ORIGINAL�ARTICLE

ABSTRACT
Objective:	 To	 compare	 the	 anti-hyperglycemic	 and	 anti	 hyperlipidemic	 activities	 of	 ethanolic	 extract	 of	
Glycyrrhiza	glabra	(licorice)	roots	with	the	standard	drugs	metformin	and	glimepiride	in	streptozotocin	induced	
diabetic	rats.
Study	Design:	Experimental	study.	
Place	and	Duration	of	Study:	Animal	House	of	Basic	Medical	Science	Institute	(BMSI).	Jinnah	post	graduate	
medical	center	(JPMC),	Karachi	conducted	from	May	2018	till	August	2018.	
Materials	and	Methods:	Total	seven	groups	of	Wistar	albino	rats	comprising	six	rats	in	each	were	included.	
Study	 included	 negative	 control	 and	 positive	 control	 groups,	 to	 which	 0.9%	 of	 sodium	 chloride	 was	
administered.	 	 Other	 five	 groups	 of	 streptozotocin	 induced	 diabetic	 rats	 were	 treated	 with	 metformin,	
glimepiride,	rosuvastatin,	ethanolic	extract	of	Glycyrrhiza	glabra	(licorice)	roots	at	a	dose	of	200	mg/kg	and	
400mg/kg,	respectively.	The	treatment	was	given	for	28	days	followed	by	the	laboratory	estimation	of	fasting	
blood	glucose	(FBG),	fasting	serum	insulin,	Glycosylated	Hemoglobin	A1c	(HbA1c),	total	lipid	profile	and	serum	
amylase	were	evaluated.	
Results:	A	significant	decrease	was	observed	in	all	the	glycemic	indices	at	both	doses	of	Glycyrrhiza	glabra	
(licorice)	i.e.	200	mg/kg	and	400mg/kg,	but	a	more	rampant	decrease	is	observed	at	the	dose	of	400mg/kg.	
Similarly,	both	concentrations	of	extract	showed	significant	decrease	in	all	lipidemic	indices	that	included	HDL-
C,	VLDL-C,	LDL-C,	total	cholesterol	(TC),	Triglycerides	(TG)	and	the	serum	amylase	levels.
Conclusion:	 This	 study	 concludes	 that	 the	 licorice	 herb	 has	 sufficient	 anti	 hyperglycemic	 and	 anti	
hyperlipidemic	 effects	 in	 diabetic	 rats	 without	 any	 aberration	 in	 pancreatic	 enzymes,	 hence	 it	 might	 be	
beneficial	as	additional	dietary	supplements	for	the	effective	management	of	diabetes	mellitus	along	with	
standard	drugs.

Key	Words:	Diabetes Mellitus, Hyperglycemia, Hyperlipidemia, Licorice.

2	
by	2040	throughout	the	world. This	alarming	illness	
is	mainly	of	two	types	i.e.	type	1	which	is	caused	by	
relative	 insulin	 deficiency	 while	 type	 2	 is	 mainly	

3	
attributed	to	insulin	resistance. Along	with	other	co-
morbidities,	 dyslipidemia	 is	 also	 associated	 with	
poorly	controlled	diabetes	mellitus	which	can	lead	to	
multiple	micro	and	macro	vasculopathies	including	
coronary	heart	disease	and	stroke	that	explains	early	

1
mortalities	and	morbidities	in	diabetic	patients.
The	oral	treatment	regimen	for	diabetes	mellitus	is	
classified	 in	 to	 insulin	 sensitizers,	 insulin	

4	
secretagogues	 and	 miscellaneous	 group. The	
management	 and	 control	 of	 diabetes	 by	 these	
synthetic	 drugs	 without	 adverse	 effects	 is	 a	 great	
challenge	because	mostly	all	these	oral	anti	hyper	
glycemic	 medications	 have	 various	 distressing	
complications	 with	 development	 of	 resistance	 	 	 	 	 	 	 	

5 , 6 	
on	 enduring	 exploitation. Furthermore,	
conventionally	used	most	oral	hypoglycemic	drugs	
have	 more	 side	 effects	 on	 which	 is	 the	 awful	

Diabetes	 mellitus	 is	 a	 metabolic	 disorder	
characterized	 by	 hyperglycemia	 along	 with	
weakened	 metabolism	 of	 carbohydrate	 and	 other	
essential	 energy	 yielding	 fuels,	 such	 as	 lipids	 and	

1
proteins.” 	 Recently,	 the	 International	 Diabetes	
Federation	 (IDF)	 has	 reported	 that	 around	 415	
million	people	were having	diabetes	mellitus	in	2015		
and	this	figure	is	assumed	to	raise	up	to	642	million	

Introduction

Anti-Hyperglycemic	and	Anti-Dyslipidemic	Activities	of	Glycyrrhiza	Glabra	
Root	Extract	In	Diabetic	Rats

1 2 3 4 5 6
Jabbar	Ahmed	Qureshi ,	Zahida	Memon ,	Kauser	Ismail ,	Fizza	Saher ,	Vanita	Motiani ,	Zain	Mushtaq

Correspondence:
Dr. Jabbar Ahmed Qureshi
Assistant Professor
Department of Pharmacology
Ziauddin University, Karachi
E-mail: drjabbar.qureshi@hotmail.com

1,2,3 4 5
Department of Pharmacology/Oral Biology /Student

Ziauddin University, Karachi
6 Department of Medicine
 Agha khan University Hospital, Karachi

Funding Source: NIL; Conflict of Interest: NIL
Received: August 06, 2019; Revised: February 26, 2020
Accepted: February 27, 2020

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7	
outcome	of	poorly	controlled	diabetes. Herbal	drugs	
remain	the	focus	of	attraction	by	the	researchers	not	
only	in	ancient	times	but	still	today	a	large	number	of	
World's	population	believes	that	herbal	medications	

8	
are	sole	remedies	for	a	range	of	diseases. There	are	
about	 45000	 plants	 which	 possess	 different	
medicinal	 properties	 including	 anti	 hyperglycemic	
and	anti-dyslipidemic	activities.	G.glabra	is	the	root	
of	Glycyrrhiza	inflates	(Fabaceae)	which	is	commonly	
known	as	sweet	wood	or	licorice.	It	is	regularly	used	
herb	for	culinary	and	ayurvedic	purposes	in	South	

9,12
Asia	 since	 long	 time. 	 According	 to	 current	
literature,	 G.glabra	 is	 medically	 used	 for	 multiple	
purposes	 such	 an	 antioxidant,	 antidote	 for	 peptic	
ulcers	 and	 gastritis	 and	 prevention	 as	 well	 as	

13
treatment	 	of	common	cold. 	Furthermore,	it	has	
potent	 anti-tussive	 activity,	 muscle	 relaxing	
property,	 weight	 reduction	 potential,	 immune	
boosting	action	via	increasing	WBC	counts	and	anti-

14
diuretic	 and	 anti-inflammatory	 effects. 	 The	
naturally	 active	 constituents	 of	 G.glabra	 are	
glycyrrhizin,	 liquiritins,	 liquiritigenin,	 glycyrrhizin	
acids	and	flavones.	Glycyrrhizin	is	the	major	saponin	
in	licorice	root	and	its	metabolite	glycyrrhetinic	acid	

15	
is	 main	 pharmacologically	 active	 form. Together	
these	 flavonoids	 confirm	 significant	 anticancer,	

16
antioxidative,	 antimicrobial,	 and	 antiviral	 effects. 	
Moreover,	 licorice	 also	 reduces	 the	 liver	 damage	
significantly	 owing	 to	 its	 antioxidant	 and	 anti-
inflammatory	properties	as	indicated	by	Chen	et	al.	

17
in	2014.
However,	none	of	the	studies	mentioned	above	have	
aimed	to	find	out	the	antidyslipidemic	properties	of	
G.glabra.	 Therefore,	 in	 our	 study	 we	 have	 used	
G.glabra	on	rats	to	find	out	its	effects	on	the	different	
lipidemic	parameters.	Moreover,	we	also	aimed	to	
find	out	the	effect	of	different	doses	of	G.	glabra	on	
the	lipidemic	parameters.	Therefore,	this	study	was	
conducted	to	compare	the	anti-hyperglycemic	and	
anti	hyperlipidemic	activities	of	ethanolic	extract	of	
Glycyrrhiza	glabra	(licorice)	roots	with	the	standard	
drugs	metformin	and	glimepiride	in	streptozotocin	
induced	diabetic	rats.

Materials	and	Methods
This	was	an	experimental	study	conducted	between	
May	2018	till	August	2018	in	Animal	House	of	Basic	
Medical	 Science	 Institute	 (BMSI),	 Jinnah	 post	
graduate	medical	center	(JPMC),	Karachi.	G.glabra	

root	was	obtained	from	the	local	market	of	Karachi.	
The	plants	were	authenticated	and	identified	from	
botany	 department	 of	 Karachi	 University	 and	
taxonomy	 number	 was	 obtained.	 (Taxonomic	
number	of	Glycyrrhiza	glabra	i.e.	Licorice	is:	17234)	
The	study	was	approved	from	Ziauddin	University.
The	 G.glabra	 roots	 were	 washed	 and	 dried	
separately	in	open	air	for	48	hours.	The	roots	were	
then	minced	into	powder	using	a	mechanical	grinder.	
The	 powder	 was	 then	 mixed	 and	 infused	 with	
absolute	 ethanol	 at	 a	 1:10	 ratio	 (100	 gram	 in	 1	 L	
solvent)	for	7	days	in	separate	jars.	The	extract	was	
filtered	through	a	Whatman	No	1	filter	paper	which	
was	followed	by	rotory	evaporation	of	fíltrate	with	
the	 help	 of	 rotary	 evaporators	 so	 that	 the	
concentrated	 extract	 of	 herb	 was	 obtained	 which	
was	 free	 of	 ethanol.	 The	 crude	 extract	 was	
reconstituted	 in	 freshly	 prepared	 2.5%	 dimethyl	
sulfoxide	DMSO	and	kept	in	jar	for	evaluation	of	anti-
hyperglycemic	 and	 anti-dyslipidemic	 properties	 in	
diabetic	rats.	
Forty-two	adult	male	and	female	Wistar	albino	rats	
(aged	 7-8	 weeks,	 weighing	 180–240	 grams)	 were	
purchased	 from	 the	 animal	 house	 of	 Agha	 khan	
university	hospital.	However,	it	was	made	sure	none	
of	 the	 rats	 purchased	 suffered	 from	 any	 other	
comorbidity	that	could	have	affected	our	results.	All	
rats	were	kept	in	(25	±	3	�	C,	12	h	light/dark	cycle)	as	
well	as	the	standard	diet	and	clean	tap	water	the	rats	
were	provided.	Rats	were	divided	in	7	groups:	Group-
I	 negative	 control	 non	 diabetic	 rats;	 treated	 with	
0.9%	 sodium	 chloride	 (NaCl).	 Group	 II	 positive	
control	diabetic	rats;	treated	with	0.9%	NaCl.	Group-
III	diabetic	rats	and	was	treated	with	glimepiride	at	
0.1	mg/kg	bw.	Group-IV	diabetic	rats	and	was	treated	
with	metformin	at	10	mg/kg	bw.	Group	V	diabetic	
rats;	 treated	 with	 rosuvastatin	 10	 mg/kg/day	 bw.	
Group-	 VI	 diabetic	 rats;	 treated	 with	 Ethanolic	
Extract	of	G.glabra	at	a	dose	of	200	mg/kg	.Group-	VII	
diabetic	 rats;	 treated	 with	 Ethanolic	 Extract	 of	
G.glabra	at	a	dose	of	400	mg/kg.
With	 the	 exception	 of	 negative	 control	 group,	
diabetes	was	induced	to	all	animals	by	injecting	the	
solution	 of	 Streptozotocin	 (STZ).	 The	 solution	 was	
made	by	dissolving	dry	powder	of	STZ	in	0.1	M	citrate	

17
buffer	(pH	4.5)	that	was	used	after	filtration. 	It	was	
injected	 as	 a	 single	 dose	 of	 55	 mg/kg	 via	 intra	
peritoneal	route	(i.p)	to	overnight	fastening	rats.	On	

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rd
3 	day	1ml	blood	was	taken	from	tail	for	FBS	from	
each	 rat.	 The	 rats	 whose	 blood	 glucose	 level	 was	

18	
more	than	250mg/dl	were	considered	as	diabetic.
Herbal	extract	and	standard	treatment	were	given	to	
all	the	rats	except	positive	control	through	metallic	
feeding	syringe	orally	for	a	period	of	28	days.

th
On	29 	day,	following	overnight	food	deprivation,	the	
rats	were	given	an	anesthesia	that	consisted	of	ether	
solution	 and	 were	 sacrificed	 as	 per	 Institutional	
Animal	Ethics	Committee	(IAEC)	guidelines.	A	blood	
sample	of	10	ml	was	collected	by	cardiac	puncture	
and	was	transferred	into	vacuum	tubes	which	were	
then	centrifuged	at	3000	rpm	for	10	minutes.	After	
centrifugation,	 sera	 were	 separated	 for	 different	

19
biochemical	assays. 	Glycemic	indices	such	as	blood	
glucose	 level,	 serum	 insulin,	 Glycosylated	
Hemoglobin	 (HbA1c),	 serum	 amylase	 and	 lipid	
profile	 such	 as	 total	 cholesterol	 (TC),	 Triglycerides	
(TG),	High	density	lipoprotein-	Cholesterol	(HDL-C),	
Very	low	density	lipoproteins	(VLDL-	C),	Low	density	
lipoproteins	-	Cholesterol	(LDL-	C)	were	measured	
from	serum	samples	by	standard	enzymatic	methods	
using	commercially	available	kits	(Bartham,	Trinder,	
Richmond	and	schettler)	according	to	manufacturer	
advice	respectively.
The	 data	 was	 analyzed	 using	 the	 software	 SPSS	
version	20.0.	The	glycemic	 índices	and	lipid	 levels	
were	expressed	as	mean	±	Standard	Error	of	Mean	
(SEM)	 that	 were	 obtained	 by	 analysis	 of	 variance	
(ANOVA)	 test.	 The	 P	 values	 less	 than	 0.05	 were	
considered	statistically	significant	for	all	treatment	
groups.

Results	
Effects	 of	 Glycyrrhiza	 Glabra	 on	 Fasting	 Blood	
Glucose	Levels	
All	 the	 glycemic	 parameters	 showed	 a	 significant	
increase	in	the	positive	control	group	as	compared	to	
the	 negative	 control	 group	 at	 day	 29	 (Table	 I).	 A	
rampant	 decrease	 was	 observed	 in	 glimepiride	
group.	The	administration	of	licorice	root	extract	at	
the	dosage	of	200mg/kg	and	400mg/kg	for	29	days	to	
rats	with	hyperglycemia	(induced	by	streptozotocin	
via	 intraperitoneal	 route	 of	 administration)	 a	
significant	 reduction	 in	 the	 blood	 glucose	
concentration,	HbA1c	and	fasting	serum	insulin	 in	
comparison	to	the	result	obtained	from	the	positive	
control	group	(mentioned	in*).

Effects	of	Glycyrrhiza	Glabra	Root	Onserum	Lipid	
Concentration
Parameters	associated	with	the	lipid	profile	such	as	
TC,	TG,	HDL-	C,	VLDL-C	and	LDL-C were	considerably		
altered	in	positive	control	group	in	comparison	with	
negative	control	(Table	II).	Rosuvastatin	maximally	
normalized	these	values.	Both	doses	of	G.	glabra	also	
improved	 these	 parameters	 significantly	 as	
compared	to	positive	control	group	(Table	II).

Table	I:	Effect	of	Fas�ng	Blood	Sugar,	Hba1c	and	Serum
Concentra�on	in	Comparison	With	Nega�ve	and	Posi�ve
Control

GG:	Glycyrrhiza	Glabra
FBS:	Fas�ng	Blood	Sugar
Glycosylated Hemoglobin		
*shows	P-value	<	0.05	(highly	significant)

Table	II:	Total	Cholesterol	TC,	TG,	HDL,	VLDL,	LDL,	in	
Control	and	Diabe�c	Rats	Treated	With	Glycyrrhiza	
Glabra

GG:	Glycyrrhiza	Glabra
TG:	Triglycerides
TC:	Total	Cholesterol
HDL:	High	Density	Lipoprotein	
VLDL:	Very	Low-Density	Lipoprotein
LDL:	Low	Density	Lipoprotein
*shows	p	value	is	highly	significant

Effects	 of	 Glycyrrhiza	 Glabra	 on	 Serum	 Amylase	
Levels
There	was	significant	rise	in	serum	amylase	level	in	
positive	control	group)	when	compared	to	negative	
control.	G.glabra	at	both	dosages	reduced	these	
values	significantly	(Table	III).

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100

Control

Control



Discussion
Management	of	diabetes	by	any	means	like	with	oral	
hypoglycemic	 drugs	 or	 by	 injecting	 drugs	 such	 as	

21	
insulin	 or	 recently	 introduced	 exenatide is	 a	 big	
challenge	as	nearly	all	of	these	drugs	have	a	number	
of	 serious	 adverse	 effects	 and	 distressing	
complications.	Moreover,	these	agents	are	generally	

22
used	 in	 combination	 to	 get	 maximum	 effects. 	
Finally,	on	enduring	exploitation	resistance	develops	
gradually	resulting	 in	unsuccessful	glucose	control	

22
and	appearance	of	fearsome	complications.
In	 this	 scenario	 the	 medicinal	 plants	 are	 great	
blessing	as	not	only	they	have	the	potential	to	cure	
but	 also	 after	 diagnoses	 if	 received	 earlier	 herbal	
formulations	 derived	 from	 plants	 offer	 an	 innate	

24	
approach	for	prevention	of	complications	as	well.
Hence	 for	 purpose	 of	 evaluating	 the	 anti-
hyperglycemic	 properties	 of	 G.glabra	 we	
constructed	 a	 diabetic	 model	 of	 rats	 with	

25
streptozotocin.
Firstly,	 it	 is	 to	 be	 noted	 that	 FBS	 values	 raised	
significantly	at	both	doses	of	G.	glabra	i.e	200mg/kg	
and	400mg/kg	as	seen	in	table	I	and	comparable	with	

26
other	 studies	 done	 by	 Han	 S.	 et al. 	 The	 optimal	
blood	glucose	level	must	be	below	140	mg/dl	and	
this	sugar	level	was	achieved	more	or	less	only	in	
standard	groups.	This	finding	can	be	attributed	to	the	
presence	of	non-hydrophilic	flavonoids	that	showed	
alpha	 glucosidase	 inhibiting	 activity	 enzyme	 that	
hydrolyze	 polysaccharides	 into	 simpler	 form	 for	

27
better	absorption	of	sugars	from	small	 intestine. 	
Other	possible	mechanism	may	be	the	activation	of	
peroxisome	proliferator-activated	receptor-γ	(PPAR-
γ)	as	this	receptor	is	responsible	for	the	utilization	of	

28	
energy	and	homeostasis. Our	herb	possesses	both	
innate	alpha-amylase	inhibiting	property	along	with	
natural	PPAR-gamma	inhibitory	potential	and	thus	
modifies	 two	 different	 pathways	 of	 glucose	
metabolism	which	otherwise	will	be	provided	by	two	
different	classes	of	OHG	agents.	

Secondly,	despite	significant	lowering	of	FBS	after	29	
days	of	treatment,	G.glabra	failed	to	improve	HbA1c	
and	fasting	serum	insulin	levels	when	compared	with	
positive	control	(p	value	1.00).	The	underlying	reason	
may	be	limited	time	duration	of	treatment	i.e.	28	
days	which	might	be	insufficient	to	produce	obvious	

1,9,29,30	
changes	 in	 HbA1c	 and	 insulin	 level. As	 other	
studies	conducted	show	that	12	month	or	greater	

31	
time	span	yield	in	more	positive	result. 	Thirdly,	in	
our	study	the	diabetic	rats	that	were	treated	with	G.	
glabra	 showed	 a	 considerable	 and	 significant	
improvement	in	all	the	parameters	associated	with	
dyslipidemia	in	comparison	to	the	positive	control	
group	(p<0.001)	just	like	the	Rosuvastatin	group.The	

	

anti	 dyslipidemic	 factor	 of	 G.glabra	 could	 be	
attributed	 to	 the	 presence	 of	 phytosterols	 and	

32,33,34,35	
saponins	in	the	G.	glabra. According	to	a	study	
the	phytosterol	can	replace	the	intestinal	cholesterol	
which	 could	 lead	 to	 a	 decrease	 in	 the	 amount	 of	
cholestrol	as	it	won't	be	absorbed	properly	from	the	

37	
intestine. In	one	study,	it	was	observed	that	when	G.	
glabra	roots	when	given	as	5%	and	10%	diet	for	4	
weeks	 in	 hyper-cholesterolemic	 rats	 and	 it	 was	
observed	that	lipid	levels	were	drastically	reduced	
and	excretion	of	cholesterol	and	bile	acid	seen	 in	

35	
feces	markedly	increased. In	another	study	done	by	
Shalaby	et al.	it	was	exhibited	that	G.	glabra	reduced	
the	levels	of	TC	and	TG	with	no	significant	change	
observed	in	the	levels	of	LDL,	HDL	and	VLDL	in	male	

36	
rats. But	these	results	are	not	consistent	with	our	
study	as	our	results	show	a	mark	improvement	in	all	
parameters	related	to	dyslipidemia	which	was	also	
seen	 in	 Furukawa	 et	 al.,	 2017,	 Al-Rubeaan	 et	 al.,	
2017,	King,	2012,	Gaur	et	al.,	2014.
According	to	the	results	of	our	study	an	increase	in	
HDL	and	a	decrease	in	TC	is	observed	which	can	be	
owed	to	the	increase	stimulation	of	pre-β	HDL-C	and	
reverse	 cholesterol	 transport,	 as	 demonstrated	 in	

38	
Rodriguez	et al's	study or	due	to	the	suppression	of	
hydroxyl	 methyl	 glutaryl-CoA	 synthase	 activity	 by	
Glycyrrhizin,	the	active	component	of	G.glabra.	The	
present	study	illustrated	that	research	herb	reduces	
the	bad	and	improves	the	good	cholesterol	levels	in	
streptozotocin	induced	diabetic	rats	which	could	be	
due	to	the	saponin	content	of	G.glabra	root.	
As	pancreatitis	is	the	common	complication	of	few	

39	
oral	hypoglycemic	drugs and	is	usually	encountered	

17
clinically	as	raised	serum	amylase	levels. 	Therefore,	

Table	III:		Serum	Amylase	Level	When	Compared	With	
Control	Groups	and	G.Glabra	Groups

GG:	G.GLABRA
*shows	p	value	is	highly	significant.

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we	 aimed	 to	 evaluate	 the	 effects	 of	 our	 herb	 on	
pancreatic	enzymes	and	we	found	no	aberration	in	
this	 enzyme.	 The	 serum	 amylase	 levels	 were	
significantly	 increased	 in	 the	 diabetic	 rats	 in	
comparison	to	the	rats	in	the	positive	control	group.	
Furthermore	the	levels	of	serum	amylase	reduced	
back	 to	 an	 almost	 normal	 range	 after	 28	 days	 of	
treatment	with	G.glabra	as	seen	in	Table	III.	
This	data	is	however	scarce	regarding	the	effects	of	
this	herb	on	pancreatic	physiology	but	Xiaoying	et	al	
highlights	the	G.glabra's	positive	effect	on	the	levels	
of	 serum	 alanine	 aminotransferase	 (ALT)	 and	
aspartate	transaminase	(AST)	in	a	cadmium	induced	
hepatotoxicity	 of	 animal	 model	 	 and	 its	 reversal	

40
effect	on	inflammatory	changes	of	liver.

Conclusion
With	the	evidence	from	this	study	we	conclude	that	
G.glabra	has	significant	glucose	lowering	effects	with	
a	striking	protective	role	against	dyslipidemia.	As	an	
alternative,	this	herb	can	be	timely	utilized	for	the	
management	 of	 diabetes	 and	 associated	
dyslipidemia	 without	 any	 obvious	 irregularity	 of	
pancreatic	functions.

REFERENCES
1.	 Elberry	 AA,	 Harraz	 FM,	 Ghareib	 SA,	 Gabr	 SA,	 Nagy	 AA,	

Abdel-Sattar	E.	Methanolic	extract	of	Marrubium	vulgare	
ameliorates	 hyperglycemia	 and	 dyslipidemia	 in	
streptozotocin-induced	diabetic	rats.	International	Journal	
of	Diabetes	Mellitus.	2015;3(1):37-44.

2.	 Marwa	M	Abdel-Rahman,	Ayman	M	Mahmoud,	Bastawy	
NA,	 Eissa	 HM.	 Anti-Hyperlipidemic	 and	 Myocardial	
Enhancing	 Effects	 of	 Berberine	 in	 High	 Fat	
Diet/StreptozotocinInduced	Diabetic	Rats;	Possible	Role	of	
Adiponectin.	Nutrition	&	Food	Scienc	International	Journal	
of	Diabetes	Mellitus.	2017;2(1):1-7.

3.	 Patel	DK,	Kumar	R,	Laloo	D,	Hemalatha	S.	Diabetes	mellitus:	
An	overview	on	its	pharmacological	aspects	and	reported	
medicinal	plants	having	antidiabetic	activity.	Asian	Pacific	
Journal	of	Tropical	Biomedicine.	2012;2(5):411-20.

4.	 Thareja	 S,	 Aggarwal	 S,	 Bhardwaj	 TR,	 Kumar	 M.	 Protein	
Tyrosine	 Phosphatase	 1B	 Inhibitors:	 A	 Molecular	 Level	
Legitimate	 Approach	 for	 the	 Management	 of	 Diabetes	
Mellitus.	Medicinal	Research	Reviews.	2010;32(3):459-517.

5.	 Chaudhary	 P,	 Goel	 B,	 Ghosh	 AK.	 Antidiabetic	 activity	 of	
Adina	cordifolia	(Roxb)	leaves	in	alloxan	induced	diabetic	
rats.	 Asian	 Pacific	 Journal	 of	 Tropical	 Biomedicine.	
2012;2(3,	Supplement):S1630-S2.

6.	 Pareek	H,	Sharma	S,	Khajja	BS,	Jain	K,	Jain	GC.	Evaluation	of	
hypoglycemic	 and	 anti-hyperglycemic	 potential	 of	 Tridax	
procumbens	(Linn.).	BMC	complementary	and	alternative	
medicine.	2009;9:48.

7.	 Deepa		VS,		Rajaram		K,		Kumar		PS.		In		vitro		and		in		vivo		

antidiabetic		effect		of		Andrographis		lineata		Wall.	Ex.	Nees	
and	Andrographis	serphyllifolia	Wt.	Ic	leaf	extracts.	Afr	J	 	 	 	 	 	
PharmPharmacol.	2013;7(29):2112-21.

8.	 Feshani	 AM,	 Kouhsari	 SM,	 Mohammadi	 S.	 Vaccinium	
arctostaphylos,	 a	 common	 herbal	 medicine	 in	 Iran:	
molecular	and	biochemical	study	of	its	antidiabetic	effects	
on	 alloxan-diabetic	 Wistar	 rats.	 Journal	 of	
ethnopharmacology.	2011;133(1):67-74.

9.	 Simon	JP,	Baskaran	UL,	Shallauddin	KB,	Ramalingam	G,	Evan	
Prince	 S.	 Evidence	 of	 antidiabetic	 activity	 of	 Spirulina	
fusiformis	against	streptozotocin-induced	diabetic	Wistar	
albino	rats.	3	Biotech.	2018;8(2):129.

10.	 Venkatesh	 S,	 Madhava	 Reddy	 B,	 Dayanand	 Reddy	 G,	
Mullangi	 R,	 Lakshman	 M.	 Antihyperglycemic	 and	
hypolipidemic	effects	of	Helicteres	isora	roots	in	alloxan-
induced	 diabetic	 rats:	 a	 possible	 mechanism	 of	 action.	
Journal	of	natural	medicines.	2010;64(3):295-304.

11.	 Patel	 DK,	 Kumar	 R,	 Laloo	 D,	 Hemalatha	 S.	 Evaluation	 of	
phytochemical	and	antioxidant	activities	of	the	different	
fractions	 of	 Hybanthus	 enneaspermus	 (Linn.)	 F.	 Muell.	
(Violaceae).	 Asian	 Pacific	 Journal	 of	 Tropical	 Medicine.	
2011;4(5):391-6.

12.	 Dewanjee	S,	Das	AK,	Sahu	R,	Gangopadhyay	M.	Antidiabetic	
activity	 of	 Diospyros	 peregrina	 fruit:	 effect	 on	
hyperglycemia,	 hyperlipidemia	 and	 augmented	 oxidative	
stress	in	experimental	type	2	diabetes.	Food	and	chemical	
toxicology	 :	 an	 international	 journal	 published	 for	 the	
British	 Industrial	 Biological	 Research	 Association.	
2009;47(10):2679-85.

13.	 Lim	 TK.	 Glycyrrhiza	 glabra.	 In:	 Lim	 TK,	 editor.	 Edible	
Medicinal	and	Non-Medicinal	Plants:	Volume	10,	Modified	
Stems,	 Roots,	 Bulbs.	 Dordrecht:	 Springer	 Netherlands;	
2016.	p.	354-457.

14.	 Wang	X,	Zhang	H,	Chen	L,	Shan	L,	Fan	G,	Gao	X.	Liquorice,	a	
unique	 "guide	 drug"	 of	 traditional	 Chinese	 medicine:	 a	
review	 of	 its	 role	 in	 drug	 interactions.	 Journal	 of	
ethnopharmacology.	2013;150(3):781-90.

15.	 Li	HY,	Xu	W,	Su	J,	Zhang	X,	Hu	LW,	Zhang	WD.	In	vitro	and	in	
vivo	inhibitory	effects	of	glycyrrhetinic	acid	on	cytochrome	
P450	3A	activity.	Pharmacology.	2010;86(5-6):287-92.

16.	 Tang	ZH,	Li	T,	Tong	YG,	Chen	XJ,	Chen	XP,	Wang	YT,	et	al.	A	
Systematic	 Review	 of	 the	 Anticancer	 Properties	 of	
Compounds	 Isolated	 from	 Licorice	 (Gancao).	 Planta	
medica.	2015;81(18):1670-87.

17.	 Chen	 HJ,	 Kang	 SP,	 Lee	 IJ,	 Lin	 YL.	 Glycyrrhetinic	 acid	
suppressed	 NF-kappaB	 activation	 in	 TNF-alpha-induced	
hepatocytes.	J	Agric	Food	Chem.	2014;62(3):618-25.

18.	 de	 la	Garza-Rodea	AS,	Knaän-Shanzer	S,	den	Hartigh	JD,	
Verhaegen	 APL,	 van	 Bekkum	 DW.	 Anomer-Equilibrated	
Streptozotocin	Solution	for	the	Induction	of	Experimental	
Diabetes	in	Mice	(Mus	musculus).	Journal	of	the	American	
Association	 for	 Laboratory	 Animal	 Science	 :	 JAALAS.	
2010;49(1):40-4.

19.	 Kumar	R,	Arora	V,	Ram	V,	Bhandari	A,	Vyas	P.	Hypoglycemic	
and	hypolipidemic	effect	of	Allopolyherbal	formulations	in	
streptozotocin	 induced	 diabetes	 mellitus	 in	 rats.	
International	Journal	of	Diabetes	Mellitus.	2015;3(1):45-50.

20.	 Beeton	C,	Garcia	A,	Chandy	KG.	Drawing	blood	from	rats	
through	 the	 saphenous	 vein	 and	 by	 cardiac	 puncture.	

Anti-Hyperglycemic	and	Anti-Dyslipidemic	Activities	of	Glycyrrhiza	Glabra	RootJIIMC	2020	Vol.	15,	No.2

102



Journal	of	visualized	experiments	:	JoVE.	2007(7):266-.
21.	 Buse	JB,	Bergenstal	RM,	Glass	LC,	Heilmann	CR,	Lewis	MS,	

Kwan	 AYM,	 et	 al.	 Use	 of	 Twice-Daily	 Exenatide	 in	 Basal	
Insulin–Treated	 Patients	 With	 Type	 2	 Diabetes:	 A	
Randomized,	Controlled	Trial.	Annals	of	Internal	Medicine.	
2011;154(2):103-12.

22.	 Bray	GA,	Frühbeck	G,	Ryan	DH,	Wilding	JPH.	Management	
of	obesity.	The	Lancet.	2016;387(10031):1947-56.

23.	 Kalra	S,	Mukherjee	JJ,	Venkataraman	S,	Bantwal	G,	Shaikh	S,	
Saboo	B,	et	al.	Hypoglycemia:	The	neglected	complication.	
Indian	 journal	 of	 endocrinology	 and	 metabolism.	
2013;17(5):819-34.

24.	 Parasuraman	 S,	 Thing	 GS,	 Dhanaraj	 SA.	 Polyherbal	
formulation:	 Concept	 of	 ayurveda.	 Pharmacognosy	
Reviews.	2014;8(16):73-80.

25.	 Rani	R,	Dahiya	S,	Dhingra	D,	Dilbaghi	N,	Kim	K-H,	Kumar	S.	
Evaluation	 of	 anti-diabetic	 activity	 of	 glycyrrhizin-loaded	
nanoparticles	 in	 nicotinamide-streptozotocin-induced	
diabetic	rats.	European	Journal	of	Pharmaceutical	Sciences.	
2017;106:220-30.

26.	 Han	S,	Hagan	DL,	Taylor	JR,	Xin	L,	Meng	W,	Biller	SA,	et	al.	
Dapagliflozin,	a	selective	SGLT2	inhibitor,	improves	glucose	
homeostasis	in	normal	and	diabetic	rats.	Diabetes.	2008.

27.	 N.	 Murugaiyan,	 G.	 Gnanamuthu,	 Rajendran	 SS,	
Rameshkumar	 K.	 Phytochemical	 Screening,	 Antibacterial	
Activity	and	Identification	of	Bioactive	Compound(s)	in	the	
Leaves	 of	 Bell	 Weed	 (Dipteracanthus	 prostratus)	 for	
Medicinal	 Purpose.	 World	 Journal	 of	 Medical	 Sciences	
2015;12(3):277-84.

28.	 Nakagawa	K,	Kishida	H,	Arai	N,	Nishiyama	T,	Mae	T.	Licorice	
Flavonoids	 Suppress	 Abdominal	 Fat	 Accumulation	 and	
Increase	 in	 Blood	 Glucose	 Level	 in	 Obese	 Diabetic	 KK-
A<sup>y</sup>	 Mice.	 Biological	 and	 Pharmaceutical	
Bulletin.	2004;27(11):1775-8.

29.	 Subhasree	N,	Kamella	A,	Kaliappan	I,	Agrawal	A,	Dubey	GP.	
Antidiabetic	 and	 antihyperlipidemic	 activities	 of	 a	 novel	
polyherbal	 formulation	 in	 high	 fat	 diet/streptozotocin	
induced	 diabetic	 rat	 model.	 Indian	 journal	 of	

pharmacology.	2015;47(5):509-13.
30.	 Ghadermazi	R,	Khoshjou	F,	Hossini	Zijoud	SM,	Behrooj	H,	

Kheiripour	 N,	 Ganji	 M,	 et	 al.	 Hepatoprotective	 effect	 of	
tempol	 on	 oxidative	 toxic	 stress	 in	 STZ-induced	 diabetic	
rats.	Toxin	Reviews.	2018;37(1):82-6.

31.	 Ramzi	 	GA,	 	Puneeth	 	HR,	 	Shivmadhu	 	C,	 	Madhu	 	AC.	
Antagonistic	 effects	 of	 combination	 of	 flaxseed	 oil	 and	
spirulina	platensis	oil	on	their	biological	prop-erties.	Int	J	
Pharm	Pharm	Sci.	2015;7:122-7

32.	 Furukawa	S,	Fujita	T,	Shimabukuro	M,	Iwaki	M,	Yamada	Y,	
Nakajima	Y,	et	al.	Increased	oxidative	stress	in	obesity	and	
its	impact	on	metabolic	syndrome.	The	Journal	of	clinical	
investigation.	2017;114(12):1752-61.

33.	 Al-Rubeaan	K,	Almashouq	MK,	Youssef	AM,	Al-Qumaidi	H,	
Al	 Derwish	 M,	 Ouizi	 S,	 et	 al.	 All-cause	 mortality	 among	
diabetic	 foot	 patients	 and	 related	 risk	 factors	 in	 Saudi	
Arabia.	PLOS	ONE.	2017;12(11):e0188097.

34.	 Srivastava	 M,	 Misra	 P.	 Enhancement	 of	 Medicinally	
Important	Bioactive	Compounds	in	Hairy	Root	Cultures	of	
Glycyrrhiza,	 Rauwolfia,	 and	 Solanum	 Through	 In	 Vitro	
Stress	Application.	In:	Malik	S,	editor.	Production	of	Plant	
Derived	Natural	Compounds	through	Hairy	Root	Culture.	
Cham:	Springer	International	Publishing;	2017.	p.	117-32.

35.	 Prasad	 K.	 Secoisolariciresinol	 Diglucoside	 (SDG)	 Isolated	
from	 Flaxseed,	 an	 Alternative	 to	 ACE	 Inhibitors	 in	 the	
Treatment	 of	 Hypertension.	 The	 International	 Journal	 of	
Angiology	:	Official	Publication	of	the	International	College	
of	Angiology,	Inc.	2013;22(4):235-8.

36.	 Thomas	M,	Leelamma	S,	Kurup	PA.	Effect	of	Blackgram	Fiber	
(Phaseolus	mungo)	on	Hepatic	Hydroxymethylglutaryl-CoA	
Reductase	 Activity,	 Cholesterogenesis	 and	 Cholesterol	
Degradation	 in	 Rats.	 The	 Journal	 of	 Nutrition.	
1983;113(6):1104-8.

37.	 A.Shalaby	 M,	 Ibrahim	 HS,	 Mahmoud	 EM,	 Mahmoud	 AF.	
SOME	 EFFECTS	 OF	 GLYCYRRHIZA	 GLABRA	 (LIQUORICE)	
ROOTS	 EXTRACT	 ON	 MALE	 RATS.	 Egyptian	 Journal	 of	
Natural	Toxins.	2004;1:83-94.

Anti-Hyperglycemic	and	Anti-Dyslipidemic	Activities	of	Glycyrrhiza	Glabra	RootJIIMC	2020	Vol.	15,	No.2

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