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

<div>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, <svg height="8.54217pt" id="M13" style="vertical-align:-0.2063894pt" version="1.1" viewbox="-0.0498162 -8.33578 34.8136 8.54217" width="34.8136pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M504 89L488 119C453 85 428 69 416 69C408 69 405 75 412 102L462 304C492 438 460 451 436 451S388 441 356 423C311 397 229 336 170 256H168L189 340C208 418 200 451 177 451C144 451 82 413 24 352L40 322C65 345 98 369 108 369C114 369 119 363 112 335L28 -3L36 -12C54 -3 83 4 112 10C125 73 138 122 153 174C205 258 328 382 376 382C395 382 399 369 384 305L330 93C312 25 323 -12 351 -12C378 -12 439 21 504 89Z" id="g50-111"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="512" vert-adv-y="512"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,10.332,0)"><path d="M556 331V384H55V331H556ZM556 140V193H55V140H556Z" id="g54-34"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,21.95,0)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,28.281,0)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g></svg>. <svg height="13.9756pt" id="M14" style="vertical-align:-3.7426pt" version="1.1" viewbox="-0.0498162 -10.233 51.7753 13.9756" width="51.7753pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.872)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,6.079,.855)"><path d="M622 479C622 589 545 650 400 650H146L140 618C229 609 230 602 215 527L135 132C117 43 112 41 27 32L18 0H305L313 32C213 40 205 44 222 132L251 284L324 262H365C484 269 622 333 622 479ZM528 477C528 356 420 305 344 305C300 305 276 314 259 321L303 554C311 597 313 600 331 606C345 611 361 614 379 614C463 614 528 580 528 477Z" id="g50-81"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="640" vert-adv-y="640"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,17.871,0)"><path d="M530 -6V57L144 261V263L530 468V530L81 290V234L530 -6Z" id="g54-91"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,29.489,0)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,35.82,0)"><path d="M117 -12C153 -12 178 12 178 50C178 84 153 110 118 110C84 110 59 84 59 50C59 12 84 -12 117 -12Z" id="g50-47"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="237" vert-adv-y="237"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,38.901,0)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,45.232,0)"><path d="M158 548H390L417 615L410 623H122L83 318C105 326 143 337 185 337C296 337 350 275 350 188C350 116 308 42 225 42C164 42 122 74 100 93C90 101 82 99 72 92C60 82 51 68 50 59C48 46 52 38 66 24C82 9 125 -12 172 -12C225 -11 292 15 346 59C408 108 437 166 437 226C437 309 371 397 242 397C214 397 170 382 133 369L158 548Z" id="g50-54"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g></svg>, for healthy control rats versus others.</div>

Evidence-Based Complementary and Alternative Medicine

fig5

Figure 5

Figure 5: Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats 