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Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis.
Xiong, X, Wang, P, Su, K, Cho, WC, Xing, Y
Pharmacological research. 2020;160:105056
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Coronavirus- 2019 (COVID-19) infection, the cause of a global pandemic, can lead to respiratory failure and death. Whilst no specific antiviral drugs or vaccines were available in the early stages of the outbreak, in China Chinese Herbal Medicine (CHM) had been widely used since the beginning. This systematic review and meta-analysis compared the efficacy of CHM to conventional Western medicine treatments for COVID-19 infections, involving 2275 patients from 18 trials. The outcome suggested that the use of CHM exhibited many positive effects on the course of the disease, including fever severity, length of hospital stay, cough, fatigue, anti-inflammatory markers and lung imaging, therefore presenting a promising treatment for reducing the severity and duration of the disease, whilst having little to no side effects. The trials included various formulations predominantly based on traditional Chinese herbal medicine, with the therapeutic principles of ‘dispelling cold’, ‘relieving exterior’, ‘dissipating phlegm’, ‘clearing away heat’, ‘invigorating spleen’, and ‘replenishing qi’. In the included trials a total of 100 different herbs were identified. The five most frequently used herbs being Liquorice Root (Glycyrrhiza spp.), Baikal Skullcap Root (Scutellaria baicalensis), Pinellia Rhizome (Pinelliae tematae), Forsythia Fruit (Forsythia suspensa), and Bitter Apricot Seed (Armeniacae amarum). The treatment course ranged from 5 to 15 days and the most common dosage were tea preparations. The authors describe the meta-analysis as one of the larger ones conducted so far and briefly discuss some of the therapeutic effects and mechanisms of the herbs most used. This meta-analysis yields evidence for alternative strategies in the support and management of COVID-19 infections.
Abstract
Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle.
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'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients.
Doykov, I, Hällqvist, J, Gilmour, KC, Grandjean, L, Mills, K, Heywood, WE
F1000Research. 2020;9:1349
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‘Long COVID’ or the persistence of symptoms after SARS-CoV-2 infection, such as fatigue, is becoming increasingly common. As the emergence of the virus is still relatively recent in research terms, little is known about the long-term impact of the viruses infection. This study sought to generate further insights into the management and diagnostic of long COVID, by assessing a range of inflammatory markers from blood serum samples. Examined were 10 samples of health care workers with previous asymptomatic or moderate SARS-CoV-2 infections, compared to 10 samples of SARS-CoV-2 naive health care workers. The serum was analyzed by mass spectrometry using a customized panel of the 96 immune response associated proteins. Despite being mild to moderate cases, the results showed that even 40-60 days after infection, significant disturbance in the immune systems inflammatory response could be observed. Particularly markers that reflect anti-inflammatory pathways and mitochondrial stress. The study highlighted six of the most noteworthy proteins and included a brief description of their role. The authors suggest that analysing proteins by using targeted proteomic technology, could serve as a cost-effective strategy to further investigate the changes in inflammatory responses post SARS-CoV-2 infection. Which could help to aid the identification of potential treatment targets in the future. Relevant findings from this small study for clinical practice are that even mild to moderate SARS-CoV-2 infection can alter the inflammatory responses for months afterwards.
Abstract
'Long Covid', or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.
3.
Medical and Dietary Uses of N-Acetylcysteine.
Šalamon, Š, Kramar, B, Marolt, TP, Poljšak, B, Milisav, I
Antioxidants (Basel, Switzerland). 2019;8(5)
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N-Acetylcysteine (NAC) is an antioxidant naturally found in plants of the Allium species such as onions. As well as having antioxidant and anti-inflammatory properties, it is also needed to make glutathione which is an important antioxidant in cells. NAC has been used as a drug since the 1960s and is a popular dietary supplement. NAC is considered safe but the results of clinical trials are controversial or incomplete. This aim of this review is to provide a balanced view of further uses of NAC as a dietary supplement. It discusses the antioxidant properties in relation to conditions such as heart disease, diabetes and ageing; its medical uses, in the complementary treatment of cancer, as a sports supplement and as an anti-aging supplement. More information is needed on NAC and further clinical trials looking at its use in neurodegenerative diseases, addiction, and mental health disorders are underway. This may be relevant to the supplement users and may also help people suffering from chronic degenerative conditions.
Abstract
N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.
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The cytokine storm of severe influenza and development of immunomodulatory therapy.
Liu, Q, Zhou, YH, Yang, ZQ
Cellular & molecular immunology. 2016;13(1):3-10
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The influenza virus is responsible for millions of severe cases and 250 000–500 000 deaths each year. Newly emerging influenza viruses have continued to challenge medical and public health systems. These infections in humans are accompanied by an aggressive pro-inflammatory response and insufficient control of an anti-inflammatory response, a combination of events called ‘cytokine storm’. The authors review the mechanisms involved with a cytokine storm and note that there is great interest in the association between polymorphisms (individual genetic variations) and host susceptibility, which may help explain why some individuals, but not others, seem relatively resistant to cytokine storm. The authors also review the use of immune modulating treatments and conclude that the most promising therapeutic approach may be a combination of S1PR (sphingosine-1-phosphate receptor 1) agonists¬, PPAR (peroxisome proliferator-activated receptor) agonists, COX-2 (cyclooxygenase-2) inhibitors, and antioxidants, including vitamin C, N-acetylcysteine (NAC), Glycyrrhizin (a compound from liquorice), polyphenols and flavonoids (plant-based antioxidants), and should be further studied in randomised clinical trials.
Abstract
Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as 'cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.
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Effect of shiitake (Lentinus edodes) extract on antioxidant and inflammatory response to prolonged eccentric exercise.
Zembron-Lacny, A, Gajewski, M, Naczk, M, Siatkowski, I
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2013;64(2):249-54
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Shiitake (Lentinus edodes) is a popular culinary and medicinal mushroom. It contains numerous active compounds including ergothioneine which has anti-inflammatory and antioxidant properties. This study evaluated the antioxidant and anti-inflammatory effect of shiitake extract in healthy men exposed to exercise-induced muscle damage. Fourteen healthy males participated in this placebo-controlled crossover study. Subjects ingested shiitake extract or placebo for 10 days prior to exercise, with a 30 day period between the two phases of the crossover. Bloods were drawn at 20 minutes, 24 hours and 48 hours after exercise. There was no statistically significant difference between the shiitake and the placebo group in the inflammation related parameters measured. But there was a significant change in certain compounds suggesting an increased antioxidant activity in the shiitake group. The authors conclude that shiitake does not affect the inflammatory response following exercise but has antioxidant action, and that further studies are needed to make recommendations for use of shiitake by athletes.
Abstract
The shiitake (Lentinus edodes) extract is purported to have potent antioxidant, anti-inflammatory and regenerative properties due to presence of many bioactive compounds such as ergothioneine. This study was designed to assess the antioxidant and anti-inflammatory activity of shiitake extract in healthy men exposed to exercise-induced skeletal muscles damage. Subjects ingested shiitake mushroom extract (700 mg, two times per day) or placebo for 10 days prior to two separate exercise trials (crossover study). The exercise session involved 90 min run at 65% VO2max (0% gradient) and 15-min eccentric phase at 65% VO2max (-10% gradient). Subjects experienced creatine kinase (peak 461±206 IU/L) and leukocytes (peak 9.82 x 103/μL) elevations indicating muscle damage and inflammation. Exercise altered plasma IL-6 (peak 5.29±0.78 pg/mL), IL-10 (peak 24.75±6.22 pg/mL) and IL-1β (peak 0.54±0.09 pg/mL) levels but did not affect tumour necrosis factor α (TNF-α) level relative to baseline. Shiitake extract did not demonstrate any effect on immune cells number and inflammatory mediators level, with the exception of IL-10. Thiol redox status (GSHtotal-2GSSG/GSSG) and niric oxide (NO) concentration increased after shiitake extract whereas H2O2 and 8-isoprostanes did not change. In conclusion, shiitake mushroom extract had no effect on markers of inflammation following prolonged eccentric exercise but demonstrated an antioxidant activity through the regulation of nitric oxide concentration and thiol redox status.