Leonurin monohydrochloride

Leonurine (hydrochloride), a major alkaloid compound extracted from Leonurus japonicas Houtt. (Labiatae), is considered to have antitumor roles.

In Vitro:Leonurine hydrochloride significantly inhibits the proliferation of H292 cells in a time- and dose-dependent manner, and induces G0/G1 cell-cycle arrest. Coincidentally, Leonurine hydrochloride treatment at a dose of 10, 25, and 50 μM for 24 h increases apoptotic ratio from 4.9±0.43% to 11.5±1.12%, 19.3±1.16%, and 61.3±6.69%, respectively. The inhibition effect of Leonurine hydrochloride on H292 cells is associated with the loss of MMP and the generation of ROS. The phosphorylation level of p38 is increased and Akt phosphorylation is reduced by Leonurine hydrochloride treatment. Furthermore, Leonurine hydrochloride treatment increases the expression levels of caspase-3, caspase-9 and Bax/Bcl-2[1]. In RAW 264.7 cells and mouse bone marrow monocytes (BMMs), Leonurine hydrochloride suppresses RANKL-induced osteoclastogenesis and actin ring formation in a dose-dependent manner. Leonurine hydrochloride targets RANKL-induced osteoclastogenesis and bone resorption at an early stage. Molecular analysis demonstrates that Leonurine hydrochloride attenuates RANKL-induced NF-κB signaling by inhibiting the phosphorylation and degradation of IκBα and NF-κB p65 nuclear translocation. Leonurine hydrochloride inhibits the RANK-TRAF6 association triggered by RANKL binding and the phosphatidylinositol 3-kinase (PI3K)/Akt axis, without significantly affecting the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and AP-1 signaling pathways. Leonurine hydrochloride attenuates the RANKL-stimulated expression of osteoclast-related genes including NFATc1, tartrate resistant acid phosphatase (TRAP), cathepsin K, and osteoclast-associated receptor (OSCAR)[2]. Leonurine hydrochloride significantly increases the [Ca2+]i, PLC activity, and relative production of PKC protein in myometrial cells[3].

In Vivo:In in vivo experiments, leonurine hydrochloride treatment elevates the ET level and ET/NO ratio in rats with induced abortions and up-regulated ETA mRNA expression, but there is no change in ETB mRNA[3]. In in vivo experiments, compared with the model group, Leonurine hydrochloride treatment markedly reduces the volume of bleeding and intrauterine residual, and significantly shortens the duration of bleeding. From the contraction curve, Leonurine hydrochloride notably reinforces the frequency and tension of uterine contractions. Leonurine hydrochloride remarkably elevates the serum estradiol level in rats, but has no obvious effect on progesterone level[4].

References:
[1]. Mao F, et al. Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria-dependent pathway. Pharm Biol. 2015;53(11):1684-90. [2]. Yuan FL, et al. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways. Bone. 2015 Jun;75:128-37. [3]. Li X, et al. Effect of leonurine hydrochloride on endothelin and the endothelin receptor-mediated signal pathway in medically-induced incomplete abortion in rats. Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):299-303. [4]. Li X, et al. Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):375-80.