Effect of hydroalcoholic extract of Berberis integerrima and resveratrol on ovarian morphology and biochemical parameters in Letrozole-induced polycystic ovary syndrome rat model: An experimental study

Background: Resveratrol and Berberis integerrima (B. integerrima) are known to be natural antioxidants and regulators of human metabolism. However, the effects of resveratrol and B. integerrima on the ovarian morphology in polycystic ovary syndrome (PCOS) are not obvious. Objective: This study aimed to determine the effect of the hydroalcoholic extract of B. integerrima in combination with resveratrol on some biochemical parameters and ovarian morphology in the letrozole-induced PCOS rat. Materials and Methods: Seventy adult female Sprague-Dawley rats aged 10-12 weeks weighing 200 ± 20 gr were randomly divided into seven groups (n = 10/each). Group I): normal; Group II): vehicle; Group III): letrozole-induced PCOS 1 mg/kg letrozole orally, rats receiving 1 cc normal saline orally; Group IV): PCOS + receiving 150 mg/kg metformin orally; Group V): PCOS + receiving 20 mg/kg resveratrol orally; Group VI): PCOS + 3 gr/kg barberry orally; and Group VII): PCOS + receiving 3 gr/kg barberry and 20 mg/kg resveratrol orally. All animals were followed-up for 63 days. The biochemical parameters and histological assessments of ovaries were performed. Results: Resveratrol alone and/or in combination with B. integerrima treatment in rats led to a significant decrease in low-density lipoprotein, triglyceride, malondialdehyde , and tumor necrosis factor-alpha concentrations (p = 0.02). The groups IV, V, VI, and VII showed a decrease in insulin resistance and an increase in the superoxide dismutase, total antioxidant capacity, and high-density lipoprotein (p = 0.01). No significant difference was observed between the level of serum glucose in the treatment groups. Number of cystic follicles had a significant decrease in barberry, resveratrol, and their combination groups (p < 0.001). Conclusion: Resveratrol, B. integerrima, and their combination as natural products with fewer side effects might be effective as an alternative medicine in treatment of PCOS. Key words: Barberry, Resveratrol, Polycystic ovary syndrome, Ovary, Rat

Antimicrobial and Cytotoxic Activity of Cuminum Cyminum as an Intracanal Medicament Compared to Chlorhexidine Gel

Introduction: The aims of this study were i) to define the chemical constituents of Cuminum cyminum (cumin) essential oil, ii) to compare the antimicrobial activity of this oil to that of chlorhexidine (CHX) and co-trimoxazole on planktonic and biofilm forms of bacteria isolated from the teeth with persistent endodontic infection and iii) to compare the cytotoxicity of these medicaments on L929 fibroblasts. Methods and Materials: Three groups of microorganisms [aerobic bacterial mixture, anaerobic bacterial mixture and Enterococcus faecalis (E .faecalis)] were isolated from the teeth with persistent apical periodontitis. Zone of inhibition (ZOI), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and time-kill tests were performed to assess the antimicrobial efficacy of the medicaments. Further, a cytocompatibility analysis of the medicaments was performed on L929 fibroblasts. The results obtained from disc diffusion test and mean cell viability values of the experimental medicaments were analyzed using two-way and one-way analysis of variance (ANOVA). Results: Seventeen constituents were recognized in cumin oil (predominantly cumin aldehyde and γ-terpinene). Co-trimoxazole showed the greatest ZOI followed by cumin and CHX. The smallest MIC and MBC belonged to co-trimoxazole followed by cumin and CHX for all groups of bacteria except for E. faecalis for which the MBC of cumin was smaller than co-trimoxazole. The results of time-kill assay revealed that all medicaments totally inhibited the bacterial growth in all groups after 24 h. CHX was the most cytotoxic solution while there were no significant differences between the cytocompatibility of different concentrations of cumin essential oil and co-trimoxazole. Conclusion: Cumin exhibited a strong antimicrobial efficiency against the microbial flora of the teeth with failed endodontic treatments and it was biocompatible for L929 mouse fibroblasts.Keywords: Antibacterial Activity; Chlorhexidine; Co-trimoxazole; Cuminum Cyminum; Cytotoxicity; Intracanal Medicamen

Thiazolopyrimidine derivatives as novel class of small molecule tyrosinase inhibitor

Abstract Tyrosinase, the rate-limiting enzyme of melanogenesis, plays a crucial role in hyperpigmentation. As a result, in this study, a novel class of thiazolopyrimidine derivatives was developed and synthesized as tyrosinase inhibitor. The structure of derivatives was characterized using various spectroscopy techniques, including FTIR, Mass, 1H-NMR, and 13C-NMR. Next, the inhibitory activities of all derivatives were examined against tyrosinase, and, 6a as the most potent compound, exhibited an IC50 value of 28.50 µM. Furthermore, the kinetic study of 6a was performed to better understand the inhibitory mechanism and its type of inhibition. The UV/Vis spectra analysis was also executed to provide valuable evidence supporting the inhibitory mechanism of compound 6a in the context of tyrosinase inhibition. Also, molecular docking and dynamic molecular study of 6a were executed to study its interactions within the enzyme’s binding site

The anti-Alzheimer potential of novel spiroindolin-1,2-diazepine derivatives as targeted cholinesterase inhibitors with modified substituents

Abstract In this study, a new series of spiro indolin-1,2-diazepine were designed, synthesized, and screened for their cholinesterase inhibitory activities. A novel, green, high-yielding approach was constructed to synthesize spiro indolin-1,2-diazepine derivatives through a cascade reaction of different isatins, malononitrile and 1,1-enediamines (EDAMs) via sequential four-component reactions to produce the target compounds with good to excellent yields. Next the inhibitory potencies of all derivatives were determined spectroscopically at 415 nm using the modified Ellman method. The results of the in vitro screening indicated that 5l with spiroindolin-1,2-diazepine core bearing 5-NO2 at R1 and 4-OH at R2 was the most potent and selective AChE inhibitor with an IC50 value of 3.98 ± 1.07 µM with no significant inhibition against BChE while 5j was the most active analog against both AChE and BChE enzymes. The structure–activity relationships suggested the variation in the inhibitory activities of derivatives was affected by different substitutions on the indolinone ring as well as the phenyl moiety. The enzyme kinetic studies of the most potent compound 5l at five different concentrations and acetylthiocholine substrate (0.1–1 mM) by Ellman's method revealed that it inhibited AChE in a mixed mode with a K i of 0.044 μM. A molecular docking study was performed via induced fit docking protocol to predict the putative binding interaction. It was shown that the moieties used in the initial structure design play a fundamental role in interacting with the enzyme's binding site. Further, molecular dynamics simulations with the Schrödinger package were performed for 5l in a complex with AChE and revealed that compound 5l formed the stable complex with the enzyme. The MTT toxicity assessments against the neuroblastoma cell line were executed, and no toxicity was seen for 5l under the tested concentrations

New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches

Abstract The simple and greener one-pot approach for the synthesis of biscoumarin derivatives using catalytic amounts of nano-MoO3 catalyst under mortar-pestle grinding was described. The use of non-toxic and mild catalyst, cost-effectiveness, ordinary grinding, and good to the excellent yield of the final product makes this procedure a more attractive pathway for the synthesis of biologically remarkable pharmacophores. Accordingly, biscoumarin derivatives were successfully extended in the developed protocols. Next, a computational investigation was performed to identify the potential biological targets of this set of compounds. In this case, first, a similarity search on different virtual libraries was performed to find an ideal biological target for these derivatives. Results showed that the synthesized derivatives can be α-glucosidase inhibitors. In another step, molecular docking studies were carried out against human lysosomal acid-alpha-glucosidase (PDB ID: 5NN8) to determine the detailed binding modes and critical interactions with the proposed target. In silico assessments showed the gold score value in the range of 17.56 to 29.49. Additionally, molecular dynamic simulations and the MM-GBSA method of the most active derivative against α-glucosidase were conducted to study the behavior of selected compounds in the biological system. Ligand 1 stabilized after around 30 ns and participated in various interactions with Trp481, Asp518, Asp616, His674, Phe649, and Leu677 residues

Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

In the current study, a series of dihydropyrimidinone derivatives were rationally designed as β-glucuronidase inhibitors. These designed compounds were successfully synthesized and characterized through various spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and EI-MS. A structure-activity relationship (SAR) of synthesized derivatives to inhibit β-glucuronidase was also established. In vitro biological evaluations revealed that 4i as the most potent compound in this series has an IC50 value of 31.52 ± 2.54 μM compared to the standard D-saccharic acid 1,4-lactone (IC50 = 41.32 ± 1.82 µM). Also, molecular docking and dynamics studies of the most potent compound are performed to evaluate interactions between the active compound and binding site

The Promising Therapeutic and Preventive Properties of Anthocyanidins/Anthocyanins on Prostate Cancer

As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options

Assessing Emissions of Volatile Organic Componds from Landfills Gas

Background: Biogas is obtained by anaerobic decomposition of organic wastes buried materials used to produce electricity, heat and biofuels. Biogas is at the second place for power generation after hydropower and in 2000 about 6% of the world power generation was allocated to biogas. Biogas is composed of 40–45 vol% CO2, 55–65 vol% CH4, and about 1% non-methaneVOCs, and non-methane volatile organic compounds. Emission rates are used to evaluate the compliance with landfill gas emission regulations by the United States Environmental Protection Agency (USEPA). BTEX comounds affect the air quality and may be harmful to human health. Benzene, toluene, ethylbenzene and xylene isomers that are generally called BTEX compounds are the most abundant VOCs in biogas. Methods: Sampling of VOCs in biogas vents was operated passively or with Tedlar bags. 20 samples were collected from 40 wells of old and new biogas sites of Shiraz’ landfill. Immediately after sampling, the samples were transferred to the laboratory. Analysis of the samples was performed with GC-MS. Results: The results showed that in the collection of the old and new biogas sites, the highest concentration of VOCs was observed in toluene (0.85ppm) followed by benzene (0.81ppm), ethylbenzene (0.13ppm) and xylene (0.08ppm). Conclusion: The results of the study showed that in all samples, most available compounds in biogas vents were aromatic hydrocarbon compounds.These compounds’ constituents originate from household hazardous waste materials deposited in the landfill or from biological/chemical decomposition processes within the landfill

Linarin, a Glycosylated Flavonoid, with Potential Therapeutic Attributes: A Comprehensive Review

Many flavonoids, as eminent phenolic compounds, have been commercialized and consumed as dietary supplements due to their incredible human health benefits. In the present study, a bioactive flavone glycoside linarin (LN) was designated to comprehensively overview its phytochemical and biological properties. LN has been characterized abundantly in the Cirsium, Micromeria, and Buddleja species belonging to Asteraceae, Lamiaceae, and Scrophulariaceae families, respectively. Biological assessments exhibited promising activities of LN, particularly, the remedial effects on central nervous system (CNS) disorders, whereas the remarkable sleep enhancing and sedative effects as well as AChE (acetylcholinesterase) inhibitory activity were highlighted. Of note, LN has indicated promising anti osteoblast proliferation and differentiation, thus a bone formation effect. Further biological and pharmacological assessments of LN and its optimized semi-synthetic derivatives, specifically its therapeutic characteristics on osteoarthritis and osteoporosis, might lead to uncovering potential drug candidates

Wound healing effect of Carum carvi L. on the incised skin wound in male rats: Histopathology, total protein and biomechanical evaluations

Abstract Background The skin has several functions, one of the most important of which is to protect the internal organs from external damage and the entry of germs. Since skin and wound healing is one of the mostly concerned issues worldwide, the development of wound healing remedies is one of the main fields in modern medical research. Objectives To evaluate the effect of the hydroalcoholic extract of Cumin carvi L. seed as one of the traditional medicinal plants used for wound healing through an in vivo model. Methods Wide circular skin wounds (2 × 2 cm) were created on the dorsal area of 50 Sprague–Dawley male rats ​​following ethical principles. The animals were divided into five groups including no treatment, base gel, tetracycline treatment, 10% v/v hydroalcoholic extract of Cumin carvi L. seed treatment and 20% v/v hydroalcoholic extract of Cumin carvi L. seed treatment group. Treatment was performed within 20 days. On days 1, 3, 5, 7 and 10, photographs were taken, and the percentage of wound healing was calculated. Also, on the 10th day, the skin area was sampled for histopathology and on the 20th day, the skin was sampled for biomechanical and total protein assessments. Results The results of wound healing percentage showed that from day 3 onwards, there was a significant improvement between the group treated with 20% v/v hydroalcoholic extract of Cumin carvi L. and the negative control and basal gel groups (p < 0.05). According to histopathological and total protein content evaluations, the amount of collagen production and inflammation score in the Cumin carvi‐treated groups confirmed the healing process compared to other groups. Conclusions According to the results of this project, 20% v/v ethanolic extract of Cumin carvi L. has potential therapeutic effects in the treatment of skin wounds. Wounds are one of the health concerns, and the economic burden of wound care and healing has continued to increase over the past years.  The healing effects of C. carvi. ethanolic extract on the wound were investigated. The histopathological and macroscopical evaluations, as well as total protein content, were measured to investigate its wound healing properties