The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats
Introduction
Centella asiatica (L.) Urb., also known as gotu kola and Indian pennywort, is a perennial herbaceous creeper of the Apiaceae family, which grows to a length of 50 cm with fan shaped leaves. It is a tropical medicinal plant with a long history of therapeutic uses, e.g., dermal disorders, venous insufficiency and microangiopathy Incandela et al., 2001a, Incandela et al., 2001b. Studies have shown that Centella increased collagen synthesis in vitro and extracellular matrix accumulation in vivo Maquart et al., 1990, Maquart et al., 1999. It enhanced tensile strength in wound tissue (Suguna et al., 1996), and facilitated the wound healing process. The latter activity was attributed to the active ingredient, asiaticoside (AC), presented in Centella asiatica (Shukla et al., 1999a). Previously, we have demonstrated that Centella asiatica water extract (CE) inhibited ethanol induced gastric mucosal lesions (Cheng and Koo, 2000). In this study, the effects of CE and AC on acetic acid induced gastric kissing ulcer, which is pathologically similar to chronic gastric ulceration in humans were investigated (Tsukimi and Okabe, 1994).
Gastric ulcer healing is an orchestrated complex process. It involves resolution of inflammation and repair of gastric tissues through granulation tissue formation, re-epithelialization, and extracellular matrix remodeling. The regrowth of blood vessels into the ulcerated area, i.e., angiogenesis, plays a pivotal role in the acceleration of ulcer healing since the neovasculature promotes nutrient supply to the healing tissues. Growth factors such as basic fibroblast growth factor (bFGF) stimulate epithelial cell proliferation and angiogenesis thus are important to the healing of gastric ulcer (Buntrock et al., 1982). On the other hand, suppression of myeloperoxidase (MPO) activity, which is a marker of neutrophil infiltration during inflammation, was found to enhance gastric ulcer healing (Tsukimi et al., 1996). In the present study, the effects of CE and AC on angiogenesis and protein expression of bFGF, epithelial cell proliferation, and MPO activity during the healing of kissing ulcers in rats were examined.
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Animals
The protocol for the use of animals in this study has been approved by the Committee in the Use of Live Animals in Teaching and Research of The University of Hong Kong. Male Sprague-Dawley rats, weighing between 130 g and 170 g, were given a standard laboratory diet (Ralston Purina Co., St. Louis, MO) and tap water ad libitum. The rats were kept inside a room with controlled temperature (22 ± 1°C), relative humidity (65–70%), and a 12 h light-dark cycle.
Preparation of Centella water extract
Centella asiatica dry plant was obtained
HPLC analysis
HPLC analysis of AC standard (Carl Roth, Germany) showed a single peak at 205 nm with a retention time of 35.4 min (Fig. 1A). CE, when fractionated into components by passing through a reverse phase column with water/acetonitrile as the mobile phase, gave a peak with the same wavelength and retention time of the AC standard (Fig. 1B). AC that was purchased from Yick-Vic Chemicals and Pharmaceutical Company also demonstrated a major peak with the same wavelength and retention time as the AC
Discussion
The present study demonstrated that water extract of Centella asiatica and its major component, asiaticoside, accelerated the healing of gastric kissing ulcers. They were found to promote angiogenesis, facilitate epithelial proliferation, and suppress MPO activity during ulcer healing stage. Similar effects were observed after 0.25 g/kg CE or 10 mg/kg AC administration, suggesting that AC may be the most active ingredient in CE that enhanced ulcer healing.
CE and AC were found to stimulate blood
Conclusion
This study suggests that CE and AC contribute to the healing of gastric ulcers with angiogenic, anti-inflammatory, and cell proliferative properties. These results provide a more in depth understanding to the gastric ulcer healing effects of CE and AC, and may stimulate further development of the Centella components into effective anti-ulcer drugs.
Acknowledgements
This study was supported by The Research Grant Council of Hong Kong (project number HKU 7267/98M). The authors would like to thank Professor Guo Ming Gu (Botanist and Pharmacologist of The Institute of Pharmacology and Toxicology, Beijing, China) for authenticating the samples of Centella asiatica and Mr. Hon Cheung Leung for his technical assistance.
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