Effects of Huoxue Chubi decoction on protein kinase B-mammalian target of rapamycin autophagy pathway in scleroderma Balb/c model mice.

Abstract

Objective: To explore the mechanisms by which Huoxue Chubi decoction (, HXCB) affects the protein kinase B (Akt)-mammalian target of rapamycin (mTOR) autophagy pathway in scleroderma Balb/c model mice.

Methods: A scleroderma model was established in male Balb/c mice, followed by daily administration of HXCB (4.6, 2.3 and 1.15 g·kg^-1·d^-1) for 4 weeks. Bodyweight, epidermal and dermal thickness, dermal collagen levels, cutaneous reactive oxygen species (ROS) levels, Akt, Phosphorylated Akt (p-Akt), mTOR, Phosphorylated mTOR (p-mTOR), B-celllymphoma-2-interacting myosin-like coiled-coil protein 1 (Beclin-1) and microtubule-associated protein A/B-light chain 3 (LC3) protein and messenger ribonucleic acid (mRNA) expression were assessed.

Results: HXCB treatment significantly reduced epidermal and dermal thickness, dermal collagen levels, ROS levels and the mRNA and protein expression of factors in the Akt-mTOR signaling pathway compared to the scleroderma model group. Conversely, mice body weight and autophagy factors Beclin-1 and LC3 were significantly increased in mice receiving HXCB treatment. Moreover, finally, ROS expression positively correlated with skin thickness, collagen contents and the mRNA expression levels of Akt, while the protein and mRNA expression levels of Akt-mTOR pathway-related factors were inversely correlated with the protein and mRNA expression of Beclin-1 and LC3.

Conclusion: HXCB can regulate autophagy by invigorating Qiand promoting blood circulation, thereby reducing blood stasis, facilitating new tissue generation, and contributing to scleroderma treatment. This effect may be attributed to the promotion of autophagy and enhancement of collagen degradation through the reduction of tissue oxidative stress elicited by HXCB.