Sinomenine HCl

Sinomenine hydrochloride is a blocker of the NF-κB activation and also an activator of μ-opioid receptor.

Signaling Pathways >> GPCR/G Protein >> Opioid Receptor

Signaling Pathways >> Neuronal Signaling >> Opioid Receptor

Natural Products >> Alkaloid

Research Areas >> Neurological Disease

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

NF-κB

μ-opioid receptor

Cell viability is gradually decreased with increasing Sinomenine hydrochloride concentration. The migration ability of MDA-MB-231 cells is significantly weakened by 0.25, 0.5, and 1 mM of Sinomenine hydrochloride treatment. The wound-healing assay reveals that 0.25 and 0.5 mM Sinomenine hydrochloride significantly suppress the healing of the wound. When the MDA-MB-231 cells are treated with 0.5 mM Sinomenine hydrochloride, the healing progress is about 50%, but in the group treated with 0.25 mM Sinomenine hydrochloride and the untreated control, the healing is about 80% and nearly 95%, respectively. The IB assay following inhibitor of NF-κB (IκB) antibody IP shows that the binding of NF-κB to IκB is inhibited by Sinomenine hydrochloride treatment in a dose-dependent manne[1].

I.p. Sinomenine hydrochloride produces antinociception in the hot plate and tail flick tests in male rats at 40 mg/kg, but not at lower doses (10 or 20 mg/kg). At 10 to 40 mg/kg Sinomenine hydrochloride does not produce any observable side effect such as sedation, allergy or motor impairments. At 80 mg/kg, Sinomenine hydrochloride is mildly sedative in rats. Sinomenine hydrochloride at 80 mg/kg i.p. does not produce any observable side effects in mice. I.p or p.o. Sinomenine hydrochloride at 40 or 80 mg/kg dose-dependently reduces mechanical hypersensitivity in nerve injured mice. I.p. Sinomenine hydrochloride at 40 mg/kg, but not lower doses or vehicle, significantly decreases mechanical and cold allodynia for up to 240 min without producing motor deficits or sedation[2]. At doses of 10 to 40 mg/kg, Sinomenine hydrochloride dose-dependently increases the paw withdrawal threshold. In non-chronic constriction injury (CCI) healthy rats, Sinomenine hydrochloride at the dose range of 10 to 40 mg/kg does not change the immobility behavior in the forced swimming test[3].

The MDA-MB-231 human triple negative and 4T1 mouse breast cancer cell lines are used in this study. For the experiments, the cells are grown in 24-well plates at 3.5×104 cells/well. Following incubation for 24 or 48 h in medium containing different concentrations of Sinomenine hydrochloride, proliferation of the cells are detected with Cell Counting Kit-8 solution according to the manufacturer's instructions[1].

Male Sprague-Dawley rats weighing of 250 to 300 g are used in this experiment. For the duration of action of acute Sinomenine hydrochloride study, different doses of Sinomenine hydrochloride (10 to 40 mg/kg) are administered 1 day after surgery and then paw withdrawal threshold is measured every 30 min for 4 hours. For the study involving daily Sinomenine hydrochloride treatment, mechanical hyperalgesia measure is performed 3 h after daily drug treatment. For antagonist studies, antagonists are given 10 min prior to 40 mg/kg Sinomenine hydrochloride administration[3].

[1]. Song L, et al. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis. Biochem Biophys Res Commun. 2015 Aug 28;464(3):705-10.

[2]. Gao T, et al. Analgesic effect of sinomenine in rodents after inflammation and nerve injury. Eur J Pharmacol. 2013 Dec 5;721(1-3):5-11.

[3]. Zhu Q, et al. Antinociceptive effects of sinomenine in a rat model of neuropathic pain. Sci Rep. 2014 Dec 1;4:7270.

BAY 11-7082 | Ammonium 1-pyrrolidinedithiocarbamate | SN50 | Triptolide | JSH-23 | Shikonine | Bay 11-7085 | Rocaglamide | (-)-DHMEQ | Dihydroartemisinin | Tomatidine | QNZ (EVP4593) | Baicalin | Laquinimod | Parthenolide

MOLECULAR FORMULA :

C19-H23-N-O4.Cl-H

MOLECULAR WEIGHT :

365.89

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4830 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 52,157,1956