Dual effect of the herbal matcha green tea (Camellia sinensis L. kuntze) supplement in EA.hy926 endothelial cells and Artemia salina.

ETHNOPHARMACOLOGICAL RELEVANCE: Matcha green tea (Camellia sinensis) based-supplements have been widely used since they present a greater content of phenolic compounds than traditional green tea, which is popularly used in the treatment of diabetes. However, there are few studies on the effectiveness and safety of matcha supplements. AIM OF THE STUDY: This work aimed to evaluate the efficacy and safety of this supplement in endothelial cells (EA.hy926) in the hyperglycemic model and in vivo Artemia salina. MATERIALS AND METHODS: To assess the effect of Matcha herbal supplement (MHS), EA. hy926 endothelial cells were treated with 20 µg/mL of MHS for 24 h, in a hyperglycemic medium with 35 mM glucose. After treatment, cells were trypsinized and centrifuged at 4 °C and 47×g for 5 min. The pellet was used to determine the reaction products to thiobarbituric acid and the levels of nitric oxide. Electron transport chain activity and ATP levels were also evaluated. Intracellular pH, apoptosis, and mitochondrial membrane depolarization were evaluated by flow cytometry. MHS chemical characterization was performed by HPLC-UV and total phenolic content analysis. The evaluation of the antioxidant capacity of MHS was performed by 2,2-diphenyl-1-picrylhydrazyl radical scavenger assay. To determine the in vivo acute toxicity of MHS, an A. salina assay was conducted, using 0,2 mL of different concentrations of MHS (10, 50, 100, 250, 500, 750 and 1000 µg/mL). The LD50 values were obtained by interpolation of 50% (y = 50) of the dead individuals in the trend curves. RESULTS: Our data showed that MHS was able to avoid oxidative and nitrosative stress induced by hyperglycemia, demonstrating important antioxidant activity. However, it was observed that MHS reduced up to 90% the activity of the four-electron transport complexes, reducing the ATP production of the endothelial cells. In the toxicity assay performed in Artemia salina, MHS showed mild toxicity (LD50 = 0,4 mg/mL). The major compounds found in MHS were epigallocatechin gallate, epicatechin, rutin, kaempferol, and quercetin. CONCLUSIONS: This data draws attention to the fact that supplements with high content of phenolic compounds, capable of avoiding oxidative and nitrosative stress can have a dual effect and, simultaneously to antioxidant activity, can induce toxicity in different cell types.

Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges.

The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.