Category Archives: Berberine

Berberine Prevents Osteoporosis from Steroids in Rats

Abstract

Preventive effects of berberine on glucocorticoid-induced osteoporosis in rats.

Glucocorticoids are widely used to treat chronic diseases such as rheumatoid arthritis and asthma. However, long-term glucocorticoid therapy can result in serious side effects, such as osteoporosis. The present study investigated the preventive effects of berberine on glucocorticoid-induced osteoporosis in rats. Male Sprague Dawley rats were treated with vehicle, glucocorticoid, glucocorticoid and berberine, or glucocorticoid and calcium carbonate with vitamin D (3) for 12 weeks. The proximal tibiae of all rats were processed without decalcification for quantitative bone histomorphometry, and femur mechanical testing as well as bone mineral density (BMD) were analyzed. A significant decrease was found in the glucocorticoid-treated group compared with the control group in such indices as biomechanical quality, BMD, trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), mineral apposition rate (MAR), bone formation rate/total tissue area (BFR/TV), and bone formation rate/trabecular bone surface (BFR/BS). In addition, significantly increased trabecular separation (Tb.Sp), osteoclast number/trabecular bone volume (Oc.N/BV), and osteoclast surface/trabecular bone surface (Oc.S/BS) were observed in the glucocorticoid-treated group, compared with the control group. Berberine and calcium carbonate with vitamin D (3) prevented the decrease in biomechanical quality, BMD, BV/TV, Tb.N, Tb.Th, MAR, BFR/TV, and BFR/BS, as well as increased Tb.Sp, Oc.N/BV, and Oc.S/BS in glucocorticoid-induced osteoporotic rats. The present results suggest that berberine prevents glucocorticoid-induced osteoporosis by inhibiting bone resorption and improving bone formation.

Xu D, Yang W, Zhou C, Liu Y…
Planta Med. Nov 2010
PMID: 20577944

Berberine + D3 + K1 + Hop Rho Iso-α-Acids Improve Bone in Postmenopausal Women

Abstract

Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial.

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D(3) and 500 microg vitamin K(1), twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D(3) and vitamin K(1) produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

Holick MF, Lamb JJ, Lerman RH, Konda VR…
J. Bone Miner. Metab. May 2010
PMID: 20024591

Ukrain No Benefit in Rats #3

Abstract

Effect of intermittent three-month treatment with different doses of Ukrain on subregional bone mineral density of the femur of ovariectomized rats.

Ukrain, thiophosphoric acid alkaloid derivative from Chelidonium majus L., was administered i.p. to ovariectomized rats in doses of 7, 14 and 28 mg/kg every other day for 10 days, followed by a 10-day break, and the procedure was performed five times. At the end of long-term treatment with Ukrain (24 h after the last dose of the drug) the rats’ right femora were harvested and the bone densitometric parameters of the whole bone and distal metaphyseal and basicervical subregions were assessed using the dual-energy X-ray absorptiometry (DXA) densitometric method. The present results show a decrease in bone mineral density in groups of ovariectomized rats that received 7 mg/kg and 14 mg/kg of Ukrain versus untreated ovariectomized animals. Administration of Ukrain at a dose of 28 mg/kg did not significantly alter bone parameters of ovariectomized rats.

Jabłoński M, Gorzelak M, Patyra M, Jagiello-Wójtowicz E
Drugs Exp Clin Res 1998
PMID: 10190095

Berberine Prevents Bone Loss in Rats

Abstract

The effect of kampo formulae on bone resorption in vitro and in vivo. II. Detailed study of berberine.

We previously isolated berberine from aqueous extracts of tsu-kan-gan, a Kampo formula used for the treatment of osteoporosis. Berberine caused an inhibitory effect on parathyroid hormone (PTH)-stimulated bone resorption in neonatal mouse bone. In this report we describe the inhibitory effect of berberine on the formation of osteoclast-like multinucleated cells (OCLs) in the co-culture of mouse osteoblastic cells and bone marrow cells in the presence of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], PTH and interleukin-1alpha (IL-1alpha). Berberine dose-dependently inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive OCLs induced by 1alpha25(OH)2D3, PTH and IL-1alpha. We prepared OCLs in the co-culture of osteoblastic cells and bone marrow cells. The effect of berberine on pit formation by OCLs was examined using dentin slices. As OCLs are terminally differentiated multinucleated cells, the survival of OCLs affects the bone-resorbing activity of OCLs. This prompted us to count the number of TRAP-positive OCLs on the slices. Berberine dose-dependently inhibited pit formation and caused a decrease in the number of TRAP-positive OCLs. Calcitonin (CT) inhibited pit formation without affecting the number of OCLs. Berberine accelerated the cell death in OCLs cultivated on a culture plate, but CT did not affect the cell death of OCLs. This suggests that the decrease in the number of OCLs on dentin slices may be due to apoptotic cell death in OCLs. In fact, Hoechst 33258 staining revealed that the treatment of OCLs with berberine resulted in condensed nuclei and a decrease in cell size. Oral administration of the berberine (30 and 50 mg/kg/d) to ovariectomized rats prevented a decrease in bone mineral density (BMD) of the lumbar vertebra without affecting the weight of the uterus and plasma concentration of estradiol. These results suggested that berberine prevented a decrease in BMD in vivo by inhibiting osteoclastic bone resorption.

Li H, Miyahara T, Tezuka Y, Namba T…
Biol. Pharm. Bull. Apr 1999
PMID: 10328560

Review: Ukrain Influence on Bone status

Abstract

Ukrain (NSC-631570) influences on bone status: a review.

Ukrain, a thiophosphoric acid alkaloid derivative of Chelidonium majus L., was shown to affect bone tissue metabolism as assessed in densitometric and biomechanical studies in rats. Its action could be slightly osteopenic at the highest doses administered to intact animals for a prolonged period of time. This phenomenon is possibly related to Ukrain’s inhibitory effect on spontaneous locomotor activity of treated animals and/or to the stimulatory effect of the drug on the osteoclastic activity via the macrophage system. By far, the most important finding seems to be the anabolic effect of Ukrain on bone in ovariectomized rats, which is most probably related to induced increase in the production of gonadal hormones, predominantly estrogens. In this regard, the postmenopausal population of female patients treated for malignancies with Ukrain (and obviously the most numerous one) meritis clinical attention as far as the antiosteoporotic effects of this drug are concerned.

Jabłoński M
Drugs Exp Clin Res 2000
PMID: 11345045

Ukrain No Benefit in Rats #2

Abstract

Intermittent three-month treatment with Ukrain in intact and ovariectomized rats. Part II: Effect on bone mineral density of the femur.

Ukrain, an acid alkaloid derivative of Chelidonium majus L., was administered intraperitoneally to ovariectomized and control sexually mature female rats at doses of 7, 14 and 28 mg/kg once daily for 10 days, followed by 10-day break. This procedure was repeated five times. At the end of the Ukrain treatment (24 h after the last dose of the drug) the right femora of the rats were harvested and the bone densitometric parameters of the whole bone and distal metaphysial and intertrochanteric subregions were assessed using the dual energy x-ray absorptiometry densitometric method. The results showed no apparent decrease in bone mineral density in groups of rats studied. A nearly significant (p = 0.08) decrease of bone mineral content was observed in ovariectomized rats treated with 14 mg/kg of Ukrain.

Jabłoński M, Gorzelak M, Patyra M, Jagiełło-Wójtowicz E
Drugs Exp Clin Res 2000
PMID: 11345047

Berberine Promotes Osteoblasts in Mouse Cells

Abstract

Berberine promotes osteoblast differentiation by Runx2 activation with p38 MAPK.

Berberine (BBR) has been implicated in bone biology. Although BBR reduces osteoporosis by enhancing BMD and inhibiting osteoclast activity, the effects of BBR on osteoblasts during the process of osteogenesis have not been thoroughly studied. In osteoblastic cells, BBR enhanced the expression of osteogenic marker genes including osteopontin and osteocalcin and promoted the transcriptional activity of the key osteogenic transcription factor Runx2. In osteoblasts, BBR increased the binding of Runx2 to the promoter region of osteopontin. The recruitment of co-factors such as p300 and HDAC1 to the promoter regions of osteopontin and osteocalcin was regulated by BBR, resulting in an enhancement in the expression of those genes. Furthermore, BBR activated p38 mitogen-activated protein kinase (MAPK) and increased cyclooxygenase 2 (COX2) expression, which are key factors in osteoblast differentiation. Consistently, a p38 MAPK-specific inhibitor attenuated the effect of BBR on osteogenesis, whereas p38 MAPK overexpression augmented BBR-induced osteogenic gene expression. Moreover, BBR stimulated bone area formation in calvarial organ culture. Taken together, these findings indicate that BBR promotes osteoblast differentiation through activation of Runx2 by p38 MAPK. Therefore, BBR may be a potential therapeutic agent to treat bone-related disorders including osteoporosis.

Lee HW, Suh JH, Kim HN, Kim AY…
J. Bone Miner. Res. Aug 2008
PMID: 18410224

Berberine Inhibits Osteoclasts in Mouse Cells

Abstract

Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways.

Berberine, an isoquinoline alkaloid isolated from several medicinal plants, has been reported to possess anti-bacterial, anti-inflammatory and antitumor properties. Although berberine also inhibits osteoclastogenesis and bone resorption, the molecular machinery for its inhibitory effects remains unknown. This study focused on the suppressive effects of berberine on receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis and survival. Berberine inhibited RANKL-mediated osteoclast formation and survival while having no cytotoxic effects on bone marrow macrophages or osteoblastic cells. Berberine attenuated RANKL-induced activation of NF-kappaB through inhibiting phosphorylation at the activation loop of IkappaBalpha kinase beta, phosphorylation and degradation of IkappaBalpha, and NF-kappaB p65 nuclear translocation. RANKL-induced Akt phosphorylation was strongly inhibited by berberine; however, neither monocyte/macrophage-colony stimulating factor (M-CSF)-induced nor insulin-induced Akt activation was inhibited by the drug. Under M-CSF- and RANKL-deprived condition, berberine increased the active form of caspase-3 in osteoclasts. By contrast, berberine did not potentiate the activation of caspase-3 in M-CSF-deprived bone marrow macrophages. These findings indicate that berberine inhibits osteoclast formation and survival through suppression of NF-kappaB and Akt activation and that both pathways in the osteoclast lineage are highly sensitive to berberine treatment.

Hu JP, Nishishita K, Sakai E, Yoshida H…
Eur. J. Pharmacol. Feb 2008
PMID: 18083161

Berberine Increases Bone Density in Rats

Abstract

Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model.

The effects of berberine in senescence accelerated mice P6 (SAMP6) were investigated to learn whether the alkaloid affects bone mineral density (BMD). Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.

Li H, Miyahara T, Tezuka Y, Tran QL…
Biol. Pharm. Bull. Jan 2003
PMID: 12520186 | Free Full Text

Ukrain No Benefit in Rats

Abstract

Effect of intermittent three-month treatment with different doses of Ukrain on subregional femoral bone mineral density of sexually mature female rats.

Sexually mature but still growing female Wistar rats received i.p. injections of Ukrain (7, 14 or 28 mg/kg in a volume of 0.5 ml/100g) every other day for 10 days, followed by a 10-day break, and this procedure was performed five times. The control animals received the same volume of injected water. At the end of the experiment the rat right femora were harvested and the bone densitometric parameters of the entire bone, distal metaphyseal and basicervical subregions were assessed using the dual-energy X-ray absorptiometry (DXA) densitometric method. No significant changes were observed in the bone mineral density in experimental groups in comparison with control animals that received the vehicle. A slight decrease in the bone mineral content value was observed in the distal metaphyseal region in animals that were treated with the highest dose of Ukrain.

Gorzelak M, Jabłoński M, Patyra M, Jagiello-Wójtowicz E
Drugs Exp Clin Res 1998
PMID: 10190094