck-Like Protein Containing CARD) using RT-PCR were measured. Protein levels of NLRP3 inflammasome and cleaved caspase-1 were determined by Western blot. Furthermore, immunohistochemical examinations of caspase-3, NF-Ò¡B and claudin-1 were performed. RESULTS: Major identified constituents of CGE were flavonoids, phenolic acids, phytosterols, beside five isolated phytoconstituents (ß-sitosterol, triacontanol fatty alcohol, ß-sitosterol-3-O-ß-glucoside, rosmarinic acid, 6-O-p-coumaroyl-ß-D-fructofuranosyl α-D-glucopyranoside). The percentage of the phenolic, flavonoid and steroid contents in CGE were 20.55, 6.74 and 98.09 µg of gallic acid, quercetin and ß-sitosterol equivalents/mg extract, respectively. In DSS-induced mice, CGE treatment ameliorated DAI, body weight loss and colon shortening. CGE attenuated the DSS-induced colonic histopathological alternations, inflammatory cell infiltration and histological scores. CGE elevated GSH, SOD and catalase levels, and suppressed MDA, pro-inflammatory mediators (MPO and NO) as well as cytokines levels in colonic tissues. Moreover, CGE downregulated LPS/TLR4 signaling, caspase-3 and NF-Ò¡B expressions. CGE treatment inhibited NLRP3 signaling pathway as indicated by the suppression of the protein expression of NLRP3 and cleaved caspase-1, and the ASC mRNA expression in colonic tissues. Additionally, CGE restored tight junction proteins' (occludin and claudin-1) expressions. CONCLUSION: Our findings provided evidence for the therapeutic potential of CGE against UC. CGE restored intestinal mucosal barrier's integrity, mitigated oxidative stress, inflammatory cascade, as well as NF-Ò¡B/TLR4 and NLRP3 pathways activation in colonic tissues. Notably, CGE in a dose of 200 mg/kg was more effective in ameliorating DSS-induced UC as compared to SAS at the same dose.

Metabolites profiling of Ziziphus leaf taxa via UHPLC/PDA/ESI-MS in relation to their biological activities.

Ziziphus plants are well recognized for their nutritive and medicinal value worldwide, albeit their chemical profile has yet to be fully reported. The secondary metabolites profile of three traditionally used Ziziphus leaf accessions was investigated via ultra-high performance liquid chromatography coupled to photodiode array and electrospray ionization mass detectors (UHPLC/PDA/ESI-MS). A total of 102 metabolites were characterized revealing the first holistic approach onto Ziziphus leaf metabolome and to include the first report of several novel flavonoids and cyclopeptide alkaloids. Fragmentation pattern for cyclopeptide alkaloids was proposed via ESI-MS. Principal component analysis (PCA) revealed close metabolite resemblance among Z. spina-christi and Z. mauritiana leaf specimens found enriched in saponins and distinct from that of Z. jujuba in which quercetin-3-O-(2-pentosyl)-rhamnoside was most abundant. Further, in-vitro antioxidant, anti-inflammatory and antidiabetic assays revealed for Z. spina-christi and Z. mauritiana strong effects compared to Z. jujuba and in correlation with their metabolites repertoire.

Phytochemical, antioxidant and antidiabetic evaluation of eight Bauhinia L. species from Egypt using UHPLC-PDA-qTOF-MS and chemometrics.

Bauhinia L. (Fabaceae) comprises ca. 300-350 plant species, many of which are traditionally used in folk medicine for their antidiabetic, antioxidant and anti-inflammatory effects. Bauhinia s.l. recently has been subdivided into 9 genera based on phylogenetic data: Bauhinia s.str., Barklya, Brenierea, Gigasiphon, Lysiphyllum, Phanera, Piliostigma, Schnella (American Phanera) and Tylosema. The aerial parts of 8 species corresponding to 5 genera were analyzed: Bauhinia forficata, Bauhinia variegata, B. variegata var. candida, Bauhinia galpinii, Schnella glabra, Piliostigma racemosa, Phanera vahlii and Lysiphyllum hookeri. Leaves and shoots were subjected to metabolite profiling via UHPLC-PDA-qTOF-MS coupled to multivariate data analyzes to identify compound compositional differences. A total of 90 metabolites were identified including polyphenols and fatty acids; flavonoid conjugates accounted for most of the metabolite variation observed. This study provides a comprehensive map of polyphenol composition in Bauhinia and phytochemical species aggregations are consistent with recent Bauhinia genus taxonomic relationship derived from phylogenetic studies. DPPH radical scavenging and α-glucosidase inhibitory assays were also performed to assess selected aspects of the antioxidant and antidiabetic potential for the examined species with respect to metabolite profiles.