Hyeon Du Jang

We investigated the effects of Rhododendron mucronulatum branch extract (RMB) on dexamethasone (DEX)-induced muscle atrophy in young adult male C57BL/6 mice. Mice received oral RMB (100, 200, or 400 mg/kg) for 4 weeks and intraperitoneal DEX (5 mg/kg) during the final 2 weeks. RMB significantly improved exercise duration and capacity at 200 and 400 mg/kg (400 mg/kg vs. DEX control: time to exhaustion, 29.5 vs. 21.3 min), and grip strength showed an increasing trend. Muscle fiber cross-sectional area and gastrocnemius weight were preserved at all doses. RMB increased the phospho-Akt/Akt ratio at 200 mg/kg, the phospho-mTOR/mTOR ratio at 400 mg/kg, and the phospho-FoxO3α/FoxO3α ratio at all doses. Atrogin-1 was suppressed at all doses and MuRF1 at 400 mg/kg, whereas MyoD and Myogenin were increased at 400 mg/kg and IGF-1 at 200 and 400 mg/kg. RMB also reduced intramuscular TNF-α and IL-6, restored antioxidant defense in muscle and serum, and increased Bcl-2. These findings suggest that RMB ameliorates DEX-induced muscle atrophy mainly by partially restoring Akt/mTOR signaling, promoting FoxO3α phosphorylation, and suppressing Atrogin-1 and MuRF1, with additional anti-inflammatory, antioxidant, and anti-apoptotic effects.

Sarcopenia, an age-related muscle atrophy disease, is a major health concern in aging societies and is closely associated with severe chronic diseases. Its primary pathogenesis involves oxidative stress-induced apoptosis in muscle cells and an imbalance in protein metabolism. This study evaluated the potential of Rhododendron mucronulatum branch extract (RMB) and its major flavonoids, taxifolin-3-O-arabinopyranoside (Tax-G) and taxifolin (Tax-A), as natural therapeutic agents for sarcopenia. Phytochemical analyses were performed using TLC, HPLC, LC-MS/MS, and NMR, and Tax-G and Tax-A were isolated from RMB. In vitro models of apoptosis and muscle atrophy were established in C2C12 cells using H₂O₂ and dexamethasone (DEX), respectively. Cell viability, myotube diameter, and protein expression related to apoptosis and muscle differentiation were assessed. All three substances reduced H₂O₂-induced apoptosis by increasing Bcl-2 and inhibiting cleaved caspase-3 and PARP. They also attenuated DEX-induced muscle atrophy by suppressing Atrogin-1, MuRF1, and FoxO3α while promoting MyoD, Myogenin, Akt, and mTOR. Although Tax-A showed the highest activity, Tax-G exhibited comparable effects with lower cytotoxicity. These findings demonstrate that RMB and its active compounds protect muscle cells by regulating apoptosis and muscle metabolism, suggesting their potential as safe and functional natural materials for the prevention of sarcopenia.

Background/Objectives: Honokiol (HK), a bioactive phenolic compound, exhibits significant anti-cancer properties. This study aimed to investigate the anti-cancer effects of HK in colorectal cancer (CRC) cells by focusing on its direct interaction with heat shock protein 27 (Hsp27) as a molecular target, and to elucidate the underlying mechanisms involved. Methods: HK was isolated via silica/ODS chromatography. Anchorage-independent growth of CRC cells was quantified using a soft agar assay with increasing HK concentrations. Apoptosis and cell cycle were analyzed by flow cytometry, and cell viability by MTS assay. Hsp27 binding to HK was validated by pull-down assay with HK-conjugated Sepharose 4B beads. Hsp27 knockdown was performed using lentiviral shRNA in CRC cells. Molecular docking of HK-Hsp27 interaction employed Schrödinger Suite 2016. Protein expressions, including chaperone and apoptotic proteins, were evaluated by Western blotting. Results: HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G₀/G₁ arrest. It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation. HK directly bound to the α-crystallin domain of Hsp27 at Asn102 and His103 residues, confirmed by computational molecular docking and site-directed mutagenesis. Hsp27 knockdown in CRC cells dramatically reduced anchorage-independent growth. HK markedly decreased Hsp27 protein levels while having less effect on other heat shock proteins in CRC cells. Conclusions: HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition, resulting in suppressed cell growth and increased apoptosis. This interaction between HK and Hsp27 may support a mechanistic foundation supporting the potential utility of HK as a natural therapeutic agent for CRC.

This study investigates the effects of pilot scale Alnus japonica hot water extract (AJHW) on muscle loss and muscle atrophy. Building on previous in vitro studies, in vivo experiments were conducted to evaluate muscle strength, mass, fiber size, protein synthesis, and antioxidant activity. The results showed that AJHW significantly restored muscle strength, increased muscle mass, enhanced the expression of muscle synthesis markers, such as Akt and mTOR, and apoptosis inhibition markers, such as Bcl-2, compared to the muscle atrophy control. Muscle degradation markers, such as Atrogin1, MuRF1, FoxO3α, and the apoptosis activation marker Bax, were decreased compared to the muscle atrophy control. Additionally, AJHW significantly boosted the activity of antioxidant factors like SOD, catalase, and Gpx, suggesting its protective role against oxidative stress-induced muscle damage. The enhanced effects were attributed to the high content of hirsutanonol and hirsutenone, which synergized with oregonin, compounds, identified through phytochemical analysis. While these findings support the potential of AJHW as a candidate for preventing muscle loss, further studies are needed to confirm its efficacy across diverse atrophy models and to elucidate its exact mechanisms.

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-β-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-β-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.