The Efficacy of Olive Leaf Extract on Healing Herpes Simplex Virus: A Randomized Double-blind Study
Lorestan University of Medical Sciences (Iran), January 29, 2021
Herpes simplex virus (HSV), as a common infection in healthy individuals, is treated symptomatically, but drug resistance and the side effects of drugs have drawn the attention of researchers to complementary medicine. Olive Leaf Extract (OLE) has antiviral effects that may treat HSV. The current study aimed to compare the clinical effects of OLE and Acyclovir on HSV-1.
Methods
This randomized double-blind clinical trial was conducted on 66 patients who had already been diagnosed with HSV-1. The participants were randomized into two groups, receiving 2% OLE cream or 5% acyclovir cream five times a day for six days. The symptoms were evaluated before, and three and six days after the interventions. Data were analyzed using the SPSS software through the Kolmogorov-Smirnov test, chi-squared, t-test, and repeated measures ANOVA.
Results
The results showed clinical symptoms decreased in both groups during the study and both medications were effective in the treatment of HSV-1. However, the OLE group experienced less bleeding (P=0.038), itching (P=0.002), and pain (P=0.001) on the third day as well as less irritation (P=0.012), itching (P=0.003) and color change (P=0.001) on the sixth day compared to the acyclovir group. The treatment course for participants in the OLE group was shorter than in the acyclovir group (P = 0.001).
Conclusion
The evidence from these trials suggests the OLE cream is superior in the healing of episodes of HSV-1 over the acyclovir cream. Future studies are recommended to investigate if OLE could be an adjunct to acyclovir treatment.
How vitamins, steroids and potential antivirals might affect SARS-CoV-2
Study indicates that some vitamins, steroids and antivirals could bind to the Spike protein, and may inhibit virus infectivity, whereas high cholesterol may enable the virus
University of Bristol (UK), January 29, 2021
Evidence is emerging that vitamin D - and possibly vitamins K and A - might help combat COVID-19. A new study from the University of Bristol published in the journal of the German Chemical Society Angewandte Chemie has shown how they - and other antiviral drugs - might work. The research indicates that these dietary supplements and compounds could bind to the viral spike protein and so might reduce SARS-CoV-2 infectivity. In contrast, cholesterol may increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious disease.
Recently, Bristol researchers showed that linoleic acid binds to a specific site in the viral spike protein, and that by doing so, it locks the spike into a closed, less infective form. Now, a research team has used computational methods to search for other compounds that might have the same effect, as potential treatments. They hope to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with a human protein (ACE2). New anti-viral drugs can take years to design, develop and test, so the researchers looked through a library of approved drugs and vitamins to identify those which might bind to this recently discovered 'druggable pocket' inside the SARS-CoV-2 spike protein.
The team first studied the effects of linoleic acid on the spike, using computational simulations to show that it stabilizes the closed form. Further simulations showed that dexamethasone - which is an effective treatment for COVID-19 - might also bind to this site and help reduce viral infectivity in addition to its effects on the human immune system.
The team then conducted simulations to see which other compounds bind to the fatty acid site. This identified some drugs that have been found by experiments to be active against the virus, suggesting that this may be one mechanism by which they prevent viral replication such as, by locking the spike structure in the same way as linoleic acid.
The findings suggested several drug candidates among available pharmaceuticals and dietary components, including some that have been found to slow SARS-CoV-2 reproduction in the laboratory. These have the potential to bind to the SARS-CoV-2 spike protein and may help to prevent cell entry.
The simulations also predicted that the fat-soluble vitamins D, K and A bind to the spike in the same way making the spike less able to infect cells.
Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modelling) in the School of Biochemistry, who modelled the spike, explained: "Our findings help explain how some vitamins may play a more direct role in combatting COVID than their conventional support of the human immune system.
"Obesity is a major risk factor for severe COVID. Vitamin D is fat soluble and tends to accumulate in fatty tissue. This can lower the amount of vitamin D available to obese individuals. Countries in which some of these vitamin deficiencies are more common have also suffered badly during the course of the pandemic. Our research suggests that some essential vitamins and fatty acids including linoleic acid may contribute to impeding the spike/ACE2 interaction. Deficiency in any one of them may make it easier for the virus to infect."
Pre-existing high cholesterol levels have been associated with increased risk for severe COVID-19. Reports that the SARS-CoV-2 spike protein binds cholesterol led the team to investigate whether it could bind at the fatty acid binding site. Their simulations indicate that it could bind, but that it may have a destabilising effect on the spike's locked conformation, and favour the open, more infective conformation.
Dr Shoemark continued: "We know that the use of cholesterol lowering statins reduces the risk of developing severe COVID and shortens recovery time in less severe cases. Whether cholesterol de-stabilises the "benign", closed conformation or not, our results suggest that by directly interacting with the spike, the virus could sequester cholesterol to achieve the local concentrations required to facilitate cell entry and this may also account for the observed loss of circulating cholesterol post infection."
Professor Adrian Mulholland, of Bristol's School of Chemistry, added: "Our simulations show how some molecules binding at the linoleic acid site affect the spike's dynamics and lock it closed. They also show that drugs and vitamins active against the virus may work in the same way. Targeting this site may be a route to new anti-viral drugs. A next step would be to look at effects of dietary supplements and test viral replication in cells."
Alison Derbenwick Miller, Vice President, Oracle for Research, said: "It's incredibly exciting that researchers are gaining new insights into how SARS-CoV-2 interacts with human cells, which ultimately will lead to new ways to fight COVID-19. We are delighted that Oracle's high-performance cloud infrastructure is helping to advance this kind of world-changing research. Growing a globally-connected community of cloud-powered researchers is exactly what Oracle for Research is designed to do."
Researchers find melatonin is effective against polycystic kidney disease
Concordia University (Canada), January 26, 2021
A hormone commonly associated with sleep-wake regulation has been found to reduce cysts in fruit flies, according to Concordia researchers. It's a finding that may affect the way we treat some kidney diseases and reduce the need for kidney transplants.
In a new paper published in the journal Molecules, alum Cassandra Millet-Boureima(MSc 19) and Chiara Gamberi, affiliate assistant professor of biology, write that melatonin was found to reduce cysts in the renal tubules of fruit flies. These tubules are also found in more complex mammals, including humans, where they are called nephrons. This study, which builds on previous studies by Millet-Boureima and Gamberi, was co-authored by Roman Rozencwaig and Felix Polyak of BH Bioscience in Montreal.
The researchers hope that their findings can be applied to treating people suffering from autosomal dominant polycystic kidney disease. ADPKD is a genetic chronic and progressive disease characterized by the growth of dozens of cysts in the nephrons. It is incurable and affects approximately 12.5 million worldwide.
Similarities big and small
Because nephrons in vertebrates are embedded in other tissue, the researchers experimented on Drosophila -- the common fruit fly.
"Drosophila conserves many of the renal pathway components found in vertebrates and have anatomically isolated renal tubes," Gamberi explains. "With microdissection, we can isolate the tubules and conduct biochemical and molecular analysis."
The researchers bred fruit flies bearing the Bicaudal C gene mutation. It is known to cause kidney cysts in all manner of living beings, from flies to frogs to mice to humans.
Over 18 days, Millet-Boureima administered melatonin to 50 Drosophila and ethanol to a control group. She then dissected the flies and scored their cysts, a process yielding a cystic index. She found that the melatonin-treated flies had much fewer and smaller cysts than the control. Because Millet-Boureima was skilled at dissecting the insects and evaluating the recovered renal tubules, she was able to avoid bias in the count.
She was also able to distinguish three separate sections of the Drosophila tubule, each with its own unique function, and assign the cysts to a particular section. After testing several compounds on the same family of cells, she observed different activities along the length of the tubule. The researchers realized that they could potentially develop targeted treatment depending on the location of the cysts in a patient's nephrons.
"Biologically speaking, this has a lot of potential that we will obviously develop," Gamberi says.
Helping without harming
Though Gamberi says melatonin has not been previously used to treat PKD, she does think it holds some promise. PKD is a chronic disease, so treatment cannot include any toxic components. This rules out chemotherapy and tumour-killing antineoplastics used in oncology, for instance. However, melatonin is entirely non-toxic and shares certain properties with antineoplastics and anti-inflammatory agents.
"We know from oncology that melatonin has two effects when it is administered with chemotherapy," Gamberi explains. "First, it acts as a drug adjuvant to the chemotherapy, making it work more effectively against cancer cells. Second, it appears to protect healthy cells from the toxicity of the chemotherapy. Basically, melatonin increases the specificity of the chemotherapy. We hope that it can have a similar positive effect when used with an anti-ADPKD drug like tolvaptan, which can damage the liver."
The researchers are keen to share their findings as quickly as possible.
"I hope there will be more research on the drugs we tested and that we get more results that will help the PKD community," Millet-Boureima says.
Gallic acid is a dual alpha/beta-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer
Saitama Medical Center (Japan), January 20, 2021
According to news reporting from Saitama, Japan, research stated, “Several plant-derived compounds have demonstrated efficacy in pre-clinical Alzheimer’s disease (AD) rodent models. Each of these compounds share a gallic acid (GA) moiety, and initial assays on this isolated molecule indicated that it might be responsible for the therapeutic benefits observed.” Higher concentrations of GA are found in blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut and tea.
The news correspondents obtained a quote from the research from Saitama Medical Center, “To test this hypothesis in a more physiologically relevant setting, we investigated the effect of GA in the mutant human amyloid beta-protein precursor/presenilin 1 (APP/PS1) transgenic AD mouse model. Beginning at 12 months, we orally administered GA (20 mg/kg) or vehicle once daily for 6 months to APP/PS1 mice that have accelerated Alzheimer-like pathology. At 18 months of age, GA therapy reversed impaired learning and memory as compared with vehicle, and did not alter behavior in nontransgenic littermates. GA-treated APP/PS1 mice had mitigated cerebral amyloidosis, including brain parenchymal and cerebral vascular beta-amyloid deposits, and decreased cerebral amyloid beta-proteins. Beneficial effects co-occurred with reduced amyloidogenic and elevated nonamyloidogenic APP processing. Furthermore, brain inflammation, gliosis, and oxidative stress were alleviated. We show that GA simultaneously elevates alpha- and reduces beta-secretase activity, inhibits neuroinflammation, and stabilizes brain oxidative stress in a pre-clinical mouse model of AD. We further demonstrate that GA increases abundance of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10, Adam10) proprotein convertase furin and activates ADAM10, directly inhibits beta-site APP cleaving enzyme 1 (BACE1, Bace1) activity but does not alter Adam10 or Bace1 transcription. Thus, our data reveal novel post-translational mechanisms for GA.”
According to the news reporters, the research concluded: “We suggest further examination of GA supplementation in humans will shed light on the exciting therapeutic potential of this molecule.”
This research has been peer-reviewed.
Black cumin’s anti-inflammatory potential may have airways/asthma benefits: RCT
University College London, January 27, 2021
Supplements containing oil from black cumin (Nigella sativa) may improve asthma control and lung function, says a new study.
The seed and oil of Nigella sativa have been used extensively in traditional medicine in many Middle Eastern and Asian countries for the treatment of a range of conditions, including some immune and inflammatory disorders.
The new study, published in Phytotherapy Research , found that one gram per day of the oil for four weeks led to significant improvements in scores of asthma control and a “remarkable reduction of peripheral blood eosinophil count,” wrote the authors
“Eosinophil cell plays a major role in asthma inflammation, and blood eosinophil count is considered to be a vital biomarker in asthma trials. To our knowledge, this is the first [randomized, double-blind, placebo-controlled trial] that showed a significant reduction of blood eosinophilia by [Nigella sativa oil (NSO)] among asthmatic patients.”
Scientists from University College London (UK) and King Abdulaziz University (Saudi Arabia) recruited 80 asthmatics and randomly assigned them to one of two equal groups. The participants received either capsules containing 500 mg of NSO twice per day or placebo for four weeks.
Data from the 60 people who completed the study (10 dropouts in each group) indicated that the black cumin supplement was associated with significant improvements in mean score on the Asthma Control Test, compared to placebo.
Black cumin oil products are commercially available through brands such as Life Extension. Structure-function claims made on the products include: “Modulates key regulators of inflammation”
In addition, the black cumin group also experienced a significant decrease in blood eosinophils: −50 versus 15 cells/microliter.
A non-statistically significant improvement in lung function, measured as forced expiratory volume in 1 second, was also associated with the black cumin supplements.
“The NSO supplementation appeared to be effective in enhancing the control of asthma symptoms with a trend in pulmonary function improvement,” wrote the researchers. “These findings may provide an evidence for the potential benefits of NSO supplementation in the clinical management of asthma. “Future studies should follow patients for a longer period and use additional outcomes to validate the benefits of NSO in asthma.”
LSD may offer viable treatment for certain mental disorders
McGill University (Quebec), January 26, 2021
Researchers from McGill University have discovered, for the first time, one of the possible mechanisms that contributes to the ability of lysergic acid diethylamide (LSD) to increase social interaction. The findings, which could help unlock potential therapeutic applications in treating certain psychiatric diseases, including anxiety and alcohol use disorders, are published in the journal PNAS.
Psychedelic drugs, including LSD, were popular in the 1970s and have been gaining popularity over the past decade, with reports of young professionals claiming to regularly take small non-hallucinogenic micro-doses of LSD to boost their productivity and creativity and to increase their empathy. The mechanism of action of LSD on the brain, however, has remained a mystery.
Studies in mice provide clues
To conduct their study, the researchers administered a low dose of LSD to mice over a period of seven days, resulting in an observable increase in the sociability of the mice. "This increased sociability occurs because the LSD activates the serotonin 5-HT2A receptors and the AMPA receptors -- which is a glutamate receptor, the main brain excitatory neurotransmitters -- in the prefrontal cortex and also activates a cellular protein called mTORC 1," explains Danilo De Gregorio, PharmD, PhD, who is a postdoctoral fellow in the Neurobiological Psychiatry Unit at McGill and the study's first author. "These three factors, taken together, promote social interaction in mice, which is the equivalent of empathy and social behaviour in humans."
The researchers note that the main outcome of their study is the ability to describe, at least in rodents, the underlying mechanism for the behavioural effect that results in LSD increasing feelings of empathy, including a greater connection to the world and sense of being part of a large community. "The fact that LSD binds the 5-HT2A receptor was previously known. The novelty of this research is to have identified that the prosocial effects of LSD activate the 5-HT2 receptors, which in-turn activate the excitatory synapses of the AMPA receptor as well as the protein complex mTORC1, which has been demonstrated to be dysregulated in diseases with social deficits such as autism spectrum disorder," as specified by Prof. Nahum Sonenberg, Professor at the Department of Biochemistry of McGill University, world renowned expert in the molecular biology of diseases and co-lead author of the study.
Using the cutting-edge technique of optogenetics, a technique where genes for light-sensitive proteins are introduced into specific types of brain cells in order to monitor and control their activity precisely using light signals, the researchers observed that when the excitatory transmission in the prefrontal cortex is de-activated, the prosocial effect of LSD was nullified, highlighting the importance of this brain region on the modulation of the behavioural effects of LSD.
Moving forward to apply the findings to humans
Having found that LSD increases social interaction in mice, the researchers are hoping to continue their work and to test the ability of LSD to treat mutant mice displaying the behavioural deficits similar to those seen in human pathologies including autism spectrum disorders and social anxiety disorders. The hope is to eventually explore whether micro-doses of LSD or some novel derivates might have a similar effect in humans and whether it could also be a viable and safe therapeutic option.
"Social interaction is a fundamental characteristic of human behaviour," notes the co-lead author Dr. Gabriella Gobbi, Professor in the Department of Psychiatry at McGill and psychiatrist at the McGill University Health Centre. "These hallucinogenic compounds, which, at low doses, are able to increase sociability may help to better understand the pharmacology and neurobiology of social behavior and, ultimately, to develop and discover novel and safer drugs for mental disorders."
Polyphenol-rich virgin olive oil reduces insulin resistance and liver inflammation and improves mitochondrial dysfunction
University of Naples (Italy), January 28, 2021
Studies from University of Naples Federico II Describe New Findings in Insulin Resistance (Polyphenol-rich virgin olive oil reduces insulin resistance and liver inflammation and improves mitochondrial dysfunction in high-fat diet fed rats)
A new study on Endocrine System Diseases and Conditions - Insulin Resistance is now available. According to news reporting originating in Naples, Italy, research stated, "Virgin olive oil is an essential component of the Mediterranean diet. Its antioxidant and anti-inflammatory properties are mainly linked to phenolic contents."
The news reporters obtained a quote from the research from the University of Naples Federico II, "This study aims to evaluate the beneficial effects of a polyphenol-rich virgin olive oil (HPCOO) or olive oil without polyphenols (WPOO) in rats fed high-fat diet (HFD). Male Sprague-Dawley rats were divided into four groups based on the different types of diet: (I) standard diet (STD); (II) HFD; (III) HFD containing WPOO, and (IV) HFD containing HPCOO. HPCOO and WPOO induced a significant improvement of HFD-induced impaired glucose homeostasis (by hyperglycemia, altered oral glucose tolerance, and HOMA-IR) and inflammatory status modulating pro-and anti-inflammatory cytokines (TNF-a, IL-1, and IL-10) and adipokines. Moreover, HPCOO and less extensively WPOO, limited HFD-induced liver oxidative and nitrosative stress and increased hepatic fatty acid oxidation. To study mitochondrial performance, oxidative capacity and energy efficiency were also evaluated in isolated liver mitochondria. HPCOO, but not WPOO, reduced H O release and aconitase activity by decreasing degree of coupling, which plays a major role in the control of mitochondrial reactive oxygen species emission."
According to the news reporters, the research concluded: "HPCOO limits HFD-induced insulin resistance, inflammation, and hepatic oxidative stress, preventing nonalcoholic fatty liver disease progression."
For more information on this research see: Polyphenol-rich virgin olive oil reduces insulin resistance and liver inflammation and improves mitochondrial dysfunction in high-fat diet fed rats.
