Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration.

BACKGROUND: Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. OBJECTIVE: This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. METHODS: A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. RESULTS: Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. CONCLUSION: DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.

The effect of ultrasound-guided acupotomy and Juanbi decoction on lumbar disc herniation: A randomized controlled trial.

BACKGROUND: Acupotomy as well as Juanbi decoction has been used in the treatment of lumbar disc herniation. However, there is no study on ultrasound-guided acupotomy combined with Juanbi decoction in the treatment of lumbar disc herniation. METHOD: This study was supported by the Sichuan Provincial Administration of Traditional Chinese Medicine [grant number: 2020LC0163] and the Science and Technology Department of Sichuan Province [grant number: 2022YFS0418]. This study was 3 center, open, randomized, controlled trial, and was carried out from December 2020 to December 2022. A total of 60 eligible patients with LDH were split into group A and group B at random. The group B received Juanbi Decoction 3 times daily for 2 weeks along with an acupotomy assisted by ultrasound. The acupotomy was administered once a week. The same protocol was used with the group A, but the Juanbi Decoction was replaced with normal saline. OBSERVATION INDEX: Visual analogue scale (VAS) score on 1 day and 1 week after treatment, VAS score, Japanese orthopedic association low back pain score(JOA) rate, Oswestry Disability Index (ODI), and low back outcome scale (LBOS) at 1, 3, 6, and 12 months after treatment in 2 groups. RESULTS: There were no significant differences in general information, VAS score before treatment, JOA, ODI, and LBOS between the 2 groups (P > .05). Intra-group comparison: VAS score, JOA rate, ODI, and LBOS were compared before and after treatment in both groups, and the differences were statistically significant (P < .05). There were significant differences in VAS and LBOS between the 2 groups at 3 and 6 months after treatment, and there were statistically significant differences in ODI and JOA rates at 3, 6, and 12 months after treatment between the 2 groups. CONCLUSION: Acupotomy aided by ultrasound combined with Juanbi Decoction significantly relieves lumbar pain and can improve lumbar function in patients with LDH, and the clinical efficacy lasts for about 6 months.