Helicobacter pylori (H. pylori) is an etiologic factor of peptic ulcer disease and gastric cancer. Virulent strains of H. pylori are correlated with the severity of gastritis, due to NF-κB activation and IL-8 expression at the epithelial level. Ellagitannins have been documented for antibacterial and anti-inflammatory activities, thus suggesting their potential use in gastritis. Recently, several authors, including our group, demonstrated that tannin-rich extracts from chestnut byproducts, at present considered agricultural waste, display promising biological activities. In this work, we detected high levels of polyphenols in hydroalcoholic extracts from chestnut leaves (Castanea sativa L.). Among polyphenols, the ellagitannin isomers castalagin and vescalagin (about 1% w/w of dry extract) were identified as potential bioactive compounds. In GES-1 cells infected by H. pylori, leaf extract and pure ellagitannins inhibited IL-8 release (IC₅₀ ≈ 28 µg/mL and 11 µM, respectively). Mechanistically, the anti-inflammatory activity was partly due to attenuation of NF-κB signaling. Moreover, the extract and pure ellagitannins reduced bacterial growth and cell adhesion. A simulation of the gastric digestion suggested that the bioactivity might be maintained after oral administration. At the transcriptional level, castalagin downregulated genes involved in inflammatory pathways (NF-κB and AP-1) and cell migration (Rho GTPase). To the best of our knowledge, this is the first investigation in which ellagitannins from plant extracts have demonstrated a potential role in the interaction among H. pylori and human gastric epithelium.

Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. pylori viability and inflammation in gastric cells. Furthermore, chestnut shells showed an important anti-inflammatory effect in gastric epithelial cells. Dietary polyphenols, including tannins, have been reported to interfere with targets of inflammation, including the nuclear factor κB (NF-κB). A promising role as a further therapeutical target for gut disorders has been recently proposed for the regulatory subunit of hypoxia-inducible factor (HIF-1α), as a potential stabilizer of intestinal barrier integrity. Therefore, the main objective of this work is the chemical characterization of several chestnut by-products (bud, spiny bur, wood, pericarp and episperm), together with the exploitation of their anti-inflammatory properties in intestinal cells, scavenging capacity, and stability following gastrointestinal digestion. The chemical characterization confirmed the presence of bioactive polyphenols in the extracts, including ellagitannins. In CaCo-2 cells stimulated by an IL-1β-IFN-γ cocktail, nearly all chestnut by-products (50 µg/mL) inhibited the release of proinflammatory mediators (CXCL-10, IL-8, MCP-1, ICAM), along with the NF-κB-driven transcription, and induced the HRE-driven transcription. The stability of the most promising extracts, identified through PCA and cluster analysis, was addressed by in vitro gastrointestinal digestion. Despite the significant reduction in total polyphenol index of chestnut bud and wood after gastric and intestinal digestion, the activity of these extracts on both scavenging and anti-inflammatory parameters remained promising. These data contribute to exploit the potential of chestnut by-products as sources of dietary polyphenols with anti-inflammatory properties at the intestinal level. Moreover, this study could represent an important step to encourage the recycling and valorization of chestnut by-products, promoting the circular economy and reducing the environmental impact related to the management of agriculture waste.

Helicobacter pylori is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in H. pylori infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of H. pylori result from early phase and chronically activated pathways. In the present study we investigated the early host response to H. pylori in non-tumoral human gastric epithelial cells (GES-1). To dissect the pathogen-specific mechanisms we also examined the response to tumor necrosis factor (TNF), a prototypical cytokine. By analyzing the activation state of NF-κB signaling, cytokine expression and secretion, and the transcriptome, we found that the inflammatory response of GES-1 cells to H. pylori and TNF results from activation of multiple pathways and transcription factors, e.g., NF-κB and CCAAT/enhancer-binding proteins (CEBPs). By comparing the transcriptomic profiles, we found that H. pylori infection induces a less potent inflammatory response than TNF but affects gene transcription to a greater extent by specifically inducing transcription factors such as CEBPβ and numerous zinc finger proteins. Our study provides insights on the cellular pathways modulated by H. pylori in non-tumoral human gastric cells unveiling new potential targets.

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 μg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin’s bioactivity mirrored the extract’s effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low μM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract’s biological activities. This study is the first to explore ellagitannins’ potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.

Cistus spp. have been traditionally used for inflammatory and infectious disorders, including gastrointestinal ailments, in the Mediterranean area. Among them, Cistus × incanus L. is one of the most frequently cited species in the literature for a variety of biological activities which include inflammatory diseases. Cistus spp. aerial parts are rich in polyphenols such as condensed and hydrolysable tannins, procyanidins, and flavonoids, which show gastroprotective activities. The purpose of the present study is to investigate the biological activities of a hydroalcoholic extract from Cistus × incanus L. aerial parts in gastric epithelial cells (GES-1) infected with H. pylori. The extracts inhibited IL-8 and NF-κB induced by H. pylori and showed antibacterial activity after simulated digestion. Since our previous paper reported interesting results on the ability of Castanea sativa Mill. leaf extract to decrease inflammatory conditions in H. pylori-infected gastric cells, the combination of Castanea sativa and Cistus × incanus extracts was also investigated, showing strong anti-inflammatory activity and inhibition of bacterial adhesion. This association of botanicals is proposed herein as a novel food supplement capable of counteracting gastric inflammatory conditions.

Background: Cannabis sativa L. (C. sativa) has a long history of medicinal use. Its inflorescences contain bioactive compounds like non-psychotropic cannabidiol (CBD), which is well known for its anti-inflammatory potential in skin conditions such as psoriasis, and psychotropic Δ-9-tetrahydrocannabinol (THC). Keratinocytes, the main cells in the epidermis, are crucial for regulating skin inflammation by producing mediators like IL-8 when stimulated by agents like TNFα. Methods: This study explores the anti-inflammatory effects of a standardized C. sativa extract (CSE) with 5% CBD and less than 0.2% THC in human keratinocytes challenged by TNFα. The aim of this study is to analyze the specific contributions of the main constituents of CSE to inflammatory responses in human keratinocytes by fractionating the extract and examining the effects of its individual components. Results: MTT assays showed that CSE was non-toxic to HaCaT cells up to 50 μg/mL. CSE inhibited NF-κB activity and reduced IL-8 secretion in a concentration-dependent manner, with mean IC₅₀ values of 28.94 ± 10.40 μg/mL and 20.06 ± 2.78 μg/mL (mean ± SEM), respectively. Fractionation of CSE into four subfractions revealed that the more lipophilic fractions (A and B) were the most effective in inhibiting NF-κB, indicating that cannabinoids and cannflavins are key contributors. Pure CBD is one of the most active cannabinoids in reducing NF-κB-driven transcription (together with THC and cannabigerol), and due to its abundance in CSE, it is primarily responsible for the anti-inflammatory activity. Conclusions: This study highlights CBD’s significant role in reducing inflammation in human keratinocytes and underscores the need to consider the synergistic interactions of several molecules within C. sativa extracts for maximum efficacy. Standardized extracts are essential for reproducible results due to the variability in responses.