Search Results (115)

Background/Objectives: Sarcopenia is characterized by progressive skeletal muscle loss and impaired myogenic differentiation and is closely associated with inflammation and metabolic dysfunction. Methods: This study investigated the protective effects of Momordica charantia extract against dexamethasone-induced sarcopenia and explored the underlying mechanisms using network pharmacology, C2C12 cell-based assays, Western blotting, and molecular docking. Network pharmacology analysis identified quercetin, ascorbic acid, and tocopherol as major active compounds associated with targets related to inflammation, extracellular remodeling, and metabolic dysfunction. Results: M. charantia extract (MCE) did not markedly reduce cell viability at concentrations up to 100 μg/mL and improved dexamethasone-induced morphological impairment of myotubes. The extract reduced MAFbx, MMP-2, and MMP-9 expression while restoring phosphorylated p38, MyoD, and myogenin expression, indicating suppression of atrophy- and remodeling-related responses, together with the recovery of myogenic signaling. Among the major identified compounds, all attenuated dexamethasone-induced myotube atrophy and quercetin showed the most pronounced morphological recovery. Molecular docking analysis targeting p38α showed the highest binding affinity for α-tocopherol, followed by quercetin and ascorbic acid, supporting potential interactions between the major compounds and p38 MAPK-related signaling. Conclusions: Collectively, these findings suggest that M. charantia attenuates sarcopenic changes by promoting myogenic differentiation and modulating the p38 MAPK-associated pathways. Full article

The purpose of this study was to evaluate the effects of multi-strain lactic acid bacteria (LAB) fermentation on the functional and antidiabetic properties of pumpkin (Cucurbita moschata) puree using integrated physicochemical, biochemical, and cellular analyses. Fermentation induced significant (p < 0.05) physiochemical changes, including a decrease in pH from 6.2 to 6.5 to 3.5–3.6, increased titratable acidity, and higher viable cell counts, indicating active microbial fermentation. Levels of reducing and soluble sugars (glucose, fructose, sucrose, and maltose) decreased significantly due to microbial utilization during fermentation. Fermented pumpkin puree exhibited markedly enhanced antioxidant activity, with DPPH radical scavenging activity increasing from 45% in the control to 83.2%, while ABTS radical scavenging activity increased from 33% to 42%. In vitro enzyme inhibition assays demonstrated enhanced antidiabetic potential, with α-amylase inhibition increasing from 7% to 60% and α-glucosidase inhibition from 10% to 70%. Moreover, glucose uptake in insulin-resistant L6 myotubes was significantly enhanced, indicating improved cellular glucose utilization. HPLC analysis revealed significant enrichment of phenolic compounds, particularly trans-ferulic acid (3894 µg/g), gallic acid (1996 µg/g), and caffeic acid (1894 µg/g), suggesting microbial-mediated release and biotransformation of bound phenolics during fermentation. Correlation analysis showed strong positive relationships among phenolic content, antioxidant activity, and enzyme inhibition. Among the tested LAB strains, Lactobacillus plantarum and Lactobacillus paracasei competitively exhibited the highest functional and anti-diabetic properties. Overall, LAB fermentation effectively enhanced the functional and antidiabetic properties of pumpkin puree. Full article

The skeletal muscle (SkM) secretome has been widely studied since the establishment of its endocrine function. Extracellular vesicles (EVs) are the most recently identified elements of the SkM secretome. These nano-sized lipid-bound vesicles carry molecular cargo and function as a means of intercellular communication. The effect of exercise on SkM EV micro-RNA cargo (miRNAs) remains a challenge to elucidate. Electrical pulse stimulation (EPS) was applied to C2C12 myotubes at high (30 Hz) and low (2 Hz) frequencies. EVs released during 10 h of stimulation were isolated and characterized and used to treat myoblasts. Their miRNA cargo was sequenced. EVs were used to treat myoblasts (2.19 × 10⁸ EVs per mL) to determine the effects on myoblast migration and differentiation. Sequencing revealed over 300 known miRNAs packaged into myotube EVs. Many were differentially expressed after EPS, either positively or negatively. Muscle-important miRNAs were present (miR-206 was 4.8-fold more prevalent than any other miRNA). EV treatments improved myoblast migration and differentiation without a frequency-specific influence. Gene Ontology analysis based on differentially expressed miRNAs between control and EPS-EVs indicates an effect of EPS frequency on muscle EV signaling. Full article

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K⁺) and calcium (Ca²⁺) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K⁺ currents and voltage-dependent Ca²⁺ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K⁺ current profiles: SK4+/EAG−/Kir−, SK4−/EAG+/Kir−, and SK4−/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from −20 mV to −70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca²⁺ conductance observed. Their activation threshold (~−30 mV) and half-activation voltage (V/2 ≈ −12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1). Full article

Following surgical interventions or acquired trauma, fibrosis often inhibits muscle and skin regeneration. Nintedanib, an antifibrotic drug for lung fibrosis, may help prevent orofacial fibrosis. This study evaluates Nintedanib’s potential for inhibiting myofibroblast differentiation and affecting the fusion of orofacial myoblasts into myotubes. Rat gingival fibroblasts and satellite cells (SCs) were isolated and cultured with TGF-β1 to induce myofibroblast differentiation and prevent myotube formation. Adding 1 and 10 ng/mL TGF-β1 significantly increased the percentage of myofibroblasts. Although Nintedanib did not affect the percentage of myofibroblasts, it strongly decreased the total number of fibroblasts and myofibroblasts. Additionally, Nintedanib at a concentration of 2 μM markedly reduced the expression of Ki-67 in fibroblasts and myofibroblasts. In the SC cultures, 0.2 ng/mL TGF-β1 reduced the fusion index of SCs. Treatment with 2 μM Nintedanib significantly increased the fusion index of SCs. Furthermore, MyoD and MyoG gene expression in SCs was also significantly enhanced by Nintedanib at a concentration of 2 μM. Nintedanib promotes myotube formation while inhibiting (myo)fibroblast proliferation. This dual action stresses its potential as an anti-fibrotic therapy after orofacial surgery or traumatic injury affecting muscle tissue. Full article

Oxidative stress is a primary driver of diabetic nephropathy (DN), highlighting the urgent need for potent natural antioxidants. This study explored the reno-protective potential and associated mechanisms of Rhinacanthus nasutus aqueous extract (AE). Phytochemical profiling via Q Exactive HF Orbitrap LC–MS/MS and serum pharmacochemistry analysis identified 38 constituents, among which 25 bioavailable constituents (e.g., caffeic acid and naringenin) might be the key bioactive ones. In the L6 myotubes in vitro assays, AE (75 μg/mL) was observed to upregulate the PI3K/AKT and GLUT4 signaling cytokines, coinciding with enhanced glucose uptake, as confirmed by Western blot with insulin as a positive control. Furthermore, in STZ-induced DN rats, AE could reduce MDA levels (0.58 vs. 1.44 nmol/mgprot) and restore T-SOD, CAT, and GSH-Px levels (170.57, 51.93, 63.68 vs. 114.93, 40.84, 50.99 mgprot). The protective effects were accompanied by the modulation of PI3K/AKT/mTOR signaling axis. These findings suggest that AE exerts dual efficacy involving glucose uptake regulation and oxidative stress inhibition. Consequently, Rhinacanthus nasutus represents a promising natural antioxidant resource with potential for the management of DN. Full article

The interaction between the gut microbiota and human health has gained increasing recognition, accelerating advances in microbiome research. While early studies have emphasized probiotics, concerns regarding antibiotic resistance and adverse effects, such as sepsis, have shifted research interest towards heat-treated microbial cells or postbiotics. This study investigated the therapeutic potential of heat-killed postbiotic Enterococcus faecalis EF-2001—one of the most widely used postbiotics worldwide—for the prevention and treatment of muscle atrophy. In vitro, mouse C2C12 myotubes were pretreated with heat-killed postbiotic EF-2001 (50–500 μg/mL) for 48 h and then treated with dexamethasone (100 μM) to induce muscle atrophy. In vivo, male Sprague Dawley rats were treated with low-dose (3 mg/kg) and high-dose (30 mg/kg) EF-2001 for efficacy studies. Heat-killed postbiotic EF-2001 attenuated cellular and DNA damage in dexamethasone-induced C2C12 myotubes. Specifically, heat-killed postbiotic EF-2001 increased AKT phosphorylation while suppressing Atrogin-1 expression, thereby alleviating muscle atrophy. In a Sprague Dawley rat model, heat-killed postbiotic EF-2001 significantly reduced dexamethasone-induced muscle loss by regulating muscle atrophy-associated signaling pathways, including Atrogin-1 expression. Collectively, these findings demonstrate that heat-killed EF-2001 alleviates dexamethasone-induced muscle atrophy and support its potential as a postbiotic. This study provides a solid foundation for future human clinical studies by establishing preclinical evidence for the biological activity of heat-killed EF-2001. Full article

Type 2 diabetes mellitus (T2DM) can be traditionally treated by edible and medicinal species rich in flavonoids and triterpenoids known for their metabolic benefits. Cucumis prophetarum L. has shown antioxidant and antidiabetic properties in decoction extracts. Since solvent polarity strongly influences the extraction of secondary metabolites, this study investigated the hydroalcoholic extracts of C. prophetarum L. to explore their chemical composition and insulin-sensitizing potential. Hydroalcoholic extracts from the leaf, stem, and root of C. prophetarum L. were analyzed by UV-Vis spectroscopy, ATR-FTIR, and UHPLC-ESI-QqTOF–MS/MS to profile their secondary metabolites. The insulin-sensitizing potential of each extract was assessed using an in vitro model of palmitic-acid-induced insulin resistance in L6 skeletal muscle cells, followed by Western blot analysis of key insulin-signaling proteins. Flavonoid glycosides such as apigenin-C,O-dihexoside, apigenin-malonylhexoside, and luteolin-C,O-dihexoside were abundant in leaf and stem extracts, while cucurbitacins predominated in the root. MTT assay confirmed that hydroalcoholic stem and root extracts of C. prophetarum L. were non-cytotoxic to L6 myotubes, whereas the leaf extract reduced viability only at higher concentrations. Oil Red O staining revealed a pronounced decrease in lipid accumulation following stem and root extract treatment. Consistently, the stem extract enhanced insulin signaling through the activation of the IRS-1/PI3K/Akt pathway, while the root extract primarily modulated the AMPK–mTOR pathway. Importantly, both extracts promoted GLUT4 translocation to the plasma membrane, highlighting their complementary mechanisms in restoring insulin sensitivity. Hydroalcoholic extracts of C. prophetarum L. alleviate insulin resistance through multiple molecular mechanisms, with bioactivity and composition differing markedly from previously reported in the decoctions, which highlight a promising source of insulin-sensitizing phytochemicals and underscore the importance of solvent selection in maximizing therapeutic potential. Full article

Capsaicin, a naturally occurring polyphenol, is known to affect energy expenditure and muscle fatigue and modulate contractions in skeletal muscle. The L-type Ca²⁺ channels are known to be an important ion channel involved in the various muscle functions and the effect of capsaicin on the skeletal L-type Ca²⁺ channels is currently unknown. In this study, the effects of capsaicin and capsaicin analogs on depolarization-induced Ca²⁺ effluxes through L-type Ca²⁺ channels in transverse tubule membranes from rabbit skeletal muscle and L-type Ca²⁺ currents recorded using the whole-cell patch clamp technique in rat myotubes were examined. Capsaicin, in the concentration range of 3–100 µM, inhibited depolarization-induced Ca²⁺ effluxes. The effect of capsaicin was not reversed by TRPV1 antagonist SB-366791 (10 µM). While vanilloids (30 µM) including vanillin, vanillyl alcohol, and vanillylamine were ineffective, other capsaicinoids (30 µM) including dihydrocapsaicin, nonivamide, and nordihydrocapsaicin significantly inhibited Ca²⁺ effluxes, suggesting that hydrocarbon chains are required for inhibition. In rat myotubes, capsaicin inhibited L-type Ca²⁺ currents with an IC₅₀ value of 27.2 μM in the presence of SB-366791. Furthermore, in docking studies and molecular dynamic simulations, capsaicinoids with an aliphatic tail showed stronger binding and stable bent conformations in CaV1.1, forming hydrogen bonds with Ser1011 and Thr935 and hydrophobic/π–alkyl contacts with Phe1008, Ile1052, Met1366, and Ala1369, resembling the binding mode of amlodipine. In conclusion, the results indicate that the function of L-type Ca²⁺ channels in mammalian skeletal muscle was inhibited by capsaicin and capsaicin analogs in a TRPV1-independent manner. Full article

Probiotics have been studied for their potential to treat chronic diseases. This study examined the use of Lacticaseibacillus rhamnosus BST.L-601 as an anti-diabetic symbiotic with sweet potato for fermentation. The medium supplemented with sweet potato showed increased productivity and enhanced storability. The anti-diabetic effect of fermented BST.L-601 was evaluated using the C2C12 myotube and a type 2 diabetes mellitus (T2DM)-induced db/db (Lepr^db/Lepr^db) mouse model. Treatment with heat-killed BST.L-601 increased glucose uptake by 125% and α-glucosidase inhibition in a dose-dependent manner without cytotoxicity for myotubes. 8 weeks of oral administration of BST.L-601 led to anti-diabetic activities in various biomarkers in the mouse model, including lowered fasting blood glucose by 88% and elevated mRNA expression of glucose metabolism-related factors IRS-1 (510%) and GLUT4 (181%) from skeletal muscle. Moreover, the improvement of induced T2DM in mice was supported by blood serum analysis. Immunohistochemistry showed increased insulin and decreased glucagon secreted from β and α cells in the pancreas islet. Microbiota analysis demonstrated elevated microbiome diversity in mice treated with BST.L-601. Furthermore, the safety and probiotic properties of the strain were confirmed. These results suggest that BST.L-601 fermented with sweet potato could be a functional symbiotic used to improve diabetes, particularly T2DM. Full article

Ten previously undescribed pyrrolidine alkaloids, namely penicipyrrolidines O–X (1–10), were isolated from the mangrove-derived fungus Penicillium sp. DM27, along with five known compounds (11–15). Their structures were determined by comprehensive analysis of HRESIMS and NMR spectroscopic data, and the absolute configurations were established based on biosynthetic considerations and TDDFT-ECD calculations. All isolates were evaluated for their glucose uptake capacity. Notably, penicipyrrolidine P (2) significantly enhanced cellular glucose uptake in L6 myotubes by 3.83-fold, demonstrating activity comparable to that of metformin, whereas penicipyrrolidines Q and R (3 and 4) showed relatively weaker effects. Full article

Background: Skeletal muscle aging is characterized by impaired myogenic differentiation, disrupted circadian rhythms, elevated oxidative stress, and mitochondrial dysfunction. Rutin, a natural flavonoid with antioxidant properties, has been suggested to mitigate aging processes; however, its effects on circadian regulation and muscle homeostasis remain unclear. Methods: In vitro, differentiated C2C12 myotubes were treated with D-galactose (D-gal, 20 g/L) with or without rutin (20 μM). In vivo, C57BL/6 mice were supplemented with rutin (100 mg/kg b.w.) via oral gavage in a D-gal-induced aging mouse model (150 mg/kg b.w., i.p.). Results: D-gal induced cellular senescence, impaired myogenic differentiation, disrupted circadian oscillations, increased oxidative stress, and compromised mitochondrial function. Rutin treatment restored myotube formation, enhanced circadian rhythmicity of differentiation-related genes, and corrected the antiphase patterns of Per2 and Rorc. It also reduced reactive oxygen species and malondialdehyde levels; increased superoxide dismutase, catalase, and glutathione peroxidase activity; improved ATP production and membrane potential; and decreased mitochondrial oxidative aging, as confirmed by pMitoTimer imaging. Furthermore, rutin reinstated the rhythmic expression of oxidative phosphorylation proteins and Pgc1α. In vivo, rutin supplementation enhanced muscle performance (prolonged hanging time) and oxidative capacity, particularly at night (ZT14–ZT16), without altering muscle fiber-type distribution, and normalized circadian rhythmicity of core clock genes. Conclusions: Rutin attenuates D-gal-induced cellular senescence by modulating circadian rhythms, reducing oxidative stress, and improving mitochondrial function. Importantly, its in vivo effects on muscle performance and circadian regulation suggest that rutin is a promising therapeutic strategy to counteract skeletal muscle aging and sarcopenia. Full article

Disuse-induced muscle atrophy (DMA), commonly resulting from immobilization, is driven by chronic inflammation and oxidative stress, which disrupts the balance between protein synthesis and degradation. Quinic acid (QA), a natural compound with known antioxidant and anti-inflammatory properties, was investigated for its potential to counteract muscle atrophy. Using a DMA-induced immobilization model in male C57BL/6N (8 weeks) mice, we found that oral QA administration significantly restored the weight and cross-sectional area of atrophic muscles and improved muscle function, as measured by grip strength and treadmill performance. QA also reduced the expression of pro-inflammatory cytokines (Tnf, Il6, and Myostatin) and E3 ubiquitin ligases (Trim63 and Fbxo32), while increasing antioxidant enzyme levels and serum IL-15 in DMA. In tumor necrosis factor-α-stimulated L6 myotubes, QA reversed inflammation- and oxidative stress-induced gene changes, suppressed NF-ĸB activation, and downregulated protein degradation pathways mediated by FoxO3α. Furthermore, QA restored the expression of myogenesis-related genes and reactivated PI3K/Akt and mTOR/p70S6K/4EBP1 signaling pathways, enhancing protein synthesis. Collectively, our findings demonstrate that QA mitigates immobilization-induced muscle atrophy by modulating inflammation, oxidative stress, and key anabolic and catabolic signaling pathways. These results suggest that QA is a promising functional compound for preserving skeletal muscle health under conditions of disuse. Full article

Background: Skeletal muscle is essential not only for structural integrity but also metabolic homeostasis. Muscle atrophy, the loss of muscle mass and function, is closely linked to chronic and metabolic disorders and is driven by chronic inflammation, oxidative stress, impaired myogenesis, and disrupted protein homeostasis. The present study aimed to evaluate the protective effects and underlying mechanisms of Rosa canina extract (RCE), a polyphenol-rich plant known for its antioxidant and anti-inflammatory properties, in vitro and in vivo models of muscle atrophy. Methods: We investigated the effects of RCE in TNF-α-treated L6 myotubes and a mouse model (eight-week-old male C57BL/6N) of immobilization-induced muscle atrophy. Markers of inflammation, oxidative stress, myogenesis, protein turnover, and anabolic signaling were analyzed via RT-PCR, Western blotting and ELISA. Muscle mass, performance, micro-CT imaging, and histological cross-sectional area were assessed in vivo. Results: RCE suppressed pro-inflammatory cytokines, restored antioxidant enzyme expression, and preserved myogenic markers. It inhibited muscle proteolysis by downregulating the genes involved in protein degradation and promoted protein synthesis by via activation of the PI3K/Akt/mTOR pathway. In mice, RCE mitigated muscle mass loss, preserved fiber cross-sectional area, improved strength and endurance, and restored muscle volume. Conclusions: RCE attenuated muscle atrophy by targeting inflammation, oxidative stress, proteolysis, and impaired anabolism. These findings highlight RCE as a promising natural therapeutic for preserving muscle health and metabolic homeostasis. Full article

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. Full article