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Medicinal plants are precious gifts of nature, which may serve as a source of food and medicine to humans. Phyllanthus emblica L has held a unique position in the Indian (Ayurvedic), Turkish, Unani, and Tibetan medicinal systems for centuries. Its nutritional, therapeutic and healing potentials have made it a valid research option for the development of novel drug formulations with few side effects. The presence of vitamin C, alkaloids, ellagitannins, gallic acid, emblicanin A and emblicanin B, flavonoids (especially rutin and quercetin), and a variety of biological molecules, makes P. emblica, a valued medicinal plant. This review article summarizes the recent literature relevant to the nutritional, health, and therapeutic benefits of P. emblica, such as potential chemo-preventive, anti-diabetic, anti-microbial, anti-inflammatory, analgesic, anti-mutagenic, antioxidant, diuretic, aphrodisiac, UV protectant, and anti-aging activities. Its applications in memory enhancing, respiratory, skin and ophthalmic disorders, and detoxification including that of snake venom, are also highlighted. It additionally reviews retrospective studies on P. emblica at the molecular level, for disease management and control. P. emblica is an important medicinal plant with many benefits. It has been used for centuries and generations as a source of food because of its unique restorative and rejuvenating potential. Thus, in light of the sum of these investigations, new studies could be designed to explore valuable bioactive compounds present throughout in nature in the form of plants

The management of chronic obstructive pulmonary disease (COPD) is fundamentally still heavily dependent on the use of bronchodilators and corticosteroids. Therefore, there is a need for alternative, more effective and safer therapeutic approaches. In particular, since inflammation in COPD lungs is often poorly responsive to corticosteroid treatment, novel pharmacological anti-inflammatory approaches are needed to optimally treat COPD patients. There have been multiple attempts to develop drugs that inhibit recruitment and activation of inflammatory cells, such as macrophages, neutrophils and T-lymphocytes, in the lungs of patients with COPD or target inflammatory mediators that are important in the recruitment or activation of these inflammatory cells or released by such cells. This review article focuses on novel classes of anti-inflammatory drugs that have already been tested in humans as possible treatments for patients with COPD.

ntroduction: The treatment of uncontrolled asthma has improved because of triple therapy that includes a long-acting muscarinic antagonist (LAMA) and biological drugs, but several patients are resistant to corticosteroids and/or cannot achieve adequate asthma control using such therapies. Areas covered: Herein, the authors review the current and emerging synthetic pharmacotherapy for uncontrolled asthma to overcome obstacles and limitations of biological therapies. The authors also provide their expert perspectives and opinion on the treatment of uncontrolled asthma. Expert opinion: LAMAs should be added to inhaled corticosteroid/long-acting β2-agonist combinations much earlier than currently recommended by the Global Initiative for Asthma strategy because they can influence the course of small airways disease, reducing lung hyperinflation and improving asthma control. Biological therapies are a major advance in the treatment of severe asthma, but their use is still very limited for several reasons. An alternative to overcome the use of biological therapies is to synthesize compounds that target inflammation-signaling pathways. Several pathways have been identified as potential targets to design either therapeutic or prophylactic drugs against asthma. Some new compounds have already been tested in humans, but results have often been disappointing probably because existing phenotypic and endotypic variants may unpredictably limit the therapeutic value of blocking a specific pathway in most asthmatics, although there may be a substantial benefit for a subgroup of patients.

Oxylipins are signaling molecules originated by fatty acids that modulate vascular and bronchial tone, bronchial secretion, cytokine production and immune cell activity. The unbalanced production of pro-inflammatory and pro-resolving (i.e., anti-inflammatory) oxylipins has a relevant role in the pathogenesis of pulmonary inflammation like in cystic fibrosis (CF). We analyzed by LC-MRM/MS 65 oxylipins and 4 fatty acids in resting saliva from 69 patients with CF and 50 healthy subjects (controls). The salivary levels of 48/65 oxylipins were significantly different between CF patients and controls. Among these, EpETE, DHET, 6ketoPGE1 and HDHA were significantly higher in saliva from CF patients than in controls. All these molecules display anti-inflammatory effects, i.e., releasing of bronchial and vascular tone, modulation of cytokine release. While 20-hydroxyPGF2A, PGB2, EpDPE, 9 K-12-ELA, bicyclo-PGE2, oleic acid, LTC4, linoleic acid, 15oxoEDE, 20 hydroxyPGE2 and DHK-PGD2/PGE2 (mostly associated to pro-inflammatory effects) resulted significantly lower in CF patients than in controls. Our data suggest that the salivary oxylipins profile in CF patients is addressed toward a global anti-inflammatory effect. Although these findings need be confirmed on larger populations in prospective studies, they will contribute to better understand the pathogenesis of CF chronic inflammation and to drive targeted therapies based on the modulation of oxylipins synthesis and degradation.

Background Irritable bowel syndrome (IBS) is one of the most frequent and recurrent gastrointestinal diseases. However, up to now, no pharmacological agent has been approved to treat IBS. Emerging evidence showed that inflammation has a vital role in enhancing nervous system sensitivity and perception of abdominal pain in subjects with IBS. Propolis is an herbal substance with a broad spectrum of antioxidants, anti-inflammatory, and prebiotic properties, which might exert beneficial effects to reduce the severity of IBS. The current clinical trial aims to evaluate the efficacy of propolis supplementation on IBS. Methods This single-center, randomized, double-blind, placebo-controlled clinical trial will be performed to evaluate the effect of propolis supplementation in adult patients with IBS diagnosed with Rome IV criteria. Fifty-two eligible patients will randomly be allocated to receive a propolis tablet (450 mg, containing 100 mg polyphenol compounds) or identical placebo, twice daily for 6 weeks. The primary outcome of the trial is an improvement in IBS severity from baseline to the sixth week of intervention. The secondary outcomes include the change in weight, waist circumference, and IBS quality of life. We will use the paired sample t test or Mann-Whitney U test for the within-group comparison and independent sample t test or Wilcoxon rank-sum and chi-square test or Fisher’s exact test for the between-group comparison. Besides, a multivariable-adjusted mean effect will be computed using the ANCOVA test. Discussion We hypothesize that propolis supplementation would be useful for treating IBS through its antioxidants, anti-inflammatory, and prebiotic properties. This trial will show the results of propolis supplementation, whether positive or negative, on IBS. If the current trial confirms our hypothesis, propolis supplementation can be a new choice in adjunctive therapy of IBS. Trial registration Iranian Registry of Clinical Trials IRCT20190708044154N1. Registered on 26 December 2019. Updated on 13 February 2020. https://en.irct.ir/trial/40983 Sponsor Tabriz University of Medical Sciences, Tabriz, Iran

Vincenzo Quagliariello,1,* Raffaele Vecchione,2,* Alberta De Capua,2 Elena Lagreca,2 Rosario Vincenzo Iaffaioli,3 Gerardo Botti,4 Paolo A Netti,2 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, Italia; 2Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Naples, Italy; 3Multidisciplinary Studies in Oncology and Mediterranean Diet, Piazza Nicola Amore, Naples, Italy; 4Scientific Direction, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, Italia*These authors contributed equally to this workCorrespondence: Vincenzo QuagliarielloDivision of Cardiology, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, Napoli, ItaliaTel +390815903349Email quagliariello.enzo@gmail.comIntroduction: CoenzymeQ10 (CoQ10) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ10 is based on its very low oral bioavailability and instability that limit dramatically its effects as a cardioprotective agent. Herein, we loaded CoQ10 in high bioavailable nano-emulsions (NEs) coated with chitosan or chitosan and hyaluronic acid in order to improve its performance.Methods: We tested cardioprotective and hepatoprotective effects of CoQ10-loaded nano-carriers against Doxorubicin and Trastuzumab toxicities in cardiomyocytes and liver cells through analysis of cell viability, lipid peroxidation, expression of leukotrienes, p65/NF-kB and pro-inflammatory cytokines involved in anticancer-induced cardio and hepatotoxicity.Results: Nano-carriers showed high stability and loading ability and increased cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. We observed that these effects are mediated by the inhibition of lipid peroxidation and reduction of the inflammation. CoQ10-loaded nano-emulsions showed also strong anti-inflammatory effects reducing leukotriene B4 and p65/NF-κB expression and Interleukin 1β and 6 production during anticancer treatments.Discussion: Anthracyclines and Human epidermal growth factor receptor (HER2) inhibitors have shown significant anticancer effects in clinical practice but their use is characterized by cardiotoxicity and hepatotoxicity. Nano-carriers loaded with CoQ10 showed cardio and hepatoprotective properties mediated by reduction of oxidative damages and pro-inflammatory mediators. These results set the stage for preclinical studies of cardio and hepatoprotection in HER2+ breast cancer-bearing mice treated with Doxorubicin and Trastuzumab.Keywords: cardio-oncology, nano-medicine, Coenzyme Q10, doxorubicin, trastuzumab, inflammation

Skeletal muscle atrophy is the consequence of various conditions, such as disuse, denervation, fasting, aging, and disease. Even if the underlying molecular mechanisms are still not fully understood, an elevated oxidative stress related to mitochondrial dysfunction has been proposed as one of the major contributors to skeletal muscle atrophy. Researchers have described various forms of nutritional supplementation to prevent oxidative stress-induced muscle wasting. Among a variety of nutrients, attention has also focused on polyphenols, a wide range of plant-based compounds with antioxidant and inflammatory properties, many of which have beneficial effects on human health and might retard skeletal muscle loss and function impairment. The purpose of this review is to describe polyphenol actions in skeletal muscle atrophy prevention. Published articles from the last 10 years were searched on PubMed and other databases. Polyphenols are important molecules that should be considered when discussing possible strategies against muscle atrophy. In particular, the collected studies describe, for each polyphenol subclass, the beneficial effect on muscle mass preservation in various skeletal muscle disorders. In these examples, the polyphenol compounds appear to mainly act by reversing mitochondrial dysfunction. Given that the current information on polyphenols is mostly restricted to basic studies, more comprehensive research and additional studies should be performed to clarify their mechanisms of action in improving skeletal muscle functions during atrophy.

Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin.

Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.

Growing evidence supports the hypothesis that dietary factors may play a role in systemic low-grade chronic inflammation. Summary evidence from randomized controlled trials has shown substantial effects on biomarkers of inflammation following the adoption of plant-based diets (including, but not limited to, the Mediterranean diet), while consistent findings have been reported for higher intakes of whole grains, fruits, and vegetables and positive trends observed for the consumption of legumes, pulses, nuts, and olive oil. Among animal food groups, dairy products have been shown to have the best benefits on biomarkers of inflammation, while red meat and egg have been shown to have neutral effects. The present review provides an overview of the mechanisms underlying the relation between dietary factors and immune system, with a focus on specific macronutrient and non-nutrient phytochemicals (polyphenols) and low-grade inflammation. Substantial differences within each macronutrient group may explain the conflicting results obtained regarding foods high in saturated fats and carbohydrates, underlying the role of specific subtypes of molecules (i.e., short-chain fatty acids or fiber vs. long chain fatty acids or free added sugars) when exploring the relation between diet and inflammation, as well as the importance of the food matrix and the commixture of foods in the context of whole dietary patterns. Dietary polyphenols and oligopeptides have been hypothesized to exert several functions, including the regulation of the inflammatory response and effects on the immune system. Overall, evidence suggests that dietary factors may affect the immune system regardless of obesity-related inflammation.

The herbal plant Petroselinum crispum (P. crispum) (Mill) is commonly available around the world. In this study, the leaves of the herbal plant P. crispum were collected from the central region of Al-Kharj, Saudi Arabia, to explore their in vitro pharmacological activity. Essential oil from the leaves of P. crispum was isolated using the hydrodistillation method. The composition of P. crispum essential oil (PCEO) was determined using Gas chromatography-mass spectrometry (GC-MS). A total of 67 components were identified, representing approximately 96.02% of the total volatile composition. Myristicin was identified as the principal constituent (41.45%). The in vitro biological activity was assessed to evaluate the antioxidant, antimicrobial, and anti-inflammatory potential of PCEO. PCEO showed the highest antimicrobial activity against Candida albicans and Staphylococcus aureus among all the evaluated microbial species. In vitro anti-inflammatory evaluation using albumin and trypsin assays showed the excellent anti-inflammatory potential of PCEO compared to the standard drugs. An in silico study of the primary PCEO compound was conducted using online tools such as PASS, Swiss ADME, and Molecular docking. In silico PASS prediction results supported our in vitro findings. Swiss ADME revealed the drug likeness and safety properties of the major metabolites present in PCEO. Molecular docking results were obtained by studying the interaction of Myristicin with an antifungal (PDB: 1IYL and 3LD6), antibacterial (PDB: 1AJ6 and 1JIJ), antioxidant (PDB: 3NM8 and 1HD2), and anti-inflammatory (3N8Y and 3LN1) receptors supported the in vitro results. Therefore, PCEO or Myristicin might be valuable for developing anti-inflammatory and antimicrobial drugs.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro-inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first-line systemic therapy in moderate-to-severe forms of inflammation. HS has been proposed to be mainly an auto-inflammatory disease associated with but not initially provoked by bacteria. Therefore, it has to be assumed that the pro-inflammatory milieu previously observed in HS skin is not solely dampened by the bacteriostatic inhibition of DNA-dependent RNA polymerase. To further clarify the mechanism of anti-inflammatory effects of rifampicin, ex vivo explants of lesional HS from 8 HS patients were treated with rifampicin, and its effect on cytokine production, immune cells as well as the expression of Toll-like receptor 2 (TLR2) were investigated. Analysis of cell culture medium of rifampicin-treated HS explants revealed an anti-inflammatory effect of rifampicin that significantly inhibiting interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α production. Immunohistochemistry of the rifampicin-treated explants suggested a tendency for it to reduce the expression of TLR2 while not affecting the number of immune cells.

International audience; The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline-catalyzed Mannich reaction followed by the addition of BF3.OEt2, which generates a highly electrophilic aza-ortho-quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one-pot process provides access for the first time to tetrahydroquinolines with a cis-2,3 and trans-3,4 configuration. As proof of concept, we demonstrate that a three-step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2-selective BET bromodomain inhibitor with anti-inflammatory effect.

To date, just over a hundred phenanthrenoid dimers have been isolated. Of these, forty-two are completely phenanthrenic in nature. They are isolated from fourteen genera of different plants belonging to only five families, of which Orchidaceae is the most abundant source. Other nine completely acetylated and five methylated dimers were also defined, which were effective in establishing the position of the free hydroxyls of the corresponding natural products, from which they were obtained by semi-synthesis. Structurally, they could be useful chemotaxonomic markers considering that some substituents are typical of a single-family, such as the vinyl group for Juncaceae. From a biogenetic point of view, it is thought that these compounds derive from the radical coupling of the corresponding phenanthrenes or by dehydrogenation of the dihydrophenanthrenoid analogs. Phenanthrenes or dihydroderivatives possess different biological activities, e.g., antiproliferative, antimicrobial, antiinflammatory, antioxidant, spasmolytic, anxiolytic, and antialgal effects. The aim of this review is to summarize the occurrence of phenanthrene dimers in the different natural sources and give a comprehensive overview of their structural characteristics and biological activities.

The A\(_{2A}\) adenosine receptor (A\(_{2A}\)AR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A\(_{2A}\)AR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A\(_{2A}\)AR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.

Recent evidence highlights Parkinson's disease (PD) initiation in the gut as the prodromal phase of neurodegeneration. Gut impairment due to microbial dysbiosis could affect PD pathogenesis and progression. Here, we propose a two-hit model of PD through ceftriaxone (CFX)-induced dysbiosis and gut inflammation before the 6-hydroxydopamine (6-OHDA) intrastriatal injection to mimic dysfunctional gut-associated mechanisms preceding PD onset. Therefore, we showed that dysbiosis and gut damage amplified PD progression, worsening motor deficits induced by 6-OHDA up to 14 days post intrastriatal injection. This effect was accompanied by a significant increase in neuronal dopaminergic loss (reduced tyrosine hydroxylase expression and increased Bcl-2/Bax ratio). Notably, CFX pretreatment also enhanced systemic and colon inflammation of dual-hit subjected mice. The exacerbated inflammatory response ran in tandem with a worsening of colonic architecture and gut microbiota perturbation. Finally, we demonstrated the beneficial effect of post-biotic sodium butyrate in limiting at once motor deficits, neuroinflammation, and colon damage and re-shaping microbiota composition in this novel dual-hit model of PD. Taken together, the bidirectional communication of the microbiota-gut-brain axis and the recapitulation of PD prodromal/pathogenic features make this new paradigm a useful tool for testing or repurposing new multi-target compounds in the treatment of PD.

Non-vitamin K antagonist oral anticoagulants (NOACs) should be the preferred anticoagulant strategy for preventing ischemic stroke in patients with atrial fibrillation (AF) at increased thromboembolic risk and for treating deep venous thromboembolism (DVT) in the general population. Beyond their inhibiting action on the activated factor X (FXa) or thrombin (FIIa), NOACs showed some pleiotropic anti-inflammatory effects. The present review aimed to describe the role of FXa and FIIa in the inflammation pathway and the potential anti-inflammatory effects of NOACs.

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

Coffee contains human health-related molecules, namely polyphenols that possess a wide range of pharmacological functions, and their intake is associated with reduced colon cancer risk. This study aimed to assess the changes in the anti-inflammatory and antioxidant activity of coffee after simulated gastrointestinal digestion. The evaluation of intracellular reactive oxygen species (ROS) levels in the HT-29 human colon cancer cell line and three in vitro spectrophotometric assays were performed to determine the antioxidant activity of the samples. Characterization of coffee composition was also assessed through a Q-Orbitrap high-resolution mass spectrometry analysis. The results highlighted that the levels of polyphenols in the digested coffee brews were higher than those of the non-digested ones. All assayed samples decreased the levels of intracellular ROS when compared to untreated cells, while digested coffee samples exhibited higher antioxidant capacity and total phenolic content than not-digested coffee samples. Digested coffee samples showed a higher reduction in interleukin-6 levels than the not-digested samples in lipopolysaccharide-stimulated HT-29 cells treated for 48 h and fewer cytotoxic effects in the MTT assay. Overall, our findings suggest that coffee may exert antioxidant and anti-inflammatory properties, and the digestion process may be able to release compounds with higher bioactivity.

Clodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

Objective To date, there are no FDA approved medications for treatment of early COVID-19 infection. Recently, use of melatonin, a naturally occurring tryptophan-derivative synthesized in the pineal gland and immune cells, has been suggested as an early treatment option for COVID-19. Melatonin has known anti-inflammatory, immunomodulatory, and protective antioxidant mechanisms that may attenuate the severity of COVID-19 symptoms. The objective of the present narrative review is to discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19. Methods The MeSH terms “COVID-19” and “viral diseases” were manually searched on PubMed and relevant articles were included. Results Results showed that melatonin acts to reduce reactive-oxygen-species mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19. Conclusions These conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis.

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental and computational models. Previously established protocols were used to perform qualitative and quantitative phytochemical screening in MEMC. A computational study, including molecular docking and ADME/T analyses, was performed. The quantitative phytochemical analysis revealed the total phenolic and flavonoid contents as 148.67 and 24 mg/g, respectively. Antioxidant activity was assessed by examining the reducing power of MEMC, resulting in absorbance of 1.87 at 400 µg/mL, demonstrating a strong reduction capacity. The extract exhibited significant protection against blood clotting and showed the highest protein denaturation inhibition at 500 µg/mL. In both the acetic acid-induced writhing and formalin-induced paw-licking models, MEMC resulted in significant potential pain inhibition in mice. In the computational analysis, 4-hydroxybenzaldehyde, orcinol glucoside, curcapital, crassifogenin C, and 2,6-dimethoxy-benzoic acid displayed a strong predictive binding affinity against the respective receptors. These findings indicated that M. capitulata possesses significant pharmacological activities to an extent supported by computational studies.

The term spondyloarthritis (SpA) encompasses a heterogeneous group of inflammatory musculoskeletal diseases with several common genetic background and clinical features, including the possible involvement of the axial skeleton with peripheral mono- or oligo- arthritis and frequently coexisting skin, eye and intestinal manifestations. When the sacroiliac joints or other parts of the spine or thoracic wall are predominantly affected at magnetic resonance or X-ray imaging with inflammatory back pain, the disease is classified as axial SpA and the therapeutic choices are significantly different compared to cases of peripheral arthritis. Moving from the narrow effectiveness and safety profiles of non-steroidal anti-inflammatory drugs, there has been a significant research effort aimed at identifying new treatments based on our better understanding of the pathogenesis of SpA. Indeed, in parallel with the solid data demonstrating that IL-17 and IL-23 are key cytokines in the development of enthesitis and spondylitis, monoclonal antibodies interfering with this pathway have been developed for the treatment of axial SpA. Furthermore, the IL-17/IL-23 axis is key to extra-articular manifestations such as inflammatory bowel disease, uveitis, and psoriasis which are frequent comorbidities of SpA. Currently available drugs act through these mechanisms recognizing IL-23 and targeting IL-17, such as secukinumab and ixekizumab. These therapeutic approaches are now envisioned in the international treatment recommendations for psoriatic arthritis with an axial phenotype as well as for ankylosing spondylitis (AS). We will provide herein a concise comprehensive overview of the clinical evidence supporting the use of these and other drugs acting on IL-23 and IL-17 in axial SpA.