Qigu capsule (芪骨胶囊) alleviates dexamethasone-induced muscle dysfunction through mitochondrial biogenesis

doi:10.19852/j.cnki.jtcm.2025.04.004

Abstract

Abstract:

OBJECTIVE: To explore the potential molecular mechanism of Qigu capsule (芪骨胶囊，QGC) improve the functional performance of skeletal muscle.

METHODS: The primary components of QGC were analyzed using high-performance liquid chromatography (HPLC). Muscle dysfunction was established in male C57BL/6 mice treated with dexamethasone (1 mg/kg body weight, i.p., six weeks). Rotarod test, mitochondrial ultrastructure, respiratory chain complex V activity, succinate dehydrogenase (SDH) activity, adenosine triphosphate (ATP) content, and reactive oxygen species (ROS) levels were assessed. The mitochondrial biogenesis-related protein expressions were analyzed using Western blot or polymerase chain reaction (PCR).

RESULTS: QGC treatment enhanced Rotarod test performance. Additionally, QGC significantly alleviated dexamethasone-induced mitochondrial damage, reduced mitochondrial swelling, increased respiratory chain complex enzyme activity, SDH activity, ATP content, and decreased ROS levels. PCR and western blot results revealed that QGC enhanced mitochondrial biogenesis via adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC-1α) signaling pathway.

CONCLUSIONS: QGC ameliorates dexamethasone-induced skeletal muscle dysfunction by activating AMPK/ PGC-1α, which might be developed as a therapeutic agent for treating age-related muscle weakness.

Key words: sarcopenia, muscle weakness, AMP-activated protein kinases, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, organelle biogenesis, Qigu capsule

SHI Jinyu, GE Haiya, YANG Zongrui, ZHAN Hongsheng. Qigu capsule (芪骨胶囊) alleviates dexamethasone-induced muscle dysfunction through mitochondrial biogenesis[J]. Journal of Traditional Chinese Medicine, 2025, 45(4): 739-746.

Figures/Tables 4

Figure 1 HPLC chromatograms A: HPLC chromatogram of Qigu capsule; B: HPLC chromatogram of standard samples; a: echinacoside; b: naringin; c: resveratrol; d: icariin; QGC: Qigu capsule; HPLC: high-performance liquid chromatograph.

Figure 2 Mitochondrial ultrastructure and number of gastrocnemius in each group A: TEM images of NC group samples; B: TEM images of DEX group samples; C: TEM images of QGC group samples; D: the number of mitochondria in each group. The red arrows represent normal mitochondria, the yellow arrows represent swollen mitochondria, and the green arrows represent vacuolated mitochondria. NC group: without any treatment; DEX group: treated with dexamethasone sodium phosphate 1 mg/kg body weight/d for six weeks; QGC group: treated with dexamethasone sodium phosphate 1 mg/kg body weight/d plus Qigu capsule for six weeks. NC: normal control; DEX: dexamethasone; QGC: Qigu capsule; TEM: transmission electron microscopy. All data are presented as the mean ± standard deviation (n = 12). Compared with NC group, aP < 0.01; compared with DEX group, bP < 0.01.

Table 1 Comparison of complex V activity, SDH activity, ATP content and ROS levels

Group	n	Complex V activity (nmol/min/g)	SDH activity (nmol/min/g)	ATP content (μmol/g)	ROS levels
NC	12	105.2±6.5	422.2±17.3	27.1±2.2	218.1±9.2
DEX	12	67.8±4.4^a	294.6±16.8^a	15.9±0.6^a	310.9±7.6^a
QGC	12	86.2±5.5^b	381.7±21.9^b	20.1±0.9^b	250.5±4.7^b

Figure 3 Effect of QGC on mitochondrial biogenesis A: copy number of mtDNA; B: mRNA expression levels of PGC1-α; C: mRNA expression levels of NRF1, D: mRNA expression levels of TFAM; E: AMPK/PGC-1α signaling pathway-related protein expressions in each group were detected using western blot; F: Western blot analysis of the protein expression of p-AMPK in each group; G: Western blot analysis of the protein expression of PGC-1α in each group; H: western blot analysis of the protein expression of NRF1 in each group; I: Western blot analysis of the protein expression of TFAM in each group. NC group: without any treatment; DEX group: treated with dexamethasone sodium phosphate 1 mg/kg body weight/day for six weeks; QGC group: treated with dexamethasone sodium phosphate 1 mg/kg body weight/day plus qigu capsule for six weeks. NC: normal control; DEX: dexamethasone; QGC: Qigu capsule;.mtDNA: mitochondrial DNA; AMPK: adenosine 5'-monophosphate-activated protein kinase; p-AMPK: phospho- adenosine 5'-monophosphate-activated protein kinase; PGC-1α：peroxisome proliferator-activated receptor-γ coactivator 1-alpha; NRF1: nuclear respiratory factor 1; TFAM: transcription factor A, mitochondrial; GAPDH: glyceraldehyde-3-phosphate dehydrogenase. All data are presented as the mean ± standard deviation (n = 12). Compared with NC group, aP < 0.01; compared with DEX group, bP < 0.01; compared with DEX group, cP < 0.05.

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