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.

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.

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.

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.

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.

Cytotoxic Potential of Centaurea bruguierana ssp. belangerana: The MTT Assay.

The genus Centaurea with an extensive background in Iranian traditional medicine represents more than 70 species in Iran that some of them are endemic to Iran. A variety of secondary metabolites has been isolated from this genus thus far. Sesquiterpene lactones and flavonoids have been reported as main compounds of C.bruguierana. Methanolic extract and different fractions of the whole fruiting samples of Centaurea bruguierana ssp.belangerana (Asteraceae) were examined for cytotoxicity against various cell lines using MTT cytotoxicity assay in order to identify active fraction(s). The chloroform and ethyl acetate fractions of plant have demonstrated significant cytotoxicity against colon adenocarcinoma and breast ductal carcinoma cell lines, which chloroform fraction, exhibited the most potent in vitro cytotoxic activity against colon adenocarcinoma cell line, and therefore, can be considered as the potential fraction through main compounds of plant against the adenocarcinoma colon cancer cell line. Moreover, only chloroform fraction was moderately active against Swiss embryo fibroblast cell lines while the other fractions were nontoxic. To summarize, the chloroform fraction of C.bruguierana demonstrated better cytotoxic activity against all of the tested cell lines compared with the other fractions; and promisingly in some cases represented moderate to very good cytotoxicity that suggests more investigations about its phytochemical properties.