Yog lawm,fisetintuaj yeem thim rov qab kev laus. Yog li ntawd, bulk fisetin hmoov tau nyiam los ntawm kev lag luam vim nws lub peev xwm los xaiv cov hlwb senescent. Cellular senescence yog ib qho tseem ceeb ntawm cov txheej txheem lom neeg uas ua rau kev ua haujlwm poob qis thiab hnub nyoog - ntsig txog kab mob. Nyob rau hauv xyoo tas los no, fisetin bulk hmoov tau txais kev saib xyuas thoob plaws rau nws qhov kev ua haujlwm dual ntawm kev tshem cov hlwb senescent thiab tswj senescence- ntsig txog secretory phenotypes.
Yuav Fisetin Reverse Aging?
Dab tsi yogFisetin?
Fisetin (molecular formula C₁₅H₁₀O₆, molecular hnyav 286.24 g / mol) yog flavonol compound. Nws yog ib txwm muaj nyob rau hauv txiv hmab txiv ntoo thiab zaub xws li strawberries, txiv apples, persimmons, dos, thiab dib. Strawberries muaj qib siab tshaj plaws ntawm fisetin, kwv yees li 16.0 mg / 100 g tshiab qhov hnyav. Apples muaj txog 2.69 mg / 100 g. Qhov nruab nrab txhua hnub noj zaub mov ntawm fisetin yog kwv yees li ntawm 0.4 mg / hnub. Cov qib no yog qis dua li cov koob tshuaj uas tau tshaj tawm hauv cov kev tshawb fawb sim.
Cov qauv molecular ntawm fisetin yog tus cwj pwm los ntawm 3',4'-dihydroxy hloov pauv ntawm lub nplhaib B thiab 3-hydroxy thiab 7-hydroxy hloov pauv ntawm C nplhaib. Cov kev tshawb fawb theoretical qhia tias pKa qhov tseem ceeb ntawm plaub qhov chaw sib cais (C3, C7, C3', thiab C4') yog 7.55, 8.67, 10.49, thiab 12.60, raws li. Cov txiaj ntsig no qhia tau hais tias fisetin feem ntau muaj nyob rau hauv ib qho kev sib xyaw protonated hauv lub cev pH.
Los ntawm kev xav txog kev lag luam, fisetin bulk hmoov ntsib ntau yam teeb meem. Ua ntej, ntshiab tej fisetin muaj dej solubility tsawg heev. Qhov no txwv nws qhov kev sib cais ntawm qhov ncauj formulations. Thib ob, fisetin tau txais qhov tseem ceeb ua ntej - dhau cov metabolism. Qhov no ua rau qhov ncauj bioavailability tsawg. Thib peb, nws cov photothermal stability tseem xav tau kev txhim kho. Cov kev txwv no yuav tsum tau tsim cov thev naus laus zis hauv kev tsim cov khoom noj khoom haus, cov khoom noj khoom haus, thiab cov khoom siv tshuaj.
Selective Induction ntawm Apoptosis hauv Senescent Cells
Fisetin ua raws li tus neeg sawv cev senolytic. Nws xaiv tshem tawm cov hlwb senescent es tsis yog cov cell proliferating ib txwm. Qhov kev xaiv no feem ntau cuam tshuam nrog kev hloov pauv apoptotic rhiab heev ntawm cov hlwb senescent.
Hauv cov hlwb ib txwm muaj, qhov sib npaug dynamic muaj nyob nruab nrab ntawm anti-apoptotic proteins thiab pro-apoptotic proteins. Anti-apoptotic proteins feem ntau suav nrog cov tswv cuab ntawm Bcl-2 tsev neeg, xws li Bcl-2, Bcl-xL, thiab Bcl-W. Pro-apoptotic proteins muaj xws li Bax thiab Bak. Txhawm rau kom tsis txhob muaj qhov programmed cell tuag, senescent hlwb nce qhov kev qhia ntawm Bcl-2 tsev neeg los tiv thaiv apoptotic proteins. Qhov no ua rau lawv resistant rau apoptotic signals. Txawm li cas los xij, qhov kev hloov pauv no tseem ua rau muaj qhov tsis zoo uas cov tshuaj senolytic tuaj yeem tsom.
Pure bulk fisetin ncaj qha khi rau thiab inhibits anti-apoptotic proteins, suav nrog Bcl-2, Bcl-xL, thiab Bcl-W. Qhov no txo qis permeability pib ntawm mitochondrial txheej membrane. Nws kuj txhawb kev tso tawm ntawm cytochrome c rau hauv cytoplasm. Yog li ntawd, lub caspase cascade yog qhib, ua rau apoptosis nyob rau hauv senescent hlwb.
Cov kev tshawb fawb tau pom tias cov hmoov fisetin feem ntau khi rau Bcl-2 tsev neeg cov proteins los ntawm cov txheej txheem meej meej. Molecular dynamics simulations ntxiv tau lees paub tias fisetin tuaj yeem ua tau zoo nyob hauv cov hnab ris hydrophobic ntawm cov proteins.
Inhibition ntawm PI3K / AKT Signaling Pathway
PI3K / AKT txoj kev taw qhia ua lub luag haujlwm tseem ceeb hauv kev ciaj sia ntawm cov hlwb senescent. Kev ua kom tsis tu ncua ntawm txoj kev no ua rau muaj kev ua haujlwm metabolic ntawm senescent hlwb. Nws kuj txhawb kev tsim cov SASP yam thiab suppresses apoptosis los ntawm phosphorylating downstream substrate BAD thiab ua kom NF-κB.
Nyob rau hauv telomerase- tsis muaj cov qauv kev laus ntxov ntxov, cov kws tshawb fawb pom tias qib phosphorylation ntawm AKT thiab qib kev qhia ntawm cov tshuaj tiv thaiv -apoptotic protein Bcl-2 tau ntau dua hauv cov ntaub so ntswg ntawm lub raum ntawm G3 Tert-/- nas dua li cov nas qus. Tom qab kev kho fisetin, ob qho tib si pAKT thiab Bcl-2 qib txo qis.
Ntxiv RNA sequencing tsom xam pom tias bulk fisetin hmoov tswj AKT signaling txoj kev los ntawm inhibiting kev qhia ntawm Stc1 (stanniocalcin 1) noob. Stc1 tau tshaj tawm los tsim cov tshuaj tiv thaiv-apoptotic los ntawm kev ua kom txoj hauv kev PI3K/AKT. Hauv G3 Tert-/- nas, Stc1 mRNA qib tau nce siab. Txawm li cas los xij, kev kho fisetin txo nws txoj kev qhia.
Antioxidant thiab Anti-inflammatory teebmeem
Fisetin muaj cov pab pawg polyphenolic hydroxyl. Cov pab pawg no muab nws muaj zog antioxidant kev ua haujlwm. Kev tshawb fawb qhia fisetin scavenges · OOH, O₂·⁻, thiab · OH dawb radicals zoo dua Trolox thiab ascorbic acid. Nws kuj pab kho oxidatively puas proteins thiab amino acids.
Bulk fisetin hmoov tuaj yeem pab tswj kev mob. Nws suppresses NF-κB txoj hauv kev, uas tswj cov kab mob xws li IL-6, TNF- , thiab IL-8. Hauv cov hlwb senescent, DNA puas activates NF-κB signaling. Fisetin cuam tshuam nrog cov txheej txheem no thiab txo SASP ntau lawm. Qhov no yuav pab txo qis cov teebmeem ntawm cov hlwb senescent ntawm cov ntaub so ntswg nyob ze.
Qhov Kev Tshawb Fawb Tau Ua Rau Fisetin Hauv Kev Laus?
• Fisetin thiab vascular laus
University of Colorado Boulder tab tom khiav Phase II kev sim tshuaj (NCT06133634). Txoj kev tshawb no yog randomized, ob -dig muag, thiab cov placebo- tswj. Cov kws tshawb fawb tab tom sim fisetin hauv cov neeg laus hnub nyoog 65 thiab laus dua. Cov neeg koom nrog noj 20 mg / kg / hnub rau ob lub voj voog 3 hnub nrog qhov sib txawv ntawm 2 lub lis piam. Lub hom phiaj tseem ceeb yog ntsuas cov kev hloov hauv cov hlab ntsha. Cov kws tshawb fawb tseem yuav kawm txog aortic txhav, p16-zoo T hlwb, thiab SASP yam. Kev sau cov ntaub ntawv tseem ceeb yuav tsum ua kom tiav hauv lub Peb Hlis 2026.
• Fisetin rau Kev Kho Mob Tom Qab Tshuaj Kho Mob
Txoj kev tshawb fawb PROFFi (NCT06113016) yog kev sim ntau theem II. Nws kawm fisetin ua ke nrog kev tawm dag zog hauv cov neeg muaj mob qog noj ntshav mis. Qhov kev sim tau tso npe rau 200 tus poj niam postmenopausal nrog theem I-III mob qog noj ntshav mis. Cov neeg koom nrog noj cov hmoov fisetin ntau ntawm 20 mg / kg / hnub rau 3 hnub txhua 14 hnub tshaj 16 lub lis piam. Lub ntsiab lus kawg yog kev txhim kho hauv 6-feeb taug kev deb (6MWD). Kev tso npe kawm pib thaum Lub Xya Hli 2024 thiab tseem tab tom txuas ntxiv.
• Tsawg-Khab Ntev-Tsev Kawm Fisetin
Ib qhov kev sim Danish hu ua Fisetin LOW (NCT07195318) tab tom kawm ntev -lub sij hawm qis- siv koob tshuaj fisetin. Txoj kev tshawb no yog triple - dig muag, randomized, thiab placebo- tswj. Cov neeg laus hnub nyoog 50 thiab laus dua noj 100 mg / hnub rau 7 lub lis piam. Cov kws tshawb fawb tab tom sim kev nyab xeeb thiab tiv thaiv- cov teebmeem inflammatory. Lub ntsiab biomarker yog suPAR, uas txuas nrog rau kev mob ntev thiab kev laus. Lwm cov cim suav nrog SASP yam, p16INK4a, p21CIP1/WAF1, -klotho, GDF-15, FGF-21, thiab cov qhab nia frailty. Kev sau cov ntsiab lus tseem ceeb yuav tsum nyob rau lub Kaum Hlis 2026. Kev soj ntsuam yuav txuas ntxiv mus txog xyoo 2035.
• Kev nyab xeeb thiab kam rau ua
Cov kev tshawb fawb Phase I thiab II tam sim no qhia tias fisetin feem ntau ua tau zoo - zam. Txawm li cas los xij, feem ntau cov kev tshawb fawb tseem me me. Kev siv tshuaj kuj txawv ntawm qhov kev sim. Ntev - cov ntaub ntawv kev nyab xeeb lub sij hawm tseem txwv. Pure fisetin hmoov kuj tseem muaj qhov ncauj bioavailability tsawg, uas yuav txo tau qhov ua tau zoo. Cov formulations sib txawv tuaj yeem cuam tshuam cov khoom xyaw nquag thiab nqus.
Fisetin Powder siv rau dab tsi?
Raws li cov ntaub ntawv pov thawj tam sim no, lub hauv paus kev tshawb fawb rau fisetin bulk hmoov ua tus neeg sawv cev kho mob tau tsim ua ntej. Nws qhia txog kev tiv thaiv - kev laus muaj peev xwm los ntawm ntau lub tshuab. Cov no muaj xws li inducing apoptosis nyob rau hauv senescent hlwb, inhibiting SASP ntau lawm, thiab tshem tawm dawb radicals. Cov kev tshawb fawb tsiaj pom tias fisetin tuaj yeem txhim kho cov ntaub so ntswg ua haujlwm thiab ua kom lub neej noj qab haus huv.
Rau cov neeg siv B2B, fisetin tuaj yeem siv rau ntau txoj hauv kev.
• Ua ntej, nws tuaj yeem siv los ua raw khoom rau kev noj haus.
Bulk fisetin hmoov ua hauj lwm raws li ib tug active ingredient nyob rau hauv anti- laus formulations. Nws tuaj yeem ua ke nrog cov vitamins, minerals, lossis lwm yam nroj tsuag rho tawm, xws li quercetin thiab resveratrol. Advanced formulation technologies, suav nrog nano-encapsulation thiab phospholipid complexes, yuav pab txhim kho nws bioavailability.
• Qhov thib ob, fisetin tuaj yeem siv rau hauv cov khoom noj uas muaj txiaj ntsig.
Nws yog qhov tsim nyog rau kev tiv thaiv- cov zaub mov ua haujlwm laus, cov khoom noj hloov pauv, thiab cov khoom noj khoom haus uas tsim los rau kev laus noj qab haus huv hauv nruab nrab- cov neeg laus thiab cov neeg laus.
• Thib peb, fisetin tuaj yeem siv los ua cov tshuaj pleev ib ce.
Cov kev tshawb fawb qhia tias cov hmoov fisetin ntau tuaj yeem pab txo UVB-induced photoaging puas rau ntawm daim tawv nqaij. Yog li, nws muaj peev xwm siv tau los tiv thaiv - cov khoom tu tawv nqaij laus.
• Plaub, fisetin tuaj yeem siv los ua tshuaj nruab nrab.
Raws li cov khoom siv lead ua, nws cov qauv yuav raug kho kom zoo los tsim cov derivatives nrog ntau dua senolytic kev ua haujlwm thiab kev xaiv zoo dua.
Txawm li cas los xij, qhov loj - kev loj hlob ntawm kev lag luam fisetin loj tseem ntsib ntau yam kev nyuaj. Ntau qhov siab dua - qhov zoo tshaj plaws randomized tswj kev sim yog xav tau los ntxiv dag zog rau cov pov thawj kho mob. Kev tswj hwm txoj hauv kev rau cov khoom noj khoom haus senolytic kuj yuav tsum tau qhia meej thoob plaws lub tebchaws thiab cheeb tsam. Tsis tas li ntawd, formulation technologies tseem xav tau ntxiv standardization.
Xaus:
Raws li cov pov thawj uas twb muaj lawm, bulk fisetin exerts nws los tiv thaiv - laus los ntawm ib tug dual mechanism ntawm antioxidant kho thiab senescent cell clearance. Nws muaj peev xwm ua kom pom tseeb muaj peev xwm txhim kho lub hnub nyoog -txog biomarkers thiab lub cev lub cev ua haujlwm los ntawm qhov kev txiav no- ntug txheej txheem ntawm lub hom phiaj senescent cell clearance, txhawb los ntawm tib neeg cov ntaub ntawv kho mob ua ntej.
Los ntawm kev xav txog kev lag luam, kev ruaj khov ntawm cov khoom siv siab -purity fisetin raw cov ntaub ntawv thiab cov txheej txheem tsim cov thev naus laus zis uas txhim kho bioavailability yog cov txuas tseem ceeb hauv cov saw hlau. Nrog rau hauv - kev tshawb fawb tob rau hauv cov txheej txheem lom neeg ntawm kev laus thiab kev sib sau ntawm cov ntaub ntawv soj ntsuam, cov nqi lag luam ntawm fisetin ua cov khoom siv raw rau kev cuam tshuam kev laus yuav maj mam paub. Rau B2B cov neeg siv khoom, xaiv cov khoom siv raw khoom nrog lub suab zoo tswj thiab loj - nplai ntau lawm yog qhov kev txiav txim siab tseem ceeb rau kev nkag mus rau lub lag luam tawm tshiab no.
Guanjie Biotech tsom mus rau kev tshawb fawb, kev tsim kho, thiab tsim cov hmoov fisetin thiab cog lus los muab cov khoom tshiab, siab -cov khoom raw khoom zoo rau cov neeg siv khoom thoob ntiaj teb. Peb cov neeg siv khoom network npog ntau dua 100 lub teb chaws, muab qhov kawg- rau- cov kev pabcuam kawg los ntawm cov khoom siv raw mus rau kev txhawb nqa. Yog xav paub ntxiv, thov hu rau:info@gybiotech.com.
Cov ntaub ntawv:
[1] Clinical Trial: NCT06133634. Fisetin txhawm rau txhim kho vascular muaj nuj nqi hauv cov neeg laus. University of Colorado Boulder. (Hnub pib kawm tiav: Lub Peb Hlis 2026)
[2] Clinical Trial: NCT06113016 (PROFFi). Multicenter Phase II Randomized, Placebo-Txoj Kev Tshawb Fawb Kev Ntsuas Fisetin Ua ke nrog kev tawm dag zog rau kev ua haujlwm rov qab ua haujlwm tom qab siv tshuaj khomob thaum ntxov-Cov tsos mob ntawm tus mob cancer mis.
[3] Kev sim tshuaj kho mob: NCT07195318 (Fisetin LOW). Triple-Qhov muag tsis pom kev, Randomized, Placebo-Controlled Trial Investigating Low-Dose Fisetin Supplementation in Middle-Cov neeg laus thiab cov laus. Denmark.
[4] Zhu, Y., et al. Lub Achilles pob taws ntawm cov hlwb senescent: los ntawm cov ntawv sau mus rau cov tshuaj senolytic. Kev laus Cell.
[5] Yousefzadeh, MJ, et al. Fisetin yog ib qho tshuaj kho mob uas txuas ntxiv kev noj qab haus huv thiab kev ua neej. EBioMedicine. 2018; 36:18-28.
[6] Yousefzadeh MJ, Zhu Y., McGowan SJ, et al. Fisetin yog ib qho tshuaj kho mob uas txuas ntxiv kev noj qab haus huv thiab kev ua neej. EBioMedicine. 2018, 36:18-28.
[7] Zhu Y., Doornebal EJ, Pirtskhalava T., et al. Cov neeg ua haujlwm tshiab uas tsom cov hlwb tsis muaj zog: flavone, fisetin, thiab BCL-XL inhibitors, A1331852 thiab A1155463. Aging (Albany, NY). 2017, 9(3): 955-963.
[8] Yang HH, Yang C., Chen HL, et al. Fisetin Alleviates Diabetic Aortic Aging los ntawm inhibiting Pi3k-Akt-Bcl-2/Bcl-xl Pathway thiab Clearing Senescent Cells. Kev tshawb fawb Phytotherapy. 2025.
