α7 Nicotinic Acetylcholine Receptor is a Novel Mediator of Sinomenine Anti-Inflammation Effect in Macrophages Stimulated by Lipopolysaccharide

Abstract

Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effects and has been used for rheumatoid arthritis treatment in China. This study aims to verify the hypothesis that SIN acts on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit the activation of macrophages stimulated by lipopolysaccharide. The prototypical α7nAChR antagonist α-bungarotoxin and mecamylamine attenuated the effect of SIN on tumor necrosis factor-α and interleukin-6 in RAW264.7 murine macrophage-like cells and primary peritoneal macrophages of mouse induced by lipopolysaccharide. With the knockdown of α7nAChR expression in RAW264.7 cells by small interfering RNA, the inhibitory effect of SIN on tumor necrosis factor-α and interleukin-6 was reversed. Sinomenine decreased p65 expression in nuclear and increased IκBα expression in cytoplasm, and these effects were reversed by the α7nAChR small interfering RNA as well. These results indicate that the anti-inflammatory effects of SIN on macrophages in vitro depend on α7nAChR.

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

“…This is termed cholinergic anti-inflammatory pathway678. We have shown that anisodamine (Ani) promotes the binding of α7nAChR to endogenous acetylcholine and blocks muscarinic receptors910.…”

Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery

“…Phytoconstituents have several limitations such as non‐uniformity in dose and poor bioavailability, higher metabolism and larger biodistribution characteristics. There are limited data available on polyphenolic concentration in human tissues . In another way, the polyphenols have only 2–20% oral bioavailability.…”

“…In another way, the polyphenols have only 2–20% oral bioavailability. Majority of the polyphenols are instantly metabolized via methylation, sulphation, glucuronidation and eliminated by liver, which results into poor bioavailability …”

“…Another flavonoidal compound is quercetin, which is detected in plasma as glucuronide, sulphate and unconjugated form . Thus, in RA, all herbal constituents suffer from limited solubility and permeability, higher metabolization, dose unadjustment and poor bioavailability …”

“…There are limited data available on polyphenolic concentration in human tissues. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] In another way, the polyphenols have only 2-20% oral bioavailability. Majority of the polyphenols are instantly metabolized via methylation, sulphation, glucuronidation and eliminated by liver, which results into poor bioavailability.…”