The genetic, morphological and taxonomic diversity of the genus Sorbus is due to homoploid and polyploid hybridisation, autopolyploidy and apomixis, which also influence the production and diversity of secondary metabolites, especially flavonoids. The aim of this study was to investigate the relationships and variations of flavonoids in terms of hybrid origin and ploidy level between the parental species and their hybrid derivatives. The sampling design included leaf material of the following Sorbus accessions from ten natural localities: parental taxa (di-, tri- and tetraploids of S. aria; diploid S. torminalis and S. aucuparia) and their di-, tri- and tetraploid hybrid derivatives from crosses of S. aria × S. torminalis (subg. Tormaria) as well as the tetraploid S. austriaca and S. bosniaca, which originate from crosses of S. aria × S. aucuparia (subg. Soraria). We analysed the flavonoid profiles from the leaf fractions by LC-MS. A total of 23 flavonoids were identified, including apigenin and luteolin derivatives, which distinguish the hybrid groups from each other. This profiling highlights the distinctiveness of the Tormaria and Soraria accessions and emphasises the potential of the subg. Tormaria for further research on bioactive compounds in biological studies.

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.

Among natural products, essential oils from aromatic plants have been reported to possess potent anticancer properties. In this work, we aimed to perform the cytotoxic concentration range screening and antiproliferative activity screening of chemically characterized Thymus vulgaris L. essential oil. In vivo bioassay was conducted using the brine shrimp lethality test (BSLT). In vitro evaluation of antiproliferative activity was carried out on three human tumor cell lines: breast adenocarcinoma MCF-7, lung carcinoma H460 and acute lymphoblastic leukemia MOLT-4 using MTT assay. Essential oil components thymol (36.7%), p-cymene (30.0%), γ-terpinene (9.0%) and carvacrol (3.6%) were identified by gas chromatography/mass spectrometry. Analyzed essential oil should be considered as toxic/highly toxic with LC50 60.38 µg/mL in BSLT and moderate/weakly cytotoxic with IC50 range 52.65–228.78 µg/mL in vitro, according to evaluated cytotoxic criteria. Essential oil induced a dose-dependent inhibition of cell proliferation in all tested tumor cell lines and showed different sensitivity. Dose dependent toxicity observed in bioassay as well as the in vitro assay confirmed that brine shrimp lethality test is an adequate method for preliminary toxicity testing of Thymus vulgaris L. essential oil in tumor cell lines.

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.

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.