Curcumin Derivative J-147 Na-emeso AD, Mgbochi ịka nká, Nsogbu Mgbakasị Obi (UN)

Nyocha J-147

Curcumin bụ polyphenol na ihe na-arụ ọrụ nke Turmeric na Ginger.Curcumin nwere ọtụtụ uru pụtara na ịgwọ ọtụtụ ọrịa, mana n'ihi enweghị ikike ya ịgafe Ọbara-Brain Barrier (BB), enwere oke adịghị ike.

Ihu ọma, J147 (CAS:1146963-51-0) bu ihe ndi ozo nke Curcumin na Cyclohexyl-Bisphenol A (CBA) bu ogwu ogwu na adi nma. Emepụtara ya maka iji ọgwụgwọ ọnọdụ neurodegenerative metụtara ịka nká. J147 nwere ike ịgafe BBB n'ime ụbụrụ (ike) ma mee ka mmepụta mkpụrụ ndụ neuronal.

N'adịghị ka ọgwụ ndị dị ugbu a kwadoro maka Ọrịa Alzheimer, J147 abụghị onye na-egbochi acetylcholinesterase ma ọ bụ onye na-eme ihe na phosphodiesterase, ma ọ na-eme ka cognition nwee ọgwụgwọ dị mkpirikpi.

Na nke a, anyị ga-atụle otu esi emepụta ihe curcumin J147 na-agwọ ọrịa Ọrịa Alzheimer (AD), nsogbu ịda mbà n'obi (UN) na mgbochi ịka nká.

Nke a bụ ọdịnaya:

1. Mụtakwuo maka J-147 Work (Mechanism)
2. Elele ngwa ngwa nke J-147
3. J-147 Na-agwọ Ọrịa Alzheimer (AD)
4. J-147 Na-emeso Nsogbu Aging
5. J-147 Na-agwọ Ọrịa Nrụrụ Isi (UN)
6. Nyocha banyere J-147
7. Ebe ịzụta J-147 ntụ ntụ

Mụtakwuo maka J-147 Work (Mechanism)

Ruo 2018, nsonaazụ J-147 na sel nọgidere bụrụ ihe omimi ruo mgbe ụlọ ọrụ Salk Institute Neurobiologists kpebiri ihe mgbagwoju anya. Ọgwụ na-arụ ọrụ site na njikọta na ATP synthase. Mkpụrụ mitochondrial a na-agbanwe mmepụta nke ike cellular, ya mere, na-achịkwa usoro ịka nká. Ọnụnọ nke mgbakwunye J-147 na sistemụ mmadụ na-egbochi nsị metụtara afọ nke na-esite na mitochondria na-adịghị arụ ọrụ na mmepụta nke ATP.

Usoro J-147 nke ime ihe ga-emekwa ka ogo nke usoro ntanetị dị iche iche gụnyere NGF na BDNF. E wezụga nke ahụ, ọ na-arụ ọrụ na ọkwa beta-amyloid, nke na-adị elu mgbe niile n'etiti ndị ọrịa nwere Alzheimer na mgbaka. Mmetụta J-147 gụnyere ịkwụsịlata ọganihu Alzheimer, igbochi ncheta ncheta, na ịbawanye mmepụta nke sel neuronal.

Elele ngwa ngwa nke J-147

❶ Meziwanye Ọrụ Mitochondrial na Ogologo Ndụ

Na-egbochi Ọrịa Alzheimer

Na-eme ka Memory dịkwuo mma

Bra Na-eto Brain

❺ Na-echebe Neurons

Nwere Ike Imezi Ọrịa Shuga

Ights Na-alụso Mgbu Na Neuropathy ọgụ

❽ Mee Ka Nchegbu Ka Mma

J-147 Na-emeso Ọrịa Alzheimer (AD)

J-147 na AD: Ndabere 

Ka ọ dị ugbu a, usoro nchọpụta ọgwụ kachasị mkpa maka ọrịa na-adịghị na-agwọ ọrịa na-adabere na njikọta njikọta dị elu maka otu ọrịa kpọmkwem. Maka ọrịa Alzheimer (AD), ihe a na-elekwasị anya bụ amyloid beta peptide (Ass) nke na-eme ka ezinụlọ Alzheimer nwee ọrịa. Otú ọ dị, n'ihi na afọ ahụ bụ ihe kachasị dị ize ndụ maka AD, anyị nyochapụtara atụmatụ nchọpụta ọgwụ ọzọ nke na-adabere na nrụpụta ọrụ na ọtụtụ ụdị ọdịbendị sel nke ọrịa metụtara afọ karịa naanị amyloid metabolism. N'iji usoro a, anyị chọpụtara ikike dị egwu, nke na-arụsi ọrụ ike, mkpụrụ ndụ neurotrophic nke na-eme ka ncheta dị na mkpanaka nkịtị, ma gbochie ọnwụ nke protein synaptic na ntụgharị uche nke ihe atụ AD transgenic.

J 147 na AD: Nyocha sitere na Mice na ụmụ oke

NKWA NKE: N'agbanyeghị ọtụtụ afọ nke nyocha, enweghị ọgwụ na-agbanwe ọrịa maka ọrịa Alzheimer (AD), ọrịa na-egbu egbu, na-arịa ọrịa neurodegenerative. Nyocha maka ọgwụgwọ ndị nwere ike ịnweta na ụdị AD nke na-adaberekarị na nyocha ogige tupu usoro ọgwụgwọ dị, si otú a na-egosipụta mgbochi ọrịa kama ịme mgbanwe ọrịa. Ọzọkwa, usoro a maka nyocha anaghị egosipụta ngosipụta ahụike nke ndị ọrịa AD nke nwere ike ịkọwa ọdịda nke ịsụgharị ogige ndị a kọwara dị ka ndị bara uru n'ụdị anụmanụ maka ọrịa na-agbanwe ogige na ogige ahụike. O doro anya na a chọrọ ụzọ ka mma iji nyocha ọgwụ ọgwụ maka AD.

METHODS: Iji gosipụta nke ọma ọnọdụ ahụike, anyị jiri usoro nyocha ọzọ metụtara ọgwụgwọ nke ụmụ oke AD na ọkwa na ọrịa ahụ mgbe usoro ọgwụgwọ amalitelarị. Akara (ụmụ ọnwa 20) ụmụ oke nje AD (APP / swePS1DeltaE9) nwere ike dị ike, na-arụsi ọrụ ike, mmelite ncheta na ngwongwo neurotrophic akpọrọ J147. A na-eji nyocha akparamàgwà, akụkọ ihe mere eme, ELISA na Western blotting iji chọpụta mmetụta nke J147 na ebe nchekwa, amyloid metabolism na ụzọ neuroprotective. A nyochakwara J147 na ụdị mpempe akwụkwọ nke na-emetụta ụbụrụ na ụmụ oke C57Bl / 6J ma jiri ya tụnyere didpezil. Ejikọtakwara nkọwa banyere ọgwụ na nchekwa nke J147.

IHE: Data e gosipụtara ebe a na-egosi na J147 nwere ikike iji zọpụta ụkọ ọgụgụ uche mgbe a na-elekọta ya na njedebe oge na ọrịa ahụ. Ikike nke J147 iji melite ebe nchekwa na ụmụ irighiri AD bụ ihe jikọrọ ya na ntinye nke ihe NGF (ihe nrịba akwara) na BDNF (ụbụrụ na-akpata neurotrophic factor) yana ọtụtụ protein ndị na-anabata BDNF ndị dị mkpa maka mmụta na ebe nchekwa. Ntụle dị n'etiti J147 na donepezil na ihe atụ nke scopolamine gosipụtara na ọ bụ ezie na ogige abụọ ahụ dị n'iji ichekwa oge nchekwa oge dị mkpirikpi, J147 dị elu karịa na-echekwa ebe nchekwa gbasara ohere na njikọta nke abụọ ahụ rụpụtara nke ọma maka ncheta ihe ọmụma na ncheta.

Mmechi na J-147 maka AD

J147 bụ ihe ọhụrụ na-akpali akpali nke nwere nnukwu ike, nchekwa na ọmụmụ ụmụ anụmanụ yana ọnụ na-arụ ọrụ. J147 bụ ọgwụgwọ AD nwere ike ịnweta n'ihi ike ya inye ozugbo cognition na-aba uru, na ya nwekwara ikike ịkwụsị na ikekwe gbanwee ọrịa na ụmụ anụmanụ na-arịa ọrịa dịka egosipụtara na ọmụmụ ndị a.

J-147 Na-emeso Nsogbu Aging

J-147 na Egbochi ịka nká: Ndabere 

Icemụ irighiri ọgwụgwọ J147 nwere ebe nchekwa na cognition ka mma, arịa ọbara ka mma na ụbụrụ na usoro ihe ọmụmụ ndị ọzọ

Antonio Currais, onye otu Prọfesọ David Schubert nke Cellular Neurobiology Laboratory dị na Salk kwuru, sị: “Na mbido, ume a bụ ịnwale ọgwụ a n’ihe atụ anụmanụ ọhụrụ nke yitere 99% nke ikpe Alzheimer. “Anyị buru amụma na anyị ga-ahụ ụdị a Mgbochi nká mmetụta, ma J147 mere ka òké ndị ochie yie ka ha bụ ụmụaka, na-adabere n'ọtụtụ usoro ọmụmụ. ” "Ọ bụ ezie na ọtụtụ ọgwụ ndị e mepụtara n'ime afọ 20 gara aga na-eleba anya na amyloid plaque nkwụnye ego na ụbụrụ (nke bụ ihe e ji mara ọrịa ahụ), ọ nweghị onye gosipụtara na ọ dị mma n'ụlọ ọgwụ ahụ," ka Schubert na-ekwu.

Afọ ole na ole gara aga, Schubert na ndị ọrụ ibe ya malitere ịbịaru ọgwụgwọ nke ọrịa ahụ site n'akụkụ ọhụrụ. Kama ịchọta amyloid, ụlọ nyocha ahụ kpebiri na ọ gaghị etinye aka na isi ihe kpatara ọrịa - agadi. N'iji mpempe akwụkwọ na-adabere na cell na-egbu egbu na-emetụta ụbụrụ agadi, ha mepụtara J147.

Na mbụ, ndị otu ahụ chọpụtara na J147 nwere ike igbochi na ọbụlagodi iwepụ ncheta na ọrịa Alzheimer na ụmụ oke nwere ụdị ụdị eketa nke Alzheimer, ụdị oke oke eji eme ihe. Agbanyeghị, ụdị ọrịa a gụnyere naanị ihe dịka 1% nke nsogbu Alzheimer. Maka onye ọ bụla ọzọ, ịka nká bụ isi ihe kpatara nsogbu, ka Schubert na-ekwu. Ndị otu ahụ chọrọ ịchọpụta nsonaazụ nke onye na-a drugụ ọgwụ ọjọọ na ụdị ụmụ oke na-eto ngwa ngwa ma nwee ụdị nkwarụ nke yiri nke ahụ na-emetụta ọrịa ụmụ mmadụ.

J-147 na mgbochi ịka nká: Nnwale nyocha nnwale na ụmụ oke

N'ime ọrụ ọhụrụ a, ndị nchọpụta jiri usoro nyocha dị iche iche wee tụọ okwu nke mkpụrụ ndụ ihe nketa niile dị n'ụbụrụ, yana ihe karịrị 500 obere irighiri ihe ndị metụtara metabolism na ụbụrụ na ọbara nke otu atọ nke ụmụ oke na-eto ngwa ngwa. Groupszọ atọ nke oke oke na-eto ngwa ngwa gụnyere otu nke dị obere, otu nke ochie na otu nke ochie ma ọ na-enye J147 ka ha na-aka nká.

Mmụ ochie ndị natara J147 mere nke ọma na ebe nchekwa na ule ndị ọzọ maka cognition ma gosipụtakwara mmegharị moto siri ike karị. Mụ oke ejiri J147 mesoo nwekwara akara ngosi ole na ole nke Alzheimer na ụbụrụ ha. N'ụzọ dị oke mkpa, n'ihi ọtụtụ data anakọtara na ìgwè atọ nke ụmụ oke, ọ ga-ekwe omume igosipụta na ọtụtụ akụkụ nke okwu mkpụrụ ndụ na metabolism na ụmụ oke ochie nyere J147 yiri nke ụmụ anụmanụ na-eto eto. Ndị a gụnyere akara maka ụba metabolism metabolism, belata ụbụrụ mbufụt na belata etoju nke oxidized ọdụdụ asịd na ụbụrụ.

Mmetụta ọzọ pụtara ìhè bụ na J147 gbochiri nsị nke ọbara site na microvessels dị na ụbụrụ nke ụmụ oke ochie. Currais na-ekwu, sị: “Ọbara ndị e mebiri emebi bụ ihe a na-ahụkarị n'ịka nká, n'ozi Alzheimer kwa, ọ na-akawanye njọ.

Mmechi na J-147 maka nsogbu ịka nká

Mmụ oke nri J147 emeela ka ike gwụ ike ma belata ụbụrụ mbufụt. mgbochi ịka nká n'ime anụmanụ.

Ndị otu si Salk Institute gosipụtara na onye na-a drugụ ọgwụ a na-arụ ọrụ nke ọma na ụdị òké nke ịka nká nke anaghị ejikarị eme nchọpụta Alzheimer. Mgbe a na-agwọ ọrịa ndị a na J147, ha nwere ncheta na cognition ka mma, arịa ọbara dị mma na ụbụrụ na ihe ndị ọzọ gbasara ahụike.

J-147 Na-agwọ Ọrịa Nrụrụ Isi (UN)

J-147 na UN: Ndabere

Nsogbu nke ịda mbà n'obi (UN) bụ nsogbu uche siri ike metụtara ụkọ nke monoamine neurotransmitters, ọkachasị ọdịiche nke 5-HT (5-hydroxytryptamine, serotonin) na ndị natara ya. Ọmụmụ ihe anyị gara aga na-atụ aro na nnukwu ọgwụgwọ na akwụkwọ akụkọ curcumin emepụta J147 gosipụtara mmetụta yiri antidepressant site na ụbụrụ na-arịwanye elu nke ụbụrụ na-ebute neurotrophic (BDNF) na hippocampus nke ụmụ oke. Ọmụmụ ihe a dị ugbu a gbasaa na nchọpụta anyị gara aga wee nyochaa mmetụta yiri nke antidepressant nke nnukwu ọgwụgwọ nke J147 maka ụbọchị 3 na ụmụ oke ụmụ nwoke ICR yana mkpa ọ dị na ndị na-anabata 5-HT1A na 5-HT1B na akara ngosi CAMP-BDNF.

J-147 na UN: Nyocha sitere na Mice na ụmụ oke

Ụzọ: J147 na doses nke 1, 3, na 9 mg / kg (site na gavage) ka emere maka ụbọchị 3, na oge mgbochi ime mkpagharị na nyocha a na-amanye na ọdụ nkwụsị ọdụ (FST na TST). Ejiri iji nyocha redioligand jikọtara njikọta nke J147 na 5-HT1A na 5-HT1B nnata. Ọzọkwa, a na-eji agonist 5-HT1A ma ọ bụ 5-HT1B ma ọ bụ onye na-emegide ya chọpụta ụdị ntinye 5-HT na-etinye aka na mmetụta antidepressant-dị ka J147. A na-atụkwa mkpụrụ ndụ ihe nrịba ama dị ka cAMP, PKA, pCREB, na BDNF iji chọpụta usoro ọrụ.

Results: Nsonaazụ gosipụtara na nnukwu ọgwụgwọ nke J147 mere ka ọ ghara ịda mbà na FST na TST n'ụzọ dabara adaba. J147 gosipụtara njikọta dị elu na vitro na onye nnata 5-HT1A nke a kwadebere site na anụ ahụ anụ ahụ ma bụrụ onye na-esighi ike na onye nnata 5-HT1B. Emechiri mmetụta ndị a nke J147 site na mbido na onye na-emegide 5-HT1A NAD-299 ma mekwaa ka 5-HT1A agonist 8-OH-DPAT. Otú ọ dị, onye na-anabata ihe nnabata 5-HT1B NAS-181 agbanweghị n'ụzọ dị mma ịgbanwe mmetụta nke J147 na omume-ịda mbà n'obi. Ọzọkwa, mmeghe nke NAD-299 gbochiri mmụba J147 na-abawanye na CAMP, PKA, pCREB, na okwu BDNF na hippocampus, ebe 8-OH-DPAT kwalitere nsonaazụ nke J147 na okwu ndị a.

Mmechi na J-147 maka nsogbu ịda mbà n'obi (UN)

Nsonaazụ na-egosi na J147 na-ebute mmetụta yiri antidepressant dị ọsọ ọsọ n'oge oge ọgwụgwọ ụbọchị 3 na-eweghị ndidi ọgwụ. Ihe ndị a nwere ike ịbụ onye mgbasa ozi 5-HT1A na-adabere na CAMP / PKA / pCREB / BDNF.

Nyocha banyere J-147

T-006: Otu esi eme ka uzo a di nma J-147

J147 bụ phenyl hydrazide sitere na curcumin na-emepụta ihe.

※ J147 nwere ọkara ndụ nke elekere 2.5 na ụbụrụ, 1.5 elekere na plasma, 4.5min na microsomes mmadụ, na <4min na igwe microsomes.

Ngwọta ọgwụgwọ na-adịghị ala ala na J147 chebere akwara sciatic site na-arịa ọrịa shuga na-aga n'ihu na-eme ka ọ ghara ịdị na-agba ọsọ nke nnukwu eriri na-eme ka ọ bụrụ na otu ụzọ nke J147 na-agbanwe ngwa ngwa ma jiri nwayọọ nwayọọ gbanwee allodynia na-emetụ aka.

Treatment Usoro ọgwụgwọ J147 na-achịkwa BACE, si otú a na-abawanye APP (nkwụsị APP na-ezighi ezi mechara mee A rise).

Α Akụkụ mitochondrial oc-F1 nke ATP synthase (ATP5A) dị ka ebumnuche molecule dị elu nke J147, protein a mụtara na mbụ nke ịka nká… nwere mgbochi mgbochi na ATP5a.

J147 weghachiri ogo nke acylcarnitines na-egosi mmetụta dị mma na ike mitochondrial.

NM Na ndị nnata NMDA, T-006 gbochie oke mbubata Ca2 +.

※ T-006 nwere ọrụ nchekwa na sistemụ a site na igbochi ụzọ MAPK / ERK ma weghachite ụzọ PI3-K / Akt.

Der Ihe ndi ozo dika 3j (analogic nke J147 dicyanovinyl) nwere ike igbochi oligomerization na fibrillation nke am-amyloid peptides ma chebe sel neuronal site na t-amyloid-induced cytotoxicity.

Ebe Tozụta ntụ ntụ J-147?

Iwu iwu nke nootropic a ka na-abụkarị esemokwu mana ọ gaghị egbochi gị ịnweta ngwaahịa ziri ezi. A sị ka e kwuwe, J-147 Alzheimer na-anwale ule ụlọ ọgwụ. Can nwere ike ịzụta ntụ ntụ na ụlọ ahịa n'ịntanetị ka ị nwetara ihe ùgwù iji tụnyere ọnụahịa J-147 gafee ndị na-ere ahịa dị iche iche. Agbanyeghị, ịkwesịrị ijide n'aka na ị na-azụ ahịa site na ndị na-eweta ọrụ bara uru yana nyocha ụlọ nyocha nke onwe.

Ọ bụrụ na ị chọrọ ụfọdụ J-147 maka ọrịre, lelee na ụlọ ahịa anyị. Anyị na-enye ọtụtụ nootropics n'okpuru njikwa njikwa. Nwere ike ịzụta na nnukwu ma ọ bụ mee otu ịzụta dabere na ebumnuche psychonautic gị. Rịba ama na ọnụahịa J-147 bụ enyi na enyi naanị mgbe ị zụrụ n'ọtụtụ buru ibu.

Reference

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