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The SARS‐CoV‐2 COVID‐19 pandemic has emerged as an unprecedented emergency state in healthcare system and global challenge. In recent decade, the function of exogenous H2S in the treatment of respiratory diseases has been investigated using H2S‐donor agents. Ferula foetida is a medicinal plant that is traditionally used in respiratory diseases including asthma and viral respiratory diseases. The oleo‐gum of this plant is a rich source of several organic sulfides including thiophenes, disulfides and polysulfide derivatives, which can act as H2S‐donor agents. The purpose of this study was to investigate the efficacy of Covexir® (F. foetida oleo‐gum) treatment as a rich source of H2S‐donor compounds in clinical presentations of patients with COVID‐19. The efficacy of Covexir® was evaluated in a randomized, double‐blind, placebo‐controlled trial in outpatients with COVID‐19. Covexir® could significantly inhibit cough when compared to the placebo group (p <.01 and p < 001, respectively). Moreover, there was a significant difference (p < 001) between the two groups in dyspnea symptom at follow‐up interval of 7 day after receiving Covexir®. Furthermore, on days 3 and 7, statistically significant differences were observed in myalgia, anorexia, anosmia, and sense of taste severity between two groups. Our findings revealed that Covexir® was very safe in the treatment of COVID‐19 patients with mild to moderate symptoms and it can be recommended to improve clinical presentations of patients with COVID‐19 such as cough, shortness of breath, myalgia, anorexia, anosmia, and sense of taste. [ABSTRACT FROM AUTHOR]

Urolithins are the gut metabolites produced from ellagitannin‐rich foods such as pomegranates, tea, walnuts, as well as strawberries, raspberries, blackberries, and cloudberries. Urolithins are of growing interest due to their various biological activities including cardiovascular protection, anti‐inflammatory activity, anticancer properties, antidiabetic activity, and antiaging properties. Several studies mostly based on in vitro and in vivo experiments have investigated the potential mechanisms of urolithins which support the beneficial effects of urolithins in the treatment of several diseases such as Alzheimer's disease, type 2 diabetes mellitus, liver disease, cardiovascular disease, and various cancers. It is now obvious that urolithins can involve several cellular mechanisms including inhibition of MDM2‐p53 interaction, modulation of mitogen‐activated protein kinase pathway, and suppressing nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activity. Antiaging activity is the most appealing and probably the most important property of urolithin A that has been investigated in depth in recent studies, owing to its unique effects on activation of mitophagy and mitochondrial biogenesis. A recent clinical trial showed that urolithin A is safe up to 2,500 mg/day and can improve mitochondrial biomarkers in elderly patients. Regarding the importance of mitochondria in the pathophysiology of many diseases, urolithins merit further research especially in clinical trials to unravel more aspects of their clinical significance. Besides the nutritional value of urolithins, recent studies proved that urolithins can be used as pharmacological agents to prevent or cure several diseases. Here, we comprehensively review the potential role of urolithins as new therapeutic agents with a special focus on the molecular pathways that have been involved in their biological effects. The pharmacokinetics of urolithins is also included. [ABSTRACT FROM AUTHOR]

Background and purpose: Methamphetamine (METH) abuse has devastating consequences on the nervous system. There are limited therapy choices in METH abuse with reduced effectiveness and elevated recurrence rates. Thymoquinone (TQ), the most bioactive constituent of Nigella sativa seeds exerts neuroprotective effects mainly via antioxidant properties. This study aimed to evaluate the effect of TQ against METH-induced striatal neurotoxicity and hyperlocomotor activity in mice. Experimental approach: Our groups of animals received METH (10 mg/kg) four times a day with 2 h intervals. Normal saline or TQ (5, 10, or 20 mg/kg) was injected intraperitoneally 30 min before METH administration. Control and sham groups received vehicle or TQ, respectively. The rectal temperature and behavioral tests including the open field for locomotor activity and rotarod for motor coordination were evaluated. The level of superoxide dismutase (SOD), as well as pathological changes, were also assessed in the striatum region. Findings/Results: No significant differences in rectal temperatures were observed among treated groups. Administration of METH increased locomotor activity and did not change motor coordination. TQ co-administration with METH significantly reduced the central and total locomotion and the mean latency to fall off the rotarod in a dose-dependent manner compared with the METH group. TQ also alleviated the METH-induced decrease in the activity of SOD.TQ, especially at the high dose, reduced the METH-induced reactive gliosis level. Conclusion and implications: In conclusion, TQ prevents the enhanced locomotor activity, antioxidant impairment, and morphological striatal damage caused by METH in mice. TQ may be a potential candidate for the treatment of specific METH-induced brain disorders or neurological diseases. [ABSTRACT FROM AUTHOR]

Objective: Methamphetamine (METH) increases dopamine, norepinephrine and serotonin concentrations in the synaptic cleft, and induces hyperactivity. The current management of acute METH poisoning relies on supportive care and no specific antidote is available for treatment. The main objective of this review was to present the evidence for effectiveness of the herbal medicine in alleviating the adverse effects of METH abuse. Materials and Methods: Literature search was performed using the following electronic databases: MEDLINE, Scopus, PubMed and EMBASE. Results: Plant-derived natural products ginseng and sauchinone reduced METH-induced hyperactivity, conditioned place preference and neurological disorder. Garcinia kola decreased METH-induced hepatotoxicity, raised METH lethal dose, and restored the METH-impaired cognitive function. Repeated administration of baicalein resulted in attenuation of acute binge METH-induced amnesia via dopamine receptors. Activation of extracellular-regulated kinase in the hypothalamus by levotetrahydropalmatine facilitated the extinction of METH-induced conditioned place preference and reduced the hyperactivity. Other herbal medicine from various parts of the world were also discussed including hispidulin, silymarin, limonene, resveratrol, chlorogenic acid and barakol. Conclusion: Based on the current study, some natural products such as ginseng and levo-tetrahydropalmatine are promising candidates to treat METH abuse and poisoning. However, clinical trials are needed to confirm these finding. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disease and the leading cause of dementia worldwide. Epidemiological studies support the important role of diet in prevention and improvement of AD. In Traditional Persian Medicine (TPM), there is multiple dietary guidelines to prevent and alleviate dementia and memory impairment. Pharmacological studies have been shown that most of the TPM-recommended dietary items can improve memory and cognitive decline and possess antiamyloidogenic, etc. activities. Among them, garlic (Allium sativum) and its compounds, S-allyl-cysteine and diallyl-disulfide, coconut (Cocos nucifera) oil, saffron (Crocus sativus) and crocin and crocetin, honey, fish, lemon balm (Melissa officinalis) and its major compounds rosmarinic acid, raisin and resveratrol, rose flowers (Rosa damascna) and geraniol, ginger (Zingiber officinale) and its 6-gingerol and 6-shogaol, cumin (Cuminum cyminum) and its main component cuminaldehyde have been found to possess stronger anti-AD activities. Most of these items exhibited antioxidant and AChE inhibitory activities and decreased lipid peroxidation. They also possessed anti-amyloidogenic effects, reduced cerebral plaques and Aβ-species, suppressed cerebral inflammation and alterations in tau protein and inhibited Aβ-induced apoptosis through various mechanisms. Noticeably, there are similarities between TPM anti-AD diet and the typical Mediterranean diet whose beneficial effects on AD have been widely demonstrated. Given the importance of traditional medicine systems in discovering new medicines and nutraceuticals for curing ailments, considering TPM anti-AD dietary recommendations in future research would be helpful. [ABSTRACT FROM AUTHOR]

Objective: The present study was conducted to find cytotoxic compounds from oleo-gum-resin of Ferula assa-foetida (asafoetida). Materials and Methods: A dichloromethane extract of asafoetida was subjected to different chromatography analyses (including column chromatography, preparative thin layer chromatography and high performance liquid chromatography) to isolate its bioactive sesquiterpene coumarins. The structures of isolated compounds were elucidated through 1H-NMR spectra interpretation and comparison with those reported in the literature. To measure the cytotoxic activity of pure compounds, a non-fluorescent substrate called resazurin (alamarBlue®) was used in this study. Human breast and prostate cancer cell lines (MCF-7 and PC-3, respectively) and a normal human embryonic stem cell (NIH) were treated with different concentrations (50, 25, 12.5 and 6.25 µg/mL) of pure compounds. Results: In this study, 10 sesquiterpene coumarins were isolated from oleo-gum-resin of F. assa-foetida and cytotoxic activity of 6 compounds was tested against MCF-7 and PC-3 cell lines and NIH cells. Badrakemin acetate (7), ferukrinone (8) and deacetyl kellerin (10) were found for the first time in the oleo-gum-resin of F. assafoetida. Gummosin (4) showed moderate cytotoxic activity with IC50 values of 30 and 32.1 µg/mL against PC-3 and MCF-7 cell lines, respectively. None of the isolated compounds showed toxicity against NIH as a normal human cell line. Conclusion: The preferential cytotoxic activity of gummosin against cancer cell lines is reported for the first time in this study. [ABSTRACT FROM AUTHOR]

Based on World Health Organization reports, resistance of bacteria to well-known antibiotics is a major global health challenge now and in the future. Different strategies have been proposed to tackle this problem including inhibition of multidrug resistance pumps and biofilm formation in bacteria and development of new antibiotics with novel mechanism of action. Flavonoids are a large class of natural compounds, have been extensively studied for their antibacterial activity, and more than 150 articles have been published on this topic since 2005. Over the past decade, some promising results were obtained with the antibacterial activity of flavonoids. In some cases, flavonoids (especially chalcones) showed up to sixfold stronger antibacterial activities than standard drugs in the market. Some synthetic derivatives of flavonoids also exhibited remarkable antibacterial activities with 20- to 80-fold more potent activity than the standard drug against multidrug-resistant Gram-negative and Gram-positive bacteria (including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). This review summarizes the ever changing information on antibacterial activity of flavonoids since 2005, with a special focus on the structure-activity relationship and mechanisms of actions of this broad class of natural compounds. [ABSTRACT FROM AUTHOR]