Category Archives: Berberine

Ukrain Prevents Bone Loss in Rats

Abstract

Effect of six-month treatment with Ukrain on early osteoporosis induced by ovariectomy in rats. Part I: Preliminary studies of bone parameters.

Ukrain, thiophosphoric acid alkaloid derivatives from Chelidonium majus L. was administered intraperitoneally in a dose of 28 mg/kg (equivalent to 0.1 LD50) every other day for six months to female rats with ovariectomy-induced early osteoporosis. Administration of Ukrain was started on the second day after the surgical operation. At the end of the long-term treatment with Ukrain each rat was tested for the strength of both humeri and some parameters of rat femur were measured. The body weight of ovariectomized rats was also examined. The present results show that the decrease in the mechanical strength of the humeral bones and some changes in the femur caused by ovariectomy were prevented by the six-month treatment with Ukrain. However, in both ovariectomized groups and in ovariectomized rats pretreated with Ukrain an increase of body weight was observed.

Jagiełło-Wojtowicz E, Kleinrok Z, Nowicky JW, Jabłonski M…
Drugs Exp Clin Res 1996
PMID: 8899324

AMPK Activators: Lipoic Acid, Metformin, EGCG, Berberine, Resveratrol Can Inhibit Bone Resorption in Mice

Abstract

AMP kinase acts as a negative regulator of RANKL in the differentiation of osteoclasts.

AMP-activated protein kinase (AMPK) has been reported to stimulate differentiation and proliferation of osteoblasts, but the role of AMPK in the physiology of osteoclasts has not been investigated.
Osteoclasts were differentiated from mouse BMMϕs. TRAP-positive multinucleated cells were considered to be osteoclasts using TRAP staining, and resorption area was determined by incubation of cells on dentine discs. Signaling pathways were investigated using Western blotting and RT-PCR.
RANKL induced phosphorylation/activation of AMPK-α in BMMϕs and stimulated formation of TRAP-positive multinucleated cells. Pharmacological inhibition of AMPK with compound C and siRNA-mediated knockdown of AMPK-α1, the predominant α-subunit isoform in BMMϕs, increased RANKL-induced formation of TRAP-positive multinucleated cells and bone resorption via activation of the downstream signaling elements p38, JNK, NF-κB, Akt, CREB, c-Fos, and NFATc1. STO-609, an inhibitor of CaMKK, completely blocked the RANKL-induced activation of AMPK-α, but KN-93, an inhibitor of CaMK, did not. siRNA-mediated TAK1 knockdown also blocked RANKL-induced activation of AMPK-α. The AMPK activators metformin, (-)-epigallocatechin-3-gallate, berberine, resveratrol, and α-lipoic acid dose-dependently suppressed formation of TRAP-positive multinucleated cells and bone resorption.
AMPK negatively regulates RANKL, possibly by acting through CaMKK and TAK1. Thus, the development of AMPK activators may be a useful strategy for inhibiting the resorption of bone that is stimulated under RANKL-activated conditions.

Lee YS, Kim YS, Lee SY, Kim GH…
Bone Nov 2010
PMID: 20696287