The analgesic activities of Stauntonia brachyanthera and YM11 through regulating inflammatory mediators and directly controlling the sodium channel prompt

Abstract

The analgesic studies on Stauntonia brachyanthera, a traditional Chinese folk medicine used to treat headache, pains and inflammatory diseases in local areas, showed that the EtOH extracts (EESB) and the characteristic ingredient YM11 could significantly inhibit the acetic acid-induced writhing responses by 43.1% and 78.95%, and decrease the xylene-induced ear edemas by 48.9% and 21.4%, respectively. EESB could significantly increase pain threshold of mice in hot-plate test, but the effect of YM11 was not obviously. Further study in formalin test showed the inhibitory effect of YM11 in 2nd phase was more significant than that in 1st phase, revealed the peripheral analgesic activity of YM11. The ELISA and Western Blot analysis suggested that the analgesic mechanisms of YM11 were related to the inhibitions of the expressions of TNF-α, IL-1β and IL-6, and down-regulations of Nav1.8 protein in the left side of L4–6 DRG regulated by MAPKs, in which the levels of p-ERK, p-JNK and p-p38 were all decreased. In addition, the electrophysiological experiments indicated YM11 could reduce the Nav1.8 currents by 46.01% in small-diameter DRG neurons. Therefore, the analgesic activity of S. brachyanthera might be based on the regulation of inflammatory mediators and the directly control of the sodium channel prompt.

Newly Discovered Action of HpTx3 from Venom of Heteropoda venatoria on Nav1.7 and Its Pharmacological Implications in Analgesia

“…Furthermore, the effects of HpTx3 are somewhat similar to those of the centrally acting drugs that generally inhibit both of two phases equally [46]. The findings that HpTx3 and morphine, a drug that can be used as the positive control in studying central analgesic activities [47], exhibited similar analgesic effects support the conclusion. The experimental results suggest that HpTx3 can affect some central nervous system-mediated behaviors.…”

“…However, how the HpTx3 affects the nervous system-mediated behaviors needs further investigation. Considering that HpTx3 could inhibit the pain-like behaviors caused by chemical or thermal stimuli in the mouse pain models prepared with induction of formalin, acetic acid, complete Freund's adjuvant, and hot plate, we speculate that the analgesic action of HpTx3 might involve blocking the release of prostaglandins and some other inflammation-inducing substances, because these inflammation pain models could induce pain-like behavior by releasing these bioactive components to excite nociceptive nerve endings [47].…”

“…Hot plate test was conducted according to the method described [47]. The hot plate test apparatus (model YSL-21, Jinan, China) was placed in a quiet room, and the temperature was set at 55 ± 1 • C. After each mouse was placed at the hot plate, its nociceptive responses (hind-paw licking or jumping) and nociceptive threshold (paw withdrawal latency) were observed and recorded.…”

Evaluation on Analgesic and Anti‐Inflammatory Activities of Total Flavonoids from Juniperus sabina

“…This test was performed according to the method described by Meng et al [ 18 ]. Each female mouse was kept on a hot plate having a constant temperature of 55 ± 5°C, and response time was recorded as the time elapsed before the mouse responded by licking of a hind paw.…”

Discovery of a Novel Nav1.7 Inhibitor From Cyriopagopus albostriatus Venom With Potent Analgesic Efficacy

“…According to a previous method ( Meng et al, 2017 ), a hot plate apparatus (model YLS-21A, Jinan, China) maintained at 55 ± 1°C, was used to measure the pain threshold of mice subjected to a thermal stimulus. Each female mouse was placed on hot plate to observe its pain response (hind-paw-licking or jumping) acted as its own control.…”