Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation and destruction, leading to significant pain and disability. Adenosine deaminase (ADA) is identified as a biomarker for RA’s inflammatory process. This study aims to investigate the potential of flavonoids and phenolic acids to inhibit ADA activity (in silico) and evaluate their anti-inflammatory effects in a RA model (in vivo). Methods: The molecular docking study was conducted using YASARA Structure 19.12.14. software following the Auto Dock 4.2 protocol. A rat model with pristane-induced arthritis was used to test the anti-inflammatory effect of selected polyphenols. The consistency of the development of the rat model was evaluated through the following indicators artistic score, paw volume, and body weight. Quercetin was administered intragastrically at doses of 150 and 400 mg/kg over 15 days. The C-reactive protein (CRP) level in serum was measured with an automatic biochemical analyzer. Statistical analyses were performed using SPSS 29.0.2.0. Results: Molecular docking simulations showed flavonoids inhibited ADA activity with inhibition constants ranging from 0.012 mM to 0.190 mM. In the in vivo RA model, quercetin significantly reduced joint inflammation and serum CRP levels at a higher dose of 400 mg/kg. Conclusion: Quercetin shows promise as an anti-inflammatory agent for RA by targeting ADA, suggesting that flavonoid-rich plant extracts could enhance RA treatment.

Abstract The study aimed to analyse the potential of Lamiaceae essential oils, extracts, and hydrolats against bacterial biofilms. Bacterial cells Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus cereus were exposed to Thymus vulgaris L. (thyme), Salvia officinalis L. (sage), Mentha × piperita L. (mint) essential oils, extracts, and hydrolats. The result of the minimal inhibitory concentration assessment shows the highest antibacterial potential for essential oils, followed by extracts and hydrolats respectively. The anti-biofouling capacity revealed that thyme essential oil has the highest potential for biofilm prevention for all tested bacteria, reducing up to 91% of biofilm, followed by mint (88%) and sage (87%) essential oil. While the thyme extract (84%), sage extract (83%) and hydrolat (77%) we less effective. The chemical composition of thyme essential oil showed a high percentage of monoterpene hydrocarbons and oxygenated monoterpenes, among which p-cymene and thymol were the most predominant. The bacterial cell membrane integrity assessment shows a significant increase in dead cells by increasing the concentration of thyme essential oil. The findings of our research indicate that the choice of herbal preparation significantly affects the active components, thereby influencing both antibacterial and anti-biofouling capabilities. Lamiaceae essential oils show great potential for biofilm management and represent a good candidate for antibacterial application in pharmacy, medicine, and industry.

Triterpenes are very important secondary metabolites with wide structural diversity and significant role in pharmacy and medicine.In the present research, a comparative study of pharamacological activities of the triterpene fractions obtained from several plant species belonging to Lamiaceae family, was carried out. In-vitro anti-proliferative activity was performed using a standardproliferation assay based on tetrazolium salts. In vitro anti-inflammatory activity of triterpene fractions was determined by an assay of inhibition of albumin denaturation. In general, the triterpene fractions obtained from plant species belonging to Lamiaceae family showed a strong anti-proliferative activity and anti-inflammatory activity.The triterpene fraction of Rosmarini folium showed the strongest anti-proliferative activity (GI50range from 4 to 37 μg/ml) and the strongest anti-inflammatory activity in the range from 57.27% to 80.69%. This comparative study provides scientific evidence to support the traditional use of Lamiacae plant species for medical purposes as anti-inflammatory and anti-proliferative medicines.

Aim There are more and more herbal preparations that are used for the purpose of treatment and improvement of the clinical manifestation of vaginitis not only by patients themselves, but also by healthcare professionals. Plant species, St. John's wort, chamomile, calendula, yarrow, shepherd's purse and tea tree oil are all well known for their anti-inflammatory, antimicrobial and wound healing activity. This paper presents the results of a clinical study in which three herbal formulations/vagitories, based on extracts of St. John's wort, chamomile, calendula, yarrow, shepherd's purse and tea tree oil, were investigated for their effectiveness on vaginitis. Methods This was a randomized controlled clinical study that included 210 women with diagnosed vaginitis. Patients were divided into two basic groups, women in reproductive period and postmenopausal period. Three subgroups including 30 patients each received one of the three vagitorie formulations for 5 days, after which the effects on subjective and objective symptoms were monitored. Results Three types of vagitories based on plant extracts had a positive effect in the treatment of vaginitis. Vagitories based on tea tree oil showed better efficiency compared to vagitories with St. John's wort and vagitories based on extracts of five plants. Women in postmenopausal group reported better tolerability of St. John's wort-based and five herbs-based vagitories compared to tea tree oil based vagitories. Conclusion Investigated vagitories showed a positive effect on both objective and subjective symptoms of vagitnis. No serious side effects were reported.

Hyperuricemia is a potential marker of cardiovascular diseases, and its relation to hypertension and arteriosclerosis, as well as the outcomes of certain cardiovascular events, is interesting. The research was carried out a sample of 50 subjects of both sexes, who were either on allopurinol or febuxostat treatment. Effects of allopurinol and febuxostat on concentrations of uric acid and some lipid fractions (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol) were observed in 25 subjects on allopurinol treatment, and in 25 subjects on febuxostat treatment, who were chosen by defined criteria, with each patient serving as his or her control. The total observation period was six months and the cut was made after the first three Original Research Article Ziga Smajic et al.; JPRI, 32(35): 44-54, 2020; Article no.JPRI.63434 45 months and at the end of the research. Evaluating the effectiveness of allopurinol in subjects with hyperuricemia, it was established that concentrations of uric acid decreased by 126.28±20.36 μmol/L, at the end of the research, compared to the initial concentration. In subjects who used febuxostat, at the end of the research, concentrations of uric acid decreased by 252.80±94.17 μmol/L, compared to the initial concentration. Evaluating the effectiveness of febuxostat on concentrations of lipid fractions, a statistically significant increase of 0.17±0.02 mmol/L in concentrations of HDL and a statistically significant decrease of 0.37±0.14 mmol/L in concentrations of LDL were noted. Subjects with gout treated with allopurinol had significantly lower average concentrations of cholesterol compared to subjects with gout and metabolic syndrome (p=0.001). Subjects with gout and metabolic syndrome had significantly higher concentrations of LDL at the beginning and the end of the research, regardless of therapy (p=0.045;p=0.049, respectively). Both drugs showed effectiveness in the treatment of hyperuricemia, and a certain effect on concentrations of lipid fractions.

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.

In the present study, we investigated the antiproliferative activity of essential oil from leaves of Melissa officinalis L. grown in Southern Bosnia and Herzegovina. In vitro evaluation of antiproliferative activity of the M. officinalis essential oil was carried out on three human tumor cell lines: MCF-7, NCI-H460 and MOLT-4 by MTT assay. M. officinalis essential oil was characterized by high percentage of monoterpenes (77,5%), followed by the sesquiterpene fraction (14,5%) and aliphatic compounds (2,2%). The main constituents of the essential oil of M. officinalis are citral (47,2%), caryophyllene oxide (10,2%), citronellal (5,4%), geraniol (6,6%), geranyl acetate (4,1%) and βcaryophyllene (3,8%). The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with GI50 values of <5, 6±2 and 31±17 μg/mL, respectively. The results revealed that M. officinalis L. essential oil has a potential as anticancer therapeutic agent.

BACKGROUND Currently, used oral antiplatelet drugs are both limited and associated with the risk of treatment failure/resistance. Research in this area is hence highly desired. A series of xanthene-3-ones derivatives, we had synthesized, showed us that these derivatives had antiplatelet activity. As far as we know, no research on the effects of xanthen-3-ones in this area has been done. OBJECTIVE The aim was to study the antiplatelet potential of a series of synthesised 9-phenylxanthene- 3-ones and to find the ideal structural feature(s) for antiplatelet potential and determine the mechanism of action. METHODS The compounds were synthesized from 1,2,4-triacetoxybenzene and various benzaldehydes. The reaction proceeded smoothly under acidic alcoholic conditions, furnishing the desired products in good yields. The compounds were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. RESULTS Initial screening showed that a majority of the synthesized derivatives had substantial antiplatelet potential. None of the compounds were able to block cyclooxygenase 1 or thromboxane synthase. The mechanism appeared to be based on antagonism of thromboxane effects. The most potent compound 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one had better potential to block collagen induced platelet aggregation than clinically used acetylsalicylic acid. CONCLUSION The last mentioned derivative is promising for further in vivo testing.

Introduction: We studied the chemical composition and antimicrobial, antioxidant, and antiproliferative activities of essential oils from flowers of Lavandula angustifolia grown in Southern Bosnia and Herzegovina. Methods: The chemical profile of essential oil was evaluated by means of gas chromatography-mass spectrometry. Antimicrobial activity was tested against six bacterial strains. The antioxidant activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test and the antiproliferative activity against three human cancer cell lines, MCF-7, NCI-H460, and MOLT-4, were investigated using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide tests. Results: In L. angustifolia essential oil, monoterpene alcohols were the most represented class of volatiles (51.8%), including linalool, lavandulol, and terpinen-4-ol, α-terpineol as the major components, followed by monoterpene esters (22.6%). The most important antibacterial activity of essential oil was expressed on Gram-negative strains. Investigated essential oil was able to reduce DPPH radicals into the neutral DPPH-H form (inhibitory concentration 50% [IC50] = 0.421 mg/ml), and this activity was dose dependent. The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with IC50 values of 17, 94, and 97 µg/ml, respectively. The result of the antiproliferative assay indicates that MOLT-4 cell line was the most sensitive to investigated essential oil. Conclusion: The results revealed that L. angustifolia essential oil may be important growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent antiproliferative activity against MOLT-4 cells.