Meta Analysis And Network Pharmacology Of Traditional Chinese Medicine In The Treatment Of Primary Osteoporosis

R e s e a r c h b a c k g r o u n dP ri m ar y o s t eo p o ro s i s(P OP)i s a m u l t i fact o ri al d i s eas e rel at ed t o l o w b o n e m as s an d i n cr ea s ed b o n e fr a gi l i t y.It m ai n l y i n cl u d es s en i l e o s t e o p o ro s i s(S OP)an d p o s t m en o p au s al o s t eo p o ro s i s(P M OP).P OP i s u su al l y r el at ed t o t h e l o s s o f p o s t m en o p au s al es t ro g en o r t h e d et eri o rat i o n o f a g e-r el at e d b o n e m i cr o s t ru ct u re.Wi t h t h e i n cre as i n g a g i n g p o p u l at i o n an d t h e i n cre as i n g p ro p o rt i o n o f p o s t m en o p au s al wo m en i n C h i n a,t h e i n ci d en ce o f P OP i n cre as es ye a r b y ye ar,wh i ch s e ri o u s l y a ffe ct s t h e q u al i t y o f l i fe o f p at i en t s.Al t h o u gh wes t ern m ed i ci n e h as a c ert ai n e ffect o n t h e t reat m en t o f P OP,i t s ad v e rs e rea ct i o n s ca n n o t b e u n d er es t i m at ed,an d t h e t reat m en t p l an n e ed s t o b e i m p ro v e d.In re cen t ye ars,ex p ert s an d s ch o l ars h av e p u b l i s h ed m an y cl i n i cal r es e arch l i t e r at u re o n t r ad i t i o n al C h i n es e m ed i ci n e i n t h e t reat m en t o f P OP,wh i ch p ro v i d e s a l a rge n u m b e r o f t h eo ret i cal an d d a t a s u p p o rt f o r cl i n i cal p ra ct i c e,b u t l ack o f s t ri ct s ys t em at i c ev al u at i o n o f t h es e l i t e rat u res;t h e effe ct i v e a ct i v e i n g red i e n t s,t arg et s a n d m ech a n i s m s o f t h es e d ru g s ar e n o t co m p l et el y cl e a r,wh i ch n e ed fu rt h er s t u d y.R e s e a r c h o b j e c t i v eM et a an al ys i s was u s ed t o ev al u at e t h e c l i n i cal e ffi ca c y an d m ed i cat i o n ch ar act eri s t i cs o f t ra d i t i o n al C h i n es e m e d i ci n e i n t h e t r eat m e n t o f P OP,s o a s t o p ro v i d e a r el i ab l e ev i d en ce-b as e d b as i s fo r t h e p r ev en t i o n a n d t reat m en t o f P OP b y t r ad i t i o n al C h i n es e m ed i ci n e;At t h e s am e t i m e,ex cav a t e i t s co re d ru g co m b i n at i o n,an d r ev eal t h e p o s s i b l e m e c h an i s m o f i t i n t h e t reat m en t o f P OP t h ro u gh n et wo r k p h arm a co l o gi c al m et h o d s,s o as t o p r o v i d e r ef er en c e fo r s u b s eq u en t cl i n i cal a p p l i cat i o n an d ex p eri m en t al r es e arch.R e s e a r c h o b j e c t i v eM et a-an al ys i s was u s ed t o ev al u at e t h e c l i n i cal e ffi ca c y an d m ed i cat i o n ch ar act eri s t i cs o f C h i n es e m ed i ci n e i n t h e t r eat m en t o f P OP,s o as t o p ro v i d e rel i ab l e ev i d en c e-b as ed e v i d en c e fo r t h e p rev en t i o n an d t r eat m en t o f P OP b y C h i n es e m ed i ci n e.A t t h e s am e t i m e,t h e co re d ru gs i n t h e l i t e rat u r e i n cl u d ed i n t h e M et a an al ys i s we re ex cav at ed,an d t h e e ffe ct i v e a ct i v e c o m p o n en t s,t arget s an d m ech an i s m o f a ct i o n o f co r e d ru gs i n t h e t re at m e n t o f P OP w ere rev e al ed b y n et wo rk p h arm aco l o g y m et h o d,s o as t o p ro v i d e ref er en c e fo r s u b s eq u en t cl i n i cal a p p l i cat i o n an d ex p eri m en t al r es e arch.R e s e a r c h m e t h o d1.Li t er at u res o n r a n d o m i z ed co n t ro l l e d t ri al s(R C Ts)o f t rad i t i o n al C h i n es e m ed i ci n e(TC M)i n t h e t reat m en t o f P OP p u b l i s h ed i n m aj o r d at ab as es at h o m e a n d ab ro ad we re co m p reh en s i v el y r et ri ev ed fro m C NK I,C h i n a Bi o m ed i c al Li t erat u r e Dat ab as e,Wan fan g P eri o d i cal Dat ab as e,V IP Fu l l-t ex t Dat ab as e,Bi o m ed i cal In fo rm at i o n Dat ab as e o f N a t i o n al M ed i cal Li b r ar y o f t h e Un i t e d S t at es,Ex cer P t a M ed i ca D at ab as e,C o ak l an d Li b r ar y an d Web o f S ci en c e.Th e ret ri ev al d at e was fro m t h e es t a b l i s h m en t o f t h e d at ab as e t o Oct o b er 3 1,2 0 2 1.Li t erat u re s cre en i n g w as car ri e d o u t ac co r d i n g t o t h e i n cl u s i o n an d ex cl u s i o n cri t er i a o f t h e r es e arch.Aft er s cre en i n g t h e l i t erat u r e t h at m eet s t h e req u i rem en t s,t h e b as i c i n fo rm at i o n ch ar act e ri s t i c t ab l e o f t h e l i t e rat u re was d es i gn ed an d t h e rel ev an t d at a o f t h e i n cl u d ed l i t erat u r e was ex t rac t ed t o ev al u at e t h e q u al i t y o f t h e l i t erat u re.Th e o ri gi n a l d at a o f t h e i n cl u d ed l i t erat u r e w er e an al yz ed b y R e Vm an 5.3 0 s o ft wa re.T h e rel ev an t r es u l t s w ere ex p res s ed b y d r awi n g fo r es t m ap.If t h er e was o n l y o n e l i t erat u r e i n cl u d ed i n t h e o u t co m e i n d ex,d es cri p t i v e an al ys i s was p er fo rm ed.If t h e n u m b er o f l i t e r at u re i n cl u d ed i n t h e o u t co m e i n d i cat o rs i s m o re t h an 1 0,t h e p u b l i cat i o n b i as o f t h e l i t er at u re s h o u l d b e an al yz ed b y d rawi n g fu n n e l p l o t s;i f t h e h et ero g en ei t y o f t h e res u l t s o b t ai n ed b y M et a-an al ys i s i s t o o l arge,s u b g ro u p an al ys i s s h o u l d b e co n d u ct ed o n t h e s o u rc es o f h et ero g en ei t y.At t h e s am e t i m e,s e n s i t i v i t y an al ys i s w a s co n d u ct e d t o ev al u at e t h e s t ab i l i t y an d rel i ab i l i t y o f t h e res e ar ch r es u l t s;an d t h e co r e d ru gs i n t h e ap p l i cat i o n o f p res c ri p t i o n s i n t h e l i t erat u r e w er e m i n ed b y co r rel at i o n an al ys i s.2.Th e effe ct i v e a ct i v e i n g red i en t s an d a ct i o n t arg et s o f t h e co re d ru gs wer e s c re en ed b y T C M S P d at ab as e.Th e P OP d i s e as e t a rg et n am es w ere co l l ect ed i n Gen ec ar d s,OM IM,D ru g B an k,TTD,an d P h arm GKB d at ab as es.Th e i n t ers e ct i o n o f d ru g t a r get s an d d i s eas e t a rget s w as t ak e n,an d t h e d ru g-eff ect i v e i n g re d i en t s-i n t ers ect i o n t arg et n et wo rk d i a gr am was d r awn.Th e i n t ers ect i o n t a rg et s wer e i m p o rt ed i n t o S TR ING p l at fo rm fo r p ro t ei n i n t era ct i o n an al ys i s,an d i m p o rt ed i n t o C yt o s c a P e s o ft wa re t o o p t i m i z e P P I n et wo rk an d co n d u ct t o p o l o gi cal a n al ys i s,s o as t o s c re en p o t e n t i al i m p o rt an t t arget s.T h en,t h e ce l l co m p o s i t i o n,m o l ecu l ar fu n ct i o n,b i o l o gi c al p ro ces s es an d s i gn al i n g p at h w a ys i n v o l v ed i n t h e co m m o n t arg et s we re a n al yz e d o n t h e M et as c a P e p l at fo rm,an d t h e i t em s wi t h h i gh en ri ch m en t wer e d es c ri b ed.An al yz e t h e p o t en t i a l m ech an i s m o f d ru g act i o n.R e s e a r c h r e s u l t s1.M et a an a l ys i s res u l t sA t o t al o f 2 3 0 1 a r t i cl es we re ret ri ev e d fro m d o m es t i c a n d fo r ei gn d at ab as es,an d 2 6 a rt i cl es w er e i n cl u d e d aft e r s c re en i n g fo r i n cl u s i o n a n d ex cl u s i o n cri t eri a.T h e p u b l i cat i o n an d p u b l i cat i o n t i m e o f t h e l i t er at u r e wer e co n c en t rat ed i n 2 0 0 3-2 0 2 1.T h e q u al i t y o f t h e l i t er at u re w as a cce p t ab l e.Th e o b s erv at i o n i n d ex es i n cl u d ed t o t al e ff ect i v e rat e,b o n e m i n e ra l d en s i t y,TC M s ym p t o m s co r e,b o n e p ai n s co re,b o n e m et ab o l i c m ark er s,s af et y an d m ed i cat i o n ch a ra ct e ri s t i cs o f t h e i n cl u d ed l i t er at u r e.Th e res u l t s w er e as fo l l o ws.To t al effe ct i v e rat e : 2 4 art i cl es r ep o rt ed t h at t h ere w as n o h et e ro gen ei t y i n t h e gro u p(I 2 = 1 9 %,P = 0.2 0),co m b i n ed e ff ect(M D = 1.2 0,9 5 % C I[ 1.1 5,1.2 5 ],Z = 9.0 1,P < 0.0 0 0 0 1),t h e d i ffer en c e w as s t at i s t i cal l y s i gn i fi can t,s u g g es t i n g t h at t r ad i t i o n al C h i n es e m ed i ci n e t r eat m en t o f P OP cu rat i v e effe ct i s re m ark ab l e.S u b g ro u p an al ys i s o f t h i s s t u d y s h o w ed t h at C h i n es e m ed i ci n e g r o u p(M D = 1.1 4,9 5 % C I [ 1.0 8,1.2 1 ],Z = 4.7 5,P <0.0 0 0 0 1),C h i n es e m e d i ci n e co m b i n ed w i t h w es t e rn m e d i ci n e gro u p(M D =1.2 4,9 5 % C I [ 1.1 7,1.3 1 ],Z = 7.7 0,P < 0.0 0 0 0 1),t h e d i ffe ren ce w as s t at i s t i cal l y s i gn i fi ca n t,s u g ges t i n g t h at C h i n es e m ed i ci n e,C h i n es e m ed i ci n e co m b i n ed wi t h w es t ern m ed i ci n e i n t h e t reat m e n t o f P OP cu rat i v e e ff ect i s rem a rk ab l e.Lu m b ar v ert eb ral b o n e d en s i t y : 2 1 a r t i cl es rep o rt ed t h at t h ere w as h et ero g en ei t y i n t h e gr o u p(I 2 = 9 3 %,P < 0.0 0 0 0 1).T h e r es u l t s o f s u b g ro u p an al ys i s s h o wed t h at t h e d i ff er en c e w as s t at i s t i cal l y s i gn i fi ca n t b et w een t h e C h i n es e m ed i ci n e g r o u p(M D = 0.0 5,9 5 % C I [ 0.0 2,0.0 7 ],Z = 3.2 6,P =0.0 0 1)an d t h e C h i n es e m ed i ci n e c o m b i n ed wi t h wes t ern m ed i ci n e g ro u p(M D = 0.1 3,9 5 % C I [ 0.0 6,0.1 9 ],Z = 4.0 3,P < 0.0 0 0 1),s u g g es t i n g t h at C h i n es e m ed i ci n e a n d C h i n es e m ed i ci n e c o m b i n ed wi t h w es t ern m ed i ci n e h av e s i gn i fi ca n t t h e rap e u t i c e ff ect s o n i m p ro v i n g l u m b a r v ert e b ral b o n e d en s i t y i n p at i en t s w i t h P OP.La rg e t ro ch an t eri c b o n e m i n er al d en s i t y : 4 art i cl es r ep o rt ed t h at t h er e was h et ero g en ei t y wi t h i n t h e gro u p(I 2 = 6 8 %,P = 0.0 2),co m b i n ed effe ct(M D = 0.0 3,9 5 % C I [-0.0 1,0.0 7 ],Z = 1.3 3,P = 0.1 8),t h e d i ffe ren ce w as n o t s t at i s t i cal l y s i gn i fi can t,s u g g es t i n g t h at t h er e i s n o s u ffi ci en t ev i d en c e t h at t rad i t i o n al C h i n es e m ed i ci n e c an i m p ro v e t h e b o n e m i n eral d e n s i t y o f P OP p at i en t s.Bo n e m i n e ral d en s i t y o f gre at e r t r o ch an t e r: 4 l i t er at u r es rep o rt ed t h at t h e co m b i n ed effe ct s h o wed g re at h e t ero gen ei t y(I 2 =6 8 %,P =0.0 2),(M D=0.0 3,9 5 %C I[-0.0 1,0.0 7 ],Z=1.3 3,P =0.1 8),s u g ges t i n g t h at t h e re i s n o t en o u gh ev i d en ce t h at t rad i t i o n al C h i n e s e m ed i ci n e can i m p ro v e t h e b o n e m i n eral d en s i t y o f g r eat e r t ro ch an t er i n p at i en t s wi t h P OP.Ward ’ s t ri an gl e b o n e m i n er al d en s i t y : 5 art i cl es rep o rt ed t h at t h ere was h et ero g en ei t y wi t h i n t h e g ro u p(I 2 = 9 1 %,P < 0.0 0 0 0 1),c o m b i n ed e ffe ct(M D = 0.0 3,9 5 % C I [-0.0 1,0.0 7 ],Z = 1.4 2,P = 0.1 6),t h e d i ffe ren ce w as n o t s t at i s t i cal l y s i gn i fi can t,s u g ges t i n g t h at ev i d en c e i s n o t en o u gh t o p ro v e t h at t rad i t i o n al C h i n es e m e d i ci n e ca n i m p ro v e Wa rd ’ s t ri an g l e b o n e m i n er al d en s i t y i n p at i en t s w i t h P OP.TC M s ym p t o m s c o re : 1 2 l i t erat u r es r ep o rt ed t h at t h ere was h et ero g en ei t y i n t h e gr o u p(I 2 = 9 8 %,P < 0.0 0 0 0 1).Aft er s u b g ro u p an al ys i s,t h e r es u l t s s h o w ed t h at t rad i t i o n al C h i n es e m ed i ci n e g ro u p(M D =-1.7 7,9 5 %C I [-2.5 0,-1.0 5 ],Z = 4.8 2,P < 0.0 0 0 0 1),t rad i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h wes t e rn m ed i ci n e gro u p(M D =-2.5 6,9 5 % C I [-4.0 6,-1.0 5 ],Z = 3.3 3,P = 0.0 0 0 9),t h e d i ffe ren ce was s t at i s t i cal l y s i gn i fi c an t,s u g g es t i n g t h at t rad i t i o n al C h i n es e m ed i ci n e an d t ra d i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h wes t e rn m ed i ci n e c an i m p ro v e t h e s ym p t o m s o f P OP p at i e n t s.Bo n e p ai n s co re : 1 0 l i t erat u r es rep o rt ed t h at t h ere was h et ero g en ei t y i n t h e gr o u p(I 2 = 9 5 %,P < 0.0 0 0 0 1).Aft er s u b g ro u p an al ys i s,t h e res u l t s s h o wed t h at t h e t r ad i t i o n al C h i n es e m e d i ci n e gr o u p(M D =-1.8 0,9 5 % C I[-2.4 8,-1.1 3 ],Z = 5.2 6,P < 0.0 0 0 0 1),t r ad i t i o n al C h i n es e m e d i ci n e co m b i n ed wi t h wes t e rn m ed i ci n e gro u p(M D =-1.4 4,9 5 % C I [-2.0 2,-0.8 6 ],Z = 4.9 0,P < 0.0 0 0 0 1),t h e d i ff er en c e wa s s t at i s t i cal l y s i gn i fi can t,s u g ges t i n g t h at t rad i t i o n al C h i n es e m ed i ci n e an d t ra d i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h wes t ern m ed i ci n e h av e s i gn i fi can t t h era p eu t i c e ff ect s i n red u ci n g b o n e p ai n i n p at i e n t s wi t h P OP.S eru m OC : 8 l i t era t u res r ep o rt e d t h at t h ere was h et ero g en e i t y i n t h e gr o u p(I 2 = 8 2 %,P < 0.0 0 0 0 1).Aft er s u b g ro u p an al ys i s,t h e res u l t s s h o wed t h at t h e t r ad i t i o n al C h i n es e m ed i ci n e gro u p(M D = 1.5 4,9 5 % C I [ 0.9 9,2.0 8 ],Z = 5.5 5,P < 0.0 0 0 0 1),t rad i t i o n al C h i n e s e m ed i ci n e co m b i n e d wi t h wes t e rn m ed i ci n e gro u p(M D = 1.2 3,9 5 % C I [ 0.2 0,2.2 6 ],Z = 2.3 5,P = 0.0 2),t h e d i ffe ren ce was s t at i s t i cal l y s i gn i fi c an t,s u g g es t i n g t h at t rad i t i o n al C h i n es e m ed i ci n e an d t rad i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h w es t ern m ed i ci n e h av e s i gn i fi ca n t t h e r ap eu t i c e ff ect s i n i m p ro v i n g s e ru m OC i n p at i en t s wi t h P OP.S eru m P INP : Fi v e art i cl es rep o rt ed t h at t h ere w as n o h et ero g en ei t y i n t h e g ro u p(I 2 = 0 %,P = 0.8 0),an d t h e co m b i n ed effe ct(M D = 4.7 8,9 5 % C I[ 3.6 6,5.9 1 ],Z = 8.3 2,P < 0.0 0 0 0 1).Th e d i ffe ren ce w as s t at i s t i c al l y s i gn i fi can t,s u g ges t i n g t h at t r ad i t i o n al C h i n es e m e d i ci n e h as r em ark ab l e t h erap eu t i c effe ct i n i m p ro v i n g s eru m P INP i n p at i en t s wi t h P OP.S eru m B-A LP : Th re e l i t er at u res rep o rt ed t h at t h er e w as h et er o g en ei t y i n t h e g ro u p(I 2 = 8 1 %,P = 0.0 0 5).Aft er s u b g ro u p a n al ys i s,t h e res u l t s s h o wed t h at t rad i t i o n al C h i n es e m ed i ci n e gro u p(P < 0.0 5)an d t r ad i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h wes t e rn m ed i ci n e gro u p(M D = 3.8 9,9 5 %C I [ 1.8 2,5.9 5 ],Z = 3.6 9,P = 0.0 0 0 2),t h e d i ff ere n ce was s t at i s t i c al l y s i gn i fi can t,s u g g es t i n g t h at t ra d i t i o n al C h i n es e m ed i ci n e a n d t rad i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h we s t ern m ed i ci n e h a v e s i gn i fi c an t t h erap eu t i c effe ct s i n i m p ro v i n g s er u m B-A LP i n p at i en t s wi t h P OP.S eru m TR AC P-5 b : F o u r a rt i cl es r ep o rt ed t h at t h e re was h et e ro g en ei t y i n t h e gro u p(I 2 = 5 3 %,P = 0.0 9).Th e res u l t s o f s u b gr o u p an al ys i s s h o wed t h at t h e d i ff ere n c e w as s t at i s t i cal l y s i gn i f i can t b et w een t h e C h i n es e m ed i ci n e gr o u p(M D =-0.3 4,9 5 % C I [-0.6 2,-0.0 7 ],Z = 2.4 4,P = 0.0 1)an d t h e C h i n es e m ed i ci n e co m b i n ed wi t h w es t ern m ed i ci n e g ro u p(M D =-0.7 6,9 5 %C I [-1.0 2,-0.5 0 ],Z = 5.7 4,P < 0.0 0 0 0 1),s u g ges t i n g t h at C h i n es e m ed i ci n e i s effe ct i v e i n red u c i n g s er u m TR AC P-5 b i n p at i en t s wi t h POP.Trad i t i o n al C h i n es e m ed i ci n e co m b i n ed wi t h wes t e r n m ed i ci n e h as o b v i o u s t h erap eu t i c eff ect o n re d u ci n g s e ru m TR AC P-5 b i n P OP p at i en t s.Serum β-CTX : Six literatures reported that there was heterogeneity in t h e g ro u p(I 2 = 9 9 %,P < 0.0 0 0 0 1),an d t h e co m b i n ed e ff ec t am o u n t(S M D= 0.4 2,9 5 % C I [-1.0 7,1.9 2 ],Z = 0.5 5,P = 0.5 8).T h e d i ff eren ce w as n o t s t at i s t i cal l y s i gn i fi c an t,s u g g es t i n g t h at t h ere w as n o s u ffi ci en t ev i d en ce t o s h o w t h at t ra d i t i o n al C h i n es e m e d i ci n e was effe ct i v e i n red u ci n g s eru mβ-CTX levels in patients with POP.Fas t i n g 2-h o u r u ri n a r y C a / c r : 5 art i cl es r ep o rt ed t h at t h er e w as n o h et ero g en ei t y wi t h i n t h e g ro u p(I 2 = 1 5 %,P = 0.3 2),co m b i n ed effe ct(M D=-0.0 5,9 5 % C I [-0.0 9,-0.0 2 ],Z = 2.8 5,P = 0.0 0 4),t h e d i ff eren ce was s t at i s t i cal l y s i gn i fi c an t,s u g g es t i n g t h a t t rad i t i o n al C h i n es e m ed i ci n e i s eff ect i v e i n r ed u ci n g fas t i n g 2-h o u r u ri n a r y C a / c r i n p at i en t s wi t h P OP.S eru m es t rad i o l : T h ree art i cl es rep o rt ed t h at t h er e w as n o h et ero g en ei t y i n t h e gro u p(I 2 = 0 %,P = 0.5 2),an d t h e co m b i n e d eff ect(S M D =1.0 4,9 5 % C I [ 0.7 5,1.3 4 ],Z = 6.9 8,P < 0.0 0 0 0 1).T h e d i ffe ren ce w as s t at i s t i cal l y s i gn i fi c an t,s u g ges t i n g t h at t rad i t i o n al C h i n es e m ed i ci n e h as rem a rk ab l e t h er ap eu t i c eff ect i n i m p ro v i n g s e ru m es t r ad i o l i n p at i en t s wi t h P OP.M ed i cat i o n ch a ra ct e ri s t i cs : A t o t al o f 2 0 k i n d s o f t r ad i t i o n al C h i n es e m ed i ci n e we re u s ed i n 2 6 ref er en c es,wi t h 6 7 k i n d s o f d ru gs,a n d t h e t o t al u s e freq u en c y was 2 8 0 t i m es.Th e t o p s i x d ru gs w er e R ad i x R eh m an n i ae,R a d ix An g el i c ae S i n en s i s,R h i z o m a Dr yn ari a e,Fru ct u s C o rn i,H erb a Ep i m e d i i,an d R ad i x As t ra gal i.D ru g cat e go ri es t o b l o o d d ru gs,b l o o d d ru gs,Yan g m e d i ci n e,Qi m e d i ci n e,Yi n m ed i ci n e m o r e;co r e d ru g co m b i n at i o n s are R eh m an n i a gl u t i n o s a-C o rn u s o ffi ci n al i s,R eh m an n i a gl u t i n o s a-An g el i ca s i n en s i s,R eh m an n i a gl u t i n o s a-Ep i m ed i u m,Ac h yr an t h es b i d en t at a-An g el i ca s i n en s i s,Ep i m ed i u m-An gel i ca s i n en s i s;i n t h e as s o ci at i o n ru l es,t h e as s o ci at i o n co n fi d e n ce o f t h e t wo d ru gs was h i gh e r i n C o rn u s o ffi ci n a l i s > R eh m an n i a gl u t i n o s a,an d t h e a s s o ci at i o n co n fi d en c e o f t h e t h re e d ru gs was h i gh e r i n Cornus officinalis-> Rehmannia glutinosa.2.R es ea rch res u l t s o f n et wo rk P h a rm aco l o g yAft er s cr een i n g i n TC M S P d at ab as e,4 7 k i n d s o f s t an d ard effect i v e co m p o n en t s we re o b t ai n ed,i n cl u d i n g 2 k i n d s o f R eh m an n i a gl u t i n o s a,2 0k i n d s o f C o rn u s o ff i ci n al i s,2 k i n d s o f An g el i c a s i n en s i s a n d 2 3 k i n d s o f Ep i m ed i u m.Aft er d el et i n g t h e r ep e at ed v al u es,4 1 k i n d s o f t o t al e ff ect i v e co m p o n en t s i n t h e fo u r h erb s we re o b t ai n ed.A t o t al o f 6 7 1 e ff ect i v e co m p o n en t s co rr es p o n d i n g t arg et s we re o b t ai n ed,i n cl u d i n g 3 2 R eh m an n i a gl u t i n o s a,11 8 C o rn u s o ffi ci n al i s,6 4 An g el i ca s i n en s i s a n d 4 5 7 Ep i m ed i u m.A t o t al o f 2 1 2 t a rg et s w ere o b t ai n ed aft er d el et i n g t h e r ep e at ed t arg et s.A t o t al o f1 2 5 2 t o t al t a rget s w ere o b t ai n e d i n m u l t i p l e d at ab as es,i n cl u d i n g 1 2 d i s e as e t arget s i n OM IM d at ab as e,2 1 d i s e as e t arg et s i n Dru g Ba n k d at ab as e,2 7d i s eas e t a rget s i n TT D d at ab as e,3 d i s eas e t a rget s i n D ru g Ban k d at ab as e,an d11 8 9 d i s eas e t a rget s wer e o b t ai n ed wi t h co rr el at i o n s co re g r eat e r t h an 1 i n Gen e C ard s d at a b as e.1 2 1 7 d i s eas e t arg et s w er e o b t ai n ed aft er d el et i n g d u p l i cat e t a rget s.Th e o b t ai n ed d ru g t arg et s an d d i s ea s e t a rget s we re i n t ers e ct ed t o o b t a i n 7 5 d ru g-d i s eas e i n t ers e ct i o n t a rget s.P P I p ro t ei n i n t era c t i o n n et wo rk t o p o l o g y an al ys i s,1 5 co re t a rg et s wer e o b t ai n ed.GO fu n ct i o n al en ri ch m en t an al ys i s s h o wed t h at a t o t al o f 1 2 8 3 b i o l o gi c al p r o ces s i t em s were co l l ect e d,4 5 i t em s were o b t ai n ed i n t erm s o f cel l co m p o s i t i o n,an d1 0 0 i t em s we re o b t a i n ed i n t erm s o f m o l ecu l a r fu n ct i o n.In t erm s o f KEGG p at h wa y en ri ch m en t an al ys i s,1 6 8 en t ri es wer e o b t ai n ed..R e s e a r c h c o n c l u s i o n1.Th e u s e o f t rad i t i o n al C h i n es e m ed i ci n e i n t h e t re at m e n t o f P OP cl i n i cal cu rat i v e e ff ect,c an s i gn i fi c an t l y i m p ro v e t h e cl i n i c al s ym p t o m s o f p at i en t s,an d h i gh s afet y,l es s a d v ers e r eact i o n s;i t can al s o i m p ro v e t h e l ev el s o f b o n e m i n e r al d en s i t y an d rel at e d b o n e m et ab o l i c m a rk ers i n p at i en t s.2.On t h e b as i s o f co n v en t i o n al w es t er n m ed i ci n e t r eat m e n t co m b i n ed wi t h t rad i t i o n al C h i n es e m ed i ci n e t reat m en t,t h e cl i n i cal e ffi c ac y,i m p ro v em en t o f b o n e m i n er al d en s i t y an d b o n e m et ab o l i c m a rk ers i n p at i en t s wi t h P OP we re s i gn i fi can t l y b et t e r t h an t h o s e o f wes t ern m ed i ci n e t r eat m e n t,an d t h e ad v e rs e rea ct i o n s cau s ed b y s o m e wes t e rn m ed i ci n e co u l d b e r ed u c ed.3.In t h i s s t u d y,6 7 t r ad i t i o n al C h i n es e m e d i ci n es we re u s ed i n 2 6 art i cl es,am o n g wh i ch R eh m a n n i a gl u t i n o s a,C o rn u s o ffi ci n al i s,An g el i ca s i n en s i s an d Ep i m ed i u m we re t h e co re d ru gs fo r P OP i n t h i s s t u d y..4.Th e res u l t s o f n e t wo rk p h arm a co l o g y s u g g es t ed t h at t h e re gu l at o r y eff ect s o f R ad i x R eh m an n i ae P r ep a rat a,R ad i x An gel i c ae S i n en s i s,F ru ct u s C o rn i an d H erb a Ep i m ed i i o n b o n e m et ab o l i s m i n p at i e n t s wi t h P OP m a y b e rel at ed t o t h e act i o n o f k e y a ct i v e co m p o n en t s s u c h as q u e rc e t i n,k aem p fer o l,l uteolin and β-s i t o s t ero l o n IL6,AK T1,TN F,C AS P 3 a n d o t h er t arg et s t o re gu l at e t h e c an c er p at h wa y,AGE-R A GE s i gn al i n g p at h wa y,l i p i d an d at h ero s cl e ro s i s,ch e m i cal c ar ci n o gen-re c ep t o r act i v at i o n,P I3 K-Ak t an d o t h e r s i gn al i n g p at h w a ys.