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Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.
Biochim Biophys Acta. 2015 Apr; 1850(4):769-83.BB

Abstract

BACKGROUND

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically.

METHODS

Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration.

RESULTS

IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND.

CONCLUSIONS

The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses.

GENERAL SIGNIFICANCE

For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent.

Authors+Show Affiliations

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India. Electronic address: parames@jcbose.ac.in.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25603542

Citation

Sinha, Krishnendu, et al. "Morin Protects Gastric Mucosa From Nonsteroidal Anti-inflammatory Drug, Indomethacin Induced Inflammatory Damage and Apoptosis By Modulating NF-κB Pathway." Biochimica Et Biophysica Acta, vol. 1850, no. 4, 2015, pp. 769-83.
Sinha K, Sadhukhan P, Saha S, et al. Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway. Biochim Biophys Acta. 2015;1850(4):769-83.
Sinha, K., Sadhukhan, P., Saha, S., Pal, P. B., & Sil, P. C. (2015). Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway. Biochimica Et Biophysica Acta, 1850(4), 769-83. https://doi.org/10.1016/j.bbagen.2015.01.008
Sinha K, et al. Morin Protects Gastric Mucosa From Nonsteroidal Anti-inflammatory Drug, Indomethacin Induced Inflammatory Damage and Apoptosis By Modulating NF-κB Pathway. Biochim Biophys Acta. 2015;1850(4):769-83. PubMed PMID: 25603542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway. AU - Sinha,Krishnendu, AU - Sadhukhan,Pritam, AU - Saha,Sukanya, AU - Pal,Pabitra Bikash, AU - Sil,Parames C, Y1 - 2015/01/17/ PY - 2014/07/08/received PY - 2014/12/24/revised PY - 2015/01/12/accepted PY - 2015/1/21/entrez PY - 2015/1/21/pubmed PY - 2015/8/22/medline KW - Anti-inflammatory compound KW - Antioxidant KW - Gastropathy KW - Inflammation KW - Morin KW - NSAID SP - 769 EP - 83 JF - Biochimica et biophysica acta JO - Biochim Biophys Acta VL - 1850 IS - 4 N2 - BACKGROUND: Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. METHODS: Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. RESULTS: IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. CONCLUSIONS: The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. GENERAL SIGNIFICANCE: For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/25603542/Morin_protects_gastric_mucosa_from_nonsteroidal_anti_inflammatory_drug_indomethacin_induced_inflammatory_damage_and_apoptosis_by_modulating_NF_κB_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(15)00028-8 DB - PRIME DP - Unbound Medicine ER -