Astragalus polysaccharides improve adjuvant chemotherapy-induced fatigue for patients with early breast cancer.

This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Atractylodes lancea Rhizome Polysaccharide Alleviates MCD Diet-Induced NASH by Inhibiting the p53/mTOR Pathway.

Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease that is characterized by liver inflammation and steatosis, with possible progression to fibrosis. Currently, no drugs have been approved for the treatment of NASH. In this study, we isolated a polysaccharide from Atractylodes lancea rhizome (AP) and established a methionine- and choline-deficient (MCD) diet -induced NASH mouse model to investigate the preventive effect and potential mechanism of AP on NASH. The results showed that AP effectively reduced liver lipid accumulation and inflammation and reduced autophagy and ferroptosis in hepatocytes, thereby preventing the development of NASH. These findings suggest that AP may be a promising natural candidate for the treatment of NASH.

Astragalus polysaccharide (APS) improves the immune function in diet-induced obese (DIO) mice.

Obesity is a major health hazard, suppressing the immune system and complicating inflammatory symptoms treatment. Traditional Chinese medicine emphasizes holistic principles and syndrome-based diagnosis/therapy. Its primary focus is on enhancing overall well-being, rather than solely aiming for weight loss. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, has demonstrated promising effects in enhancing the health status of obese individuals. Therefore, this study employed DIO mouse model to explore the immunomodulatory effects of APS in obese mice. The findings revealed a dose-dependent effect of APS on obesity prevention in DIO mice. Specifically, a 4% concentration of APS significantly reduced body weight, whereas a 2% concentration tended to increase it. Furthermore, APS effectively modulated blood glucose and lipid profiles, demonstrating varying degrees of improvement in blood glucose and blood lipid-related factors. Notably, APS also facilitated the reactivation of suppressed immune function in obese mice, regulating a range of immunological variables associated with obesity and thereby maintaining homeostasis. In conclusion, the functional benefits of APS were dose-related, with a 4% concentration demonstrating promising results in obesity prevention and immune system modulation. These findings provide a potential reference for treating inflammatory conditions associated with obesity, contributing academic understanding of obesity management and immunomodulation.

Roles and mechanisms of fucoidan against dermatitis: A review.

Fucoidan is a sulfate-containing polysaccharide derived from the cell walls of brown algae and marine invertebrates. Fucoidan is widely used for the treatment of various diseases owing to its various biological activities. Dermatitis is an inflammatory reaction that affects the skin. The primary clinical manifestations include atopic dermatitis (AD or eczema) and various subtypes of contact dermatitis. The treatment of dermatitis primarily improves symptoms and reduces inflammation. However, owing to individual variations, some patients have a poor prognosis or symptom recurrence after conventional treatment. Owing to the excellent anti-allergic and anti-inflammatory activities of the low cost nature compound fucoidan, its therapeutic effect in inflammatory diseases has recently attracted the attention of researchers. This article summarizes and analyzes the advantages and pharmacological mechanisms of fucoidan against dermatitis to provide a reference for the selection of drugs for the treatment of dermatitis.

A review of chitosan polysaccharides: Neuropharmacological implications and tissue regeneration.

One of the current challenges in targeting neurological disorders is that many therapeutic molecules cannot cross the blood-brain barrier (BBB), which limits the use of natural molecules in nervous tissue regeneration. Thus, the development of new drugs to effectively treat neurological disorders would be a challenge. Natural resources are well known as a source of several therapeutic agents for the treatment of neurologic disorders. Recently, chitosan (CTS) and its derivatives from arthropod exoskeletons, have attracted much attention as a drug delivery system to transport therapeutic substances across the BBB and thanks to other neuroprotective effects including the participation to the CNS regenerations scaffolds to replicate the extracellular matrix and microenvironment of the body. This review will discuss the place of natural resource therapy in targeting neurological disorders. In particular, it will highlight recent understanding and progress in the applications of CTS as drug delivery systems and their therapeutic effects on these disorders through tissue regeneration, as well as the molecular mechanisms by which they exert these effects.

Clinical outcomes of patients receiving long-term fondaparinux for thrombotic antiphospholipid syndrome.

INTRODUCTION: Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting. MATERIALS AND METHODS: We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records. RESULTS: 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding (p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding (p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009). CONCLUSIONS: We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies.

Angelica sinensis polysaccharides ameliorate 5-FU-induced stress anemia via promoting extramedullary erythroblastic island central macrophage-mediated erythroid differentiation.

BACKGROUND: Chronic anemia, especially chemotherapy-induced anemia, is a common and intractable symptom. Puzzlingly, the conventional anemic treatment may lead to various side effects, and the mechanism of stress anemia remains unclear. METHODS: Here, peripheral blood, histopathological and transmission electron microscopical examination, colony forming test, flow cytometry, and qRT-PCR assay were used to investigate the effects of Angelia sinensis polysaccharide (ASP), one main active ingredient of Chinese herb medicine Angelica sinensis, on ameliorating 5-fluorouracil (5-FU)-induced stress anemia. RESULTS: We found that intraperitoneal injection to a C57BL/6J mouse ASP 100 mg/kg per day for consecutive 10 days or 14 days, remarkably accelerated the recovery of RBC, hemoglobin, and hematocrit in blood. ASP alleviated 5-FU-caused impairment of bone marrow cell and BFU-E enumeration. Meanwhile, ASP antagonized 5-FU promoting extramedullary erythropoiesis in the spleen, inducing splenomegaly due to stress erythroblastic islands, and occurrence of megakaryocytes and hematopoietic precursors in splenic colonies. ASP increased splenic stress BFU-E enumeration, driving BFU-E differentiation towards Pro-E and end-stage erythroblasts. Furthermore, ASP increased the number of F4/80+VCAM-1+ splenic erythroblastic island central macrophages, upregulating genetic expression of EPOR, Emp, VCAM-1, Hmox-1, Trf, TfR1, Fpn1, Spi-C, DNase2a, Tim4, MertK, and Klf1 in splenocytes. CONCLUSIONS: Our findings indicate that the possible mechanism of chemotherapy-induced anemia is related to stress erythroid maturation arrest. Whereas, ASP may promote stress erythroid differentiation via elevated EPO sensitivity in extramedullary hematopoietic organs and enhanced macrophage-mediated adhesion, iron homeostasis and transfer, and nuclear engulfment, which may represent a promising therapeutic strategy.

Anti-liver cancer effects and mechanisms and its application in nano DDS of polysaccharides: A review.

Liver cancer is the third leading cause of cancer death, with high incidence and poor treatment effect. In recent years, polysaccharides have attracted more and more attention in the research field of anti-liver cancer because of their high efficiency, low toxicity, good biocompatibility, wide sources and low cost. Polysaccharides have been proven to have good anti-liver cancer activity. In this paper, the pathways and molecular mechanisms of polysaccharides against liver cancer were reviewed in detail. Polysaccharides exert anti-liver cancer activity by blocking cell cycle, inducing apoptosis, regulating immunity, inhibiting cancer cell metastasis, inhibiting tumor angiogenesis and so on. The primary structure and chain conformation of polysaccharides have an important influence on their anti-liver cancer activity. Structural modification enhanced the anti-liver cancer activity of polysaccharides. Polysaccharides have good attenuated and synergistic effects on chemotherapy drugs. Polysaccharides can be used as functional carriers to construct intelligent nano drug delivery systems (DDS) targeting liver cancer. This review can provide theoretical support for the further development and application of polysaccharides in the field of anti-liver cancer, and provide theoretical reference and clues for relevant researchers in food, nutrition, medicine and other fields.

A sugary solution: Harnessing polysaccharide-based materials for osteoporosis treatment.

Osteoporosis, a prevalent skeletal disorder characterized by diminished bone density, compromised microstructure, and heightened fracture susceptibility, poses a growing public health concern exacerbated by aging demographics. Polysaccharides-based materials, derived from a diverse range of sources, exhibit exceptional biocompatibility. They possess a structure similar to the extracellular matrix, which can enhance cell adhesion in vivo, and demonstrate superior biological activity compared to artificial materials. This study delved into an in-depth examination of the various biomaterials and polysaccharide families associated with the treatment of osteoporosis. This article elucidates the benefits and attributes of polysaccharide-based materials in contrast to current clinical treatment modalities, delineating how these materials address prevalent challenges in the clinical management of osteoporosis. An overview of the prospective applications of polysaccharide-based materials in the future is also provided, as well as outlines the challenges that should be addressed prior to the clinical implementation of such materials.

Harnessing traditional Chinese medicine polysaccharides for combatting COVID-19.

With the global spread of COVID-19 posing ongoing challenges to public health systems, there is an ever-increasing demand for effective therapeutics that can mitigate both viral transmission and disease severity. This review surveys the landscape of polysaccharides derived from traditional Chinese medicine, acclaimed for their medicinal properties and potential to contribute to the COVID-19 response. We specifically focus on the capability of these polysaccharides to thwart SARS-CoV-2 entry into host cells, a pivotal step in the viral life cycle that informs transmission and pathogenicity. Moreover, we delve into the concept of trained immunity, an innate immune system feature that polysaccharides may potentiate, offering an avenue for a more moderated yet efficacious immune response against various pathogens, including SARS-CoV-2. Our comprehensive overview aims to bolster understanding of the possible integration of these substances within anti-COVID-19 measures, emphasizing the need for rigorous investigation into their potential applications and underlying mechanisms. The insights provided here strongly support ongoing investigations into the adjunctive use of polysaccharides in the management of COVID-19, with the anticipation that such findings could lead to a deeper appreciation and clearer elucidation of the antiviral potentials inherent in complex Chinese herbal remedies.

Polysaccharide nanosystems for osteoarthritis therapy: Mechanisms, combinations, and future directions.

Osteoarthritis (OA) represents a chronic degenerative joint ailment characterized by the gradual breakdown of cartilage, inflicting substantial physical and economic burdens, especially among the elderly. Given the incomplete understanding of OA's pathogenesis, there is an increasing need to develop targeted therapeutic strategies and preventive measures. Conventional pharmaceutical interventions, such as non-steroidal anti-inflammatory drugs, steroids, and opioids, though effective, are often accompanied by notable adverse effects, thus emphasizing the urgency in seeking safer and more efficient therapeutic alternatives. The rapid evolution of nanotechnology has opened the door to various nanosystems for drug delivery, offering a promising avenue to mitigate these side effects. Of particular interest, recent research has shed light on the significant potential of polysaccharide-based nanosystems in the context of OA therapy, demonstrating their capability to counter inflammation, oxidative stress, regulate chondrocyte metabolism and proliferation, and protect cartilage. Therefore, in this review, we provide an in-depth examination of the role of polysaccharide nanosystems in OA, focusing on summarizing these findings based on different mechanisms of action. Furthermore, this review explores the application of combined polysaccharide nanosystems in OA, aiming to establish a foundation for the utilization of novel drug delivery nanoplatforms in OA treatment, ultimately expanding therapeutic options for this debilitating condition.

Therapeutic potential of fucoidan in central nervous system disorders: A systematic review.

Central nervous system (CNS) disorders have a complicated pathogenesis, and to date, no single mechanism can fully explain them. Most drugs used for CNS disorders primarily aim to manage symptoms and delay disease progression, and none have demonstrated any pathological reversal. Fucoidan is a safe, sulfated polysaccharide from seaweed that exhibits multiple pharmacological effects, and it is anticipated to be a novel treatment for CNS disorders. To assess the possible clinical uses of fucoidan, this review aims to provide an overview of its neuroprotective mechanism in both in vivo and in vitro CNS disease models, as well as its pharmacokinetics and safety. We included 39 articles on the pharmacology of fucoidan in CNS disorders. In vitro and in vivo experiments demonstrate that fucoidan has important roles in regulating lipid metabolism, enhancing the cholinergic system, maintaining the functional integrity of the blood-brain barrier and mitochondria, inhibiting inflammation, and attenuating oxidative stress and apoptosis, highlighting its potential for CNS disease treatment. Fucoidan has a protective effect against CNS disorders. With ongoing research on fucoidan, it is expected that a natural, highly effective, less toxic, and highly potent fucoidan-based drug or nutritional supplement targeting CNS diseases will be developed.

Polygonatum sibiricum polysaccharide regulation of gut microbiota: A viable approach to alleviate cognitive impairment.

Polygonatum sibiricum has anti-inflammatory effects and is one of the well-known functional foods. Polygonatum sibiricum polysaccharide (PSP), as a traditional medicinal and food homologous substance, can regulate the balance of intestinal flora and short chain fatty acid levels, reduce intestinal permeability and serum endotoxin levels, and inhibit the activation of astrocytes and microglia. It can significantly alleviate neurological diseases and improve cognitive impairment. Current evidence suggests that bidirectional communication between the central nervous system and the gastrointestinal tract may affect the human nervous system, cognition, and behavior through the gut-brain axis. This article provides a systematic review, detailing the biological activity of PSP, and explores the pathogenesis of gut microbiota signaling in cognitive impairment, providing a promising strategy for improving cognitive impairment.

Dendrobium officinale Kimura et Migo polysaccharide ameliorated DNFB-induced atopic dermatitis in mice associated with suppressing MAPK/NF-κB/STAT3 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura et Migo as a valuable Chinese medicine has been used in China for more than 2000 years. Its main active components, polysaccharide (DOP), has been reported to have various pharmacological effects, including anti-inflammatory, antioxidant and alleviating AD effects. However, the precise mechanism underlying its therapeutic effect in AD remains largely unclear. AIM OF THE STUDY: The present study sought to assess the efficacy of DOP and elucidate its intricate mechanisms in ameliorating DNFB-induced AD. MATERIALS AND METHODS: Mice were sensitized with DNFB and treated with DOP application for 14 days. Treatment effects were assessed using dermatitis scores, ear thickness and scratching frequency. Epidermal thickness, mast cells and CD4+ T cells infiltration were detected by using H&E, toluidine blue staining and immunofluorescence staining respectively. Serum histamine (HIS), immunoglobulin E (IgE), thymic stromal lymphopoietin (TSLP), skin SOD, MDA, GHS, CAT, inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-4, IL-5, IL-13) and chemokine (MIP-α, MDC, MCP-1) levels were quantify by ELISA and immunohistochemistry. Additionally, qPCR and Western blot analyses were performed to assess genes and proteins expression associated with MAPK/NF-κB/STAT3 signaling pathway. RESULTS: The results indicated that DOP effectively mitigated AD-like skin lesions in mice through multiple pathways. It reduced epidermal thickness, ear thickness and scratching frequency in AD mice. Additionally, DOP mitigated inflammatory responses by decreasing the levels of inflammatory factors, as well as reducing serum levels of IgE, HIS, and TSLP. Moreover, DOP inhibited infiltration of mast cells and CD4+ T cells, suppressed the expression of skin chemokines such as MDC, MCP-1, and MIP-α, and enhanced filaggrin content in AD mice. Furthermore, DOP significantly boosted antioxidant capacity, as well as significantly reduced the expression of JAK1, STAT3, NF-κB p65, IκBα, ERK1/2, and p38 proteins and phosphorylated proteins such as p-JAK1, p-STAT3, p-NF-κB p65, p-IκBα, p-ERK1/2, and p-p38. CONCLUSIONS: These findings suggested that DOP has significant anti-AD activity, primarily through reducing inflammatory responses, improving antioxidant capacity, repairing the skin barrier, and down-regulating key genes and proteins in MAPK/NF-κB/STAT3 signaling pathway, and that this study may provide valuable insights into the development of innovative therapies for the treatment of AD.

Polysaccharide of Atractylodes macrocephala Koidz alleviates NAFLD-induced hepatic inflammation in mice by modulating the TLR4/MyD88/NF-κB pathway.

Non-alcoholic fatty liver disease (NAFLD) not only could cause abnormal lipid metabolism in the liver, but also could cause liver inflammation. Previous studies have shown that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) could alleviate animal liver inflammatory damage and alleviate NAFLD in mice caused by high-fat diet(HFD), but regulation of liver inflammation caused by NAFLD has rarely been reported. In this study, an animal model of non-alcoholic fatty liver inflammation in the liver of mice was established to explore the protective effect of PAMK on the liver of mice. The results showed that PAMK could alleviate the abnormal increase of body weight and liver weight of mice caused by HFD, alleviate the abnormal liver structure of mice, reduce the level of oxidative stress and cytokine secretion in the liver of mice, and downregulate the mRNA expression of TLR4, MyD88, NF-κB and protein expression of P-IκB, P-NF-κB-P65, TLR4, MyD88, NF-κB in the liver. These results indicate that PAMK could alleviate hepatocyte fatty degeneration and damage, oxidative stress and inflammatory response of the liver caused by NAFLD in mice.

Natural polysaccharides as promising reno-protective agents for the treatment of various kidney injury.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

Repurposing of the analgesic Neurotropin for MASLD/MASH treatment.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased in recent decades. Approximately 25% of patients with MASLD progress to metabolic dysfunction-associated steatohepatitis, which is characterized by hepatic steatosis plus hepatocyte damage, inflammation, and fibrosis. We previously reported that Neurotropin (NTP), a drug used for relieving pain in Japan and China, inhibits lipid accumulation in hepatocytes by preventing mitochondrial dysfunction. We hypothesized that inhibiting hepatic steatosis and inflammation by NTP can be an effective strategy for treating MASLD and tested this hypothesis in a MASLD mouse model. METHODS: Six-week-old C57BL/6NJ male mice were fed a normal diet and normal drinking water or a high-fat diet with high fructose/glucose water for 12 weeks. During the last 6 weeks, the mice were also given high-dose NTP, low-dose NTP, or control treatment. Histologic, biochemical, and functional tests were conducted. MitoPlex, a new proteomic platform, was used to measure mitochondrial proteins, as mitochondrial dysfunction was previously reported to be associated with MASLD progression. RESULTS: NTP inhibited the development of hepatic steatosis, injury, inflammation, and fibrosis induced by feeding a high-fat diet plus high fructose/glucose in drinking water. NTP also inhibited HSC activation. MitoPlex analysis revealed that NTP upregulated the expression of mitochondrial proteins related to oxidative phosphorylation, the tricarboxylic acid cycle, mitochondrial dynamics, and fatty acid transport. CONCLUSIONS: Our results indicate that NTP prevents the development of hepatic steatosis, injury, and inflammation by preserving mitochondrial function in the liver and inhibits liver fibrosis by suppressing HSC activation. Thus, repurposing NTP may be a beneficial option for treating MASLD/metabolic dysfunction-associated steatohepatitis.

Alleviated diabetic osteoporosis and peripheral neuropathic pain by Rehmannia glutinosa Libosch polysaccharide via increasing regulatory T cells.

Diabetic peripheral neuropathy (DPN) and diabetic osteoporosis (DOP) are conditions that significantly impact the quality of life of patients worldwide. Rehmanniae Radix Preparata, a component of traditional Chinese medicine with a history spanning thousands of years, has been utilized in the treatment of osteoporosis and diabetes. Specifically, Rehmannia glutinosa Libosch polysaccharide (RGP), a key bioactive compound of Rehmanniae Radix Preparata, has demonstrated immune-modulating properties and beneficial effects on hyperglycemia, hyperlipidemia, and vascular inflammation in diabetic mice. Despite these known actions, the precise mechanisms of RGP in addressing DOP and DPN remain unclear. Our study aimed to explore the impact of RGP on osteoporosis and peripheral neuropathic pain in diabetic mice induced by streptozotocin (STZ). The findings revealed that RGP not only improved hyperglycemia and osteoporosis in STZ-induced diabetic mice but also enhanced osteogenesis, insulin production, and nerve health. Specifically, RGP alleviated distal pain, improved nerve conduction velocity, nerve fiber integrity, and immune cell balance in the spleen. Mechanistically, RGP was found to upregulate HDAC6 mRNA expression in regulatory T cells, potentially shedding light on novel pathways for preventing DOP and DPN. These results offer promising insights for the development of new therapeutic approaches for diabetic complications.

Fucoidan as a Promising Drug for Pain Treatment: Systematic Review and Meta-Analysis.

Fucoidan is a polymer of L-fucose and L-fucose-4-sulphate naturally found in marine sources that inhibits p-selectin, preventing neutrophil recruitment to the site of injury. Fucoidan is employed in many studies as a tool to investigate the contribution of neutrophils to pain, showing analgesic effects. We performed a systematic review and meta-analysis to quantify the analgesic effects of pretreatment with fucoidan reported in the available preclinical studies. In addition, we summarized the articles which have studied the therapeutic effects of fucoidan in pathological pain at preclinical and clinical levels. The results of this systematic review reveal that pretreatment with fucoidan is a powerful tool which reduces neutrophil infiltration by 70-90% at early time points. This meta-analysis showed that preventative treatment with fucoidan produced a significant pain reduction. In addition, several preclinical studies have observed that fucoidan treatment reduces the pain that is associated with various pathologies. Finally, fucoidan has also been tested in several clinical trials, with some degree of analgesic efficacy, but they were mostly small pilot studies. Considering all the above information, it can be concluded that fucoidan is not only a preclinical tool for studying the role of neutrophils in pain but also a promising therapeutic strategy for pain treatment.