PeerJ · 7 authors, 3 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
This study found that Callistemon citrinus leaf extract significantly reduced gastric ulcer severity in obese rats given indomethacin, decreasing ulcer index from 14 mm to 3-5 mm. The extract lowered inflammatory enzymes (MPO, COX-2, 5-LOX) and pro-inflammatory cytokines (TNFα, IL-6, leptin) while increasing adiponectin. These findings suggest C. citrinus may be a promising natural gastroprotective agent for obese individuals at risk of NSAID-induced gastric ulcers.
**Background:** Obesity increases the risk of gastrointestinal diseases, including gastric ulcers. Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin (IND) are commonly used but cause gastric mucosal damage. Callistemon citrinus (Myrtaceae) has known antioxidant, anti-inflammatory, and hepatoprotective properties, but its gastroprotective effects had not been studied. This study evaluated the gastroprotective effect of C. citrinus leaf extract on IND-induced gastric ulcers in obese female Wistar rats.
**Methods:** Nulliparous female Wistar rats (4 months old, 210-230 g) were divided into groups (n=6 each). In stage 1 (15 weeks), Group 1 received standard chow (control), Group 2 received a high fat-sugar diet (HFSD; 40% fat lard, 40% margarine, 20% sucrose per 100 g food, 5.37 kcal/g), and Group 3 received HFSD plus daily oral C. citrinus extract (250 mg/kg). In stage 2, after 15 weeks, additional groups were added: Group 4 (IND only), Group 5 (single dose C. citrinus 250 mg/kg + IND), and Group 6 (omeprazole 30 mg/kg + IND). All groups except control received a single oral dose of IND (30 mg/kg) after 12 h fasting. After 4 h, animals were sacrificed. Stomachs were examined macroscopically and histologically (H&E staining). Ulcer index (mm) was calculated as lesion length × severity factor. Inflammatory enzyme activities (MPO, COX-1, COX-2, 5-LOX) and cytokine levels (TNFα, IL-6, leptin, adiponectin) were measured in stomach homogenates. Oxidative stress markers (AOPP, MDA, HNE) were also assessed. Statistical analysis used one-way ANOVA with Tukey or LSD post-hoc tests (p ≤ 0.05).
**Key Results:** The HFSD group had 22% higher final body weight than control (286 ± 70 g vs 234 ± 30 g, p < 0.05), while HFSD + C. citrinus increased only 7% (251 ± 50 g). HFSD increased visceral fat deposition 2.6-fold (34 ± 1.9 g vs 13 ± 0.6 g) and fat percentage to 28% vs 5% in control. C. citrinus reduced these to 17% fat and 26 ± 0.6 g visceral fat. IND alone produced severe gastric ulcers (ulcer index 14 ± 0.37 mm). HFSD + IND had ulcer index 8 ± 0.40 mm (41% inhibition). Chronic C. citrinus + IND reduced ulcer index to 3 ± 0.34 mm (71% inhibition). Single-dose C. citrinus + IND gave 5 ± 0.37 mm (67% inhibition), similar to omeprazole (5 ± 0.37 mm, 70% inhibition). Histology showed that C. citrinus preserved gastric mucosal architecture and reduced inflammatory cell infiltration. MPO activity was significantly lower in C. citrinus-treated groups vs IND and HFSD+IND groups (p < 0.05). COX-1 activity was maintained near control in HFSD + C. citrinus + IND, while COX-2 activity was significantly reduced. 5-LOX activity was also significantly decreased by C. citrinus. Inflammatory biomarkers: HFSD + IND had highest leptin (904.7 ± 12.8 mg/dl), TNFα (3489.4 ± 28.2 mg/dl), IL-6 (179.5 ± 6.9 mg/dl), and AOPP (6.4 ± 0.1 µmol/L), and lowest adiponectin (13.9 ± 0.9 mg/dl). Chronic C. citrinus significantly reduced leptin (454.6 ± 12.8), TNFα (3058.9 ± 28.2), IL-6 (116.6 ± 6.9), and AOPP (2.2 ± 0.1), while increasing adiponectin (31.0 ± 0.9). MDA and HNE levels were also lower in C. citrinus groups.
**Clinical Implications:** This study demonstrates that C. citrinus leaf extract has significant gastroprotective effects against IND-induced gastric ulcers in obese rats, likely through anti-inflammatory and antioxidant mechanisms. The extract reduced pro-inflammatory cytokines (TNFα, IL-6, leptin), inhibited key inflammatory enzymes (MPO, COX-2, 5-LOX), and preserved COX-1 activity. These effects were comparable to omeprazole, a standard proton pump inhibitor. Given the high prevalence of obesity and NSAID use, C. citrinus could be a promising natural alternative or adjunct for preventing NSAID-induced gastric ulcers. However, human studies are needed to confirm efficacy and safety. The study also highlights that obesity exacerbates NSAID-induced gastric damage, supporting the need for gastroprotective strategies in obese patients requiring NSAIDs.