Proteomic and metabolomic approaches elucidate the molecular mechanism of emodin against neuropathic pain through modulating the gamma-aminobutyric acid (GABA)-ergic pathway and PI3K/AKT/NF-κB pathway.

Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.

The pathogenesis and treatment mechanism of Parkinson's disease from the perspective of traditional Chinese medicine.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with no treatment currently available to modify its progression. Traditional Chinese medicine (TCM) has gained attention for its unique theoretical basis and clinical effects. Many studies have reported on the clinical effects and pharmacological mechanisms of Chinese herbs in PD. However, few studies have focused on the treatment mechanisms of anti-PD TCM drugs from the perspective of TCM itself. PURPOSE: To elaborate the treatment mechanisms of anti-PD TCM drugs in the perspective of TCM. METHODS: We performed a literature survey using traditional books of Chinese medicine and online scientific databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others up to July 2021. RESULTS: TCM theory states that PD is caused by a dysfunction of the zang-fu organs (liver, spleen, kidney, and lung) and subsequent pathogenic factors (wind, fire, phlegm, and blood stasis). Based on the pathogenesis, removing pathogenic factors and restoring visceral function are two primary treatment principles for PD in TCM. The former includes dispelling wind, clearing heat, resolving phlegm, and promoting blood circulation, while the latter involves nourishing the liver and kidney and strengthening the spleen. The anti-PD mechanisms of the active ingredients of TCM compounds and herbs at different levels include anti-apoptosis, anti-inflammation, and anti-oxidative stress, as well as the restoration of mitochondrial function and the regulation of autophagy and neurotransmitters. CONCLUSION: Chinese herbs and prescriptions can be used to treat PD by targeting multiple pharmacological mechanisms.