Dermal irritation and sensitization study of Euphorbia neriifolia latex and its anti-inflammatory efficacy
Keywords:
Euphorbia neriifolia, Latex, Dermal irritation, Antiinflammatory, Triterpenes, EupholAbstract
The presence of polycyclic diterpene esters in Euphorbia plants sap makes it highly irritant and notably corrosive causing burning pain of skin. The toxic nature of the Euphorbia is discouraging their uses despite the possible manifold therapeutic potentials. Euphorbia neriifolia (Euphorbiaceae) commonly known as Thuar is a sacculant shrub commonly and abundantly found as hedge plant in Central India. This study was designed to screen the physiochemical properties of latex and dermal irritation potential of its different solvent fractions targeting to retain the triterpene content high to extract therapeutic utilization. Physico-chemical, qualitative and quantitative phytochemical, dermal irritation and sensitization profile and topical anti-inflammatory activity of E. neriifolia latex were studied. Fresh latex contains 10.95 % solid with 18.32 % total resinous matter, and 24.50 % and 16.23 % of total diterpene and triterpene respectively. Petroleum ether fractionation showed 63.80 % yield with rich presence of steroid and triterpenoid. Pet. ether fraction was found to be apparently nonirritating with a PII score of 0.43/0.11 for erythema and edema according to Draize Dermal Classification System. Chloroform, acetone and water fractions are skin irritating due to presence of high diterpene content where as pet. ether fraction is rich in triterpene showing nonirritant activity. Topically latex pet. ether fraction at 750 and 500 mg/ml dose showed 42.40 and 35.25 % inhibition of carrageenan induced paw edema. Anti-inflammatory activity of latex pet. ether fraction is due to presence of triterpenes euphol, nerifoliol and cycloartenol. This study explores safe topical use profile of E. neriifolia latex retaining its anti-inflammatory efficacy.
References
Webster GL. Plant dermatitis. Irritant plants
in the spurge family (Euphorbiaceae).
Clinical Dermatology 1986; 4(20): 36-45.
Hohmann J, Molnar J. Euphorbiaceae
diterpenes: Plant toxins or promising
molecules for the therapy? Acta Pharm.
Hung. 2004; 74: 149-157.
Newall CA, Anderson LA, Phillipson JD.
Herbal medicines. London: The
Pharmaceutical Press; 1996. p. 109.
Betancur-Galvis LA, Morales GE, Forero
JE, Roldan J. Cytotoxic and antiviral
activities of Colombian medicinal plant
extract of the Euphorbia genus. Mem Inst
Oswaldo Cruz 2002; 97: 541-546.
Singla AK, Pathak K. Phytoconstituents of
Euphorbia species. Fitoterapia 2009; 61:
-516.
Guerreroy RO, Guzman AL. Bioactivities
of latexes from selected tropical plants. Rev
Cubana Plant Med. 2004; 9(1): Accessed
– March 10, 2008. Available at:
http://scielo.sld.cu/scielo.php?pid=S1028-
&script=sci_arttext.
Ilyas M, Perveen M, Muhaisen HMH,
Basudan OA. A novel triterpene
(Nerifolione) a potent anti-inflammatory
and antiarthritic agent from Euphorbia
neriifolia. Hamdard-Medicine (Pakistan)
; 46(2): 97-102.
Shi QW, Su XH, Kiyota H. Chemical and
pharmacological research of the plants in
genus Euphorbia. Chemical Review 2008;
(10): 4295-4327.
Vogg G, Mattes E, Rothenburger J,
Hertkorn N, Stefan A, Sandermann JH.
Tumor promoting diterpenes from
Euphorbia leuconeura L. Phytochemistry
; 51: 289-295.
Baloch IB, Baloch MK, Saqib QN. Tumorpromoting diterpene esters from latex of
Euphorbia cauducifolia L. Helvetica
Chimica Acta 2005; 88: 3145-3150.
Kirtikar KR. Basu BD. Indian Medicinal
Plants. 2nd ed. Dehradun, India:
International Book Distributors; 1996. p.
Anonymous. The Wealth of India: Raw
Material. Vol III. D-E. New Delhi, India:
CSIR Publication; 1952. p. 226.
Pandey GS. Bhavaprakasa Nighantu. In:
Mishra B, editors. Indian Materia Medica.
Varanashi, India: Chaukhambha Bharti
Academy; 1992. p. 76-77 and 308.
ICMR report. Multicentric randomized
controlled clinical trial of Kshaarasootra
(Ayurvedic medicated thread) in the
management of fistula-in-ano. Indian
Journal of Medical Research (B) 1991; 94:
-185.
Amin KMY, Faridi MA, Asif M, Khan NA.
The efficacy and safety of Euphorbia
neriifolia – Unani antiarthritic drug. Indian
Journal of Pharmacology 1995; 27: 60.
Rashik AM, Shukla A, Patnaik GK,
Dhawan BN, Kulshrestha DK. Wound
healing activity of latex of Euphorbia
neriifolia Linn. Indian Journal of
Pharmacology 1996; 28(2): 107-109.
Ponsinet G, Ourisson G.
Chemotexonomical studies of the family
Euphorbiaceae. (Article in German)
Phytochemistry 1968; 7: 89-98.
Ilyas M, Praveen M, Amin KMY.
Nerifolione, a triterpene from Euphorbia
neriifolia. Phytochemistry 1998; 48: 561-
Mallavadhani UV, Satyanarayana KVS,
Mahapatra A, Sudhakar AVS. A new
tetracyclic triterpene from the latex of
Euphorbia neriifolia. Natural Product
Research 2004; 18(1): 33-37.
Indian Pharmacopoeia. Government of
India, Ministry of Health and Family
Welfare. New Delhi, India: The Controller
of Publications; 1996. p. A89-99.
Paech T, Tracy MV. Modern Methods in
Plant Analysis. Berlin: Springer Verlog;
p. 387.
Kinghorn AD, Evans FJ. Skin irritants of
Euphorbia fortissima. Journal of Pharmacy
and Pharmacology 1975; 27(5): 329-333.
Organization for Economic Co-operation
and Development. Guidelines for Testing of
Chemicals, Section 4: Health Effects.
Subsection 404: Acute Dermal
Irritation/Corrosion. Version 1: 1992.
DeGroot AC. Patch Testing, Test
Concentrations and Vehicles for 2800
Allergens. Amsterdam: Elsevier Science;
Derelanko MJ, Hollinger MA. Handbook of
toxicology. In: Bonnette KL, Rodabaugh
DD, Wilson CW, editors. Dermal irritation
and sensitization. 2nd ed. USA: CRC Press
LLC; 2002. p. 141-213.
Lira AAM, Sester EA, Carvalho ALM,
Strattmann RR, Albuquerque MM,
Wanderley AG, Santana DP. Development
of lapachol topical formulation: Antiinflammatory study of a selected
formulation. AAPS Pharmaceutical Science
and Technology 2008; 9(1): 163-168.
Lam TSK, Wong OF, Leung CH, Fung HT.
A case report of ocular injury by Euphorbia
plant sap. Hong Kong Journal of
Emergency Medicine 2009; 16(4): 267-270.
Pitts JF, Barker NH, Gibbons DC, Jay JL.
Manchineel keratoconjunctivitis. British
Journal of Ophthalmology 1993; 77(5):
-288.
Nadkarni AK. Indian Materia Medica. vol.
Bombay, India: Popular prakashan; 1976.
p. 424-426.
Harborne JB. Phytochemical Methods (A
guide to Modern Techniques of Plant
Analysis). 1st ed. London: Chapman and
Hall; 1973. p. 100-141.
Upadhyay R, Samiyeh R, Tafazuli A.
Tumor promoting and skin irritant diterpene
esters of Euphorbia virgata latex.
Neoplasma 1981; 28(5): 555-558.
Mizuo Mizuno MZ, Tanaka T, Iinuma M,
Guang-Yi X, Qing H. A diterpenes from
Euphorbia antiquorum. Phytochemistry
; 28(2): 553-555.
Ng AS. Diterpenes from Euphorbia
neriifolia. Phytochemistry 1990; 29: 662-
Alberto Marco J, Sanz-Cervera JF, Checa J,
Palomares E, Fraga BM. Jatrophane and
tigliane diterpenes from latex of Euphorbia
obtusifolia. Phytochemistry 1999; 52(3):
-485.
Baslas RK, Agarwal R. Chemical
investigation of some anticancer plants of
Euphorbia genus. Indian Journal of
Chemistry 1980; 19B: 717-718.
Koh LL, Ng AS, Tan GK. Structure of a
diterpene from Euphorbia neriifolia. Acta
Cryst. 1992; C48: 753-754.
Mukherjee PK. Quality control of herbal
drugs: An approach to evaluation of
botanicals. 1st ed. New Delhi, India:
Business Horizons; 2002. p. 410-418.
Bigoniya P, Rana AC. Radioprotective and
In-vitro cytotoxic sapogenin from
Euphorbia neriifolia (Euphorbiaceae) Leaf.
Tropical Journal of Pharmaceutical
Research 2009; 8(6): 521-530.
Bonta IL, Noordhoek J. Anti-inflammatory
mechanism of inflamed –tissue factor.
Agents and Actions 1973; 3(5): 348-356.
Appendino G, Szallasi A. Euphorbium:
Modern research on its active principle,
resiniferatoxin, revives an ancient medicine.
Life Science 1997; 60: 681-696.
Fenandez-Arche A, Saenz MT, Arroyo M,
De la Puerta R, Garcia MD. Topical antiinflammatory effect of tirucallol, a
triterpene isolated from Euphorbia lactea
latex. Phytomedicine 2010; 17(2): 146-148.
Akihisa T, Yasukawa K, Oinuma H,
Kasahara Y, Yamanouchi S, Takido M,
Kumaki K, Tamura T. Triterpene alcohols
from the flowers of Compositae and their
anti-inflammatory effects. Phytochemistry
; 43: 1255-1260.
Yasukawa K, Akihisa T, Oinuma H,
Kaminaga T, Kanno H, Kasahara Y,
Tamura T, Kumaki K, Yamanouchi S,
Takido M. Inhibitory effect of taraxastanetype triterpenes on tumor promotion by 12-
O-tetradecanoyl-phorbol-13-acetate in twostage carcinogenesis in mouse skin.
Oncology 1996; 53: 341-344.
Akihisa T, Yasukawa K, Kimura Y, Takase
S, Yamanouchi S, Tamura T. Triterpene
alcohols from Camellia and Sasanqua oils
and their anti-inflammatory effects.
Chemical and Pharmaceutical Bulletin
; 45(12): 2016-2023.
Bani S, Kaul A, Jaggi BS, Suri KA, Suri
OP, Sharma OP. Anti-inflammatory activity
of the hydrosoluble fraction of Euphorbia
royleana latex. Fitoterapia 2000; 71(6):
-662.
Kedei N, Lundberg DJ, Toth A, Welburn P,
Garfield SH, Blumberg PM.
Characterization of the interaction of
ingenol 3-angelate with protein kinase C.
Cancer Research 2004; 64: 3243-3255.
Hergenhahn M, Kusumoto S, Hecker E. On
the active principles of the spurge family
(Euphorbiaceae)-V. Extremely skin-irritant
and moderately tumor-promoting diterpene
esters from Euphorbia resinifera Berg.
Cancer Research and Clinical Oncology
; 108(1): 98-109.
