Current Perspective in the Discovery of Anti-aging Agents from Natural Products

Natural Products and Bioprospecting, May 2017

Aging is a process characterized by accumulating degenerative damages, resulting in the death of an organism ultimately. The main goal of aging research is to develop therapies that delay age-related diseases in human. Since signaling pathways in aging of Caenorhabditis elegans (C. elegans), fruit flies and mice are evolutionarily conserved, compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human. Natural products have special resource advantage and with few side effect. Recently, many compounds or extracts from natural products slowing aging and extending lifespan have been reported. Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C. elegans or other species, and the prospect in developing anti-aging medicine from natural products.

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Current Perspective in the Discovery of Anti-aging Agents from Natural Products

Current Perspective in the Discovery of Anti-aging Agents from Natural Products Ai-Jun Ding . Shan-Qing Zheng . Xiao-Bing Huang . Ti-Kun Xing . Gui-Sheng Wu . Hua-Ying Sun . Shu-Hua Qi . Huai-Rong Luo 0 1 2 3 4 0 G.-S. Wu H.-R. Luo Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou 646000, Sichuan , China 1 A.-J. Ding S.-Q. Zheng X.-B. Huang T.-K. Xing University of Chinese Academy of Sciences , Beijing 100039 , China 2 A.-J. Ding S.-Q. Zheng X.-B. Huang T.-K. Xing G.-S. Wu H.-Y. Sun H.-R. Luo State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, Yunnan , China 3 H.-R. Luo (&) Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences , 134 Lanhei Road, Kunming 650201, Yunnan , China 4 S.-H. Qi Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences , Guangzhou 510301, Guangdong , China Aging is a process characterized by accumulating degenerative damages, resulting in the death of an organism ultimately. The main goal of aging research is to develop therapies that delay age-related diseases in human. Since signaling pathways in aging of Caenorhabditis elegans (C. elegans), fruit flies and mice are evolutionarily conserved, compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human. Natural products have special resource advantage and with few side effect. Recently, many compounds or extracts from natural products slowing aging and extending lifespan have been reported. Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C. elegans or other species, and the prospect in developing antiaging medicine from natural products. Aging; Natural products; Anti-aging; Drug screening 1 Introduction 2.2 Proteostasis and Aging DR pathway cAMP AMPK NAD SIR-2.1 TSC1/2 TOR S6K eIF Translation IIS pathway APP-1 AGE-1 DAF-18 p p IST-1 PDK-1 DpAF-16 p AKT-1 SGK-1 AKT-2 DAF-2 Germline signal KRI-1 TECR-1 JNK DA DAF-12 Mitochondrial dysfunction Inflamation, Apotosis, Senescence Immune CUB-like genes ROS Protein Homeostasis, DNA lesions MAPK PMK-1 Pathogen signal Nuclear SIR-2.1 DAF-16 DAF-12 SKN-1 DR effects Detoxification, Stress, Immune, Apotosis Reproduction Detoxification I I P C n n s i l h a t c n i a em tax h s HN H N N O O O is e s a a n e i e c r l a a a i e ll c m c e i r t a a u u b L o c S S : e s o n in n t I c s ea g laa , ;se lev m itn D-g iton ikn le in lau ]9 o 4 e g 1 by cun tcy dP a r [ s e 1 e , d f r t 6 e c ry an c n 1 c i in a du rg to 2 ]8 id F n e a E 1 % x A i in m g 1 .5 io D ice lho am in ,7 8 tn d c 1 2 a n m c fl n 1 a t g i l san: and rf n a [ a s en in g b ta N c v in e r g n / s o c r lee ap -1 e r u : d n p d ts e . se N e s im re ra ag C ilf SK HN H O 2 , t n IS - a n I ti id ea g n x -a ) n a o r 6 m it d ti o e n tc IL s a a ( o : f p o r p in la u e g e s -6 sa re ic i e , m rso ikn c n r t u in ad ed ecn lre ]0 i n n n I I I e t s: d c n n n n a a a I I H O I I m c a 2 n , 1 .enC ifseanp ]03 irseaen tirssea tiiadon tr[ssse o l 1 c g x [ n t a i- n e t a m g an idx in tin sed iton sea laug po a re re ro :is cn ,t p s i n p a d e n s .0% ixd a f o ] tivy sm leo :37 tin 311 ti i d e a [ c n o ia d 1 a ah m isv an H g c e in e n ree an TU it-agn igngm iruM []130 .cS ilfsep ,ir2S n n A a I I O O t ) r 3 e p an OD rek )[1 s ito se em D icn ign a iv (M t an tu t % la a e .7 u % eh la y : d x u a am ]4 r n % io te a 0 t . n sga an 6 a m [1 n n n I I I O O NH N 2 H ls in a d ic ir e m p e s h e t n a :a lla lp t y e ea ta h t r n p e o r e o rc so a id g u re L( tr yZ o S C ic m S 14 t to in ,2 [ - op se -F 16 i p a A -F tan it-a rec D A , n g D e an i in t d v ti d % la n a n a d a .00 gu ,3 m in C ilf SK I I , g M gu , no s: [1 e yg ti n y R a r ega ahg a : h e iec tpo ilfo .le tpo ed ]5 in .1 6 s 4 e -2 -1 o 1 s p [ R F rpo tan rcean IgS DA d id i in d n x t n a o % la a i y t .0 u , t n 0 g 43 tiicv isnm :cea s:1 red -C a a i n n N g ch a a U n e m g n , i g le a 1 g m n e p i-a g ig . se K tn ing a C ilf SE n n A a I I i i e F ] s A 7 .0% tiox rcea gD [14 21 an sga an 14 re D .m ean .e sep K D m C ilf PM I I in f ry m te o r te eb ro li in d u f o m ien irc c rana and s b O O O N N HN O a u eh rm e e g e tf fo idm itdo ) trsa can ro ed an en le? A ra ev iz ti i c D f b o id o en un A o m n x ic d i N t e r o n a d ( oo m u H O u m s e s a c a g r g a u r s o a S S c i s o l n a i c u i q m a e rg h a C S ic ph in g h seng troo seea itlan taed n y r u l a c g l r t am in re ce n d - ap in an i tan ilfse tead ,ino c t an li c e e p t d e n u n s e e a a g n y re g ,h t c n t iv sm in ti it i la ow ]62 c n % u r a a 0 g g [1 h . e l g c 9 r a g in e :e up on inn g m r -a g ic d u ra i n m an en le tn ig n A a I O O H H O O H O suo fo itir yn [1 tnm iton gnn ised se3e a i x a sc in sa o sp e b re ic a n m c tr c se co ed in fo g u a G in nd id , t i x 2 a l ts io X u a t P g r n e a G r ia : , ,t t a 7 an en im HD ]6 id m e x ] e h A 16 o 5 d sc g [ ti 6 ra i in 2 an [1 lu ic t L n la 2 :s E c o u E ta R sa rh eg F r A v c r N I I s t n ,tn ryo g ti- iad ta lin n x m , an a o d it am tem isg e n fl s s a ropo :ice irpon ssaey tieann p m f r c o e d b n ced le m /t a y t tiicv isnm i-en teh and teh i-aagng ecaghm lt-saacgo ltiagung tiseokn titiavng ,]67168 itn ing D re cy ca [1 n A a I e lsa isd c o i n e m s e n h i H O H H H O O O O H H O H O O , e n ag in I3K l a a h m sp p se P e fe to a g fn li au rce tiin i n -1 n b i i % ea tg h .0 m A 0% in 3 . 1 5 NH NH H O NH 2 H N O H O O O e l n 0 m e e 3 m se v u [3 in le fl in re n e e e i n e r s h , e s e a t n g a th rec gn itao 22 rec rfu in ig l p in s y s n t d % a e h HN H m ] y 6 t in 7 iv sm 1 ti i e [ c n sa tn a a h re a g c n e icn ixd i g m o a i - g % t i n .0 an tn ig 3 A a 3 e a e a e a NH O O NH N H N H H C O m ] ty 6 in 7 iv sm 1 ti i e [ c n sa tn a a h re a g c n e icn ixd i g m o a i - g % t i n .0 an tn ig 6 A a 1 N O N m ] ty in 67 iv sm 1 ti i e [ c n sa tn a a h re a g c n e icn ixd i g m o a i - g % t i n .0 an tn ig 5 A a 1 C C m ] ty in 76 iv sm 1 ti i e [ c n sa tn a a h re a g c n e icn ixd i g m o a i - g % t i n .0 an tn ig 5 A a 2 NH N S O HN l l C N S H N N m ] ty in 76 iv sm 1 ti i e [ c n sa tn a a h re a g c n e icn ixd i g m o a i - g % t i n .0 an tn ig 2 A a 1 HN O O O tin tI , g s in a ) i s l D nd itr lo iad I a th yk o SA in ra n r a in te (N ap teo ,s a sn g e s i p no ru th fo itr te d t o th u e a r c itcv tryo tre itno iad ,isa lsee am tod am tao lity m m d -2 am se a u n fl u fl e o OX in is in rh sp O S O N H N H NH g th ly g ceu ta lcu in g l rew illn icay red lep sav l-o tron trd doo to eop irod idp co an lb sed in ac i 2 O O N n e o m i ti e c a n fi c a e li t d p a p re icd a t d se a n F o sp io A rop ilfe tac D p y ng d an lg it n e a a d v m e i c t y in an ac t iv sm it i e v d c n s d n a ah rae a a n e in ing tsc g c c i g m c u a u d i n .0% red rpo - g tn ig 1 A a 2 c i l t a io ic ib n t li n H H Chemicals Structure With anti-aging activities in two aging models 51-28-5 2,4-Dinitrophenol 91-53-2 Ethoxyquin 1001645-58-4 SRT1720 307297-39-8 Epitalon 34592-47-7 Thiazolidine carboxylic acid 133550-30-8 AG-490 4431-00-9 Aurintri-carboxylic acid OH O OH OH 15.0% increase in mean lifespan and regulating p66ShcA [355] Table 4 continued 91742-10-8 Chemicals HA-1004 (dihydrochloride) Structure 103745-39-7 HA-1077 (Fasudil) 5108-96-3 Pyrrolidine dithiocarbamate 75529-73-6 Amperozide hydrochloride 145915-58-8 DAPH (4,5dianilinophthalimide) BRL 15572 433695-36-4 BRL 50481 18.0% increase in mean lifespan and inhibiting protein kinase [354] 15.0% increase in mean lifespan and inhibiting protein kinase [354] 16.0% increase in mean lifespan and inhibiting NF-jB [356] Table 4 continued 53177-12-1 EUK-8 Chemicals Structure A.-J. Ding et al. Anti-aging activity and proposed anti-aging mechanism Cl- Mn3+ 98299-40-2 Hexahydro-siladiphenidol 142273-20-9 Kenpaullone 83846-83-7 Ketanserin tartrate 13614-98-7 Minocycline hydrochloride Table 4 continued Chemicals 66104-23-2 Pergolide methanesulfonate Structure 497-27-8 58-33-3 7681-67-6 4-Phenyl-3 Furoxancarbonitrile Promethazine hydrochloride Propionylpromazine hydrochloride Trans-3,5dimethoxy-4fluoro-4hydroxystilbene Trans-2,4,5trihydroxystilbene 78416-81-6 Trequinsin hydrochloride Table 4 continued 274-85-1 138090-06-9 Chemicals 1,2,4-Triazolo[1,5a]pyridine (R,R)-cis-Diethyltetrahydro-2,8chrysenediol 2390-54-7 Thioflavin T 175698-05-2 3,3-Diethyl-2pyrrolidinone 631-64-1 Dibromoacetic acid 82-76-8 N-Phenyl periacid(ANSA) Structure 51314-51-3 Benzimidazole derivative M084 References 6 n in 9 n e []46 isaen []65 eanm i-cndu ,and isaen []66 eanm iseaen []68 eanm ]69 a l , e r sou lta ean 70P ]1 e e M ] d rc A 3 an n i 7 g 1 n laem tilanu li[gn ifseap a l ] in reg ng n 4 a 7 1. L. 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Ai-Jun Ding, Shan-Qing Zheng, Xiao-Bing Huang, Ti-Kun Xing, Gui-Sheng Wu, Hua-Ying Sun, Shu-Hua Qi, Huai-Rong Luo. Current Perspective in the Discovery of Anti-aging Agents from Natural Products, Natural Products and Bioprospecting, 2017, 1-70, DOI: 10.1007/s13659-017-0135-9