The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

The JAK/STAT signaling pathway: from bench to clinic.

Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

/pdf/therapeutic-potential-of-flavonoids-in-pain-and-inflammation-4nda4vio3q.pdf

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.

Catechin, the name of which is derived from catechu of the extract of Acacia catechu L [...].

https://www.mdpi.com/1420-3049/24/3/528/pdf

Catechin in Human Health and Disease

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of the underlying cause of the disorder, age is the strongest risk factor for developing these maladies, suggesting that changes that occur in the aging brain put it at increased risk for neurodegenerative disease development. Moreover, since there are a number of different changes that occur in the aging brain, it is unlikely that targeting a single change is going to be effective for disease treatment. Thus, compounds that have multiple biological activities that can impact the various age-associated changes in the brain that contribute to neurodegenerative disease development and progression are needed. The plant-derived flavonoids have a wide range of activities that could make them particularly effective for blocking the age-associated toxicity pathways associated with neurodegenerative diseases. In this review, the evidence for beneficial effects of multiple flavonoids in models of AD, PD, HD, and ALS is presented and common mechanisms of action are identified. Overall, the preclinical data strongly support further investigation of specific flavonoids for the treatment of neurodegenerative diseases.

https://www.mdpi.com/1422-0067/20/12/3056/pdf

The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases

Japanese matcha is a type of powdered green tea, grown in a traditional way. Shading of the plants during the growth period enhances the processes of synthesis and accumulation of biologically active compounds, including theanine, caffeine, chlorophyll and various types of catechins. Green tea contains four main catechins, i.e., (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG), of which the latter is the most active and abundant and matcha is their best condensed source. Due to its unique chemical composition and prized flavour, which sets it apart from other tea beverages, it is considered the highest quality tea. Its health-promoting properties are attributed to the high content of antioxidant and anti-inflammatory substances. Studies confirming the high antioxidant potential of tea beverages claim that it originates from the considerable content of catechins, a type of phenolic compound with beneficial effects on human health. Due to its potential for preventing many diseases and supporting cognitive function, regular consumption of matcha may have a positive effect on both physical and mental health. The aim of this review was to compile the health benefits of matcha tea. It is the first such review to be undertaken, and presents its main bioactive compounds in a systematic manner.

https://www.mdpi.com/1420-3049/26/1/85/pdf

Health Benefits and Chemical Composition of Matcha Green Tea: A Review

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders worldwide Its incidence is gradually increasing because of an aging demographic Therefore, AD prevention and modification is important to improve the health status of older adults Oxidative stress is a component of the pathological mechanisms underlying AD It is caused by a disruption of the balance between reactive oxygen species and antioxidant molecules This imbalance also causes neuroinflammation Catechins, which are bioactive components of tea, have antioxidative and anti-inflammatory effects Moreover, other potential properties related to AD prevention and modification have been reported in in vitro and in vivo studies Several clinical studies have also been conducted to date The current review summarizes recent updates and perspectives of the effects of catechins on AD based on the molecular mechanisms and related clinical studies

https://www.mdpi.com/1420-3049/23/9/2357/pdf

Effects of Tea Catechins on Alzheimer’s Disease: Recent Updates and Perspectives

Influenza and the common cold are acute infectious diseases of the respiratory tract. Influenza is a severe disease that is highly infectious and can progress to life-threating diseases such as pneumonia or encephalitis when aggravated. Due to the fact that influenza infections and common colds spread easily via droplets and contact, public prevention measures, such as hand washing and facial masks, are recommended for influenza prophylaxis. Experimental studies have reported that tea catechins inhibited influenza viral adsorption and suppressed replication and neuraminidase activity. They were also effective against some cold viruses. In addition, tea catechins enhance immunity against viral infection. Although the antiviral activity of tea catechins has been demonstrated, the clinical evidence to support their utility remains inconclusive. Since the late 1990s, several epidemiological studies have suggested that the regular consumption of green tea decreases influenza infection rates and some cold symptoms, and that gargling with tea catechin may protect against the development of influenza infection. This review briefly summarizes the effect of tea catechins on influenza infection and the common cold with a focus on epidemiological/clinical studies, and clarifies the need for further studies to confirm their clinical efficacy.

https://www.mdpi.com/1420-3049/23/7/1795/pdf

Effect of Tea Catechins on Influenza Infection and the Common Cold with a Focus on Epidemiological/Clinical Studies

Theanine, a major amino acid in green tea, exhibits a stress-reducing effect in mice and humans. Matcha, which is essentially theanine-rich powdered green tea, is abundant in caffeine. Caffeine has a strong antagonistic effect against theanine. The stress-reducing effect of matcha was examined with an animal experiment and a clinical trial. The stress-reducing effect of matcha marketed in Japan and abroad was assessed based on its composition. The stress-reducing effect of matcha in mice was evaluated as suppressed adrenal hypertrophy using territorially-based loaded stress. High contents of theanine and arginine in matcha exhibited a high stress-reducing effect. However, an effective stress-reducing outcome was only possible when the molar ratio of caffeine and epigallocatechin gallate (EGCG) to theanine and arginine was less than two. Participants (n = 39) consumed test-matcha, which was expected to have a stress-reducing effect, or placebo-matcha, where no effect was expected. Anxiety, a reaction to stress, was significantly lower in the test-matcha group than in the placebo group. To predict mental function of each matcha, both the quantity of theanine and the ratios of caffeine, EGCG, and arginine against theanine need to be verified.

https://www.mdpi.com/2072-6643/10/10/1468/pdf

Stress-Reducing Function of Matcha Green Tea in Animal Experiments and Clinical Trials

Catechins, phytochemicals contained mainly in green tea, exhibit antiviral activity against various acute infectious diseases experimentally. Clinical evidence supporting these effects, however, is not conclusive. We performed a placebo-controlled, single-blind, randomized control trial to evaluate the clinical effectiveness of consumption of catechins-containing beverage for preventing acute upper respiratory tract infections (URTIs). Two hundred and seventy healthcare workers were randomly allocated to high-catechin (three daily doses of 57 mg catechins and 100 mg xanthan gum), low-catechin (one daily dose of 57 mg catechins and 100 mg xanthan gum), or placebo (0 mg catechins and 100 mg xanthan gum) group. Subjects consumed a beverage with or without catechins for 12 weeks from December 2017 through February 2018. The primary endpoint was incidence of URTIs compared among groups using a time-to-event analysis. A total of 255 subjects were analyzed (placebo group n = 86, low-catechin group n = 85, high catechin group n = 84). The URTI incidence rate was 26.7% in the placebo group, 28.2% in the low-catechin group, and 13.1% in the high-catechin group (log rank test, p = 0.042). The hazard ratio (95% confidence interval (CI)) with reference to the placebo group was 1.09 (0.61–1.92) in the low-catechin group and 0.46 (0.23–0.95) in the high-catechin group. These findings suggest that catechins combined with xanthan gum protect against URTIs.

https://www.mdpi.com/2072-6643/12/1/4/pdf

Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial

What is known and objective Acute kidney injury (AKI) often occurs in hospitalized patients, and it is an increasing problem worldwide. Recently, clinical studies have shown that there is a strong association between drug-induced AKI and poor outcomes, including the progression of chronic kidney disease and end-stage renal disease; however, limited data are available on drug-induced AKI. The purpose of this study was to clarify the rank-order of the association of all drugs with AKI using a spontaneous reporting system database. Methods We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analysed. Results and discussion Based on 5 195 890 reports of all adverse events, we obtained 12 964 reports of AKI caused by all drugs and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for AKI. The most frequently reported drugs were valaciclovir hydrochloride (ROR, 24.88; 95% CI: 23.1-26.8), eldecalcitol (ROR, 14.23; 95% CI, 11.68-17.33), edaravone (ROR, 14.03; 95% CI, 11.76-16.75), acyclovir (ROR, 11.17; 95% CI, 9.55-13.1), piperacillin-tazobactam (ROR, 9.23; 95% CI, 7.72-11.0), and spironolactone (ROR, 7.36; 95% CI, 6.12-8.86). What is new and conclusion A comprehensive study using a pharmacovigilance database enabled us to identify the drugs that most frequently induce AKI, raising physicians' awareness of the drugs in use for patients with potentially decreased renal function.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcpt.12748

Daisuke Furushima

Papers

Effects of Tea Catechins on Alzheimer’s Disease: Recent Updates and Perspectives

Effect of Tea Catechins on Influenza Infection and the Common Cold with a Focus on Epidemiological/Clinical Studies

Stress-Reducing Function of Matcha Green Tea in Animal Experiments and Clinical Trials

Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial

Surveillance of drugs that most frequently induce acute kidney injury: A pharmacovigilance approach.