Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes.

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.

Ellagitannins from Castanea sativa Mill. Leaf Extracts Impair H. pylori Viability and Infection-Induced Inflammation in Human Gastric Epithelial Cells.

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.

Physiological and Transcriptomic Evaluation of Drought Effect on Own-Rooted and Grafted Grapevine Rootstock (1103P and 101-14MGt).

Grapevines worldwide are grafted onto Vitis spp. rootstocks in order to improve their tolerance to biotic and abiotic stresses. Thus, the response of vines to drought is the result of the interaction between the scion variety and the rootstock genotype. In this work, the responses of genotypes to drought were evaluated on 1103P and 101-14MGt plants, own-rooted and grafted with Cabernet Sauvignon, in three different water deficit conditions (80, 50, and 20% soil water content, SWC). Gas exchange parameters, stem water potential, root and leaf ABA content, and root and leaf transcriptomic response were investigated. Under well-watered conditions, gas exchange and stem water potential were mainly affected by the grafting condition, whereas under sever water deficit they were affected by the rootstock genotype. Under severe stress conditions (20% SWC), 1103P showed an "avoidance" behavior. It reduced stomatal conductance, inhibited photosynthesis, increased ABA content in the roots, and closed the stomata. The 101-14MGt maintained a high photosynthetic rate, limiting the reduction of soil water potential. This behavior results in a "tolerance" strategy. An analysis of the transcriptome showed that most of the differentially expressed genes were detected at 20% SWC, and more significantly in roots than in leaves. A core set of genes has been highlighted on the roots as being related to the root response to drought that are not affected by genotype nor grafting. Genes specifically regulated by grafting and genes specifically regulated by genotype under drought conditions have been identified as well. The 1103P, more than the 101-14MGt, regulated a high number of genes in both own-rooted and grafted conditions. This different regulation revealed that 1103P rootstock readily perceived the water scarcity and rapidly faced the stress, in agreement with its avoidance strategy.

Exploring In Vitro the Combination of Cistus × incanus L. and Castanea sativa Mill. Extracts as Food Supplement Ingredients against H. pylori Infection.

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.

Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases.

Plants rich in hydrolyzable tannins were traditionally used all over the world for a variety of chronic inflammatory disorders, including arthritis, colitis, and dermatitis. However, the knowledge of their immunological targets is still limited though fundamental for their rational use in phytotherapy. The recent advances regarding the pathogenesis of inflammatory-based diseases represent an opportunity to elucidate the pharmacological mechanism of plant-derived metabolites with immunomodulatory activity. This review collects recent articles regarding the role of hydrolyzable tannins and their gut metabolites in Th1, Th2, and Th17 inflammatory responses. In line with the traditional use, rheumatoid arthritis (RA), inflammatory bowel diseases (IBDs), psoriasis, atopic dermatitis (AD), and asthma were the most investigated diseases. A substantial body of in vivo studies suggests that, beside innate response, hydrolyzable tannins may reduce the levels of Th-derived cytokines, including IFN-γ, IL-17, and IL-4, following oral administration. The mode of action is multitarget and may involve the impairment of inflammatory transcription factors (NF-κB, NFAT, STAT), enzymes (MAPKs, COX-2, iNOS), and ion channels. However, their potential impact on pathways with renewed interest for inflammation, such as JAK/STAT, or the modulation of the gut microbiota demands dedicate studies.

Unveiling the Ability of Witch Hazel (Hamamelis virginiana L.) Bark Extract to Impair Keratinocyte Inflammatory Cascade Typical of Atopic Eczema.

Hamamelis virginiana L. bark extract is a traditional remedy for skin affections, including atopic dermatitis/eczema (AD). Hamamelis preparations contain tannins, including hamamelitannin (HT), although their pharmacological role in AD is still unknown. This study aimed to study the rational for its topical use by considering the impact of crucial biomarkers on AD pathogenesis. A standardized extract (HVE) (0.5−125 µg/mL) was compared to hamamelitannin (HT), its main compound (0.5−5 µg/mL), in a model of human keratinocytes (HaCaTs), challenged with an AD-like cytokine milieu (TNF-α, IFN-γ, and IL-4). HVE inhibited the release of mediators involved in skin autoimmunity (IL-6 and IL-17C) and allergy (TSLP, IL-6, CCL26, and MMP-9) with a concentration-dependent fashion (IC50s < 25 µg/mL). The biological mechanism was ascribed, at least in part, to the impairment of the NF-κB-driven transcription. Moreover, HVE counteracted the proliferative effects of IL-4 and recovered K10, a marker of skin differentiation. Notably, HT showed activity on well-known targets of IL-4 pathway (CCL26, K10, cell proliferation). To the best of our knowledge, this work represents the first demonstration of the potential role of Hamamelis virginiana in the control of AD symptoms, such as itch and skin barrier impairment, supporting the relevance of the whole phytocomplex.

Anti-Inflammatory and Anti-Acne Effects of Hamamelis virginiana Bark in Human Keratinocytes.

Cutibacterium acnes (C. acnes) is recognized as one of the main triggers of the cutaneous inflammatory response in acne vulgaris, a chronic skin disorder with a multifactorial origin. Witch hazel (Hamamelis virginiana L.) is a plant widely used for skin inflammatory conditions, with some preliminary anti-inflammatory evidence on the skin, but lacking data on acne conditions. This study aimed to evaluate the effect of a glycolic extract from Hamamelis virginiana bark (HVE) versus C. acnes-induced inflammation in human keratinocytes (HaCaT). Phytochemical investigations of HVE identified hamamelitannin (HT) and proanthocyanidins as the most abundant compounds (respectively, 0.29% and 0.30% w/wextract). HVE inhibited C. acnes-induced IL-6 release (IC50: 136.90 µg/mL), by partially impairing NF-κB activation; however, no antibacterial or antibiofilm activities were found. In addition, HVE showed greater anti-inflammatory activity when TNF-α was used as a proinflammatory stimulus (IC50 of 38.93 µg/mL for IL-8 release), partially acting by antioxidant mechanisms, as shown for VEGF inhibition. The effects of HVE are primarily based on the proanthocyanidin content, as HT was found inactive on all the parameters tested. These results suggest further investigations of HVE in other inflammatory-based skin diseases.

The Nutraceutical Properties of Sumac (Rhus coriaria L.) against Gastritis: Antibacterial and Anti-Inflammatory Activities in Gastric Epithelial Cells Infected with H. pylori.

Sumac (Rhus coriaria L.) is a spice and medicinal herb traditionally used in the Mediterranean region and the Middle East. Since we previously demonstrated Sumac biological activity in a model of tumor necrosis factor alpha (TNF-α)-induced skin inflammation, the present work is aimed at further demonstrating a potential role in inflammatory disorders, focusing on gastritis. For this purpose, different polar extracts (water-W, ethanol-water-EW, ethanol-E, ethanol macerated-Em, acetone-Ac, ethylacetate-EtA) were investigated in gastric epithelial cells (GES-1) challenged by TNF-α or H. pylori infection. The ethanolic extracts (E, EW, Em) showed the major phenolic contents, correlating with lower half maximal inhibitory concentrations (IC50s) on the release of interleukin-8 (IL-8, <15 µg/mL) and interleukin-6 (IL-6, <20 µg/mL) induced by TNF-α. Similarly, they inhibited IL-8 release (IC50s < 70 µg/mL) during Helicobacter pylori (H. pylori) infection and exhibited a direct antibacterial activity at comparable concentrations (minimum inhibitory concentration (MIC) = 100 µg/mL). The phenolic content and the bioactivity of EW were maintained after simulated gastric digestion and were associated with nuclear factor kappa B (NF-κB) impairment, considered the main putative anti-inflammatory mechanism. On the contrary, an anti-urease activity was excluded. To the best of our knowledge, this is the first demonstration of the potential role of Sumac as a nutraceutical useful in H. pylori-related gastritis.

Impact of Cooking on Bioactive Compounds and Antioxidant Activity of Pigmented Rice Cultivars.

Pigmented rice cultivars, namely Venere and Artemide, are a source of bioactive molecules, in particular phenolics, including anthocyanins, exerting a positive effect on cardiovascular systems thanks also to their antioxidant capacity. This study aimed to determine the total phenol index (TPI), total flavonoids (TF), total anthocyanins (TA) and in vitro antioxidant capacity in 12 batches of Venere cultivar and two batches of Artemide cultivar. The rice was cooked using different methods (boiling, microwave, pressure cooker, water bath, rice cooker) with the purpose to individuate the procedure limiting the loss of bioactive compounds. TPI, TF and TA were spectrophotometrically determined in both raw and cooked rice samples. Rice samples of Artemide cultivars were richer in TPI (17.7-18.8 vs. 8.2-11.9 g gallic acid/kg in Venere rice), TF (13.1 vs. 5.0-7.1 g catechin/kg rice for Venere rice) and TA (3.2-3.4 vs. 1.8-2.9 g Cy-3glc/kg for Venere rice) in comparison to those of Venere cultivar; as well, they showed higher antioxidant capacity (46.6-47.8 vs. 14.4-31.9 mM Trolox/kg for Venere rice). Among the investigated cooking methods, the rice cooker and the water bath led to lower and comparable losses of phenolics. Interestingly, the cooking water remaining after cooking with the rice cooker was rich in phenolics. The consumption of a portion of rice (100 g) cooked with the rice cooker with its own cooking water can supply 240 mg catechin and 711 mg cyanidin 3-O-glucoside for Venere rice and 545 mg catechin and 614 mg cyanidin 3-O-glucoside for Artemide rice, with a potential positive effect on health.