title: Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced inflammatory bowel disease.
abstract: BACKGROUND
  Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects of Withania somnifera in Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation.
  
  
  METHODS
  The study included (i) preparation of gel formulation from aqueous Withania somnifera root extract (WSRE), (ii) biochemical assays to determine its performance potential, (iii) testing of formulation efficacy in TNBS-induced IBD rat model, and (iv) histo-patholgical studies to assess its healing and muco-regenerative effect in IBD-induced rats. For this purpose, concentration dependant antioxidant activity of the extracts were evaluated using biochemical assays like (a) inhibition of lipid peroxidation, (b) NO scavenging, (c) H2O2 scavenging, and (d) ferric reducing power assay.
  
  
  RESULTS
  The extract, at 500 μg/ml, the highest concentration tested, showed 95.6% inhibition of lipid peroxidation, 14.8% NO scavenging, 81.79% H2O2 scavenging and a reducing capacity of 0.80. The results were comparable with standard antioxidants, ascorbic acid and curcumin. WSRE treatment positively scored on histopathological parameters like necrosis, edema, neutrophil infiltration. The post treatment intestinal features showed restoration at par with the healthy intestine. In view of these results, gel formulation containing an aqueous extract of W. somnifera, prepared for rectal application was tested for its anti-inflammatory activity in TNBS-induced rat models for IBD. Commercially available anti-inflammatory drug Mesalamine was used as the standard in this assay.
  
  
  CONCLUSIONS
  Dose of the rectal gel applied at 1000 mg of WSRE per kg rat weight showed significant muco-restorative efficacy in the IBD-induced rats, validated by histo-pathological studies.
authors.affiliation: Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, Pune 411 023, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pawar
authors.forename: Suhit
authors.initials: S
authors.lastname: Gilda
authors.forename: Siddhesh
authors.initials: S
authors.lastname: Sharma
authors.forename: Suresh
authors.initials: S
authors.lastname: Jagtap
authors.forename: Anant
authors.initials: A
authors.lastname: Paradkar
authors.forename: Kakasaheb
authors.initials: K
authors.lastname: Mahadik
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Ranjekar
authors.forename: Abhay
authors.initials: A
authors.lastname: Harsulkar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005782:Gels; D006861:Hydrogen Peroxide / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009609:Nitrous Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014302:Trinitrobenzenesulfonic Acid; D032341:Withania
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005782:Gels; D010936:Plant Extracts; D014302:Trinitrobenzenesulfonic Acid; D006861:Hydrogen Peroxide; D009609:Nitrous Oxide