Mehmet Akyuz

Cisplatin is a widely used chemotherapeutic agent; however, its clinical utility is frequently limited by dose‐dependent adverse effects, particularly hepatotoxicity and nephrotoxicity. Luteolin, a naturally occurring flavonoid abundant in various medicinal plants, exhibits well‐documented antioxidant and anticancer activities. This study investigated whether Luteolin isolated from Pistacia terebinthus fruits could attenuate Cisplatin‐induced organ toxicity while enhancing its antiproliferative effects. For the in vivo experiments, 48 male Swiss albino mice (9–10 weeks old, 26–30 g) were randomly assigned to eight groups ( n = 6/group): control, Cisplatin, Luteolin (25, 50, or 100 mg/kg), and Cisplatin plus Luteolin (25, 50, or 100 mg/kg). Cisplatin (10 mg/kg/day, intraperitoneally) and/or Luteolin (25–100 mg/kg/day, orally) were administered for 14 consecutive days. Serum biochemical parameters, oxidative stress markers, antioxidant enzyme activities, and tissue injury‐related biomarkers were evaluated in liver and kidney tissues. Cisplatin administration significantly increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and glucose levels, whereas co‐treatment with Luteolin markedly attenuated these alterations in a dose‐dependent manner. In addition, Luteolin restored Cisplatin‐induced disturbances in oxidative stress and antioxidant defense markers, including malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), HSP70 levels, superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S‐transferase (GST) activities in liver and kidney tissues. To support the in vivo findings, in vitro antiproliferative assays were performed using Saos‐2 osteosarcoma, HTB‐9 bladder cancer, A549 lung cancer, and BEAS‐2B normal epithelial cell lines. Cells were treated with Luteolin (5–200 µM) alone or in combination with Cisplatin IC50 concentrations for 24–48 h, and cell viability was assessed using the WST‐1 assay. Co‐treatment with Luteolin significantly enhanced Cisplatin‐induced growth inhibition in cancer cells while exerting limited cytotoxicity in normal cells. Luteolin alone also demonstrated concentration‐dependent antiproliferative activity. In conclusion, Luteolin exerted marked hepatorenal protective effects and enhanced the antiproliferative activity of Cisplatin in experimental models. These findings suggest that Luteolin may represent a promising adjunctive candidate for reducing Cisplatin‐associated toxicity while improving therapeutic responsiveness.

Schiff bases have various pharmacological activities due to the azomethine (–C=N–) group. Usnic acid is the most famous lichen metabolite and it contains two carbonyl groups to synthesize the Schiff base derivatives with primary amines. Therefore, in the current study, the known Schiff base derivatives 2–5 of usnic acid (1) were synthesized to explore their antidiabetic, neuroprotective, antioxidant, antidepressant and anti-Parkinson’s disease properties. Among the tested compounds, compound 4 exhibited the strongest antidiabetic and antidepressant activities, inhibiting α-glycosidase, α-amylase and MAO-A enzyme activities, respectively. Moreover, all of the tested compounds strongly scavenged the ABTS and DPPH radicals and the ABTS radical scavenging activities of 3 and 4 were found to be higher than the commercial antioxidants BHA and trolox. None of the tested compounds showed any significant anti-Parkinson’s disease activity or neuroprotective action. In conclusion, compound 4 can be suggested as a drug candidate molecule for further studies due to its strong antioxidant, antidiabetic and antidepressant properties.

Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in plants. In this study, antiglaucoma, antidiabetic, anticholinergic, and antioxidant effects of Coumestrol were evaluated and compared with standards. To determine the antioxidant activity of coumestrol, several methods—namely N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD^•+)-scavenging activity, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS^•+)-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH^•)-scavenging activity, potassium ferric cyanide reduction ability, and cupric ion (Cu²⁺)-reducing activity—were performed. Butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, and butylated hydroxytoluene (BHT) were used as the reference antioxidants for comparison. Coumestrol scavenged the DPPH radical with an IC₅₀ value of 25.95 μg/mL (r²: 0.9005) while BHA, BHT, Trolox, and α-Tocopherol demonstrated IC₅₀ values of 10.10, 25.95, 7.059, and 11.31 μg/mL, respectively. When these results evaluated, Coumestrol had similar DPPH^•-scavenging effect to BHT and lower better than Trolox, BHA and α-tocopherol. In addition, the inhibition effects of Coumestrol were tested against the metabolic enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), and α-glycosidase, which are associated with some global diseases such as Alzheimer’s disease (AD), glaucoma, and diabetes. Coumestrol exhibited K_i values of 10.25 ± 1.94, 5.99 ± 1.79, 25.41 ± 1.10, and 30.56 ± 3.36 nM towards these enzymes, respectively.

: Five metabolites were isolated by chromatographic methods from the fruit stems of P. vera and their chemical structures were characterized as masticadienonic acid (1), tirucallol (2), masticadienolic acid (3), pistachionic acid (4) and inulobiose (5) via FT-IR, 1H-NMR, 13C-NMR, 1D-NMR and 2D-NMR. Pistachionic acid (4), a new shikimic acid derivative, was isolated from the ethanol extract for the first time. The hexane, chloroform, ethanol extracts and pure metabolites exhibited antidiabetic properties by inhibiting α- glycosidase and α-amylase enzymes at different rates. Their inhibitory effects against the α- glycosidase enzyme were also higher than that of the acarbose (IC50=10.30 mg/mL). Masticadienolic acid (3) (IC50=0.03 mg/mL), masticadienonic acid (1) (IC50=0.13 mg/mL) and hexane extract (IC50=0.09 mg/mL) with the lowest IC50 values were found to be most active substances. Nevertheless, the inhibitory effect of acarbose against the α-amylase enzyme was determined to be higher than the inhibition effects of the extracts and pure metabolites. According to the IC50 values, the best inhibitors against the α-amylase were ethanol extract (IC50=5.17 mg/mL), pistachionic acid (4) (IC50=7.35 mg/mL), tirucallol (2) (IC50=7.58 mg/mL) and masticadienolic acid (3) (IC50=8.22 mg/mL), respectively among the applications. In addition, anticholinesterase properties of the extracts and pure metabolites were investigated by testing the inhibitory properties against acetylcholine esterase (AChE) and butrylcholine esterase (BChE) enzymes activities. The results showed that the anticholinesterase properties of all extracts and pure metabolites were weaker than those of the commercial cholinesterase inhibitors, neostigmine and galantamine, and all applications reduced the activity of these enzymes at very high concentrations.

In this study, the antioxidant activity of the ethanolic extract of Colocasia esculenta tubers were determined by four different antioxidant tests including DPPH and ABTS radicals scavenging activities, metal chelating activity and reducing power. The scavenging effect of extract of C. esculenta tubers and standards on DPPH radical at the highest concentration (600 µg mL-1) decreased in the following order: Vitamin C˃Trolox˃C. esculenta˃BHA and were found as 95.4, 93.6, 83.8 and 78.8 %, respectively. The scavenging effect of C. esculenta tuber extract and standards on ABTS radical at the highest concentration (100 µg mL-1) decreased in the order: Trolox = BHA˃C. esculenta and were found as 100, 100, 94.6%, respectively. The metal chelating capacity of extract of C. esculenta tubers and standards decreased in the order of C. esculenta˃BHA˃Trolox at lowest concentration (100 µg mL-1) and was found to be 78.0, 76.0, 63.5 %, respectively. Reducing power of extract of C. esculenta tubers and standards at the highest concentration (600 µg mL-1) followed the order: BHA˃Trolox˃C. esculenta. Total phenolic compound and flavonoid amounts of C. esculenta tubers were designated as 2400 mg GAE/kg extract and 2050 mg QE/kg extract, respectively.