Protective effect of Cissus quadrangularis on neutrophil mediated tissue injury induced by aspirin in rats

https://doi.org/10.1016/j.jep.2005.08.076Get rights and content

Abstract

Cissus quadrangularis (family: Vitaceae) is well known for the treatment of gastric disorders in traditional medicine, owing to its rich source of carotenoids, triterpenoids and ascorbic acid, and has received considerable attention regarding its role in human nutrition. In the search of new potential antiulcer agents, the present study evaluated the ethanol extract of Cissus quadrangularis (CQE) against the gastric toxicity induced by aspirin in rats. The optimum protective dose of 500 mg/kg of extract was selected by the pretreatment of gastric ulcers with different doses of CQE (250, 500 and 750 mg/kg) for 7 days which showed ulcer protection by 40, 71.2 and 72.6%, respectively, as compared to ranitidine (RTD) (30 mg/kg) by 71.9% in the aspirin model. In addition, results have shown that administration of aspirin increases lipid peroxidation status, xanthine oxidase (XO), myeloperoxidase and decrease in selenium–glutathione peroxidase activities in the gastric mucosa, resulting in mucosal damage at both cellular and subcellular level. Pretreatment with CQE ameliorated the observed effect significantly in the gastric mucosa of ulcerated rats. These findings suggest that the gastroprotective activity of CQE could be mediated possibly through its antioxidant effect as well as by the attenuation of the oxidative mechanism and neutrophil infiltration.

Introduction

In recent times, many medicinal plants continue to provide valuable therapeutic agents for the treatment of ulcers both in modern medicine and by the traditional system throughout the world. Since chemical compounds are known to have undesirable side-effects, the present study focused on natural products.

Cissus quadrangularis Linn. Wall. Ex. Wight (family: Vitaceae) is an edible plant, commonly known as “bone setter” found in hotter parts of India, Ceylon, East Africa and Malaysia and Thailand. Cissus quadrangularis is used as a common food supplement in southern India. Stem parts of Cissus quadrangularis were collected from Native Care and Cure Center, India and were duly authenticated by Dr. P. Brindha, Pharmacology Department, Captain Srinivasa Murthy Drug Research Institute, Arumbakkam, Chennai 600106. A voucher specimen PP. 502 has been deposited in the department.

The stout fleshy quadrangular stem is traditionally used for the treatment of gastritis, bone fractures, skin infections, constipations, eye diseases, piles, anemia, asthma, irregular menstruation, burns and wounds (Asolkar et al., 1992, Kritikar and Basu, 2000). Cissus quadrangularis has potent fracture healing property, antimicrobial, antiulcer, antioxidative, cholinergic activity and beneficial effect on cardiovascular diseases (Udupa and Prasad, 1964, Subbu, 1970, Anoop and Jagdeesan, 2002, Murthy et al., 2003, Jainu and Devi, 2003). Previously, we have demonstrated that methanolic extract of Cissus quadrangularis possesses antiulcer and cytoprotective property in indomethacin-induced gastric mucosal injury (Jainu and Devi, 2004). Due to its widespread health use and pharmacologic actions, this study will highlight the health promoting and therapeutic effects of Cissus quadrangularis.

The phytochemical analysis of the plant showed the presence of Vitamin C, β-carotene, two asymmetric tetracyclic triterpenoids, β-sitosterol, α-amyrin, α-amyrone and three stillbene derivatives, quadrangularins A, B, C, etc. (Chopra et al., 1956, Attawish et al., 2002).

Some experimental studies have demonstrated that oxygen-generated free radicals derived from infiltrated neutrophils and enhanced lipid peroxidation play important roles in the pathogenesis of acute gastric lesions induced by aspirin (Konturek et al., 1994). Substances that are able to hinder their formation or capture the free oxygen radicals formed are thus potential antiulcerogenic agents.

These facts form the basis for a study of whether the antioxidant mechanisms are involved in CQE mediated protection in aspirin-induced gastric damage. The objective of the study is to investigate the effect of CQE on neutrophil infiltration tissue injury induced by aspirin in order to reveal the mechanism underlying the antiulcer effect of the plant.

Section snippets

Preparation of alcoholic extract

Dried parts of Cissus quadrangularis were coarsely powdered and 1 kg of this powdered plant material was soaked in ethanol for 48 h and extracted by soxhlet extraction. The extract was vacuum dried and was stored at −4 °C until further use. The yield of the extract was 5.2% (w/w) of powdered ethanolic extract. For administration, the extract was dissolved in distilled water and used for the present study.

Animals

Male albino rats’ weighing 150–200 g were purchased from Tamil Nadu University of Veterinary

Results

Rats that received oral doses of 0.5, 1.5, 3.0 and 5.0 g/kg, did not manifest any clinical signs of toxicity. None of the doses tested could produce mortality in rats during the treatment period. In tests on rats, we found that doses of CQE up to 5 g/kg were non-toxic and we were unable to establish its oral LD50 value.

Aspirin administered rats showed multiple gastric mucosal lesions, most often 1–2 mm in size or petechial, bleeding at the moment of the observation. The CQE showed significant

Discussion

The results of this study demonstrate that the CQE possesses antiulcer property as evidenced by its significant inhibition in the formation of gastric lesions induced by aspirin. The acute toxicity tests on rats showed that doses of CQE up to 5 g/kg were non-toxic and the oral LD50 value might be higher than this dose.

Aspirin caused rise in the lipid peroxidation status possibly due to the activation of neutrophils, which play an important role in the damaging activity (Yoshikawa et al., 1992).

Acknowledgement

The authors would like to thank Dr. P. Brindha for his expert comments and suggestions in regard to this work.

References (23)

  • R. DelaPureta et al.

    Effect of minor components of virgin olive oil on topical anti-inflammatory assays

    Zetschrift Fur Naturforschong

    (2000)

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