A randomized double-blind active-controlled clinical trial on the efficacy of topical basil (Ocimum basilicum) oil in knee osteoarthritis.

Background: Basil is a widely used herb in Persian medicine and is gaining recognition as a functional food worldwide. Aim of the study: This trial aimed to assess the effectiveness of a traditional formulation of basil oil in comparison with diclofenac gel in treating knee osteoarthritis, considering its established anti-inflammatory, anti-nociceptive, and anti-oxidative properties. Materials and methods: One hundred eligible patients were equally randomized to the traditional basil oil (containing sesame oil) and diclofenac gel groups. They used their respective topical treatments thrice daily for 4 weeks. Various measurements were taken at the beginning of the study, 2, and 4 weeks after starting the intervention, including the 8-m walk test, knee pain (based on visual analog scale), flexion angle of the knee joint, analgesic consumption, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Results: No significant differences were observed between the basil oil and diclofenac gel groups in any of the measured outcomes. However, significant improvements were noted within each group for most variables. Conclusion: Topical application of the traditional formulation of basil oil appears to improve clinical symptoms and certain functional indicators of knee osteoarthritis to a similar extent as diclofenac gel. This suggests that basil oil could be considered an effective management option for this condition. Clinical Trial Registration: https://irct.behdasht.gov.ir/, identifier IRCT2017081711341N7.

A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Peppermint and menthol: a review on their biochemistry, pharmacological activities, clinical applications, and safety considerations.

In this manuscript, we conducted a comprehensive review of the diverse effects of peppermint on human health and explored the potential underlying mechanisms. Peppermint contains three main groups of phytochemical constituents, including essential oils (mainly menthol), flavonoids (such as hesperidin, eriodictyol, naringenin, quercetin, myricetin, and kaempferol), and nonflavonoid phenolcarboxylic acids. Peppermint exhibits antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, anti-cancer, anti-aging, and analgesic properties and may be effective in treating various disorders, including gastrointestinal disorders (e.g., irritable bowel syndrome, dyspepsia, constipation, functional gastrointestinal disorders, nausea/vomiting, and gallbladder stones). In addition, peppermint has therapeutic benefits for psychological and cognitive health, dental health, urinary retention, skin and wound healing, as well as anti-depressant and anti-anxiety effects, and it may improve memory. However, peppermint has paradoxical effects on sleep quality and alertness, as it has been shown to improve sleep quality in patients with fatigue and anxiety, while also increasing alertness under conditions of monotonous work and relaxation. We also discuss its protective effects against toxic agents at recommended doses, as well as its safety and potential toxicity. Overall, this review provides the latest findings and insights into the properties and clinical effects of peppermint/menthol and highlights its potential as a natural therapeutic agent for various health conditions.

Chemical Composition and Antifungal and Antibiofilm Effects of Vitex pseudo-negundo Essential Oil against Pathogenic Fungal Strains.

Background: Vitex pseudo-negundo is a plant of the Lamiaceae family that grows in different parts of the world and the vicinity of seasonal rivers in Iran. Methods: The chemical composition of the Vitex pseudo-negundo essential oils was distilled and evaluated using gas chromatography/mass spectrometry. The antifungal activity of the essential oils against the fungal strains was analyzed by broth microdilution methods as suggested by the Clinical and Laboratory Standards Institute. Furthermore, the antibiofilm activity of the Vitex pseudo-negundo essential oils was assessed using the XTT reduction assay. Results: Based on GC/MS analysis, the major components of the Vitex pseudo-negundo essential oils were α-pinene, α-terpinyl acetate, limonene, and (E)-caryophyllene. The growth of tested yeasts was inhibited at concentrations ranging from 2 to 64 µl/mL. Vitex pseudo-negundo fruit essential oil was the most effective in inhibiting yeast growth. Moreover, the essential oils exhibited antifungal activity against filamentous fungi strains. Additionally, the biofilm formation of Candida albicans was inhibited by the leaf, flower, and fruit of the essential oils. Conclusion: Considering the significant antifungal activities of these essential oils, they can be considered a potential source for formulating novel agents to control fungal infections.

Phenyl-quinoline derivatives as lead structure of cholinesterase inhibitors with potency to reduce the GSK-3ß level targeting Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Unfortunately, there is no effective treatment for this condition, so there is a growing interest in developing new anti-AD agents. In this research project, a series of phenyl-quinoline derivatives were designed as potential anti-AD agents. These derivatives were substituted at two different positions on benzyl and phenyl rings. The structures of the derivatives were characterized using techniques such as IR spectroscopy, 1H NMR, 13C NMR, and elemental analysis. During the in vitro screening, the derivatives were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was observed that most of the derivatives showed higher selectivity against BChE compared to AChE. Among the derivatives, analog 7n (with a methoxy group at R1 and a 4-bromine substituent at R2 exhibited the highest potency, with a 75-fold improvement in the activity compared to the positive control. Importantly, this potent analog demonstrated no toxicity at the tested concentration on SH-SY5Y cells, indicating its potential as a safe anti-AD agent. The level of GSK-3ß was also reduced after treatments with 7n at 50 µM. Overall, this study highlights the design and evaluation of phenyl-quinoline derivatives as promising candidates for developing novel anti-AD agents.

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

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 Ki 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.

Hydroalcoholic extract of Glycyrrhiza glabra root combined with Linum usitatissimum oil as an alternative for hormone replacement therapy in ovariectomized rats.

Objective: Plant-derived estrogens (phytoestrogens) with structural similarity to primary female sex hormones could be suitable replacements for sex hormones. Therefore, the effects of the licorice root extract and Linum usitatissimum oil on biochemical and hormonal indices in the serum and uterine stereological changes in ovariectomized rats were evaluated. Design: In this study, 70 adult female rats were randomly divided into seven groups including 1) control group, 2) sham-operated group, 3) ovariectomized (OVX) group, 4) OVX rats that received 1 mg/kg estradiol for 8 weeks at the day of post-operation, 5) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil for 8 weeks at the day of post-operation, 6) OVX rats which received 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation, and 7) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil + 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation. After eight weeks, alkaline phosphatase activity, as well as calcium, estradiol, and progesterone concentrations were assessed and tissue samples of the uterus were serologically examined. Results: The results indicated that after 8 weeks of OVX the alkaline phosphatase activity (Mean = 637.7 IU/L) increased and the calcium (Mean = 7.09 mg/dl), estradiol (5.30 pmol/L), and progesterone (Mean = 3.53 nmol/L) reduced compared to other groups. Moreover, stereological changes in the uterus in ovariectomy groups were seen compared to the other groups. The treatment with Linum usitatissimum oil and licorice extract had a significant therapeutic effect on biochemical factors and stereological changes compared to the ovariectomized group. Conclusion: The results of this study showed that the combination of Linum usitatissimum oil with licorice extract showed the high potential of hormone replacement therapy in the reduction of OVX complications.

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 µM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 µM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 µM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 µM) and 8a (IC50 = 12.96 µM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 µM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Development and characterization of a fucoidan-based nanoemulsion using Nigella sativa oil for improvement of anti-obesity activity of fucoxanthin in an obese rat model.

The anti-obesity activity of encapsulated fucoxanthin in fucoidan-based nanoemulsion was investigated. Then, high-fat diet (HFD) induced-obese rats were fed along with different treatments including administration of encapsulated fucoxanthin (10 mg/kg and 50 mg/kg/day), fucoidan (70 mg/kg), Nigella sativa oil (250 mg/kg), metformin (200 mg/kg), and free form of fucoxanthin (50 mg/kg) by oral gavage daily for 7 weeks. The study discovered that fucoidan-based nanoemulsions with a low and high dose of fucoxanthin had droplet size in the range of 181.70-184.87 nm and encapsulation efficacy of 89.94-91.68 %, respectively. Also exhibited 75.86 % and 83.76 % fucoxanthin in vitro release. The TEM images and FTIR spectera confirmed the particle size and encapsulation of fucoxanthin, respectively. Moreover, in vivo results revealed that encapsulated fucoxanthin reduced body and liver weight compared with a HFD group (p < 0.05). Biochemical parameters (FBS, TG, TC, HDL, LDL) and liver enzymes (ALP, AST, and ALT) were decreased after fucoxanthin and fucoidan administration. According to the histopathological analysis, fucoxanthin and fucoidan attenuated lipid accumulation in the liver.

The healing effects of thymoquinone on experimentally induced traumatic tendinopathy in rabbits.

OBJECTIVES: Thymoquinone is a major bioactive compound present in the black seeds of the Nigella sativa. Tendon injuries are almost 50% of all musculoskeletal injuries. The recovery of tendon after surgery has become a significant challenge in orthopedics. DESIGN: The purpose of this study was to investigate the healing effect of thymoquinone injections in 40 New Zealand rabbits tendon traumatic models. MATERIALS AND METHODS: Tendinopathy was induced by trauma using surgical forceps on the Achilles tendon. Animals were randomly divided into 4 groups: (1) normal saline injection (control), (2) DMSO injection, (3) thymoquinone 5% w/w injection, and (4) thymoquinone 10% w/w injection. Forty-two days after surgery, biochemical and histopathological evaluations were done, and biomechanical evaluation was conducted 70 days after surgery. RESULTS: Breakpoint and yield points in treatment groups were significantly higher compared to control and DMSO groups. Hydroxyproline content in the 10% thymoquinone receiving group was higher than all groups. Edema and hemorrhage in the histopathological evaluation were significantly lower in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control and DMSO groups. Collagen fibers, collagen fibers with fibrocytes, and collagen fibers with fibroblasts were significantly higher in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control groups. CONCLUSIONS: Thymoquinone injection in the tendon in the concentration of 10% w/w is a simple and low-cost healing agent that could enhance mechanical and collagen synthesis in traumatic tendinopathy models in rabbit.

Cinnamomum verum J. Presl. Bark essential oil: in vitro investigation of anti-cholinesterase, anti-BACE1, and neuroprotective activity.

BACKGROUND: Cinnamomum verum J. Presl. (Lauraceae), Myrtus communis L. (Myrtaceae), Ruta graveolens L. (Rutaaceae), Anethum graveolens L. (Apiaceae), Myristica fragrans Houtt. (Myristicaceae), and Crocus sativus L. (Iridaceae) have been recommended for improvement of memory via inhalation, in Iranian Traditional Medicine (ITM). In this respect, the essential oils (EOs) from those plants were obtained and evaluated for cholinesterase (ChE) inhibitory activity as ChE inhibitors are the available drugs in the treatment of Alzheimer's disease (AD). METHODS: EOs obtained from the plants under investigation, were evaluated for their potential to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro based on the modified Ellman's method. The most potent EO was candidate for the investigation of its beta-secretase 1 (BACE1) inhibitory activity and neuroprotectivity. RESULTS: Among all EOs, C. verum demonstrated the most potent activity toward AChE and BChE with IC50 values of 453.7 and 184.7 µg/mL, respectively. It also showed 62.64% and 41.79% inhibition against BACE1 at the concentration of 500 and 100 mg/mL, respectively. However, it depicted no neuroprotective potential against ß-amyloid (Aß)-induced neurotoxicity in PC12 cells. Also, identification of chemical composition of C. verum EO was achieved via gas chromatography-mass spectrometry (GC-MS) analysis and the major constituent; (E)-cinnamaldehyde, was detected as 68.23%. CONCLUSION: Potent BChE inhibitory activity of C. verum EO can be considered in the development of cinnamon based dietary supplements for the management of patients with advanced AD.

Accelerating effect of Shilajit on osteogenic property of adipose-derived mesenchymal stem cells (ASCs).

BACKGROUND: Shilajit has been widely used remedy for treating a numerous of illness such as bone defects in Iran traditional folk medicine since hundreds of years ago. The aim of the present study was to explore the effect of Shilajit on the osteogenic differentiation of human adipose-derived mesenchymal stem cells (ASCs) in two- (2D) and three-dimensional (3D) cultures. MATERIALS AND METHODS: ASCs were seeded in 3D 1% alginate (Alg) hydrogel with or without Shilajit (500 µg/mL) and compared with 2D cultures. Then, characterization was done using electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), alkaline phosphatase (ALP) activity, alizarin red staining and Raman confocal microscopy. RESULTS: Adding Shilajit had no impact on the Alg scaffold degradability. In the 3D hydrogel and in the presence of osteogenic medium (OM), Shilajit acted as enhancer to increase ALP activity and also showed osteoinductive property in the absence of OM compared to the 2D matched groups at all time points (days 7 and 21 both P = 0.0006, for 14 days P = 0.0006 and P = 0.002, respectively). In addition, calcium deposition was significantly increased in the cultures exposed to Shilajit compared to 2D matched groups on days 14 (P < 0.0001) and 21 (P = 0.0003 and P = 0.003, respectively). In both 3D and 2D conditions, Shilajit induced osteogenic differentiation, but Shilajit/Alg combination starts osteogenic differentiation in a short period of time. CONCLUSION: As Shilajit accelerates the differentiation of ASCs into the osteoblasts, without changing the physical properties of the Alg hydrogel, this combination may pave the way for more promising remedies considering bone defects.

Investigating the Effect of Hydroalcoholic Extract of Licorice Root to Prevent Ovariectomy-Mediated Complications.

Introduction: The importance of women's health and the quality of life after menopause is a critical issue. To prevent disability and menopause complications as well as avoid the side effects of hormone replacement therapy (HRT), in this study, licorice hydroalcoholic extract (Glycyrrhiza uralensis roots) was evaluated as a natural remedy. Methods: Seventy-two female Sprague-Dawley rats were divided into six groups: control group, Sham-operated group, Glycyrrhiza (Gly) 30% group, and ovariectomized group as well as two ovariectomized groups treated with Gly 10% and Gly 30%. Normal saline and different treatments were administered orally for 8 weeks. At the end of the study, calcium, alkaline phosphatase, estrogen, and progesterone levels in the ovariectomized rats were determined. Moreover, the stereological and histopathological changes in uterine tissue in all groups were determined. Phytochemical analyses were also performed to determine the total phenolic content and antioxidant potential of the extract. Result: The hydroalcoholic extract of licorice root exhibited considerable effect to improve calcium, estrogen, and progesterone levels in the ovariectomized rats. Also, hydroalcoholic extract of licorice root successfully decreases the amount of alkaline phosphatase (ALP) level. The stereological and histopathological findings confirmed the therapeutic potential of this extract. The considerable effects of hydroalcoholic extract of licorice root could be due to high amounts of phytoestrogens with similar estrogen-like structures. Considerable total phenolic content and antioxidant activity were also seen in licorice root extract. Conclusion: Hydroalcoholic extract of licorice root due to containing high amounts of phytoestrogens with similar chemical structures to estradiol notably improves biochemical parameters as well as stereological and histopathological markers of uterine tissues in ovariectomy rats, so it could be a potential agent for prevention and/or treatment as hormone replacement therapy in healthy middle-aged and/or older women.

The effect of hydroalcoholic extract of Psidium guajava L. on experimentally induced oral mucosal wound in rat.

BACKGROUND: The aim of this study was to evaluate the biological effects of hydroalcoholic extract of Psidium guajava L leaves and phenytoin as a standard agent on the induced oral mucosal wound. METHODS: Hundred seventy Sprague Dawley rats were grouped in 5 clusters randomly. Oral mucosal wounds were induced in all rats except for the control group. Phenytoin and guajava leaf extract were used as a mouthwash. Twelve rats from the 5 groups were euthanized on day 7th and 10th, and 10 rats from each group were sacrificed on the 14th day. Interleukin-6 and total antioxidant capacity were determined in the serum. The tissues were evaluated for pathological and stereological assessments. Phytochemical analyses were performed on the hydroalcoholic extract of Psidium guajava L to determine the antioxidant potency. RESULTS: Total phenolic content test and DPPH analysis demonstrated the high potential of antioxidant capacity of Psidium guajava L. Decreasing IL-6 and increasing TAC were seen in the guajava hydroalcoholic extract and phenytoin groups. The difference of IL-6 between the wound treated guajava group and the wounded group was significant. The wound treated guajava group and wound treated phenytoin group on the 14th day increased the number of fibroblast cells and volume density of sub-mucosae effectively to the same thickness to be considered as a healed sub-mucosae layer. The volume density of the epithelium changes showed statistically significant different responses based on gender. CONCLUSION: In conclusion, hydroalcoholic extract of Psidium guajava L leaves might exert theraputic effects on oral mucositis.

Synthesis, molecular docking, and cytotoxicity of quinazolinone and dihydroquinazolinone derivatives as cytotoxic agents.

BACKGROUND: Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a-e and dihydroquinazolinone 10a-f compounds were designed, synthesized as cytotoxic agents. METHODOLOGY: All derivatives (5a-e and 10a-f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software. RESULTS AND DISCUSSION: Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87-205.9 µM against HCT-116 cell line and 14.70-98.45 µM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 µM after 72 h, respectively, indicated the plausible activities of the synthesized compounds. CONCLUSION: The compounds quinazolinone 5a-e and dihydroquinazolinone 10a-f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.

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.

Synthesis and anti-Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain.

BACKGROUND: Conventional treatment for toxoplasmosis have severe side effects and the inability to completely eradicate the disease. Therefore, the acquisition of new anti-Toxoplasma drugs has always been of interest among researchers. In the present study, we prepare a new indole-triazole derivatives and evaluated their potential anti-parasitic activity against tachyzoites of Toxoplasma RH strain. MATERIALS AND METHODS: In this study, after synthesis of the two new compounds of indole-triazole, the effect of their different concentrations (2-1024 µg/ml) were determined on Toxoplasma tachyzoites using flow cytometry. Furthermore, tachyzoites were exposed to different concentrations of compounds (4, 16, 64, 265, 1024 µg/ml) for 1.5 h and their infectivity were evaluated in BALB/c mice. RESULTS: The flow cytometry results indicated the benzyl derivative of indole-triazole in various concentrations had a lethal effect on tachyzoites between 11.93% and 89.66%, while the naphthalene derivative had a lethality of 26.63%-66.82%. The infectivity analysis showed that the survival time of mice at concentrations of 1024 µg/ml and 512 µg/ml of benzyl derivatives was significantly increased (P = 0.008 and P = 0.016, respectively), compared to that in the negative control group. Furthermore, survival time of mice was statistically significant at the concentration of 1024 µg/ml for naphthyl derivative (P = 0.012). CONCLUSION: Findings of the current study suggested indole triazole compounds, based on their structure and enzymes targeting, have a considerable effect on tachyzoites of T. gondii RH strain and can be considered as a new anti-Toxoplasma agent.

Does application of honey improve surgical outcome in pilonidal cyst excision with secondary intention healing? A prospective randomized placebo-controlled clinical trial.

BACKGROUND: Pilonidal sinus disease (PSD) is a common chronic inflammatory debilitating illness caused by ingrowth of hair into the skin. Excision and healing by secondary intention is one of the acceptable managements. The post-operative wound care needs frequent and time-consuming follow-ups. Honey is considered to be a traditional remedy for wound healing. The current study aimed at finding if application of honey could improve surgical outcome in pilonidal cyst excision with secondary intention healing. METHODS: This study was designed as a randomized placebo-controlled parallel assignment interventional (clinical trial) study conducted at the surgical ward of Shahid Beheshti Hospital affiliated to the Yasuj University of Medical sciences, Yasuj, Iran, and was consisted of the 48 patients who underwent surgical resection for PSD with secondary intention healing (24 patients in intervention and placebo-controlled groups). The main element of honey medicinal gel was the unheated natural honey of Dena Biosphere Reserve within the Zagros Mountains. Patients' wounds were visited by a surgeon and a nurse on the days 7, 15, 30, 45, 60, and 90 post-operation. The surgical outcomes including the time to complete wound healing, pain intensity, odor, discharge at the site of surgery, use of analgesics, the time of to return to the daily activities, and occurring of any side effects including infection, erythema, and bleeding were all recorded. RESULTS: In intervention group, there was significantly lower wound healing time, the lower time to return to the daily activities, lower mean wound volume at the days of 30, 45, 60, and 90 of the follow-up, higher mean post-operative pain level at the days of 15, 30, 45, 60, and 90 of the follow-up, and more usage of analgesics at the days of 15, 30, 45, and 60 of the follow-up. There was no significant difference between intervention and placebo-controlled groups according to the foul smell and fluid discharge at the site of the operation. There were no side effects and complications in both groups of the study. CONCLUSIONS: Application of honey after resection surgery with secondary wound healing is associated with a better surgical outcome and could eventually decrease healing time and reduce duration of return to normal activities, but could increase post-operation pain and analgesic consumption, and no effect on foul smell and discharge. TRIAL REGISTRATION: The project was found to be in accordance to the ethical principles and the national norms and standards for conducting research in Iran with the approval ID and date of IR.YUMS.REC.1399.088 and 2020.05.30 respectively, and is the result of a residency dissertation to get the specialty in general surgery, which has been registered with the research project number 960508 in the Vice Chancellor for Research and Technology Development of Yasuj University of Medical Sciences, Yasuj, Iran, URL: https://ethics. RESEARCH: ac.ir/EthicsProposalViewEn.php?id=144742.

Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease.

Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assay confirmed high potency of the title compounds. Among them, compounds 7l and 7b demonstrated high activity toward AChE and BChE with IC50 values of 0.050 and 0.039 µM, respectively. Both compounds showed very good self-induced Aß aggregation and AChE-induced inhibitory activity (79.4 and 71.4% for compound 7l and 61.8 and 58.6% for compound 7b, respectively). Also, 7l showed good anti-BACE1 activity with IC50 value of 1.65 µM. The metal chelation test indicated the ability of compounds 7l and 7b to chelate biometals (Zn2+, Cu2+, and Fe2+). However, they showed no significant neuroprotectivity against Aß-induced damage in PC12 cells. Evaluation of in vitro hepatotoxicity revealed comparable toxicity of compounds 7l and 7b with tacrine. In vivo studies by Morris water maze (MWM) task demonstrated that compound 7l significantly reversed scopolamine-induced memory deficit in rats. Finally, molecular docking studies of compounds 7l and 7b confirmed establishment of desired interactions with the AChE, BChE, and BACE1 active sites.