Yaobishu Regulates Inflammatory, Metabolic, Autophagic, and Apoptosis Pathways to Attenuate Lumbar Disc Herniation

Abstract

Objective. Here, we aimed to explore the main mechanism of Yaobishu (YBS) in lumbar disc herniation (LDH). Methods and Results. Eighteen compounds that might act on LDH were obtained through a combination of network pharmacology prediction and identification by high-performance liquid chromatography-mass spectrometry. The key compounds were palmitic acid and trans-4-hydroxy-3-methoxycinnamate (cinnamate). KEGG analysis demonstrated that palmitic acid target genes mainly regulate the PPAR signaling pathway, Ras signaling pathway, and fatty acid metabolism. Cinnamate target genes were primarily involved in chemical carcinogenesis-receptor activation, lipid and atherosclerosis, the HIF-1 signaling pathway, and nitrogen metabolism. The rat LDH model was constructed using autologous nucleus pulposus tissue implantation. Differential expression gene (DEGs) related to metabolism (CDKN1A and UHRF1), inflammation (S100A9 and SOCS3), autophagy (DCN and LEPR), and apoptosis (CTSW and BCL2A1) in dorsal root ganglion (DRG) tissues of the control and LDH groups was evaluated by RNA-Seq. TNF-α stimulated DRG neuronal cells were used to establish an in vitro LDH model. YBS, palmitic acid, and cinnamate reduced the expression of substance P, CGRP, S100A9, CTSW, and cleaved caspase-3, while enhancing the expression of CDKN1A, UHRF1, PCNA, Ki67, SOCS3, DCN, LEPR, and BCL2A1, as well as telomerase activity. Pearson’s correlation analysis confirmed that DCN was positively correlated with BCL2A1, indicating that autophagy might be negatively correlated with apoptosis in LDH. YBS, palmitic acid, and cinnamate reduced the Siegal neurological score and serum IL-1β and IL-18 levels, while increasing changes in the hind paw mechanical withdrawal threshold. The RNA-Seq results further showed that YBS downregulated S100A9 and CTSW expression, while upregulating SOCS3, CDKN1A, UHRF1, DCN, LEPR, and BCL2A1 expression. Conclusion. YBS and its compounds, palmitic acid, and cinnamate, attenuated LDH by regulating the inflammatory, metabolic, autophagic, and apoptotic pathways. Our results might improve the theoretical and experimental basis for clinical applications of LDH disease treatment.

Analysis of miRNA-199-5p expression levels in serum samples of patients with lumbar disc degeneration

“…A study reported that miRNA-199 increases apoptosis in different diseases, such as acute myeloid leukemia (AML) (28). Studies have also shown a link between oxidative stress and disc herniation, which is associated with apoptosis (8,29).…”

“…According to a previous report, disc degeneration makes the disc vulnerable due to a loss of elasticity and firmness (7). Inhibition of apoptosis has been mentioned in relation to the treatment of lumbar disc herniation (8). Moreover the relationship between mechanical stress and disc degeneration -due to aging and genetic factors-has been reported to be associated with disc collapse (9.…”

Sesamin-mediated high expression of BECN2 ameliorates cartilage endplate degeneration by reducing autophagy and inflammation

“…Because of several medical and surgical complications of discectomy, containing infection, nerve injury, symptomatic re-protrusion and secondary surgical injury, conservative treatment is considered to be a first-line option for most cases [ 6 ]. Traditional Chinese medicine is a conservative treatment approach for diseases, and it also has been demonstrated to effectively alleviate the symptoms of LDD [ 7 ]. Sesamin, a natural lignin health compound separated from sesame seeds, is generally used as a Chinese medicinal herb with various biological activities: anti-inflammatory [ 8 ], anti-oxidation [ 9 ], anti-cancer effects [ 10 ] and ameliorates rheumatoid arthritis [ 11 ].…”