Anti-mycobacterial activity of Piper longum L. fruit extracts against multi drug resistant Mycobacterium Spp.
Keywords:
Piper longum, piperine, bioassay guided fractionation, NMR, Mycobacterium, tuberculosisAbstract
A long tradition of using pepper as to fight against several ailments by the local tribal people is still in the practice, in many parts of the rural India. So utilizing this tribal knowledge base for this highly medicinal plant, an attempt was made to isolate some novel natural bioactive compounds with potential activity against multidrug resistant (MDR) Mycobacterium. A bioassay guided fractionation of Pippali (Piper longum L.) was performed in five different organic solvents and their activities were monitored against different pathogenic bacteria including MDR Mycobacterium. Different fractions were screened for the bioactivity against Mycobacterium, and the structure of bioactive compound was characterized with H1 and C13 NMR. An ethyl acetate fraction of Pippali extract was found active against M. smegmatis (3000µg ml-1) and M. tuberculosis (39 µg ml-1). It also shows very significant activity against other bacterial strains like E.coli (152 µg ml- 1), Staphylococcus aureus (14 µg ml-1), Salmonella typhi (180 µg ml-1), Enterococcus faecalis (15 µg ml-1), and Pseudomonas aeruginosa (52 µg ml-1). This fraction of ethyl acetate was then purified and characterized as piperine [5-(1, 3-benzodioxol-5-yl)-1-piperidin-1- ylpenta-2,4-dien-1-one], a well known alkaloid from this plant. Bioactivity guided fractionation concludes that Piperine is the only active ingredients in various fractions of fruit extract evaluated for antibacterial activity. Fraction having piperine has significant activity against multi drug resistant strains of Mycobacterium spp. than other purified fractions of fruit extract. The current finding encourages us to develop new alternative medicine that includes piperine alone and/or in combination with other drugs to fight against the drug resistance among Mycobacterial strains.
References
.Altmann KH. Microtubule-stabilizing
agents: a growing class of important
anticancer drugs. Curr Opi Chem Biol
; 5: 424-431.
.Tanaka JCA, da Silva CC, de Oliveira
AJB, Nakamura CV. Antibacterial
activity of indole alkaloids from
Aspidosperma ramiflorum. Braz J Med
Biol Res 2006; 39: 387-391.
.Cohen ML. Epidemiology of drug
resistance: implications for a postantimicrobial era. Science 1992; 257:
-5.
.Neu HC. The crisis in antibiotic
resistance. Science 1992; 257:1064-1073.
.Yurdakok K, Sahin N, Ozmert E,
Berkman E. Shigella gasteroenteritis:
Clinical and epidemiological aspects and
antibiotic susceptibility. Acta Paediatr J
; 39: 681-3.
.Nardi GM, Felippi R, Dalbo S, Siqueirajunior JM, Arruda DC, Delle Monache F,
Timbola AK, Pizzolatti MG, Ckless K,
Ribeiro do-Valle RM. Anti- inflammatory
and antioxidant effects of Croton
celtidifolius bark. Phytomed 2003; 10:
-184.
.Essawi T, Srour M. Screening of some
palestinian medicinal plants for
antibacterial activity. J Ethnopharmacol
; 70: 343-349.
.Tomoko N, Takashi A, Hiromu T, Yuka I,
Hiroko M, Munekazu I, Totshiyuki T,
Tetsuro I, Fujio A, Iriya I, Tsutomu N,
Kazuhito W. Antibacterial activity of
extracts preparated from tropical and
subtropical plants on methicillin-resistant
Staphylococcus aureus. J health Sci 2002;
: 273-276.
.Iwu MW, Duncan AR, Okunji CO. New
antimicrobials of plant origin. In: Janick,
J. (eds.) Perspectives on new crops and
new uses. ASHS Press Alexandria, VA,
USA, p. 1999; 457-462.
. Taylor JLS, Rabe T, McGaw LJ,
Jäger AK,van Staden J. Towards the
scientific validation of traditional
medicinal plants. Plant Growth Regul
; 34: 23-37.
. Ncube NS, Afolayan AJ, Okoh AI.
Assessment techniques of antimicrobial
properties of natural compounds of plant
origin: current methods and future trends
Afr J Biotech 2008; 7: 1797-1806.
. Ikram M, Inamul H. Screening of
medicinal plants for antimicrobial
activities. Fitoterapia 1984; 55: 62-64.
. Izzo AA, Carlo DI, Biscardi G,
Fusco D, Mascolo R, Borreli N, Capasso
F, Fasulo F, Autore MP. Biological
screening of Italian medicinal plants for
antibacterial activity. Phytother Res 1995;
: 281-286.
. Bhattacharjee I, Chatterjee SK,
Chatterjee S, Chandra G. Antibacterial
potential of Argemone mexicana solvent
extracts against some pathogenic bacteria.
Mem Inst Oswaldo Cruze Rio de Janeiro
; 6: 645- 648.
. Mitscher LA, Drake S, Gollapudi
SR, Okwute SK. A modern look at
folkloric use of anti-infective agents. J
Nat Prod 1987; 50: 1025–1040.
. Basso LA, Pereira DA, Silva LH,
Fett Neto AG, Azevedo Jr WFD, Moreira
FD.Targets for treatment of malaria,
tuberculosis and T-Cell mediated
diseases. Mem Inst Oswaldo Cruz Rio De
Janeiro 2005; 6: 575-606.
. Ahn JW. Cytotoxic limonoids
from Melia azedarach var. japonica.
Phytochem 1994; 36: 1493-1496.
. Silva O, Duarte A, Cabrita J,
Pimentel M, Diniz A, Gomez E.
Antimicrobial activity of Guinea-Bissau
traditional remedies. J Ethnopharmacol
; 50: 53-59.
. Iwu MM, Duncan RA and Okunji
CO. New Antimicrobials of Plant Origin.
In: Perspectives on New Crops and New
Uses, Janick, J. (eds.). ASHS Press,
Alexandria, Virginia, 1999; 457-462.
. Scheck AC, Perry K, Hank NC,
Clark WD. Anticancer activity of extracts
derived from the mature roots of
Scutellaria baicalensis on human
malignant brain tumor cells. Biomed
Centr Complement Alternat Med 2006; 6:
. Stohr JR, Xiao PG, Bauer R.
Constituents of Chinese Piper species and
their inhibitory activity on prostaglandin
and leukotriene biosynthesis in vitro. J
Ethnopharmacol 2001; 75: 133-139.
. Shoji N, Umeyama A, Saito N,
Takemoto T, Kajiwara A, Ohizumi Y.
Dehydropipernonaline, an amide
possessing coronary vasodilating activity,
isolated from Piper longum L. J Pharm
Sci 1986; 75: 1188-1189.
. Lee SE. Mosquito larvicidal
activity of pipernonaline, a piperidine
alkaloid derived from long pepper, Piper
longum. J Am Mosq Control Assoc 2000;
: 245-247.
. Rege NN, Thatte UM, Dahanuker
SA. Adaptogenic properties of six
rasayana herbs used in Ayurvedic
medicine. Phytother Res 1999; 13: 275-
. Tripathi DM, Gupta N, Lakshmi
V, Saxena KC, Agrawal AK. Antigiardial
and immune stimulatory effect of Piper
longum on giardiasis due to Giardia
lamblia. Phytother Res 1999; 13: 561-
. Hu RQ, Davies JA. Effects of
Piper nigrum L. on epileptiform activity
in cortical wedges prepared from DBA/2
mice. Phytother Res 1997; 11: 222–225.
. Takumi I, Mizuho I, Siho T, Yuzi
I, Hideyuki Y. Piperine, a pepper
ingredient, improves the hepatic increase
in free fatty acids caused by 2, 3, 7, 8-
tetra chlorodibenzo-p-dioxine. J Health
Sci 2008; 54: 551-58.
. Jalalpure SS, patil M.B., Prakash
NS, Hemlata K and Manvi FV.
Hepatoprotective activity of fruit of Piper
longum Linn. Ind J of Pharmaceu Sci
; 65: 363-366.
. Chandrashekhar RB, Jithan A,
Narsimha RY, Malla RV. Fabrication and
investigations on hepatoprotective activity
of sustained release biodegradable
piperine microspheres. Int J Phar Sci and
Nano Tech 2008; 1: 87-96.
. Bauer AW, Kirby WM, Sherris
JC, Turck M. Antibiotics susceptibility
testing by a standardized single disc
method. Am J Clin Pathol 1996; 45: 493-
. National Committee for Clinical
Laboratory Standards. Reference method
for broth dilution antifungal susceptibility
testing of yeasts: Approved Standard
M27-A. NCCLS, Villanova, PA 1997.
. Reddy PS, Jamilk K,
Madhusudhan P, Anjani G, Das B.
Antibacterial activity of isolates from
Piper longum and Taxus baccata.
Pharmaceutical Biol 2001; 39: 236-238
. Das B, Kundu J, Bachar SC,
Uddin MA, Kundu JK. Antitumor and
antibacterial activity of ethyl acetate
extracts of Ludwigia hyssopifolia L. and
its active principle piperine. Pak J Pharm
Sci 2007; 20:128-31.
