A review of phytochemistry and pharmacology perspectives of Clitoria ternatea L.

Dingding Zhang,Zhuoyang Cheng,Xiaoxiao Huang

Key Laboratory of Computational Chemistry-Based Natural Antitum Drug Research &Development,Liaoning Province,School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China

AbstractClitoria ternatea L.,belonging to the family Fabaceae and subfamily Papilonaceae,is an herbaceous perennial legume valued for its medicinal importance.Pharmacological investigations on this plant have shown it has a variety of medicinal properties,including antibacterial activities,antitumor activities,antioxidant activities,memory enhancing activities,wound healing activities,antipyretic activities and antiasthmatic activities.However,there are few studies on the chemical constituents of C.ternatea. The present research reviewed the chemical constituents and biological activities of C.ternatea to provide references for further research on this plant.

Keywords: Clitoria ternatea L.;chemical compositions;pharmacological effects

1 Introduction

Clitoria ternatea

L.,also known as butterfly pea in China and Aparajita or Aparajit in India,

is a member of

Fabaceae

family

[1-4].

C.ternatea

is a kind of perennial herb legume with strong vitality and persistence

[5].Due to its multiple uses,it has been widely distributed and naturalized throughout the tropics by human introduction [6].It has been used as a drug since ancient times [7].The roots and leaves of

C.ternatea

are used as one of the ingredients in the traditional Ayurvedic medicine system.The roots,stems and flowers are used to treat snake bites and scorpion strings [1].The flowers are a considerable source for the development of anticancer drugs and the leaves are recommended for the treatment of different types of skin wounds [8,9].

C.ternatea

contains phytochemical constituents with important pharmacological activities.Several kinds of secondary metabolites,including triterpenoids,flavanols,and lignans,have been isolated from

C.ternatea

.Its extracts possess numerous pharmacological activities including antimicrobial,antipyretic,anti-inflammatory,analgesic,diuretic,local anesthetic,antidiabetic,and insecticidal activities [4].The diversified pharmacological activities show that it has great medical value.This review mainly summarized the previous studies on the pharmacological activities of

C.ternatea

,in order to lay the foundation for future research.

2 Chemical composition

Several studies have identified the chemical constituents with defined structure in

C.ternatea

,including flavonoids,a pentacyclic triterpenoid and lignans.

2.1 Flavonoids

13 anthocyanins were isolated from

C.ternatea

,including delphinidin 3-

O

-(6′′-

O

malonyl)-

β

-glucoside (

1

),delphinidin 3-

O

-(6′′-

O

malonyl)-

β

-glucoside-3′-

O

-

β

-glucoside (

2

),delphinidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside-3′,5′-di-

O

-

β

glucoside,ternatin C5 (

3

),pelargonidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside (

4

),cyanidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside (

5

),cyanidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside-3′-

O

-

β

-glucoside (

6

),petunidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside (

7

),petunidin 3-

O

-(6′′-

O

-malonyl)-

β

-glucoside 5′-

O

-

β

glucoside

(

8

),delphinidin 3-

O

-

β

-glucoside (

9

),delphinidin 3,3′-di-

O

-

β

-glucoside (

10

),delphinidin 3,3′,5′-tri-

O

-

β

-glucoside (

11

),delphinidin 3,5-di-

O

-

β

-glucoside (

12

),and delphinidin 3,5-di-

O

-(6-

O

-acetyl)-

β

-glucoside (

13

) [10].Ternatins C1-C5 (

14

-

18

),ternatins D3 (

19

),preternatins A3(

20

) and preternatins C4 (

21

) in

C.ternatea

were also reported [11-13].A flavone,named quercetin(

22

),has been isolated from

C.ternatea

in the past reports [14]

.

The structures of these flavonoids are shown in Fig.1.

Fig.1 Flavonoids in C.ternatea

(to be continued)

Continued fig.1

2.2 Lignans

In 2016,three new norneolignans,clitorienolactone A-C (

23-25

),were isolated from the roots of

C.ternatea

(Fig.2)

[15]

.

Fig.2 Lignans in C.ternatea

2.3 Pentacyclic triterpenoid

One pentacyclic triterpenoid,called taraxerol(

26

),was identified from

C.ternatea

(Fig.3) [16]

.

Fig.3 Pentacyclic triterpenoid in C.ternatea

3 Pharmacological activities

3.1 Antibacterial activity

Clitoria

has three varieties,namely

Clitoria ternatea

L.Var.ternatea Hook.F.(white),

Clitoria ternatea

L.Var.ternatea Hook.F.(blue) and

Clitoria ternatea

L.Var.Pleniflora Fantz.(blue var).In 2017,Rajesh Kumar T et al.studied the antibacterial activities of extracts of the leaves and roots of

Clitoria ternatea

L varieties by agar diffusion methods [5].The acetone extracts of the leaves and roots were tested against

E.coli

.The inhibition zones of acetone extracts of the roots were 12 mm,14 mm and 16 mm,respectively.The inhibition zones of acetone extracts of the leaves were 18 mm,16 mm and 13 mm,respectively.The results showed that the roots of

C.ternatea

(white root) and

C.ternatea

(blue var) had better bacteriostatic effect than

C.ternatea

(blue).Furthermore,Mahmad N et al.validated the antibacterial activity of

in vivo

and

in vitro

ethanolic anthocyanin extracts of

C.ternatea

against

Bacillus subtilis

,

Staphylococcus aureus

and

Escherichia coli

in 2018 [17].The results showed that both

in vivo

and

in vitro

ethanolic extracts from vivid blue flowers of

C.ternatea

showed the best antibacterial activity against the same bacteria(

B.subtilis

),with inhibition zones of 11 mm and 10 mm respectively.

3.2 Antitumor activity

Selective promotion of cancer cell apoptosis is one of the main indicators of evaluating whether drugs can cure cancer.In 2015,Shivaprakash P et al.investigated the antitumor activity of the methanolic extract of

Clitoria ternatea

L.flower (MECT)against SK-BR-3 (Human breast carcinoma),MCF-7 (Human breast adenocarcinoma),Hep3B (Human hepatocellular carcinoma),K562 (Human leukemia cells),and 8505C (Human anaplastic thyroid cancer)cell lines by MTT assay [8].The results showed that MECT had the best cytotoxic effect on MCF-7,with ICvalue of 27.2 ± 2.6

μ

g/mL,while ICvalues of SK-BR-3,Hep3b,K-562 and 8505C were 47.2 ± 2.6

μ

g/mL,72.5 ± 3.6

μ

g/mL,48.5 ± 1.8 and ＞ 100

μ

g/mL,respectively.In addition,they demonstrated whether MECT induced MCF-7 cancer cell death through apoptosis.Normally,the caspase-3 in a dormant state is activated upon apoptotic stimulation.The activated caspase-3 leads to DNA breakage and cell apoptosis.Therefore,they tested the content of DNA fragments and caspase-3 activity to prove that MECT induced apoptosis of MCF-7 cells.This study demonstrated that MECT showed its antitumor activity by inducing the apoptosis of MCF-7 cells.

3.3 Antioxidant activity

Oxidative stress is the main cause of several chronic and degenerative diseases [18].The antioxidant properties of

C.ternatea

have been assayed by utilizing free radical scavengers such as Ferric reducing power assay (FRAP),super oxide dismutase (SOD),1,2-diphenyl picrylhydrazyl(DPPH) and total polyphenols [19].The results showed that

C.ternatea

had antioxidant activity.The results of previous studies also proved that the antioxidant activity of

C.ternatea

flowers was related to the flavonoids,tannins and phenols contained in it [1].

3.4 Memory enhancing activity

It has been reported that cerebral perfusion insufficiency and ischemic brain damage will lead to the gradual decline of cognitive and memory functions [20].Damodaran T et al.studied the effect of methanolic extracts of

C.ternatea

on improving the cognitive and long-term hippocampal potentiation deficits induced by chronic cerebral hypoperfusion in rats [21].They established the model of chronic cerebral hypoperfusion in rats by subjecting male Sprague-Dawley rats (200-300 g)to permanent bilateral common carotid artery occlusion (PBOCCA) or sham surgery.The rats were orally administered

C.ternatea

root extracts at doses of 100,200 or 300 mg/kg on day 28 postsurgery and tested using behavioral tests (open-field test,passive avoidance task,and Morris water maze)and electrophysiological recordings (under urethane anesthesia).Treatment with

C.ternatea

root extract at the doses of 200 and 300 mg/kg resulted in a significant enhancement in memory performance in chronic cerebral hypoperfusion rats induced by PBOCCA.The results showed that

C.ternatea

root extract ameliorated synaptic function,which might improve the cognitive behavior.Clitorienolactone A (

15

) and clitorienolactone B (

16

) have shown memory enhancing activity in other studies [14].

3.5 Wound healing activity

Factors leading to skin wounds can cause inflammation and tissue damage.This inflammatory reaction will accelerate the synthesis of dermal enzymes (elastase,hyaluronidase,matrix metalloproteinase,etc.) and lead to degradation of extracellular matrix.Maity N et al.evaluated the wound healing potential of standardized

C.ternatea

leaf extract based on different enzymatic models,which are mostly associated with skin wounds [9].The methanol extract and fractions were screened for hyaluronidase,elastase,and matrix metalloproteinase-1 (MMP-1) inhibitory activity compared with standard oleanolic acid.The results showed that the extract of

C.ternatea

leaf had significant (

P

＜ 0.001) hyaluronidase(IC18.08 ± 0.46

μ

g/mL) and MMP-1 (

P

＜ 0.05)inhibitory activities,while the elastase inhibition was insignificant (IC42.68 ± 0.46

μ

g/mL).The experiment validated the traditional use of

C.ternatea

and recommended it for the treatment of different types of skin wounds.

3.6 Antipyretic activity

The methanol extract of

Clitoria ternatea

L.root (MECTR) was evaluated for its antipyretic potential on normal body temperature and yeastinduced pyrexia in albino rats by Parimaladevi B et al.[22].The results indicated that MECTR had a significant antipyretic effect on yeast-provoked elevation of body temperature in rats,and its effect was comparable to that of paracetamol (standard drug).Thus,the current pharmacological evidence supports the folklore claim of this plant as an antipyretic agent.

3.7 Antiasthmatic activity

In the Taur D J’s study,ethanol extract of

Clitoria ternatea

root (ECTR) was evaluated for the acute toxicity and antiasthmatic activity using milk induced leucocytosis and eosinophilia in mice,egg albumin induced mast cell degranulations in rats and passive cutaneous anaphylaxis in rats at different doses [23].Results showed that the antiallergic activity and mast cell protection against degranulation of ECTR might be due to the presence of flavonoids and saponins.Another study demonstrated that ethanolic extract of

C.ternatea

flowers could be considered as a potential therapeutic alternative for allergy-induced asthma [14].It can be concluded that ECTR may be useful in the treatment of asthma.

3.8 Other pharmacological activity

In Chandru G’s study,female rats were administered orally with the raw extract of

Clitoria ternatea

(RECT) at the dose of 250 mg/kg for 30 d to observe their reproductive stimuli and fertility effect,while normal cleaning water (normal slain 0.9%,0.5 mL/kg/d) was used in the control groups [24].The results showed that the reproductive effect of preliminary test of RECL could stimulate the safe synthesis of estrogen.According to another study,clitorienolactones A (

14

) (5 mg/kg) and clitorienolactones B (

15

) (20 mg/kg) showed 41%and 49% inhibition of AChE respectively,while a standard drug,donepezil (1 mg/kg) showed 42%inhibition of this enzyme [14].

4 Conclusion

So far,18 compounds have been isolated from

C.ternatea

,including flavonoids,pentacyclic triterpenoids and lignans with antibacterial,antitumor,antioxidant,wound healing,antipyretic,and antiasthmatic activities.This review summarized the pharmacological effects and chemical constituents of

C.ternatea

,in order to provide references for further phytochemistry and pharmacological research on

C.ternatea

.