NEPHROPROTECTIVE ACTIVITY OFORTHOSIPHON STAMINEUS

Synopsis for M. Pharm Dissertation submitted to the

Rajiv Gandhi University of Health Sciences Karnataka, Bengaluru

Submitted By

Mr. PERAM MALLIKARJUNA

1stYear M.Pharm

Under the guidance of

Dr. B. A. SHANMUGA SUNDARAMM. Pharm, Ph.D

HOD, DEPT. OF PHARMACOLOGY

DEPARTMENT OF PHARMACOLOGY

BENGALURU INSTITUTE OF PHARMACY EDUCATION AND RESEARCH

KOGILU MAIN ROAD, YALAHANKA, BENGALURU-64

2011-13

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BENGALURU.

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / PERAM MALLIKARJUNA
M PHARM, PART –I
PRESENT ADDRESS:
ADITYA BENGALURU INSTITUTE OF PHARMACY EDUCATION AND RESEARCH,
BEHIND ANNAPURNESWARI TEMPLE,
YELHANKA, KOGILU ROAD,
BENGALURU-64, KARNATAKA.
2. /

NAME OF THE INSTITUTION

/ ADITYA BANGLORE INSTITUTE OF PHARMACY EDUCATION AND RESEARCH
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACOLOGY.
4. / DATE OF ADMISSION OF COURSE / 23rd July 2011
5. / TITLE OF TOPIC
NEPHROPROTECTIVE ACTIVITY OF ORTHOSIPHON STAMINEUS
6.
6.4.
7.
8. / BRIEFRESUMEOF THE INTENDED WORK
6.1Need for the study :
Herbal remedies are effective in the treatment of various ailments. Very often these drugs are unscientifically exploited and/ or improperly used. Therefore these plant drugs deserve detailed studies in the light of modern medicine science. The detailed investigation and documentation of plants used in local health traditions and pharmacological evaluation of these plants and their taxonomical relatives can lead to the development of invaluable plant drugs for many diseases.
Therefore based on the above facts, as no preclinical screening has been carried out regarding the nephroprotective activity of the Orthosiphon stamineus Benth, the present study has been undertaken to evaluate the nephroprotective activity of the given herbal drug in gentamicin induced nephrotoxicity in rats.
  1. Preliminary phytochemical screening.
  2. Pharmacological study
Acute oral toxicity study
Nephroprotective activity
Biochemical evaluation
Body weight
Serum creatinine
Blood urea
Urinary protein
Glutathione (GSH)
2.2 Histopatholagical studies
3. Invitro antioxidant studies
3.1. DPPH scavenging activity
3.2. Nitric oxide scavenging activity
3.3. Superoxide Dismutase scavenging activity (Alkaline DMSO method)
3.4. Lipid peroxidation
3.5. Reduction of ferric ion by ortho-phenanthroline colour method.
6.2 Review of the literature :
1.Doan et al. (1992) herbal remedies are widely used alongside modern drugs. They assessed the diuretic effect of four tradition Vietnamese herbal remedies, all claimed to produce an increase of diuresis.
2.Nguyen et al., (1992) studied the diterpenes from Orthosiphon stamineus and their nitric oxide inhibitory activity. From the Meoh extract of Orthosiphon stamineus, all the newly isolated diterpenes exhibited close dependent inhibition of nitric oxide production, with an IC 50 value of 35.0 mm comparable to the positive control of L-NMMA; ic (50), 35.7 mm.
3.Mariam and Asmawi, (1996) studied the hypoglycaemic activity of the aqueous extract of Orthosiphon stamineus.
4.Ohashik et al, (2000) demonstrated the antihypertensive activities of Orthosiphon stamineus and showed an inhibitory effect on the contractile responses on rat thoracic aorta smooth muscle stimulated with Kcl before hand.
5.Yam et al., (2007) in an experiment, DPPH radicals scavenging FE (3+) induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus were determined.
6.Nirdney and Muangman (1991) proved that folio orthosiphonis showed favourable and non favourable effect of the stone prevention. Uric acid and uric acid containing stone may be prevented by the increased alkalinity of the urine after drinking Orthosiphon tea we feel that orthosiphon may be beneficial in prevention of uric acid stone formation.
7.Englert and Harnischfeger (1992) an aqueous extract of Orthosiphon folium, given orally, enhance considerably ion excretion in rat to a level comparable to that obtained witn furosemide.
8.Bartanov et al., nephrophyte includes arctostaphylos uva ursi L., Orthosiphon stamineus Benth, Poligonum aviculase L., Desmodium canadense (L.) exerted a nephroprotective effect that was confirmed by decreasing the creatinine and urea conc and by dropping proteinuria, increase of GFR and diuresis compared with controls.
6.3Objectives of the study :
  • Plant materials have shown apparent antinephrotic or nephroprotective activity and may provide the basis for strategies following the adverse effects of heavy metals, antibiotics, analgesics and other prescription drugs, amantina mushroom and aflatoxins and industrial agents.
  • Traditionally herbal drugs are most commonly used for curing various diseases. Protective effect of Orthosiphon stamineus Benth have been noted against the nephrotoxic effects of gentamicin and mercuric chloride. I have found to known traditionally in olden days Orthosiphon stamineus has been used for nephroprotective activity but no scientific researchers had been made on Orthosiphon stamineus. So an attempt was made to evaluate the nephroprotective activity of Orthosiphon stamineus on gentamicin induced nephrotoxicity in rat model for studying nephroprotectivity.
Chemical compounds causes much of side effects when compared to herbal extract so focus of this herbal extract of Orthosiphon stamineus Benth is selected.
MATERIALS AND METHODS:
BOTANICAL INFORMATION
DESCRIPTION OF THE PLANT
Orthosiphon stamineus Benth
Family: Lamiaceae (Labiateae)
Genus: Orthosiphon
Survey of literature on the plant selected for the present work, Orthosiphon stamineus (Benth)
ETHNOBOTANICAL SURVEY
Orthosiphon stamineus. Syn. Orthosiphon aristatus, Orthosiphon spicatus
Java tea, cat’s whiskers
VERNACULAR NAMES
English: Cat’s whiskers
French: The de Java
Tamil: Poonai meesai.
Tongan: Kava I Pusi
DISTRIBUTION AND HABITAT
Naturally it was found along the road sides in stream bottoms and wet places often a cultivated plant in villages and gardens at elevations upto 200 m and sometimes along roadsides available throughout india.
Height: 1-2’
Habit: Herb
Soil: Moist garden soil.
BOTANICAL CHARACTERS
Slender perennial herb to 2 m high, the branchlets 4 – angled, sparsely pubescent to glabrescent, sometimes purplish. Leaves petiolate, the petioles 1-2(4.5) cm long, pubescent, the blades lanceolate to ovate or rhombic, 2-9 X 1-5 cm, chartaceous to membraneous, cuneate at base, acute to acuminate at apex, coarsely serrate at margin, glabrous to pubuscent on both surfaces, racemes 10-15 cm long, the verticals lax, distant, the bracts sessile, ovate, 1-2 mm long ciliolate, the pedicels 4 mm long; calyx curved-campanulate, the tube 3 m long at anthesis, conerved, scabridulous on nerves, the upper lip ovate to 3 X 2.5 mm, the lower lip longer, the median lobes acuminate-aristate: the tube 10-15 mm long straight, strigose-tomentose without, the upper lip shallowly 4-lobed, recurved, the lower lip as long as upperlip, concave, stamens glabrous, coiled in bud, the anther purple; style 5-6 cm long, glabrous clavate and briefly 2-lobes at apex, white distally; nutlets ovoid – oblong to 2 mm long, glabrous, rugose .
  1. EXPERIMENTAL ANIMALS
Healthy adult male/female wistar rats (150-200 gms) age 60-90 days were used for the study. The animals were housed in well ventilated room temperature and humidity controlled environments with natural day night cycle in polypropylene cages. They were fed up with standard food pellets diet from central animal house, RMMC, Annamalai University, Chidambaram – 602 002 and water ad libitum throughout the experimental period.
The animals were housed for one week prior to the experiments to acclimatize the laboratory conditions. The animals were randomly distributed into 5 different groups with 6 animals in each groups. The experimental protocol was approved by the institutional animal ethics committee (IAEC).
7.1 Source Of Data :
  1. Library: Aditya BIPER , Bengaluru.
b. e-library: Aditya BIPER, Bengaluru.
c. Practices data’s based on laboratory studies.
7.2 Method of collection of data:
  • Data on drug and excipients are collected from the drug information centre, patents, reference books, text books, catalogs etc.
  • Data will be collected from the prepared formulations, in-vitro dissolution studies and stability studies. In- vitro dissolution studies will be used as criteria for assessing the enhancement of oral bioavailability of poorly aqueous soluble drug.
7.3 Does the study require any investigations or interventions to be Conducted on patients or other humans or animals? If so, please Describe in brief.
Yes, the entire experimental models require usage of laboratory animals.
7.4 Has ethical clearance been obtained from your institute in case 7.3?
Applied for IAEC approval. The same will be submitted once get the approval.
List of references:
  1. A.I.Bartanov, E.A.Bartonovo. Nephroprotective effect of nephrophyte in drug nephropathy induced by urographin. Euromedica hannoeve (2005): 40-41.
  2. Akowuah, A.G, Zhari, I., Norhayati, I, Sadikuma. Radical Scavenging activity of methanolic extracts of Orthosiphon stamineus. Pharm. Biology (2005) 42(8): 629-635.
  3. Bartel, S.H., Bohmer, M. Serum creatinine determination withoutr protein precipitation. Clin chem.. Acta 1972. 37: 193-196.
  4. Beauchamp, D., Gourde, P., Theriauh, G., Bergaron, M.G. Age dependent gentamicin experimental nephrotoxicity. J.Pharmacol. Exp. Thes. 1992; 260(2): 444-449.
  5. Beaux, D., Fleureantin, J. Mortier, F., Effects of Orthosiphon stamineus Benth. Hieracium pilosella L., Sambucusnigr L. and Actostaphylos uvaursi (L) spreng in rats Phytoter Res. 1999. 13(3):222-225.
  6. Casadebaig – laton J. Jacob, Metal. Adsorbed plant extracts, use of extracts of dried seeds of Orthosiphon stamineus benth. Pharm Acta helvetiae (1989) 64(8): 220-224.
  7. Chencplinccnamba, TR. Screening of Taiwanese crude drugs for antibacterial activity against streptococcus mutans. J.Ethnopharmacol (1989) 27(3):285-295.
  8. Devasagayam, TPA, tilak, J.C, Bollorkk. Review; Free racidals and antioxidants in human health; curr stat fut prosp JAPI 2004, 52: 794-804.
  9. Doan, D.D, Nguyen, N.H, Doan, H.K. Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies. J.Ethnopharmacol. 1992; 36(3): 225-231.
  10. Englert, J., Harnischfeger, G., Diuretic action of Orthosiphon stamineus extract in rats. Planta Med (1992 June) 58(3): 237-238.
  11. Farruch, A, Iqbal ahmadzafar mehmood. Antioxidant and free radical scavenging properties of twelve traditionally used Indian medicinal plants. Turk.J.Biol. 30 (2006): 177-183.
  12. Galyutova, G.I., N.A.Benson. Comparative evaluation of the diuretic activity of leaves and leaf tissue culture biomass of Orthosiphon stamineus Benth. Restitelnye resursy (1990) 26(4):559-565.
  13. Golamreza karimi, Mohammed ramezani. Cisplastin nephrotoxicity and protection by milk thistle extracts in rats. Ecam advance access. 2005. july 26. 1-4.

9. / NAME AND SIGNATURE OF THE CANDIDTE
10. / REMARKS OF THE GUIDE / RECOMMENDED AND FORWARDED
11.1 / NAME OF THE GUIDE / Dr. Shanmuga Sundaram
11.2 / SIGNATURE OF GUIDE
11.3 / CO-GUIDE / NOT APPLICABLE
11.4 / HEAD OF THE DEPARTMENT / Dr. Shanmuga Sundaram
11.5 / SIGNATURE OF HOD
12.1 / REMARKS OF THE PRINCIPAL / RECOMMENDED AND FORWARDED
12.2 / PRINCIPAL / Dr. B. A. VISHWANATH M. Pharm, Ph.D.,
PRINCIPAL
ABIPER, BENGALURU-64
12.3 / SIGNATURE OF PRINCIPAL