Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma.

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Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19).

Flavonoids are a class of natural substances present in plants, fruits, vegetables, wine, bulbs, bark, stems, roots, and tea. Several attempts are being made to isolate such natural products, which are popular for their health benefits. Flavonoids are now seen as an essential component in a number of cosmetic, pharmaceutical, and medicinal formulations. Quercetin is the major polyphenolic flavonoid found in food products, including berries, apples, cauliflower, tea, cabbage, nuts, and onions that have traditionally been treated as anticancer and antiviral, and used for the treatment of allergic, metabolic, and inflammatory disorders, eye and cardiovascular diseases, and arthritis. Pharmacologically, quercetin has been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia, and Theileria parasites. Additionally, it has shown beneficial effects against Alzheimer's disease (AD), and this activity is due to its inhibitory effect against acetylcholinesterase. It has also been documented to possess antioxidant, antifungal, anti-carcinogenic, hepatoprotective, and cytotoxic activity. Quercetin has been documented to accumulate in the lungs, liver, kidneys, and small intestines, with lower levels seen in the brain, heart, and spleen, and it is extracted through the renal, fecal, and respiratory systems. The current review examines the pharmacokinetics, as well as the toxic and biological activities of quercetin.

The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin.

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects

Dendritic cells’ (DCs) ability to present antigens and initiate the adaptive immune response confers them a pivotal role in immunological defense against hostile infection and, at the same time, immunological tolerance towards harmless components of the microbiota. Food products can modulate the inflammatory status of intestinal DCs. Among nutritionally-derived products, we investigated the ability of quercetin to suppress inflammatory cytokines secretion, antigen presentation, and DCs migration towards the draining lymph nodes. We recently identified the Slpi expression as a crucial checkpoint required for the quercetin-induced inflammatory suppression. Here we demonstrate that Slpi-KO DCs secrete a unique panel of cytokines and chemokines following quercetin exposure. In vivo, quercetin-enriched food is able to induce Slpi expression in the ileum, while little effects are detectable in the duodenum. Furthermore, Slpi expressing cells are more frequent at the tip compared to the base of the intestinal villi, suggesting that quercetin exposure could be more efficient for DCs projecting periscopes in the intestinal lumen. These data suggest that quercetin-enriched nutritional regimes may be efficient for suppressing inflammatory syndromes affecting the ileo-colonic tract.

Secretory Leukoprotease Inhibitor (Slpi) Expression Is Required for Educating Murine Dendritic Cells Inflammatory Response Following Quercetin Exposure.

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications.

https://www.mdpi.com/2218-273X/10/1/59/pdf

Neuroprotective Effects of Quercetin in Alzheimer's Disease.

In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

Quercetin, Inflammation and Immunity

Simple Summary During the weaning period, the change of feed and separation from ewe induce weaning stress and may affect the growth and health of kids. The application of antibiotics could relieve weaning stress; however, their prophylactic application coerces researchers to find antibiotic alternatives to relieve weaning stress. Fucoidan is a natural plant extract widely used in animal production with antioxidant and immune-modulatory properties resulting in beneficial effects on the intestinal tract. In the present study, fucoidan dietary supplementation boosted antioxidant and immune functions, improved the morphology of the intestinal tract and promoted the growth performance of kids. These results indicated that fucoidan could be used to alleviate weaning stress in kids. Abstract The purpose of this study was to evaluate the effects of fucoidan dietary supplementation on growth performance, organs’ relative weight, serum anti-oxidation markers, immune function indices and intestinal morphology in weaned kids. A total of 60 2-month-old weaned castrated male kids (Chuanzhong black goat) were used for this 30-day experiment and randomly allocated to four groups. The control group (CON) fed a basal diet, while the other three groups were provided with the same diet further supplemented with fucoidan at 0.1%, 0.3% or 0.5%, namely, F1, F2 and F3 groups, respectively. The results indicated that dietary fucoidan supplementation significantly increased (p < 0.05) the activity of catalase (CAT) when compared to the CON group on day 15. Moreover, the addition of fucoidan at 0.3% and 0.5% significantly increased (p < 0.05) the activities of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD). On day 30, dietary fucoidan supplementation significantly reduced (p < 0.05) the feed conversion rate (FCR), contents of tumor necrosis-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), while it significantly increased (p < 0.05) the activity of total superoxide dismutase (T-SOD), the content of immunoglobulin G (IgG) and the villus height (VH) of the duodenum. Moreover, dietary 0.3% and 0.5% fucoidan supplementation significantly increased (p < 0.05) the villus height (VH) of the jejunum and ileum and significantly reduced (p < 0.05) the crypt depth (CD) of ileum. In conclusion, dietary fucoidan had positive effects on growth performance, serum anti-oxidation, immune function and intestinal morphology of weaned kids.

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The Effects of Fucoidan Dietary Supplementation on Growth Performance, Serum Antioxidant Capacity, Immune Function Indices and Intestinal Morphology in Weaned Kids

Simple Summary Weaning stress has negative effects on the growth and intestinal health of goat kids. The application of antibiotics can relieve weaning stress; however, their prophylactic application has motivated researchers to find alternatives to antibiotics for mitigating the weaning stress. Fucoidan is a natural polysaccharide with antioxidant and immune-modulatory properties, and it has shown beneficial effects on intestinal barrier function. In this study, dietary supplementation of fucoidan improved the small intestinal barrier function and cecal microflora in weaned goat kids. These results suggested that fucoidan can be used as a promoter of gut health in weaned goat kids. Abstract The purpose of this study was to evaluate the effects of fucoidan supplementation on serum biochemical parameters, small intestinal barrier function, and cecal microbiota of weaned goat kids. A total of 60 2-month-old weaned castrated male goat kids (Chuanzhong black goat) were used in this 30-day experiment. The goat kids were randomly divided into four groups: a control group (CON) fed the basal diet, and three other groups supplemented with 0.1%, 0.3%, and 0.5% fucoidan in the basal diet (denoted as F1, F2, and F3 groups, respectively). The results indicated that dietary fucoidan supplementation decreased (p < 0.05) the activity of lactate dehydrogenase (LDH) and the content of glucose (GLU) as measured on day 15. As measured on day 30, dietary fucoidan increased (p < 0.05) the content of total protein (TP) and decreased the activity of aspartate aminotransferase (AST), and supplementation with 0.3% and 0.5% fucoidan decreased (p < 0.05) the activity of LDH. Dietary fucoidan decreased (p < 0.05) the content of D-lactic acid (D-LA) and the activity of diamine oxidase (DAO). Dietary fucoidan increased (p < 0.05) the activity of catalase (CAT) in the duodenum. Dietary 0.3% and 0.5% fucoidan enhanced (p < 0.05) the activity of glutathione peroxidase (GSH-Px) in the ileum, the activity of total superoxide dismutase (T-SOD) in the jejunum and ileum, and the activity of CAT in the ileum. Dietary 0.3% and 0.5% fucoidan reduced the contents of malondialdehyde (MDA) in the duodenum, jejunum, and ileum and the content of hydrogen peroxide (H2O2) in the duodenum. Dietary fucoidan increased (p < 0.05) the content of secretory immunoglobulin A (sIgA) in the duodenum. Supplementation of 0.3% and 0.5% fucoidan upregulated (p < 0.05) the gene expression of ZO-1 and claudin-1 in the duodenum, jejunum, and ileum, and dietary supplementation of 0.3% and 0.5% fucoidan upregulated (p < 0.05) the gene expression of occludin in the jejunum and ileum. The 16S rRNA high-throughput sequencing results showed that at the phylum level, dietary fucoidan increased (p < 0.05) the abundance of Bacteroidetes while decreasing (p < 0.05) the abundance of Firmicutes. At the genus level, dietary 0.3% and 0.5% fucoidan increased (p < 0.05) the abundances of Unspecified_Ruminococcaceae, Unspecified_Bacteroidale, Unspecified_Clostridiales, and Akkermansia. In conclusion, dietary fucoidan supplementation had positive effects on intestinal permeability, antioxidant capacity, immunity function, tight junctions, and the cecal microflora balance in weaned goat kids.

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Effects of Dietary Fucoidan Supplementation on Serum Biochemical Parameters, Small Intestinal Barrier Function, and Cecal Microbiota of Weaned Goat Kids

Shengnan Wang

Papers

Quercetin, Inflammation and Immunity

The Effects of Fucoidan Dietary Supplementation on Growth Performance, Serum Antioxidant Capacity, Immune Function Indices and Intestinal Morphology in Weaned Kids

Effects of Dietary Fucoidan Supplementation on Serum Biochemical Parameters, Small Intestinal Barrier Function, and Cecal Microbiota of Weaned Goat Kids