Protective effect of 6-paradol in acetic acid-induced ulcerative colitis in rats.

Abstract

BACKGROUND:

Ulcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory cells, leading to ulceration and haemorrhage through cytotoxic reactive oxygen species. 6-Paradol, a dietary component in several plants belonging to the Zingiberaceae family, has shown anti-inflammatory and antioxidant activities. Current study evaluates the effect of 6-paradol in amelioration of ulcerative colitis in rats for the first time.

METHODS:

6-Paradol (95% purity) was obtained from seeds of Aframomum melegueta. Rats were divided randomly into six groups (n = 8). Group one was administered normal saline; group two was treated with the vehicle only; group three, sulfasalazine 500 mg/kg; and groups four, five, and six, were given 6-paradol (50, 100, 200, respectively) mg/kg orally through gastric gavage for 7 days. Colitis was induced on 4th day by intrarectal administration of 2 ml acetic acid (3%), approximately 3 cm from anal verge. On 8th day, rats were sacrificed, and distal one-third of the colon extending proximally up to 4 cm from anal orifice was taken for biochemical and gross examination. Two centimetres of injured mucosal portion was taken for histopathological investigations. SPSS (ver.26) was used for statistical analysis.

RESULTS:

Colonic and serum glutathione (GSH) levels decreased, while colonic and serum malondialdehyde (MDA), colonic myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6), serum tumour necrosis factor-α (TNF-α) levels, and colon weight to length ratio were increased significantly in the colitis untreated group compared to normal control. Treatment with 6-paradol considerably improved all these parameters, especially at a dose of 200 mg/kg (p < 0.001), revealing non-significant differences with sulfasalazine 500 mg/kg and normal control (p = 0.998). Sulfasalazine and 6-paradol in a dose dependent manner also markedly reversed mucosal oedema, atrophy and inflammation, cryptic damage, haemorrhage, and ulceration. There were non-significant differences between low and medium doses and between medium and high doses of 6-paradol for IL-6 and serum MDA levels.

CONCLUSION:

6-Paradol demonstrated protection against acetic acid-induced ulcerative colitis, probably by anti-inflammatory and antioxidant actions.

• Authors: Misbahuddin Rafeeq, Hussam Aly Sayed Murad, Hossam Mohammed Abdallah, Ali M El-Halawany
• Journal: BMC complementary medicine and therapies (BMC Complement Med Ther) Vol. 21 Issue 1 Pg. 28 (Jan 13 2021) ISSN: 2662-7671 [Electronic] England
• PMID: 33441125 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Ketones
• Guaiacol
• 6-paradol
• Glutathione
• Acetic Acid

Topics

• Acetic Acid (toxicity)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Colitis, Ulcerative (chemically induced, metabolism)
• Colon (drug effects, metabolism)
• Glutathione (metabolism)
• Guaiacol (analogs & derivatives, pharmacology)
• Ketones (pharmacology)
• Male
• Rats
• Rats, Sprague-Dawley
• Seeds (chemistry)
• Zingiberaceae (chemistry)