Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

Abstract

Background/Aims: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1

“…As one of the active chemical compounds extracted from the roots of Paeonia lactiflora , PF has been reported to possess the analgesic activity against inflammatory pain 12,14 . It was worth noting that PF curbed NLRP3 inflammasome activation in Mϕs recruited into the inflamed skin tissues (Fig.…”

Antineuroinflammatory and Neuroprotective Effects of Gyejibokryeong-Hwan in Lipopolysaccharide-Stimulated BV2 Microglia

“…Cinnamomum cassia Presl, a constitutive agent in GBH, has been shown to exhibit anti-inflammatory effects in murine BV2 microglia cells, and Paeonia suffruticosa Andrews, another element of GBH, has been reported to induce antioxidative stress effects in rat pheochromocytoma PC-12 cells [14, 15]. Moreover, amygdalin, a component of Prunus persica Batsch, induces neurotrophic effects via the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway in PC12 cells [16], paeoniflorin, a component of Paeonia suffruticosa Andrews and Paeonia lactiflora Pallas, reduces proinflammatory cytokines in CNS via the activation of Akt-NF- κ B signaling pathway in vivo and in vitro [17], and cinnamic acid, a component of Cinnamomum cassia Presl, upregulates the expression of SOCS3 in glial cells via the CREB pathway [18].…”

A 12 week, randomized, double-blind, placebo-controlled clinical trial for the evaluation of the efficacy and safety of HT083 on mild osteoarthritis

“…[ 9 ] A recent study reported that paeoniflorin, obtained from P. lactiflora can mitigate inflammatory pain by suppressing Akt-NF-kB pathway. [ 10 ] C. myrrha , a native plant to Northeastern Africa, has been used to treat rheumatoid arthritis, sinusitis, and other illnesses. [ 11 ] Both C. myrrha and P. lactiflora have been historically used as natural antinociceptives since ancient times, and both have proven functions against peripheral and central pains.…”