TANG Zeling,CHEN Liping,MA Mengling,et al.Verbascoside inhibits inflammatory stress response in skeletal muscles through promoting mitochondrial function[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(9):68-74.
TANG Zeling,CHEN Liping,MA Mengling,et al.Verbascoside inhibits inflammatory stress response in skeletal muscles through promoting mitochondrial function[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(9):68-74. DOI: 10.16305/j.1007-1334.2025.z20241231001.
Verbascoside inhibits inflammatory stress response in skeletal muscles through promoting mitochondrial function
To explore whether verbascoside (VB) alleviates lipopolysaccharide (LPS)-induced inflammatory stress in skeletal muscle by enhancing mitochondrial function, and explore its mechanism of protecting skeletal muscles.
Methods
2
①C57BL/6J mice were randomly divided into normal, model, traditional Chinese medicine (TCM) groups. The normal group was intraperitoneally injected with 0.9% sodium chloride solution for 7 consecutive days, once a day. The model group was intraperitoneally injected with 0.9% sodium chloride solution for 6 consecutive days, and on the 7th day, LPS solution 5 mg/kg was intraperitoneally injected, once a day. In the TCM group, 150 mg/kg VB solution was intraperitoneally injected for 6 consecutive days, and on the 7th day, 5 mg/kg LPS solution was intraperitoneally injected, once a day. Grip strength and the ratio of wet weight to body weight of the gastrocnemius muscle (GW/BW ratio) were measured. ②C2C12 mouse myoblast cells were divided into normal, model, as well as low-, medium- and high-dose TCM groups. The normal group was cultured routinely; The model and TCM groups were cultured in medium supplemented with LPS (200 μg/L); VB was added to the TCM groups at final concentrations of 0.1 μmol/L, 1 μmol/L and 10 μmol/L, respectively. Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation; Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-6 levels; Western blot was used to analyze Desmin and mitochondrial fusion protein 2 (MFN2) expressions; Immunofluorescence staining was used to detect Desmin, NF-κB, MFN2 expressions.
Results
2
①Compared with the normal group, mice in the model group had significantly lower grip strength and GW/BW ratio (
P
<
0.01); After VB intervention, the maximum grip strength and GW/BW ratio of mice increased compared with the model group (
P
<
0.01,
P
<
0.05). ②In C2C12 cells, compared with the normal group, the model group showed decreased proliferation at 6 h, 12 h, 24 h (
P
<
0.05,
P
<
0.01) , increased IL-6 level (
P
<
0.01). After 24 h, mitochondrial MFN2 and intracellular Desmin expression levels decreased (
P
<
0.05), intranuclear NF-κB level increased (
P
<
0.01). Compared with the model group, 1 μmol/L VB intervention increased cell proliferation at 6 h, 12 h, 24 h (
P
<
0.05,
P
<
0.01,
P
<
0.01), decreased IL-6 level at 12 h, 24 h (
P
<
0.01); After intervention for 24 h, mitochondrial MFN2 and intracellular Desmin expression levels increased (
P
<
0.05), intranuclear NF-κB level decreased (
P
<
0.01).
Conclusion
2
VB improves mitochondrial function, reduces NF-κB expression, inhibits excessive synthesis of inflammatory factors, thereby slowing down skeletal muscle atrophy.
关键词
Keywords
references
ZHANG H , WANG J , XI J , et al . Functional fitness and risk factors of older patients with diabetes combined with sarcopenia and/or frailty: a cross-sectional study [J]. Nurs Open , 2024 , 11 ( 1 ): e2042 .
PONGKITWITOON B , PUTALUN W , TRIWITAYAKORN K , et al . Anti-inflammatory activity of verbascoside- and isoverbascoside-rich Lamiales medicinal plants [J]. Heliyon , 2024 , 10 ( 1 ): e23644 .
CHEN L K , WOO J , ASSANTACHAI P , et al . Asian working group for Sarcopenia: 2019 consensus update on Sarcopenia diagnosis and treatment [J]. J Am Med Dir Assoc , 2020 , 21 ( 3 ): 300 - 307 .
PALLA A R , RAVICHANDRAN M , WANG Y X , et al . Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength [J]. Science , 2021 , 371 ( 6528 ): eabc8059 .
YEO D , KANG C , JI L L . Aging alters acetylation status in skeletal and cardiac muscles [J]. Geroscience , 2020 , 42 ( 3 ): 963 - 976 .
QIAN Y , CHEN C , MA L , et al . CD38 Deficiency Promotes inflammatory response through activating Sirt1/NF‑κB-mediated inhibition of TLR2 expression in macrophages [J]. Mediators Inflamm , 2018 , 2018 : 8736949 .
AIMAITI M , WUMAIER A , AISA Y , et al . Acteoside exerts neuroprotection effects in the model of Parkinson's disease via inducing autophagy: network pharmacology and experimental study [J]. Eur J Pharmacol , 2021 , 903 : 174136 .
WILEY C D , CAMPISI J . The metabolic roots of senescence: mechanisms and opportunities for intervention [J]. Nat Metab , 2021 , 3 ( 10 ): 1290 - 1301 .
RASHID M A , TANG J J , YOO K H , et al . The selective cyclooxygenase-2 inhibitor NS398 ameliorates cisplatin-induced impairments in mitochondrial and cognitive function [J]. Front Mol Neurosci , 2023 , 16 : 1295991 .
MATSUKAWA S , KAI S , SEO H , et al . Activation of the β‑adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production [J]. PLoS One , 2021 , 16 ( 5 ): e0251921 .
HAMOUDI D , BOUREDJI Z , MARCADET L , et al . Muscle weakness and selective muscle atrophy in osteoprotegerin-deficient mice [J]. Hum Mol Genet , 2020 , 29 ( 3 ): 483 - 494 .
SUKHAREVA K S , SMOLINA N A , CHURKINA A I , et al . Desmin mutations impact the autophagy flux in C2C12 cell in mutation-specific manner [J]. Cell Tissue Res , 2023 , 393 ( 2 ): 357 - 375 .
SCHREPFER E , SCORRANO L . Mitofusins, from mitochondria to metabolism [J]. Mol Cell , 2016 , 61 ( 5 ): 683 - 694 .
NISR R B , SHAH D S , GANLEY I G , et al . Proinflammatory NF-κB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading [J]. Cell Mol Life Sci , 2019 , 76 ( 24 ): 4887 - 4904 .
ABAD-JIMENEZ Z , VEZZA T , LOPEZ-DOMENECH S , et al . Impact of Roux-en-Y Gastric Bypass on mitochondrial biogenesis and dynamics in leukocytes of obese women [J]. Antioxidants (Basel) , 2022 , 11 ( 7 ): 1302 .
LI J , WANG Y , WU T , et al . Baicalein suppresses high glucose-induced inflammation and apoptosis in trophoblasts by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway [J]. Placenta , 2022 , 121 : 126 - 136 .
LIU X , SUN J , YUAN P , et al . Mfn2 inhibits proliferation and cell-cycle in Hela cells via Ras-NF‑κB signal pathway [J]. Cancer Cell Int , 2019 , 19 : 197 .