The effect of tyrosol on diclofenac sodium-induced acute nephrotoxicity in rats.

Although diclofenac (DCF) is a nonsteroidal anti-inflammatory drug that is considered safe, its chronic use and overdose may show some toxic effects. The protective effect of tyrosol (Tyr) pretreatment against DCF-induced renal damage was investigated in this study. The 32 rats used in the study were randomly divided into four groups of eight rats each. According to the data obtained, it was determined that creatinine, urea, and blood urea nitrogen (BUN) levels increased in serum samples of the DCF group. Besides, the levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity decreased and the malondialdehyde (MDA) level increased in the kidney tissue. However, no change was observed in catalase (CAT) activity. Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (Tnf-α) levels increased and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels decreased. No change was detected in the level of interleukin 1 beta (IL-1ß). When the DCF+Tyr group and the DCF group were compared, it was assessed that Tyr had a curative effect on all biochemical parameters. Also, kidney damages, such as degeneration and necrosis of tubular epithelium and congestion of veins, were obviated by treatment with tyrosol in histopathological examinations. It was determined that Tyr pretreatment provided a protective effect against nephrotoxicity induced by DCF with its anti-inflammatory and antioxidant properties.

Enzyme Inhibition and Antioxidant Activities of Asparagus officinalis L. and Analysis of Its Phytochemical Content by LC/MS/MS.

In the study, water, ethanol, methanol, dichloromethane, and acetone extracts of Asparagus officinalis L. were obtained by maceration. DPPH⋅, ABTS⋅+ , FRAP, and CUPRAC methods determined the antioxidant capacities of all extracts. Moreover, the in vitro effects of extracts on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase (CA)-I, CA-II and α-Glycosidase were investigated. At a 10 µg/ml concentration, the extract with the highest Fe3+ reduction capacity was ethanol (AE), and the extract with the highest Cu2+ reduction capacity was acetone (AA). AE for AChE (IC50 =21.19 µg/ml) and α-Glycosidase (IC50 : 70.00 µg/ml), methanol (AM) for BChE (IC50 =17.33 µg/ml), CA-I and II (IC50 =79.65 and 36.09 µg/ml, respectively) showed the most potent inhibition effect. The content analysis of acetone extract was performed with LC/MS-MS, the first three phytochemicals found most were p-Coumaric acid, rutin, and 4-hydroxybenzoic acid (284.29±3.97, 135.39±8.19, and 102.06±5.51 µg analyte/g extract, respectively).

Investigation of the effects of safranal on the experimentally created rheumatoid arthritis model in rats.

Rheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-α, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.

Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats.

The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.

Some phenolic natural compounds as carbonic anhydrase inhibitors: An in vitro and in silico study.

This paper presents experimental and molecular docking studies on the inhibitory effects of tyrosol, hydroxytyrosol, luteolin, diosmetin, caffeic acid, luteolin 7-O-glycoside, and apigenin 7-O-glycoside from olive (Olea europaea L.) leaf against human carbonic anhydrase (hCA, E.C.4.2.1.1) isozymes I and II. After these isozymes were separately purified, their activities were determined using the esterase activity. IC50 values for hCA I and II were calculated as 2.02-11.38 µM and 2.23-9.05 µM, respectively. The compounds were identified as CA inhibitors, with Ki values in the ranges of 1.66-9.17 µM for the hCA I isozyme and 1.49-14.21 µM for hCA II. The inhibitory effects of these natural compounds were also compared to acetazolamide, which is a potent inhibitor of both CA isozymes. Our results may contribute to the synthesis of new CA inhibitors and pave the way for new drug design in the treatment of a number of diseases including cancer, obesity, diabetes, and glaucoma.

The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats.

One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3 ) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3 -treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3  + ESC groups, and NF-κB increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3  + ESC group compared to AlCl3 group. It was also determined that AlCl3 -induced tissue injury was significantly prevented by ESC co-treatment.

Evaluation of the effects of Cyclotrichium niveum on brain acetylcholinesterase activity and oxidative stress in male rats orally exposed to lead acetate.

Cyclotrichium niveum is an endemic plant for Turkey and it appears to have in vitro antioxidant and acetylcholinesterase inhibition properties. To the best of our knowledge, there has been no study on the in vivo effects of this plant. Therefore, the purpose of this study was to evaluate the effects of C. niveum on lead (Pb)-acetate-induced potential alterations in brain acetylcholinesterase activity, as well as oxidative stress in male rats. The rats were randomly assigned to control, Pb-acetate, C. niveum and Pb-acetate+ C. niveum groups. Pb-acetate was provided in drinking water (500 ppm), and C. niveum was administered via orogastric gavage (4 ml/kg) for 30 days. The acetylcholinesterase activity in the brain significantly decreased only in the Pb-acetate group. The malondialdehyde level significantly increased, and the reduced glutathione activity decreased in the Pb-acetate group. The reduced glutathione and glutathione-S-transferase activities of the C. niveum group were higher than the control group. No Pb was detected on a ppb level in the brain tissue of the control and C. niveum groups, while it was detected in the brains of the rats in the Pb-acetate and Pb-acetate+ C. niveum groups (185+8.98 ppb and 206+56.65 ppb, respectively). The data collected in this study suggested that C. niveum may reduce inhibition of brain AChE activity and oxidative stress against Pb-acetate-induced alterations in the brain of male rats.

Inhibitory properties of some heavy metals on carbonic anhydrase I and II isozymes activities purified from Van Lake fish (Chalcalburnus Tarichi) gill.

In this study, CA I and II isoenzymes were purified from Van Lake fish gills by using Sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography and to determine the effects of some metals on the enzyme activities. For purified CA I isoenzyme, yield, specific activity, and purification fold were obtained as 42.07%, 4948.12 EU/mg protein, and 116.61 and for CA II isoenzyme, 7%, 1798.56 EU/mg protein, and 42.38 respectively. Activity of CA was determined by measuring "CO2-hydratase activity". Purity control was checked by SDS-PAGE. In vitro inhibitory effect of Cu2+, Ag+, Cd2+, Ni2+ metal ions, and arsenic (V) oxide were also examined for both isozymes activities. Whereas Cu2+, Ag+, Cd2+, and Ni2+ ions showed inhibitory effects on both isozymes, arsenic (V) oxide showed activation effect. IC50 values were calculated by drawing activity %-[I] graphs for metal ions exhibiting inhibitory effects. IC50 values were determined as 3.39, 6.38, 13.52, and 206 µM for CA I isozyme and 6.16, 20.29, 46, and 223 µM for CA II isozyme respectively.

Inhibitory and Activating Effects of Some Flavonoid Derivatives on Human Pyruvate Kinase Isoenzyme M2.

Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of <60 µM. IC50 values of compounds 3-8 were calculated as 134, 415, 145, 163, 295 µM, and 3.5 mM, respectively. The molecules 9-12 showed an activation effect with values of AC50 of less than 90 µM. The IC50 values of the derivatives 13-17 were calculated as 115, 150, 200, 221, and 275 µM, respectively. The results show that catechin derivatives can be probably used as lead compounds for the design of PKM2 enzyme activators and inhibitors.

Purification of glucose-6-phosphate dehydrogenase and glutathione reductase enzymes from the gill tissue of Lake Van fish and analyzing the effects of some chalcone derivatives on enzyme activities.

Glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) are metabolically quite important enzymes. Within this study, these two enzymes were purified for the first time from the gills of Lake Van fish. In the purifying process, ammonium sulfate precipitation and 2',5'-ADP Sepharose 4B affinity column chromatography techniques for glucose-6-phosphate dehydrogenase, temperature degradation and 2',5'-ADP Sepharose 4B affinity column chromatography for glutathione reductase enzyme were used. The control of the enzyme purity and determination of molecular weight were done with sodium dodecyl sulfate polyacrylamide gel electrophoresis. K(M) and V(max) values were determined with Lineweaver-Burk plot. Besides, the effects of some chalcone derivatives on the purified enzymes were analyzed. For the ones showing inhibition effect, % activity-[I] figures were drawn and IC50 values were determined. K(i) value was calculated by using Cheng-Prusoff equation.

Purification and characterization of carbonic anhydrase from Agri Balik Lake trout gill (Salmo trutta labrax) and effects of sulfonamides on enzyme activity.

Carbonic anhydrase (CA) was purified from Agri Balik Lake trout gill (fCA) by affinity chromatography on a sepharose 4B-tyrosine-sulfanilamide column. The fCA enzyme was purified with about a 303.9 purification factor, a specific activity 4130.4 EU (mg-protein)(-1), and a yield of 79.3 by using sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The molecular weight determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was found to be about 29.9 kDa. The kinetic parameters, K(M) and V(max) were determined for the 4-nitrophenyl acetate hydrolysis reaction. Some sulfonamides were tested as inhibitors against the purified CA enzymes. The Ki constants for mafenide (1), p-toluenesulfonamide (2), 2-bromo-benzene sulfonamide (3), 4-chlorobenzene sulfonamide (4), 4-amino-6-chloro-1-3 benzenedisulfonamide (5), sulfamethazine (6), sulfaguanidine (7), sulfadiazine (8), and acetozazolamide (9) were in the range of 7.5-108.75 µM.

Examination of changes in enzyme activities of erythrocyte glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in rats given Naringenin and Lead acetate.

In our study, controlled experimental groups were performed by giving substances Lead acetate, Naringenin and Naringenin + Lead acetate to rats in vivo conditions Changes in the glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzyme activities in erythrocytes of rats in these groups were compared to the Control group. An inhibition significant degree for G6PD enzyme activity was observed in all groups when compared to the Control group (p < 0.001). While inhibition significant degree for 6PGD enzyme activity was observed in Lead acetate groups (p < 0.001), no significant effect was observed in the Naringenin and Naringenin + Lead acetate groups (p > 0.05). In addition, lead levels in the groups of rats were determined using an inductively coupled plasma mass spectrometer (ICP-MS) device. As a result of measurements by the ICP-MS device, lead levels were found as an average of 42.9 ± 2.51, 36.71 ± 1.13, 172.16 ± 9.63, and 95.07 ± 5.87 ppm in the Control, Naringenin, Lead acetate and Naringenin + Lead acetate groups, respectively. Our results were shown that Naringenin has protective effects on the Lead acetate induced oxidative stress erythrocytes in rat.

Investigation of the effects of some phenolic compounds on the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from human erythrocytes.

Polyphenols are the important compounds that have various bioactivities. They constitute vital active agents of not only daily diet but also natural medicines that are used traditionally. It is generally considered that they are safe because they are natural. In some conducted studies, different negative effects of these compounds were mentioned. Twelve phenolic compounds have been assayed to determine the effect of inhibition on glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro studies, the enzymes were purified from human erythrocytes using 2',5'-ADP Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid, ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin, only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect. Chlorogenic acid, p-coumaric acid, and syringic acid did not exhibit an effect on the activity of the two enzymes.

Bisphenol AF Caused Reproductive Toxicity in Rats and Cineole Co-Treatment Exhibited Protective Effect.

Bisphenol AF (BPAF) is increasingly used and now found in products intended for human consumption. The protective effect of 1,8-cineole (CIN) against BPAF-induced reproductive toxicity was investigated. Four groups were created, with each group consisting of eight rats: control, BPAF (200 mg/kg), CIN (200 mg/kg), and BPAF + CIN groups. The results demonstrated that the BPAF group exhibited a decline in testosterone levels and a decrease in sperm parameters compared with the control. Additionally, higher levels of MDA were observed, along with lower levels of GSH and GPx activity. CAT activity also decreased slightly. Tnf-α, Nf-κB levels were significantly higher, and caspase-3 expression was elevated, while PCNA expression decreased. BPAF significantly increased tissue degeneration compared with the control. However, the BPAF + CIN group showed statistically significant improvements in sperm parameters, except for concentration. They also exhibited an increase in testosterone levels and an improvement in MDA and GSH levels compared with the BPAF group. However, GPx activity partially enhanced. Tnf-α and Nf-κB levels were significantly reduced, and caspase-3 levels declined while PCNA and Bcl-2 levels increased. The Johnsen Testicular Biopsy score showed a substantial increase. Overall, these results suggest that CIN co-treatment in rats enhanced reproductive health and exhibited antioxidant, antiapoptotic, and anti-inflammatory properties against BPAF-induced testicular damage.

Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: an In Vitro and In Silico Approach.

INTRODUCTION: In this study, it was aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. BACKGROUND: Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM), which are considered amongst the most important diseases of today's world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, it is important to develop drugs with high therapeutic efficacy and better pharmacological profile. OBJECTIVE: This study sets out to determine the related enzyme inhibitors used in the treatment of AD and T2DM, which are considered amongst the most important diseases of today's world. METHODS: In the current study, the in vitro and in silico effects of dienestrol, hesperetin, L-thyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α-glycosidase enzyme activities were investigated. RESULTS: All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 µM and 0.83±0.195 µM, respectively. In addition, dienestrol, T3 and dobutamine molecules showed a more substantial inhibition effect than tacrine. Dobutamine molecule showed the most substantial inhibition effect for BChE enzyme, and IC50 and Ki values were determined as 1.83 µM and 0.845±0.143 µM, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the α-glycosidase enzyme, were determined as 13.57 µM and 12.33±2.57 µM, respectively. CONCLUSION: According to the results obtained, it may be said that the molecules used in the study are potential inhibitor candidates for AChE, BChE and α-glycosidase.

Carvacrol showed a curative effect on reproductive toxicity caused by Bisphenol AF via antioxidant, anti-inflammatory and anti-apoptotic properties.

Bisphenol AF (BPAF) is an endocrine disruptor, and human exposure to these chemicals is growing in industrialized nations. BPAF has been demonstrated in studies to have toxic effects on reproductive health. This study examined the effects of oral exposure to BPAF on the reproductive system and the protective effects of carvacrol in rats. From 32 Wistar albino rats, four separate groups were set up for this purpose. Carvacrol 75 mg/kg and BPAF 200 mg/kg were administered by oral gavage method. Rat sperm parameters and serum testosterone levels were measured after 28 days of administration. The study looked at the MDA in the testis tissues, as well as CAT, GPx, and GSH as antioxidants parameters, NF-κB and TNF-α as inflammatory markers, caspase-3 and Bcl-2 as apoptosis parameters, and PCNA as cell proliferation markers. In addition, testis tissues underwent histological evaluation. As a result, in rats exposed to only BPAF, sperm counts declined, testosterone levels reduced, oxidative stress, inflammation, and apoptosis increased, and cell proliferation decreased. Furthermore, severe disruptions in tissue architecture and decreased spermatogenesis were reported. In contrast, sperm parameters improved, testosterone levels increased, oxidative stress and inflammation decreased, and apoptosis was prevented in the carvacrol-treated group compared to the BPAF-only group. It was also found that spermatogenesis was maintained, and structural abnormalities in testicular tissue were mostly avoided with an increase in PCNA expression. According to the findings, despite BPAF-induced testicular and reproductive toxicity, carvacrol had therapeutic potential due to its anti-inflammatory, antioxidant, cell proliferation-increasing, and anti-apoptotic activities.

Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model.

The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-α and NF-κB levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. PRACTICAL APPLICATIONS: Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.

Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1ß), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

Oleuropein and Verbascoside - Their Inhibition Effects on Carbonic Anhydrase and Molecular Docking Studies.

Recently, carbonic anhydrase (CA, E.C.4.2.1.1) inhibitors from natural product have paved the way for novel drug design in the treatment and prevention of some global diseases such as glaucoma, diabetes, and cancer. For this purpose, the inhibition effects of oleuropein and verbascoside from olive (Olea europaea L.) oil on human carbonic anhydrase I, and II (hCA I, and II) isoenzymes were evaluated in the current study. The inhibition effects of both natural compounds were determined by the esterase activity (in vitro). IC50 value of oleuropein and verbascoside was calculated as 1.57 and 1.73 µM for hCA I isoenzyme, respectively. At the same manner, K i values were determined as 1.25 ± 0.42 and 2.00 ± 0.42 µM, respectively. Then, IC50 value of each compound for hCA II isoenzyme was calculated as 2.23 and 1.90 µM, respectively. Similarly, K i values were determined as 2.37 ± 0.87 µM and 1.49 ± 0.33 µM, respectively. Also, the inhibitory effects and potent binding mechanisms of oleuropein and verbascoside on hCA I, and II isoenzymes were realized by molecular docking studies. Consequently, both natural phenolic compounds demonstrated the potent inhibition profiles against the both isoenzymes. Therefore, we believe that these results may break new ground in the drug development for the treatment of some global disorders.