Osteoporosis is characterized by reduction in bone mass and microarchitectural deterioration of the bone, which causes bone fragility and fracture susceptibility. Ishige sinicola, a brown alga, reportedly affects osteoblast differentiation. However, its protective effect on estrogen deficiency-induced bone loss has not been elucidated. This study aimed to investigate the effect of I. sinicola extract (ISE) on ovariectomy (OVX)-induced bone loss in vivo and osteoclastogenesis in vitro. Female Sprague-Dawley rats were randomly assigned to the sham-operated (SHAM) group and four OVX subgroups: SHAM, OVX, ISE20 (20 mg/kg), ISE200 (200 mg/kg), and estradiol (10 μg/kg). After 6 weeks of treatment, the bone mineral density (BMD), femur indices, and serum biomarker levels were measured. Furthermore, the effects of ISE on osteoclastogenesis and the expression of osteoclast-specific markers were measured. ISE administration improved the trabecular bone structure, bone biomechanical properties, BMD, and bone mineralization degree. In addition, the levels of serum bone turnover markers were decreased in the ISE group compared with those in the OVX group. Moreover, ISE inhibited osteoclast formation by downregulating NFATc1, TRAP, c-Src, c-Fos, and cathepsin K without any cytotoxic effects on RANKL-induced osteoclast formation. Therefore, we suggest that ISE has therapeutic potential in postmenopausal osteoporosis.

Microbial fermentation provides a valorization strategy, through biotransformation, to convert plant-derived raw materials into health-promoting agents. In this study, we have investigated the antioxidative activity of Abelmoschus manihot fermented with various Bacillaceae strains from specific environments and demonstrated the anti-inflammatory effects of Bacillus licheniformis CP6 fermented A. manihot extract (FAME) in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. Of 1500 bacteria isolated from various specific environments, 47 extracellular protease- and amylase-producing strains with qualified presumption safety status, belonging to the family Bacillaceae, were selected for A. manihot fermentation. Among them, strain CP6, a halophilic bacterium isolated from Tongyeong seawater in Korea and identified as B. licheniformis, showed the highest antioxidant activity. In particular, FAME exerted anti-inflammatory effects on LPS-stimulated Raw264.7 macrophages. Consequently, FAME had a potent inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages, without cytotoxicity. Moreover, FAME downregulated LPS-induced pro-inflammatory mediator and enzyme levels in LPS-induced Raw264.7 cells, including IL-1β, IL-6, TNF-α, iNOS, and COX-2, compared to levels when cells were incubated in A. manihot extract (IAME). Further detailed characterization indicated that FAME suppresses inflammation by blocking NF-κB via IKK phosphorylation inhibition and IκB-α degradation and by downregulating NO production, and inflammatory mediators also decreased NF-κB translocation. Furthermore, FAME inhibited LPS-stimulated activation of MAPKs, including ERK1/2, JNK, and p38, compared to that with either IAME. Therefore, we suggest that FAME could be used for inflammation-related disorders.

Osteoporosis is one of the most common bone diseases, occurring due to an imbalance between bone formation and bone resorption. The aim of this study was to investigate the effects of Ishige sinicola, a brown alga, on osteoblast differentiation through the activation of the bone morphogenetic protein 2 (BMP-2)/runt-related transcription factor 2 (Runx2) signalling pathway in MC3T3-E1 cells. A cell proliferation assay, alkaline phosphatase (ALP) activity assay, alizarin red staining, and expression analysis of osteoblastic genes were carried out to assess MC3T3-E1 cell proliferation and osteoblastic differentiation. We found that I. sinicola extract (ISE) increased cell proliferation in a dose-dependent manner. Ishige sinicola extract markedly promoted ALP activity and mineralization. Alizarin red S staining demonstrated that ISE treatment tended to increase extracellular matrix calcium accumulation. Moreover, ISE up-regulated the osteoprotegerin/receptor activator of nuclear factor κB ligand ratio. Ishige sinicola extract also increased the protein expression levels of type 1 collagen, ALP, osteocalcin, osterix, BMP-2, and Runx2. Therefore, ISE showed potential in stimulating osteoblastic bone formation, and it might be useful for the prevention and treatment of osteoporosis.

Background/Objectives: Fatigue results from prolonged physical exertion and is characterized by declining physical performance. This study assessed anti-fatigue potential of an allithiamine garlic complex (AGC) in a mouse model of forced swimming-induced fatigue. Methods: Male ICR mice were assigned to five groups (n = 8 per group)—sedentary control (normal control), forced swimming test control (FST-C), FST + AGC at 100 mg/kg (AGC100), FST + AGC at 500 mg/kg (AGC500), and FST + red ginseng at 500 mg/kg (positive control, PC). Fatigue was induced by forced swimming (15 min/day) for 1 week, after which the treatments were administered orally once daily for 7 days. On days 0 and 7, weight-loaded FSTs (5% of body weight) were conducted to measure immobility time, and mice were euthanized on day 7 for biochemical analysis (serum, liver, and gastrocnemius muscle). Results: On day 7, both AGC doses significantly reduced immobility time compared with the FST-C group, and immobility time in the AGC500 group did not differ significantly from that in the PC group. AGC significantly reduced serum lactate, free fatty acids, and ammonia levels, whereas decreases in lactate dehydrogenase, creatine kinase, and blood urea nitrogen were not statistically significant. AGC increased glycogen content in the liver and skeletal muscle. AGC upregulated the protein expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the skeletal muscle, suggesting an association with AMPK/SIRT1/PGC-1α signaling. AGC treatment reduced malondialdehyde levels and increased superoxide dismutase activity relative to the FST-C group. Conclusions: Collectively, these findings demonstrated that AGC enhances exercise endurance and alleviates fatigue by activating the AMPK/PGC-1α signaling pathway, indicating its potential as a functional ingredient for mitigating high-intensity exercise-induced fatigue.