Potential applications of antofine and its synthetic derivatives in cancer therapy: structural and molecular insights.

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure-activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments.

Chemical composition and biological activities of the Algerian Cymbalaria muralis aerial parts.

In the present study we report data about antioxidant (DPPH, ß-Carotene, reducing power), anti-inflammatory (xylene-induced ear oedema in mice (76 ± 1.0%) and membrane stabilisation (100%)) and antimicrobial (Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, Pseudomonas arugenosa ATCC27853 and Fusarium oxysporum ATCC62506) activities of the ethanolic extract from the Algerian Cymbalaria muralis P. Gaertn., B. Mey. & Scherb (CME). The LC-ESIMS analysis of CME chemical profile allowed to identify antirrhinoside (1), catalpol (2), linarioside (3), glucosyringic acid (4), angoroside C (5), apigenin 7-O-glucoside (6), acacetin 7-O-ß-D-glucopyranoside (7), apigenin (8), chrysoeriol 7-rutinoside (9), diosmin (10) and linarin (11). The evaluated total phenolic and flavonoid contents support the biological activities.

Potential Therapeutic Targets of Resveratrol in the Prevention and Treatment of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a feared component in over 200 interstitial pulmonary diseases, which are characterized by increased alveolar wall thickness, excessive scarring, and aberrant extracellular matrix restructuring that, ultimately, affect lung compliance and capacity. As a result of its broad range of biological activities, including antioxidant, anti-inflammatory, antiapoptotic, and many others, resveratrol has been shown to be an effective treatment for respiratory system diseases, including interstitial lung disease, infectious diseases, and lung cancer. This work reviews the known molecular therapeutic targets of resveratrol and its potential mechanisms of action in attenuating PF in respiratory diseases, including cancer, COVID-19, interstitial lung diseases (ILDs) of known etiologies, idiopathic interstitial pneumonia, and ILDs associated with systemic disorders, such as rheumatoid arthritis, systemic sclerosis, Schrödinger's syndrome, systemic lupus erythematosus, and pulmonary hypertension. The current issues and controversies related to the possible use of resveratrol as a pharmaceutical drug or supplement are also discussed.

LC-MS profile, in vitro acetylcholinesterase inhibitory, antibacterial and hemostatic properties of Ranunculus bullatus extract.

The ethanol extract from aerial parts of Ranunculus were investigated for its chemical composition by LC-ESI-MS/MS technique, which allowed to identify a series of glycosylated flavonoids and one phenolic acid. RBEE extract showed acetyl-cholinesterase inhibition higher than the reference compound Galantamine at a concentrationof 200 µg/mL. A moderate antibacterial activity of the extract was also obtained against Staphylococcus aureus ATCC43300, Citrobacter freundii ATCC8090, and Proteus vulgaris ATCC29905 at a concentration 100 µg. Additionally, a good reduction in plasma coagulation time at 200 µL was also observed for RBEE.

Chemical constituents, in vitro anti-inflammatory, antioxidant and hemostatic activities of the n-butanol extract of Hyacinthoides lingulata (Poir.) Rothm.

The phytochemical profile obtained from LC-ESI-MS/MS analysis of the n-butanol extract (BEHL) from the North African endemic plant Hyacinthoides lingulata (Poir.) Rothm. brought about the identification of ten glycosylated derivatives of apigenin and luteolin flavones. For the same plant extract, in vitro anti-inflammatory (hypotonic induced hemolysis and heat induced haemolysis assay) and antioxidant (DPPH and ß-Carotene) activities were evaluated observing high inflammatory inhibition by protecting membrane stability of erythrocyte in both heat (84.70 ± 0.24%) and hypotonic induced hemolysis (79.45 ± 0.12%). A remarkable hemostatic effect was also established by measuring the coagulation time (15.95 ± 1.05 s at a dose of 1 mg/mL) of decalcified plasma related to its phytochemical content. It is the first report on combined chemical components and biological evaluation of this specific plant.

Anti-inflammatory and hemostatic effects of Linaria reflexa Desf.

The work presented here was aimed to investigate the in vivo anti-inflammatory and in vitro hemostatic activities of Linaria reflexa extract and to establish the relationship between its bioactivity and chemical composition. Twenty-three secondary metabolites were identified, most of them are good anti-inflammatory agents, in line with data by carrageenin-induced rat paw edema assays of the n-butanol extract showing high anti-inflammatory inhibition (63.90%) of edema swelling in the rat paw at the dose 200 mg/kg after 4 h. Furthermore, both extent of inflammatory response and tissue injury were prevented keeping the levels of rate myeloperoxidase (60.16%) and of malondialdehyde, which is the final product of lipid peroxidation generated by free radicals (58.58%). The same extract showed also a remarkable hemostatic effect established by measuring the coagulation time of decalcified plasma (45 s), related to its flavonoid glycosides content.

Chemical composition, in vitro antioxidant, anticholinesterase and antibacterial activities of Linaria scariosa Desf.

The study was performed on the dichloromethane (DCM), ethyl acetate (EAc) and n-butanol (Bu) fractions (F) obtained from the 80% ethanol extract of Linaria scariosa Desf. aerial parts, collected in the North Eastern region of Algeria. Remarkable total phenolic and flavonoid contents were obtained, mainly for EAcF. These results were in accordance with the antioxidant activity of EAcF against DPPH, ABTS, CUPRAC and reducing power tests. DCMF and BuF exhibited significant cholinesterase activity inhibition of BChE and AChE. Moreover, EAcF displayed only moderate antibacterial activities, especially against S. aureus. The biological results were correlated to the chemical components, deduced by both GC-MS analysis of the fractions and the isolation of hemipholin, pectolinarigenin, antirride, antirrinoside, pectolinarin and linariosise, some of which known to exhibit potent effects on the tested biological activities. The study provides the first biological and chemical investigation on Linaria scariosa Desf (unresolved name).

Isolation and Biological Properties of the Natural Flavonoids Pectolinarin and Pectolinarigenin-A Review.

Flavonoids are metabolites widely distributed in plants and commonly present in foods, such as fruits and vegetables. Pectolinarin, which belongs to the flavone subclass, has attracted considerable attention due to its presence in many medicinal plants. It has turned out to be a good biological agent especially due to its antioxidant, anti-inflammatory, antidiabetic, and antitumor activities, evaluated both in vitro and in vivo. Its aglycone, the metabolite pectolinarigenin, is also known for a series of biological properties including anti-inflammatory and antidiabetic effects. In the first overview on the two metabolites here presented, their collection, isolation and the results of their biological evaluation are reported.

Centaurea microcarpa Coss. & Dur. (Asteraceae) extracts: New cyanogenic glucoside and other constituents.

The phytochemical investigation of both chloroform and ethyl acetate extracts of Centaurea microcarpa Coss. & Dur. led to the isolation of a new cyanogenic glucoside 6'-methacrylate prunasin (3) together with seven known compounds: hydroxy-11ß,13-dihydro onopordaldehyde (1), ß-sitosterol (2), daucosterol (4), nepetin (5), prunasin (6), astragalin (7) and 7-O-ß-D-glucopyranosyl centaureidin (8). Their structures were established by spectral analysis, mainly UV, IR, ESI-MS, 1D & 2D-NMR experiments (COSY, HSQC, HMBC and ROESY).

Iridoids and anti-inflammatory properties of n-butanol extract of Linaria tingitana Boiss. & Reut.

The analysis of the n-butanol extract of Linaria tingitana (BELT) by HPLC-DAD-ESI/MS allowed the identification of four iridoids structurally confirmed by NMR and ESI-MS/MS extensive experiments data. The subjection of BELT to the anti-inflammatory activity showed that it exhibited a concentration dependent stabilisation of HRBC membrane, inhibition of protein denaturation and nitric oxide scavenging effect in the in vitro process. These results were confirmed in the in vivo experiments which showed that BELT was found to be most pronounced at 200 mg/kg after carrageenan injection which significantly reduced the swelling in both early and late phases of carrageenan-evoked oedema, as well as a significant reduce at the accumulation of infiltrating cells, inhibition of the myeloperoxidase activity and suppressed the lipid peroxidation. These results were supported by the histological analysis which revealed the reduction of oedema and cells infiltration, this might be influenced by the synergistic action of the above isolated compounds.

Glycosyl flavonoid profile, in vivo antidiabetic and in vitro antioxidant properties of Linaria reflexa Desf.

Aerial parts of Linaria reflexa, used in North African folk medicine for treating certain skin diseases, were investigated by HPLC-DAD-ESI/MS technique able to identify the glycosyl flavonoids pectolinarin (1), isolinariin A (2), isolinariin B (3), linariin (4), isolinariin D (5) and isolinariin E (6) as the most abundant components in both hydroalcoholic (HAE) and ultrasound-assisted (UAE) extracts profiles. Metabolite 5, isolated and fully characterised by extensive nuclear magnetic resonance (NMR) analysis, has been very recently reported from L. japonica together with the compound 6. Good antioxidant activities (DPPH radical scavenging, ß-carotene bleaching and reducing power assays) were observed for the extracts. The remarkable antidiabetic activity displayed by UAE (300 mg/kg) has yielded the most marked decrease in blood glucose levels of the alloxan diabetic rats (-72.09%), greater than the effects by the drug glybenclamide (-63.29%). This study reports the first correlation of antidiabetic activity of Linaria sp. extracts with their chemical composition.

Chemical constituents and biological activities of the genus Linaria (Scrophulariaceae).

This is a review on 95 references dealing with the genus Linaria (Scrophularioideae-Antirrhineae tribe), a known genus of the Scrophulariaceae family, which comprises about 200 species mainly distributed in Europe, Asia and North Africa. The use of some Linaria species in folk medicine has attracted the attention for chemical and biological studies. This report is aimed to be a comprehensive overview on the isolated or identified known and often new metabolites from the 41 Linaria species so far cited. It is organised presenting first the phytochemical classes of alkaloids, polyphenols including flavonoids, the latter being quite diffused and mostly present as flavones, flavonols and their glycosides, and terpenoids including iridoids and steroids. Second, the results from biological investigation on plant extracts, pure natural products isolated from Linaria species and some synthetic derivatives are reported, with antitumour, anti-acetylcholinesterase, anti-inflammatory and analgesic, antioxidant and antibacterial activities.