Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)/silent information regulator 1 (Sirt-1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) mitochondrial biogenesis pathway and the Akt/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration.

Vigeo is a mixture of fermented extracts of Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK) manufactured using the traditional Korean nuruk fermentation method. Although the bioactive effects of ESM, AJN, and AJK have already been reported, the pharmacological effects of Vigeo have not been proven. Therefore, in this study, we investigated whether Vigeo had inhivitory effects on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo and receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclastogenesis and the related mechanism in vitro. Vigeo administration conferred effective protection against bone loss induced by excessive inflammatory response and activity of osteoclasts in LPS-induced inflammatory osteoporosis mouse model. In addition, Vigeo significantly suppressed the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by RANKL and inhibited F-actin formation and bone resorbing activity without any cytotoxicity. Moreover, Vigeo significantly inhibited RANKL-induced phosphorylation of p38, ERK, JNK, IκB, and AKT and degradation of IkB. Additionally, Vigeo strongly inhibited the mRNA and protein expression of c-FOS and NFATc1 and subsequently attenuated the expression of osteoclast specific marker genes induced by RANKL. We demonstrated for the first time the anti-osteoporosis effect of Vigeo, suggesting that it could be a potential therapeutic candidate for the treatment of osteoclast-mediated inflammatory bone diseases.

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) significantly affects disease prognosis and patient survival. The impact of conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic DMARDs (b/tsDMARDs) on RA-ILD prognoses remains unclear. This study aimed to investigate the effects of csDMARDs and b/tsDMARDs on RA-ILD progression and prognosis based on pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and symptom changes. Methods: This multicenter, retrospective, observational study included patients with RA-ILD at 13 referral hospitals in South Korea. The participants were categorized into csDMARD-only and b/tsDMARD-exposed groups. RA-ILD prognosis was assessed over a 24-month follow-up period using serial PFTs (the forced vital capacity [FVC] and diffusing capacity of the lungs for carbon monoxide [DLCO]), HRCT findings, and clinical symptom changes. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare disease progression risk while adjusting for baseline lung function, RA disease activity, and glucocorticoid use. Results: Among 127 eligible patients, 22 (17.3%) were exposed to b/tsDMARDs, predominantly abatacept and tocilizumab. During a mean follow-up of 2.8 years, 65 (51.2%) patients experienced RA-ILD progression. A higher baseline Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR) (adjusted hazard ratio [aHR]: 1.344, 95% confidence interval [CI]: 1.136–1.590, p = 0.001) and initially prescribed prednisone dose (aHR: 1.078, 95% CI: 1.011–1.151, p = 0.023) were significant prognostic factors for ILD progression. No statistically significant difference in progression risk was observed between the csDMARD-only and b/tsDMARD-exposed groups (aHR: 0.937, p = 0.851). Conclusions: The RA-ILD prognosis was more strongly influenced by disease activity, rather than the type of DMARD used. These findings emphasize the importance of maintaining low RA disease activity to improve RA-ILD prognosis.

Swiprosin-1 (SWS1/EFhd2) is a calcium-binding adaptor protein involved in cytoskeletal regulation, but its physiological role in bone homeostasis remains largely undefined. To elucidate its function in osteoclast biology, we examined SWS1 expression and activity during osteoclastogenesis using primary murine bone marrow-derived macrophages, siRNA-mediated knockdown, and SWS1 knockout (KO) mice. SWS1 was predominantly localized to the nucleus in precursor cells and redistributed to the F-actin ring in mature osteoclasts. Receptor activator of nuclear factor-kappa B ligand stimulation significantly downregulated SWS1 mRNA expression. Loss of SWS1 enhanced osteoclast formation, F-actin ring integrity, and bone resorption, accompanied by elevated expression of osteoclastogenic markers. In vivo, male SWS1 KO mice exhibited deteriorated trabecular bone microarchitecture with increased osteoclast numbers. Mechanistically, SWS1 deficiency intensified αvβ3 integrin-associated cytoskeletal signaling and upregulated Akt, MAPK, NF-κB, and PLCγ2 pathways. These results indicate that SWS1 negatively regulates osteoclast differentiation and function by restraining cytoskeletal reorganization and downstream signaling. Collectively, our findings establish SWS1 as a novel modulator of osteoclast activity and a potential therapeutic target for osteolytic bone disorders.

Chung CH. Chonnam Med J. 2020 Sep;56(3):212-213. https://doi.org/10.4068/cmj.2020.56.3.212

Background/Objectives: Muscle atrophy, defined by diminished muscle mass and function, is a notable concern associated with aging, disease, and glucocorticoid treatment. Pueraria montana var. lobata extract (PMLE) demonstrates multiple bioactive properties, such as antioxidant, anti-inflammatory, and metabolic regulatory activities; however, its role in muscle atrophy has not been extensively investigated to date. This study examined how PMLE influences both muscle cell differentiation and dexamethasone (DEX)-induced muscle degeneration by focusing on the underlying molecular mechanisms. Methods: This study examined the effects of PMLE on myogenic differentiation and DEX-induced muscle atrophy. C2C12 myoblasts were treated with PMLE (10–100 ng/mL) and assessed for changes in the expression of myogenesis-related genes and activation of Akt/mTOR and AMPK/SIRT1/PGC-1α signaling cascades. In vivo, a DEX-induced muscle atrophy model was used to assess muscle mass, fiber morphology, and molecular changes. Results: PMLE PMLE promoted muscle cell development by increasing the expression of MyHC, MyoD, and myogenin while activating protein synthesis and mitochondrial biogenesis pathways. PMLE counteracted DEX-induced myotube atrophy, restoring myotube diameter and promoting cellular fusion in vitro. In vivo, PMLE mitigated muscle degradation in fast-twitch muscle groups and reversed DEX-induced suppression of key anabolic and mitochondrial pathways. Conclusions: These findings suggest that PMLE promotes myogenic differentiation and protects against muscle atrophy by regulating critical molecular pathways, indicating its promise as a treatment candidate for conditions involving muscle wasting. Further studies are required to assess its clinical application and long-term safety efficacy.