Int J Pharm Pharm Sci, Vol 7, Issue 2, 30-33Review Article


A REVIEW ON PHYTOCHEMICAL CONSTITUENTS AND PHARMACOLOGICAL ACTIVITIES OF CLINACANTHUS NUTANS

MUHAMMAD SHAHZAD ASLAM*, MUHAMMAD SYARHABIL AHMAD, AWANG SOH MAMAT

School of Bioprocess Engineering, University Malaysia Perlis, Kompleks Pusat Pengajian, Jejawi 3, 02600 Arau, Perlis, Malaysia.
Email: Muhammad.shahzad.aslam@hotmail.com

Received: 14 Aug 2014 Revised and Accepted: 15 Sep 2014

ABSTRACT

Clinacanthus nutans commonly known as Belalai gajah (Malay), Phaya yo (Thai) is traditionally used medicinal plant. The plant is used in skin rashes, snake bites, lesions caused by herpes simplex virus, diabetic myelitis, fever, diuretics and green tea and served as fresh drink. The phytochemical constituents existing in the plant comprise lupeol, b –sitosterol, stigmasterol, Botulin, myricyl alcohol C-glycosyl flavones (vitexin, isovitexin, shaftoside, isomollupentin 7-O-b -glucopyranoside, orientin and isoorientin),sulfur-containing glucosides, cerebrosides mixer, a monoacylmonogalactosylglycerol,13-hydroxy-(13-S)-phaeophytin b, Pupurin-18-phytyl ester, phaeophorbide and chlorophyll derivatives. Pharmacological studies reported anti-Papillomavirus Infectivity, anti-viral activity on varicella-zoster virus, anti-inflammatory activity, anti-herpes Simplex virus type 1 and type 2 activity, anti-oxidant and protective effect against oxidative induced hemolysis.

Keywords: Clinacanthus nutans, Anti-viral, Anti-oxidant, Glycosides, Herpes Simplex Virus.

INTRODUCTION

Clinacanthus nutans (CN) have been used in traditional medicine in Thailand and Malaysia. Its therapeutic potential has not been explored completely. It is commonly known as Belalai gajah, Sabah Snake Grass in Malaysia [1], phaya yo or phaya plongtong in Thailand [2] and Giro de flores, cocodrilo flor, e zui hua in chinese language [4]. Clinacanthus nutans (Burm. f.) Lindau is the accepted name of this species and Clinacanthus nutans var. robinsonii Benoist, Clinacanthus burmanni Nees, Justicia nutans Burm. f. are their synonyms[5]. It is distributed in Thailand, Indonesia, Malaysia,Vietnam and china (Guangdong, Guangxi, Hainan, Yunnan)[3].

Taxonomy [3]

Kingdom: Plantae (Plants)

Class: Equisetopsida C. Agardh

Subclass: Magnoliidae Novák ex Takht.

Superorder: Asteranae Takht.

Order: Lamiales Bromhead

Family: Acanthaceae Juss

Genus: Clinacanthus Nees

Table 1: Common names of Clinacanthus nutans all around the world [2-4]

Common names Language

Belalai gajah

Sabah Snake Grass

 Malay

Twist of flowers

Alligator flower

e zui hua

 Chinese

Phaya yo

Phaya plongtong

 Thai

Table 2: Synonyms of Clinacanthus nutans [5]

Clinacanthus nutans (Burm. f.) lindau Accepted name
Clinacanthus nutans var. robinsonii Benoist Synonym
Clinacanthus burmanni Nees Synonym
Justicia nutans Burm. f. Synonym

Traditional uses

In Malaysia, the fresh leaves are boiled with water and consumed as herbal tea. It is used for treating skin rashes and snake bites, lesions caused by herpes simplex virus, diabetic myelitis, fever and diuretics [6][7]. In Thailand, an alcoholic extract of fresh leaves is used externally for treatment of skin rashes, snake and insect bite, herpes simplex virus (HSV), and varicella-zoster virus (VZV) lesions. The leaves can be consumed as raw material or mixed with other juices such as apple juice, sugarcane or green tea and served as fresh drink [8].

Fig. 1: Leaves and Flower of Clinacanthus nutans


Fig. 2: Clinacanthus nutans


Table 3: Traditioanl uses of Clinacanthus nutans

Country Part use Application
Malaysia Fresh leaves

In Malaysia, the fresh leaves are boiled with water and consumed as herbal tea

It is commonly used in traditional Malaysia for its nourshing and anti-oxidant property. It is also used economical in house regimens for cancer patient [6-7, 9]

Thailand

Indonesia

 Leaves It is used for treating skin rashes and snake bites, lesions caused by herpes simplex virus, diabetic myelitis, fever and diuretics[8]
Thailand Fresh leaves In Thailand, an alcoholic extract of fresh leaves is used externally for treatment of skin rashes, snake and insect bite, herpes simplex virus (HSV), and varicella-zoster virus (VZV) lesions. The leaves can be consumed as raw material or mixed with other juice such as apple juice, sugarcane or green tea and served as fresh drink [8]

Phytochemistry

Clinacanthus nutans contains lupeol (1), b–sitosterol (2)[17], stigmasterol(3) [16] Botulin[18] and myricyl alcohol [10][11]. It also contain six known C-glycosyl flavones isolated from the n-BuOH- and water soluble portion of the methanolic extract of the stems and leaves of C. nutans collected in Thailand such as vitexin (4), isovitexin, shaftoside (5), isomollupentin 7-O-b –glucopyranoside (6), orientin (7) and isoorientin[12].





Five sulfur-containing glucosides were isolated from the n-BuOH-soluble portion of a methanolic extract of the stems and leaves of plant material [13]. A mixture of cerebrosides (8) and a monoacyl monogalactosyl glycerol[(2S)-1-O-linolenoyl- 3-O-b-D- galactopyranosylglycerol](9) were isolated from the EtOAc-soluble fraction of the ethanolic extract of the fresh leaves of C. nutans [14].

13-hydroxy- (13-S)-phaeophytin b, Pupurin-18-phytyl ester and Phaeophorbide a were isolated from leaves of hexane and chloroform extract of C. nutans [15]. Trigalactosyl and digalactosyl diglycerides(10) were isolated form the leave extract and possess anti-herpes simplex virus effect [19].

Hexane and chloroform leave extract of C. nutans contain, 132-hydroxy- (132-S) -chlorophyll-b, 132-hydroxy- (132-R)-chlorophyll-b,132- hydroxy-(132-S)- phaeophytin-b,132-hydroxy-(132-R)- phaeophytin-b, 132-hydroxy-(132-S)-phaeophytin-a,132-hydroxy-(132-R)-phaeophytin-a, purpurin-18- phytyl ester and phaeophorbide-a [20].

Three chlorophyll derivatives (phaeophytins) (11-13) were isolated from the chloroform extract of Clinacanthus nutans Lindau leaves. Three of these were known compounds with structures related to chlorophyll a and chlorophyll b namely 132-hydroxy- (132-R)- phaeophytin b, 132-hydroxy- (132-S)- phaeophytin-a and 132-hydroxy-(132-R) -phaeophytin [21].

(11-13)

Pharmacological activities reported

Fig. 3: Chemical structures of Clinacanthus nutans

Pharmacological activity

Part

use

 Extract/Fraction/Isolate Dose tested/ route of administration Animals/Cell line culture

Experimental

model (In Vivo / In Vitro)

 Results Reference
Cholinergic modulation L Methanol 250 mg/kg, 500 mg/kg, 1 000 mg/kg bw Male mice In vivo A 22
Cytotoxic Study ---------- Stock solution in DMSO

0.01,0.005,0.001, 0.0005, 0.0001

and 0.00001%

 Koi Fin cell line (KFC) In-vitro B 23
Anti-Papillomavirus Infectivity ---------- Stock solution in DMSO Different concentrations in different compounds 293FT cells In-vitro C 24
Anti-inflammatory activity L n-BuOH-soluble fraction ---------------------- ---------------- In-vitro D 25
virucidal Activity ----------- ethanol extracts ------------------------ ----------------- In-vitro E 26

Anti-viral

Activity on varicella-zoster virus.

 L Crude extract ----------------------- --------------- In-vitro F 27

Dengue Virus

Type 2 Infection

 L hexane and chloroform 34, 5, 20, 25 μg/ml C6/36 cell line, A549 cell line In-Vitro G 28
Anti-herpes Simplex Virus type 1 Activity L Ethyl Acetate Extract 1.9,2, 4, 8, 19, 38, 76,152ug/ml Vero cells

in vitro on

the Vero cells by using plaque reduction assay

 H 29
Acute toxicity Study L ethanolic 5.44g/Kg bw rats In vivo I 30
Anti-herpes Simplex Virus type 2 Activity L -------------------- ------------------- Baby hamster kidney cell line In-vitro J 31

Anti-oxidant,

protective effect against oxidative induced hemolysis

 L ethanolic ------------------- ---------------- In-vitro K 32

A= AChE activity was found highest in mice liver, followed by brain, kidney and heart

B= result was reported as 50% cytotoxicity concentration. C. nutans plant extract at 0.005% and 0.01% damaged KFC cells and had the cytotoxic effect to the cell in those concentrations.

C= This study demonstrates anti-HPV16 PsV infection of C. nutans compounds (136C and 136D) that inhibit the early step of infection by direct binding between HPV particles and host cell receptor and also prevent HPV16 PsVs internalization. These suggest the potential

role of the compounds on prevention of HPV infection.

D= It possess anti-inflammatory activity

E= virucidal against HSV-2 in vitro.

F= In a series of in vitro models a crude extract of the leaves showed significant inhibitory activity on VZV.

G=The results showed that out of four compounds, compound 2 could inhibit the production of viral RNA as well as viral protein when the DV2 infected cells were cultured in the compound. This novel property should be further investigated for action on DV infection in the molecular level. This compound may be developed for treatment of DV infection.

H= The results showed that the crude ethyl acetate extract of C. nutans exerted inhibitory effects on HSV-1 action

I= internal organ has No abnormalities

J= The result showed that extract inhibit plaque formation by HSV-2

K= The ethanolic extract of CN had an antioxidant activity and protective effect against free radical-

Induced hemolysis.

Clinical trials

Clinical trials have reported the successful use of a C. nutans preparation (cream) for treatment of genital herpes and varicella-zoster lesions in patients [33-36].

CONFLICT OF INTERESTS

Declared None

REFERENCES

  1. Roosita K, Kusharto CM, Sekiyama M, Fachrurozi Y, Ohtsuka R. Medicinal plants used by the villagers of a Sundanese Community in West Java, Indonesia. J Ethnopharmacol 2008;115:72-81.
  2. Smitinand T. “Thai Plant Names (Botanical Names-VernacularNames),” Royal Forest Department, Phahonyothin, Bangkhen, Bangkok, Thailand; 1980. p. 88.
  3. Tropicos. org. Tropicos | Name-Clinacanthus nutans (Burm. f.) Lindau. [online] Available From: http://www.tropicos.org/Name/50058310[Accessed 12 Aug. 2014].
  4. Taxonomic Hierarchy of COL-China 2012. " Clinacanthus nutans." Encyclopedia of Life; Available from; http://eol.org/pages/5634686/names/common_names.[Accessed 12 August 2014].
  5. Flora of China Editorial Committee. Flora of China (Curcurbitaceae through Valerianaceae with Annonaceae and Berberidaceae). In CY Wu, PH Raven, DY Hong (eds.) Fl China. Science Press & Missouri Botanical Garden Press: Beijing & St. Louis; 2011;19:1–884.
  6. Tuntiwachwuttikul P, Pootaeng-on Y, Phansa P, Taylor WC. Cerebrosides and a monoacylmonogalactosyglycerol from Clinacanthus nutans. Chem Pharm Bull 2004;52(1):27-32.
  7. Sakdarat S, Shuyprom A, Dechatiwongse Na Ayudhya T, Waterman PG, Karagianis G. Chemical composition investigation of Clinacanthus nutans Lindau leaves. Thai J Phytopharmacol 2006;13(2):13-24.
  8. Sakdarat S, Shuyprom A, Pientong C, Ekalaksananan T, Thongchai S. Bioactive constituents from the leaves of Clinacanthus nutans Lindau. Bioorg Med Chem 2009;17:1857-60.
  9. P’ng XW, Akowuah GA, Chin JH. Acute oral toxicity study of Clinacanthus nutans in mice. Int J Pharm Sci Res 2012;3:4202-5.
  10. Boongerd K. “The Chemical Constituents of Clinacanthus burmanii,” M. Sc. Thesis, Chulalongkorn University, Bangkok, Thailand; 1967.
  11. Dampawan P, Huntrakul C, Reutrakul V, Raston CL, White AH. J Sci Soc Thailand 1996;3:14-26.
  12. Terpenoids Teshima K, Kaneko T, Ohtani K, Kasai R, Lhieochaiphant S, Picheansoonthon C, et al. Natural Medicines 1997;51:557
  13. Teshima K, Kaneko T, Ohtani K, Kasai R, Lhieochaiphant S, Picheansoonthon, et al. Sulfur-containing glucosides from Clinacanthus nutans. Phytochem 1998;48:831-5.
  14. Tuntiwachwuttikul P, Pootaeng-On Y, Phansa P, Taylor WC. Cerebrosides and a onoacylmonogalactosylglycerol from Clinacanthus nutans. Chem Pharm Bull (Tokyo) 2004;52(1):27-32.
  15. Ayudhya TDN, Sakdarat S, Shuyprom A, Du an gpen Pattaraadilok JB, Waterman PG, Karagianis G. Chemi-cal constituents of the leaves of Clinacanthus nutans Lin-dau. Thai J Phytopharm 2001;8(1):1.
  16. Dampawan P. Studies of the chemical constituents of Clinacanthus nutans (Acanthaceae) and Zingiber cassumunar Roxb (Doctoral dissertation, Master thesis, Mahidol University, Bangkok, Thailand; 1976.
  17. Dampawan Pimchit, Huntrakul Charus, Reutrakul Vichai, Raston CL, White A H. Constituents of Clinacanthus nutans and the crystal structure of LUP-20 (29)-ene-3-one. J Sci Soc Thailand 1977;3:14-26.
  18. Lin J, Li HM, Yu JG. Studies on the chemical constituents of niu xu hua (Clinacanthus nutans). Zhongcaoyao 1983;14:337-8.
  19. Janwitayanuchit W, Suwanborirux K, Patarapanich C, Pummangura S, Lipipun V, Vilaivan T. Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides. Phytochem 2003;64(7):1253-64.
  20. Sakdarat S, Shuyprom A, Ayudhya TDN, Waterman PG, Karagianis G. Chemical composition investigation of the Clinacanthus nutans Lindau leaves. Thai J Phytopharm 2006;13(2):13-24.
  21. Sakdarat S, Shuyprom A, Pientong C, Ekalaksananan T, Thongchai S. Bioactive constituents from the leaves of clinacanthus nutans Lindau. Bioorg Med Chem 2009;17(5):1857-60.
  22. Lau KW, Lee SK, Chin JH. Effect of the methanol leaves extract of Clinacanthus nutans on the activity of acetylcholinesterase in male mice. J Acute Disease 2014;3(1):22-5.
  23. Haetrakul T, Tangtrongpiros J, Suthamnajpong N, Chansue N. Cytotoxicity concentration of acyclovir and clinacanthus nutans (Burm. f.) lindau extract to koi fin cell line. Thai J Vet Med 2010;108:29-32.
  24. Sookmai W, Ekalaksananan T, Pientong C, Sakdarat S, Kongyingyoes B. The anti-papillomavirus infectivity of Clinacanthus nutans compounds. Srinagarind Med J 2011;26:240-3.
  25. Kittisiripornkul S. “The Antiinflammatory Action and Toxicological Studies of Extracts from Clinacanthus nutans,” M. Sc. Thesis, Faculty of Science, Mahidol University, Bangkok, Thailand; 1984.
  26. Jayavasu C, Chavalittumrong P, Polachandara K. Dechatiwongse na ayudhaya t jongtrakulsiri s. Bull Dept Med Sci 1992;34:154-8.
  27. Thawaranantha D, Balachandra K, Jongtrakulsiri S, Chavalittumrong P, Bhumiswasdi J, Jayavasu C. Siriraj Hosp. Gaz Thailand 1992;44:285-91.
  28. Sittiso S, Ekalaksananan T, Pientong C, Sakdarat S, Charoensri N, Kongyingyoes B. Effects of compounds from Clinacanthus nutans on dengue virus type 2 infection. Srinagarind Med J 2010;25:272-5.
  29. Thongchai S, Ekalaksananan T, Pientong C, Aromdee C, Seubsasana S, Sukpol, C, et al. Anti-herpes simplex virus type 1 activity of crude ethyl acetate extract derived from leaves of clinacanthus nutans lindau. J Sci Technol Mahasarakham University 2010;27(4):318-26.
  30. Chavalittumrong P, Attawish A, Rugsamon P, Chuntapet P. Toxicological study of clinacanthus nutans (Burm. f.) Lindau. Bull Dep Med Sci 2013;37(4):323-38.
  31. Jayavasu C, Dechatiwongse T, Balachandra K, Chavalittumrong P, Jongtrakulsiri S. The virucidal activity of clinacanthus nutans lindau extracts against herpes simplex virus type-2: an in vitro study. Bull Dep Med Sci 2013;34(4):153-8.
  32. Pannangpetch P, Laupattarakasem P, Kukongviriyapan V, Kukongviriyapan U, Kongyingyoes B, Aromdee C. Antioxidant activity and protective effect against oxidative hemolysis of Clinacanthus nutans (Burm. f) Lindau. Songklanakarin J Sci Technol 2007;29(1):1-9.
  33. Jayavasu C, Balachadra K, Sangkitjaporn S, Maharungraungrat A. Com. Dis. J. (Thailand) 1992;18:152-61.
  34. Sangkitporn S, Polchan K, Thawatsupa P, Bunchob M, Chawalittumrong P. Bull Dept Med Serv (Thailand) 1993;18:226-31.
  35. Sangkitporn S, Chaiwat S, Balachadra K, Dechatiwongse Na-AyudhayaT, Bunjob M, Jayavasu C. Treatment of herpes zoster with Clinacanthus nutans (bi phaya yaw) extract. J Med Assn Thailand 1995;78:624-7.
  36. Charuwichitratana S, Wongrattanapasson N, Timpatanapong P, Bunjob M. Herpes zoster: treatment with Clinacanthus nutans cream. Int J Dermatol 1996;35:665-6.