Fucoidan from Cladosiphon okamuranus enhances antioxidant activity and prevents reproductive dysfunction in polystyrene microplastic-induced male rats.

Plastic pollution, including microplastic, has emerged as a severe environmental and public health problem. The health risks, especially in the case of reproductive damage caused by polystyrene microplastic (PS-MP) exposure, are emerging problems that need to be solved. This study aimed to investigate the effects of fucoidan extracted from Cladosiphon okamuranus on the polystyrene microplastic-induced oxidative stress of the Leydig (LC540) cells and reproductive damage in male rats. The oxidative stress of the LC540 cells and reproductive damage in the rats were induced by PS-MP. The fucoidan treatment reduces nitric oxide (NO) and reactive oxygen species generation in the LC540 cells. In the animal study, fucoidan treatment enhanced enzymatic antioxidant activities (glutathione peroxidase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase) and reduced malondialdehyde and nitric oxide production. Fucoidan supplementation also downregulates tumor necrosis factor-alpha, interleukin-6, and caspase-3 expression. Additionally, fucoidan upregulates testosterone levels, prevents the reduction of epithelium thickness, and reduces the area of the seminiferous tubule lumen. According to these conditions, fucoidan from Cladosiphon okamuranus prevents reproductive damage by downregulating oxidative stress and pro-inflammatory cytokines. Therefore, fucoidan can be used as a source of food supplements or functional food ingredients for reproductive or testicular damage management.

Fermented jellyfish (Rhopilema esculentum) collagen enhances antioxidant activity and cartilage protection on surgically induced osteoarthritis in obese rats.

Collagen has been considered a key treatment option in preventing damage to the articular cartilage over time and supporting the healing process, following the onset of osteoarthritis (OA). This study aimed to investigate the effect of collagen fermented from jellyfish (FJC) by Bacillus subtilis natto on anterior cruciate ligament transection with medial meniscectomy (ACLT + MMx)-induced knee OA in high-fat diet (HFD)-induced obesity in rats. The male Sprague-Dawley rats were fed an HFD for 6 weeks before ACLT + MMx surgery, after which they were administered a daily oral gavage of saline (control, OA, and OBOA), either with FJC (20 mg/kg, 40 mg/kg, and 100 mg/kg body weight) or glucosamine sulfate as a positive control (GS; 200 mg/kg body weight) for 6 weeks. Treatment with FJC decreased the fat weight, triglyceride, and total cholesterol levels in obese rats. Additionally, FJC downregulated the expression of some proinflammatory cytokines, including tumor necrosis factor-α, cyclooxygenase-2, and nitric oxide; suppressed leptin and adiponectin expression; and attenuated cartilage degradation. It also decreased the activities of matrix metalloproteinase (MMP)-1 and MMP-3. These results demonstrated that FJC showed a protective effect on articular cartilage and also suppressed the degradation of cartilage in an animal OA model, suggesting its potential efficacy as a promising candidate for OA treatment.

Seahorse Protein Hydrolysate Ameliorates Proinflammatory Mediators and Cartilage Degradation on Posttraumatic Osteoarthritis with an Obesity Rat Model.

Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.

Hippocampus kuda protein hydrolysate improves male reproductive dysfunction in diabetic rats.

The global prevalence of diabetes mellitus is rapidly increasing. This disease is associated with many complications including male reproductive dysfunctions and infertility. Seahorse ( Hippocampus kuda) is a marine teleost fish well known for its beneficial effects on the reproductive system in traditional Chinese medicine books. Recently, several studies have been shown that the enzymatic hydrolysate of seahorse has multiple pharmacological activities. This study aimed to investigate the seahorse peptide hydrolysate (SH) ameliorative effects on the diabetic-induced male reproductive dysfunction in rat models. The in vivo studies were carried out with three different doses of SH (4, 8, and 20 mg/kg) and the diabetes condition was induced by administrating with streptozotocin (35 mg/kg) and fed a 40% high-fat diet. Seahorse hydrolysate (20 mg/kg) inhibited lipid peroxidation, increased antioxidant enzyme activity, and restored seminiferous tubules morphology in testis. Moreover, it improved reproductive dysfunction by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, sperm count, and motility. According to these results, we suggested that SH exhibited amelioration effects on the reproductive dysfunction.

Echinacea purpurea Ethanol Extract Improves Male Reproductive Dysfunction With Streptozotocin-Nicotinamide-Induced Diabetic Rats.

As lifestyle changes, the prevalence of diabetes increases every year. Diabetes-induced male reproductive dysfunction is predominantly due to increased oxidative stress and then results in sperm damage and infertility. Echinacea purpurea is a traditional medicinal herb and is well-known for its immune-modulatory, antioxidative, anti-inflammatory, anticancer, and antiviral activities. The Toll-like receptor 4 (TLR4) plays a critical role in innate immune responses leading to nuclear factor (NF)-κB phosphorylation and release of proinflammatory cytokines including nitric oxide (NO), interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α. However, the relation between Echinacea purpurea extract and TLR4 remains unclear. This study aimed to investigate the protective effects on male reproduction of Echinacea purpurea ethanol extract (EPE) against diabetic rats and whether the anti-inflammatory effects were through the TLR4 pathway. Diabetic male Sprague-Dawley (SD) rats were induced by streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). EPE was tested in three doses (93, 279, and 465 mg/kg p.o. daily) for 4 weeks. Besides, metformin administration (100 mg/kg/day) was treated as a positive control. Results indicated that EPE administration for about 4 weeks improved hyperglycemia and insulin resistance. Additionally, EPE increased sperm motility, protected sperm morphology and mitochondrial membrane potential, as well as protein for testosterone synthesis enzyme. In sperm superoxide dismutase, catalase, and glutathione antioxidants were increased, whereas proinflammatory cytokines, such as NO, IL-1ß, and TNF-α were decreased. The testis protein content of TLR4 and downstream phospho-NF-κB p65 also were reduced. The EPE might reduce the production of proinflammatory cytokines via TLR4 pathways and improve diabetes-induced male infertility.

Nanoparticles of Antroquinonol-Rich Extract from Solid-State-Cultured Antrodia cinnamomea Improve Reproductive Function in Diabetic Male Rats.

PURPOSE: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. MATERIAL AND METHODS: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. RESULTS: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. CONCLUSION: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.

Blue Mussel (Mytilus edulis) Water Extract Ameliorates Inflammatory Responses and Oxidative Stress on Osteoarthritis in Obese Rats.

PURPOSE: To investigate the effects of Mytilus edulis water extract (MWE) on an anterior cruciate ligament transection and a partial medial meniscectomy surgery to induced osteoarthritis (OA) with the high-fat diet (HFD)-induced obese rats. METHODS: The male Sprague-Dawley rats were fed with HFD for 4 weeks before surgery. The OA rats were orally administered with MWE (108.5, 217.0, and 542.5 mg/kg) for 6 weeks. RESULTS: The administration of MWE affected weight loss, triglycerides content, and total cholesterol level. MWE also enhanced the activity of superoxide dismutase and decreased lipid peroxidation degree. Moreover, MWE reduced proinflammatory cytokines level, alleviated inflammation and swelling of the osteoarthritic knee, and reduced loss of proteoglycan in articular cartilage tissue. CONCLUSION: MWE suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis rats under obesity condition. Therefore, MWE has the potential to act as an alternative for osteoarthritis treatment.

Oral supplementation of fucoxanthin-rich brown algae extract ameliorates cisplatin-induced testicular damage in hamsters.

Oxidative stress is recognized as a common pathology that affects up to half of all men infertile. Fucoxanthin possesses antioxidant activity, and several investigators have reported anti-inflammatory action. This study extracted powder of Sargassum glaucescens by acetone to obtained fucoxanthin rich-brown algae extract (FXE). The objective of this study was to evaluate the ameliorative effects of fucoxanthin extract from Sargassum glaucescens on lipopolysaccharide-induced inflammation in RAW264.7 macrophage cells and its protective effects of against Cisplatin (CP)-induced reproductive damage in hamsters. Eighty male Syrian hamsters were injected with and without CP, then daily oral gavage with various concentrations of fucoxanthin for 5 days. Treatment with FXE reduced the level of reactive oxygen species and malondialdehyde in RAW 264.7 cells and the rats' testis as well as protective effects on mitochondrial membrane potential. The FXE administration also improved testosterone level and alpha-glucosidase activity. The sperm count also increased after treated with FXE, whereas sperm abnormality was reduced. Histopathological analysis showed that FXE successfully improved the seminiferous tubules morphology. According to these findings, fucoxanthin extract from Sargassum glaucescens can be used as an alternative for the treatment of testicular damage.

Vitellaria paradoxa Nut Triterpene-Rich Extract Ameliorates Symptoms of Inflammation on Post-Traumatic Osteoarthritis in Obese Rats.

PURPOSE: To investigate the ameliorative effects of Vitellaria paradoxa (VP) nut extract for an anterior cruciate ligament transection with medial meniscectomy (ACLT+MMx)-induced osteoarthritis (OA) in high-fat diet (HFD)-induced obese rats. METHODS: The rats were fed by HFD for 5 weeks before surgery-induced OA. Rats were treated orally with three different doses of VP nut extract (111.6, 223.2, and 446.4 mg/kg) for 8 weeks. RESULTS: The VP nut triterpene-rich extract decreased the level of triglycerides and increased high-density lipoprotein-cholesterol. The level of nitric oxide, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α decreased after treatment with VP nut triterpene-rich extract, especially in high-doses. The VP nut triterpene-rich extracts also alleviated swelling in the knee OA, weight-bearing difference, and suppressed cartilage degradation. CONCLUSION: The Vitellaria paradoxa nut triterpene-rich extract suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis with an obesity rat model. As such, Vitellaria paradoxa nut triterpene-rich extract can be used as an alternative for osteoarthritis treatment.

In vitro anti-inflammatory effects of curcumin on mast cell-mediated allergic responses via inhibiting FcεRI protein expression and protein kinase C delta translocation.

Allergy is a hypersensitivity reaction when exposed to certain environmental substances. It shows high relation between immunoglobulin E (IgE) binding to a specific receptor (FcεRI), pro-inflammatory cytokines, and mediators with allergic inflammation responses. Curcumin is a yellow pigment isolated from the turmeric. Curcumin possesses antioxidant and anti-inflammatory properties as well as exhibits significant chemopreventive activity. This study was aimed to investigate the in vitro assessment of the regulation of curcumin on allergic inflammatory responses on rat basophil leukemia (RBL)-2H3 and human pre-basophils (KU812) cell lines. Curcumin showed the activity against histamine and ß-hexosaminidase releases from both IgE-mediated and A23187-induced cells degranulation. The morphological observation also confirmed that curcumin inhibits cells degranulation. IgE-mediated allergic responses and significantly induced mast cells intracellular reactive oxygen species (ROS) production. Curcumin reduced ROS production from IgE-mediated or A23187-induced cells degranulation. Curcumin also successfully reduced FcεRI expressions and some pro-inflammatory cytokines, such as interleukin (IL)-4 and IL-13. Furthermore, curcumin inhibited protein kinase C (PKC)-δ translocation from cytosolic to particulate. These results suggested that curcumin can alleviate both the IgE-mediated and calcium ionosphere A23187-stimulated allergic responses through reducing the release of the allergic mediators.

Histological evidence of chitosan-encapsulated curcumin suppresses heart and kidney damages on streptozotocin-induced type-1 diabetes in mice model.

High blood glucose in diabetic patients often causes cardiovascular diseases (CVDs) that threats to human life. Curcumin (Cur) is known as an antioxidant agent, possesses anti-inflammatory activity, and prevents CVDs. However, the clinical application of curcumin was limited due to its low bioavailability. This study aimed to investigate the ameliorative effects of chitosan-encapsulated curcumin (CEC) on heart and kidney damages in streptozotocin-induced type-1 diabetes C57BL/6 mice model. The results showed that Cur- and CEC-treatments downregulated the blood sugar and total cholesterol level as well as enhanced insulin secretion. However, blood pressure, triglycerides content, and very low-density lipoprotein-cholesterol content were not changed. Histochemistry analysis revealed that both curcumin and chitosan-encapsulated curcumin ameliorated cell hypertrophy and nucleus enlargement in the left ventricular of heart and reduced fibrosis in the kidney, especially after the chitosan-encapsulated curcumin treatment. Our study suggested that chitosan can effectively enhance the protective effect of curcumin on the heart and kidney damages in type-1 diabetes mice model.

Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model.

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

A dietary polysaccharide from Eucheuma cottonii downregulates proinflammatory cytokines and ameliorates osteoarthritis-associated cartilage degradation in obese rats.

Osteoarthritis (OA) is a common form of arthritis, which is characterized by the degeneration of articular cartilage, leading to joint dysfunction. Oral drug therapy seems to ameliorate some signs and symptoms of OA, but may be accompanied by side effects and does not appear to be effective long-term. Seaweed has received much attention for pharmacological application due to its various biomedical properties, including the anti-inflammation, antitumor, and antioxidant effects. This study investigated the ameliorative effects of a dietary polysaccharide from Eucheuma cottonii extract (ECE) on an anterior cruciate ligament transection with partial medial meniscectomy surgery (ACLT+MMx) to induce OA in high-fat diet (HFD)-induced obese rats. Male Sprague-Dawley rats were fed an HFD for 12 weeks before ACLT+MMx surgery, after which they were administered a daily oral gavage of saline (Sham, OB Sham, and OBOA) and either low-dose ECE (100 mg per kg body weight), high-dose ECE (400 mg per kg body weight), or glucosamine sulfate as a positive control (OBOAGS; 200 mg per kg body weight) for 5 weeks. Treatment with ECE decreased the body weight, triglyceride and total cholesterol (TC) levels, and the TC/high-density lipoprotein (HDL)-C ratio in the obese rats. Additionally, ECE downregulated the expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and leptin, and suppressed nuclear factor-kappa B and extracellular-signal-regulated kinase-1/2 expression, resulting in a decrease in the levels of matrix metalloproteinase (MMP)-1 and MMP-13 and prostaglandin-E2 and attenuated cartilage degradation. These results demonstrate that the dietary polysaccharide from ECE can suppress OA development in obese rats, suggesting its potential efficacy as a promising candidate for OA treatment.

Dietary polysaccharide-rich extract from Eucheuma cottonii modulates the inflammatory response and suppresses colonic injury on dextran sulfate sodium-induced colitis in mice.

Inflammatory bowel disease (IBD) is a known medical burden in most developed countries and a significant cause of morbidity. The IBD label includes Crohn's disease (CD) and ulcerative colitis (UC). Pharmacological and surgical intervention are the two main management approaches for IBD. Some drugs have been developed for IBD therapy, but accessibility is limited due to high costs. Furthermore, these agents have demonstrated inactivity over long-term treatment courses. Therefore, an urgent need is present for new treatment options that are safe, able to sustain clinical remission, and improve mucosal gut healing. Seaweed has received much attention in the pharmacological field owing to its various biomedical properties, including the prolongation of blood clotting time, as well as antitumor, anti-inflammation, and antioxidant effects. This study therefore aimed to examine the effects of a dietary polysaccharide-rich extract obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium (DSS) for 7 days. DSS-induced mice were treated with either one of three different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment and blood samples were collected. The disease activity index (DAI) and inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-10) were measured. After treatment for 7 days, EC extract administration protected against weight loss and decreased the colon weight per length ratio. EC extract administration also decreased pro-inflammatory cytokine expression, increased IL-10 levels, and reduced colonic damage. Therefore, a dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel inflammation, thereby becoming a promising candidate for the treatment of colitis.

Amelioration effects of nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea on reproductive function of diabetic male rats.

PURPOSE: Nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea (PAC) and its amelioration effects on reproductive function in diabetic rats were investigated. MATERIALS AND METHODS: PAC encapsulated in silica-chitosan nanoparticles (Nano-PAC) was prepared by the biosilicification method. The diabetic condition in male Sprague Dawley rats was induced by high-fat diet and streptozotocin (STZ). Three different doses of Nano-PAC (4, 8, and 20 mg/kg) were administered for 6 weeks. Metformin and control of nanoparticles (Nano-con) were taken as positive and negative controls, respectively. RESULTS: The average particle size was ~79.46±1.63 nm, and encapsulation efficiency was ~73.35%±0.09%. Nano-PAC administration improved hyperglycemia and insulin resistance. In addition, Nano-PAC ameliorated the morphology of testicular seminiferous tubules, sperm morphology, motility, ROS production, and mitochondrial membrane potential. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) antioxidant, as well as testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were increased, whereas proinflammatory cytokines TNF-α, IL-6, and IFN-γ were decreased. CONCLUSION: In the present study, we successfully nanoencapsulated PAC and found that a very low dosage of Nano-PAC exhibited amelioration effects on the reproductive function of diabetic rats.

Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats.

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in females. Obesity and mechanical injuries caused by OA are attributed to joint loading, cartilage disintegration, and bone loss, as well as inflammation. Pharmacological and non-pharmacological treatments can be used for OA. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on rats with diet-induced obesity. OA was induced by an anterior cruciate ligament transection and a partial medial meniscectomy (ACLT + MMx). The male SD rats were fed with a high-fat diet (HFD) for 4 weeks to induce obesity before causing ACLT + MMx to induce OA. The OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with an HFD. We observed that the swelling in the knee joint was alleviated and the hind paw weight distribution was rectified after feeding them with fucoidan and that there was no significant effect on the weight gain and feed intake. Fucoidan administration indicated no significant variation on the high-density lipoprotein (HDL)-Cholesterol level, but it did indicate reduced plasma triglycerides and low-density lipoprotein (LDL)-Cholesterol levels. In addition, the weight-bearing tests showed an improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.