Limonin Inhibits IL-1<i>β</i>-Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

<div>Limonin interacts with Nrf2 in a docking study. A ribbon model is used to demonstrate the binding mode between the receptor protein Nrf2 and limonin ligand small molecules. (a) Limonin was able to dock strongly within the Nrf2 binding site (<svg height="12.7112pt" id="M49" style="vertical-align:-3.403299pt" version="1.1" viewbox="-0.0498162 -9.3079 74.6948 12.7112" width="74.6948pt" 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="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,5.59,0)"><path d="M781 0V26C717 32 712 38 712 100V450C659 439 604 437 525 437H445V477C445 549 456 603 476 630C493 653 512 666 543 666C593 666 621 631 642 607C653 596 663 597 675 604C684 610 693 621 697 630C702 640 701 652 692 665C679 681 646 712 584 713C540 710 483 685 436 640C419 666 381 691 319 693C270 688 231 670 195 643C141 602 119 557 110 529C103 505 99 479 99 457V437H52L26 408L29 397H99V104C99 36 92 32 33 26V0H245V25C184 32 178 38 178 104V397H366V100C366 37 360 32 302 26V0H512V26C451 32 445 38 445 100V397H582C631 397 633 390 633 345V100C633 37 625 32 570 26V0H781ZM366 437H178V464C178 535 192 583 208 607C222 630 244 651 285 651C338 651 376 618 396 587C385 568 379 549 375 535C370 515 366 489 366 463V437Z"></path></g><g transform="matrix(.013,0,0,-0.013,15.964,0)"><path d="M524 0V26C466 32 460 36 460 104V297C460 393 411 449 331 449C302 449 276 437 248 419C223 402 201 387 181 372V451C137 432 90 420 42 411V388C96 378 102 374 102 310V104C102 38 97 33 29 26V0H246V26C187 32 181 36 181 104V339C211 365 250 390 290 390C357 390 381 345 381 276V109C381 40 374 32 315 26V0H524Z"></path></g><g transform="matrix(.013,0,0,-0.013,23.075,0)"><path d="M135 536C164 536 186 560 186 587C186 617 164 639 136 639C109 639 85 617 85 587C85 560 109 536 135 536ZM252 0V26C188 32 181 38 181 106V451C138 433 90 420 39 412V388C99 379 102 374 102 312V106C102 38 95 32 32 26V0H252Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.402,0)"><path d="M298 36L289 62C276 55 253 45 228 45C202 45 169 60 169 141V397H276C289 405 292 426 282 437H169V574L155 576L90 509V437H45L17 408L21 397H90V107C90 28 125 -12 188 -12C198 -12 213 -8 230 1L298 36Z"></path></g><g transform="matrix(.013,0,0,-0.013,30.406,0)"><path d="M478 437H297V411C355 404 361 392 349 355C329 292 285 174 257 106L167 356C153 394 158 404 205 411L204 437H2V411C57 404 66 391 88 336C117 265 162 144 202 30C208 13 209 0 204 -15C199 -28 191 -49 173 -84C149 -128 130 -153 98 -172C81 -184 73 -193 73 -209C73 -233 101 -257 129 -257C143 -257 156 -252 161 -232C175 -179 197 -122 264 38C333 203 364 286 390 339C417 395 425 403 478 411V437Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.142,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.405,0)"><path d="M535 230V280H52V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,59.036,0)"><path d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,65.277,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,68.241,0)"><path d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"></path></g></svg> kcal/mol). (b) This proposed binding interacts with Ser555, Gly603, and Ala556 on Nrf2. (c) The binding of the Nrf2 pocket is shown with a space-filling model.</div>

Oxidative Medicine and Cellular Longevity

fig6

Figure 6

Figure 6: Limonin Inhibits IL-1<i>β</i>-Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2 

Oxidative Medicine and Cellular Longevity

Limonin Inhibits IL-1β-Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

Figure 6