The Effect of Xialiqi Capsule on Testosterone-Induced Benign...

Research ArticleThe Effect of Xialiqi Capsule on Testosterone-InducedBenign Prostatic Hyperplasia in Rats

Hongcai Cai 12 Guowei Zhang1 Zechen Yan 3 and Xuejun Shang 1

1Department of Andrology Jinling Hospital Affiliated to Southern Medical University Nanjing Jiangsu 210002 China2Family Planning Research InstituteCenter of Reproductive Medicine Tongji Medical CollegeHuazhong University of Science and Technology Wuhan Hubei 430030 China3Department of Surgery e First Affiliated Hospital Zhengzhou University Zhengzhou Henan 450052 China

Correspondence should be addressed to Zechen Yan yanzechenqqcom and Xuejun Shang shangxj98163com

Received 9 April 2018 Accepted 13 September 2018 Published 30 September 2018

Academic Editor Chang G Son

Copyright copy 2018 Hongcai Cai et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Benign prostatic hyperplasia (BPH) is common among elderly men of which inflammation oxidative stress proliferative andapoptotic changes play important roles Xialiqi (XLQ) capsule a traditional Chinese herbal formula is used as a potential drug intreating BPH This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH inrats Fifty male Sprague-Dawley rats were randomly divided into 5 groups sham control BPH model high and low dose of XLQand finasteride as a positive control group All groups were treated with appropriate drugsnormal saline for 28 consecutive daysProstate weights were recorded histopathological changes and content of IL-8 TNF-120572 DHT SODMDA caspase-3 and PCNA ofthe prostate were determined Animals with BPH demonstrated significantly increased prostate weights and prostate index higherlevels of IL-8 TNF-120572 DHT MDA and PCNA but lower activity of SOD and reduced expression of caspase-3 After treatmentwith XLQ significant reductions of prostate weights prostate index IL-8 TNF-120572 DHT MDA and PCNA increased activity ofSOD and higher level of caspase-3 were shown The present study indicates that XLQ can effectively prevent the development ofTP-induced BPHmodel through mechanisms of anti-inflammation antioxidation antiproliferation and proapoptosis

1 Introduction

Benign prostatic hyperplasia (BPH) is a common andrologi-cal disease among the elderly males BPH is remarkably char-acterized by histological proliferation of the epithelial cells inthe transitional zone of the prostate which leads to lower uri-nary tract symptoms (LUTS)The constriction of the urethracan result in increased frequency urgency and hesitancy ofurination and compromised urine flow which eventuallyimpacts the quality of life [1 2] Up to now the pathophys-iology of BPH is not fully clarified although many attemptshave been made in the past decades

Commonly testicular hormones and aging are two coreelements attributed to the genesis and development of BPHMoreover pathways of proliferationapoptosis and inflam-mation as long as oxidationantioxidation are considered tobe involved in the development of BPH which have beensupported by many researches during the past decades [3ndash7]

Medicinal therapy remains the first line treatment formost patients Given the importance of DHT in the devel-opment of BPH inhibitors of 5120572-reductase (eg finasterideand dutasteride) which prevents the conversion of DHT fromtestosterone and reduces DHT level and thereby suppresseshyperplastic growth of theprostateareused in theclinical treat-ment of BPH [8] Nevertheless finasteride-associated unto-ward reactions are regularly reported including gynecomas-tia headache dizziness chest pain upper respiratory infec-tions decrease libido erectile dysfunction and male infer-tility due to a reduced sperm count [9ndash12] Such side effectscause the limitation of conventional drugs used for BPH andnevertheless might be prevented by other safe agents

Xialiqi (XLQ) capsule is a traditional Chinese herbalformula considered as a multicomponent agent composingof eight herbs (Astragali Radix Ligustri Lucidi FructusCinnamoni Cortex Talcum Phellodendri Amurensis CortexAmber Prunellae Spica and Litchi Semen see in Table 1)

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2018 Article ID 5367814 9 pageshttpsdoiorg10115520185367814

2 Evidence-Based Complementary and Alternative Medicine

Table 1 Composition of XLQ capsule

Latin name Amount (g) Ratio () SourceAstragali Radix 70 461 Inner Mongolia ChinaLigustri Lucidi Fructus 14 92 Zhejiang ChinaCinnamoni Cortex 28 18 Guangxi ChinaTalcum 14 92 Liaoning ChinaPhellodendri Amurensis Cortex 7 46 Jilin ChinaAmber 21 14 Liaoning ChinaPrunellae Spica 21 138 Jiangsu ChinaLitchi Semen 21 138 Guangdong ChinaTotal 1519 100

which as a whole produces an effect of antiproliferation pro-apoptosis anti-inflammation analgesia and microcircula-tion improvement as previously reported [13ndash18] For in-stance Prunellae Spica as one of the main components ofXLQ capsules is reported to reduce the levels of the propro-liferative factors (Cyclin D1 and CDK4) as well as downreg-ulate the proangiogenic factors and increase the proapop-totic BaxBcl-2 rate [17] And Litchi Semen can inhibit theproliferation of HepG2 cells which may be concerned withthe property of proapoptosis [15] Another major componentAstragali Radix is reported to play a potential anti-inflam-matory activity which is widely used in oriental medicinefor tonifying the immune response and improving circulation[14] Recently XLQ capsule has been used in the treatment ofBPH at the early and midstage achieving a sound result asthose clinical drugs (unpublished) Although previous stud-ies have observed the pharmacological effects of similar tradi-tional herbal formula [4 19ndash22] there have been no studiesof XLQ capsule on its possible protective effects against BPH

Therefore the current study was aiming to investigate therole of XLQ capsule in the development of BPH by establish-ing a testosterone-induced BPH model in rats Our researchwill help to provide an experimental basis for the develop-ment of new agents for the prevention and treatment of BPHon clinic

2 Material and Methods

21 Drugs The herbal medicine of XLQ capsule was pur-chased from Shijiazhuang Yiling Pharmaceutical Co Ltd(Shijiazhuang Hebei China Z20123085) in February 2015The composition of XLQ capsule is listed in Table 1 The pow-der of the medicine was dissolved in adequate normal saline(NS) according to different doses and stored in 4∘C beforeuse

22 Animals Fifty specific pathogen free (SPF) grade adultmale Sprague-Dawley (S-D) rats weighed 200 to 250 gwere purchased from Department of Comparative MedicineJinling Hospital Affiliated to Nanjing University School ofMedicine (Nanjing Jiangsu China) for the study The ratswere kept on a standard laboratory diet and water ad libitumandwere adapted to laboratory environment (20-26∘C) under

a 12 h light-dark cycle for one week before experiment Allexperiments were performed according to the National Insti-tutes of Health Guide for the care and use of Laboratory Ani-mals and international ethical guidelines and were approvedby Institutional Animal Care and Use Committee of JinlingHospital Affiliated to Nanjing University School of Medicine(SYXK (M) 2012-0047)

23 Establishment of Testosterone Propionate-Induced RatModel of BPH Establishment of BPH rat model and experi-mental procedures were carried out as previously described[7] The rats were assigned into five groups randomly (10ratsgroup) And with the exception of the sham operationcontrol group four groups of rats were anesthetized withintraperitoneal injection of phenobarbital (50 mgkg) andcastrated aseptically to remove bilateral testes All castratedrats were injected with testosterone propionate (TP ZhejiangXianju Pharmaceutical Co Ltd Taizhou Zhejiang China)05 mgkgd (dissolved in corn oil) subcutaneously (SC) oneweek after castration The BPH model was induced through28 consecutive days of TP treatment which was further con-firmed by histopathological examination of prostate tissueThen one group was served as a model group while theother three served as experimental groups The experimentalgroups were treated with high dose (120 gkgd) and lowdose (061 gkgd) ofXLQ by intragastric administration (ig)for 28 days Finasteride dissolved in ultrapure water (08mgkgd ig HangzhouMerck China J20120071) was servedas a positive control group

Body weight (BW) of the rats were recorded every weekthroughout the whole study Following the final injectionand overnight fasting the rats were anesthetized with pen-tobarbital (50 mgkg intraperitoneal injection ip) Bloodsampleswere collected and prostate tissueswere immediatelyseparated and weighed Prostate lobes sections were fixedwith 4 paraformaldehyde for histological and immunohis-tochemical analysis and the remaining prostate sectionswerestored at -80∘C for further analysis

24 Assessment of Prostate Weight (PW) and Prostatic Index(PI) PW and BWof the rats were recorded in all groupsThePI was computed as PWBW times100 and the mean PI ratioswere computed in each group The percentage of inhibition

Evidence-Based Complementary and Alternative Medicine 3

of PW and PI was computed as follows 100ndash[(TndashC)(BndashC)times100] where C B and T are the values of the control groupBPH group and treatment group respectively

25 Histopathological Examination Theprostate tissues werefixed in 10 formalin immediately for 24 h Prostate sampleswere then paraffin-embedded and sectioned at thickness of 5120583m After dewaxing and rehydration prostate sections weremounted on slides and stained with hematoxylin and eosin(HampE) for routine histological examination under a lightmicroscopy (Olympus Tokyo Japan)

26 ELISAAssay of Interleukin- (IL-) 8 Tumor Necrosis Factor(TNF)-120572 and DHT Expressions of IL-8 TNF-120572 and DHTin the serum and prostate tissues were measured by enzyme-linked immunosorbent assay (ELISA) kits according to themanufacturerrsquos instructions (AMEKO Inc Shanghai China)The absorbance was recorded at 450 nm and values arerecorded as permL for serumandpermgprotein for the pros-tate

27 Immunohistochemical Staining of ProliferatingCell NuclearAntigen (PCNA) Immunohistochemistry was carried out onthickness of 4 120583m sections after deparaffinization Antigenwas retrieved by citrate buffer (pH 60) with 95∘C (micro-wave) for 10 min followed by peroxides quenching with 3 H2O2in PBS for 10min After washing with PBS the sections

were preblocked with normal goat serum for 10 min Theslides were incubated with the primary antibody anti-PCNA(mouse monoclonal antibody ab29 Abcam CambridgeUK) in a dilution of 1 200 for overnight at 4∘C Next thesections were incubated with biotinylated secondary anti-bodies in a dilution of 1 1000 for 1 h Following a washingstep with PBS the streptavidin-HRP was added Lastly thesections were rinsed with PBS and developed with diamino-benzidine tetrahydrochloride substrate (DAB) in 10 minEach of the sections was observed for more than three ran-dom regions at times 200 and times 400

28 Measurement of Superoxide Dismutase (SOD) ActivityandMalondialdehyde (MDA) Concentration SOD activity inthe serum and prostate were determined by a commerciallyavailable kit (Beyotime Nantong China) following the man-ufacturing instructions The absorbance was determined at450 nm and SOD activity is expressed as UL serum andUmg protein Concentration of MDA in the serum andprostate were detected by a commercial kit (AMEKO IncShanghai China) following the manufacturerrsquos instructionsThe absorbance was also determined at 450 nm after addingstop solution within 10min andMDA values are expressed asnmol MDAL serum pmol MDAg protein

29 Immunofluorescent Assay of Caspase-3 Similar experi-mental procedures were carried out as those in immunohis-tochemistry until the step of primary antibody reaction ofwhich the slides were incubated with anti-caspase-3 (rabbitmonoclonal antibody ab32150 Abcam Cambridge UK) ina dilution of 1100 for overnight at 4∘C After three times of

rinsing with PBS sections were incubated with secondaryantibody at a dilution of 1500 in PBS with 15 normalblocking serum at room temperature for 50 min The slideswere rinsed three times with PBS and were counterstainedwith DAPI (sc-3598 Santa Cruz Biotech CA USA) tovisualize the nuclei

210 Statistical Analysis Graph Pad Prism 60 (GraphPadSoftware Inc La Jolla CA USA) was adopted for statisticalanalyses Data are expressed as the mean plusmn SEM One-wayANOVAwas used for comparisons of group data followed bythe post hoc test (Dunnetts test)The 005 level of probabilitywas considered as statistical significant

3 Results

31 XLQ Decreased the PW and PI of BPH Rats Rats in theBPH group demonstrated significantly greater PW and PIthan those in the sham operation control group while PW inthe XLQ-treated groups were markedly reduced compared tothemodel group (Table 2 and Figure 1(a)) Finasteride-treatedgroup also exhibited with obvious decreases in PW and PINo significant differences in BW changes were observedamong groups Compared with the control the percentagesof inhibition on PW in high dose of XLQ low dose of XLQand finasteride groups were 4818 2649 and 5954respectively and the percentages of inhibition on PI were4754 2732 and 5792 respectively (Table 2)

32 XLQ Prevented the Morphological Changes of ProstaticTissues in BPH Rats There were no morphological changesin the lining epithelium or the acini of the sham operationcontrol group Cuboidal epithelial cells of regular size wereobserved However after TP-induction disrupted morphol-ogy in the prostate epitheliawas shownby significant thicken-ing hypertrophy and hyperplasia with papillary projectionsin the lining epithelium or the acini And widening of thelumen diameter without remarkable expansion in the stromawas also found in the model group

After treatment mild epithelial hyperplasia was shownin finasteride-treated group compared with the model groupSimilar reduction in epithelial hyperplasia was also shownin XIQ-treated animals compared with BPH animals Noremarkable inflammatory cells were detected in the XLQ- orfinasteride-treated groups (Figure 1(b))

33 XLQ Alleviated the Inflammation in BPH Rats A signifi-cant increase in serum IL-8 and TNF-120572 level was shown inthe BPH group (1712 plusmn 073 ngml and 180 plusmn 006 ngmlrespectively Plt001) compared with the sham operationcontrol group (571 plusmn 065 ngml and 055 plusmn 004 ngmlFigure 2(a)) On the contrary rats in the finasteride-treatedgroup demonstrated a significantly reduction of serum IL-8 and TNF-120572 level (1048 plusmn 076 ngml and 113 plusmn 005ngml respectively Plt001) compared with the BPH groupSimilar to finasteride-treated group significant reductions inIL-8 and TNF-120572 levels were also shown in the XLQ-treatedgroups compared with the BPH group (742 plusmn 071 ngml and


Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

lowast

lowast

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

1500

1000

500

600 4

3

2

1

0

400

200

Pros

tate

wet

wei

ght (

mg)

Pros

tate

inde

x (m

gg)

Body

wei

ght (

g)

0 0

(a)

HE

times 20

0H

Etimes

400

Normal Control BPH Model FinasterideHigh dose XLQ Low dose XLQ

(b)

Figure 1 Effects of XLQ on the histopathological appearance of the prostate prostate weight body weight and prostate index of BPH rats(a) Effects ofXLQ on prostate weight body weight and prostate index (b) Effects ofXLQ on the histopathological appearance of the prostateUp hematoxylin and eosin (HampE) staining times200 down HampE staining times400 lowast versus the sham operation control group Plt001 Δ versusthe model of BPH group Plt001 versus the high-dose XLQ group Plt001 998771 versus the low-dose XLQ group Plt001 Error bars indicateSEM

Table 2 Effects of XLQ capsule on prostate weight body weight and prostate index

Group (n=10) PW (mg) BW (g) PI (mgg) InhibitionPW PI

Sham operation control 47138plusmn1796 44556plusmn1927 106plusmn006 BPH model control 132615plusmn6020lowast 45944plusmn2110 289plusmn018lowast High-dose XLQ Capsule 91433plusmn3608Δ 45344plusmn1608 202plusmn008Δ 4818 4754Low-dose XLQ Capsule 109976plusmn4628Δ 46056plusmn1348 239plusmn011Δ 2649 2732Finasteride 81725plusmn5399Δ998771 44600plusmn1108 183plusmn010Δ998771 5954 5792lowast versus the sham operation control group Plt001 Δ versus the model of BPH group Plt001 versus the high-dose XLQ group Plt001 998771 versus the low-dose XLQ group Plt001 BW body weight PI prostate index PW prostate weight XLQ Xialiqi

084plusmn 005 ngml in the high-dose group respectivelyPlt001932 plusmn 060 ngml and 108 plusmn 007 ngml in the low-dosegroup respectively Plt001) Moreover among the treatmentgroups high-dose XLQ group decreased the most signifi-cantly

In the prostate similar results of IL-8 and TNF-120572 levelwere shown of which the high-dose XLQ-treated group(8986 plusmn 665 ngmg and 991 plusmn 063 pgmg respectivelyPlt001 Figure 2(a)) decreased the most significantly com-pared to the model of BPH group (17404 plusmn 524 ngmgand 1826 plusmn 081 pgmg respectively) and finasteride-treatedgroup (12606 plusmn 752 ngmg and 1241 plusmn 081 pgmg respec-tively Plt001)

34 XLQ Downregulated the Expression of DHT in BPH RatsA significant increase in serum DHT level was shown inthe BPH group compared with the sham operation controlgroup (1804 plusmn 062 ngm versus l751 plusmn 067 ngml Plt001Figure 2(b)) On the contrary a significantly reduction ofserum DHT level was displayed in the finasteride-treatedgroup (1011 plusmn 078 ngml Plt001) compared with the BPHgroup Likewise significant reductions in DHT levels wereobserved in theXLQ-treated groups (1102plusmn 080 ngml in thehigh-dose group Plt001 1224 plusmn 066 ngml in the low-dosegroup Plt001) compared with the BPH group However nosignificant difference was found between the high-dose XLQand finasteride-treated group (Pgt005)


lowast

lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0

25

20

15

10

5

0

20

15

10

05

00

TNF-

in

seru

m (n

gm

l)TN

F-

in p

rost

ate (

pgm

g)

IL-8

in se

rum

(ng

ml)

IL-8

in p

rost

ate (

pgm

g)

150

100

50

200

0

(a)

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0DH

T in

seru

m (n

gm

l)D

HT

in p

rost

ate (

pgm

g)

150

100

50

250

200

0

(b)

IHC

times200


IHC

times400

PCN

APC

NA

(c)

Figure 2 Effects of XLQ on the expression levels of IL-8 TNF-120572 DHT and PCNA in BPH rats (a) Effects of XLQ on the expression levelsof IL-8 TNF-120572 in the serum and prostate of BPH rats (b) Effects of XLQ on the expression levels of DHT in the serum and prostate of BPHrats (c) Effects of XLQ on the expression of PCNA in the prostate of BPH rats IHC immunohistochemistry lowast versus the sham operationcontrol group Plt001 Δ versus the model of BPH group Plt001 versus the high-dose XLQ group Plt001 998771 versus the low-dose XLQgroup Plt001 Error bars indicate SEM

In the prostate similar results of DHT level were shownof which the finasteride-treated group (10063 plusmn 578 pgmgFigure 2(b)) decreased most significantly compared to BPHgroup (18614 plusmn 626 pgmg Plt001) and XIQ-treated groups(10983plusmn 693 pgmg in the high-dose group Plt001 13359plusmn574 pgmg in the low-dose group Plt001)

35 XLQ Inhibited the Expression of PCNA in the ProstateThe expression of PCNA protein was elevated in the prostatetissues among BPH group comparing with the sham groupAfter treatment the expression of PCNA reduced in thefinasteride-treated group compared to the BPH groupReduction of expression of PCNA protein was also observedin the XIQ-treated groups in comparison to the BPH group(Figure 2(c))

36 XLQ Regulated the Level of SOD and MDA in BPHRats A significant decreased activity in serum SOD level wasdiscovered in the BPH group compared with the sham

operation control group (11605 plusmn 606 UL versus 24880plusmn 649 UL Plt001 Figure 3(a)) Conversely a significantlyincrease activity in serum SOD level was revealed in thefinasteride-treated group (19034 plusmn 666 UL Plt001) com-pared to the model group Likewise the XLQ-treated groupsalso demonstrated significant higher SOD levels in serum(21852 plusmn 783 UL and 19272 plusmn 638 UL in the high-and low-dose group respectively Plt001) Moreover amongthe treatment groups high-dose XLQ group increased themost significantly but no significant difference was exhibitedbetween the low-dose XLQ and finasteride-treated group(Pgt005) Conversely significant increased content of MDAin serum was indicated in the model of BPH group (2262 plusmn078 nmolL Plt001) compared to sham operation controlgroup (682 plusmn 060 nmolL) Among the treatment groupshigh-dose XLQ group seemed to decrease the most signifi-cantly (1140 plusmn 051 nmolL) And no difference was observedbetween the low-dose XLQ and finasteride-treated group


lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)

Figure 3 Effects of XLQ on the activity of SOD concentration of MDA and expression level of caspase-3 in BPH rats (a) Effects of XLQ onthe activity of SOD and concentration of MDA in the serum and prostate of BPH rats (b) Effects of XLQ on the expression of caspase-3 inthe prostate of BPH rats Magnificationtimes200 lowast versus the sham operation control group Plt001 Δ versus the model of BPH group Plt001 versus the high-dose XLQ group Plt001 998771 versus the low-dose XLQ group Plt001 Error bars indicate SEM

In the prostate similar results of SOD and MDA levelwere shown of which the high-dose XLQ-treated group (167plusmn 005 Ug and 12681 plusmn 784 pmolg respectively Plt001Figure 3(a)) changed themost significantly compared toBPHgroup (087plusmn 003Ug and 23108plusmn 940 pmolg respectivelyPlt001) and finasteride-treated group (146 plusmn 009 Ug and15439 plusmn 853 pmolg respectively Plt005)

37 XLQ Promoted the Expression of Caspase-3 in the ProstateTheexpression of caspase-3 protein significantly decreased inthe prostate tissues among BPH group compared to the shamgroup Expression of caspase-3 protein was reduced in theXIQ-treated groups comparing to the BPH group Further-more an increase of the expression of caspase-3 was also ob-served in the finasteride-treated group after treatment (Fig-ure 3(b))

4 Discussion

In the current study we discovered that XLQ capsule (120gkgd and 061 gkgd ig for 28 d) treatment couldsignificantly inhibit the development of TP-induced BPHwhich was confirmed by reduction in elevated PW PI and

histopathological changes Compared with the BPH ratsreductions in IL-8 TNF-120572 DHT MDA and PCNA levelsin both the prostate and serum and increases in SOD andcaspase-3 were found suggesting that XLQ might be aneffective drug for BPH treatment Above all this study willbe the first to provide experimental evidence for the widerapplication of XLQ capsule in clinics in the future

In previous studies using rat models changes in PWand histomorphology have been an important indicator forthe inhibitory effects of substances on the development ofBPH [23 24] BPH is commonly characterized by hyperplasiaof the epithelium and stroma in the prostate which resultsin an increase of the PW The hyperplastic prostate tissuemay gradually constrict the urethral canal to cause partialor sometimes even complete obstruction leading to lowerurinary tract obstruction [25] For these reasons by moni-toring the changes of PW previous studies have tested theinhibitory roles of various agents on BPH development Inthe present study XLQ reduced the PW PI and histologicalabnormalities in TP-induced BPH rats consistently as previ-ous studies [23 24] which supports the idea thatXLQ inhibitsBPHdevelopmentWhat ismoreXLQ at a dose of 120 gkgdseemed to achieve maximum efficacy in this BPH rat model


Inflammation is commonly presented in BPHwhichmaycause tissue injury and cytokines secreted from inflamma-tory cells can drive angiogenesis and local growth factorproduction in the tissues as a self-protection response [26]IL-8 and TNF-120572 as proinflammatory cytokines which areconsidered as potent growth factors for prostatic epithelialand stromal cells increase in BPH models according toprevious studies [7 27] Thus agents with the propertiesof anti-inflammation in BPH have been reported by manyresearches [28 29] In our study significant reduction ofTNF-120572 and IL-8 levels was determined in both serum andprostate in XLQ-treated groups compared to control groupsThis might suggest that anti-inflammation is involved in themechanisms of XLQ capsule in treating BPH although moreinvestigation of other cytokines would further strengthen ourconclusion

DHT an active metabolite of testosterone catalyzed by5120572-reductase is an important causative factor in BPH devel-opment [30] DHT can easily bind to ARs due to its higheraffinity to the androgen receptor (AR) which stimulates thegrowth for the epithelial and stromal cells in the prostate[8] Therefore DHT is basically responsible for prostaticepithelial and stromal cell hyperplasia [31] Finasteride as anelective drug targeting on 5120572-reductase has been reportedto reduce DHT levels in the serum and prostate of BPH[32 33] However because of the adverse effects the use of5120572- reductase inhibitors (eg dutasteride and finasteride) hasbeen limited [12 34] In our current study significant reduc-tions in DHT levels of the serum and prostate were observedinXLQ-treated groups compared with the BPHmodel groupas did the finasteride-treated group

Oxidative stress can possibly cause damage to the cellstissues even to organs by impairing important biomoleculesand cells which is considered as an important factor account-ing for the pathogenesis of BPH [35 36] Conversely antioxi-dants usually exist as compounds or enzymes could competewith oxidative substrates thus protecting the cellular struc-ture [37] Previous studies have demonstrated reductions ofantioxidant levels in both serumandprostate of BPHanimalswhile increasing oxidant in BPH model [22 24] In ourstudy we have found increased activity of SOD and decreasedcontent of MDA in XLQ-treated groups compared to controlgroups of which high dose of XLQ group changed themost significantly which is similar to previous studies Thesefindings support the opinion that XLQ capsule may treat BPHthrough the mechanism of antioxidation

PCNA a 36-kD DNA polymerase delta auxiliary proteinis specifically expressed in proliferating cell nuclei By far theexpression of PCNA in cell has been identified as a markerfor the G1S phase of the cell cycle which is related to thepathogenesis of BPH development [29 38] In our presentstudy a significant increased PCNA expression was detectedin the model group However this could be inhibited byXLQ administration as evidenced by immunohistochem-istry Caspase-3 an apoptotic biomarker is crucial for apop-tosis involved in the pathogenesis of BPH as testified bymanystudies [3 28] Consistent with previous reports our studyshowed that XLQ administration significantly increased thecaspase-3 levels in a TP-induced BPH rat model These

findings might suggest that the effects of XLQ on BPH devel-opment involve antiproliferative and proapoptotic activityalthough more researches are still needed

The drawback inherent to this study is that we did notcarry out experiments about the side effects of XLQ capsulesuch as hepatotoxicity and nephrotoxicity Therefore it isnecessary to monitor liver and renal function during XLQtreatment in the future study In addition due to castratedmodel of BPH it is impossible to detect the influence onmalereproductive system along with the long-term treatment It isstill unknown which ingredient of the compounds conducesto the activity of anti-BPH Moreover the specific signalingpathways involved to play the role of bioactivity remainselusive Last rodentmodel of BPHused in this study is indeedrather different from human beings [39] which will limitthe application of our results for human beings Accordinglymore researches upon the cellular and molecular levels likethe involvement of androgen and androgen receptor path-ways are still needed to further elucidate the underlyingmechanisms of XLQ in the treatment of BPH

In conclusion this study firstly demonstrates that XLQcapsule can reduced PW and PI and protect the morphologyof prostate tissue by the mechanisms of anti-inflammationantioxidation downregulation of DHT antiproliferation andproapoptosis of experimental BPH rats Therefore theseresults reveal that XLQ capsule effectively inhibits the devel-opment of TP-induced BPH rat model which strongly sup-ports the application of using XLQ capsule therapeutically inthe treatment of BPH in future

Data Availability

All data generated or analyzed during this study are includedin this article (and its supplementary materials)

Conflicts of Interest

Theauthors have declared that they have no conflicts of inter-est

Authorsrsquo Contributions

Hongcai Cai contributed to conception and design of thestudy Hongcai Cai and Guowei Zhang contributed to exper-iment performance Hongcai Cai contributed to statisticalanalysis and all authors are responsible for the interpretationHongcai Cai contributed to drafting and revising the manu-script all authors gave final approval of the manuscript tobe published Zechen Yan and Xuejun Shang contributedequally

Acknowledgments

This work was supported by the National Science amp Technol-ogy Pillar Program during the Twelfth Five-year Plan Period(2012BAI32B03)

Supplementary Materials

Supplementary Table S1 effects of XLQ on the level of IL-8and TNF-120572 in the serum and prostate Supplementary Table


S2 effects of XLQ on the concentration of DHT in the serumand prostate Supplementary Table S3 effects of XLQ onthe activity of SOD and concentration of MDA in the serumand prostate (Supplementary Materials)

References

[1] M Gacci G Corona M Salvi et al ldquoA systematic review andmeta-analysis on the use of phosphodiesterase 5 inhibitorsalone or in combination with alpha-blockers for lower urinarytract symptoms due to benign prostatic hyperplasiardquo Eur Urolvol 61 no 5 pp 994ndash1003 2012

[2] N D Patel and J K Parsons ldquoEpidemiology and etiology of be-nign prostatic hyperplasia and bladder outlet obstructionrdquoIndian Journal of Urology vol 30 no 2 pp 170ndash176 2014

[3] R T Atawia M G Tadros A E Khalifa H A Mosli and A BAbdel-Naim ldquoRole of the phytoestrogenic pro-apoptotic andanti-oxidative properties of silymarin in inhibiting experimen-tal benign prostatic hyperplasia in ratsrdquo Toxicology Letters vol219 no 2 pp 160ndash169 2013

[4] H ZhengW Xu J Lin J Peng and Z Hong ldquoQianliening cap-sule treats benign prostatic hyperplasia via induction of pro-static cell apoptosisrdquo Molecular Medicine Reports vol 7 no 3pp 848ndash854 2013

[5] H Jang W-J Bae S-M Yuk et al ldquoSeoritae Extract ReducesProstate Weight and Suppresses Prostate Cell Proliferation ina Rat Model of Benign Prostate Hyperplasiardquo Evidence-BasedComplementary and Alternative Medicine vol 2014 Article ID475876 7 pages 2014

[6] D Xu L Wang X Mei B Li J Lv and S Xu ldquoProtective effectsof seahorse extracts in a rat castration and testosterone-inducedbenign prostatic hyperplasia model and mouse oligosperma-tism modelrdquo Environmental Toxicology and Pharmacology vol37 no 2 pp 679ndash688 2014

[7] X Yang L Yuan C Xiong C Yin and J Ruan ldquoAbacopterispenangiana exerts testosterone-induced benign prostatichyperplasia protective effect through regulating inflammatoryresponses reducing oxidative stress and anti-proliferativerdquoJournal of Ethnopharmacology vol 157 pp 105ndash113 2014

[8] C Carson III and R Rittmaster ldquoThe role of dihydrotestoster-one in benign prostatic hyperplasiardquo Urology vol 61 no 4 pp2ndash7 2003

[9] G J Gormley E Stoner R C Bruskewitz et al ldquoThe effect offinasteride in men with benign prostatic hyperplasiardquoe NewEngland Journal of Medicine vol 327 no 17 pp 1185ndash1191 1992

[10] M C Uygur E Gur A I Arik U Altug and D Erol ldquoErec-tile dysfunction following treatments of benign prostatic hyper-plasia A prospective studyrdquo Andrologia vol 30 no 1 pp 5ndash101998

[11] A K Patel and C R Chapple ldquoMedical management of lowerurinary tract symptoms in men current treatment and futureapproachesrdquo Nature Clinical Practice Urology vol 5 no 4 pp211ndash219 2008

[12] K Chiba K Yamaguchi F Li M Ando andM Fujisawa ldquoFin-asteride-associated male infertilityrdquo Fertility and Sterility vol95 no 5 pp 1786e9ndash1786e11 2011

[13] H-X Sun F Qin and Y-J Pan ldquoIn vitro and in vivo immuno-suppressive activity of Spica Prunellae ethanol extract on theimmune responses in micerdquo Journal of Ethnopharmacology vol101 no 1ndash3 pp 31ndash36 2005

[14] M Ryu E H Kim M Chun et al ldquoAstragali Radix elicitsanti-inflammation via activation of MKP-1 concomitant withattenuation of p38 and Erkrdquo Journal of Ethnopharmacology vol115 no 2 pp 184ndash193 2008

[15] A H Xiong W J Shen L Y Xiao and J H Lv ldquoEffect ofSemen Litchi containing serum on proliferation and apoptosisof HepG2 cellsrdquo Zhong Yao Cai vol 31 no 10 pp 1533ndash15362008

[16] K-M Lau K-K Lai C-L Liu et al ldquoSynergistic interaction be-tween Astragali Radix and Rehmanniae Radix in a Chineseherbal formula to promote diabetic wound healingrdquo Journal ofEthnopharmacology vol 141 no 1 pp 250ndash256 2012

[17] W Lin L Zheng Q Zhuang et al ldquoSpica prunellae promotescancer cell apoptosis inhibits cell proliferation and tumorangiogenesis in amousemodel of colorectal cancer via suppres-sion of stat3 pathwayrdquo BMC Complementary and AlternativeMedicine vol 13 article 144 2013

[18] L Gao C Li ZWang et alNatural Product Research (FormerlyNatural Product Letters) vol 29 no 6 pp 493ndash510 2014

[19] I S Shin M Y Lee H K Ha C S Seo and H-K ShinldquoInhibitory effect of Yukmijihwang-tang a traditional herbalformula against testosterone-induced benign prostatic hyper-plasia in ratsrdquo BMC Complementary and Alternative Medicinevol 12 article 48 2012

[20] J Lin J ZhouWXu ZHong and J Peng ldquoQianliening capsuleinhibits benign prostatic hyperplasia angiogenesis via the HIF-1120572 signaling pathwayrdquo Experimental and erapeutic Medicinevol 8 no 1 pp 118ndash124 2014

[21] X Zhong J Lin J ZhouWXu andZHong ldquoAnti-proliferativeeffects of qianliening capsules on prostatic hyperplasia in vitroand in vivordquoMolecularMedicine Reports vol 12 no 2 pp 1699ndash1708 2015

[22] E Park M-Y Lee W-Y Jeon N Lee Ch-S Seo and H-KShin ldquoInhibitory Effect of Yongdamsagan-Tang Water Extracta Traditional Herbal Formula on Testosterone-InducedBenignProstatic Hyperplasia in Ratsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2016 Article ID 1428923 8 pages2016

[23] M L Arruzazabala R Mas VMolinaMNoaD Carbajal andN Mendoza ldquoEffect of D-004 a Lipid Extract from the CubanRoyal Palm Fruit on Atypical Prostate Hyperplasia Induced byPhenylephrine in Ratsrdquo Drugs in R amp D vol 7 no 4 pp 233ndash241 2006

[24] A E Ammar A Esmat M D H Hassona M G Tadros A BAbdel-Naim and E S T Guns ldquoThe effect of pomegranate fruitextract on testosterone-induced BPH in ratsrdquoe Prostate vol75 no 7 pp 679ndash692 2015

[25] C G Roehrborn ldquoMale lower urinary tract symptoms (LUTS)and benign prostatic hyperplasia (BPH)rdquo Medical Clinics ofNorth America vol 95 no 1 pp 87ndash100 2011

[26] M Scott Lucia and J R Lambert ldquoGrowth factors in benignpro-static hyperplasia Basic science implicationsrdquo Current UrologyReports vol 9 no 4 pp 272ndash278 2008

[27] G Penna B Fibbi S Amuchastegui et al ldquoThe vitamin D re-ceptor agonist elocalcitol inhibits IL-8-dependent benign pro-static hyperplasia stromal cell proliferation and inflammatoryresponse by targeting the RhoARho kinase and NF-kB path-waysrdquoe Prostate vol 69 no 5 pp 480ndash493 2009

[28] K Chung H An S Cheon K Kwon and K Lee ldquoBee venomsuppresses testosterone-induced benign prostatic hyperplasia


by regulating the inflammatory response and apoptosisrdquo Exper-imental Biology and Medicine vol 240 no 12 pp 1656ndash16632015

[29] C Kim K Chung S Cheon J Lee Y Park and H An ldquoRiceHull Extract Suppresses Benign Prostate Hyperplasia by De-creasing Inflammation and Regulating Cell Proliferation inRatsrdquo Journal of Medicinal Food vol 19 no 8 pp 746ndash754 2016

[30] J Miller and T H Tarter ldquoCombination therapy with dutas-teride and tamsulosin for the treatment of symptomatic en-larged prostaterdquo Clinical Interventions in Aging vol 4 pp 251ndash258 2009

[31] A Mizokami E Koh K Izumi et al ldquoProstate cancer stromalcells and LNCaP cells coordinately activate the androgen recep-tor through synthesis of testosterone and dihydrotestosteronefrom dehydroepiandrosteronerdquo Endocrine-Related Cancer vol16 no 4 pp 1139ndash1155 2009

[32] WD Steers ldquo5alpha-reductase activity in the prostaterdquoUrologyvol 58 Suppl 1 no 6 pp 17ndash24 2001 discussion 24

[33] S Aggarwal S Thareja A Verma T R Bhardwaj and MKumar ldquoAn overview on 5120572-reductase inhibitorsrdquo Steroids vol75 no 2 pp 109ndash153 2010

[34] A M Traish J Hassani A T Guay M Zitzmann and M LHansen ldquoAdverse Side Effects of 5120572-Reductase InhibitorsTher-apy Persistent Diminished Libido and Erectile Dysfunctionand Depression in a Subset of Patientsrdquo e Journal of SexualMedicine vol 8 no 3 pp 872ndash884 2011

[35] Z Durackova ldquoSome current insights into oxidative stressrdquoPhysiological Research vol 59 no 4 pp 459ndash469 2010

[36] U K Udensi and P B Tchounwou ldquoOxidative stress in prostatehyperplasia and carcinogenesisrdquo Journal of Experimental ampClinical Cancer Research vol 35 no 1 article 139 35 pages 2016

[37] M Sarbishegi M Khani S Salimi M Valizadeh and F S AvalldquoAntiproliferative and antioxidant effects of withania coagulansextract on benign prostatic hyperplasia in ratsrdquoNephro-UrologyMonthly vol 8 no 1 Article ID e33180 pp 1ndash7 2016

[38] A Bantis A Giannopoulos M Gonidi et al ldquoExpression ofp120 Ki-67 and PCNA as proliferation biomarkers in imprintsmears of prostate carcinoma and their prognostic valuerdquoCyto-pathology vol 15 no 1 pp 25ndash31 2004

[39] K Andersson R Soler and C Fullhase ldquoRodent models forurodynamic investigationrdquoNeurourology andUrodynamics vol30 no 5 pp 636ndash646 2011

Stem Cells International

Hindawiwwwhindawicom Volume 2018


MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine


Behavioural Neurology

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom


Table 1 Composition of XLQ capsule

Latin name Amount (g) Ratio () SourceAstragali Radix 70 461 Inner Mongolia ChinaLigustri Lucidi Fructus 14 92 Zhejiang ChinaCinnamoni Cortex 28 18 Guangxi ChinaTalcum 14 92 Liaoning ChinaPhellodendri Amurensis Cortex 7 46 Jilin ChinaAmber 21 14 Liaoning ChinaPrunellae Spica 21 138 Jiangsu ChinaLitchi Semen 21 138 Guangdong ChinaTotal 1519 100

which as a whole produces an effect of antiproliferation pro-apoptosis anti-inflammation analgesia and microcircula-tion improvement as previously reported [13ndash18] For in-stance Prunellae Spica as one of the main components ofXLQ capsules is reported to reduce the levels of the propro-liferative factors (Cyclin D1 and CDK4) as well as downreg-ulate the proangiogenic factors and increase the proapop-totic BaxBcl-2 rate [17] And Litchi Semen can inhibit theproliferation of HepG2 cells which may be concerned withthe property of proapoptosis [15] Another major componentAstragali Radix is reported to play a potential anti-inflam-matory activity which is widely used in oriental medicinefor tonifying the immune response and improving circulation[14] Recently XLQ capsule has been used in the treatment ofBPH at the early and midstage achieving a sound result asthose clinical drugs (unpublished) Although previous stud-ies have observed the pharmacological effects of similar tradi-tional herbal formula [4 19ndash22] there have been no studiesof XLQ capsule on its possible protective effects against BPH

Therefore the current study was aiming to investigate therole of XLQ capsule in the development of BPH by establish-ing a testosterone-induced BPH model in rats Our researchwill help to provide an experimental basis for the develop-ment of new agents for the prevention and treatment of BPHon clinic

2 Material and Methods

21 Drugs The herbal medicine of XLQ capsule was pur-chased from Shijiazhuang Yiling Pharmaceutical Co Ltd(Shijiazhuang Hebei China Z20123085) in February 2015The composition of XLQ capsule is listed in Table 1 The pow-der of the medicine was dissolved in adequate normal saline(NS) according to different doses and stored in 4∘C beforeuse

22 Animals Fifty specific pathogen free (SPF) grade adultmale Sprague-Dawley (S-D) rats weighed 200 to 250 gwere purchased from Department of Comparative MedicineJinling Hospital Affiliated to Nanjing University School ofMedicine (Nanjing Jiangsu China) for the study The ratswere kept on a standard laboratory diet and water ad libitumandwere adapted to laboratory environment (20-26∘C) under

a 12 h light-dark cycle for one week before experiment Allexperiments were performed according to the National Insti-tutes of Health Guide for the care and use of Laboratory Ani-mals and international ethical guidelines and were approvedby Institutional Animal Care and Use Committee of JinlingHospital Affiliated to Nanjing University School of Medicine(SYXK (M) 2012-0047)

23 Establishment of Testosterone Propionate-Induced RatModel of BPH Establishment of BPH rat model and experi-mental procedures were carried out as previously described[7] The rats were assigned into five groups randomly (10ratsgroup) And with the exception of the sham operationcontrol group four groups of rats were anesthetized withintraperitoneal injection of phenobarbital (50 mgkg) andcastrated aseptically to remove bilateral testes All castratedrats were injected with testosterone propionate (TP ZhejiangXianju Pharmaceutical Co Ltd Taizhou Zhejiang China)05 mgkgd (dissolved in corn oil) subcutaneously (SC) oneweek after castration The BPH model was induced through28 consecutive days of TP treatment which was further con-firmed by histopathological examination of prostate tissueThen one group was served as a model group while theother three served as experimental groups The experimentalgroups were treated with high dose (120 gkgd) and lowdose (061 gkgd) ofXLQ by intragastric administration (ig)for 28 days Finasteride dissolved in ultrapure water (08mgkgd ig HangzhouMerck China J20120071) was servedas a positive control group

Body weight (BW) of the rats were recorded every weekthroughout the whole study Following the final injectionand overnight fasting the rats were anesthetized with pen-tobarbital (50 mgkg intraperitoneal injection ip) Bloodsampleswere collected and prostate tissueswere immediatelyseparated and weighed Prostate lobes sections were fixedwith 4 paraformaldehyde for histological and immunohis-tochemical analysis and the remaining prostate sectionswerestored at -80∘C for further analysis

24 Assessment of Prostate Weight (PW) and Prostatic Index(PI) PW and BWof the rats were recorded in all groupsThePI was computed as PWBW times100 and the mean PI ratioswere computed in each group The percentage of inhibition











3 Results






Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

lowast

lowast

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

1500

1000

500

600 4

3

2

1

0

400

200

Pros

tate

wet

wei

ght (

mg)

Pros

tate

inde

x (m

gg)

Body

wei

ght (

g)

0 0

(a)

HE

times 20

0H

Etimes

400


(b)









lowast

lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0

25

20

15

10

5

0

20

15

10

05

00

TNF-

in

seru

m (n

gm

l)TN

F-

in p

rost

ate (

pgm

g)

IL-8

in se

rum

(ng

ml)

IL-8

in p

rost

ate (

pgm

g)

150

100

50

200

0

(a)

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0DH

T in

seru

m (n

gm

l)D

HT

in p

rost

ate (

pgm

g)

150

100

50

250

200

0

(b)

IHC

times200


IHC

times400

PCN

APC

NA

(c)







lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)




4 Discussion












Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of





























3 Results






Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

lowast

lowast

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

1500

1000

500

600 4

3

2

1

0

400

200

Pros

tate

wet

wei

ght (

mg)

Pros

tate

inde

x (m

gg)

Body

wei

ght (

g)

0 0

(a)

HE

times 20

0H

Etimes

400


(b)









lowast

lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0

25

20

15

10

5

0

20

15

10

05

00

TNF-

in

seru

m (n

gm

l)TN

F-

in p

rost

ate (

pgm

g)

IL-8

in se

rum

(ng

ml)

IL-8

in p

rost

ate (

pgm

g)

150

100

50

200

0

(a)

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0DH

T in

seru

m (n

gm

l)D

HT

in p

rost

ate (

pgm

g)

150

100

50

250

200

0

(b)

IHC

times200


IHC

times400

PCN

APC

NA

(c)







lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)




4 Discussion












Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of




















Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

lowast

lowast

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

1500

1000

500

600 4

3

2

1

0

400

200

Pros

tate

wet

wei

ght (

mg)

Pros

tate

inde

x (m

gg)

Body

wei

ght (

g)

0 0

(a)

HE

times 20

0H

Etimes

400


(b)









lowast

lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0

25

20

15

10

5

0

20

15

10

05

00

TNF-

in

seru

m (n

gm

l)TN

F-

in p

rost

ate (

pgm

g)

IL-8

in se

rum

(ng

ml)

IL-8

in p

rost

ate (

pgm

g)

150

100

50

200

0

(a)

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0DH

T in

seru

m (n

gm

l)D

HT

in p

rost

ate (

pgm

g)

150

100

50

250

200

0

(b)

IHC

times200


IHC

times400

PCN

APC

NA

(c)







lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)




4 Discussion












Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of




















lowast

lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0

25

20

15

10

5

0

20

15

10

05

00

TNF-

in

seru

m (n

gm

l)TN

F-

in p

rost

ate (

pgm

g)

IL-8

in se

rum

(ng

ml)

IL-8

in p

rost

ate (

pgm

g)

150

100

50

200

0

(a)

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

10

5

0DH

T in

seru

m (n

gm

l)D

HT

in p

rost

ate (

pgm

g)

150

100

50

250

200

0

(b)

IHC

times200


IHC

times400

PCN

APC

NA

(c)







lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)




4 Discussion












Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of




















lowast

lowast

lowast

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

Finasteri

de contro

l

High-doses

of XLQ

Low-doses of X

LQ

Sham

operatio

n contro

lModel o

f BPH

20

15

25

10

5

0

20

15

25

10

05

00

SOD

in se

rum

(Ul)

SOD

in p

rost

ate (

Ug

)

MD

A in

seru

m (n

mol

l)

MD

A in

pro

stat

e (pm

olg

)

200

300

100

0

200

300

100

0

(a)


Casp

ase-

3D

API

Mer

ged

(b)




4 Discussion












Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of



























Data Availability






Acknowledgments






References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of





















References














































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of




































of




Disease Markers



OncologyJournal of





PPAR Research



Volume 2018


Journal of

ObesityJournal of



















The Effect of Xialiqi Capsule on Testosterone-Induced Benign...

Documents

Transcript of The Effect of Xialiqi Capsule on Testosterone-Induced Benign...