Anti-Inflammatory Principles Los Ntawm Cov Koob Ntawm Pinus Taiwanensis Hayata Thiab Hauv Silico Studies Ntawm Lawv Cov Txheej Txheem Los Tiv Thaiv Kev Laus Ⅱ

Cov koob ntoo thuv tau muab rho tawm nrog methanol thiab muab faib nrog hexanes, ethylacetate, thiab dej kom tau peb txheej soluble, feem. Covanti-inflammatoryfeem, covethyl acetate txheej, tau raug mus txuas ntxiv cov pa chromatoCov txheej txheem nraaj sib xyaw ua ke, thiab tsib yam tsis tau piav qhia tau pom zoosuav nrog ob lub lignans tshiab, 1-[(70 R,80 S)-70 ,90 -dihydroxy-70 -(4-hydroxyphenyl)propan-80 -yloxy] benzoic acid1), 1-[(70 R,80 S)-70 ,90 -dihydroxy-70 -(4-hydroxy-3-methoxyphenyl)-propan-80 -yloxy] -2-hydroxybenzoic acid (2), ib tug tshiab diterpenoid, (13E,12R) -12 -hydroxyagathicacid (3), ib qho monoterpenoid, 5-isopropyl-3-oxocyclohex-1-ene-1-carboxylic acid (4), thiab ibphenylpropane, styraxinolic acid (5). Cov qauv tshuaj ntawm cov tshuaj tshiab notau tsim nrog kev pab los ntawm NMR spectral elucidation thiab MS spectrometric tsom xam. Ntxiv mus, xya caum-ob lub tebchaw paub, suav nrog ib qho steroid, -sitosterol (6); ib sesquiterpenoid, (-)-oplopan-4-ib -10- -O- -D-glucoside (7); ibcoumarin, umbelliferone (8); ibalkaloid, indole -3-aldehyde (9); plaub diterpenoids,

Nyem qhov no kom tau txais Anti-Aging Cistanche Cream

3-methoxyphenyl)-1-propanone (64), 3-hydroxy-1-(4-hydroxyphenyl)-1-propanone (65),2-(4-hydroxyphenyl) acetic acid (66phenylacetic acid (),67yog vanillic acid,68), benzoicacid (69), vanillin (70), p-hydroxyacetophenone (71sodium salicylate (),72), vanillic acid4-O- (L-rhamnoside)73), trans- ferulic acid (74), sodiump-coumarate (75), p-coumaricacid (76), trans-methylp-coumarate (77), feem, tau txheeb xyuas los ntawm kev tshuaj xyuas ntawmlawv cov ntaub ntawv lub cev thiab spectroscopic nrog cov uas tau luam tawm yav dhau los (cov ntaub ntawv uas paubCov khoom sib txuas tau muab rau hauv Cov Khoom Siv Ntxiv Ntxiv Ntxiv B).

3.1. Tus Qauv Elucidation of Compounds 1–5

Compound1 tau cais tawm raws li cov khoom siv kho qhov muag tsis muaj xim tsis muaj xim, thiab cov molecularformula tau muab raws li C16H16O6 los ntawm HR-ESI-MS tsom xam ([M− H]−, m/z 303.0855, ib.rau C16H15O6, 303.0869, Figure S1). IR spectrum qhia tias muaj hydroxyl(3412 cm−1 ) thiab pawg carbonyl conjugated (1598 cm−1 ). Cov1Cov ntaub ntawv H-NMR (Daim duab S2)pom cov cim rau obpara- hloov aromatic moieties [δH 6.72 (2H, d, J = 8.4 Hz,H-30 , -50 ), 6.86 (2H, d, J = 8.8 Hz, H-2, -6), 7.24 (2H, d,J = 8.4 Hz, H-20 , -60 ib.), 7.83(2H, d, J = 8.8 Hz, H-3, -5)], ob lub methines oxygenated [δH 4.48 (1H, m, H-80 ib.), 4.85(1H, d, J = 5.6 Hz, H-70 )], thiab ob lub methines [δH 3.81 (1H, dd, ib.J {{0}} 0, 4.0 Hz, H-90 a), thiab 3.86 (1H, dd,J {{0}}.0, 5.6 Hz, H-90 b)] ib. Cov13C thiab DEPT NMR spectra (Daim duab S3)ntawm1 tso tawm kaum rau carbons, sib xws rau ib pawg methylene, ob lub pa oxygenatedcarbons, kaum ob aromatic carbons, thiab ib tug conjugated carbonyl (Table1). Cov2 J- thiab3 J- HMBC kev sib raug zoo ntawm H-2, -6 rau C-1 thiab 4; los ntawm H-3, 5 rau C-1 thiab 7; los ntawm H-20, 60 rauC-40 thiab 70 ; los ntawm H-70 rau C-80 thiab 90 ; thiab los ntawm H-80 rau C-1, ntsig txog, tau pom hauvHMBC spectrum ntawm1 (Daim duab S4). Ntxiv mus, qhov sib txuas loj loj tas li ntawm H-70 thiab H-80 (J = 5.6 Hz) txhawb cov txheeb ze configuration ntawm1 ntawm C-70 /C-80 raws lipeb[44]. Cov kev teeb tsa tiag tiag ntawm C-70 thiab C-80 ntawm1 tau txiav txim los ntawm hluav taws xob ncigKev tsom xam dichroism (ECD). Cov paj rwb zoo ntawm 230 nm (∆ε ntxiv rau 0.17) nthuav tawm ib qho 8S configuration rau1, raws li cov ntaub ntawv luam tawm [37,38] thiab 70 R kuj yogtxiav txim siab. Lwm yam 2D ​​spectra (Daim duab S5-S7) tau muab tag nrho cov haujlwm ntawm proton thiabcarbon signals. Raws li, tus qauv ntawm1 tau muab ua 1-[(70 R,80 S)-70 ,90 - dihydroxy-7 0 -(4-hydroxyphenyl)propan-80 -yloxy] benzoic acid raws li qhia hauv daim duab1. 

Cov mis molecular ntawm2 tau muab ua C17H18O8 raws li HR-ESI-MScov ntaub ntawv analytical (m/z 349.0936 [M − H]−, Daim duab S8). Kev nqus hauv IR spectrum(3425 thiab 1541 cm−1 ) qhia txog hydroxyl thiab conjugated carbonyl functionalities,raws. Hauv kev sib piv ntawm NMR spectra ntawm1 thiab2, nws tuaj yeem pom tias lawvmuaj qhov sib txawv aromatic moieties. Ob pawg ABX-coupled aromatic nplhaib thiab ib qhomethoxy pawg tuaj yeem kuaj pom hauv1H- (Daim duab S9) thiab13Cov ntaub ntawv C-NMR (Figure S10).ntawm2 (Table1), thiab nws pom zoo tias qhov sib xyaw2 muaj ob trisubstituted es tsispara- disubstituted aromatic moieties. Qhov tseem ceeb HMBC kev sib raug zoo (Daim duab S11) los ntawmH-3 rau C-1, C-5, thiab C-7; los ntawm H-6 rau C-4; los ntawm OCH3-30 rau C-30 ; los ntawm H-60 rau C-40 thiabC-70; los ntawm H-70 rau C-10 , C-20 , C-80 thiab 90 ; los ntawm H-80 rau C-1, ntsig txog, tsim qhov ntawdtus qauv ntawm2 kuj yog ib tug neolignan skeleton. Los ntawm kev sib txuas ntawm kev sib txuas lojtas li (J7,8 = 5.2 Hz) thiab cov paj rwb zoo ntawm 230 nm (∆ε ntxiv rau 1.14), qhov tseebconfiguration ntawm2 tau muab ua tuspeb- thiab (70 R,80 S)-form, tib yam li1 [44,45]. Lwm yam2D spectra (Daim duab S12–S14) tau muab tag nrho cov haujlwm ntawm proton thiab carbon signals.Cov fifindings xaus cov qauv ntawm2 as 1-[(70 R,80 S)-70 ,90 -dihydroxy-70 -(4-hydroxy{2}}methoxyphenyl)propan -80 -yloxy]-2-hydroxybenzoic acid (Daim duab1). 

Compound3 tau txais raws li cov hmoov tsis muaj xim thiab nws cov mis molecular yogmuab raws li C20H30O5 raws li HR-ESI-MS analytical data (m/z 349.2024 [M − H]−, Daim duab S15). Compound3 pom qhov nqus siab siab ntawm 3450 (OH), thiab 1648 (carboxylic)acid) cm−1 hauv nws IR spectrum. Nws yog pov thawj los ntawm cov13C-NMR spectrum (Daim duab S16) hauvuas ob carboxylic functionalities tau soj ntsuam ntawmδC 167.2 (C-15) thiab 181.5 (C-19). Hauvnws1H-NMR (Daim duab S17), lub resonances ntawmδH 4.03 (1H, ib,J = 9.2, 2.8 Hz, H-12) thiabδC 75.5 (C-12) qhia tias muaj ib pawg cawv thib ob. Terminal methylenepab pawg tuaj yeem tsim los ntawm cov proton resonances ntawmδH 4.53 (1H, s, H-17a) thiab4.91 (1H, s, H-17b), thiab cov pa roj carbon dioxide ntawmδC 106.9 (C-17) thiab 150.2 (C{5}}), feem.Ob pawg methyl ntawmδH 0.63 (3H, s, CH3-20) thiab 1.21 (3H, s, CH3-18) tau txuas nroglub quarternary carbons (C-10 thiab C-4) ua pov thawj los ntawm HMBC kev sib raug zoo (Daim duab S18).Cov nyhuv tiv thaiv ntawm pawg carboxylic ntawm C -4 ua rau kev hloov pauv ntawm CH3-20 (δH 0.63), qhia nws- kev teeb tsa [46]. Tsis tas li ntawd, kev hloov tshuaj lom neeg ntawm H-17a (δH 4.53) tshwm sim hauv cheeb tsam upfield, tawm tswv yim 12R configuration [47]. Hauv nws HMBCspectrum, kev sib raug zoo ntawm H-12 rau C-9, C-14, thiab C-16; los ntawm H-17 rau C-7 thiab C-9;los ntawm CH3-16 rau C-12 thiab C-14; los ntawm CH3-18 rau C-3, C-4 thiab C-19; los ntawm CH3-20 rau C-1, C-5,C-9 thiab C-10, raws li txoj cai, tsim cov qauv qauv ntawm3 raws li tau hais dhau losrau 12-hydroxyagathic acid [46]. Txawm li cas los xij, C-13 configuration ntawm3 tau txiav tximraws liE los ntawm NOESY analytical data (Daim duab S19), uas tso tawm NOE cov teebmeem ntawmH-5/H-9, H-5/H-18, thiab H-12/H{5}}. Ntxiv mus, NOE ntawm H-14 thiab CH3-16, uas yuav tsum tau sau tseg hauv 12-hydroxyagathic acid [46], tsis pom nyob rau hauv3. Lwm yam2D spectra (Daim duab S20-S21) muab tag nrho cov haujlwm ntawm proton thiab carbon signals.Qhov tseeb, cov qauv ntawm3 tau tsim los ua (13E,12R) -12-hydroxyagathic acid asqhia (Daim duab1).

HR-ESI-MS spectrum ntawm4 tau nthuav tawm [M− H]− ion ncov atm/z 181.0855 (Daim duab S22), raws li cov qauv pseudomolecular ntawm C10H13O3. Qhov nqusncov ntawm 3456 thiab 1635 cm-1 Nyob rau hauv nws IR spectrum tso tawm hydroxyl thiab conjugated carbonylpawg, raws. Ob methine protons ntawmδH 2.09 (1H, m, H-5) thiab 6.32 (1H, dd,J = 2.4, 1.2 Hz, H-2), ob pawg methylene ntawmδH 1.84 (1H, m, H-4a), 2.02 (1H, m, H-4b), 2.50 (1H, ua,J = 19.2, 9.2, 4.8, 2.4 Hz, H-6a) thiab 2.70 (1H, dddd,J = 19.2, 5.2, 5.2, 1.2 Hz,H-6b), thiab ib txheej ntawm isopropyl protons ntawmδH 0.88 (3H, d, J = 6.8 Hz, CH3-9), 0.98 (3H, d, J = 6.8 Hz, CH3-10) thiab 2.31 (1H, hept,J = 6.8 Hz, H-8) tshwm nyob rau hauv lub1H-NMR spectrumntawm4 (Daim duab S23). Tsis tas li ntawd, ib qho conjugated carbonyl carbon ntawmδC 174.8 (C-7), thiab ib qhocarboxyl carbon ntawmδC 205.7 (C-3) tuaj yeem pom hauv nws13C- thiab DEPT NMR spectra(Daim duab S24). Qhov pom HMBC kev sib raug zoo (Daim duab S25) los ntawm H-2 mus rau C-7; los ntawm H-4 musC-3; los ntawm H-6 rau C-1, C-2, thiab C-5; los ntawm CH3-9 rau C-5, thiab CH3-10; los ntawm CH3-10 rau C-8,raws, tsim qauv ntawm4 as 5-isopropyl-3-oxocyclohex-1-ene-1-carboxylicacid (daim duab1). Lwm yam 2D ​​spectra (Daim duab S26-S28) muab tag nrho cov haujlwm ntawm protonthiab carbon signals. Txawm li cas los xij, stereochemistry ntawm C-5 tseem tsis tau txiav txim siab.

Compound5 muaj cov qauv molecular C11H14O5 txiav txim los ntawm ib tug deprotonatedMolecular ion ncov hauv hom tsis zoo HR-ESI-MS tsom xam (m/z 225.0767 [M − H]−, Daim duabS29). Hauv nws IR spectrum, hydroxyl (3421 cm−1 thiab carboxyl (1 572cm−1 ) functionalities yuav raug kuaj. Cov1H-NMR spectrum (Daim duab S30) qhia ob qhov ntevcoupling aromatic protons ntawmδH 6.86 (1H, d, J = 2.4 Hz, H-4) thiab 7.31 (1H, d,J = 2.4 Hz, H-6), ib pawg methoxy ntawmδH 3.56 (2H, t, J = 6.8 Hz, H-9), thiab ib txheej ntawmpropanol protons ntawmδH 1.82 (2H, tt,J {{0}}.0, 6.8 Hz, H-8), 2.61 (2H, t,J {{0}}.0 Hz, H-7) thiab 3.56(2H, t, J = 6.8 Hz, H-9 ib. Ntxiv mus, ib pawg carboxylic tau nyob ntawmδC 176.2 (C-10) nyob rau hauvnws13C-NMR spectrum (Daim duab S31). Planar qauv ntawm5 tau tsim los ntawm qhov tseem ceebHMBC kev sib raug zoo (Daim duab S32) ntawm OCH3-3 rau C-3; H-6 rau C-2, C-4, C-7, thiab C-10; H-7rau C-4, C-5, thiab C-8; H-9 rau C-7, thiab C-8, feem. Lwm yam 2D ​​spectra (Daim duab S33-S35)tau muab tag nrho cov haujlwm ntawm proton thiab carbon signals. Cov pov thawj saum toj no qhiatus qauv ntawm5 as 2-hydroxy-5-(3-hydroxypropyl)-3-methoxybenzoic acid (Daim duab1), uas twb tau tshaj tawm raws li styraxinolic acid nyob rau hauv cov ntaub ntawv hluavtaws yav dhau los [48]. Txawm li cas los xij, qhov kev tshawb fawb tam sim no yog thawj daim ntawv tshaj tawm ntawm5 los ntawm tej yam ntuj tso.

3.2. Anti-Inflammatory Activity

Inflammation yog ib qho ntawm cov kev tiv thaiv tus kheej tseem ceeb uas txhawb nqa los ntawm cov kab mob,tus kab mob, qhov txhab, lossis lwm yam ib puag ncig. Nws yog thawj cov lus teb ntawm kev tiv thaiv kab mobsystem tiv thaiv kab mob thiab irritation. Neutrophils belongs rau ntau homntawm macrophage thiab ua lub luag haujlwm tseem ceeb hauv kev mob, thiab feem ntau yog thawj lymphocytes kom ncav cuag thaj tsam muaj kab mob [49]. Neutrophils secrete ib series ntawm cytotoxins xws lisuperoxide anion thiab elastase hauv kev teb rau kev ua kom lub cev tiv thaiv kab mob [50]. HauvXyoo tsis ntev los no, ntau yam kab mob tib neeg tau pom tias muaj feem xyuam nrog neutrophiloverexpression [51–55]. Kev sib raug zoo ntawm kev mob thiab mob qog noj ntshav tau tsim, thiab cov kws sau ntawv tau taw qhia tias kev tsim cov qog nqaij hlav cancer ncaj qharau o [49]. Yog li ntawd, cov tshuaj tiv thaiv kab mob tshiab yog tsim nyog raukawm ntxiv txog kev kho mob cancer. Plaub caug-peb qhov sib cais tau raug tshuaj xyuas rauinhibition ntawm superoxide anion tiam thiab elastase tso tawm los ntawm tib neeg neutrophilsteb rau fMLF/CB [56] (saib Cov Khoom Siv Ntxiv, Table S2). Qhov tseem ceeb hauvhibitory results (Table2) qhia tias tsuas yog45, 47, 48, 49, thiab50 (Daim duab2) tso tawmib qho tseem ceeb inhibition ntawm superoxide anion tiam, nrog IC50 tus nqi xws li3.3 ± 0.9 rau7.7 ± 0.9 µM piv nrog rau qhov zoo tswj LY294002 (IC50 1.1 ± 0.3 µM). Ntxiv mus,48, 50, thiab51 (Daim duab2) qhia qhov tseem ceeb inhibition ntawm elastase tso tawmnrog IC50 muaj nuj nqis xws li 5.3± 0.2 rau 8.3± 0.8 µM piv nrog qhov zootswj LY294002 (IC50 3.2 ± 1.0 µM) (Table2). Cov tshuaj48 thiab50 tso tawm ob qho tib siinhibitions ntawm superoxide anion tiam thiab elastase tso tawm, qhia lawv ntau yamanti-inflammatory bioactivities. Cov koob ntawmP. morrisonicola covtau tshaj tawm tias muajib qho tshuaj tiv thaiv kab mob hauv RAW 264.7 macrophages [13]. Cov kws sau ntawv tau qhia tiasepicatechin thiabp-coumaric acid qhia nyob rau hauvP. morrisonicola covtej zaum yuav yog cov khoom xyaw nquag.Hauv kev tshawb fawb tam sim no, tag nrho cov active compounds muaj cov pob txha flavone zoo sib xwsrau ntawm epicatechin thiabp-coumaroyl moiety kuj tuaj yeem pom hauv49, 50, thiab51. Qhov no qhia tias flavonoid thiabp-coumaroyl pab pawg ua haujlwm tuaj yeem pab txhawbcov tshuaj tiv thaiv kab mob bioactivity nyob rau hauv txoj kev tshawb no. Cov txiaj ntsig bioassay no qhia tiasflavonoids ua lub luag haujlwm tseem ceeb hauvPinushom tshuaj tiv thaiv kab mob bioactivity.

Rooj 2.Inhibitory teebmeem ntawm purified compounds ntawm superoxide anion tiam thiab elastase tso tawmlos ntawm tib neeg neutrophils teb rau fMLF/CB.

Daim duab 2.Cov qauv ntawm cov qauv kev tiv thaiv kab mob45, 47, 48, 49, 50, thiab51. 

3.3. Molecular Docking Study

Lub hnub nyoog cuam tshuam txog kev poob qis hauv GH qib yog suav tias yog cov tsos mob ntawm neuroendocrinekev laus [57]. Qhov tshwm sim no muaj nyob hauv ntau hom tsiaj xws li tib neeg, hauv tsevdev, thiab kuaj nas [57]. Hauv tib neeg, GH qib hauv plasma pib txo qisnrog hnub nyoog tom qab tag nrho lub cev maturation thiab txuas ntxiv mus rau lub xyoo caum ntawm lub neej [57]. Ghrelin tau txheeb xyuas tias yog cov ligand endogenous rau GHSR thiab yog tus tswj hwm tseem ceeb ntawmGH secretion [18,19]. Ghrelin koom nrog ntau yam physiological thiab pathophysiologicalmechanisms nyob rau hauv tib neeg xws li kev laus [24,25]. Tsis tas li ntawd, ghrelin tej zaum yuav xav txogmuaj feem xyuam rau cov kev tiv thaiv kab mob. Kev ua kom lub cev tiv thaiv kab mob tau txwv los ntawm ghrelinKev kho mob los ntawm inhibition ntawm NF-κB activation thiab tom qab MCP-1 secretion [26]. Ib qho hluavtaws ghrelin analog loj hlob hormone-tso peptide-2 (GHRP-2) tau tshaj tawmkom txo tau cov kab mob inflammatory yam nyob rau hauv arthritic nas, thiab nws txhawb kom lub cev tiv thaiv kab mob.tau kho los ntawm kev ua kom cov ghrelin receptors [27]. Neeb et al. kuj tau npajtxoj cai ntawm o raws li kev tiv thaiv kev laus [58]. Yog li, raws li covAnti-inflammatory bioassay cov ntaub ntawv sim,45, 47, 48, 49, 50, thiab51 (Daim duab2) qhiaCov teebmeem tseem ceeb inhibitory thiab raug xaiv los txiav txim siab lawv lub peev xwm khi rau lubghrelin receptor. Ua ntej docking simulation, haiv neeg ligand (8QX) suav nrog hauv 6KO5PDB fifile tau rov docked rau validation. Kev sib cuam tshuam ntawm 8QX thiab 6KO5 thiab covQhov zoo tshaj plaws pose ntawm xam cov txiaj ntsig tau pom zoo sib xws thiab rov ua dua nrog cov ntaub ntawv ib txwm muaj(cov ntaub ntawv tsis qhia). Cov txiaj ntsig tau qhia qhov tseeb ntawm qhov kev simulation uas twb muaj lawmthiab txhawb kev suav ntxiv.

Qhov qis tshaj khi zog ntawm txhua lub ligand tau suav hais tias yog qhov zoo tshaj plaws conformation. Covbinding affinities yog teev nyob rau hauv Table3. Kev loj hlob hormone-tso peptide 6 (GHRP-6) yogsiv los ua ib qho kev tswj xyuas zoo rau docking rau lub hnab ntawv khi ntawm ghrelin receptor raws li nyob rau hauv pebtsab xov xwm dhau los. Txawm hais tias AutoDock Vina tsis yog tsim los rau docking ntawm peptidesthiab cov proteins, ntau cov txiaj ntsig tau zoo tau luam tawm hauv cov ntawv tshaj tawm dhau los [59–61]. Yog li ntawd, hauv txoj kev tshawb no, GHRP-6 tau raug suav ua ntej los txiav txim qhov tseeb ntawmtam sim no docking qauv thiab cov txiaj ntsig tau zoo sib xws (Daim duab3A). Piv nrog GHRP-6,cov binding zog ntawm49, 50, thiab51 tau qis dua−10.3 kcal / mol (Table3). Qhov noqhia tias49, 50, thiab51 tuaj yeem ntsaws rau hauv hnab tshos ntawm ghrelin receptor zoo ib yam lossistxawm zoo dua li ntawm GHRP-6. Rau49, hydrogen bonds tuaj yeem pom ntawmob pawg carbonyl (C-4 thiabp-coumaroyl) thiab Arg283, C-5 hydroxyl thiab Gln120,C-7 hydroxyl thiab Tyr313, thiab C-40 hydroxyl thiab Cys304, feem. Arg199 tsim apa hydrogen daim ntawv cog lus nrog ib pawg carbonyl ntawmp-coumaroyl. Ntxiv rau,49 yogtxuas rau Arg283, Arg102, Asp99, Phe279, Phe312, Leu181, thiab Pro200 residues ntawmlub ghrelin receptor ntawm ntau yam teebmeem xws li covπ- cation,π-anion,π–π T-shaped, thiabπ- alkyl kev sib cuam tshuam. Cov no tso cai compound49 thiab protein los tsim ib qho chaw ruaj khov(Daim duab3B). 50 tau khi nrog Asp99, Arg102, Gln120, Arg283, Leu103, Asn305, thiabArg199 los ntawm ntau yam hydrogen bonds, thaum lwm yam kev sib cuam tshuam (π- cation,π-anion,π–π T-shaped, thiabπ-alkyl) kuj tau pom nrog Asp99, Arg102, Arg283, Phe279, Phe312,Leu 181, thiab Leu 210 (Fig3C). 51 kuj tsim hydrogen lossis carbon-hydrogen bondsnrog Tyr313, Ser123, Arg283, Arg102 thiab Asn305, nrog rau lwm yam kev sib cuam tshuam (π- cation,π-anion,π-sigma,π–π T-shaped, thiabπ-alkyl) txuas nrog Asp99, Arg283, Arg102, Leu181,Phe312, thiab Pro200 residues ntawm ghrelin receptor tuaj yeem kuaj pom (Daim duab3D). Piv rautshuaj sib xyaw45, 47, thiab48 nrog49, 50, thiab51, cov pab pawg qub tau muaj cov flavonoidpob txha tsuas yog thaum pawg tom kawg muaj qab zib thiab coumaroyl moieties. Nws tau tshaj tawm tiaspawg coumaroyl txuas rau ntawm cov suab thaj yog qhov tseem ceeb rau kev sib txuas nrog rau ghrelinreceptor [34]. Cov qauv sib txawv ntawm GHSR cuam tshuam nrog acyl acid moiety ntawm ghrelinua rau kev hloov pauv ntawm ghrelin receptor rau hauv kev teeb tsa nquag [43]. Ntxiv mus, lub hnab ntawv khi ntawm GHSR yog bifurcated los ntawm tus choj ntsev ntawm Glu124.thiab Arg283, thiab cheeb tsam no yog nplua nuj nyob rau hauv hydrophobic amino acids [43]. Raws li pebcov ntaub ntawv, cov qhab nia docking ntawm49, 50, thiab51 tau siab dua cov45, 47, thiab48, qhopom zoo kom muaj peev xwm khi tau zoo dua. Cov yam ntxwv tseem ceeb ntawm cov qauv yog covcoumaroyl pawg ntau dua li cov piam thaj moieties thiab qhov no tuaj yeem ua pov thawj ntxiv los ntawm covkev soj ntsuam ntawm ntau cov tebchaw muaj coumaroyl functionalities. Hauv qhov kev tshawb fawb no, lubcov khoom xyaw nquag49, 50, thiab51 muaj tsis tau tsuas yog anti-inflammatory bioactivity tab sis kujlub ghrelin receptor binding peev xwm. Qhov no qhia tau hais tias tus thov anti-aging teebmeem ntawmPine koob tshuaj yej kuj tseem yog raws li cov tshuaj yej ghrelin zoo li cov tebchaw.

4. Cov lus xaus

Tag nrho ntawm xya caum-tsib cais cais suav nrog kaum tsib yam tsis tau piav qhia yog puri-txheeb xyuas los ntawm methanol extracts ntawmP. taiwanensiskoob. Lawv cov qauv tau characterizedlos ntawm spectroscopic thiab spectrometric analyses. Plaub caug-peb purified compounds tautshuaj xyuas lawvanti-inflammatory kev ua silos ntawminhibition ntawm superoxide anion tiamthiabelastase tso tawm ntawm tus qauv neutrophil. Cov txiaj ntsig qhia tias45, 47, 48, 49, 50, thiab51 muaj qhov tseem ceebanti-inflammatory muaj peev xwm. Ntxiv molecular dockingsuav cov txiaj ntsig tau txais kev txhawb nqa49, 50, thiab51 qhia txog kev khi affinity rau tus activehnab tshos ntawm ghrelin receptor. Yog li ntawd, lub crude extracts thiab purified constituents ntawmP. taiwanensismuaj peev xwm tsim los ua cov tshuaj tiv thaiv kab mob ua npaws tshiab lossiscov khoom xyaw zaub mov.

Cov khoom siv ntxiv:Cov hauv qab no muaj nyob online ntawm, Daim Ntawv Ntxiv A: Ua tiav cov txheej txheem rho tawm thiab cais tawm,Daim Ntawv Ntxiv B: Cov ntaub ntawvntawm paub cov tebchaw, Table S1: Kev tshuaj xyuas ua ntej bioactivity ntawm koob ntawmP. taiwanensisntawm superoxideanion tiam thiab elastase tso tawm los ntawm tib neeg neutrophils teb rau fMLF / CB,Tab S2: Inhibitory teebmeem ntawm purified compounds ntawm superoxide anion tiam thiab elastasetso tawm los ntawm tib neeg neutrophils teb rau fMLF/CB, Daim duab S1–S35: HRMS thiab NMR spectra ntawmcov tshuaj tshiab

1–5. Tus sau kev koom tes:Conceptualization, P.-CK thiab JTCT; Methodology, P.-CK thiab T.-LH;Kev Tshawb Fawb, Y.-CL, AMK thiab M.-LY; Resources, S.-YW; Cov ntaub ntawv curation, Y.-CL thiab G.-HY;Kev Sau Ntawv—kev npaj ua ntej, P.-CK thiab Y.-CL; Sau — tshuaj xyuas thiab kho, P.-CK Txhuacov kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:Txoj kev tshawb no tau txhawb nqa los ntawm Ministry of Science thiab Technology, Taiwan (MOST). CovKev tshawb fawb tau txhawb nqa ib feem los ntawm Kev Kawm Qib Siab Sprout Project, Ministry of Education rau covHeadquarters ntawm University Advancement ntawm National Cheng Kung University (NCKU).

Institutional Review Board Statement:Txoj kev tshawb no tau ua nrog kev pom zoo los ntawm Lub Tsev HaujlwmSaib xyuas lub tsev kho mob Chang Gung Memorial (IRB No. 201800369A3).Cov Lus Qhia Txog Kev Pom Zoo:Daim ntawv qhia tuaj yeem muab tau raws li qhov kev thov.

Cov ntaub ntawv muaj nyob:Cov ntaub ntawv qub tuaj yeem tau txais los ntawm tus kws sau ntawv raws li kev thov.

Kev lees paub:Cov kws sau ntawv kuj ua tsaug rau Chang Gung Memorial Tsev Kho Mob (CMRPD1B0281~3,CMRPF1D0442~3, CMRPF 1F0011~3, CMRPF1F0061~3 thiab BMRP450 muab rau T.-LH) rauib feem ntawm kev txhawb nqa nyiaj txiag ntawm kev tshawb fawb tam sim no. Cov kws sau ntawv ua tsaug lees paub txog kev siv NMRCov cuab yeej siv los ntawm Instrument Center ntawm National Cheng Kung University.

Kev tsis sib haum xeeb ntawm kev txaus siab:Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.

Cov ntaub ntawv

1. Xie, Q. Liu, Z.; Li, Z. Tshuaj muaj pes tsawg leeg thiab antioxidant kev ua ntawm cov roj yam tseem ceeb ntawm rauPinustaxa nyob rau Suav teb.Molecules2015, 20, 9380–9392. [CrossRef] 

2. Kim, KY; Chung, HJ Flavor compounds ntawm Pine sprout tshuaj yej thiab Pine koob tshuaj yej.J. Agric. Khoom noj khoom haus Chem.2000, 48, 1269–1272. [CrossRef] 

3. Park, G.; Paudyal, DP; Hwang, I.; Tripathi, GR; Yaj, Y.; Cheong, H. Kev tsim cov fermented koob rho tawm los ntawm cov ntoo thuv liab thiablawv functional characterization.Biotechnol. Bioprocess Eng.2008, 13, 256. [CrossRef]

4. Idžojtic, M.; Kajba, D.; Franji'c, J. Sib txawv ntawm F1 hybridsP. nigraJF Arnold× P. sylvestrisL., P. nigraJF Arnold× P. densifloraSiebold et Zucc.,P. nigraJF Arnold× P. thunbergianaFranco thiab lawv cov niam txiv hom los ntawm koob volatile muaj pes tsawg leeg.Biochem.Syst. Ecol.2005, 33, 427–439. [CrossRef] 

5. Kim, YS; Shin, DH Volatile Cheebtsam thiab tshuaj tua kab mob los ntawm Pine koob (Pinus densiflfloraS. and Z.) rho tawm.Khoom noj khoom haus Microbiol.2005, 22, 37–45. [CrossRef] 

6. Dob, T.; Berramdane, T. Essential roj muaj pes tsawg leeg ntawmPinus halepensisMill. los ntawm peb cheeb tsam sib txawv ntawm Algeria.J. Essent. Roj Res.2007, 19, 40–43. [CrossRef] 

7. Nam, AM; Tomi, F.; Gibernau, M. Casanova, J.; Bighelli, A. Composition thiab tshuaj variability ntawm koob roj los ntawmPinus halepensisloj hlob hauv Corsica.Chem. Biodivers.2016, 13, 380–386. [CrossRef] 

8. Sib, E.; UAS, O.; Demirci, IB; Ba¸ser, KHC Cov ntsiab lus ntawm cov roj yam tseem ceeb ntawmPinus nigraArnold los ntawm Qaib Cov Txwv.Turk. J. Cheem.2010, 34, 313–325.