Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Abstract

Background This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10) Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Sodium nitroprusside improved the quality of Radix Saposhnikoviae through constructed physiological response under ecological stress

“…Pharmacodynamics is the best method to obtain a comprehensive and accurate assessment of botanical quality. The main effects of Radix Saposhnikoviae are antipyretic, analgesic, and anti-inflammatory 2 , and the main active ingredients are chromones 42 . For 0.5 mmol/L SNP on the 3rd day, the contents of prim- O -glucosylcimifugin, cimifugin, 4′- O -β- d -glucosyl-5- O -methylvisamminol, and sec- O -glucosylhamaudol increased by 88.3%, 325.0%, 55.4%, and 283.8%, respectively, especially, the improved high-active components such as cimifugin and sec- O -glucosylhamaudol were even more remarkable.…”

“…This medicinal plant is rich in various bioactive components, including chromone, coumarin, and polysaccharides. The pharmacological activities of Radix Sposhnikoviae are diverse and valuable, such as antipyretic, analgesic, anti-inflammatory, rheumatic, anti-tumor, and antioxidant 2 . With the increase in population and farmland, as well as years of over-harvesting, the wild resources of S. divaricata have been depleted and cannot meet the market requirements of more than 5000t per year hence the cultivated have become a primary source, which accounts for more than 70% of the market share 3 .…”

Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats

“… 14 The JNK and p38 MAPK signaling pathways increase the release of proinflammatory cytokines and result in the concomitant upregulation of autophagy in SNL-induced neuropathic pain. 15 Moreover, inhibiting JNK and p38/MAPK phosphorylation suppresses the inflammation response in microglia and alleviates the inflammatory pain in mice, and lidocaine inhibition of ERK-NF-κB pathway activation achieves the same effect in rats with CIBP. 16 , 17 In bone cancer pain, up-regulated MAPK pathways activate astrocytes and microglia to affect pain sensation by an over-expression of inflammatory factors, including IL-1β, IL-6, and TNF-α.…”

Sodium Nitroprusside Improved the Quality of Radix Saposhnikoviae through Constructed Physiological State under Adversity

“…The herbal medicine Radix Saposhnikoviae, one of the most commonly botanicals in Asian countries, comes from the root and rhizome of the Saposhnikovia divaricata (Trucz.) Schischk of the Umbelliferae family (1), contains chromone, coumarin, polysaccharides, and other components, with pharmacological activities such as antipyretic, analgesic, anti-inflammatory, rheumatic, anti-tumor, and antioxidant (2). At present, the wild resources of Radix saposhnikoviae have been basically depleted and fail to meet the market requirements, and the cultivated have become a basic source.…”