Sarmentosamide, Anti-Aging Compound Los ntawm Marine-Derived Streptomyces Sp. PAB 042

Apr 28, 2023

Abstract:Ntau cov ntaub ntawv bioactive tau raug cais tawm ntawm cov kab mob marine, suav nrog alkaloids, peptides, lipids, zoo li mycosporineamino acids,glycosidesthiab isoprenoids. Ib txhia ntawmcov compound no muajmuaj peev xwm lojhauvkev lag luam tshuaj pleev ib cevim lawvyees duab tiv thaivanti-aging, thiabAnti-oxidant kev ua haujlwm. Hauv qhov kev tshawb fawb no, cistanche (1) raug cais tawm ntawmmarine-derivedStreptomycessp. APmarine042, tom qab uas nws muaj peev xwm mustxo cov tawv nqaij laustau kuaj hauv vitro. cistanche (1) tau pom qhov tseem ceebtxo UVB-inducedmatrix metalloproteinase-1 (MMP-1) qhiaHauv tib neeg dermal fibroblasts (NHDFs)los ntawm inhibiting lub extracellular teeb liab-regulated kinase(ERK) thiab c-Jun N-terminal kinase (JNK)phosphorylation, uas yog txoj hauv kev tswj hwm txoj hauv kev ntawm MMP-1 kev hloov pauv. Ntxiv thiab,peb tau lees paub tias cistanche (1) txo cov qog necrosis factor-alpha (TNF- ), inducedMMP{0}} tso tawm hauv NHDFs, thiabtau nthuav tawm kev ua haujlwm dawb-radical scavenging, raws li qhia los ntawm2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Yog li ntawd, peb txoj kev tshawb fawb qhia tias cistanche (1tuaj yeem yog ib qho kev cog lusanti-aging agentuas ua los ntawm downregulation ntawm MMP -1 qhia.

Ntsiab lus:cistanche; Streptomycessp. APmarine042;anti-aging; MMP{0}}; UVB; TNF-

anti-aging cistanche

Nyem qhov no kom tau txais cov ntaub ntawv ntau ntxiv txog Cistanche Rau Kev Laus Daim tawv nqaij-Tshuaj


1. Taw qhia

Cov tawv nqaij lausyog induced los ntawm ob txheej txheem tseem ceeb, uas tshwm sim los ntawm intrinsic thiab extrinsic yam.Extrinsic agingfeem ntau yog tshwm sim los ntawm raug rau ib puag ncig yam xws li huab cua muaj kuab paug [1] thiab ultraviolet (UV) hluav taws xob [2]. UV teeb yog tsim los ntawm UVA (315-400 nm), UVB (280-315 nm),thiab UVC (200-280 nm), uas UVB rays paub tias nkag mus rau hauv daim tawv nqaij thiab ua rau tawv nqaij.kev yees duab [3]. UVB-induced daim tawv nqaij photoaging ua rau DNA puas [4] thiab cov kab mob reactive oxygen(ROS) tiam [5] thiab cuam tshuam cov matrix extracellular [6]. Intrinsic aging yog tshwm sim los ntawm lub ntujCov txiaj ntsig ntawm kev hloov pauv ntawm lub cev, xws li caj ces, cov tshuaj hormones, thiab cov txheej txheem metabolic [7]. Ntxiv mus, inflammatory cytokines, xws li qog necrosis factor-alpha (TNF) ), interleukin 1 alpha/beta(IL-1 / ), thiab interleukin 6 (IL-6), muaj hnub nyoog nce ntxiv. Hauv particular, qog necrosisyam- (TNF ) paub tias kom ceev cov degradation ntawm extracellular matrix (ECM) Cheebtsam ntawmupregulating qhia thiab kev ua ntawm matrix metalloproteinases (MMPs) nyob rau hauv cov laus daim tawv nqaij [8]. MMP{0}} yogFeem ntau tso tawm los ntawm fibroblasts nyob rau hauv lub dermis, thiab secreted MMP -1 yog lub luag hauj lwm rau degradationntawm dermal collagen, uas txhawb cov qauv ntawm daim tawv nqaij thiab kev ua haujlwm. Yog li, kev hloov pauv ntawm MMP-1kev qhia hauv dermal fibroblasts tuaj yeem yog lub hom phiaj zoo rau kev txhim kho kev tiv thaiv kev lauscov khoom xyaw tshuaj pleev ib ce.

anti-aging cistanche

Cov kev tshawb fawb yav dhau los tau tshaj tawm tias UVB hluav taws xob induces ROS (reactive oxygen hom ntau lawm thiab ua rau kev ua kom intracellular signaling pathways thiab transcription yam (piv txwv li, AP-1, NF-kB) [9. Cov kev hloov pauv no yog tswj hwm los ntawm mitogen. -activated protein kinasesMAPKs), uas induce MMP-1 thiab proinflammatory cytokines. Muaj peb yam MAPKamilies koom nrog hauv UVB/ROS stimuli: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal

kinase (NK), thiab p38.Peb txoj kev tshawb fawb tau txheeb xyuas tus kab mob Streptomyces sp. APmarine042 extract uas pom muaj zog inhibitory nyhuv ntawm MMP-1 qhia. Tom qab ntawd, ib qho MMP-1 inhibitory compound tau txheeb xyuas hauv no Streptomyces sp. APmarine042 extract thiab nws cov qauv tshuaj raug txheeb xyuas los ntawm NMR kev tshawb xyuas kev pab (1), ib qho chaw nrog hexadienamide moiety 101. Peb mam li tshawb xyuas ntxiv seb puas muaj qhov sib xyaw ua ke no-inhibited MMP-1 qhia hauv UVB-irradiated thiab TNFa-induced human dermal. fibroblasts nrog rau nws lub luag haujlwm hauv kev tswj hwm ntawm cov kev taw qhia hauv qab. Tsis tas li ntawd, peb tau soj ntsuam the antioxidant kev ua ntawm cistanche(1) ntawm 2, 2-diphenyl-1-picrylhydrazyl (DPPHI)radical scavenging assay.

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2. Cov txiaj ntsig thiab kev sib tham

2.1. cistanche (1) Kev rho tawm thiab kev txheeb xyuas

cistanche (1) raug cais los ntawm kev sib xyaw ntawm HPLC-UV thiab bioactivity-guided cais. Raws li kev sib piv ntawm NMR cov ntaub ntawv (Cov Khoom Siv Ntxiv) ntawm cov khoom sib xyaw uas tau txheeb xyuas hauv qhov kev tshawb fawb no (tom qab no hu ua compound 1") rau cov uas tau tshaj tawm yav dhau los, compound 1 tau txheeb xyuas tias cistanche. kuj ua raws li cov lus ceeb toom dhau los, uas txhawb ntxiv qhov kev pab cuam 1 (Daim duab 1).

anti-aging cistanche

Daim duab 1.Cov qauv tshuaj ntawm cistanche (1).


2.2. Cytotoxic Effects of cistanche (1) on Human Dermal Fibroblasts

Txhawm rau tshawb xyuas cov teebmeem cytotoxic ntawm cistanche, tib neeg dermal fibroblasts (NHDFor human foreskin fibroblast cells (Hs68) tau kho nrog cistanche ntawm qhov sib txawv (6, 12, 25, 50, 100 ug / mL) rau 24 teev, tom qab ntawd lub cell. suav cov khoom siv-8 (CCK-8) ​​kev soj ntsuam tau ua kom muaj nuj nqis ntawm cell viability. Dej-soluble tetrazolium ntsev (WST-8) hauv CCK-8 daws tau txo los ntawm dehydrogenase cov dej num hauv cov cell muab cov xim daj-xim xim forazan dye, tus nqi uas yog proportional rau tus naj npawb ntawm cov cell nyob. Raws li qhia hauv daim duab 2, cistanche tsis ua rau pom cov teebmeem cytotoxic hauv NHDF lossis Hs68 hlwb ntawm qhov ntau ntawm {{15} } ug/ml

anti-aging cistanche

Daim duab 2. Cell viability test ntawm cistanche ntawm fibroblasts. (ab) Cell viability ofcistanche-khoTib neeg dermal fibroblasts (NHDF) (a) thiab tib neeg foreskin fibroblast cells (Hs68) (b) hlwb ntawm 24 h tau ntsuas los ntawm CCK (cell suav cov khoom siv) ntsuas. * p < 0 05, ** p < 0.01vs. pab pawg tsis kho).

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2.3. cistanche (1) Inhibits MMP-1 Kev nthuav qhia thiab tso tawm hauv UVB-irradiated NHDF Cells

Tom ntej no, NHDFs nyob rau hauv qhov tsis muaj thiab muaj UVB hluav taws xob (25 mJ / cm2) tau kho nrog cistanche (2.5 ug / mL) rau lub sijhawm luv luv, thiab cov txheeb ze MMP-1 mRNA qhia theem tau txheeb xyuas los ntawm ntau lub sijhawm. Kev txheeb xyuas PCR. cistanche tau pom tias txo qis MMP-1 mRNA qib nce mus txog 16 feem pua ​​​​thiab 17 feem pua ​​​​ntawm qhov tsis tuaj (Daim duab 3a) thiab qhov muaj (Daim duab 3bof UVB, raws li. nkag mus rau hauv lub epidermis thiab mus txog rau lub Upper dermis, uas ua rau lub tsim ntawm reactive oxygen hom (ROS) MMP zus tau tej cov, thiab collagen synthesis downregulation. Yog li ntawd, peb txoj kev tshawb nrhiav los tshawb xyuas seb cistanche-inhibited MMP -1 secretion hauv UVB-irradiated. NHDF hlwb. Cov qib secretion ntawm MMP-1 hauv xov tooj ntawm tes kab lis kev cai tau ntsuas los ntawm ELISA, thiab cov txheeb ze ntawm MMP-1secretion tau normalized rau otal protein nyob rau hauv tag nrho cov cell lysates, uas yog ntsuas los ntawm ib tug bicinchoninic acid (BCA) protein quantification assay. UVB irradiation (25 mJ/cm2) remarkably nce MMP-1secretion (8.3-fold) piv rau pawg tsis-UVB-irradiated (Daim duab 3c) thiab cistanche -inhibited MMP -1 secretion nyob rau hauv UVB-irradiated NHDF hlwb nyob rau hauv ib tug npaum li cas ntawm koob tshuaj.


anti-aging cistanche

Daim duab 3. Cov nyhuv cistanche ntawm metalloproteinase-1 (MMP-1) qhia hauv UVB-irradiatedNHDFs. (a,b) Tus txheeb ze mRNA qib ntawm MMP-1 hauv NHDF hlwb irradiated UVB (25 mJ/cm2) los yog kho nrog cistanche (2.5 ug/mL) rau 16 teev. RPLPO noob tau siv los ua kev tswj hwm sab hauv. * p < {{10}}.05.*** p < 0.001 (C) Tom qab UVB irradiation (25 mJ/cm2) , cistanche hauv cov xov xwm tsis muaj ntshav tau raug kho rau 48 h, thiab tom qab ntawd cov txheeb ze tso tawm ntawm MMP-1 rau hauv xov tooj ntawm tes kab lis kev cai tau soj ntsuam los ntawm ELISA### p < 0.001 (vs. non-UVB tswj pawg); ** p <0.01; *** p <0.001 (UVB-irradiated tswj pawg).


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