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Graphical abstract Highlights • Sesamin reduced TLR4 expression in LPS-stimulated microglial cells. • Sesamin alleviated LPS-induced production of proinflammatory mediators in BV2 microglial cells through the TLR4 pathway. • Sesamin protected against PC12 neuron cell death via inhibition of microglial activation. • Sesamin directly protected against PC12 neuron cell death from neurotoxic effects. Abstract Sesamin, one of the most abundant lignans in sesame seeds and oils, is well known for neuroprotective activity. However, its effects on toll-like-receptor 4 (TLR4), the key innate immune receptor implicated in microglia activation and neuroinflammation has not been reported. Our study demonstrated that sesamin significantly diminished LPS-stimulated TLR4 expression result in the reduction of nitric oxide (NO), prostaglandin E 2 (PGE 2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in BV2 microglia by suppressing JNK and NF-κB pathway. While conditioned medium from LPS-stimulated microglia-induced PC12 cell death, sesamin pre-treatment on microglia abrogated the cytotoxic effects of pro-inflammatory mediators. Our result also demonstrated the direct effect of sesamin in ameliorating PC12 cell death induced by activated microglial-conditioned medium. These results suggested that sesamin alleviated inflammation-induced neurodegeneration via inhibition of TLR4 expression and microglial activation resulting in diminishing the neurotoxicity effect. Sesamin might be a potential agent for neurodegenerative diseases prevention. [ABSTRACT FROM AUTHOR]

Objective To investigate the biological effects of the Mucuna pruriens ( M. pruriens ) seed extracts that lacked l -DOPA, which was formerly reported as the active ingredient, on erectile dysfunction (ED) both in vitro and in vivo . Methods Seed of M. pruriens plant that cultivated in Mae Taeng District, Chiang Mai Province, Thailand, was collected. Component of its seeds were extracted and isolated into 2 fractions using methanol, polar and nonpolar. Each fraction was investigated for phytochemicals using gas chromatography and mass spectroscopy and was screened for biological activity in vitro using three different cell lines. The most biological active fraction was used to treat both streptozotocin (STZ)-induced diabetes mellitus-erectile dysfunction (DM-ED) male Wistar rats and normal rats ( n = 6 per groups) to compare the effect on sexual behavior parameters, including number of intromission, mounting and ejaculation, with that of rats given Sildenafil by individually pairing with their female counterparts. Penile tissues and serums were collected to determine histological structure, related gene expression and biomolecules. Results The phytochemicals of the polar fraction were possibly catechol and its derivatives plus polyphenols, whereas the nonpolar fraction consisted of lipid derivatives. l -DOPA was not detected in either of the extracts. The polar fraction was able to up-regulate the expression of ED-related genes including eNOS and nNOS in vitro which subsequently promotes nitric oxide production and maintains intracellular cyclic guanosine monophosphate levels. When administrated to DM-ED rats, the polar extract significantly improved all sexual behavior parameters in DM-ED rats compared to untreated group (18.3 ± 1.8 to 10.8 ± 2.9 for intromission, 9.8 ± 2.2 to 5.7 ± 1.3 for mounting, and 1.8 ± 0.6 to 0.2 ± 0.4 for ejaculation). That effect might due to the ability of the extract to stimulate the expression of eNOS and nNOS which results in nitric oxide production and subsequently maintains cyclic guanosine monophosphate levels in penile tissue. Moreover, this extract may also prevent penile tissue deterioration due to diabetes. Conclusions The polar extract of M. pruriens seed can be used for ED therapy, especially in patients with metabolic diseases including diabetes. The action of the extract might be due to catechol and its derivatives and polyphenols. [ABSTRACT FROM AUTHOR]

Sesamin, a major lignan in sesame seeds and oils, is well known for its health promotion activity. However, its effects on bone cell functions are infrequently observed. In the study, the effects of sesamin on the differentiation of human mesenchymal stem cells (MSCs), osteoblasts, were examined. The differentiation of cells into osteoblasts suggested that sesamin (SE) in combination with osteogenic factors (OS) significantly increased calcium deposition. Although the osteoblastic differentiation markers including bone morphogenetic protein 2 ( BMP-2 ), type I collagen ( COL1A1 ) and alkaline phosphatase ( ALP ) of each cell donor showed different expressions both in gene type and time point, the increasing trends of COL1A1 and ALP were observed within the condition of OS + SE being compared with OS treatment. Increased ALP activity in OS + SE treatment could mediate the stimulatory effect of sesamin on osteoblast differentiation. Increased phosphorylation of p38 and ERK were related to increasing of ALP activity and mineralization in OS + SE treatment. Hence, it is suggested that sesamin enhanced osteoblast differentiation via activation of those MAPK signalling cascades. All results present that sesamin benefits differentiation of osteoblast progenitors towards functional bone forming cells, osteoblast. Thereby, sesamin would be a potential food supplement promoting bone health. [ABSTRACT FROM AUTHOR]

Twenty-five dogs were included in a randomized, double-blind trial to assess the efficacy of doxycycline (DOX) orally administered twice a day at 4 mg/kg/day (n = 12) for the treatment of osteoarthritis of the hip. Chondroitin sulfate (CS; 525 mg/day) was used as a positive control (n = 13). Dogs were re-examined monthly for 6 months after initiation of treatment. The assessment protocol included clinical score, radiographic findings and serum osteoarthritis biomarkers. Dogs treated with DOX showed statistically significant improvements (p < 0.05) in lameness, joint mobility, pain on palpation, weight-bearing and overall score at 2, 6, 4, 4 and 4 months, respectively, after treatment. Biomarker levels of CS-WF6 epitope and hyaluronan were significantly increased and decreased (p < 0.05) at 2 and 3 months after treatment compared to pretreatment. These results showed that DOX had a positive therapeutic effect in dogs with osteoarthritis. [ABSTRACT FROM AUTHOR]

Abstract: Serum chondroitin sulfate epitope (WF6) and hyaluronic acid (HA) levels were determined to be of clinical relevance to an anterior cruciate ligament (ACL) injury. This cross-sectional study recruited participants from two distinct groups. Group A was comprised of 74 healthy controls, and group B consisted of 33 ACL injury patients. Serum samples were taken and assayed by a competitive immunoassay with monoclonal antibody WF6. Serum HA was also determined by an ELISA-based assay using biotinylated HA-binding proteins. Both groups A and B shared similar values of age, body mass index, white blood cell count and percentage of polymorphonuclear cells. ESR levels were also shown to be within normal limits. The serum WF6 epitope levels of group B were significantly higher than those of group A, whereas serum HA levels were not different between the two groups. The serum WF6 epitope level is more sensitive to changes in articular cartilage due to a non-inflammatory instability condition than the serum HA level, and should prove to be one of the most promising assays for early post-traumatic arthritis detection. [Copyright &y& Elsevier]

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 ± 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 ± 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 ± 100.05 ng/ml) was significantly lower than that in the non-HD group (136 ± 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 ± 59.71 ng/ml) was lower than that in the non HD group (245.45 ± 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs. [ABSTRACT FROM AUTHOR]

Summary: Objective: Serum hyaluronan (HA) is ubiquitously distributed in connective tissues. Circulating HA is degraded by hepatic sinusoidal endothelial cell. The aim of the present study was to evaluate serum HA levels and to determine their importance in dengue fever (DF)/dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) patients. Methods: Serum HA levels were measured by an ELISA-based method in 16 patients with DF, 14 patients with DHF and 10 patients with DSS. The HA levels were compared with those in 48 acute hepatitis A patients; 8 healthy blood donors serve as controls. Results: In acute phase, mean serum HA levels significantly increased in patients with DSS (7316.3±10,359.0ng/ml) in comparison to patients with hepatitis A (93.8±50.4ng/ml; P <0.0001), and healthy controls (48.3±16.3ng/ml; P <0.0001). Serum levels of HA in patients with DSS rapidly decreased during the convalescent phase, but were still significantly higher than those in healthy controls (915.2±1294.8, and 48.3±16.3ng/ml; P <0.0005). Conclusions: The increased HA in dengue patients could be attributed to sinusoidal endothelial damage rendering the endothelium incapable of HA clearance. The elevation of HA production may involve the pathogenesis of dengue infection. Further studies are needed to determine whether the increase in the HA production or decrease in its clearance is responsible for the elevated serum HA. [Copyright &y& Elsevier]