Preclinical Development of Mahanine-Enriched Fraction from Indian Spice <i>Murraya koenigii</i> for the Management of Cancer: Efficacy, Temperature/pH stability, Pharmacokinetics, Acute and Chronic Toxicity (14-180 Days) Studies

<table class="table-group" id="tab5"><tr><td><table class="table"><tr><td class="thead-hr" colspan="8"><hr/></td></tr><tr class="thead"><td class="align_left">Sample</td><td class="align_center">Dose (mg/kg BW)</td><td class="align_center"><svg height="11.9316pt" id="M62" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 25.3434 11.9316" width="25.3434pt" 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="M645 631C614 643 545 666 457 666C215 666 23 519 23 283C23 90 158 -16 337 -16C412 -16 489 2 522 10C543 39 590 127 606 167L580 181C519 89 459 18 348 18C201 18 122 136 122 287C122 464 244 632 435 632C544 632 602 595 608 472L639 475C643 526 645 581 645 631Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.619,3.132)"><path d="M810 0V30C751 35 744 40 744 106V296C744 396 694 451 614 451C583 451 558 438 537 425C512 409 485 391 454 368C434 420 390 451 342 451C309 451 285 439 260 424C228 405 206 387 185 372V453C141 434 90 421 43 413V386C102 378 105 373 105 309V106C105 41 96 35 29 30V0H243V30C194 35 185 41 185 106V335C216 360 256 389 297 389C357 389 384 348 384 275V106C384 41 374 35 312 30V0H530V30C475 35 465 41 465 104V294C465 313 464 324 463 336C502 367 539 389 576 389C637 389 663 346 663 274V109C663 41 653 35 593 30V0H810Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,16.181,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,20.267,3.132)"><path d="M482 0V30C420 38 407 48 370 103L273 248C308 299 331 332 352 357C387 397 401 404 463 409V439H277V409C318 405 324 400 307 369C290 337 270 307 251 279L194 367C175 396 180 402 220 409V439H18V409C74 401 87 395 117 349L204 213C173 168 147 130 119 95C78 46 67 38 5 30V0H195V30C144 38 143 47 162 79C181 112 202 149 225 181L297 70C314 43 307 35 264 30V0H482Z"></path></g></svg> (ng/mL)</td><td class="align_center">Area under the curve <svg height="12.689pt" id="M63" style="vertical-align:-3.40067pt" version="1.1" viewbox="-0.0498162 -9.28833 49.3674 12.689" width="49.3674pt" 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="M300 -147C201 -63 143 98 143 270S200 602 300 686L282 710C136 610 70 450 70 271V270C70 89 136 -72 282 -170L300 -147Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.498,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.013,0,0,-0.013,12.724,0)"><path d="M716 650H478V622C549 617 570 605 575 566C579 535 582 493 582 401V326C582 161 537 40 393 40C269 40 205 133 205 294V521C205 611 213 617 291 622V650H33V622C111 615 120 611 120 521V272C120 154 148 80 208 34C252 0 309 -14 368 -14C434 -14 501 7 548 55C605 116 623 201 623 319V401C623 493 626 536 629 563C633 605 656 618 716 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.292,0)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.039,0)"><path d="M275 270C275 450 212 609 64 710L45 686C145 604 203 442 203 270S147 -63 45 -147L64 -170C213 -68 275 89 275 270Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,35.537,3.132)"><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"></path></g><g transform="matrix(.0091,0,0,-0.0091,39.969,3.132)"><path d="M556 236V289H56V236H556Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,45.529,3.132)"><path d="M329 433H203L239 587L230 596L147 534L123 433H57L30 395L34 388H115L61 129C37 16 59 -12 85 -12C147 -12 222 58 260 98L241 125C212 95 160 62 144 62C132 62 127 71 138 126L192 386L305 394L329 433Z"></path></g></svg> (ng·h/mL)</td><td class="align_center"><svg height="12.0444pt" id="M64" style="vertical-align:-3.29106pt" version="1.1" viewbox="-0.0498162 -8.75334 36.6201 12.0444" width="36.6201pt" 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="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.013,0,0,-0.013,8.226,0)"><path d="M716 650H478V622C549 617 570 605 575 566C579 535 582 493 582 401V326C582 161 537 40 393 40C269 40 205 133 205 294V521C205 611 213 617 291 622V650H33V622C111 615 120 611 120 521V272C120 154 148 80 208 34C252 0 309 -14 368 -14C434 -14 501 7 548 55C605 116 623 201 623 319V401C623 493 626 536 629 563C633 605 656 618 716 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.864,0)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,26.541,3.132)"><path d="M1000 227C1000 351 905 451 780 451C658 451 590 380 530 279C465 385 388 451 261 451C168 451 38 376 38 210C38 98 121 -12 261 -12C381 -12 448 59 508 160C573 53 652 -12 780 -12C879 -12 1000 64 1000 227ZM485 199C434 109 370 25 271 25C188 25 133 117 133 241C133 355 189 414 249 414C357 414 426 302 485 199ZM903 204C903 70 852 25 790 25C681 25 611 136 552 240C603 330 669 414 768 414C855 414 903 321 903 204Z"></path></g></svg> (ng·h/mL)</td><td class="align_center"><svg height="11.5564pt" id="M65" style="vertical-align:-2.26807pt" version="1.1" viewbox="-0.0498162 -9.28833 35.3443 11.5564" width="35.3443pt" 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="M620 675H597C578 656 570 650 541 650H144C112 650 104 653 94 675H72C59 618 42 552 23 493L53 491C71 534 88 564 105 585C124 608 144 615 238 615H290L197 121C182 40 174 34 88 28L82 0H361L367 28C275 34 266 38 281 121L374 615H441C522 615 543 608 553 583C562 560 566 531 565 493L597 494C603 551 612 629 620 675Z"></path></g><g transform="matrix(.013,0,0,-0.013,8.285,0)"><path d="M300 -147C201 -63 143 98 143 270S200 602 300 686L282 710C136 610 70 450 70 271V270C70 89 136 -72 282 -170L300 -147Z"></path></g><g transform="matrix(.013,0,0,-0.013,12.783,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.023,0)"><path d="M368 703H309L44 -163H104L368 703Z"></path></g><g transform="matrix(.013,0,0,-0.013,24.384,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,30.624,0)"><path d="M275 270C275 450 212 609 64 710L45 686C145 604 203 442 203 270S147 -63 45 -147L64 -170C213 -68 275 89 275 270Z"></path></g></svg> (h)</td><td class="align_center">Mean residence time [MRT (h)]</td><td class="align_center"><svg height="12.2578pt" id="M66" style="vertical-align:-3.29568pt" version="1.1" viewbox="-0.0498162 -8.96212 23.8949 12.2578" width="23.8949pt" 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="M620 675H597C578 656 570 650 541 650H144C112 650 104 653 94 675H72C59 618 42 552 23 493L53 491C71 534 88 564 105 585C124 608 144 615 238 615H290L197 121C182 40 174 34 88 28L82 0H361L367 28C275 34 266 38 281 121L374 615H441C522 615 543 608 553 583C562 560 566 531 565 493L597 494C603 551 612 629 620 675Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.176,3.132)"><path d="M810 0V30C751 35 744 40 744 106V296C744 396 694 451 614 451C583 451 558 438 537 425C512 409 485 391 454 368C434 420 390 451 342 451C309 451 285 439 260 424C228 405 206 387 185 372V453C141 434 90 421 43 413V386C102 378 105 373 105 309V106C105 41 96 35 29 30V0H243V30C194 35 185 41 185 106V335C216 360 256 389 297 389C357 389 384 348 384 275V106C384 41 374 35 312 30V0H530V30C475 35 465 41 465 104V294C465 313 464 324 463 336C502 367 539 389 576 389C637 389 663 346 663 274V109C663 41 653 35 593 30V0H810Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,14.738,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,18.824,3.132)"><path d="M482 0V30C420 38 407 48 370 103L273 248C308 299 331 332 352 357C387 397 401 404 463 409V439H277V409C318 405 324 400 307 369C290 337 270 307 251 279L194 367C175 396 180 402 220 409V439H18V409C74 401 87 395 117 349L204 213C173 168 147 130 119 95C78 46 67 38 5 30V0H195V30C144 38 143 47 162 79C181 112 202 149 225 181L297 70C314 43 307 35 264 30V0H482Z"></path></g></svg> (h)</td></tr><tr><td class="thead-hr" colspan="8"><hr/></td></tr><tr><td class="align_left">MEF<sub>M2</sub></td><td class="align_center">300 (P.O.)</td><td class="align_center">1536</td><td class="align_center">6332</td><td class="align_center">9984</td><td class="align_center">5.3</td><td class="align_center">8.15</td><td class="align_center">2.5</td></tr><tr><td class="align_left">Mahanine</td><td class="align_center">Equivalent to 300 (P.O.) of MEF<sub>M2</sub></td><td class="align_center">984</td><td class="align_center">4823</td><td class="align_center">5254</td><td class="align_center">1.8</td><td class="align_center">3.9</td><td class="align_center">2</td></tr><tr class="table-tr"><td colspan="8"><hr class="tbody-hr"/></td></tr></table></td></tr></table>

<div>Comparative pharmacokinetic parameters of MEF<sub>M2</sub> and mahanine in rats.</div>

BioMed Research International

tab5

Table 5

Table 5: Preclinical Development of Mahanine-Enriched Fraction from Indian Spice <i>Murraya koenigii</i> for the Management of Cancer: Efficacy, Temperature/pH stability, Pharmacokinetics, Acute and Chronic Toxicity (14-180 Days) Studies 

Table 5 | Preclinical Development of Mahanine-Enriched Fraction from Indian Spice Murraya koenigii for the Management of Cancer: Efficacy, Temperature/pH stability, Pharmacokinetics, Acute and Chronic Toxicity (14-180 Days) Studies 