Rhynchophylline Attenuates LPS‐induced Pro‐inflammatory Responses through Down‐regulation of MAPK/NF‐κB Signaling Pathways in Primary Microglia

Abstract

Excessive activation of microglial cells has been implicated in various types of neuroinflammation. Suppression of microglial activation would have therapeutic benefits, leading to the alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of rhynchophylline (RIN), a tetracyclic oxindole alkaloid component isolated from Uncaria rhynchophylla (Miq.) Jacks., on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated microglia. The results showed that RIN markedly reduced the production of nitric oxide (NO), prostaglandins E(2) (PGE(2) ), monocyte chemoattractant protein (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in LPS-activated microglia. The mRNA expression levels of iNOS and COX-2 were also depressed by RIN in a concentration-dependent manner. Further studies revealed that RIN blocked IκBα phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). In summary, these data suggest that RIN suppresses inflammatory responses of microglia and may act as a potential therapeutic agent for various neurodegenerative diseases involving neuroinflammation.

Pharmacological Effects of Active Compounds on Neurodegenerative Disease with Gastrodia and Uncaria Decoction, a Commonly Used Poststroke Decoction

“…Their pharmacological activities were extensively studied which have been shown to exert anti-inflammatory [54–56], antioxidative [57, 58], and neuroprotective [57, 59–64] effects in CNS. Anti-inflammatory effects of rhynchophylline and isorhynchophylline were found in primary cultured rat cortical microglia.…”

“…More recently, another study investigated the action of rhynchophylline on the productions of proinflammatory mediators and its potential mechanisms in LPS-activated microglia. The study showed that rhynchophylline reduced the productions of nitric oxide, prostaglandin E2 (PGE 2 ), MCP-1, TNF- α , and IL-1 β [56]. Besides, mRNA levels of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) were also suppressed by rhynchophylline [56].…”

“…The study showed that rhynchophylline reduced the productions of nitric oxide, prostaglandin E2 (PGE 2 ), MCP-1, TNF- α , and IL-1 β [56]. Besides, mRNA levels of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) were also suppressed by rhynchophylline [56]. The molecular mechanisms for the inhibitions were due to the blocking of the NF- κ B activation and the suppression of ERK and p38 phosphorylations in activated microglia [56].…”

“…Besides, mRNA levels of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) were also suppressed by rhynchophylline [56]. The molecular mechanisms for the inhibitions were due to the blocking of the NF- κ B activation and the suppression of ERK and p38 phosphorylations in activated microglia [56]. Apart from rat primary microglia, rhynchophylline and isorhynchophylline effectively suppressed the release of nitric oxide, TNF- α , and IL-1 β via suppressions of iNOS protein level, ERK and p38 phosphorylations, and degradation of I κ B α in LPS-activated murine N9 microglial cell line, with isorhynchophylline showing more potent inhibition [55].…”

Effect of rhynchophylline on the expression of p-CREB and sc-Fos in triatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference rats

“…In the central nervous system, Rhy could be beneficial for memory impairment induced by the dysfunction of cholinergic systems in the brain [4]. Rhy is also effective in sedation, anti-convulsion, anti-epilepsy, and [6][7][8][9][10], thus it is widely used in traditional Chinese medicines prescribed mainly to treat ailments in the central nervous and cardiovascular systems, such as lightheadedness, convulsions, numbness, and hypertension. The molecular structure of Rhy was shown in Fig.…”