Clinacanthus nutans (Burm.f.) Lindau

Last updated: 26 April 2016

Scientific Name

Clinacanthus nutans (Burm.f.) Lindau

Synonyms

Clinacanthus siamensis Bremek., Justicia nutans Burm. f., Clinacanthus burmanni Nees [Illegitimate], Clinacanthus burmanni var. robinsonii Benoist, Clinacanthus nutans var. robinsonii Benoist [1]

Vernacular Name

Malaysia Belalai gajah [2]
English Sabah snake grass [2]
China E zhui hua [2][3]
Indonesia Ki tajam (Sunda); dandang gendis (Java) [2]
Thailand Salet phangphong [2], phak lin khiat, phak man kai, phayaa plong kham, phayaa-plong-thong, phayaa yo, pho so chang [3]
Vietnam Mảnh cộng; lá cầm; bìm bịp; xương khỉ [2].

Geographical Distributions

Clinacanthus nutans is distributed in Yunnan, Guangxi, Guangdong, Hainan provinces of China, Thailand, Vietnam, Malaysia, Indonesia and other parts of southern Asia. [2][4]

Botanical Description

C. nutans is a member of the Acanthaceae family. [1] It can grow up to 3 m high with pubescent branches. [4][5]

The stems are terete, striate and glabrescent. [4][5]

The leaves are simple, opposite, narrowly elliptic oblong or lanceolate, measuring 2.5-13 cm long and 0.5-4 cm wide, apex acute or acuminate, margin exsculptate-dentate or subentire, base cuneate, obtuse, rounded or truncate often oblique, pubescence on the nerves, the leaf blade are lanceolate-ovate, lanceolate or linear-lanceolate; surfaces pubescent when young then glabrescent except abaxially pilose along veins, secondary veins 4-6 on each side of midvein and abaxially elevated; the petioles are 0.3-2 cm long, sulcate, bifariously pubescent. [4][5]

The flowers are in dense cymes at the top of the branches and their branchlets; cymes 5–8 flowered, often terminating with drooping horizontal branches but themselves erect, subsecund, combined into a large lax, leafy panicle; each flower has calyx densely patently glandular-pubescent, about 1 cm long; corolla glandular-pubescent, about 3.5 cm, dull red with green base; lower lip (turned upwards) with yellow streaks, apically sordidly yellow or greenish yellow; 2 stamens, inserted in the throat, more or less appressed against the upper lip; ovary is compressed, 2-celled, 2 ovules in each cell; having style filiform and shortly bidentate. [4][5]

The capsule is oblong, basally contracted into a short, solid stalk, 4-seeded. [4][5]

Cultivation

No documentation

Chemical Constituent

Methanol extracts of C. nutans stems and leaves have been found to contain flavonoids (e.g. vitexin; isovitexin; shaftoside; isomollupentin 7-O-β-glucopyranoside; orientin and isoorientin) [6] and sulfurous glycosides (e.g. clinacosides A-C; cycloclinacosides A1 and A2). [7]

>Ethanol extracts of C. nutans leaves have been found to contain nine cerebrosides and monoacylmonogalactoylglycerol. [8]

Chloroform extracts of C. nutans leaves was found to contain chlorophyll derivatives (e.g. 132-hydroxy-(132-R)-phaeophytin b; 132-hydroxy-(132-S)-phaeophytin a; 132-hydroxy-(132-R)-phaeophytin a; 132-hydroxy-(132-S)-phaeophytin b; 132-hydroxy-(132-S)-chlorophyll b; 132-hydroxy-(132-R)-chlorophyll b; purpurin 18 phytyl ester; phaeophorbide a) and fatty acids (e.g. n-pentadecanol; eicosane; 1-nonadecene; heptadecane; dibutylphthalate; n-tetracosanol-1; heneicosane; behenic alcohol; 1-heptacosanol; 1,2-benzenedicarboxylic acid; mono(2-ethylhexyl)-ester; nonadecyl heptafluorobutyrate; eicosayl trifluoroacetate; dinonyl ester; phthalic acid; dodecyl nonylester). [9][10]

Plant Part Used

Leaves [11]

Traditional Use

C. nutans is well known anti-snake venom amongst the traditional healers of Thailand. The mechanism of action of this plant is believed to be attributed to its anti-cell lysis property rather than as an anti-neuromuscular transmission blocker. They also use the plant to treat scorpion bites and nettle rash. [12][13] Thai traditional healers make use of the plant to treat fever. [13]

Indonesian and Thai traditional healers make use of C. nutans to treat dysentery. The Indonesians take a handful of the the fresh leaves, boiled them in 5 glasses of water until the water level recedes to about 3 glasses and the decoction is given in a dose of 1 glass each time. The plant also has been used to treat diabetes by boiling 7-21 fresh leaves in 2 glasses of water until the water level recedes to 1 glass and this is given twice daily. Dysuria is treated by taking 15g of fresh leaves and boiling them for 15 minutes. The decoction is consumed once daily. [14]

Preclinical Data

Pharmacology

Antiviral activity

In Thailand the leaves of C. nutans had been used by traditional healers to treat herpes infections. Jayavasu et al. did a study to compare the ability of C. nutans leaves to inactivate herpes simplex virus type-2 (HSV-2) against that of acyclovir. They found that the extracts of the leaves of C. nutans was able to inhibit plaque formation by HSV-2 in baby hamster kidney cell line. [15]

Compounds (132-hydroxy-(132-R)-phaeophytin b, 132-hydroxy-(132-S)-phaeophytin a and 132-hydroxy-(132-R)-phaeophytin a) isolated from chloroform extract of dried leaves of C. nutans completely inhibited activity of pre-compound-treated HSV-1 strain F (the HSV-1Fwas pre-treated for 60 min) on Vero cells after 72 hours incubation (IC50 = 1.96-3.11 nM) compared to pre-acyclovir-treated (5 µg/mL anti-viral drug; also pre-treated for 60 min) using plaque reduction assay. Pre-compound-treated Vero cells (was pre-treated for 60 min) showed 100% inhibition after 72 hours incubation than post-compound-treated cells (the Vero cells initially infected with HSV-1F and then was pre-treated for 60 min). [16]

Both fractions CL03 (50-200 µg/mL) and CL21 (5-80 µg/mL) from ethanol extract of C. nutans leaves reduced quantity of HSV-2’s DNA in a dose-dependent manner (12.99-70.96% and 7.65-62.94% DNA intensities respectively) compared to untreated control. These fractions also reduced the quantity of eight HSV-2’s proteins (20, 40, 44, 55, 69, 78, 125 and 146 KDa proteins) in a dose-dependent manner (144-15946 µg/mL and 50-15657 µg/mL) compared to untreated control (2396-16799 µg/mL). [17]

Compound 2 isolated from crude extract (hexane and chloroform) of dried leaves of C. nutans (5-34 µg/mL) inhibited the replication of dengue virus 2 (DV2) on pre-treated type II human lung alveolar epithelial cell carcinoma A549. [18]

Crude extract (organic solvents) of C. nutans leaves actively inhibited multiplication of varicella-zoster virus (VZV) in inactivation treatment (5000 PFU/mL cell-free VZV mixed with growth media containing extract or control) with 50% inhibitory dose of 1:9600 compared to acyclovir control (ID50 = 30 µM) using plaque reduction assay [19].

With the recent outbreak of Influenza A (H1N1) globally, Wirotesangthong et al. studied the effectiveness of C. nutans  leaf extract on influenza virus infection. They studied its effects against the following viruses: influenza virus A/New Caledonia/20/99 (H1N1), mouse-adapted influenza virus A/Guizhou/54/89 (A/G)(H3N2) and mouse-adapted influenza virus B/Ibaraki/2/85 (B/I) were used in the NA inhibition assay, and mouse-adapted influenza viruses A/PR/8/34 (H1N1), A/G and B/I were used in the in vitro antiviral assay. They found that the extract was superior in its ability to protect the mouse against influenza virus infection as compared to oseltamivir. [20]

Immunomodulatory activity

Ethanol extract of C. nutans dried leaves (0.5-5.0 µg/mL) significantly (p < 0.05) increased the proliferation of lymphocytes from peripheral blood mononuclear cells (PMBCs) of healthy adult human (stimulation index of 1.14-1.36) compared to untreated control (stimulation index of 1.00). However, at dose of 2.5 and 5.0 mg/mL, the extract significantly (p < 0.05) reduced the lymphocyte proliferation (stimulation index of 0.69-0.75) compared to untreated control (stimulation index of 1.00). Ethanol extract of C. nutans dried leaves (1 and 5 mg/mL) significantly (p < 0.05) reduced the activity of natural killer cells (from PMBCs of healthy adult human) (0.01 and 42.04 lytic units x 10-7 PMBCs) compared to untreated control (103.10 ±56.64 lytic units x 10-7 PMBCs). Ethanol extract of C. nutans dried leaves (2.5 and 5 mg/mL) induced the production of interleukin 4 (from PMBCs of healthy adult human) (40 and 1200 pg/mL) compared to untreated control (<16 pg/mL) by using enzyme linked immunosorbent assay. [21]

Anti-inflammatory activity

Wanikiat et al. found the extracts of the leaves of C. nutans to possess a strong anti-inflammatory activity corroborating further its extensive used as an anti-inflammatory medicine. This effect they said was partly due to its ability to inhibit the neutrophil responsiveness as evidenced by the significant inhibtiion of myeloperoxidase (MPO) activity. [22]

Antivenom activity

C. nutans is a plant used extensively by traditional healers of southern Thailand and North-western Malaysia as a remedy for envenomation be it snakes or venomous insects like scorpions and bees effectively. The method of using it is yet to be documented. Cherdchu et al. did not find any antivenin activity. What they test against was its ability to neutralise the inhibitory effects of neurotoxins of Naja naja siamensis on neuromuscular transmission [12]. However, there are other components in the venom of the snake upon which the plant could neutralise as reported by Watson in Botanical Medicine in Clinical practice where he cited the possiblity of anti-cell lysis as an explanation [12][13].

Antioxidant activity

The role of free radicals in the pathophysiology of diseases has been very well established. Today many researchers are looking into plants as a source of antioxidants. Amongst the subject of study is C. nutans, the antioxidant properties of ethanolic extract of the leaves of C. nutans was caught the interest. They found that this extract had an antioxidant activity and protective effect against free radical-induced haemolysis. This is evidenced by the fact that it could scavange DPPH with a maximum scavenging activity of 67.65±6.59% and with IC50 of 110.4±6.59 μg/mL; the FRAP value was 17 mg ascorbate equivalent to one gram of the extract. The extract demonstrated a significant inhibition of peroxide production in rat macrophages stimulated by phorbol myristate acetate (PMA) and protected red blood cell against AAPH-induced hemolysis with an IC50 of 359.38±14.02 mg/mL. [24]

Chloroform, methanol and aqueous extracts of C. nutans leaves were tested for their scavenging activity on 1,1-diphenyl-2-picrylhydrazyl radicals. Chloroform extract showed the highest scavenging activity (7852.63 ±449.90 µg Trolox equivalent/g) compared to other extracts (<6000 µg Trolox equivalent/g).Chloroform, methanol and aqueous extracts of C. nutans leaves were tested for their scavenging activity on galvinoxyl radicals. Chloroform extract showed the highest scavenging activity (12248.82 ±173.50 µg Trolox equivalent/g) compared to other extracts (<3000 µg Trolox equivalent/g). Aqueous extract of C. nutans leaves (100 µg/mL) showed nitric oxide scavenging activity with 32.33 ±0.97% inhibition. [25]

Cytotoxic activity

Compounds (132-hydroxy-(132-R)-phaeophytin b, 132-hydroxy-(132-S)-phaeophytin a and 132-hydroxy-(132-R)-phaeophytin a) isolated from crude extract of C. nutans dried leaves (5.89-6.21 µM) showed no cytotoxicity effect on African green monkey kidney cell line (Vero cells) using crystal violet assay. [16]

>Ethanol extract of C. nutans leaves (1 and 100 µg/mL) significantly (p<0.05) increased the percentage of human keratinocyte HaCaT cells survival (pre-treated with interferon-γ and tumour necrosis factor-α) compared to untreated control using MTT assay. Fractions (CL03 and CL21) from ethanol extract of C. nutans leaves showed no cytotoxicity effect on human laryngeal carcinoma cells (HEp-2) (50% cytotoxic concentration (CC50) >300 µg/mL) compared to untreated control. [26]

Compounds (1-4) isolated from extract of C. nutans dried leavesshowed cytotoxicity effect on A549 cells (adenocarcinomic human alveolar basal epithelial cells) with CC50 of 25-50 µg/mL using MTT assay compared to untreated control. [18]

Chloroform extract of C. nutans leaves (25-100 µg/mL) significantly inhibited the growth of cultured human cancer cell lines in a dose-dependent manner (p < 0.05), i.e. liver hepatocellular carcinoma (29.97-38.76%), lung cancer cells (39.14-55.82%), gastric cancer cells (25.05-31.25%), colon adenocarcinoma (22.25-56.73%), erythroleukemia (36.52-41.97%, cervical cancer cells (32.32-91.28%) and Burkitt’s lymphoma cells (38.01-88.97%) using MTT assay compared to normal cells. Methanol extract of C. nutans leaves (12.5-100 µg/mL) significantly inhibited the growth of cultured human cancer cell lines in a dose-dependent manner (p < 0.05), i.e. liver hepatocellular carcinoma (25.00-41.88%) and colon adenocarcinoma (13.21-30.33%) using MTT assay compared to normal cells. The same extract at a concentration of 100 µg/mL also significantly inhibited the growth of neuroblastoma cancer cells (22.08 ±1.22%) and gastric cancer cells (21.32 ±1.43%) using the same assay. Aqueous extract of C. nutans leaves (12.5-100 µg/mL) significantly inhibited the growth of cultured human cancer cell lines in a dose-dependent manner (p < 0.05), i.e. liver hepatocellular carcinoma (14.89-27.42%),   colon adenocarcinoma (16.56-27.57%), erythroleukemia (19.56-36.31%) and Burkitt’s lymphoma cells (12.48-40.94%) using MTT assay compared to normal cells. The same extract at concentrations of 50 and 100 µg/mL also significantly inhibited the growth of neuroblastoma cancer cells (13.80 ±0.70% and 23.22 ±0.63%) using the same assay. [25]

 

Toxicity

Acute toxicity

Methanol extract of C. nutans leaves (0.9 and 1.8 g/kg body weight) given orally to male albino Swiss mice (25-35 g of body weight) respectively for 14 days showed no toxic effect (LD50 > 1.8 g/kg body weight), neither death nor significant changes on body weights and relative organ weights. [27]

Clinical Data

Clinical findings

Antivaricella-zoster virus infection

A randomised, placebo-controlled trial of efficacy of topical formulation of Clinacanthus nutans extract was done on 51 patients with varicella-zoster virus infection. The results obtained showed that lesion crusting occurs within 3 days of application and healing within 7 days. The medication was applied 5 times per day for 7-14 days until lesion healed. Pain scores were also reduced significantly. No side effects were observed during the course of treatment. [28]

Treatment of Recurrent Aphthous ulcer

Timpawat and Vajrabhaya did a double blind controlled trial to evaluate the efficacy of Clinacanthus nutans Lindau in orabase in the treatment of recurrent aphthous stomatitis. Forty three (43) patients were recruited for this trial and the efficacy was tested against triamcinolone acetonide in orabase and placebo. They found that Clinacanthus nutans Lindau in orabase provide better healing of the ulcer as compared to placebo but was less so when compared to triamcinolone acetonide in orabase. [29]

Precautions

No documentation

Side effects

No documentation

Pregnancy/Breast Feeding

No documentation

Age limitation

No documentation

Adverse reaction

No documentation

Interaction & Depletion

No documentation

Interaction with drug

No documentation

Interaction with other Herbs

No documentation

Contraindications

No documentation

Case Report

No documentation

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation

References

  1. The Plant List. Clinacanthus nutans (Burm.f.) Lindau.Ver 1.1. [homepage on the Internet]. c2013 [updated on 2012 April 18; cited on 2016 Apr 5]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2727901
  2. Complementary and Alternative Healing University. Clinacanthus nutans (Burm. f.) Lindau [homepage on the internet] [updated; 2011 Aug 12; cited on 2016 April 26]. Available from: http://alternativehealing.org/Sabah_snake_grass.html
  3. Quattrocchi U. CRC World Dictionary of Plant Names: Common Names, Scientific Names, Eponyms, Synonyms, and Etymology. Volume II C-D. Boca Raton, FL: CRC Press LLC; 1999 p. 320.
  4. Floras of China. Clinacanthus nutans. [homepage on the internet]. c2013 No date [cited on 2016 April 26]. Available from: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200021997
  5. Asean herbal and medicinal plants. [homepage on the internet] Clinacanthus nutans (Burm. f.) Lindau; 2010 [cited on 2016 February 26]. Available from: http://www.scribd.com/doc/112146724/ASEAN-Herbal-and-Medicinal-Plants-2010
  6. Teshima KI, Kaneko T, Ohtani K, et al. C-glycosyl flavones from Clinacanthus nutans. Natural Medicines. 1997;51(6):557.
  7. Teshima KI, Kaneko T, Ohtani K, et al. Sulfur-containing glucosides from Clinacanthus nutans. Phytochemistry. 1998;48(5):831-835.
  8. Tuntiwachwuttikul P, Pootaeng-On Y, Phansa P, et al. Cerebrosides and a monoacylmonogalactosylglycerol from Clinacanthus nutans. Chemical and Pharmaceutical Bulletin (Tokyo). 2004;52(1):27-32.
  9. Sakdarat S, Shuyprom A, Pientong C, et al. Bioactive constituents from the leaves of Clinacanthus nutans Lindau. Bioorganic & Medicinal Chemistry. 2009;17(5):1857-1860.
  10. Sakdarat S, Shuyprom A, Na Ayudhya TD, et al. Chemical composition investigation of the Clinacanthus nutans Lindau leaves. Thai Journal of Phytopharmacy. 2006;13(2):13-24.
  11. Heinrich M, Jager AK editor. Ethnopharmacology: postgraduate pharmacy series. UK: John Wiley & Sons, 2015; p.324.
  12. Watson R, Preedy VR. Botanical medicine in clinical practice. London, UK: CABI, 2008; p.819.
  13. Vandebroek I, Pieroni A. Traveling cultures and plants: the ethnobiology and ethnopharmacy of human migrations. New York: Berghahn Book, 2009; p.112.
  14. H Arief Hariana. 262 tumbuhan obat dan khasiatnya. Jakarta: Penebar Swadaya Grup, 2013; p.184.
  15. Jayavasu C, Dechatiwongse T, Balachandra, et al. The virucidal activity of clinacanthus nutans lindau extracts against herpes simplex virus type-2: an in vitro study. Bulletin of the Department of Medical Sciences- Warasan Krom Witthayasat Kanphaet. 2013;34(4):153-158.
  16. Sakdarat S, Shuyprom A, Pientong C, et al. Bioactive constituents from the leaves of Clinacanthus nutans Lindau. Bioorganic & Medicinal Chemistry. 2009;17(5):1857-1860.
  17. Vachirayonstien T, Promkhatkaew D, Bunjob M, et al. Molecular evaluation of extracellular activity of medicinal herb Clinacanthus nutans against herpes simplex virus type-2. Natural Product Research. 2010;24(3):236-245.
  18. Sittiso S, Ekalaksananan T, Pientong C, et al. Effects of compounds from Clinacanthus nutans on dengue virus type 2 infection. Srinagarind Medical Journal. 2010;25(Suppl):272-275.
  19. Thawaranantha D, Balachandra K, Jongtrakulsiri S, et al. In vitro antiviral activity of Clinacanthus nutans on varicella-zoster virus. Siriraj Hospital Gazette. 1992;44(4):284-291.
  20. Wirotesangthong M, Nagai T, Yamada H, et al. Effects of Clinacanthus siamensis leaf extract on influenza virus infection. Microbiology and immunology. 2009;53(2), 66-74.
  21. Sriwanthana B, Chavalittumrong P, Chompuk L. Effect of Clinacanthus nutans on Human Cell-mediated Immune Response in vitro. Thai J. Pharm. Sci. 1996; 20(4):261-267.
  22. Wanikiat P, Panthong A, Sujayanon P, Yoosook C, Rossi AG, Reutrakul V. The anti-inflammatory effects and the inhibition of neutrophil responsiveness by Barleria lupulina and Clinacanthus nutans extracts. J Ethnopharmacol. 2008;116(2):234-44.
  23. Cherdchu C, Poopyruchpong N, Adchariyasucha R, et al. The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom. Southeast Asian J Trop Med Public Health. 1977;8(2):249-54.
  24. Pannangpetch P, Laupattarakasem P, Kukongviriyapan V, et al. Antioxidant activity and protective effect against oxidative hemolysis of Clinacanthus nutans (Burm.f) Lindau. Songklanakarin J. Sci. Technol. 2007; 29(Suppl. 1):1-9.
  25. Yong YK, Tan JJ, Teh SS, Mah SH, Ee GC, Chiong HS, Ahmad Z. Clinacanthus nutans extracts are antioxidant with antiproliferative effect on cultured human cancer cell lines. Evidence-Based Complementary and Alternative Medicine. 2013;2013:462751.
  26. Thongrakard V, Tencomnao T. Modulatory effects of Thai medicinal plant extract on proinflammatory cytokines-induced apoptosis in human keratinocyte HaCaT cells. African Journal of Biotechnology. 2010;9(31):4999-5003.
  27. P'ng XW, Akowuah GA, Chin JH. Acute oral toxicity study of Clinacanthus nutans in mice. International Journal of Pharmaceutical Sciences & Research. 2012;3(11):4202.
  28. Sangkitporn S, Chaiwat S, Balachandra K, et al. Treatment of herpes zoster with Clinacanthus nutans (bi phaya yaw) extract. J Med Assoc Thai. 1995;78(11):624-7.
  29. Timpawat S, Vijrabhava L. Clinical evaluation of Clinacanthus nutans Lindau in orabase in the treatment of recurrent aphthous stomatitis. Mahidol Dental Journal. 1994;14(1):10-16.