ʻO ka Curcumin Derivative J-147: He lāʻau lapaʻau maikaʻi loa no ka maʻi o Alzheimer, anti-aging, a me ka maʻi kaumaha nui (MDD)

J-147 Loiloi

ʻO Curcumin kahi polyphenol a me ka ʻāpana hana o Turmeric a me Ginger. He nui nā pōmaikaʻi i loaʻa i ka Curcumin i ka mālama ʻana i nā maʻi he nui, akā ma muli o ka hiki ʻole ke hele i ka Blood-Brain Barrier (BB), aia nā maopopo palena.

ʻO ke kumu, J147 (CAS:1146963-51-0) he Curcumin a me Cyclohexyl-Bisphenol A (CBA) i loaʻa mai kahi lāʻau neurogenic a me neuroprotective ikaika. Ua hoʻomohala ʻia no ka hoʻohana ʻana i ka mālama ʻana i nā kūlana neurodegenerative e pili ana me ka ʻelemakule. Hiki iā J147 ke keʻa i ka BBB i ka lolo (ikaika) a hoʻoulu i ka hana neuronal stem cell.

ʻAʻole like me nā lāʻau i kū i kēia manawa i ʻae ʻia no ka maʻi ʻo Alzheimer, ʻaʻole ʻo J147 ka mea kāohi acetylcholinesterase a i ʻole ka mea kāohi phosphodiesterase, akā hoʻonui ia i ka ʻike me kahi lapaʻau pōkole.

Ma kēia pou, e kūkākūkā mākou pehea ka curcumin derivative J147 e mālama ai i ka maʻi ʻo Alzheimer (AD), kahi maʻi depressive nui (MDD) a me Anti-ʻelemakule.

Eia ka ʻike i loko:

1. E aʻo hou aʻe e pili ana i ka J-147 Work (Mechanism)
2. Nā Pōmaikaʻi Nānā wikiwiki o J-147
3. Hoʻolālā ʻo J-147 i ka maʻi ʻo Alzheimer (AD)
4. Hoʻolālā ʻo J-147 i ka pilikia ʻelemakule
5. Hoʻomaʻamaʻa ʻo J-147 i ka maʻi depressive nui (MDD)
6. Nā noiʻi hou aʻe e pili ana iā J-147
7. Kahi e kūʻai ai i ka pauka J-147

E aʻo hou aʻe e pili ana i ka J-147 Work (Mechanism)

A hiki i ka makahiki 2018, noho pohihihi ka hopena J-147 ma ke keena a hiki i ka wehe ʻana o ka Salk Institute Neurobiologists i ka nane. Hana ka lāʻau ma ke hoʻopaʻa ʻana iā ATP synthase. Hoʻololi kēia protein mitochondrial i ka hana ʻana o ka ikehu cellular, no laila, ke kaohi ʻana i ke kaʻina ʻelemakule. Ke kū nei ka hoʻohui J-147 i loko o ka ʻōnaehana kanaka e pale i nā mea ʻawa e pili ana i nā makahiki i hopena ʻia mai ka mitochondria pono ʻole a me ka hana nui o ATP

E hoʻonui pū ka mīkini J-147 i ka pae o nā neurotransmitters like ʻole me NGF a me BDNF. Ma waho aʻe, hana ia ma nā pae beta-amyloid, i kiʻekiʻe mau i waena o nā mea maʻi me Alzheimer a me ka dementia. ʻO nā hopena J-147 me ka hoʻolōʻihi i ka holomua o Alzheimer, pale i ka hemahema hoʻomanaʻo, a hoʻonui i ka hana ʻana o nā hunaola neuronal.

Nā Pōmaikaʻi Nānā wikiwiki o J-147

❶ Hoʻonui i ka hana Mitochondrial a me ka lōʻihi

Ven Pale i ka maʻi ʻo Alzheimer

Ves Hoʻonui i ka hoʻomanaʻo

Ows ulu ka lolo

Ects Pale i nā Neuron

❻ Hiki ke hoʻomaikaʻi i ka maʻi diabetes

Ights Kaua ʻeha a me Neuropathy

❽ Hiki ke hoʻomaikaʻi i ka pīhoihoi

J-147 Mālama ʻO ka maʻi Alzheimer (AD)

J-147 a me AD: kāʻei kua 

I kēia manawa, hoʻokumu ʻia ka paradigm ʻimi lāʻau nui no nā maʻi neurodegenerative ma luna o nā ligana pili kiʻekiʻe no nā pahuhopu kikoʻī hoʻokahi maʻi. No ka maʻi o Alzheimer (AD), ʻo ka mea nui ka amyloid beta peptide (Ass) e hoʻopili i nā maʻi maʻi maʻi ʻohana Alzheimer. Eia nō naʻe, no ka mea ʻo ia ka makahiki ʻoi aku ka makaʻu o ka AD, ua ʻimi mākou i kahi papa hana ʻike lāʻau ʻē aʻe i hoʻokumu ʻia i ka pono ma nā ʻano moʻomeheu o nā pūnaewele o nā maʻi pili pili makahiki ma mua o ka metabolism amyloid wale nō. Ke hoʻohana nei i kēia ala, ua ʻike mākou i kahi mole mole neurotrophic ikaika loa e kōkua i ka hoʻomanaʻo ʻana i nā rodents maʻamau, a pale i ka nalo ʻana o nā protein synaptic a me ka hoʻohaʻahaʻa noʻonoʻo i kahi hoʻohālikelike AD mouse.

J 147 a me AD: Ka nānā ʻana i ka derivation hoʻokolohua ma Mice

INTRODUCTION: ʻOiai nā makahiki o ka noiʻi ʻana, ʻaʻohe lāʻau e hoʻololi ai i ka maʻi no ka maʻi o Alzheimer (AD), kahi maʻi neurodegenerative pili i ka makahiki. ʻO ka loiloi no nā mea hoʻoponopono kūpono i nā rodent models o AD i hilinaʻi nui ʻia i ka hoʻāʻo ʻana i nā mea hoʻohui ma mua o ka loaʻa ʻana o ka pathology, a laila hoʻohālikelike ʻia ka pale ʻana i ka maʻi ma mua o ka hoʻololi ʻana i nā maʻi. Eia kekahi, ʻaʻole hōʻike kēia ala i ka kānana i ka hōʻike olakino o nā mea maʻi AD i hiki ke wehewehe i ka hana ʻole e unuhi i nā mea hoʻohui i ʻike ʻia he maikaʻi i nā ʻano holoholona i nā hoʻololi ʻana i nā maʻi i nā hoʻokolohua hoʻokolohua. ʻIke i kahi ala ʻoi aku ka maikaʻi i ka loiloi mua ʻana o ka lāʻau lāʻau no AD e koi ʻia.

KANAKA: I mea e hōʻike pono ai i kahi hoʻonohonoho maʻi, ua hoʻohana mākou i kahi hoʻolālā kānana ʻē aʻe e pili ana i ka mālama ʻana i nāʻiole AD ma kahi pae i ka maʻi ke hele mua nā maʻi pilikino. ʻO nā ʻiole AD transgenic AD (20-mahina) kahiko (APP / swePS1DeltaE9) hānai ʻia i kahi mana nui loa, hana waha, hoʻonui i ka hoʻomanaʻo a me nā mole neurotrophic i kapa ʻia ʻo J147. Ua hoʻohana ʻia nā hoʻomeʻina hana cognitive, histology, ELISA a me Western blotting e hoʻāʻo i ka hopena o J147 i ka hoʻomanaʻo, amyloid metabolism a me nā ala neuroprotective. Ua hoʻokolokolo pū ʻia ʻo J147 i kahi hiʻohiʻona scopolamine-induced o ka hōʻino hoʻomanaʻo ʻana i nāʻiole C57Bl / 6J a hoʻohālikelike ʻia i ka donepezil. Hoʻopili pū ʻia nā kikoʻī e pili ana i ka lāʻau lapaʻau a me ka palekana o J147.

Nā hopena: Hōʻike ka ʻikepili ma aneʻi i ka hiki iā J147 ke hoʻopakele i nā hemahema o ka ʻike ke lawelawe ʻia ma kahi pae hope loa o ka maʻi. Hoʻohui ʻia ka hiki o J147 e hoʻomaikaʻi i ka hoʻomanaʻo i nāʻiole AD ʻelemakule me ka hoʻokomo ʻana o nā kumu neurotrophic NGF (mea ulu ulu nerve) a me BDNF (lolo i loaʻa i ka neurotrophic factor) a me nā protein BDNF-pane pane i mea nui no ke aʻo ʻana a me ka hoʻomanaʻo. ʻO ka hoʻohālikelike ma waena o J147 a me donepezil i ka hoʻohālikelike scopolamine i hōʻike ʻia ʻoiai ua like nā ʻano like ʻelua i ka hoʻopakele ʻana i ka hoʻomanaʻo wā pōkole, ʻoi aku ka ʻoi o J147 i ka hoʻopakele ʻana i ka hoʻomanaʻo spatial a me kahi hui pū o nā mea ʻelua i hana maikaʻi loa no ka hoʻomanaʻo a me ka hoʻomanaʻo cued.

Ka Hopena ma J-147 no AD

ʻO J147 kahi hui hou hoihoi loa i ikaika loa, palekana i ka hoʻopaʻa holoholona ʻana a me ka hana waha. ʻO J147 kahi mea kūpono AD therapeutic ma muli o kona hiki ke hoʻolako koke nā pono ʻike, a he hiki nō paha iā ia ke kū a maliʻa ke hoʻohuli i ka holomua o ka maʻi i nā holoholona simptomas e like me ka hōʻike i kēia mau noiʻi.

Hoʻolālā ʻo J-147 i ka pilikia ʻelemakule

J-147 a me ʻO kaʻelemakule: Kahua Manawa 

ʻO nāʻiole i mālama ʻia me J147 ʻoi aku ka maikaʻi o ka hoʻomanaʻo a me ka ʻike, nā kīʻaha koko olakino i ka lolo a me nā hiʻohiʻona physiological i hoʻomaikaʻi ʻia.

"I ka manawa mua, ʻo ka impetus e hoʻāʻo i kēia lāʻau i loko o kahi ʻano holoholona i like me 99% o nā hihia o Alzheimer," wahi a Antonio Currais, he lālā no ka Laboratory Neurobiology Cellular a Professor David Schubert ma Salk. "ʻAʻole mākou i wanana e ʻike mākou i kēia ʻano Anati-oo hoi hopena, akā ua hana ʻo J147 i nā ʻiole ʻelemakule e like me ko lākou wā ʻōpio, e pili ana i nā helu physiological. " "ʻOiai ʻo ka hapa nui o nā lāʻau i hoʻomohala ʻia i loko o 20 mau makahiki i hala aku nei e māka ana i ka waiho ʻana o ka plaque amyloid i ka lolo (he hōʻailona ia o ka maʻi), ʻaʻohe mea i hōʻoia maikaʻi i ka haukapila," wahi a Schubert.

I kekahi mau makahiki i hala aku nei, ua hoʻomaka ʻo Schubert a me kāna mau hoa e hoʻokokoke i ka mālama ʻana i ka maʻi mai kahi kihi hou. Ma mua o ka target amyloid, ua hoʻoholo ke keʻena hoʻokolohua e zero i ka mea nui weliweli no ka maʻi - ʻelemakule. Ke hoʻohana nei i nā pale kelepona e pili ana i nā ʻona o ka lolo i pili i ka wā kahiko, synthesi lākou iā J147.

Ma mua, ua ʻike ka hui e hiki iā J147 ke pale a hoʻi i ka nalo ʻana o ka hoʻomanaʻo ʻana a me ka pathology o Alzheimer i nāʻiole i loaʻa kahi mana o ka hoʻoilina hoʻoilina o Alzheimer, ka mana o ka ʻiole i hoʻohana pinepine ʻia. Eia nō naʻe, ʻo kēia ʻano maʻi wale nō ma kahi o 1% o nā hihia o Alzheimer. No nā mea ʻē aʻe āpau, ʻo ka ʻelemakule ka mea nui makaʻu, wahi a Schubert. Ua makemake ka kime e ʻimi i nā hopena o ka moho lāʻau i ka lāhui o nāʻiole i kēlā makahiki me ka wikiwiki a ʻike i kahi mana o dementia e like me ke ʻano o ka maʻi kanaka e pili ana i ka makahiki.

J-147 a me Anti-ʻelemakule: ʻImi hoʻowalewale hoʻokolohua ma nāʻiole

I kēia hana hou loa, ua hoʻohana nā mea noiʻi i kahi hoʻonohonoho nui o nā hoʻokolohua e ana i ka hōʻike o nā gen āpau i ka lolo, a ʻoi aku ma mua o 500 mau mole liʻiliʻi e pili ana me ka metabolism i ka lolo a me ke koko o ʻekolu mau pūʻulu o nāʻiole ʻelemakule wikiwiki. ʻO nā hui ʻekolu o nā ʻiole ʻelemakule wikiwiki i komo i hoʻokahi ʻōpio, hoʻokahi ʻelemakule a hoʻokahi ʻelemakule akā ua hānai iā J147 i ko lākou ʻelemakule.

ʻO nā ʻiole kahiko i loaʻa iā J147 ka hana ʻoi aku ka maikaʻi ma ka hoʻomanaʻo a me nā hoʻokolohua ʻē aʻe no ka ʻike a hōʻike pū kekahi i nā neʻe kaʻa ikaika. ʻO nāʻiole i mālama ʻia me J147 he mau hōʻailona pathological hoʻi o Alzheimer i ko lākou lolo. ʻO ka mea nui, ma muli o ka nui o ka ʻikepili i hōʻiliʻili ʻia ma nā hui ʻekolu o nāʻiole, hiki ke hōʻike ʻia he nui nā ʻano o ka haʻi a me ka metabolism i loko o nāʻiole kahiko i hānai ʻia iā J147 e like loa me nā holoholona ʻōpio. Hoʻopili kēia i nā māka no ka hoʻonui ʻana i ka ikehu metabolism, hoʻemi i ka mumū o ka lolo a hoʻoliʻiliʻi i nā pae o nā momona momona oxidized i ka lolo.

ʻO kekahi hopena koʻikoʻi i kāohi ʻo J147 i ka kahe o ke koko mai nā microvessels i ka lolo o nā ʻiole kahiko. "ʻO nā kīʻaha koko i hōʻino ʻia kahi hiʻohiʻona maʻamau o ka ʻelemakule i ka nui, a ma Alzheimer, ʻoi aku ka maikaʻi o ka hewa," wahi a Currais.

Ka hopena ma J-147 no ka pilikia ʻelemakule

Ua hoʻonui kaʻiole iā J147 i ka hoʻonui ʻana i ka ikehu metabolism a hoʻemi i ka mumū o ka lolo. Ua ʻike nā kānaka noiʻi he moho lāʻau hoʻowalewale hoʻokolohua i manaʻo ʻia e paio i ka maʻi ʻo Alzheimer, i kapa ʻia ʻo J147, he pūʻali o kahi mea i manaʻo ʻole ʻia. hopena anti-ʻelemakule i nā holoholona.

Ua hōʻike ka kime o ka Salk Institute i ka hana maikaʻi ʻana o ka moho lāʻau i kahi mole ʻelemakule o ka ʻelemakule i hoʻohana ʻole ʻia ma ka noiʻi a Alzheimer I ka mālama ʻia ʻana o kēia mau ʻiole me J147, ua ʻoi aku ko lākou hoʻomanaʻo a me ka ʻike, nā kīʻaha koko olakino i ka lolo a me nā hiʻohiʻona physiological i hoʻomaikaʻi ʻia.

Hoʻomaʻamaʻa ʻo J-147 i ka maʻi depressive nui (MDD)

J-147 a me MDD: Kahope

ʻO ka maʻi kaumaha nui (MDD) kahi maʻi noʻonoʻo nui e pili ana i ka hemahema o nā neurotransmitters monoamine, e like me nā mea maʻamau ʻole o 5-HT (5-hydroxytr Egyptamine, serotonin) a me nā mea loaʻa iā ia. Ua hōʻike kā mākou noi mua ʻana i ka lapaʻau koʻikoʻi me kahi puke derivative curcumin J147 hōʻike i nā hopena antidepressant e like me ka hoʻonui ʻana o ka lolo i loaʻa i ka neurotrophic factor (BDNF) pae i ka hippocampus o nāʻiole. Ua hoʻonui ʻia ka noi o kēia manawa i kā mākou ʻike ma mua a ua ʻimi i nā hopena antidepressant e like me ka lapaʻau sub-koʻikoʻi o J147 no 3 mau lā i nāʻiole ICR kāne a me kona kūpono kūpono i nā mea loaʻa ʻo 5-HT1A a me 5-HT1B a me nā hōʻailona cAMP-BDNF i lalo.

J-147 a me MDD: Nānā i ka hoʻohālikelike derivation ma nāʻiole

Pākuhi: ʻO J147 ma nā kaha o 1, 3, a me 9 mg / kg (ma o gavage) i lawelawe ʻia no 3 mau lā, a ua hoʻopaʻa ʻia ka manawa anti-immobility i ka ʻauʻau ʻauʻau a me nā hoʻāʻo ʻana o ka huelo huelo (FST a me TST). Ua hoʻohana ʻia ka radioligand hoʻopaʻa hoʻāʻo e hoʻoholo i ka pilina o J147 i ka 5-HT1A a me ka mea loaʻa ʻo 5-HT1B. Eia kekahi, ua hoʻohana ʻia ka agonist 5-HT1A a i ʻole 5-HT1B agagonist a i ʻole kāna antagonist e hoʻoholo i kahi subtype receptor 5-HT e pili ana i nā hopena antidepressant-like o J147. Ua ana ʻia nā mole i lalo e like me cAMP, PKA, pCREB, a me BDNF e hoʻoholo i ke ʻano o ka hana.

Results: Ua hōʻike nā hopena i ka hoʻomaʻamaʻa sub-koʻikoʻi a J147 i hoʻoliʻiliʻi loa i ka manawa immobility i loko o ka FST a me ka TST ma kahi ʻano hilinaʻi lāʻau. Ua hōʻike ʻo J147 i ka pilina i loko o ka vitro i ka mea loaʻa he 5-HT1A i hoʻomākaukau ʻia mai ka ʻiʻo mice a ua liʻiliʻi ka mana ma ka mea loaʻa 5-HT1B Ua ālai ʻia kēia mau hopena o J147 e ka hana mua ʻana me kahi antagonist 5-HT1A NAD-299 a hoʻonui ʻia e kahi agonist 5-HT1A 8-OH-DPAT. Eia naʻe, ʻaʻole mahalo ʻo 5-HT1B receptor antagonist NAS-181 i nā hopena o J147 ma nā ʻano kaumaha. Eia kekahi, ʻo ka pretreatment me NAD-299 i ālai ʻia i ka hoʻonui ʻana o J147 i ka cAMP, PKA, pCREB, a me ka ʻōlelo BDNF i ka hippocampus, ʻoiai ʻo 8-OH-DPAT i hoʻonui i nā hopena o J147 i kēia mau protein.

Ka hopena ma J-147 no ka maʻi depressive nui (MDD)

Hōʻike nā hualoaʻa e hoʻokomo ʻo J147 i nā hopena antidepressant wikiwiki i loko o kahi wā mālama 3 lā me ka ʻole o ka hoʻomanawanui ʻana i ka lāʻau. Kuhi ʻia kēia mau hopena e 5-HT1A-hilinaʻi cAMP / PKA / pCREB / BDNF hōʻailona.

Nā noiʻi hou aʻe e pili ana iā J-147

※ T-006: Pehea e hoʻomaikaʻi ai i kēia ma mua o J-147

※ ʻO J147 kahi hydrazide phenyl i loaʻa mai ka curcumin hui kūlohelohe.

※ J147 he hapalua o ke ola o 2.5 hola i ka lolo, 1.5 hola i ka plasma, 4.5min i nā microsome kanaka, a me <4min i nā microsome iole.

Protected Hoʻomalu ka mālama ʻana i ka waha waha me J147 i ke aʻalolo sciatic mai ka lohi o ka mimikō holomua o ka wikiwiki me ka wikiwiki o ka lawe ʻana i ka fiber me ka wikiwiki a me ka hoʻohuli hou ʻana i ka allodynia i hoʻopili ʻia.

※ J147 mālama i lalo-regulated BACE, no laila e hoʻonui ana i ka APP (ʻo ka cleavage APP kūpono ʻole e ala aʻe iā Aβ).

※ ʻO ka subito mitochondrial α-F1 o ATP synthase (ATP5A) ma ke ʻano he kiʻekiʻena molekiola nui o J147, kahi protein i hoʻopaʻa ʻia ma mua i ka pōʻaiapili o ka ʻelemakule ... he kaukaʻi hilinaʻi ʻia ma ATP5a.

Restored J147 hoʻihoʻi i nā pae o acylcarnitines e hōʻike nei i kahi hopena maikaʻi i nā dynamics mitochondrial.

※ I nā mea loaʻa NMDA, T-006 kaohi i ke komo nui ʻana o Ca2 +.

He kuleana pale ʻo T-006 i kēia ʻōnaehana ma o ka pāpā ʻana i ke ala MAPK / ERK a me ka hoʻihoʻi ʻana i ke ala PI3-K / Akt.

※ Nā huahana like ʻole e like me 3j (dicyanovinyl-substitut J147 analogue) hiki ke kāohi i ka oligomerization a me ka fibrillation o nā peptides amy-amyloid a pale i nā hunaola neuronal mai ka cytotoxicity i hoʻokomo ʻia e ka amy-amyloid.

Ma hea e kūʻai ai i ka Powder J-147?

ʻO ka loio o kēia nootropic he iwi o ka paio akā ʻaʻole ia e pāpā iā ʻoe mai ka loaʻa ʻana o nā huahana kūpono. Ma hope o nā mea āpau, ke holo nei nā hoʻokolohua hoʻokolohua J-147 Alzheimer. Hiki iā ʻoe ke kūʻai i ka pauka i nā hale kūʻai pūnaewele ke loaʻa iā ʻoe ka pono e hoʻohālikelike i nā kumukūʻai J-147 ma waena o nā mea kūʻai aku like ʻole. Eia nō naʻe, pono ʻoe e nānā i ke kūʻai aku a puni mai nā mea hoʻolako kūpono me nā hoʻokolohua hoʻokolohua kūʻokoʻa.

Inā makemake ʻoe i kekahi J-147 no ke kūʻai aku, nānā me kā mākou hale kūʻai. Hāʻawi mākou i nā nootropics he nui ma lalo o ka kaohi maikaʻi. Hiki iā ʻoe ke kūʻai i ka nui a i ʻole ke kūʻai ʻana i hoʻokahi kūʻai aku i kāu pahuhopu psychonautic. E hoʻomaopopo ia, ʻoluʻolu ke kumukūʻai J-147 ke kūʻai wale ʻoe i nā nui.