Printer Friendly

Antinociceptive, anti-inflammatory and acute toxicity effects of Zhumeria majdae extracts in mice and rats.

Summary

Antinociceptive and anti-inflammatory effects and acute toxicity of aqueous infusion and ethanolic maceration extracts of the aerial parts of Zhumeria majdae were studied in mice and rats. Antinociceptive activity was determined using hot-plate and writhing tests. The effect of the extracts against acute inflammation was studied by acetic acid increased vascular permeability and xylene-induced ear edema in mice. The activity of the extracts against chronic inflammation was assessed using the cotton pellet test in rats. [LD.sub.50] values of the infusion and maceration extracts were 3.09 g/kg body wt., and 3.94 g/kg body wt., respectively. Phytochemical screening of the extracts indicated the presence of flavonoids and tannins. In the hot-plate test, the intraperitoneal injection of both extracts showed significant and dose-dependent antinociceptive activity in mice. Naloxone, an opioid antagonist, on pretreatment inhibited the antinociceptive activity of the extracts. The extracts exhibited antinociceptive ac tivity against acetic acid-induced writhing, which was partially blocked by naloxone. Both extracts showed significant effect against acute inflammation induced by acetic acid in mice. In the chronic inflammation test, efficacy of the extracts was similar to that of baclofen and dexamethasone in rats. It is concluded that the aqueous infusion and ethanolic maceration extract of the aerial parts of Zhumeria majdae have antinociceptive effects and this may be mediated by opioid receptors. The extracts also showed anti-inflammatory effects against acute and chronic inflammation.

Key words: Zhumeria majdae, antinociceptive activity, anti-inflammatory activity, medicinal plants.

Introduction

Species of the Labiatae are generally known for their multiple pharmacological effects, such as analgesic and anti-inflammatory activity (Hernandez-Perez et al., 1995; Hosseinzadeh and Yavari, 1999; Hosseinzadeh et al., 2000), effect on morphine dependence (Hosseinzadeh and Lari, 2000), antioxidant (Cuppett and Hall, 1998), hepatoprotective (Wasser et al., 1998), antihypoxic (Hosseinzadeh and Imenshahidi, 1999) and hypoglycemic action (Hosseinzadeh et al., 1998). Zhumeria majdae (Labiatae), vernacular name Mehrkhosh, grows in southeastern Iran. It has a strong and pleasant smell. Due to the reported use of this plant in folk medicine for stomachache and dysmenorrhea (Zargari, 1995) and the lack of any report on its antinociceptive and anti-inflammatory activities, this study was initiated.

Materials and methods

Animals

Male and female albino mice (25-30 g each) and Wistar rats weighing 150-210 g each were obtained from a randomly bred colony maintained on special diet (Khorassan Javane Go, Mashhad, I. R. Iran) in the animal house of Mashhad University of Medical Sciences. Animals were housed in a colony room under a 12/12 h light/dark cycle at 21 [+ or -] 2 [degrees]C and had free access to water and food.

Plant material

The plant was collected 120 km north of Bandarabas, fran, dried in shadow, and ground. Zhumeria majdae was identified by Ferdowsi University and voucher samples were preserved for reference in the herbarium of the Department of Pharmacognosy, School of Pharmacy, Mashhad (Voucher no. 153-2613-3).

Preparation of extracts

The plant powder was extracted using aqueous infusion and maceration with ethanol. For the infusion, 11 hot water was added to 100 g plant material, boiled for 15 min, and filtered through cloth. The extract was then concentrated in vacuo to the desired volume. For maceration, the plant powder (200 g) was macerated in 500 ml ethanol (85%, v/v) for 3 days and the mixture was subsequently filtered and concentrated in vacuo at 50 [degrees]C. The ethanolic extract was emulsified using Tween-80.

Phytochemical screening

Phytochemical screening of the extract was performed using the following reagents and chemicals (Trease and Evans, 1983): alkaloids with Dragendorff's reagent, flavonoids with the use of Mg and HCl; tannins with 1% gelatin and 10% NaCl solutions and saponins with ability to produce suds and hemolysis reaction.

Charactrization of extracts by HPLC

The separation was carried out on a millipore column (5 [micro]m, 15 x 3.9 mm) using gradient elution. Gradient was performed using water-phosphoric acid (0.1 N, 99:1) and acetonitrile-phosphoric acid (0.1 N, 99:1) at a total flow rate of 0.1 ml/min; gradient composition (min, % acetonitrile-phosphoric acid): 0.0,5; 5.0,7.5; 10,10; 15,12.5; 20,15; 25,17.5; 30,20; 35,22.5; 40,25. The extracts were dissolved in methanol and filtered through a membrane filter (0.45 [micro]m). 10-[micro]l samples of 10 g/l of aqueous and ethanolic extracts were injected into a reversed-phase column (RPC-18). The peaks were monitored at 254 nm.

Acute toxicity

Different doses of extracts were injected intraperitoneally into groups of six mice. The number of deaths was counted at 48 h after treatment. [LD.sub.50] values and corresponding confidence limits were determined by the Litchfield and Wilcoxon method (PHARM/PCS Version 4).

Antinociceptive study

* Hot-plate test: The hot-plate test was assessed using mice. The temperature of the metal surface was maintained at 55 [+ or -] 0.2 [degrees]C. Latency to a discomfort reaction (licking paws or jumping) was determined before and after drug administration. The cut-off time was 40 s.

* Writhing test: One hour after the administration of the extract, the mice were given an intraperitoneal injection of 0.7% v/v acetic acid solution (volume of injection 0.1 ml/10 g body wt.). The number of writhes produced in these animals was counted for 30 min.

Anti-inflammatory study

* Xylene-induced ear edema: Mice were divided into groups of seven. Thirty minutes after i.p. injection of the extract, diclofenac and dexamethasone, 0.03 ml of xylene was applied to the anterior and posterior surfaces of the right ear. The left ear was considered as control. Two hours after xylene application, mice were sacrificed and both ears removed. Circular sections were excised, using a cork borer with a diameter of 7 mm, and weighed. The increase in weight caused by the irritant was measured by subtracting the weight of the untreated left ear section from that of the treated right ear section.

* Vascular permeability increased by acetic acid in mice: Mice were divided into groups of seven. Thirty minutes after i.m. injection of the extract and diclofenac, mice received i.v. injection of 0.5% Evan's blue solution (5 ml/kg body wt.). Five min later, each mouse was given an i.p. injection of 0.7% acetic acid solution (10 ml/kg body wt.). Thirty minutes after i.p. administration of acetic acid, mice were sacrificed. The concentration of Evan's blue in the fluid of the peritoneal cavity was measured by the absorbance at 610 nm.

* Cotton pellet granuloma in rats: Pellets of dentistry cotton weighing 30 mg each were sterilized in an air oven at 121 [degrees]C for 20 min and impregnated with 0.4 ml of an aqueous solution of ampicillin. Under ketamine (65 mg/kg body wt.) and xylazine (6.5 mg/kg body wt.) anesthesia, two cotton pellets were implanted subcutaneously in the groin region of rats, one on each side. The extract and diclofenac were given once daily for 7 days. On Day 8, the rats were killed and the pellets and surrounding granulation tissue were dried at 60 [degrees]C for 24 h. The weight of granuloma was determined.

* Statistical analysis: The data were expressed as mean values [+ or -] S.E.M. and tested using analysis of variance followed by the multiple comparison test of Tukey-Kramer.

Results

[LD.sub.50] values of the infusion and maceration extracts were 3.09 g/kg body wt. (95% CL: 2.57, 3.72) and 3.94 g/kg body wt. (95% CL: 3.16, 4.90), and the maximum non-fatal doses were 2 g/kg body wt. and 2.8 g/kg body wt., respectively.

Phytochemical screening of the extracts indicated the presence of flavonoids and tannins and the absence of alkaloids and saponins. HPLC fingerprints of aqueous and ethanolic extracts indicated a similar pattern with minor differences (Figures 1 and 2).

In the hot plate test, administration of the aqueous and ethanolic extracts showed antinociceptive activity that was dose-dependent with a duration of action of 420 mm. The time latency of the antinociceptive effect of high doses of both extracts was more than that of morphine (Figures 3 and 5).

Naloxone (2 mg/kg body wt., i.v.) pretreatment after i.p. injection of the extracts and morphine (10 mg/kg body wt.), inhibited the antinociceptive activity of both extracts and morphine (Figures 4 and 6).

The aqueous and ethanolic extracts of Zhumeria majdae significantly reduce the number of mouse abdominal constrictions induced by a 0.7% acetic acid solution. While doubling the dose of infusion extract showed an increase in the percentage of the protection about 3 to 4 percent, the ethanolic extract at the same doses increased the percentage of protection about 20 percent, reaching 84 and 80%, respectively. Morphine and diclofenac induced protection of 92% and 80%, respectively. There was no significant difference between diclofenac (10 mg/kg body wt.) and the extracts in reduction of writhing numbers. Naloxone (2 mg/kg body wt., i.v.) pretreatment after i.p. injection of the extracts partially inhibited the antinociceptive activity of both extracts (Tables 1 and 2).

In the xylene-induced ear edema study, only the ethanolic extract showed anti-inflammatory activity which at lower doses had efficacy similar to diclofenac and dexamethasone (Tables 3 and 4). The aqueous extract showed higher activity against acute inflammation induced by acetic acid than did the ethanolic extract (Tables 5 and 6).

In the chronic inflammation (cotton-plate) test, the extracts exhibited significant and dose-dependent anti-inflammatory activity. Except for the dose of 0.8 g/kg body wt. of the aqueous extract, there were no significant differences between efficacy of the extracts and the control drugs, diclofenac and dexamethasone (Tables 7 and 8).

Discussion

The present results indicate that aqueous and ethanolic extracts of aerial parts of Zhumeria majdae have marked central and peripheral antinociceptive activity. The extracts also showed activity against acute and chronic inflammation.

With respect to LD50 values, the aqueous extract was more toxic than the maceration extract. According to a toxicity classification (Loomis, 1968), these extracts are relatively toxic.

As preliminary phytochemical results indicated, the antinociceptive and anti-inflammatory effects of the extracts may be due to their content of flavonoids and/or tannins. Other studies have demonstrated that various flavonoids such as rutin, quercetin, luteolin, hesperidin, as well as biflavonoids produce significant antinociceptive and/or anti-inflammatory activities (Bittar et al., 2000; Calixto et al., 2000; Galati et al., 1994; Ramesh et al., 1998). There are few reports on the role of tannins in antinociceptive and anti-inflammatory activities (Starec et al., 1988).

HPLC fingerprints of both extracts did not indicate a major difference supporting similar activities observed for both extracts. The aqueous and ethanolic extracts showed antinociceptive activity in the hot plate test and this effect was inhibited by naloxone. The hot plate test is a specific central antinociceptive test Parkhouse and Pleuvry, 1979). Therefore, it is possible that the extracts exerted their effects through central opioid receptors or promoted release of endogenous opiopeptides.

Antinociceptive activity of opioid agonist, opioid partial agonist, on non-steroidal anti-inflammatory agents can be determined using the writhing test (Vogel and Vogel, 1997). As the antinociceptive activity of the extracts were partially inhibited by naloxone, the extract likely acts on spinal opioid receptors such as [[mu].sub.2] [[kappa].sub.1] and [[delta].sub.2] receptors (Reisine and Pasternack, 1996), although other mechanisms of action, such as inhibition of cyclo-oxygenase, are also possible.

The antinociceptive activity of the infusion extract reached a maximum at lower doses than that of the ethanolic extract in the writhing test. This may indicate that active constituents were present in higher concentrations in the infusion extract and that high temperature had no observable effect on activity of the extract.

The infusion and ethanolic extract had significant anti-inflammatory effects in acute inflammatory tests with different efficacy in these tests. This plant may have a membrane-stabilizing effect that reduces capillary permeability and/or has inhibitory effects on the release of mediators.

The extract effectively and significantly reduced cotton pellet-induced granuloma, thereby suggesting its activity in the proliferative phase of the inflammation. As Z. majdae contains essential oils (Rustaiyan et al., 1992); the oil may have a role in anti-inflammatory activity.

It is concluded that the aqueous and ethanolic extracts of aerial parts of Zhumeria majdae have central and peripheral antinociceptive effects. Opioid receptors and the inhibition of cyclo-oxygenase enzyme may mediate these activities. The extracts also have activity against acute and especially chronic inflammation. The antinociceptive and anti-inflammatory effects of the extracts may be due to their content of flavonoids and/or tannins. However, the chemical constituents responsible for the pharmacologoical activities remain to be investigated.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

[FIGURE 5 OMITTED]

[FIGURE 6 OMITTED]
Table 1

Effect of subcutaneous injection of naloxone on the antinociceptive
effect of intraperitoneal treatment with the aqueous extract of Zhumeria
majdae on the acetic acid-induced writhing test in mice. Values are the
mean [+ or -] S.E.M. for 10 mice, *** P < 0.001, compared to control
(Tukey-Kramer test).

Treatment Dose Ear swelling Inhibition
 (per kg (mg) (%)
 body wt.)

Control 10 ml/kg 10.2 [+ or -] 0.9 -
Diclofenac 15 mg/kg 6.5 [+ or -] 0.3 * 36.27
Dexamethasone 15 mg/kg 3.4 [+ or -] 0.5 *** 66.67
Extract 0.2 g/kg 8.2 [+ or -] 0.5 19.61
Extract 0.8 g/kg 7.5 [+ or -] 0.1 26.47
Extract 1.4 g/kg 7.7 [+ or -] 0.7 24.51
Table 2

Effect of subcutaneous injection of naloxone on the antinociceptive
effect of intraperitoneal treatment with the ethanolic extract of
Zhumeria majdae on the acetic acid-induced writhing test in mice. Values
are the mean [+ or -] S.E.M. for 10 mice, *** P < 0.001, compared to
control (Tukey-Kramer test).

Treatment Dose Ear swelling Inhibi-
 (per kg (mg) tion
 body wt.) (%)

Control 10 ml/kg 10.2 [+ or -] 0.3 --
Diclofenac 15 mg/kr 6.7 [+ or -] 0.4 *** 34.42
Dexamethasone 15 mg/kg 6.5 [+ or -] 0.4 *** 36.27
Extract 0.2 g/kg 6.5 [+ or -] 0.5 *** 36.27
Extract 0.8 g/kg 7.4 [+ or -] 0.3 *** 27.45
Extract 1.4 g/kg 7.8 [+ or -] 0.5 ** 23.53
Table 3

Effect of intraperitoneal doses of the aqueous extract of Zhumeria
majdae on xylene-induced ear swelling in mice. Values are the mean [+ or
-] S.E.M. for 7 mice. * P < 0.05, *** P < 0.001, compared to control
(Tukey-Kramer).

Treatment Dose Evans blue Inhibi-
 (per kg ([micro]g/ml) tion
 body wt.) (%)

Control 10 ml/kg 4.9 [+ or -] 0.5 --
Diclofenac 15 mg/kg 1.8 [+ or -] 0.1 *** 63.27
Dexamethasone 15 mg/kg 2.1 [+ or -] 0.2 *** 57.14
Extract 0.8 g/kg 2.6 [+ or -] 0.3 *** 46.94
Extract 1.4 g/kg 3.5 [+ or -] 0.2 * 28.57
Extract 2.0 g/kg 3.8 [+ or -] 0.3 22.45
Table 4

Effect of intraperitoneal doses of the ethanolic extract of Zhumeria
majdae on xylene-induced ear swelling in mice. Values are the mean [+ or
-] S.E.M. for 7 mice, * P < 0.05, *** P < 0.001, compared to control
(Tukey-Kramer).

Treatment Dose Evans blue Inhibi-
 (per kg ([micro]g\ml) tion
 body wt.) (%)

Control 10 ml/kg 5.3 [+ or -] 0.4 --
Diclofenac 15 mg/kg 2.4 [+ or -] 0.4 *** 54.72
Dexamethasone 15 mg/kg 2.5 [+ or -] 0.3 *** 52.83
Extract 0.8 g/kg 3.4 [+ or -] 0.4 * 35.85
Extract 1.4 g/kg 4.4 [+ or -] 0.4 16.98
Extract 2.0 g/kg 4.5 [+ or -] 0.5 15.09
Table 5

Effect of intramuscular doses of the aqueous extract of Zhumeria majdae
on vascular permeability increase induced by intraperitoneal 0.7% acetic
acid in mice. Values are the mean [+ or -] S.E.M. for 7 mice, * P <
0.05, *** P < 0.001, compared to control (Tukey-Kramer).

Treatment Dose Cotton pellet Inhibi-
 (per kg (mg) tion
 body wt.) (%)

Control 10 ml/kg 102.3 [+ or -] 3.7 --
Diclofenac 15 mg/kg 31.3 [+ or -] 4.5 *** 69.40
Dexamethasone 15 mg/kg 35.3 [+ or -] 2.8 *** 65.49
Extract 0.8 g/kg 44.0 [+ or -] 5.5 *** 57.0
Extract 1.4 g/kg 34.5 [+ or -] 3.1 *** 66.28
Extract 2.0 g/kg 33.8 [+ or -] 2.5 *** 66.96
Table 6

Effect of intramuscular doses of the ethanolic extract of Zhumeria
majdae on vascular permeability increase induced by intraperitoneal 0.7%
acetic acid in mice. Values are the mean [+ or -] S.E.M. for 7 mice, * P
< 0.05, *** P < 0.001, compared to control (Tukey-Kramer).

Treatment Dose Cotton pellet Inhibi-
 (per kg (mg) tion
 body wt.) (%)

Control 10 ml/kg 101.4 [+ or -] 4.9 --
Diclofenac 15 mg/kg 31.3 [+ or -] 4.5 *** 69.13
Dexamethasone 15 mg/kg 35.3 [+ or -] 2.8 *** 62.19
Extract 0.2 g/kg 52.3 [+ or -] 4.1 *** 48.42
Extract 0.8 g/kg 34.2 [+ or -] 3.9 *** 66.27
Extract 1.4 g/kg 39.4 [+ or -] 2.5 *** 61.14
Table 7

Effect of intraperitoneal doses of the aqueous extract of Zhumeria
majdae (consecutive for 7 days) on the weight of granuloma in rats.
Values are the mean [+ or -] S.E.M. for 7 mice, *** P < 0.001, compared
to control (Tukey-Kramer).

Treatment (dose) Number of Inhibition
(per kg body wt.) Writhing (%)

Control (10 ml/kg) 71 [+ or -] 1.7 --
Naloxone, NLX (2 mg/kg) 82.0 *** [+ or -] 2.5 +13
Morphine (10 mg/kg) 5.8 *** [+ or -] 0.8 92
Morphine (10 mg/kg) 69.7 [+ or -] 2.19 2
 + NLX (2 mg/kg)
Diclofenace (10 mg/kg) 13.9 *** [+ or -] 1.6 80
Extract (0.05 g/kg) 15.2 *** [+ or -] 1.5 79
Extract (0.05 g/kg) 37.0 *** [+ or -] 1.9 48
 + NLX (2 mg/kg)
Extract (0.1 g/kg) 12.7 *** [+ or -] 1.5 82
Extract (0.1 g/kg) 39.0 *** [+ or -] 2.2 45
 + NLX (2 mg/kg)
Extract (0.2 g/kg) 10.3 *** [+ or -] 1.4 86
Extract (0.2 g/kg) 37.5 *** [+ or -] 1.7 47
 + NLX (2 mg/kg)
Table 8

Effect of intraperitoneal doses of the ethanolic extract of Zhumeria
majdae (consecutive for 7 days) on the weight of granuloma in rats.
Values are the mean [+ or -] S.E.M. for 7 mice, *** P < 0.001, compared
to control, n = 7 (Tukey-Kramer).

Treatment (dose) Number of Inhibition
(per kg body wt.) Writhing (%)

Control (10 ml/kg) 65.9 [+ or -] 1.7 -
Naloxone, NLX (2 mg/kg) 80.4 *** [+ or -] 3.1 +12
Morphine (10 mg/kg) 5.5 *** [+ or -] 1.1 92
Morphine (10 mg/kg) 62.5 [+ or -] 1.7 5
 + NLX (2 mg/kg)
Diclofenac (10 mg/kg) 14.3 *** [+ or -] 1.7 78
Extract (0.05 g/kg) 34.4 *** [+ or -] 2.2 48
Extract (0.05 g/kg) 49.0 *** [+ or -] 2.1 26
 + NLX (2 mg/kg)
Extract (0.1 g/kg) 22.6 *** [+ or -] 1.7 66
Extract (0.1 g/kg) 44.3 *** [+ or -] 2.4 33
 + NLX (2 mg/kg)
Extract (0.2 g/kg) 10.4 *** [+ or -] 1.0 84
Extract (0.2 g/kg) 32.8 *** [+ or -] 1.5 50
 + NLX (2 mg/kg)


Acknowledgment

The authors are thankful to Mr. Najafi and Mr. Soltani for plant sanples and also to the deputy of the Research Institute of Natural Resources in Hormozagan province, Iran.

References

Bittar, M, de Souza, M.M., Yunes, R.A., Lento, R., Delle Monache, F., Cechinel Filbo, V:. Antinociceptive activity of 13,II8-binaringenin, a biflavonoid present in plants of the Guttiferne. Planta Med. 66: 84-86, 2000.

Calixto, J.B., Beirith, A., Ferreira, J., Santos, A.R.; Cechinel Filho, V.; Yunes, R.A.: Naturally occurring antinociceptive substances from plants. Phytother. Res. 14: 401-418, 2000.

Cuppett, S.L., Hall, C.A.: Antioxidant activity of the Labiatae. Adv. Food. Nutr. Res. 42: 245-271, 1998.

Galati, E.M.; Monforte, M.T.; Kirjavainen, S.; Forestieri, A.M.; Trovato, A.; Tripodo, M.M. Biological effects of hesperidin, a citrus flavonoid. (Note I): antiinflammatory and analgesic activity. Farmaco. 40: 709-712, 1994.

Hernandez-Perez, M., Rabanal, R. M., de la Torre, M.C., Rodriguez, B.: Analgesic, anti-inflammatory, antipyretic and haematological effect of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives. Planta Med. 61: 505-509, 1995.

Hosseinzadeh, H., Haddad Khodaparast, M.H., Shokohizadeh, H.: Antihyperglycemic effect of Salvia leriifolia Benth. leaf and seed extract in mice. Irn. J. Med. Sci. 23: 74-80, 1998.

Hosseinzadeh, H., Imanshahidi, M.: Effect of leaf and seed of Salvia leriifolia Benth. on survival time in hypoxic mice. Irn. J. Basic Med. Sci. 2: 75-81, 1999.

Hosseinzadeh, H., Lari, P.: Effect of Salvia leriifolia extract on morphine dependence in mice. Phytother. Res. 14: 384-387, 2000.

Hosseinzadeh, H., Ramezani, M., Salmani, G-A. Antinociceptive, anti-inflammatory and acute toxicity effects of Zataria muliflora Boiss extracts in mice and rats. J. Ethnopharmacol. 73: 379-385, 2000.

Hosseinzadeh, H., Yavari, M.: Anti-inflammatory effects of Salvia leriifolia Benth. leaf extract in mice and rats. Pharmac. Pharmacol. Lett. 9: 60-61, 1999.

Loomis, T. A.: "Essential of Toxicology". Lea and Febiger, Philladelphia. pp. 67-78, 1968.

Parkhouse, J., Pleuvry, B. J.: "Analgesic Drug". Black Well, Oxford. pp. 1-5, 1979.

Ramesh, M.; Rao, Y.N.; Rao, A.V.; Prabbakar, M.C.; Rao, C.S. Muralidhar N; Reddy BM Antinociceptive and anti-inflammatory activity of a flavonoid isolated from Caralluma attenuata. J. Ethnopharmacol. 62: 63-66, 1998.

Reisine, T., Pastemack, G.: "Opioid analgesics and antagonists", in: Goodman and Gilman's, the Pharmacological Basis of Therapeutics". Eds.: J.G.Hardman, L.E. Limbird. McGrraw-Hill, New York. 9th ed. pp. 521-526, 1996.

Rustaiyan, A.; Sigari, H.; Bamoniri, A.; Weyerstahl, P.: Constituents of the essential oil of Zhumeria majdae Rech. Flavour Fragrance J. 7: 273-274, 1992.

Starec, M.; Waitzova, D.; Elis, J.: Evaluation of the analgesic effect of RG-tannin using the "hot plate" and "tail flick" method in mice. Cesk. Farm. 37: 319-321, 1988.

Trease, G.E., Evans, W.C. "Pharmacognosy". Bailliere Tindall Press, London. pp. 309-706, 1983.

Vogel, H.G., Vogel, W.H.: "Drug Discovery and Evaluation, Pharmacological Assays". Springer, Berlin, pp. 402-403: 1997.

Wasser, S., Ho, J.M., Ang, H.K., Tan, C.E.: Salvia miltiorrhiza reduce experimentally-induced hepatic fibrosis in rats. J. Hepatol. 29: 760-77 1, 1998.

Zargari, A.: "Medicinal Plants". Tehran University Press, Tehran. Vol. 4, p. 136, 1995.

Address

H. Hosseinzadeh, Department of Pharmacodynamy and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, POBox 91775-1365, Mashhad. I.R.Iran

Fax: ++98-511-8437075

e-mail: hosseinzadehh@yahoo.com
COPYRIGHT 2002 Urban & Fischer Verlag
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Hosseinzadeh, Hossein; Ramezani, Mohammad; Fadishei, Masoumeh; Mahmoudi, Masoud
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Date:Mar 1, 2002
Words:3781
Previous Article:Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata in mice *.
Next Article:Antiplasmodial activity of Aspidosperma indole alkaloids.


Related Articles
Studies on the antinociceptive, anti-inflammatory and antipyretic effects of Isatis indigotica root.
Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata in mice *.
Central nervous system activity of Leucas inflata Benth. in mice.
Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva Allemao.
Acute and chronic antiinflammatory profile of the ivy plant, Hedera helix, in rats.
Antinociceptive effect of Nidularium procerum: a Bromeliaceae from the Brazilian coastal rain forest.
Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf...
Effects of Leontice smirnowii tuber monodesmosides and crude extract in carrageenan- and histamine-induced acute inflammation model of rats.
Antinociceptive activity of the volatile oils of Hyptis pectinata L. Poit. (Lamiaceae) genotypes.
Anti-inflammatory and analgesic effects and molecular mechanisms of JCICM-6, a purified extract derived from an anti-arthritic Chinese herbal formula.

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters