Dietary tannic acid attenuates elastase-induced pulmonary inflammation and emphysema in mice.

Emphysema is one of the major components of chronic obstructive pulmonary disease (COPD), which is characterised by the destruction and enlargement of air spaces, leading to airflow limitation and dyspnoea, finally progressing to oxygen dependency. The alveolar wall destruction is due to chronic inflammation, oxidative stress, apoptosis, and proteinase/anti-proteinase imbalance. So far, there has been no effective therapy for patients with COPD. We evaluated the therapeutic efficacy of tannic acid (TA), a naturally occurring plant-derived polyphenol in the murine emphysema model. In C57BL/6 J mice, we established emphysema by intratracheal instillation of elastase (EL). Then, mice were treated with TA and evaluated 1 and 21 days post-EL instillation. After 24 h, TA treatment significantly reduced EL-induced histopathological alterations, infiltrating leukocytes, and gene expression of markers of inflammation and apoptosis. Similarly, after 21 days, TA treatment suppressed the mean linear intercept, gene expression of proteinases, and increased elastic fiber contents in the lungs when compared to the EL-alone group. Furthermore, EL induced the activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) p65 pathways in the lungs was suppressed by TA treatment. In summary, TA has the potential to mitigate EL-induced inflammation, apoptosis, proteinase/anti-proteinase imbalance, and subsequent emphysema in mice.

Anti-asthmatic effects of tannic acid from Chinese natural gall nuts in a mouse model of allergic asthma.

Asthma is a chronic inflammatory disease of the airways, which is characterized by infiltration of inflammatory cells, airway hyperresponsiveness (AHR), and airway remodeling. This study aimed to explore the role and mechanism of tannic acid (TA), a naturally occurring plant-derived polyphenol, in murine asthma model. BALB/c mice were given ovalbumin (OVA) to establish an allergic asthma model. The results revealed that TA treatment significantly decreased OVA-induced AHR, inflammatory cells infiltration, and the expression of various inflammatory mediators (Th2 and Th1 cytokines, eotaxin, and total IgE). Additionally, TA treatment also attenuated increases in mucins (Muc5ac and Muc5b) expression, mucus production in airway goblet cells, mast cells infiltration, and airway remodeling induced by OVA exposure. Furthermore, OVA-induced NF-κB (nuclear factor- kappa B) activation and cell adhesion molecules expression in the lungs was suppressed by TA treatment. In conclusion, TA effectively attenuated AHR, inflammatory response, and airway remodeling in OVA-challenged asthmatic mice. Therefore, TA may be a potential therapeutic option against allergic asthma in clinical settings.

An overview on the role of plant-derived tannins for the treatment of lung cancer.

Lung cancer is the leading cause of cancer-related death globally. Despite many advanced approaches to treat cancer, they are often ineffective due to resistance to classical anti-cancer drugs and distant metastases. Currently, alternative medicinal agents derived from plants are the major interest due to high bioavailability and fewer adverse effects. Tannins are polyphenolic compounds existing as specialized products in a wide variety of vegetables, fruits, and nuts. Many tannins have been found to possess protective properties, such as anti-inflammatory, anti-fibrotic, anti-microbial, anti-diabetic, and so on. This review aims to summarize the current knowledge addressing the anti-cancer effects of dietary tannins and their underlying molecular mechanisms. In vivo and in vitro studies provide evidences that anti-cancer effects of various tannins are predominantly mediated through negative regulation of transcription factors, growth factors, receptor kinases, and many oncogenic molecules. In addition, we also discussed the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of tannins, clinical trial results as well as our perspective on future research with tannins.

Therapeutic potential of plant-derived tannins in non-malignant respiratory diseases.

Respiratory diseases are the major cause of human illness and death around the world. Despite advances in detection and treatment, very few classes of safe and effective therapy have been introduced to date. At present, phytochemicals are getting more attention because of their diverse beneficial activities and minimal toxicity. Tannins are polyphenolic secondary metabolites with high molecular weights, which are naturally present in a wide variety of fruits, vegetables, cereals, and leguminous seeds. Many tannins are endowed with well-recognized protective properties, such as anti-cancer, anti-microbial, anti-oxidant, anti-hyperglycemic, and many others. This review summarizes a large body of experimental evidence implicating that tannins are helpful in tackling a wide range of non-malignant respiratory diseases including acute lung injury (ALI), pulmonary fibrosis, asthma, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Mechanistic pathways by which various classes of tannins execute their beneficial effects are discussed. In addition, clinical trials and our perspective on future research with tannins are also reviewed.

Tannic acid alleviates experimental pulmonary fibrosis in mice by inhibiting inflammatory response and fibrotic process.

Pulmonary fibrosis (PF) is a chronic and irreversible scarring disease in the lung with limited treatment options. Therefore, it is critical to identify new therapeutic options. This study was undertaken to identify the effects of tannic acid (TA), a naturally occurring dietary polyphenol, in a mouse model of PF. Bleomycin (BLM) was intratracheally administered to induce PF. Administration of TA significantly reduced BLM-induced histological alterations, inflammatory cell infiltration and the levels of various inflammatory mediators (nitric oxide, leukotriene B4 and cytokines). Additionally, treatment with TA also impaired BLM-mediated increases in pro-fibrotic (transforming growth factor-ß1) and fibrotic markers (alpha-smooth muscle actin, vimentin, collagen 1 alpha and fibronectin) expression. Further investigation indicated that BLM-induced phosphorylation of Erk1/2 (extracellular signal-regulated kinases 1 and 2) in lungs was suppressed by TA treatment. Findings of this study suggest that TA has the potential to mitigate PF through inhibiting the inflammatory response and fibrotic process in lungs and that TA might be useful for the treatment of PF in clinical practice.

Tannic acid prevents macrophage-induced pro-fibrotic response in lung epithelial cells via suppressing TLR4-mediated macrophage polarization.

BACKGROUND: Polarized macrophages induce fibrosis through multiple mechanisms, including a process termed epithelial-to-mesenchymal transition (EMT). Mesenchymal cells contribute to the excessive accumulation of fibrous connective tissues, leading to organ failure. This study was aimed to investigate the effect of tannic acid (TA), a natural dietary polyphenol on M1 macrophage-induced EMT and its underlying mechanisms. MATERIALS: First, we induced M1 polarization in macrophage cell lines (RAW 264.7 and THP-1). Then, the conditioned-medium (CM) from these polarized macrophages was used to induce EMT in the human adenocarcinomic alveolar epithelial (A549) cells. We also analysed the role of TA on macrophage polarization. RESULTS: We found that TA pre-treated CM did not induce EMT in epithelial cells. Further, TA pre-treated CM showed diminished activation of MAPK in epithelial cells. Subsequently, TA was shown to inhibit LPS-induced M1 polarization in macrophages by directly targeting toll-like receptor 4 (TLR4), thereby repressing LPS binding to TLR4/MD2 complex and subsequent signal transduction. CONCLUSION: It was concluded that TA prevented M1 macrophage-induced EMT by suppressing the macrophage polarization possibly through inhibiting the formation of LPS-TLR4/MD2 complex and blockage of subsequent downstream signal activation. Further, our findings may provide beneficial information to develop new therapeutic strategies against chronic inflammatory diseases.