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This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo , and albumin denaturation to evaluate the anti-inflammatory effect in vitro . The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo . Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg -1 ), quercitrin (1,235.8 mg kg-1) and gallic acid (628. 2 mg kg -1 ). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus . The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL -1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant., (© 2024 Aziz Zouhri et al., published by Sciendo.)

Gut microbiota dysbiosis is causally related to inflammatory bowel disease (IBD), and increased levels of the gut metabolite ammonia have been proposed to contribute to IBD development. In this study, we aimed to clarify the anti-colitis mechanism of gallic acid (GA) based on its ability to trap the deleterious metabolite ammonia and improve gut microbiota. Aminated product was detected in the fecal samples of mice after oral gavage of gallic acid (GA) and identified as 4-amino-substituted gallic acid (4-NH 2 -GA), thus confirming the ability of GA to trap ammonia in vivo . Then, we compared the beneficial effects of GA and 4-NH 2 -GA on dextran sulfate sodium (DSS)-induced colitis mouse and found that both compounds managed to alleviate colitis phenotypes, indicating ammonia trapping had no adverse effect on the original anti-colitis activity of GA. In addition, both GA and 4-NH 2 -GA improved the gut microbiota dysbiosis induced by DSS, and fecal microbiota transplantation was subsequently performed, which further revealed that the gut microbiota mediated the anti-colitis activity of both GA and 4-NH 2 -GA. In summary, this study clarified that GA alleviated colitis by targeting both the symptoms and root causes: it directly reduced the deleterious metabolite ammonia by forming aminated metabolites without compromising the original anti-colitis activity, and it also improved gut microbiota dysbiosis, which in turn contributed to the alleviation of colitis. Since the GA structure is presented in various polyphenols as a common building block, the novel anti-colitis mechanism obtained from GA may also apply to other complex polyphenols.IMPORTANCEThe dysbiosis of the gut microbiota and its metabolism directly cause the emergence of IBD. In this study, we aimed to clarify the anti-colitis mechanism of GA in sight of gut microbiota and its metabolite ammonia. We discovered that GA directly captured and reduced the harmful metabolite ammonia in vivo to produce the aminated metabolite 4-NH2-GA, while the amination of GA had no adverse effect on its initial anti-colitis activity. In addition, both GA and its aminated metabolite improved the gut microbiota in colitis mice, and the modified gut microbiota, in turn, helped to relieve colitis. Since the GA structure is presented in diverse polyphenols as a common building block, the novel anti-colitis mechanism targeting the symptoms and root causes might also apply to other complex polyphenols., Competing Interests: The authors declare no conflict of interest.

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats., Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology., Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide., Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Introduction: Previous studies revealed that gallic acid (GA) exerts anti-inflammation and immuno-regulatory properties. This study aims to explore the pharmacological activities of GA in collagen-induced arthritis (CIA) mouse model., Methods: Male DBA/1J mice were used to construct the CIA model. The mice were administrated with GA for 3 weeks. Clinical arthritis scores and hind paw volume were evaluated over the experimental period. qPCR and Western blot analysis were used to determine the levels of matrix metallopeptidases (MMPs) and cytokines. In addition, flow cytometry was used to measure the populations of Th17 and Treg cells. ELISAs were used to determine the cytokines in the serum and ankle joint tissues., Results: Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. Besides, treatment of GA reduced the overexpression of MMPs and modulated the dysregulation of inflammation-related cytokines. Flow cytometry showed that treatment of GA decreased the population of Th17 cells, and increased the population of Treg cells, as supported by treatment of GA regulated the Th17/Treg-related cytokines., Conclusions: GA attenuates symptoms in the CIA mouse model by anti-inflammation and regulating Th17/Treg cell imbalance., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Gallic acid (GA), also known as 3,4,5-trihydroxybenzoic acid, is a natural secondary metabolite and widely isolated from various fruits, plants and nuts. In recent years, GA has received increasing attention for its powerful anti-inflammatory properties. The purpose of this review is to clearly illuminate the pharmacological activities and related molecular mechanisms of GA in inflammatory diseases. After consulting a large number of literatures, we made a comprehensive exposition on the chemical characteristics, plant origins, pharmacokinetics and toxicity of GA, especially its pharmacological activities and mechanisms of action. Although the plant source of GA is very rich, its lower extraction rate limits the application of GA in development. It is worth mentioning that GA can not only be separated from many plants, but also be produced in large quantities through biological and chemical synthesis. According to pharmacokinetic studies, the absorption and elimination of GA after oral administration are fast, while the structural optimization or dosage form adjustment of GA is beneficial to increase its bioavailability. Promisingly, toxicity studies have shown that GA scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials. The results show that the anti-inflammatory mechanisms of GA mainly involved MAPK and NF-κB signaling pathways. It thus weakens the inflammatory response by reducing the release of inflammatory cytokines, chemokines, adhesion molecule and cell infiltration. Due to its excellent pharmacological activities, GA is expected to be a potential candidate for the treatment of various inflammation-related diseases. This paper will provide theoretical basis for the clinical application of GA and guide the future research and medicinal development of GA., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. Many of the available drugs against the disease are toxic and in certain cases parasite drug resistance is developed. The discovery of drugs for the treatment of leishmaniasis is a pressing concern. In the present work, we describe in vitro studies of the phenolic compound methyl gallate (MG) against Leishmania (Leishmania) amazonensis and its possible mechanisms of action. The in vitro activity of MG was assayed against L. amazonensis (promastigotes, axenic amastigotes, and intramacrophagic amastigotes). Cytotoxicity tests were performed with J774A.1 macrophages and THP-1 cell derived macrophages. To evaluate mechanisms of action, we analyzed cellular TNF-α, IL-12, IFN-γ, IL-10, IL-6, NO, ROS levels, arginase activity, and structural mechanisms (phagocytic and lysosomal activities) involving macrophage activation. Meglumine antimoniate and amphotericin B were used as reference drugs. It was observed that MG effectively inhibited the growth of both promastigote (IC 50 5.71 μM) and amastigote-like forms (EC 50 5.39 μM), with much higher selectivity indexes than the reference drugs, being more benign towards J774A.1 macrophages than meglumine antimoniate and amphotericin B, at 1631- and 70.92-fold respectively, with respect to the promastigote form. Additionally, MG proved to be even more active against intracellular amastigotes of the parasite (EC 50 4.24 μM). Our results showed that antileishmania activity was associated with increased TNF-α, IL-12, NO and ROS levels, as well as decreased IL-6 and decreased arginase activity. In addition, MG induced increased phagocytic capability, and lysosomal volume in macrophages; structural parameters of microbicidal activity. Taken together, our results suggest that MG may be a promising candidate for new drug development against leishmaniasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Contact lenses (CL) provide visual correction but their use may also induce several adverse effects causative of discomfort and conditions that lead to stop or discontinue their use. Discomfort is mainly caused by insufficient wetting, impairment of the antioxidant defence system and eye infections. The current work reports on a single step sonochemical coating of CL with ZnO nanoparticles (NPs), chitosan (CS) and gallic acid (GA). GA and CS are expected to improve the comfort of CL by imparting respectively antioxidant properties and enhanced wettability, while their combination with ZnO NPs provides the CL with antimicrobial properties. The ternary composite coating presents high antibacterial efficiency (>4.5 logs reduction) against S. aureus causative of CL-related conditions, and maintains good biocompatibility (>72%) with human cell lines. The obtained multi-functionality on the CL did not affect their geometry and refractive properties., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.