The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1β, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

The purpose of this study was to optimize conditions of solid-phase fermentation of lactic acid bacteria to enhance GABA contents in grains. Optimal solid-phase fermentation conditions that could enhance the GABA content after fermenting Oryza sativa (brown rice) were investigated by changing the Lactobacillus strain, fermentation temperature, fermentation time, and inoculated bacteria number. Avena sativa, Cicer arietinum, and red and brown Lens culinaris were then fermented using the optimal solid-phase fermentation conditions to measure changes in GABA content and antioxidant activity. As a result of the experiment, the optimal solid-phase fermentation conditions to enhance the GABA contents in grains were: fermentation time, 48 h; amounts of bacteria, inoculating 5% of 1 × 10⁷ CFU/mL of lactic acid bacteria; and fermentation temperature, 36 °C. When fermented under this condition, the GABA content increased from 4.64 mg/g to 6.93 mg/g (49.0%) compared to unfermented raw material. The results of the DPPH and ABTS radical scavenging activity assays confirmed that both the GABA content and radical scavenging activity were increased after fermentation. Such solid fermentation conditions developed in this study can be used to support the development of health functional food materials with enhanced GABA content and antioxidant activity.

Late-onset hypogonadism (LOH) is an age-associated condition characterized by a progressive decline in testosterone levels. It manifests as reduced libido, infertility, muscle loss, and cognitive impairment in middle-aged men. Although testosterone replacement therapy is effective, its associated side effects highlight the need for safer alternatives. Previously, we have demonstrated the efficacy of the fermented Morinda citrifolia extract (FME) in ameliorating LOH symptoms in vitro. The present study aimed to assess the in vivo efficacy of FME in mitigating LOH symptoms using an aged rat model. Thirty-three-week-old male Sprague-Dawley rats were administered either Testofen or FME daily for four weeks. Serum levels of total and free testosterone, sex hormone-binding globulin (SHBG), dihydrotestosterone, and metabolic hormones were measured. Testicular gene expression and protein expression related to steroidogenesis were also assessed. Muscle mass, physical performance (evaluated using treadmill test), and sperm quality were also assessed. FME treatment significantly increased serum testosterone levels, reduced SHBG and dihydrotestosterone concentrations, and enhanced the expression of testosterone biosynthesis-related proteins. FME downregulated degradation enzymes such as 5α-reductase and aromatase. FME also improved sperm production, progressive motility, muscle mass, and treadmill running capacity. Histological analyses confirmed tissue recovery in the testes and muscles. FME alleviated LOH-related symptoms in aged rats by modulating testosterone metabolism, enhancing reproductive and physical health, and maintaining a favorable safety profile. These findings validate the in vivo efficacy of FME and highlight its potential as a natural therapeutic candidate for managing LOH and related conditions.

Background/Objectives: Late-onset hypogonadism (LOH), characterized by declining testosterone levels with age, negatively affects the health of men, causing physical, psychological, and sexual dysfunction. Conventional testosterone replacement therapies have side effects, which has led to interest in natural alternatives. We investigated the effects of a standardized fermented Morinda citrifolia extract (FME) on oxidative stress-induced damage in TM3 Leydig and TM4 Sertoli cells. The cells were treated with H₂O₂ to simulate oxidative stress, followed by the FME treatment. Methods: Cytotoxicity assays, testosterone measurements, and gene and protein expression analyses were conducted to evaluate the restorative properties of FME. Results: The H₂O₂ treatment significantly decreased the cell viability, testosterone production, and the expression of proteins involved in testosterone synthesis and spermatogenesis, and the FME treatment improved testosterone production and restored the luteinizing hormone receptor, steroidogenic acute regulatory protein, CYP11A1, 3β-hydroxysteroid dehydrogenase, 17,20 desmolase, and 17β-hydroxysteroid dehydrogenase levels in the TM3 Leydig cells. It also reduced the expression of testosterone-degrading enzymes, aromatase and 5α-reductase. The FME treatment restored the levels of the androgen receptor and follicle-stimulating hormone receptor in the TM4 Sertoli cells. Conclusions: FME alleviates oxidative stress-induced damage in Leydig and Sertoli cells by promoting testosterone synthesis and spermatogenesis while regulating testosterone metabolism. These findings suggest that FME could be a promising candidate for the management of LOH symptoms.

Noni (Morinda citrifolia L.) juice is increasingly recognized for its potential health-promoting properties. In this research, the bioactive compounds and physiological effects of commercial noni juice products in Korea were assessed. Noni juice was found to contain high levels of total phenolics (6.39 ± 1.45 mg gallic acid equivalents (GAE)/g) and proanthocyanidins (8.64 ± 6.20 mg catechin equivalents (CE)/g). Furthermore, it exhibited potent antioxidant activities, with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activities of 44.03 ± 14.88% and 55.91 ± 2.62%, respectively, which exceeded those reported for common fruit juices such as apple, orange, and blueberry. Additionally, noni juice reduced lipid accumulation by 5.92% and reactive oxygen species (ROS) levels by 7.23% in 3T3-L1 adipocytes; improved fusion index to 81.44% and restored myotube diameter by 37.24% in dexamethasone-induced C2C12 cells; and suppressed LPS-induced nitric oxide (NO) production. These results suggested that noni juice has anti-inflammatory, anti-obesity, anti-muscle atrophy, and antioxidant properties, supporting its potential as a functional health beverage.

Although chemotherapy is a primary approach for cancer treatment, its efficacy is often compromised by the development of drug resistance and occurrence of serious side effects. To improve chemotherapy outcomes, this study aimed to evaluate the synergistic anticancer effects of fermented noni extract (FN) in combination with 5-fluorouracil (5-FU), doxorubicin (DOX), or vincristine (VIN) in A549, MCF-7, and SH-SY5Y cancer cell lines. Cells were treated with FN, anticancer drugs, or their combinations. Cell viability was assessed using XTT assays, and synergism was evaluated by calculating combination index (CI) values. Scratch wound and colony formation assays were conducted to assess cell migration and proliferation. Western blotting was used to analyze the expression of apoptosis-related proteins. Combination treatments significantly enhanced cytotoxicity (CI < 1), inhibited migration and colony formation, and induced intrinsic apoptosis. Expression ratios of BAX/BCL-2, cleaved caspase-9/caspase-9, and cleaved caspase-3/caspase-3 notably increased. These findings suggest that FN enhances the efficacy of chemotherapy drugs by promoting intrinsic apoptotic pathways and may serve as a potential natural adjuvant in cancer therapy.