Abstract:
Peptic ulcer is a gastrointestinal disorder affecting about four million people globally. Some
currently used anti-ulcer drugs have side effects such as central nervous system disorder and
depression. This necessitated a search for potent anti-ulcer compounds from natural sources.
Curculigo pilosa (CP) and Sphenocentrum jollyanum (SJ) have been identified from Nigerian
ethnomedicine for the treatment of gastric ulcer. However, there has been no scientific evidence
to support their use. This study was designed to investigate the gastroprotective activity of CP
and SJ, isolate and characterise their bioactive compounds.
Methanol extracts of CP rhizomes (FHI 111263) and SJ seeds (FHI 110510) were assessed for
acute toxicity using Lorke’s method. Forty-five Wistar rats (120-150 g, n=5) were pre-treated
with CP and SJ crude extracts (50, 100, and 200 mg/kg b.w.) for seven days before gastric ulcer
induction using indomethacin (40 mg/kg b.w.) orally. Cimetidine (100 mg/kg) was used as
standard. Percentage inhibition of ulcer was determined by the gastric ulcer index.
Histopathological evaluation, total gastric protein and in vivo antioxidant markers such as
superoxide dismutase (SOD) and Glutathione were determined. The extracts were successively
partitioned into n-hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol and aqueous
fractions. Fractions were screened for antacid and urease inhibitory activities using titrimetric
method and urease inhibitory assay with sodium bicarbonate and acetohydroxamic acid as
standards. Compounds were isolated from active fractions of CP and SJ using chromatographic
techniques. Structures of isolated compounds were elucidated using spectroscopic techniques
(MS, 1-D and 2-D NMR). Compounds were screened for urease inhibitory and antacid activities.
Data were analysed using one-way ANOVA and Dunnet multiple comparison test at α0.05.
The LD50 values of both CP and SJ extracts were > 5000 mg/kg b.w. Curculigo pilosa (50
mg/kg) gave the highest ulcer inhibition (85.4%) followed by SJ (200 mg/kg, 72.5%) compared
to cimetidine (97.5%). Histopathological evaluation of the untreated group revealed severe
lesions, necrosis and blood vessel congestion, which were ameliorated in CP and SJ extracts
treated groups. A significant increase in total gastric protein and SOD was observed in CP and SJ
treated rats. The baseline pH value (1.2) was increased by EtOAc fractions of SJ and CP at 50
and 100 mg to 1.61±0.00, 1.53±0.00 and 1.78±0.00, 1.82±0.01, respectively compared with the
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antacid activity of sodium bicarbonate: 1.53±0.00, 1.47±0.00. The n-hexane, n-butanol and
aqueous fractions of SJ gave significant urease inhibitory activity of 25.4±3.02, 28.6±0.41, and
20.2±0.96 respectively while acetohydroxamic acid gave 19.6±0.34 inhibition. Palmatine (1),
and 5 – (hydroxymethyl) furan-2-carbaldehyde (2) were isolated from CP. A new diterpene; 2, 3-
dihydroxypropyl-(E)-octadec-5-enoate, five ecdysteroids and four clerodane diterpenoids were
isolated from SJ. The isolated compounds exhibited urease inhibitory and antacid activities with
polypodine B (an ecdysteroid) having the highest urease inhibitory activity (IC50 7.0±0.56).
The gastroprotective activities of Curculigo pilosa and Sphenocentrum jollyanum were reported.
The isolated ecdysteroids exhibited significant urease inhibitory activity, which could be linked
with the anti-ulcerogenic property of the plants. These compounds could serve as leads in drug
discovery for development of novel anti-ulcer drugs.
