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. 2015:2015:824259.
doi: 10.1155/2015/824259. Epub 2015 Dec 13.

Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats

Li Lu  1 , Huang Zhijian  1 , Li Lei  1 , Chen Wenchuan  1 , Zhu Zhimin  1
Affiliations

Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats

Li Lu et al. Evid Based Complement Alternat Med. 2015.

Abstract

This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed.

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Figures

Figure 1
Figure 1
Implant surgery and postsurgery radiograph. (a) The implant was placed into the hole prepared in the tibia metaphysis. (b) Radiograph of tibia with implant after surgery.
Figure 2
Figure 2
Summary of animal grouping and treatments. Animals were randomly allocated into five groups: healthy rats as control (HC) and 4 groups of diabetic rats including (1) no additional treatment, (2) insulin, (3) berberine, and (4) berberine + insulin therapies; the treatments were given to animals for 8 weeks until being sacrificed.
Figure 3
Figure 3
Plasma BGP and ALP levels at 8 weeks after implantation. ∗ P < 0.05, for Group HC versus Group IB.
Figure 4
Figure 4
Fluorochrome double-labeling images of peri-implant osseointegration under microscopy at 10x (HC: healthy control; D: nontreated diabetic; I: insulin-treated diabetic; B: berberine-treated diabetic; IB: berberine + insulin-treated diabetic). Red was labeled by alizarin red at week 1 after surgery and green was labeled by calcein green at week 7 after surgery.
Figure 5
Figure 5
Histological images and quantitative analysis of implants 8 weeks after surgery by toluidine blue staining (10x). (a) HC: healthy control; D: nontreated diabetic; I: insulin-treated diabetic; B: berberine-treated diabetic; IB: berberine + insulin-treated diabetic. (b) Bone-to-implant contact ratio. (c) Bone area fraction occupancy ratio. Data are expressed as mean ± SD, n = 10. ∗ P < 0.05, for healthy control rats versus others.
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