Flavonoids, Anti-Inflammatory Activity and Cytotoxicity of Macfadyena Unguis-Cati L.

Ethyl acetate and ethanol extracts of unflowering aerial part of Macfadyena unguis-cati L. (Fam. Bignoniaceae) were found to be rich in phenolic compounds. From ethyl acetate extract, six flavonoids were identified, 8, methoxy, acacetin, 7-O glucoside; 6, methoxy apigenin 7-O glucoside; 4‵-O methyl scutellarin, 6-O apiosyl galactoside; acacetin, 7-O glucosyl, 8-C rhamnosyl, 3-O-α arabinofuranoside; 4‵-methyl, 6- methoxy kaempferol, 7-O, 8-C diglucoside and vicenin II were isolated, while 6, methoxy, acacetin 7-O glucoside; and quercitrin were isolated from ethanol extract. These compounds were characterized and identified by their physicochemical and spectral data. The crude ethanol extract exhibited significant anti-inflammatory activity (80.47%) and moderate cytotoxic activity against lung cell line

MS/MS-based molecular networking for mapping the chemical diversity of the pulp and peel extracts from Citrus japonica Thunb.; in vivo evaluation of their anti-inflammatory and anti-ulcer potential

Although inflammation is a beneficial response to harmful triggers, the associated diseases develop the potential for death-threatening conditions. Citrus species are valuable sources of chemical compounds with diverse structural properties that could alleviate damaging inflammation and reduce serious side effects of synthetic drugs. Kumquats are the smallest trees among the citrus family widely distributed in Asia, Europe, and North America, with little cultivation in Africa. The current study aims to conduct comprehensive chemical, anti-inflammatory and anti-ulcer studies of Citrus japonica, thus focusing attention on extensive cultivation of these species in Africa to enhance their beneficial uses. A comparative chemical profiling of peel and pulp extracts was performed via HPLC-MS/MS analysis, 164 metabolites were annotated aided by the spectral similarity networks. Around 148 of which were visualized as a species-first documentation. Phenolics were the predominant classes including methoxylated flavonoids, O/C-glycosylated flavones, and flavanones with the less common O- or C-O-triglycosyl methoxylated flavones among the genus Citrus. Moreover, the anti-inflammatory study demonstrated the significant activity of the pulp and peel extracts (200 and 400 mg/kg, p.o.) via reducing paw swelling induced by carrageenan at all-time points and decreasing the formation of TNF-α and IL-1β. Moreover, in ethanol-induced gastric ulcer rat model, the high doses of both extracts significantly improved ulcer indexes and suppressed gastric inflammation by inhibiting myeloperoxidase activity and possessed an antioxidant effect via increasing reduced glutathione, decreasing malondialdehyde, and nitric oxide. Additionally, histopathological investigations confirmed the anti-inflammatory and anti-ulcer effects. Considering the two fruit tissues, peels markedly improved inflammatory and gastroprotective properties associated with the high diversity of their flavonoid structures

Discovery of 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids as novel PPAR\u3b1 agonists with anti-hyperlipidemic and antioxidant activities: Design, synthesis and in vitro/in vivo biological evaluation

In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPAR\u3b1 agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPAR\u3b1 agonistic activity showing Emax% values of 50.80 and 90.55%, respectively, and EC50 values of 8.9 and 25.0 \u3bcM, respectively, compared to fenofibric acid with Emax = 100% and EC50 = 23.22 \u3bcM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPAR\u3b1 protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPAR\u3b1 active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg)