Severity of oxidative stress as a hallmark in COVID-19 patients.

INTRODUCTION: Understanding the mechanisms and identifying effective treatments for the COVID-19 outbreak are imperative. Therefore, this study aimed to assess the antioxidant status and oxidative stress parameters as potential pivotal mechanisms in asymptomatic, non-severe, and severe COVID-19 patients. METHODS: This study is a case-control study that was performed on patients referred to the Persian Gulf Martyrs Hospital of Bushehr University of Medical Sciences, Bushehr, Iran, from May 2021 to September 2021. A total of 600 COVID-19 patients (non-severe and severe group) and 150 healthy volunteers of the same age and sex were selected during the same period. On the first day of hospitalization, 10 ml of venous blood was taken from subjects. Then, hematological, biochemical, serological, antioxidant and oxidative stress parameters were determined. RESULTS: Our results indicated that ESR, CRP, AST, ALT, and LDH significantly augmented in the severe group as compared to the non-severe and normal groups (P ≤ 0.05). It was observed that the levels of FRAP, G6PD activity, and SOD activity significantly reduced in the non-severe patients in comparison with the severe and normal groups (P ≤ 0.05). We found that MDA content and NO metabolite markedly increased in severe patients as compared to the non-severe group. CONCLUSIONS: Taken together, it seems that the balance between antioxidants and oxidants was disturbed in COVID-19 patients in favor of oxidant markers. In addition, this situation caused more aggravation in severe patients as compared to the non-severe group.

Phytochemical analysis and anticholinesterase activity of aril of Myristica fragrans Houtt.

In this study, the ethyl acetate fraction of Myristica fragrans Houtt. was investigated for its in vitro anticholinesterase activity as well as neuroprotectivity against H2O2-induced cell death in PC12 neuronal cells and the ability to chelate bio-metals (Zn2+, Fe2+, and Cu2+). The fraction was inactive toward acetylcholinesterase (AChE); however, it inhibited the butyrylcholinesterase (BChE) with IC50 value of 68.16 µg/mL, compared with donepezil as the reference drug (IC50 = 1.97 µg/mL) via Ellman's method. It also showed good percentage of neuroprotection (86.28% at 100 µg/mL) against H2O2-induced neurotoxicity and moderate metal chelating ability toward Zn2+, Fe2+, and Cu2+. The phytochemical study led to isolation and identification of malabaricone A (1), malabaricone C (2), 4-(4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzene-1,2-diol (3), nectandrin B (4), macelignan (5), and 4-(4-(benzo[d][1,3]dioxol-5-yl)-1-methoxy-2,3-dimethylbutyl)-2-methoxyphenol (6) which were assayed for their cholinesterase (ChE) inhibitory activity. Compounds 1 and 3 were not previously reported for M. fragrans. Among isolated compounds, compound 2 showed the best activity toward both AChE and BChE with IC50 values of 25.02 and 22.36 µM, respectively, compared with donepezil (0.07 and 4.73 µM, respectively).

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.

The Hydroalcoholic Extract of Nasturtium officinale Reduces Lung Inflammation and Oxidative Stress in an Ovalbumin-Induced Rat Model of Asthma.

Background: Asthma is known as a disease that causes breathing problems in children and adults and is also associated with chronic inflammation and oxidative stress of the airways. Nasturtium officinale (NO) possesses a wide range of pharmacological properties, particularly anti-inflammation and antioxidant potentials. Thus, this study for the first time was aimed to investigate anti-inflammatory and antioxidative activities of NO extract (NOE) in an ovalbumin-induced rat model of asthma. Materials and Methods: Forty-four male Wistar rats were sensitized with ovalbumin (OVA) to induce asthma symptoms. The animals were allocated into five groups: control (C), asthmatic (A), A + NOE (500 mg/kg), NOE (500 mg/kg), and A + dexamethasone (DX, 2.5 mg/kg). After 7 days, blood and tissue samples were taken from the rats. Then, the level of inflammatory markers, oxidative stress parameters, and antioxidant enzymes activity were measured. Results: The obtained results showed that OVA-sensitive rats significantly increased the levels of pro-inflammatory cytokines IL-1B, TGF-ß, and SMA-α compared to the control group (p < 0.05), while treatment with NOE remarkably reduced the SMA-α gene expression compared to the asthma group (p < 0.05). Furthermore, it decreased the expression of IL-1B and TNF-α genes, although it was not statistically significant. The level of glutathione peroxidase (GPX) significantly reduced in A group compared to the C group (p < 0.05), whereas NOE administration significantly increased this marker (p < 0.05). Moreover, NOE attenuated inflammation and alveolar injury in the lungs of OVA-sensitive rat compared to the nontreated A group. Conclusions: Overall, our findings demonstrated that NOE somewhat is able to reduce airway inflammation by reducing inflammatory and increasing GPX activity. Indeed, further experiments investigating the impact of different extract doses are needed to confirm the antioxidant and anti-inflammatory effects of NOE.

Glucosinolates and their hydrolysis products as potential nutraceuticals to combat cytokine storm in SARS-COV-2.

INTRODUCTION: The high mortality rate in severe cases of COVID-19 is mainly due to the strong upregulation of cytokines, called a cytokine storm. Hyperinflammation and multiple organ failure comprise the main clinical features of a cytokine storm. Nrf2 is a transcription factor which regulates the expression of genes involved in immune and inflammatory processes. Furthermore, Nrf2, as a master regulator, controls the activity of NF-κB which binds to the promoter of many pro-inflammatory genes inducible of various inflammatory factors. Inhibition of Nrf2 response was recently demonstrated in biopsies from patients with COVID-19, and Nrf2 agonists inhibited SARS-CoV-2 replication across cell lines in vitro. Glucosinolates and their hydrolysis products have excellent anti-inflammatory and antioxidant effects via the Nrf2 activation pathway, reduction in the NF-κB activation, and subsequent reduced cytokines levels. CONCLUSION: Accordingly, these compounds can be helpful in combating the cytokine storm associated with COVID-19.

Phytochemical investigation and anticholinesterase activity of ethyl acetate fraction of Myristica fragrans Houtt. seeds.

In this work, n-hexane, chloroform, and ethyl acetate fractions of the methanol extract of Myristica fragrans Houtt. seeds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) via Ellman's method. It was found that all fractions depicted no anti-AChE activity, however, they were active toward BChE with IC50 values of 361.8, 215.0, and 145.8 µg/mL, respectively comparing with donepezil as the reference drug (IC50 = 1.97 µg/mL). The ethyl acetate fraction which also showed high neuroprotectivity and metal chelating ability was selected for the phytochemical analysis. Our results confirmed the presence of trimyristin and 5,7-diacetyl chrysin (reported for the first time in M. fragrans) in the corresponding fraction.

Anti-Helicobacter pylori Compounds from Oliveria decumbens Vent. through Urease Inhibitory In-vitro and In-silico Studies.

Oliveria decumbens Vent. has been used by indigenous people of southwest Iran for treating peptic ulcers and gastrointestinal infections. This study aimed to investigate the antibacterial activity of Oliveria decumbens extract and fractions and to analyze the bioactive components of the fractions. Total plant extract and different fractions of Oliveria decumbens Vent. were prepared. Antibacterial activities were evaluated against the clinical strain of Helicobacter pylori and standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa using agar dilution and disc diffusion methods. Phytochemical analysis of the fractions was performed using silica gel chromatography and 1D and 2D NMR spectroscopy. Moreover, the urease inhibitory effects of the isolated compounds were assessed in-vitro and in-silico. Three novel kaempferol derivatives and two thymol derivatives were isolated from Oliveria decumbens aerial parts, and the structures were determined by comparison with published data. The n-hexane fraction was found to exert the most significant anti-H. pylori activity with the minimum inhibitory concentration of 50 µg/mL. All fractions demonstrated antibacterial activity toward S. aureus. In-vitro urease inhibition assay showed that stigmasterol, tiliroside, and carvacrol were found to be the most potent enzyme inhibitors in the isolated compounds. Molecular interactions of the compounds with the active site of urease were supported by the molecular docking analysis. Novel bioactive compounds in Oliveria decumbens were described in this study. The antibacterial effects suggested the potential use of the compounds in pharmaceutical formulations inconsistent with the traditional use of the plant in the treatment of gastrointestinal infections.

Portulaca oleracea methanolic extract attenuate bile duct ligation-induced acute liver injury through hepatoprotective and anti-inflammatory effects.

INTRODUCTION: Cholestasis is a liver disease caused by a malfunction of the hepato-biliary system. Oxidative stress as a systemic complication is the main characteristic of cholestasis. The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of Portulaca oleracea (PO) methanolic extract on liver dysfunction and tissue damage induced by bile duct ligation (BDL) in rats. MATERIALS AND METHODS: Twenty-eight male Wistar rats were randomly divided into four groups: sham control (SC), BDL alone, SC plus 500 mg/kg methanolic extract of PO orally for 1 week, and BDL plus 500 mg/kg methanolic extract of PO orally for 1 week. After 1 week, the animals were anesthetized, and the liver and blood samples were taken from each animal. Biochemical parameters, oxidative stress biomarkers, histopathological changes, as well as the gene expression of IL-1, TNF-α, TGF-ß, and α-SMA have been evaluated. RESULTS: The methanolic extract of PO at a dose of 500 mg/kg significantly decreased the plasma levels of aminotransferases, alkaline phosphatase as compared to BDL group (P < 0.05), while it had no significant effect on the levels of oxidative stress markers in the hepatic tissue. The plasma level of malondialdehyde and ferric-reducing antioxidant power were markedly elevated in the BDL group in comparison to SC group (P < 0.05), while treatment with PO significantly reduced these markers (P < 0.05). The administration of PO attenuated hydroxyproline content, bile duct proliferation, and inflammation score in the cholestatic liver in contrast to non-treated BDL rats (P < 0.05). Moreover, the methanolic extract of PO markedly declined the expression of TNF-α and TGF-ß pro inflammatory genes in contrast to BDL rats. CONCLUSIONS: Taken together, our findings showed that PO attenuated liver injury by decreasing liver function tests, inflammation, and hydroxyproline content. As a result, it is suggested that PO can be applied in cholestatic liver damage as a therapeutic or adjuvant agent.

Preparation of Polyurethane/Pluronic F127 Nanofibers Containing Peppermint Extract Loaded Gelatin Nanoparticles for Diabetic Wounds Healing: Characterization, In Vitro, and In Vivo Studies.

Diabetic ulcer is regarded as one of the most prevalent chronic diseases. The healing of these ulcers enhances with the use of herbal extracts containing wound dressings with high antibacterial property and creating a nano-sized controlled release system. In this study, new peppermint extract was incorporated in the polyurethane- (PU-) based nanofibers for diabetic wound healing. The peppermint extract was used as an herbal antimicrobial and anti-inflammatory agent. The absorption ability of the wound dressing was enhanced by addition of F127 pluronic into the polymer matrix. The release of the extract was optimized by crosslinking the extract with gelatin nanoparticles (CGN) and their eventual incorporation into the nanofibers. The release of the extract was also controlled through direct addition of the extract into the PU matrix. The results showed that the release of extract from nanofibers was continued during 144 hours. The prepared wound dressing had a maximum absorption of 410.65% and an antibacterial property of 99.9% against Staphylococcus aureus and Escherichia coli bacteria. An in vivo study indicated on significant improving in wound healing after the use of the extract as an effective compound. On day 14, the average healing rate for samples covered by conventional gauze bandage, PU/F127, PU/F/15 (contained extract), and PU/F/15/10 (contained extract and CGN) prepared with different nanoparticle concentrations of 5 and 10 was 47.1 ± 0.2, 56.4 ± 0.4, 65.14 ± 0.2, and 90.55 ± 0.15%, respectively. Histopathological studies indicated that the wound treated with the extract containing nanofibers showed a considerable inflammation reduction at day 14. Additionally, this group showed more resemblance to normal skin with a thin epidermis presence of normal rete ridges and rejuvenation of skin appendages. Neovascularization and collagen deposition were higher in wounds treated with the extract containing nanofibrous wound dressing compared to the other groups.

Glucose-6-phosphate dehydrogenase inhibitor for treatment of severe COVID-19: Polydatin.

The COVID-19 pandemic as the largest global public health crisis is now considered as an emergency at the World Health Organization (WHO). As there is no specific therapy for SARS-CoV-2 infection at present and also because of the long time it takes to discover a new drug and the urgent need to respond urgently to a pandemic infection. Perhaps the best way right now is to find an FDA-approved drug to treat this infection. Oxidative stress and inflammation play a vital role in the progression of tissue injury in COVID-19 patients; furthermore, the G6PD activation is related to increased oxidative inflammation in acute pulmonary injury. In this regard, we propose a new insight that may be a good strategy for this urgency. Exploiting G6PD through inhibiting G6PD activity by modifying redox balance, metabolic switching and protein-protein interactions can be proposed as a new approach to improving patients in severe stage of COVID 19 through various mechanisms. Polydatin is isolated from many plants such as Polygonum, peanuts, grapes, red wines and many daily diets that can be used in severe stage of COVID-19 as a G6PD inhibitor. Furthermore, polydatin possesses various biological activities such as anti-inflammatory, antioxidant, immunoregulatory, nephroprotective, hepatoprotective, anti-arrhythmic and anti-tumor. Our hypothesis is that the consumption of antioxidants such as Polydatin (a glucoside of resveratrol) as a complementary therapeutic approach may be effective in reducing oxidative stress and inflammation in patients with COVID-19.

Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats.

INTRODUCTION: Cholestasis is caused by malfunction of the hepatobiliary system. This disorder is the result of the accumulation of bile fatty acids and other toxins in the liver. The aim of the current study was to investigate the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods. Twenty-eight male Wistar rats were randomly divided into 4 groups including sham control group received vehicle (SC-V), bile duct ligation received vehicle (BDL-V), bile duct ligation group received OM extract (BDL + OM), and sham control group received OM extract (SC + OM). One day after surgery, the animals received vehicle or methanolic extract of OM 300 mg/kg/day for 7 consecutive days by oral gavage. Finally, the animals were anesthetized and the blood samples were collected from each animal. After sacrificing of animals, liver tissue from each rat was removed and divided into three parts: one part was used for preparing of homogenized tissue, one part was fixed in 10% neutral formalin for histopathology examination, and the third part was kept in liquid nitrogen for gene expression analysis. Biomarkers of oxidative stress in the liver tissue and serum, as well as histopathological changes of the liver, were assessed. Also, the gene expression of IL-1, TNF-α, TGF-ß, and α-SMA has been measured. RESULTS: The results showed that BDL-V significantly increased the activity of ALT, AST, ALP, and total bilirubin compared to the SC-V group. The oxidative stress markers such as MDA and FRAP significantly increased due to BDL, while the CAT activity reduced in the BDL-V group compared to SC-V group. Oral treatment with OM reduced ALT and AST activity, although it was not statistically significant. OM treatment considerably increased the activity of CAT compared to BDL group. BDL-V induced a significant histological change in the liver, while treatment with OM at a dose of 300 mg/kg showed a minor effect on histopathological changes. In addition, the mRNA of IL-1, TNF-α, TGF-ß, and α-SMA significantly increased in the BDL-V group, while treatment with OM only significantly reduced TGF-ß in comparison with BDL-V rats. CONCLUSIONS: The results of the present study showed that oral administration of OM extract had a moderate protective effect on cholestasis due to BDL. Indeed, more studies with different doses of extract are needed to confirm this finding.

Phytochemical constituents and biological activities of Salvia macrosiphon Boiss.

Salvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and ß-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.

Fabrication and Characterization of Nanocomposite Hydrogel Based on Alginate/Nano-Hydroxyapatite Loaded with Linum usitatissimum Extract as a Bone Tissue Engineering Scaffold.

In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100-200 µm and the porosity range of 80-90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications.

Polyurethane/carboxymethylcellulose nanofibers containing Malva sylvestris extract for healing diabetic wounds: Preparation, characterization, in vitro and in vivo studies.

In this study, new polyurethane (PU)-based nanofibers wound dressings containing Malva sylvestris extract were prepared and their effect on diabetic wound healing process was evaluated. Different amounts of carboxymethyl cellulose (CMC) were used to improve the absorption ability of wound exudates. The result showed that the usage of 20% w/w CMC in the polymer blend; and producing of nanofibers with an average diameter of 386.5 nm, led to the gradual release of the herbal compound in 85 h and bead-free morphology. Due to the antibacterial activity of wound dressing and wound healing process, the amount of 15% w/w herbal extract was selected as the optimum. For this sample, the fluid absorption was 412.31%. The extract loaded wound dressing samples showed satisfactory effects on Staphylococcus aureus and Escherichia coli bacteria. In vivo wound-healing and histological performance observations indicated that the use of the herbal extract in wound dressing improved wound healing significantly. On day 14, the average healing rate for gauze bandage, PU/CMC, and different amounts of 5, 10, 15 and 20% w/w extract containing wound dressings was 32.1 ± 0.2%, 51.4 ± 0.4%, 71 ± 0.14%, 87.64 ± 1.02%, 95.05 ± 0.24% and 95.11 ± 0.2%, respectively. Compared to the control groups, treatments with extract loaded wound dressings were effective in lowering acute and chronic inflammations. In diabetic rat wounds, collagen deposition and neovascularization were higher in wounds treated with an herbal extract containing wound dressing compared to the wounds treated with a gauze bandage and PU/CMC treated wounds. It can be suggested that this product may be considered as a good dual anti-inflammatory-antimicrobial wound dressing candidate for improving the diabetic wound healing.

Extraction and Identification of Two Flavonoids in Phlomoides hyoscyamoides as an Endemic Plant of Iran: The Role of Quercetin in the Activation of the Glutathione Peroxidase, the Improvement of the Hydroxyproline and Protein Oxidation in Bile Duct-Ligated Rats.

BACKGROUND: Cholestatic liver disease, a serious chronic condition that develops progressive hepatic degeneration through free radicals. OBJECTIVE: The present study was designed to extract and identify two flavonoids in Phlomoides hyoscyamoides plant, native to Iran and evaluate the role of quercetin identified on the liver injury among bile ductligated rats. METHODS: This study was conducted on 25 male Wistar rats within three groups of sham control, mere bile duct-ligated, and bile duct-ligated with quercetin. The bile duct-ligated animals received quercetin at a dose of 50 mg/kg/day for 10 days, followed by biochemical tests, oxidative stress markers, activity of antioxidant enzymes and hematoxylin and eosin staining. Molecular docking was used to explore the interactive behavior of quercetin with glutathione peroxidase. RESULTS: According to analyses of the obtained extract, two main active ingredients of P. hyoscyamoides were rutin and quercetin. Bile duct-ligated group showed a significant liver necrosis, a clear increase in plasma and tissue oxidative stress parameters, and a decrease in glutathione peroxidase activity as compared to sham control group. Quercetin injection in bile duct-ligated rats resulted in significant decrease in hydroxyproline, protein carbonyl and histopathologic indexes and significant increase in glutathione peroxidase activity (P-value≤0.05). Based on the molecular docking, the quercetin was able to regulate the glutathione peroxidase activity. CONCLUSION: The quercetin acts as an enzyme inducer by renewing the glutathione peroxidase activity and inhibiting the oxidation of proteins and hence decreases the oxidative stress. These results could be a sign of confirming the positive role of quercetin in attenuating the liver damage and degeneration.

Trachyspermum ammi (L.) Sprague, superb essential oil and its major components on peptic ulcers: in vivo combined in silico studies.

BACKGROUND: Trachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on. OBJECTIVES: The present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats. METHODS: Primarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase. RESULTS: Analysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase. CONCLUSIONS: The findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent. Graphical abstract.

Oliveria decumbens, a Bioactive Essential Oil: Chemical Composition and Biological Activities.

Oliveria decumbens is an aromatic plant traditionally used for treatment of infections and gastrointestinal diseases. In the present study, the volatile oil of the plant was obtained by hydrodistillation and analyzed by GC-MS. In addition, antibacterial and anti-Helicobacter pylori activities of this essential oil were determined using disc diffusion and agar dilution methods, respectively. Insecticidal activity was assessed through topical and fumigation application of the essential oil to cabbage looper larvae. Acetylcholinesterase (AChE) inhibition by the essential oil was examined using Ellman's method. Furthermore, its cytotoxic potential against three different cancer cell lines was assessed using the MTT assay. The phenolic monoterpenoids, thymol (38.79%), and carvacrol (36.30%) were identified as major constituents of the essential oil. We observed significant antibacterial activity of the essential oil against H. pylori (MIC=20.4 µg /mL) as well as other tested bacteria, except for Pseudomonas aeruginosa. O. decumbens essential oil showed significant toxicity to cabbage looper larvae with LD50 value of 52.1 µg /larva following topical and fumigant administration. O. decumbens essential oil was considerably inhibitory to acetylcholinesterase activity (IC50 = 0.117 µg/mL). Cytotoxic assay of the volatile oil resulted in IC50 = 0.065, 0.104, and 0.141 µg/mL for MCF-7, T47D and MDA- MB-231 cell lines, respectively. According to our data, this species with high concentrations of thymol and carvacrol could be considered as a natural source for pharmaceutical products.

Effect of the methanolic extracts of different parts of Ferula assa-foetida on naloxone-induced withdrawal behavior in morphine-dependent mice.

OBJECTIVE: Ferula assa-foetida, a native species in Iran, is used for treatment of several diseases particularly for neurological disorders in Iranian Traditional Medicine. The aim of this study is to investigate the effect of methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on withdrawal syndrome in morphine-dependent mice. MATERIALS AND METHODS: Aerial parts, roots, and fruits of the plant were separately extracted with 80% MeOH. For induction of dependence, morphine (50, 50 and 75 mg/kg) was injected subcutaneously three times daily (10 am, 1 pm and 4 pm) for three days and a last dose of morphine (50 mg/kg) was administrated on the fourth day. Withdrawal syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal) 2 hr after the final dose of morphine. Different doses of the extracts were administered i.p. 60 minutes before naloxone injection and withdrawal sign was recorded 2 minutes after naloxone injection for a period of 60 minutes. RESULTS: Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg) of methanolic extract of the aerial parts of F. assa-foetida caused a significant decrease in naloxone-induced behavior. Intraperitoneal administration of different doses (10, 15, 20, 25 mg/kg) of methanolic extract of the fruit significantly reduced the naloxone-induced withdrawal behavior (p<0.001). CONCLUSION: It might be concluded that the extracts of Ferula assa-foetida affect morphine withdrawal syndrome possibly via interference with the neurotransmitters in nervous system.

"Gharikon"/"Agharikon" a Valuable Medicinal Mushroom in Iranian Traditional Medicine.

BACKGROUND: Gharikon is a well-known medicinal mushroom in Iranian traditional medicine and mentioned several times in different kinds of authentic literature. Considering both traditional and modern literature, the aim of this study is to present a review of its biological activities. METHODS: Using online databases (e.g. PubMed, Scopus, and Google Scholar) as well as reviewing traditional medicinal literature (e.g. Makhzan-ul-Adwiah, Al-Qanun fi al-Tibb); we reviewed the published literature on the pharmacological effects of Laricifomes officinalis (the most common species considered as "Gharikon"). RESULTS: Laricifomes officinalis (Polyporus officinalis) is a wood-rotting fungus that grows on different hosts such as conifers. The mushroom is native to Europe, Asia, and North America. According to the judgment of traditional medicine, its temperament is warm and dry. It has been used since the ancient times to treat sciatica, weakness of muscles, bronchitis, constipation, stomach and uterus pain, jaundice, fever and insect bites. It also has diuretic and emmenagogue effects. In recent decades, several research studies have been performed on L. officinalis. The results showed that the biological effects of L. officinalis are anti-viral (especially against smallpox, H5N1 influenza, and hepatitis C virus), anti-tuberculosis, boosting the immune system, treating dysmenorrhea, hemorrhoids, cough, rheumatoid arthritis and anticoagulant activity. A survey revealed that L. officinalis is a well-known medicinal mushroom with some formulations as dietary supplements on the market. CONCLUSION: Considering traditional literature and recent findings on biological activities that in most cases corroborate each other, it seems that Laricifomes officinalis needs more attention in new investigations, including more pharmacologic assays and clinical trials, which may lead to the development of new natural products.