Ashwagandha in brain disorders: A review of recent developments

Abstract

Ethnopharmacological relevance
Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.
Aim of the review: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.

Materials and methods
All the information and data was collected on Ashwagandha using keywords “Ashwagandha” along with “Phytoconstituents”, “Ayurvedic, Unani and Homeopathy marketed formulation”, “Brain disorders”, “Mechanism” and “Patents”. Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.

Results
Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII–X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.

Conclusion
The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

Full text

UNCORRECTED PROOF
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Keywords
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1. Introduction
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UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 1
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2. Phytoconstituents of Ashwagandha
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-56@9 
3. Historical background of Ashwagandha
-F58=H=CB5@ A98=7=B5@ GMGH9A =G H<9 DCH9BH=5@ H<9F5D9IH=7 CDH=CB HC
HF95H K=89 F5B;9 C: 8=GCF89FG K=H< @=A=H98 G=89 9::97HG =ADFCJ98 9:Q
757M 5B8 H<IG CK=B; DFCD9FHM HC A5B5;9 H<9 8=G95G9 5H 8=::9F9BH @9J9@G
=B7@I8=B; DF9J9BH=CB 5B8 7IF9 G<K5;5B8<5 =G 5B =ADCFH5BH <9F6 =B
J5F=CIG HF58=H=CB5@ GMGH9A C: A98=7=B9 DFC@=:=75@@M MIFJ985 .B5B= ,=8
8<5 !CA9CD5H<M <=B9G9 -=69H5B :F=75B 9H7 "B Withania somnifera
“GCAB=:9F5”=G 5 %5H=B KCF8 K<=7< A95BG “G@99D=B8I79F” H<IG >IGH=:M
=B; =HG IG9 9LH9BG=J9@M 5G B9IFCDFCH97H=J9 "H =G ?BCKB 6M 8=::9F9BH @C75@
B5A9G =B 8=::9F9BH D5FHG C: "B8=5
-<9 HF58=H=CB5@ "B8=5B A98=7=B5@ GMGH9A MIFJ985 5B8 <=B9G9
A98=7=B5@ GMGH9A 5F9 H<9 ACGH 5B7=9BH GMGH9AG MIFJ985 F9EI=F98 ACF9
9J=89B79G 5B8 G7=9BH=Q765G98 F9G95F7< )5HK5F8<5B 9H 5@  "B
MIFJ985 =H =G ?BCKB 5G G<K5;5B8<5 K<=7< A95BG “C8CIF C: H<9
<CFG9”5G =H FCCHG F9G9A6@9 GK95HM <CFG9 "H <5G 699B 9LH9BG=J9@M IG98
:FCA D5GH H<CIG5B8 M95FG 657? HC HF95H K=89 F5B;9 C: 8=G95G9G MIFJ98=7
DF57H=H=CB9FG HF58=H=CB5@@M IG9 =H 6M 6C=@=B; H<9 :F9G< FCCHG =B A=@? "H 5@GC
58A=B=GH9F98 6M 7FIG<=B; H<9 FCCHG =BHC QB9 DCK89F 75@@98 5G “7<IFB5”
5B8 6@9B8=B; =H K=H< RI=8G A5=B@M K5H9F A=@? <CB9M (H<9F D5FHG =B
7@I8=B; @95J9G G<CCHG G998G 5B8 69FF=9G <5J9 5@GC 699B IG98 HC =A
DFCJ9 <95@H< 5B8 =B7F95G9 @CB;9J=HM "B MIFJ98=7 GMGH9A =H =G 7@5GG=
Q98 5G “+5G5M5B5”A95BG “HCB=7”5B8 A5=B@M 57H 5G 6C8M F9>IJ9B5HCF
89:9BG9 5;5=BGH 8=G95G9 G@CKG 5;=B; 5B8 9B<5B79G A9ACFM ,5A58=
CFA5B 5B8 $9FB5 
.B5B= =G 5 HF58=H=CB5@ :CFA C: A98=7=B9 GMGH9A A5=B@M =B &=88@9
5GH 5B8 ,CIH< G=5B 7CIBHF=9G "H =G 65G98 CB H<9 DF=B7=D@9 C: 9EI=@=6
F=IA 5B8 H<9F5D=9G 9AD@CM D<MG=75@ A95BG :CF 8=G95G9 7IF=B; "H 9A
D@CMG 58A=B=GHF5H=CB C: 9=H<9F GD97=Q7 8=9H CF AC8I@5H=CB =B EI5@=HM 5B8
EI5BH=HM C: :CC8 '5HIF5@ GI6GH5B79G 9=H<9F G=B;@9 8FI;G CF 7CA6=B5H=CB
C: HKC CF ACF9 8FI;G 5F9 IG98 :CF HF95H=B; 5=@A9BHG ,<=885A5@@5MM5
9H 5@  0=H<5B=5 GCAB=:9F5 =G ?BCKB 5G G;5B8 =B .B5B= GMG
H9A 5B8 =G 89G7F=698 =B 6CC? “Kitab-ul-Hashaish” 77CF8=B; HC @=H9F5
HIF9 Asgand Nagori 5B8 Asgand Dakani 5F9 H<9 HKC J5F=9H=9G ?BCKB =B
.B5B= GMGH9A <CK9J9F Asgand Nagori =G A98=75@@M ACF9 DF9:9FF98 .8
8=B 9H 5@  "H =G IG98 9=H<9F 5G 5 G=B;@9 8FI; CF =B 7CA6=B5
H=CB /5F=CIG .B5B= :CFAI@5H=CBG 5F9 5J5=@56@9 7CBH5=B=B; Withania som-
nifera GI7< 5G <5669 G;5B8 ?IG<H5 ;5C85BH= A5>CCB G5@56 5B8 A5
>CCB N5B>5699@ BCBMACIG  "H =G IG98 :CF H<9 HF95HA9BH C:
DC@M5FH<F=H=G F<9IA5HC=8 5FH<F=H=G @IA65;C D5=B:I@ GK9@@=B;G GD9FA5
HCFF<C95 5GH<A5 @9I7C89FA5 ;9B9F5@ 896=@=HM G9LI5@ 896=@=HM 5BL=9HM
B9IFCG=G G756=9G I@79FG 5B8 @9I7CFF<C95 BCBMACIG $<5F9
'58?5FB= 
-=69H5B GMGH9A C: A98=7=B9 -,& =G CB9 C: H<9 KCF@8G C@89GH ?BCKB
HF58=H=CB5@ GMGH9AG C: A98=7=B9 "H =G DCDI@5F A5=B@M =B BCFH<9FB D5FH
C: "B8=5 =9 %585?< %5<I@ 5B8 ,D=H= 5B8 =G :C@@CK98 6M A7<=G <9F65@
8C7HCFG ,<5<  "H =G 65G98 IDCB H<9 @=H9F5HIF9 C: "B8=5B I8
8<=GH GMGH9A 5B8 =G 5@GC ?BCKB 5G ,CK5+=;D5 K<=7< F9:9FG HC G7=
9B79 C: <95@=B; ,<=885A5@@5MM5 9H 5@  Withania sominifera =G
?BCKB 5G G;5B8B5;CF= ,<5FA5 5B8 $IA5F  CF 58N=;5B8<5
,75FH9NN=B= 5B8 ,D9FCB=  =B -,& "H =G =B8=75H98 A5=B@M :CF
H<9 HF95HA9BH C: F9GD=F5HCFM 8=GCF89F <9


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Fig. 1. &5>CF D<MHC7CBGH=HI9BHG C: G<K5;5B8<5
D5H=7 8=GCF89FG 6C8M GHF9B;H<9B=B; 5B8 A5=BH5=B=B; <9AC;@C6=B @9J9@
!CAC9CD5H<M =G 5 :CFA C: HF58=H=CB5@ A98=7=B9 65G98 CB “H<9CFM
C: G=A=@5F=H=9G”K<=7< A95BG =: H<9 GI6GH5B79 75IG9G 5BM GMADHCA =B
<95@H<M D9FGCB =H K=@@ 5@GC <95@ H<9 G5A9 GMADHCAG GI779GG=J9@M =B
=@@ D9FGCB "B H<=G GMGH9A CB@M <=;<9F 8=@IH=CBG ?BCKB 5G H=B7HIF9G C:
B5HIF5@ =9 5B=A5@ D@5BHG A=B9F5@G 5B8 GMBH<9H=7 GI6GH5B79G 5F9 DF9
D5F98 :CF HF95H=B; H<9 8=G95G9 ,<=885A5@@5MM5 9H 5@  "H =G
A5=B@M GI;;9GH98 :CF H<9 HF95HA9BH C: @9DFCGM B9FJCIG 8=GCF89FG =BH9GH=
B5@ =B:97H=CB 5B8 F<9IA5H=GA =B !CA9CD5H<M FIB57<5@5A 
"B  %5=8@5K F9DCFH98 H<9 <CAC9CD5H<=7 DFCC: C: Withania somnifera
=B H<9 H<=FH=9H< 79BH9G=A5@ DCH9B7M H<FCI;< 8CI6@96@=B8 D@5796C7CB
HFC@@98 HF=5@ %5=8@5K 
"B <=B5 =H =G ?BCKB 5G "B8=5B ;=BG9B; IFF9BH@M G<K5;5B8<5
:FCA "B8=5 =G BCH 7@5GG=Q98 5G D9F <=B9G9 HF58=H=CB5@ GMGH9A -, A5M
69 8I9 HC =GC@5H=CB 5B8 8=GH5B79 C: 7CIBHF=9G 5B8 H<9=F 7I@HIF9G !CK
9J9F CB H<9 65G=G C: 7CAD5F=GCB 69HK99B J5F=CIG F9@9J5BH <9F6G K=H<
G<K5;5B8<5 =H 75B 69 75H9;CF=N98 =B -, 5G “-CB=:M *=”5B8 “-CB=:M
@CC8 5B8 GG9B79”CFA5B 5B8 $9FB5 -<CI;< <=B5 CB H<9
65G=G C: G7=9BH=Q7 F9G95F7< 5B8 9J=89B79G 5F9 ACF9 GI779GG:I@ =B DFCACH
=B; H<9 IG9G C: J5F=CIG <9F6G =B7@I8=B; Withania sominifera )5HK5F8
<5B 9H 5@ 
"B :F=75 Withania somnifera =G H<9 B5H=J9 D@5BH 5B8 A5=B@M 7CB
G=89F98 5G H<9 K998 C: 7CBH5A=B5H98 5B8 K5GH9 5F95G %95J9G 5F9
IG98 5G 8F9GG=B;G :CF =B:97H=CBG 5B8 =BR5AA5H=CBG -<9 FCCH =B H<9 :CFA
C: QB9 DCK89F A=L98 K=H< :5H C: 5B=A5@G 7FC7C8=@9 CF DMH<CB 5B8 =G
IG98 :CF GCF9G 5B8 56G79GG9G 5G C=BHA9BH !IH7<=B;G 9H 5@  "H
=G 5@GC IG98 HC 7CIBH9F57H H<9 :CI@ 6C8M C8CIF -<9 FCCHG 5F9 HF95H98 5B8
IG98 5G 9B9A5G :CF =B:97H=CBG C: H<9 F97HIA 5B8 DMF9L=5 "H =G 5@GC IG98 HC
<95@ F9@5H=CBG<=DG "H =G DF9G7F=698 6M :F=75B HF58=H=CB5@ DF57H=H=CB9FG :CF
:9J9F 7C@8 6FCB7<=5@ 8=GCF89F 5GH<A5 J9B9F95@ =B:97H=CBG GMD<=@=G
8=5FF<95 G?=B 8=G95G9G 5B8 HMD<C=8 "H =G 5@GC =B8=75H98 5G 5BH=<9@A=BH=7
5BH=F<9IA5H=GA G985H=J9 5B8 <MDBCH=7G "B H<9 3I@I HF58=H=CB C: :F=75
Withania somnifera =G IG98 HC DFCH97H D9CD@9 :FCA GCF79FM "H =G 5@GC 5D
D@=98 5G 6CIB85F=9G :CF =BG97HG %5=8@5K 
4. Common brain disorders
-<9 H9FA 6F5=B 8=GCF89F =G BCH F9GHF=7H98 HC A95B =BG5B=HM 5B8 5@
@=98 7CB8=H=CBG C: A9BH5@ 89F5B;9A9BH 6IH 5@GC =B7@I89G HC 79FH5=B 9L
H9BH H<9 9ACH=CB5@ 8=GCF89FG (:H9B H<9 9ACH=CB5@ :57HCFG K<9B 7FCGG
H<9 GH5H9 C: BCFA5@7M ;9H 89F5B;98 HC 697CA9 H<9 GMB8FCA9G C: A9B
H5@ 8=GCF89F "H =G GH5H98 H<5H H<9 6F5=B <5G  6=@@=CB B9IFCBG 5B8
957< C: H<9A 7CBB97H K=H< A5BM CH<9FG HC :CFA 7CAAIB=75H=CB B9H
KCF?G -<9G9 B9FJ9 79@@G <5J9 GD97=5@ >C6G @=?9 H<=B?=B; @95FB=B; F9
A9A69F=B; 5G K9@@ 5G HC G99 <95F 5B8 GA9@@ F5=B 79@@G KCF? @=?9
H=BM :57HCF=9G F979=J9 GIDD@=9G ;9B9F5H9 9B9F;M 7CBGHFI7H 9EI=DA9BH
5B8 ;9H F=8 C: H<9 K5GH9 F5=B 79@@G 5@GC DFC79GG 5B8 GHCF9 =B


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 2
/5F=CIG B9IFCDFCH97H=J9 DFCD9FH=9G C: D<MHC7CBGH=HI9BHG C: G<K5;5B8<5 =B DF97@=B=75@ AC89@G
)<MHC7CBGH=HI9BHG -MD9C:GHI8M
)5FH
IG98:CF
=GC@5H=CB CG9" &C89@&9H<C8 "B:9F9B79 +9:9F9B79
0=H<5:9F=B @IH5H<=CB97CB>I;5H9
+
In-vitro +CCHG  μ& &9G9B79D<5@=7B9IFCBG
9LDCG98HC
&))  =B>IFM(!
=B>IFM5B8 α,MBI7@9=B
=B>IFM
'9IFCDFCH97H=J9
GIDDF9GGCL=85H=J9
GHF9GGα,MB
5;;F9;5H=CBJ=5
H<9=B8I7H=CBC:
H<97MHCDFCH97H=J9
)"$A-(+
D5H<K5M
+56<=9H5@

0=H<5:9F=B In-vitro –μ& ,!))79@@G5<IA5B
B9IFC6@5GHCA579@@@=B9
HF5BG:97H98K=H<!"/
-5H– B;A@5B8
7C7– μ&HC
=B8I798B9IFCHCL=7=HM
+98I7H=CB=B
G97F9H98β5B8
=B8I798
B9IFCHCL=7=HM=B
5AM@C=8DF97IFGCF
DFCH9=B))
D@5GA=8
HF5BG:97H98,!
,2279@@G,!
))
-=K5F=9H5@

0=H<5BC@=89K=H<5BC@=895B8
K=H<5:9F=B
In-vivo +CCHG 5B8 A;?;
=BHF5D9F=HCB95@@M
'=7CH=B9 A;?;
=B8I7987CB8=H=CB98
D@579DF9:9F9B79=BA5@9
5@6=BCA=79
BH=588=7H=J9
F9J9FG=B;
B=7CH=B9=B8I79
7CB8=H=CB98D@579
DF9:9F9B79
IACF99H5@

0=H<5BCB9 In-vivo +CCHG 5B8 A;?; ,-3 A;?;=B>97H98
=BHF579F96FCJ9BHF=7I@5F
HCA5@90=GH5FF5HG
)FCH97H=CB5;5=BGH
CL=85H=J9GHF9GG
5B8=BR5AA5HCFM
7MHC?=B9G-'α
"%β"%
&)
)5B89M9H5@

0=H<5BCB95B8!M8FCLMK=H<5BC@=89

In-silico – – !=;<6=B8=B;5SB=HM
C:  −?75@AC@
5;5=BGH βG97F9H5G9
ACBC5A=B9CL=85G9
5B8D<CGD<C8=9GH9F5G9
BH=@N<9=A9FG CF5<9H5@

0=H<5BC@=89 In-vivo +CCHG  μAC@?; ,DF5;I985K@9MF5HG
K9F99LDCG98HC5
G=AI@5H985@H=HI89C:
 A :H
 AA!;=B5
GD97=5@@M89G=;B98
5B=A5@897CADF9GG=CB
7<5A69FDF9GGIF9
+98I7H=CB=B
B9IFC89;9BF5H=CB
F9GHCF=B;
;@IH5H<=CB9
89D@9H=CB5B8
=B7F95G9=B
;@IH5H<=CB9
6=CGMBH<9G=G
H<FCI;<'F:
D5H<K5M6M
IDF9;I@5H=CBC:
%@9J9@=B
B9IFCB5@79@@G
7CFH=7CGH9FCB9
89D9B89BH
A5BB9F
5=H<5FI9H5@

In-vitro –μ;A@ @=CA5F5H5B8
B9IFCB5@"&+
<IA5B79@@@=B9G
5;5=BGHG7CDC@5A=B9
 A&=B8I798HCL=7=HM
+9;I@5H=CBC:
B9IFCB5@79@@
A5F?9FG'–!
&)),
)5B8;@=5@
79@@A5F?9F )
5B8K=H<
IDF9;I@5H=CBC:
'85A5;9
γ!15B8
CL=85H=J9GHF9GG
+(,A5F?9FG
$CB5F9H5@



UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 2 Continued
)<MHC7CBGH=HI9BHG -MD9C:GHI8M
)5FH
IG98:CF
=GC@5H=CB CG9" &C89@&9H<C8 "B:9F9B79 +9:9F9B79
In vitro +CCHG  μ& β=B8I798HCL=7=HM=B
Caenorhabditis elegans
%KCFAG
+9J9FG98H<9
DCH9BH=5@C:β
:C@@CK986M
579HM@7<C@=B95B8
579HM@
7<C@=B9GH9F5G9
AC8I@5H=CB
F9GI@H=B;
B9IFCDFCH97H=CB
?<CCB9H5@

In-silico – – %=;5B8=BH9F57H=CBK=H<
H<9F9G=8I9G-<F
-FD,9F5B8
!=GC:<IA5B579HM@
7<C@=B9GH9F5G9
C7?=B;
G=AI@5H=CBF9GI@HG
=B<=;<6=B8=B;
5SB=HMC:H<9
@=;5B8HCH<9
F979DHCF
FCJ9F9H5@

In vitro +CCHG  μ& LCB5@5B889B8F=H=7
5HFCD<MK5G=B8I798=B
7I@HIF98F5H7CFH=75@
B9IFCBG6MHF95HA9BH
K=H<5AM@C=8
β– μ&
+9;9B9F5H=CBC:
B9IF=H=G
F97CBGHFI7H=CBC:
GMB5DG9G6CH<DF9
5B8DCGH=B
B9IFCBG
$I6CM5A59H
5@
in vivo +CCHG  μAC@?;85M
CF5@@M
05H9FA5N9H9GH&5@9
882A=79
+97CJ9F98
A9ACFM89:97HG
0=H<5BC@=89G5B8K=H<5BCG=89G In vivo – ;?;CF5@@M ))),@N<9=A9FG
8=G95G9HF5BG;9B=7A=79
+9J9FG9G
9<5J=CF5@
9Q7=HG5B8
D@5EI9D5H<C@C;M
897F95G9Gβ
@9J9@G5B8
DFCACH9G
8=G5;;F9;5H=CBC:
(@=;CA9FG
57H=J5H98
A=7FC;@=5
DFCL=A5@HCH<9
D@5EI9G897F95G9
G=;B=Q75BH@M
9B<5B79G%+)5B8
')A+'5B8
8CKBF9;I@5H=CB
C:<9D5H=7%+)
,9<;5@9H5@

0=H<5BC@=89G"/5B8/ ,D97HFCD<CHCA9HF=7
5B8 In silico –5B8 μ&
579HM@7<C@=B9GH9F5G9G
5B85B8 μ&
6IHMFM@7<C@=B9GH9F5G9
9H9FA=B5H=CBC:?=B9H=7
D5F5A9H9FGAC@97I@5F
8C7?=B;GD5GAC@MH=7
5B875@7=IA5BH5;CB=GH
57H=J=H=9G
0=H<5BC@=89"/
5F9BCB
7CAD9H=H=J9
=B<=6=HCFC:<
5B8<
0=H<5BC@=9/5F9
@=B95FA=L98HMD9
=B<=6=HCFC:<
!=;<6=B8=B;
5SB=HM:CF<
L<=6=HG
GD5GAC@MH=75B8
75@7=IA
5BH5;CB=GH=7
DCH9BH=5@
<CI8<5FM9H
5@


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 2 Continued
)<MHC7CBGH=HI9BHG -MD9C:GHI8M
)5FH
IG98:CF
=GC@5H=CB CG9" &C89@&9H<C8 "B:9F9B79 +9:9F9B79
0=H<5BC@=89# &'
K=H<5:5GHICG=B5B8GCAB=:9F=B9
In silico – – )CH9BH=5@=B<=6=H=CBC:
;9@5H=B5G9GA5=B@M
A9H5@@CDFCH9=B5G9=9
&&)5B8&&)=B
7CAD5F=GCBK=H<DCH9BH
;9@5H=B5G9=B<=6=HCFG=9
<M8FCL5A=757=8
8CLM7M7@=B9
A=BC7M7@=B9EI9F79H=B
5B8F9J9FG9
<M8FCL5A5H9
"B<=6=H=CBC:
;9@5H=B5G9G
&&)
-<9F5D9IH=75@@M
57H=J9=B=G7<9A=7
GHFC?9
<9ACFF<5;=7
GHFC?95B8
D9F=B5H5@<MDCL=7
$IA5F5B8
)5HB5=?

0=H<5BC@=895EI9CIG:F57H=CB In-vivo +CCHG 5B8
 A;?;CF5@@M
!MDCL=5H=A9
5BH=:5H=;I99T97H
GK=AA=B;D9F:CFA5B79
H=A9GK=AA=B;
=B8I798;5GHF=7
I@79F5H=CB5B8
<MDCH<9FA=5
=AAC6=@=N5H=CB=B8I798
;5GHF=7I@79F5H=CB
5IHC5B5@;9G=5
BH=GHF9GG57H=J=HM
=B8CG989D9B89BH
A5BB9F
,=B;<9H5@

0=H<5BCB9 In-vitro – μ&  μ&F9H=BC=7=B8I798
B9IFCB5@8=GHCFH=CBCB
'9IFC'5ACIG9
B9IFC6@5GHCA579@@@=B9
:C@@CK986MA&
'&
'9IFCDFCH97H=J9
9T97HGC:
0=H<5BCB9
:C@@CK986M
F98I7H=CB=B
CL=85H=J9GHF9GG
5B8DFC5DCDHCH=7
7MHC?=B9G
5F9H5@

,H=;A5GH9FC@0=H<5:9F=B5B8
K=H<5BC@=89 5B8
In silico – – "B<=6=H=CB9S7=9B7M
5;5=BGHDC@M)
F=6CG9DC@MA9F5G9
))+=B7CAD5F=GCB
HCDCH9BH=B<=6=HCFG
+)#5B8
H5@5NCD5F=6
!=;<6=B8=B;
5SB=HM:CF
75H5@MH=78CA5=B
)+)5B8
69B9Q7=5@=B
B9IFC7MHCHCL=7=HM
5B8CH<9F
B9IFC@C;=75@
8=GCF89FG@=?9
GHFC?99H7
&I?<9F>999H
5@
@M7CK=H<5BC@=89GG=HC=B8CG=89"15B8
G=HC=B8CG=891
In-vivo +CCHG – A;?;CF5@@M +9GHF5=BHGHF9GG=B8I798
;5GHF=7I@79FG=B5@6=BC
F5HGD5GG=J95JC=85B79
H9GHF979=J=B;5:CCH
G<C7? G A
9@97HF=77IFF9BH=B
5@6=BCF5HG
BH=GHF9GG5B8
=ADFCJ9A9ACFM
5B8@95FB=B;
9BHF5@
GH=AI@5H=CB
7<5F57H9F=N986M
D=@C9F97H=CB
=B7F95G98ACH=@=HM
F957H=J=HMHC
GH=AI@=
GDCBH5B9CIG
ACHCF57H=J=HM5B8
5I;A9BH98
@95FB=B;
57EI=G=H=CB
<CG5@9H5@

@M7CK=H<5BC@=89G In vivo +CCHG 5B8 A;
?;CF5@@M
@9J5H98D@IGA5N9H9GH
,C7=5@=BH9F57H=CB5B8
:998=B;@5H9B7M=B5B
IB:5A=@=5F9BJ=FCBA9BH
BH=5BL=9HM
F98I798HF=6I@=B
@9J9@G=BF5H6F5=B
5B8
BH=89DF9GG5BH
9T97H
<5HH57<5FM5
9H5@


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 2 Continued
)<MHC7CBGH=HI9BHG -MD9C:GHI8M
)5FH
IG98:CF
=GC@5H=CB CG9" &C89@&9H<C8 "B:9F9B79 +9:9F9B79
0=H<5BC@=89 In silico – – )CH9BH5B8G9@97H=J9
=B<=6=HCFC:B9IFCB5@
B=HF=7CL=89GMBH<5G9
B'(,5B8'(,CB
H<965G=GC:G9@97H=J=HM
6=B8=B;9B9F;M5B8
=BH9F57H=CBDFCQ@9
I5@G9@97H=J9
=B<=6=H=CBC:6CH<
B'(,='(,5B8
9'(,
)CH9BH=5@
B9IFCH<9F5D9IH=7
5;9BHA5=B@M:CF
8=GCF89FG
A98=5H986M
B'(,57H=J5H=CB
$IA5F9H5@

0=H<5B5A=89G5B8K=H<5BC@=89G &C89@GMGH9AIG=B;
@5F;9IB=@5A9@@5F
J9G=7@9G
FI=HG 5B8 μ;A@ 9  =B8I798@=D=8
D9FCL=85H=CB5GG5M5B8
)! =B8I798@=D=8
D9FCL=85H=CB5GG5M
"B<=6=HG@=D=8
D9FCL=85H=CB5BH=
CL=85BH
#5M5DF5?5G5A
9H5@
0=H<5B5A=895B8 In vitro FI=HG  μ;A@ +5HB9IFCB5@79@@G=9
) 79@@G79@@
J=56=@=HM5GG5M5B8
AC@97I@5FAC89@=B;
GHI8=9G'&+
)FCH97H
) 79@@G:FCA
79@@85A5;9
=B8I796M β
5AM@C=8
"B<=6=HQ6F=@
:CFA5H=CB6=B8HC
57H=J9G=H9C: β
5AM@C=8
#5M5DF5?5G5A
9H5@
:CFA5H=CB HC 7CAAIB=75H9 K=H< CH<9F 79@@G -<9 @5F;9 5ACIBH C: :I9@ 5B8
CLM;9B =G F9EI=F98 :CF DFCD9F :IB7H=CB=B; 5B8 7CCF8=B5H=CB -<9 7CA
ACB 6F5=B 8=GCF89F =G 7C@@5H98 =B =;  -<9 =B:CFA5H=CB F9@5H98 HC 8=:
:9F9BH GHI8=9G 7CB8I7H98 CB G<K5;5B8<5 9LHF57HG 5F9 GIAA5F=N98 =B
-56@9 
4.1. Ashwagandha in anxiety
BL=9HM =G 89QB98 5G ‘5B 9ACH=CB 7<5F57H9F=N98 6M :99@=B;G C: H9B
G=CB KCFF=98 H<CI;<HG 5B8 D<MG=75@ 7<5B;9G’ (J9F7CBGIADH=CB C: H5GHM
5B8 <=;<75@CF=9G :CC8 =G F9GDCBG=6@9 :CF 7<FCB=7 DCG=H=J9 9B9F;M 65@5B79
K<9F9 H<9 =B;9GH=CB C: 9B9F;M 9L7998G 9B9F;M 9LD9B8=HIF9 75IG9 HC 9L
HF5 :5H =B 6C8M K9=;<H ;5=B 5B8 C69G=HM =B< 9H 5@  -<9 =B;9G
H=CB C: <=;<75@CF=9 :CC8 <5G 5@GC 699B 5GGC7=5H98 HC J5F=CIG B9IFCDGM
7<=5HF=7 8=GCF89FG @=?9 5BL=9HM ACC8 8=GCF89FG 5B8 6=B;9 95H=B; 5G
H5BCB 9H 5@ 
)CK89F 9LHF57H C: G<K5;5B8<5 @95: GHI8=9G GI;;9GH H<5H =H <5G
5BH=5BL=9HM 5BH==BR5AA5HCFM 5B8 5BH=5DCDHCH=7 DFCD9FH=9G K<=7<
A5M 69 F97CAA9B898 HC DF9J9BHG@CK 8CKB H<9 58J9FG9 9::97HG C: C69
G=HM 5B8 =HG 5GGC7=5H98 8=G95G9 $5IF 5B8 $5IF 
-<9 <M8FC 5@7C<C@=7 9LHF57H C: FCCHG C: G<K5;5B8<5 F9DCFH98 G=;B=:
=75BH 5BH=GHF9GG 57H=J=HM ,=B;< 9H 5@  @7C<C@=7 9LHF57H C: G<
K5;5B8<5 FCCH 5B8 G998 K5G ;=J9B HC A=79  A;?; =BHF5 D9F=HCB95@
5G 5 G=B;@9 8CG9 5B8 C6G9FJ98 GK=AA=B; D9F:CFA5B79 "H K5G C6G9FJ98
H<5H H<9 GK=AA=B; H=A9 C: G<K5;5B8<5 HF95H98 A=79 8CI6@98 5G 7CA
D5F98 HC BCFA5@ 7CBHFC@ "H GI;;9GH H<5H G<K5;5B8<5 =B8I798 5 GH5;9 C:
BCBGD97=Q7 =B7F95G98 F9G=GH5B79 8IF=B; GHF9GG 7CB8=H=CB &=G<F5 9H 5@
,=B;< 9H 5@ 
G<K5;5B8<5 <5G 5 G=;B=:=75BH 5BH=GHF9GG 585DHC;9B=7 9::97H 5G F9
DCFH98 6M 5G=7 &98=75@ ,7=9B79G 5H 5@7IHH5 .B=J9FG=HM -<9M GHI8
=98 H<9 9::97H C: G<K5;5B8<5 CB 7<FCB=7 GHF9GG =B FC89BHG B 9@97
HF=7 :CCH G<C7? F979=J98 :CF 5 D9F=C8 C:  85MG DFC8I798 <MD9F;@M
Fig. 2. CAACB 6F5=B 8=GCF89FG


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 3
+9DCFH98 GHI8=9G C: G<K5;5B8<5 9LHF57HG =B7@I8=B; 8CG9 A97<5B=GA 5B8 A9H<C8 9AD@CM98 HC <=;<@=;<H =HG FC@9 =B 6F5=B F9@5H98 8=GCF89FG
LHF57H CG9 &97<5B=GA=BJC@J98 &9H<C8 "B:9F9B79 +9:9F9B79
H<5BC@=7FCCH
9LHF57HC:
G<K5;5B8<5
 A;?;CF5@@M "ADFCJ9A9BH=B=AD5=F98GD5H=5@
A9ACFM5B8CL=85H=J9GHF9GG
AC8I@5H=CBC:&@9J9@G+(,
,(5B875H5@5G9
,=;B=Q75BH=B7F95G9=B'&
F979DHCF9LDF9GG=CB
=GD<9BC@ μ;?;=B>97H98CF5@@M:CF
85MGHCA5@9,K=GG5@6=BCA=79
'9IFCDFCH97H=J9
5B85BH=CL=85BH
=ADFCJ9G
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

UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 3 Continued
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

UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
759A=5 ;@I7CG9 =BHC@9F5B79 ;5GHF=7 I@79F5H=CBG A5@9 G9LI5@ 8MG:IB7
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5B=A5@G -<9 9LHF57H C: G<K5;5B8<5 5B <CIF 69:CF9 H<9 G<C7? F98I798
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4.2. Ashwagandha in Alzheimer's
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9::97H C: G<K5;5B8<5 5B8 =HG D<MHC7CBGH=HI9BHG =B @N<9=A9FG 8=GCF89F
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5AM@C=8 β 0=H<5BCB9 5@GC :CIB8 HC =BH9BG=:M H<9 57H=J=HM C: 579HM@
7<C@=B9 ;@IH5H<=CB9 5B8 G97F9H5G9 9BNMA9 β5B8 γ 5B8 =ADFCJ98 H<9
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5SB=HM DF98=7H98 6M 8C7?=B; G=AI@5H=CB GHI8=9G  FCJ9F 9H 5@ 
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G=89G K<=7< F9J9FG98 @N<9=A9FG 8=G95G9 6M DFC8I7=B; B9IFCDFCH97H=J9
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6=H=CB 5B8 7C;B=H=J9 =AD5=FA9BH H<IG G<CK=B; DFCH97H=J9 9::97HG 5;5=BGH
DFCDCLIF 9LDCGIF9 =B F5HG 2585J 9H 5@  &9H<5BC@=7 7<@CFC:CFA
9LHF57H C: G<K5;5B8<5 9@=7=HG <=;< 79@@ J=56=@=HM 5B8 9B<5B79G ))+7
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@=B9 =B:97H98 6M β5AM@C=8 $IF5D5H= 9H 5@  IFH<9FACF9 5EI9
CIG 9LHF57H C: G<K5;5B8<5 7CBH5=B=B; 0=H<5BC@=89 89F=J5H=J9G =B7@I8
=B; K=H<5:9F=B  G<CKG DCH9BH=5@ DFCH97H=CB =B 8=::9F9BH=5H98 D<9C7<FC
AC7MHCA5 ) 79@@G =B:97H98 6M <M8FC;9B D9FCL=89 5B8 β7MHCHCL=7=HM
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4.3. Ashwagandha in Parkinson's
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5H=J9 8=GCF89F DF=A5F=@M 7<5F57H9F=N98 6M 89D@9H=CB C: 8CD5A=B9F;=7
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H=CB 5B8 89D@9H=CB =B 8CD5A=B9 @9J9@G =B FCH9BCB9 AC89@ C: Drosophila
melanogaster 6M GIDDF9GG=CB C: CL=85H=J9 GHF9GG 5B8 A=HC7<CB8F=5@ 8MG
:IB7H=CBG &5B>IB5H< 5B8 &IF5@=8<5F5  &CIG9 K<9B HF95H98
K=H< A9H<M@D<9BM@H9HF5<M8FCDMF=8=B9 G<CK98 5@H9F5H=CB =B
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H5H<=CB9 5B8 ;@IH5H<=CB9 D9FCL=8=G9 5B8 H<=C65F6=HIF=7 57=8 F957H=J9
GI6GH5B79 @9J9@G =B GHF=5HIA 5B8 =ADFCJ9A9BH =B ACHCF :IB7H=CBG +5
>5,5B?5F 9H 5@ 56
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69<5J=CIF 5BH=CL=85BH GH5HIG 5B8 @=D=8 D9FCL=85H=CB @9J9@G =B H<9
6F5=B C: )5F?=BGCBG =B8I798 A=79 +5>5,5B?5F 9H 5@  )F5?5G<
9H 5@ =B  89ACBGHF5H98 H<FCI;< in vivo F9G95F7< H<5H G<K5;5B8<5
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5B8 F=G9 =B B=HF=H9 5B8 @=D=8 D9FCL=85H=CB @9J9@G H<IG 7CIBH9F65@5B7=B;
DFCCL=85BHG 5B8 CL=85H=J9 GHF9GG =B )5F?=BGCBG 8=G95G9 )F5?5G< 9H 5@
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7@=B=75@ IG9 C: H<9 D@5BH 5G 5B 5BH=D5F?=BGCB=5B 8FI;
4.4. Ashwagandha in schizophrenia
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CIG 7<9K=B; ACJ9A9BHG 5B8 HCB;I9 DFCHFIG=CBG GID9F=CF@M 6M F98I7H=CB
=B @=D=8 D9FCL=85H=CB 5B8 =B7F95G9 =B :CF96F5=B ,( 5B8 75H5@5G9 @9J9@G
K=H< BC 9::97H CB ;@IH5H<=CB9 @9J9@G -<IG G<K5;5B8<5 A5M 69 9:Q
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9H 5@ 
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GHF9GG GMADHCAG =B G7<=NCD<F9B=5 D5H=9BHG <9B;5DD5 9H 5@ 
"B  $IA5F 5B8 7C@@95;I9G 7CB8I7H98 in silico GHI8=9G HC 9LD@CF9 DC
H9BH=5@ C: J5F=CIG D<MHC7<9A=75@G C: G<K5;5B8<5 5G B9IFCDFCH97H=J9
6M =B<=6=H=B; @I'7CBH5=B=B; '& F979DHCF IFH<9F =H DFCJ98 H<5H
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CB=GH :CF '& F979DHCF 5B8 A5M 69 IG98 :CF HF95HA9BH C: J5F=CIG B9I
FC89;9B9F5H=J9 7CB8=H=CBG $IA5F 5B8 )5HB5=? 
4.5. Ashwagandha in Huntington's disease
!IBH=B;HCBG 8=G95G9 =G 5 DFC;F9GG=J9 B9IFC89;9B9F5H=J9 8=GCF89F
7<5F57H9F=N98 6M 89GHFI7H=CB C: 65G5@ ;5B;@=5 B9IFCBG 5B8 CL=85H=J9
GHF9GG "H =G 5B 5IHCGCA5@ 8CA=B5BH =B<9F=H98 GMB8FCA9 5GGC7=5H98 K=H<
8=GHIF65B79 =B AIG7@9 :IB7H=CB 9ACH=CB5@ 8=GHIF65B79 5B8 89A9BH=5
"H 5@GC =B7@I89G @57? C: :C7IG 7CB79BHF5H=CB 89DF9GG=CB G<CFHH9FA
A9ACFM @CGG @5B;I5;9 GD997< 5B8 ACJ9A9BH DFC6@9AG &5BC<5F5B
9H 5@  &I@H=D@9 @=B9G C: in vivo 5B8 7@=B=75@ 9J=89B79G =AD@=
75H98 G<K5;5B8<5 =B HF95HA9BH C: !IBH=B;HCBG 8=GCF89F '=HFCDFC
D=CB=7 57=8 =B8I7H=CB A=A=7G H<9 56BCFA5@=H=9G G=A=@5F HC !IBH=B;
HCBG 8=GCF89F D5FH=7I@5F@M CL=85H=J9 GHF9GG ;5=H 56BCFA5@=H=9G 5B8 A=
HC7<CB8F=5@ 8MG:IB7H=CB "B<=6=H=CB C: 7CAD@9L "" :IFH<9F 75IG9G 69<5J
=CIF5@ 9BNMA5H=7 5B8 6=C7<9A=75@ 5@H9F5H=CBG G<K5;5B8<5 FCCH 9L
HF57H 5H 8CG9 C:  5B8  A;?; 8CG9 89D9B89BH@M =ADFCJ98 J5F
=CIG 5@H9F5H=CBG 5B8 G<CKG B9IFCDFCH97H=J9 DCH9BH=5@ 8CA=B5BH@M 6M
5BH=CL=85BH 57H=J=HM $IA5F 5B8 $IA5F 


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
IFH<9F H<9 =BJC@J9A9BH C: 9F;=7 GMGH9A =B !IBH=B;HCBG 8=G95G9
D5H<C;9BG=G <5G 699B F9DCFH98 G<K5;5B8<5 57HG 6M 9F;=7 GMGH9A
5B8 5BH=CL=85BH DCH9BH=5@ F9GHCF9G 579HM@ 7<C@=B9GH9F5G9 5B8 ;@IH5H<=CB9
9BNMA9 @9J9@ 5B8 =ADFCJ9G 7C;B=H=J9 :IB7H=CB H<IG A5?=B; =H GI=H56@9
75B8=85H9 :CF H<9 HF95HA9BH C: !IBH=B;HCBG 8=GCF89F $IA5F 5B8 $I
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4.6. Ashwagandha in dyslexia
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4.7. Ashwagandha in depression
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4.8. Ashwagandha in autism
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4.9. Ashwagandha in addiction
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4.10. Ashwagandha in amyotrophic lateral sclerosis
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5B8 @5HH9F =B A98I@@5 5B8 5BH9F=CF <CFB C: GD=B5@ 7CF8 5=@IF9 =B IDD9F
ACHCF B9IFCBG F9GI@H =B AIG7@9 GH=TB9GG 5B8 GD5GH=7=HM K<9F95G @CK9F
ACHCF B9IFCBG @958 HC AIG7@9 HK=H7<=B; :IFH<9F @958=B; HC 89;9B9F5H=CB
5B8 @CGG =B 7CBB97H=J=HM =B GMB5DG9 H<IG F9GI@H=B; 5HFCD<M FCKB 5B8
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D<CFM@5H=CB C: 'κ K5G DF9J9BH98 IHH5 9H 5@ 
4.11. Ashwagandha in attention de<cit hyperactivity disorder
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

UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
A5M CF A5M BCH 577CAD5BM K=H< <MD9F57H=J=HM "H =G ACF9 7CAACB =B
7<=@8F9B 5B8 C:H9B G99AG HC 69;=B =B 7<=@8<CC8 5B8 A5M 7CBH=BI9 :IF
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5B=GH=7 D5H<K5M C: G<K5;5B8<5 =B !
4.12. Ashwagandha in bipolar disorder
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5. Safety assessment studies of Ashwagandha
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9J5@I5H9 H<9 HCL=7 9::97HG C: G<K5;5B8<5 "H =G 7CBG=89F98 5G <95@H<M
G5:9 5B8 89D9B856@9 8FI; ,I657IH9 HCL=7=HM GHI8=9G K5G 7CB8I7H98 6M
D<5@9 5B8 7C@@95;I9G CB 7CA6=B5H=CB C: G<K5;5B8<5 5B8 =BG9B;
:CF  85MG =B H<F99 8CG9G 5B8 :CIB8 HC =B7F95G9 6C8M K9=;<H 5B8 @=J9F
K9=;<H 6IH =ADFCJ9A9BH =B <9A5HC@C;=75@ D5F5A9H9FG K5G C6G9FJ98
!=GHCD5H<C@C;=75@ 5B8 ;FCGG 9J5@I5H=CB C: 6F5=B ?=8B9M <95FH @=J9F
GD@99B ?=8B9M H9GH=G 5B8 CJ5F=9G K5G :CIB8 HC 69 BCFA5@ -<IG H<9
GHI8M F9J95@98 BC HCL=7 9::97HG =B F5HG D<5@9 9H 5@ 
"B 5BCH<9F GHI8M 5@7C<C@=7 9LHF57H C: G<K5;5B8<5 FCCH K5G
G7F99B98 :CF =HG 57IH9 HCL=7=HM =B ,K=GG 5@6=BC A=79 5B8 GI657IH9 HCL
=7=HM =B 0=GH5F F5HG 5H 5 8CG9 C:  A;?; 58A=B=GH9F98 =BHF5D9F=
HCB95@@M 'C ACFH5@=HM K5G :CIB8 5H H<9 H<9F5D9IH=7 8CG9 <CK9J9F =B
7F9A9BH C: 8CG9 HC  A;?; @98 HC 895H< -<IG % K5G :CIB8 HC
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9LHF57H K5G 58A=B=GH9F98 :CF  85MG 5B8 BC 7<5B;9G K9F9 F9DCFH98
=B 6@CC8 D5F5A9H9FG !CK9J9F 5 897F95G9 =B GD@99B H<MAIG
5B8 58F9B5@ K9=;<HG =B A5@9 F5HG 5B8 5B =B7F95G9 =B 57=8 D<CGD<5H5G9
7CBH9BH K5G C6G9FJ98 6IH CH<9F 6=C7<9A=75@ D5F5A9H9FG K9F9 :CIB8 HC
69 =B BCFA5@ F5B;9G =B 6CH< G9L9G ,<5F585 9H 5@ 
"B  5 GHI8M K5G 7CB8I7H98 HC 9J5@I5H9 H<9 HCL=7 9::97HG C: <M
8FC5@7C<C@=7 FCCH 9LHF57H C: G<K5;5B8<5 +CCH 9LHF57H K5G 58A=B=G
H9F98 HC F5HG 5H 8CG9 C:  A;?; CF5@@M CB79 5B8 C6G9FJ98 :CF 
85MG 'C HCL=7 9::97HG 5B8 ACFH5@=HM K5G F9DCFH98 =B 57IH9 HCL=7=HM GHI8M
IFH<9F =B GI657IH9 HCL=7=HM GHI8M F5HG K9F9 58A=B=GH9F98 H<9 9LHF57H 5H
8CG9 C:   5B8  A;?; :H9F  85MG BC 7<5B;9G K9F9 C6
G9FJ98 =B 6C8M 5B8 J5F=CIG CF;5BG K9=;<H 'C 8CG9 F9@5H98 7<5B;9G K9F9
:CIB8 =B <59A5HC@C;=75@ 5B8 6=C7<9A=75@ D5F5A9H9FG 5B8 BC HF95HA9BH
F9@5H98 <=GHCD5H<C@C;=75@ @9G=CBG K9F9 BCH98 -<IG H<9 GHI8M 7@5=A98 BC
HCL=7 9::97HG C: <M8FC5@7C<C@=7 FCCH 9LHF57H C: G<K5;5B8<5 5H 8CG9 @9J9@
C:  A;?; 6C8M K9=;<H D9F 85M =B F5HG )F56I 9H 5@ 
+979BH@M 5 GHI8M K5G 7CB8I7H98 HC 9J5@I5H9 H<9 7<FCB=7 HCL=7 9::97HG
C: G<K5;5B8<5F=G<H5 CB ?=8B9M :IB7H=CBG -<9 GHI8M =B7@I898 58A=B=G
HF5H=CB C: G<K5;5B8<5F=G<H5 HC 6CH< A5@9 5B8 :9A5@9 5@6=BC F5HG :CF 
85MG 5B8 C6G9FJ98 7<5B;9 =B G9FIA IF95 IF=7 57=8 5B8 7F95H=B=B9 @9J9@G
"B A5@9 F5HG G9FIA @9J9@G C: IF95 5B8 IF=7 57=8 8=8 BCH G<CK 5BM G=;
B=:=75BH 7<5B;9 5H 5@@ H<F99 8CG9G =9 @CK A98=IA 5B8 <=;< 8CG9 6IH
G9FIA 7F95H=B=B9 @9J9@G K9F9 :CIB8 HC 69 =B7F95G98 =B A98=IA 8CG9 @9J9@
;FCID !CK9J9F =B :9A5@9 F5HG BC G=;B=:=75BH 7<5B;9G K9F9 C6G9FJ98 =B
@9J9@G C: G9FIA IF95 IF=7 57=8 5B8 7F95H=B=B9 =B F9GD97H HC @CK A98=IA
5B8 <=;< 8CG9 @9J9@G +5<A5B 9H 5@ 
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57IH9 5B8 GI657IH9 HCL=7=HM GHI8=9G CB D5H9BH98 DC@M <9F65@ :CFAI@5
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'C ACFH5@=HM K5G C6G9FJ98 =B 57IH9 HCL=7=HM GHI8M "B GI657IH9 HCL=7
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5B8 <=GHCD5H<C@C;=75@ D5F5A9H9F :5=@98 HC 9L<=6=H 5BM G=;B=:=75BH 7<5B;9
@GC BC A5>CF 7<5B;9G =B 6=C7<9A=75@ 9BNMA9G =B7@I8=B; @=J9F 5B8 F9B5@
9BNMA9G A5=B@M , (- , )- %) %! - 5B8 ) K9F9 C6G9FJ98
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:CIB8 HC 69 G5:9 5B8 A5M :IFH<9F 69 9LD@CF98 :CF H<9F5D9IH=7 IH=@=N5
H=CB G BC HCL=7=HM K5G C6G9FJ98 =B 57IH9 GI657IH9 5B8 7<FCB=7 HCL=7
=HM GHI8=9G K<=7< 89H9FA=B9G H<9 K=89 G5:9HM A5F;=B C: G<K5;5B8<5
6. Recent patents of Ashwagandha in brain disorders
IFF9BH@M D5H9BHG 5F9 7CBG=89F98 5G H<9 ACGH G=;B=:=75BH 5B8 F9@=
56@9 GCIF79 C: =B:CFA5H=CB )5H9BHG 7CBH5=B =B:CFA5H=CB =B 5@@ 89DH<G 5B8
6F95H<G 5B8 =G 9GH=A5H98 H<5H – =B:CFA5H=CB 5F9 BCH 5J5=@56@9 5BM
K<9F9 9@G9
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7CA6=B5H=CBG K=H< CH<9F A98=7=B5@ D@5BHG :CF IG9 =B J5F=CIG 8=G95G9G =B
7@I89G 5BH=A=7FC6=5@ 5BH=@=D=89A=7 5BH=8=569H=7 5BH=DMF9H=7 5BH==B
R5AA5HCFM 5BH=5;9=B; 5BH=!"/ 5BH=5FH<F=H=7 5BH=657H9F=5 5BH=A=
7FC6=5@ 5BH=<MD9F@=D=89A=7 5BH=75B79F 6F5=B 8=GCF89FG 9H7 +979BH
D5H9BHG =B D9F=C8 :FCA  HC  <5J9 699B 9B@=GH98 =B -56@9 
7. Discussion & conclusion
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HC 9::97H=J9B9GG C: <95@H< 75F9 =BH9FJ9BH=CBG 577IF5H9@M 5B8 F9@=56@M
"B H<=G F9J=9K K9 9J5@I5H98 H<9 9::97HG C: G<K5;5B8<5 CB 6F5=B F9
@5H98 8=GCF89FG G<K5;5B8<5 5B8 =HG 9LHF57H <5J9 699B IG98 G=B79
897589G HC HF95H J5F=CIG 8=CF89FG G<K5;5B8<5 =G @5F;9@M IG98 5G 5B
=AAIBCAC8I@5HCF =B F979BH H=A9G 5B8 =B8=75H98 5BH=8=569H=7 <9D5HC
DFCH97H=J9 5BH=75B79F 5BH==BR5AA5HCFM 57H=J=HM 5G K9@@ G<K5;5B8<5
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F9@5H98 8=GCF89FG G<K5;5B8<5 =G 7<9A=75@@M 9BF=7<98 K=H< BIA9F
CIG 57H=J9 7CBGH=HI9BHG GI7< 5G K=H<5BC@=89G


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Fig. 3. ,IAA5FM C: DFCDCG98 A97<5B=GA =BJC@J98 =B AI@H=D@9 6F5=B 8=GCF89F 6M 57H=J9 7CBGH=HI9BHG C: G<K5;5B8<5 FCCH
G=HC=B8CG=89G 5B8 G9J9F5@ J5@I56@9 5@?5@C=8G H<5H <5J9 699B 9LD@CF98
H<FCI;< J5@=8 G7=9BH=Q7 5B5@MG=G -<9G9 7CBGH=HI9BHG <5J9 699B 8C7I
A9BH98 HC 69 IG9:I@ :CF 7IF=B; 6F5=B F9@5H98 8=GCF89F ,9J9F5@ GHI8=9G 5F9
69=B; 7CB8I7H98 KCF@8K=89 HC 9LD@CF9 H<9 D<5FA57C@C;=75@ 69B9QHG C:
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9F98 5G H<9 69GH A9ACFM 9B<5B7=B; HCB=7 :CF H<9 9@89F@M 5B8 7<=@8F9B "H
=G CB9 C: H<9 69GH B9FJ=B9 HCB=7G =B MIFJ985 H<9 ACGH 5B7=9BH GMGH9A C:
A98=75@ G7=9B79G ,=B;< 9H 5@  /5F=CIG DI6@=75H=CBG CB G<K5
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699B D9F79=J98 H<5H ACGH C: H<9 DI6@=G<98 85H5 5F9 65G98 CB in vitro 5B8
in vivo GHI8=9G 5B8 :9K 7@=B=75@ 85H5 =G 5J5=@56@9 HC GIDDCFH =HG 9J=89B79
C: 57H=J=H=9G =B AI@H=D@9 8=G95G9G -<9F9 =G BC 8=F97H GHI8M HC 7CAD5F9 H<9
9::97H C: G<K5;5B8<5 5B8 =HG 9LHF57H K=H< 9GH56@=G<98 5DDFCJ98 8FI;G
=B 5 ;=J9B =B8=75H=CB -<IG G<K5;5B8<5 5B8 =HG 9LHF57H AIGH 69 7CB
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DCH9BH F9;9B9F5H=J9 HCB=7 8I9 HC =HG AI@H=D@9 D<5FA57C@C;=75@ 57H=CBG
@=?9 5BH=GHF9GG 5B8 B9IFCDFCH97H=J9 "H =G IG9:I@ :CF 8=::9F9BH HMD9G C:
B9IFC89;9B9F5H=J9 8=G95G9G GI7< 5G )5F?=BGCBG !IBH=B;HCBG 5B8
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H<9 @5F;9F 89;F99 =G 8I9 HC =HG 5BH=CL=85BH 57H=J=HM BH=CL=85BH 57
H=J=HM =G 7CBG=89F56@M 8I9 HC 5 897F95G9 CF BCFA5@=N5H=CB =B F9J9FG98
@=D=8 D9FCL=85H=CB @9J9@G <5HH57<5FM5 9H 5@  5B8 =B7F95G9
CF BCFA5@=N5H=CB C: 9@9J5H98 GID9FCL=89 8=GAIH5G9 @9J9@G A5=B@M =B
79F969@@IA GHF=5HIA <=DDC75ADIG :FCBH5@ 7CFH9L 9H7 K<=7< AIGH
69 :C@@CK98 6M 57H=J=HM C: 9BNMA9G 75H5@5G9 )F5?5G< 9H 5@ 
5B8 ;@IH5H<=CB9 D9FCL=8=G9  IDH5 9H 5@  =B GHF=5HIA 7CF
H9L <=DDC75ADIG 5B8 CH<9F D5FHG C: 6F5=B G<K5;5B8<5 5@GC F9;I
@5H9G BCB9BNMA5H=7 5BH=CL=85BH @9J9@G 6M F9GHCF=B; H<9 @9J9@G C: ;@I
H5H<=CB9 K<=7< =G 5B 9B8C;9BCIG A9A69F C: 5BH=CL=85BH 89:9B79 GMG
H9A &5<9F  @IH5H<=CB9 57HG 6M F957H=B; K=H< CLM;9B :F99
F58=75@G CF;5B=7 D9FCL=89G 5B8 5@GC F9;I@5H9 9BNMA9G ;@IH5H<=CB9


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
Table 4
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.,  IB7H=CB5@:CFAI@5H=CB=B7<9K=B;;IA +98I7H=CBC:GHF9GG5B8CF9B<5B79A9BHC:9B9F;M5B8
A9BH5@7@5F=HM
.,  CADCG=H=CBG5B8&9H<C8G:CF"ADFCJ=B;,@99D.G=B;'IHF579IH=75@
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.,  'IHF579IH=75@:CFAI@5H=CB:CFHF95HA9BHC:5BL=9HM5B889DF9GG=CB BH=5BL=9HM5B85BH=89DF9GG=CB
.  &I@H=7CADCB9BH:CFAI@5H=CB:CF=ADFCJ=B;B9IFC@C;=75@:IB7H=CB -F95HA9BHC:B9IFC@C;=75@5B8B9IFCDGM7<=5HF=78=G95G9G
  DFC79GGHC9B<5B79H<96=C57H=J=HMC:5G<K5;5B8<59LHF57HG "AAIBCAC8I@5HCFM57H=J=HM5BH==BR5AA5HCFM57H=J=HM
5BH=GHF9GG57H=J=HM5BH=8=569H=757H=J=HM5B8G@99DEI5@=HM
)  "B8C@95@?M@5A=BCK=H<5GH9FC=87CB>I;5H9G5B8A9H<C8C:IG9 BH=@N<9=A9FG5BH5BL=9HM5B85BH=
89DF9GG=J9 8=GCF89FG
0(  CADCG=H=CBG:CFA9BH5@5@9FHB9GG5B8A9H<C8GC:A5?=B;5B8IG=B;H<9F9C: &9BH5@5@9FHB9GG
.,  .G9C:5K=H<5B=59LHF57H:CFH<9HF95HA9BHC:5AM@C=8F9@5H988=G95G9G AM@C=8F9@5H988=G95G9G=B7@I8=B;@N<9=A9F8=G95G9
.,  &I@H=:IB7H=CB5@:CFAI@5H=CB7CADF=G98C:B5HIF5@=B;F98=9BHG5B8A9H<C8C:
DF9D5F5H=CBA5BI:57HIF=B;H<9F9C:
BH=@N<9=A9FG5B8AI@H=D@9G7@9FCG=G
0(  IB7H=CB5@7<9K=B;;IA7CADF=G=B;D<MHCBIHF=9BHG5B8585DHC;9B=7<9F6G CCGH A9BH5@7@5F=HM5B87CB79BHF5H=CB
#)  .G9C:G<K5;5B8<59LHF57H:CFH<9HF95HA9BHC: αGMBI7@9=BCD5H<=9G αGMBI7@9=BCD5H<=9G=B7@I8=B;)5F?=BGCBG8=G95G9
$+  CGA9H=77CADCG=H=CB:CF=ADFCJ=B;G@99D8=GCF89FCFA5=BH5=B=B;899D
G@99D7CADF=G=B;K=H<5B=5GCAB=:9F5&CFIG5IGHF5@=G5B8DIF9H959LHF57HG
<FCB=7G@99D 8=GCF89FG
)  .G9C:5K=H<5B=59LHF57H:CFH<9HF95HA9BHC:89AM9@=B5H=B;8=G95G9G &I@H=D@9G7@9FCG=G8=G95G9
0(  BH=DGM7<CH=77CADCG=H=CB5B8HF95HA9BHA9H<C8G BH=G7<=NCD<F9B=5CFG7<=NC5T97H=J98=GCF89F
'  0=H<5B=5GCAB=:9F5@57H=897CADCIB8A9H<C8:CF9LHF57H=B;G5A95B8
5DD@=75H=CBC:K=H<5B=5GCAB=:9F5@57H=897CADCIB8
BH==BR5AA5HCFM
.,  '5HIF5@DFC8I7H7CADCG=H=CBG:CFHF95H=B;CFA5B5;=B;GMADHCAGC:588
!5BL=9HM5B889DF9GG=CB
-F95HA9BHC:588=7H=CB!5BL=9HM5B889DF9GG=CB
)  0=H<5BC@=89GIG9:I@:CFH<9HF95HA9BHC:B9IFC89;9B9F5H=J98=G95G9G -F95HA9BHC:B9IFC89;9B9F5H=J98=G95G9G
.,  &I@H=7CADCB9BH:CFAI@5H=CBG -F95HA9BHC:7C;B=H=J9897@=B9@N<9=A9FG8=G95G95B8
CH<9F89A9BH=5G
.,  '=7CH=B9:F99<9F65@7CADCG=H=CB:CFGAC?=B;89588=7H=CB5B8HF95HA9BHC:
G=899T97HG5B8CF5=@A9BHG:FCAGAC?=B;
BH=GAC?=B;
)  .G9C:5K=H<5B=59LHF57H:CFH<9HF95HA9BHC:B9IFCAIG7I@5F8=G95G9G ACHCFB9IFCB8=G95G9G@=?95AMCHFCD<=7@5H9F5@G7@9FCG=G
.,  CADCG=H=CBG5B8A9H<C8G:CFHF95H=B;!"/5GGC7=5H98B9IFC7C;B=H=J9
8=GCF89FG
BH=588=7H=CB
D9FCL=8=G9 5B8 ;@IH5H<=CB9,HF5BG:9F5G9 6M 57H=B; 5G GI6GHF5H9 +5
>5,5B?5F 9H 5@ 56 "H DFCACH9G :CFA5H=CB C: 89B8F=H9G H<FCI;<
 A=A9H=7 9::97H G<K5;5B8<5 5B8 =HG 9LHF57HG =ADFCJ9 9B9F;M @9J
9@G 5B8 A=HC7<CB8F=5@ <95@H< GC =H =G 9::97H=J9 5G 5B 5BL=C@MH=7 ,=B;< 9H
5@ 
CD5A=B9F;=7 57H=J=HM C: 5 8FI; 75B 9B<5B79 A9ACFM 5B8 BIA
69F C: D5D9FG 5F9 DI6@=G<98 G<CK=B; 8CD5A=B9F;=7 57H=J=HM C: G<K5
;5B8<5 FCCH 5F7< )F5?5G< 9H 5@   BIA69F C: in vivo
5B8 7@=B=75@ GHI8=9G <5J9 DFCJ98 H<9 BCCHFCD=7 57H=J=HM C: G<K5;5B8<5
5B8 =HG 9LHF57H <I@9M <9B;5DD5 9H 5@ )=B;5@= 9H
5@  '9IFCDFCH97H=J9 9::97HG C: G<K5;5B8<5 GIDDCFHG =HG 9:Q
757M =B @N9=A9FG D5H=9BHG $I6CM5A5 9H 5@ /9B &IFH<M 9H
5@ 
G<K5;5B8<5 5B8 =HG 9LHF57H <5J9 5BH=GHF9GG 5B8 5BL=C@MH=7 9::97H
5B8 H<9G9 9::97H 5F9 =BJC@J98 =B A9ACFM 9B<5B7=B; 57H=J=HM 5B8 IG98
K<9B BCFA5@ A9BH5@ 57H=J=H=9G C: <IA5B 5F9 5::97H98 MG9B7? 9H
5@  9G=89 H<9 G<K5;5B8<5 FCCH =HG @95: 9LHF57H =B8=75H98
DFC656@9 9::97H CB 5BH=CL=85BH =B8I7H=CB =B H<9 )5F?=BGCBG 8=G95G9
ACIG9 6F5=B +5>5,5B?5F 9H 5@ 56 -<9 8CD5A=B9 D@5MG 5B
=ADCFH5BH 7<5F57H9F =B ACHCF 7CBHFC@ -<9 897F95G9 @9J9@G C: 75H9
7<C@5A=B9G 5B8 CL=85H=J9 GHF9GG 5F9 H<9 =ADCFH5BH F95GCBG C: B9IFC89
;9B9F5H=CB =B )5F?=BGCBG 8=G95G9 5B8 75IG9G @CGG C: ACHCF :IB7H=CB G99B
=B )5F?=BGCBG 8=G95G9 D5H=9BHG &=G<F5 9H 5@ !5@@=K9@@ 
-<9 =B7F95G98 @9J9@G C: 75H97<C@5A=B9 5:H9F G<K5;5B8<5 HF95HA9BH
GI;;9GHG H<5H G<K5;5B8<5 =B8I79G 75H97<C@5A=B9G =B H<9 )5F?=BGCBG
8=G95G9
-<IG 69G=89 5BH=CL=85BH J5F=CIG CH<9F A97<5B=GAG 5F9 7CBG=89F98
HC 69 F9GDCBG=6@9 :CF DFCH97H=J9 9::97H C: G<K5;5B8<5 =B J5F=CIG ',
8=GCF89FG =B7@I8=B; =B<=6=H=CB C: 579HM@ 7<C@=B9GH9F5G9 57H=J=HM =B7F95G9
=B 579HM@7<C@=B9 F979DHCF 9LDF9GG=CB 5BH=@N<9=A9F =B7F95G9 9LDF9G
G=CB C: 579HM@7<C@=B9 F979DHCF C;B=H=J9 =AD5=FA9BH 5B8 8CD5A=B9 F9
79DHCF )5F?=BGCBG 8=G95G9 IFH<9F =H 5@GC 75IG9G =B<=6=H=CB =B ;@I7C
7CFH=7C=8G 5B8 =B7F95G9 =B G9FCHCB=B 7CB79BHF5H=CB GHF9GG 5B8 CH<9F F9
@5H98 8=G95G9 DFCH97H=CB C: A=HC7<CB8F=5 !IBH=B;HCBG 8=G95G9 5B8 =B
7F95G9 =B 7M7@=7 589BCG=B9 ACBCD<CGD<5H9 9F96F5@ =G7<59A=5 IF;
9H 5@  G<K5;5B8<5 =G 7<9A=


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
75@@M 9BF=7<98 K=H< BIA9FCIG 57H=J9 7CBGH=HI9BHG A5=B@M GH9FC=85@ 5@?5
@C=8G 5@CB; K=H< @57HCB9G K<=7< 5F9 F9GDCBG=6@9 :CF =HG J5F=CIG B9IFCDFC
H97H=J9 FC@9 =B ', 8=GCF89F
 DFCD9F K9@@8C7IA9BH98 D<5FA57C@C;=75@ 57H=J=HM C: H<9 D<MHC
7<9A=75@ 7CADCG=H=CB C: G<K5;5B8<5 =G @57?=B; /5F=CIG =B8=J=8I5@
7CBGH=HI9BHG <5J9 699B =GC@5H98 5B8 7<5F57H9F=G98 :CF H<9=F 6F5=B F9@5H98
8=GCF89FG 6IH GH=@@ B998 HC 8=G7CJ9F 5B8 9LD@CF9 H<9 HF95GIF9 HC =89BH=:M
H<9 7CAD@9H9 6=C57H=J9 7CBGH=HI9BHG =B H<=G D@5BH -<=G KCI@8 79FH5=B@M
<9@D HC DFCACH9 5B 9LH9BG=J9 IG9 C: G<K5;5B8<5 5B8 =HG 9LHF57H 5B8
H<9 89G=;B C: B9K DFC8I7H :CF J5F=CIG 6F5=B 8=GCF89F -<9 56CJ9 QB8=B;G
7@95F@M =B8=75H9 H<5H H<9 IG9 C: G<K5;5B8<5 5B8 =HG 7CBGH=HI9BHG <5G
5 F95GCB56@9 5B8 G7=9BH=Q7 65G=G G<K5;5B8<5 5B8 =HG 9LHF57H G<CK98
7CIBH@9GG DCH9BH=5@ 5G G5:9 5B8 57H=J9 75B8=85H9 =B 6F5=B F9@5H98 8=G
CF89FG &CF9 FC6IGH G7=9BH=Q7 9J=89B79 =B F9@5H=CB HC D<5FA57C@C;=75@
9J5@I5H=CB =B7@I8=B; 8FI; @=?9 DFCD9FH=9G B998G HC 69 D9F:CFA98 =B CF89F
HC DFCACH9 H<9A 5G 5 DCH9BH=5@ 8FI; 75B8=85H9 :CF A5F?9H98 DFC8I7HG
IFH<9F 7@=B=75@ HF=5@G C: 6=C57H=J9 7CADCIB8G 5@CB9 5B8 =B GMB9F;=GH=7
7CA6=B5H=CB 5F9 H<9 A5>CF Q9@8 K<=7< B998G 9LD@CF5H=CB @GC ACF9 F9
G95F7< 5B8 7@=B=75@ =BJ9GH=;5H=CB 5F9 B99898 HC QB8 CIH H<9 57HI5@ A97<
5B=GA 5B8 89H9FA=B9 H<9 CDH=A5@ F5B;9 C: 8CG5;9
Declaration of competing interest
-<9 5IH<CF 897@5F9G BC 7CBR=7H C: =BH9F9GH 5GGC7=5H98 K=H< H<=G DI6@=
75H=CB
Appendix A. Supplementary data
,IDD@9A9BH5FM 85H5 HC H<=G 5FH=7@9 75B 69 :CIB8 CB@=B9 5H <HHDG8C=
CF;>>9D
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<A98 + $<5B '  05G99A & $<5B 3 #  !C@=GH=7 5DDFC57< =B H<9 A5B5;9A9BH
C: 89DF9GG=CB 5 F9J=9K # "BH9; CAA !95@H<   –
?<CCB   )5B89M , -=K5F= , )5B89M +  0=H<5BC@=89  CT9FG B9IFCDFCH97H=CB
5A9@=CF5H9G GHF9GG F9G=GH5B79 5B8 DFC@CB;G H<9 @=:9 9LD97H5B7M C: 59BCF<568=H=G
9@9;5BG LD 9FCBHC@  –
BCBMACIG  9BHF5@ CIB7=@ :CF +9G95F7< =B .B5B= &98=7=B9 &=B=GHFM C: !95@H< 5B8
5A=@M 09@:5F9 CJ9FBA9BH C: "B8=5 -<9 .B5B= )<5FA57CDC9=5 C: "B8=5 '9K 9@<=
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6=CGMBH<9G=G 8IF=B; <MDCL=5 )@C, (B9   9
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5MIFJ98=7 D@5BHG IG9:I@ =B A9BH5@ <95@H< '5H )FC8 #   –
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=B A=79 )<7C; &5;  ,IDD@ , –
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)GM7<CD<5FA57C@C;M   –
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=5;BCG=G 5B8 -F95HA9BH :CIFH< 98 -<9 I=@:CF8 )F9GG
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"B<=6=H=CB C: ACFD<=B95B8 9H<5BC@A98=5H98 GH=AI@5H=CB C: A9GC@=A6=7 8CD5A=B9
B9IFCBG 6M K=H<5B=5 GCAB=:9F5 FCBH '9IFCG7=  
9@A5?9F + !  =DC@5F 8=GCF89F ' B;@ # &98   –
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=GD@5M  9J5@I5H=CB C: 9H<5BC@ 9LHF57HG C: 9BH9@@5 5G=5H=75 5B8 0=H<5B=5
GCAB=:9F5 G<CKG H<5H H<9M 75B BCBGMB9F;=GH=75@@M 5A9@=CF5H9 6=C7<9A=75@ 5B8
69<5J=CIF5@ 85A5;9G =B &)-) =B8I798 )5F?=BGCB’G AC89@ C: A=79 )@C, (B9  
9
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57H=J=HM C: 0=H<5B=5 GCAB=:9F5 ;@M7CK=H<5BC@=89G 5B 9LD9F=A9BH5@ GHI8M
)<MHCA98=7=B9   –
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)GM7<=5HF   –
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GMADHCA897@=B9 =B 7CB8I7H 8=GCF89F 5 :CIFM95F DFCGD97H=J9 GHI8M C: 5B !
G5AD@9 # A 758 <=@8 8C@9G7 )GM7<=5HFM   –
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DIH5H=J9 D@5BH 65G98 @958 7CADCIB8G :CF @N<9=A9F =G95G9 -<9F5DM CADIH =C@
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GH5B85F8=N98 0=H<5B=5 GCAB=:9F5 IB5@ FCCH 9LHF57H 5@H9FG 65G5@ 5B8
ACFD<=B9=B8I798 CD=C=8 F979DHCF ;9B9 9LDF9GG=CB 7<5B;9G =B B9IFC6@5GHCA5 79@@G
& CAD@ @H9FB5H=J9 &98   –
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C: =BR5AA5HCFM DFC79GG9G FCBH B8C7F=BC@   –
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D@5796C7CBHFC@@98 58>IB7H=J9 GHI8M C: 5B 9LHF57H C: 0=H<5B=5 GCAB=:9F5 :CF 7C;B=H=J9
8MG:IB7H=CB =B 6=DC@5F 8=GCF89F # @=B )GM7<=5HF   –
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5BH5;CB=GH=7 DFCD9FH=9G =C7<9A =CD<MG +9G CAAIB   –
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57H=J9 7CBGH=HI9BH :FCA 0=H<5B=5 GCAB=:9F5 5TCF8G DFCH97H=CB 5;5=BGH '&=B8I798
9L7=HCHCL=7=HM =B B9IFCB@=?9 79@@G &C@ '9IFC6=C@   –
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"B8=5B ;=BG9B; 9@@ &C@ %=:9 ,7=   –
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)<MHCH<9F +9G   –
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DF9J9BHG :5H 89DCG=H=CB 5B8 =BR5AA5H=CB =B H<9 J=G79F5@ :5H C: A=79 :98 5 <=;<:5H 8=9H
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K=H<5B=5 GCAB=:9F5 B=7CH=B9 =B8I798 7CB8=H=CB98 D@579 DF9:9F9B79 =B A=79 )<7C; #
  –
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G<K5;5B8<5 =B B9IFC69<5J=CIF5@ 8=GCF89FG =B8I798 6M 6F5=B CL=85H=J9 GHF9GG =B
FC89BHG 5 GMGH9A5H=7 F9J=9K 5B8 A9H5‐5B5@MG=G # )<5FA )<5FA57C@  
–
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,(  ACIG9 AC89@ C: 5AMCHFCD<=7 @5H9F5@ G7@9FCG=G LD '9IFC@  –
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H9B M95FG CB BBI +9J )GM7<C@  –
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D9F:CFA5B79 5HH9BH=CB5@ 7CBHFC@ H<9CFM ACH=CB   –
CFA5B & $9FB5 '   &9F;=B; 5MIFJ98=7 5G<K5;5B8<5 K=H< HF58=H=CB5@ <=B9G9
A98=7=B9 )5FH  CIB85H=CB =B 5G<K5;5B8<5 D<MG=C@C;=75@ 9T97HG 7@=B=75@ 9S757M
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8=9@8F=B=B8I798 7C;B=H=J9 =AD5=FA9BH 6M AC8I@5H=CB C: CL=85H=J9 GHF9GG =B F5H 6F5=B
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9J=89B79 HC =B<=6=H=CB C: <IA5B 579HM@ 7<C@=B9GH9F5G9 6M K=H<5BC@=89 5 :CF @N<9=A9F
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5B8 7C;B=H=J9 =AD5=FA9BHG 5GGC7=5H98 K=H< GMGH9A=7 =BR5AA5H=CB & CAD@
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5BH=CL=85BH 89:9BG9 =B 5;98 GD=B5@ 7CF8 5B8 =B<=6=HG 7CDD9F =B8I798 @=D=8 D9FCL=85H=CB
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!5@@=K9@@   +C@9 C: :F99 F58=75@G =B B9IFC89;9B9F5H=J9 8=G95G9G H<9F5D9IH=7
=AD@=75H=CBG :CF 5BH=CL=85BH HF95HA9BH FI;G ;=B;   –
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+9G   –
#5M5DF5?5G5A  ,HF5G6IF;  '5=F &   )CH9BH @=D=8 D9FCL=85H=CB =B<=6=HCFG
:FCA 0=H<5B=5 GCAB=:9F5 :FI=HG -9HF5<98FCB   –
#C<B #  -<9F5D9IH=7 DCH9BH=5@ C: 0=H<5B=5 GCAB=:9F5 5 F9DCFH CB
D<MHCD<5FA57C@C;=75@ DFCD9FH=9G "BH # )<5FA5 ,7= +9G   –


UNCORRECTED PROOF
S. Zahiruddin et al. Journal of Ethnopharmacology xxx (xxxx) xxx-xxx
$5BM5=M55 & =;5A65F6 , ) FCF55 , $5D=@5 , ,=B;< + +   "B J=JC 9T97H C:
<9F6 0=H<5B=5 GCAB=:9F5 CB =AAIBCAC8I@5HCFM 5B8 5BH=CL=85H=J9 DCH9BH=5@ C: A=@?
=B A=79 CC8 ;F=7 "AAIBC@   – 
$5IF - $5IF   0=H<5B=5 GCAB=:9F5 5G 5 DCH9BH=5@ 75B8=85H9 HC 5A9@=CF5H9 <=;< :5H
8=9H=B8I798 5BL=9HM 5B8 B9IFC=BR5AA5H=CB # '9IFC=BR5AA5H=CB   –
$<5F9  )  "B8=5B &98=7=B5@ )@5BHGB "@@IGHF5H98 =7H=CB5FM GH "B8=5B +9DF=BH
,DF=B;9F "B8=5 )JH %H8 '9K 9@<= "B8=5 D 
$CB5F  ,<5< ' ,=B;< + ,5L9B5 ' $5I@ ,  058<K5 + -<5?IF & $ 
)FCH97H=J9 FC@9 C: G<K5;5B8<5 @95: 9LHF57H 5B8 =HG 7CADCB9BH K=H<5BCB9 CB
G7CDC@5A=B9=B8I798 7<5B;9G =B H<9 6F5=B 5B8 6F5=B89F=J98 79@@G )@C, (B9  
9
$CC6  /C@?CK '   '9IFC6=C@C;M C: 588=7H=CB 5 B9IFC7=F7I=HFM 5B5@MG=G -<9
@5B79H )GM7<=5HFM   –
$I6CM5A5 - -C<85  $CA5HGI $  '9IF=H=7 F9;9B9F5H=CB 5B8 GMB5DH=7
F97CBGHFI7H=CB =B8I798 6M K=H<5BC@=89  F # )<5FA57C@   –
$I6CM5A5 - -C<85  $CA5HGI $  T97HG C: 5G<K5;5B8<5 FCCHG C: 0=H<5B=5
GCAB=:9F5 CB B9IFC89;9B9F5H=J9 8=G95G9G =C@ )<5FA I@@   –
$I@?5FB= , $ <=F   0=H<5B=5 GCAB=:9F5 5B "B8=5B ;=BG9B; )FC;
'9IFC)GM7<CD<5FA57C@ =C@ )GM7<=5HFM   –
$IA5F  )5@=K5@ ) )5HB5=? ' )5HB5=? +  0=H<5B=5 GCAB=:9F5 D<MHC7<9A=75@G
7CB:9F B9IFCDFCH97H=CB 6M G9@97H=J9 =B<=6=H=CB C: B'CG 5B =B G=@=7C GHI8M HC G95F7<
DCH9BH 5B8 G9@97H=J9 =B<=6=HCFG :CF <IA5B B'(, # -<9CF CADIH <9A  

$IA5F  )5HB5=? +  LD@CF=B; B9IFCDFCH97H=J9 DCH9BH=5@ C: 0=H<5B=5 GCAB=:9F5
D<MHC7<9A=75@G 6M =B<=6=H=CB C: @I'7CBH5=B=B; '& F979DHCFG 5B =B G=@=7C
GHI8M &98 !MDCH<9G9G  –
$IA5F  )5HB5=? +  "B<=6=H=CB C: ;9@5H=B5G9G &&) 5B8 &&) 6M 0=H<5B=5
GCAB=:9F5 D<MHC7<9A=75@G 7CB:9FG B9IFCDFCH97H=CB =B GHFC?9 5B =B ,=@=7C B5@MG=G
"BH9F8=G7=D ,7=   –
$IA5F ) $IA5F   T97HG C: FCCH 9LHF57H C: 0=H<5B=5 GCAB=:9F5 =B
'=HFCDFCD=CB=7 57=8=B8I798 7C;B=H=J9 8MG:IB7H=CB 5B8 CL=85H=J9 85A5;9 =B F5HG "BH
# BJ=FCB !95@H< +9G   –
$IA5F ) $IA5F   )CGG=6@9 B9IFCDFCH97H=J9 9T97H C: 0=H<5B=5 GCAB=:9F5 FCCH
9LHF57H 5;5=BGH B=HFCDFCD=CB=7 57=8=B8I798 69<5J=CF5@ 6=C7<9A=75@ 5B8
A=HC7<CB8F=5@ 8MG:IB7H=CB =B 5B 5B=A5@ AC89@ C: !IBH=B;HCB’G 8=G95G9 # &98 CC8
  –
$IA5F , ,95@  # !CK9G & # + $=H9  (?9@@C  #  "B J=HFC DFCH97H=J9
9T97HG C: 0=H<5B=5 GCAB=:9F5 % 8IB5@ FCCH 9LHF57H 5;5=BGH <M8FC;9B D9FCL=89 5B8
β‐5AM@C=8  ‐=B8I798 7MHCHCL=7=HM =B 8=T9F9BH=5H98 ) 79@@G )<MHCH<9F +9G 
 –
$IA5F ,  +5>5B5B8< &  IF5=D5B8=5B   7IH9 5B8 GI657IH9 HCL=7=HM GHI8=9G
C: 5 D5H9BH98 5BH=5BL=9HM DC@M <9F65@ :CFAI@5H=CB -CL=7C@C;M   –
$IF5D5H= $ + / H@IF= / , + ,5A=??5BBI - '5=F & ) '  G<K5;5B8<5
K=H<5B=5 GCAB=:9F5 F9J9FG9G β5AM@C=8 =B8I798 HCL=7=HM =B <IA5B B9IFCB5@ 79@@G
=AD@=75H=CBG =B !"/5GGC7=5H98 B9IFC7C;B=H=J9 8=GCF89FG !' )@C, (B9  
9
%5=8@5K &   !CAC9CD5H<=7 FI; )FCJ=B; C: 0=H<5B=5 ,CAB=:9F5 ! C7HCF5@
=GG9FH5H=CB
%MCB + ,<5MK=HN ,  ,<5MK=HN     89QB=H=CB C: 8MG@9L=5 BB MG@9L=5 
 –
&5<9F )  -<9 9T97HG C: GHF9GG 5B8 5;=B; CB ;@IH5H<=CB9 A9H56C@=GA ;9=B; +9G
+9J   –
&5=HM - 8<=?5F=  <5HH57<5FM5 $ =GK5G , 96B5H< ) $ &5<5F5B5  ,  
GHI8M CB 9J5@IH=CB C: 5BH=89DF9GG5BH 9T97H C: "A=DF5A=B9 58>IB7H K=H< GK5;5B8<5
5B8 F5A<= '9D5@ &98 C@@ #   –
&5B>IB5H< & # &IF5@=8<5F5  ,H5B85F8=N98 9LHF57H C: 0=H<5B=5 GCAB=:9F5
G<K5;5B8<5 A5F?98@M CTG9HG FCH9BCB9=B8I798 @C7CACHCF 89Q7=HG CL=85H=J9
=AD5=FA9BHG 5B8 B9IFCHCL=7=HM =B FCGCD<=@5 A9@5BC;5GH9F # CC8 ,7= -97<BC@ 
 –
&5BC<5F5B , I=@@9A=B # 6=F5A5GIB85F= + , GG5 & & ?65F & ?65F & 
 -<9 FC@9 C: F957H=J9 CLM;9B GD97=9G =B H<9 D5H<C;9B9G=G C: @N<9=A9F’G 8=G95G9
)5F?=BGCB’G 8=G95G9 5B8 !IBH=B;HCB’G 8=G95G9 5 A=B= F9J=9K (L=8 &98 9@@ %CB;9J
–
&=F>5@=@= & ! 5?<F-565H5659= , & @=N589< ! <5GG9ADCIF  &=FN5>5B=  
9B9H=7 5B8 0=H<5:9F=B  5B5@MG=G C: "F5B=5B B5HIF5@ DCDI@5H=CBG C: 0=H<5B=5
GCAB=:9F5 5B8 0 7C5;I@5BG 6M +) 5B8 !)-% '5H )FC8 CAAIB  
–
&=G<F5 %  ,=B;<   5;9B5=G ,  ,7=9BH=Q7 65G=G :CF H<9 H<9F5D9IH=7 IG9 C:
0=H<5B=5 GCAB=:9F5 5G<K5;5B8<5 5 F9J=9K @H9FB5H=J9 &98 +9J   –
&I?<9F>99 , $IA5F  )5HB5=? +  "89BH=Q75H=CB C: DCH9BH=5@ =B<=6=HCFG C: )+)
5 F9;I@5HCF C: 75GD5G9=B89D9B89BH 79@@ 895H< D5H<K5M :FCA 0=H<5B=5 GCAB=:9F5
D<MHC7<9A=75@G :CF 7CA65H=B; B9IFCHCL=7=HM 5 GHFI7HIF965G98 =BG=@=7C GHI8M #
-<9CF CADIH <9A   
'58?5FB= $ &  "B "B8=5B &5H9F=5 &98=75 H<=F8 98 " )CDI@5F )F5?5G<5B %H8
CA65M DD –
'5=8I ) , ,=B;<  $I@?5FB= , $  T97H C: 0=H<5B=5 GCAB=:9F5 FCCH 9LHF57H CB
<5@CD9F=8C@=B8I798 CFC:57=5@ 8MG?=B9G=5 DCGG=6@9 A97<5B=GAG C: 57H=CB # &98 CC8
  –
)5B89M  5B= , IHH ) ,5HH= ' $ ,IF= $  *5N= '  &I@H=:IB7H=CB5@
B9IFCDFCH97H=J9 9T97H C: 0=H<5BCB9 5 7CADCIB8 :FCA 0=H<5B=5 GCAB=:9F5 FCCHG =B
5@@9J=5H=B; 7C;B=H=J9 8MG:IB7H=CB MHC?=B9  –
)5HK5F8<5B  05FI89  )IG<D5B;585B ) <5HH '  MIFJ985 5B8 HF58=H=CB5@
<=B9G9 A98=7=B9 5 7CAD5F5H=J9 CJ9FJ=9K J=8 5G98 CAD@9A9BH @H9FB &98 
 –
)=B;5@= . )=@@= + 5H=A5 '  T97H C: GH5B85F8=N98 5EI9CIG 9LHF57H C: 0=H<5B=5
GCAB=:9F5 CB H9GHG C: 7C;B=H=J9 5B8 DGM7<CACHCF D9F:CFA5B79 =B <95@H<M <IA5B
D5FH=7=D5BHG )<5FA57C;B +9G   –
)F56I )  )5B7<5D5?9G5B , +5>    7IH9 5B8 GI6‐57IH9 CF5@ HCL=7=HM 5GG9GGA9BH
C: H<9 <M8FC5@7C<C@=7 9LHF57H C: 0=H<5B=5 GCAB=:9F5 FCCHG =B 0=GH5F F5HG )<MHCH<9F
+9G   –
)F5?5G< # <CI<5B , 2585J , $ 09GH:5@@ , +5= , ' ,=B;< , )  0=H<5B=5
GCAB=:9F5 5@@9J=5H9G )5F?=BGCB=5B D<9BCHMD9G 6M =B<=6=H=B; 5DCDHCH=7 D5H<K5MG =B
8CD5A=B9F;=7 B9IFCBG '9IFC7<9A +9G   –
)F5?5G< # 2585J , $ <CI<5B , ,=B;< , )  '9IFCDFCH97H=J9 FC@9 C: 0=H<5B=5
GCAB=:9F5 FCCH 9LHF57H =B &5B96)5F5EI5H =B8I798 ACIG9 AC89@ C: )5F?=BGCB=GA
'9IFC7<9A +9G   –
+56<=  F7=@9  %9 CT  5 CGH5 'C6@9  (I5NN5B= #  '9IFCDFCH97H=J9
9T97H C: + 5 ;@IH5H<=CB9 89F=J5H=J9 C: K=H<5:9F=B  C6H5=B98 H<FCI;< H<9
6=C7CBJ9FG=CB C: K=H<5B=5 GCAB=:9F5 % 8IB5@ 9LHF57H 6M H<9 :IB;IG 695IJ9F=5
65GG=5B5 &C@97I@9G   
+5;<5J5B  ,<5< 3   0=H<5B=5 GCAB=:9F5 5 DF97@=B=75@ GHI8M CB
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