Zanthoxylum alatum Roxb. seed extract ameliorates stress aggravated DSS-induced ulcerative colitis in mice: Plausible role on NF-κB signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum alatum (ZA) Roxb (family: Rutaceae) plant has been traditionally used for multiple indications by local healers among different communities of South Asian countries mainly in India and Bangladesh. The extracts of ZA have reported strong anti-inflammatory and anti-oxidant activities, but no scientific report is available on its efficacy in intestinal inflammatory disorders like ulcerative colitis. AIM OF THE STUDY: The overall objective of our study was to evaluate the anti-inflammatory potency of hydro-ethanolic extract of Zanthoxylum alatum seed (ZAHA) using both in-vitro NF-κB-luciferase translocation assay and in-vivo stress aggravated dextran sodium sulfate (DSS)-induced ulcerative colitis model. MATERIALS AND METHODS: The in-vitro anti-inflammatory effect of ZAHA extract was evaluated by luciferase assay in HEK293 cells. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in stress aggravated DSS-induced colitis model in C57BL/6 mice. Biochemical, histological and immunoblot analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. Characterization of the extract was done by LC-MS/MS study. RESULTS: Initial in vitro NF-κB-luciferase translocation assay showed that the hydroalcoholic extract of ZA (ZAHA) showed potent inhibitory activity for NF-κB translocation by TNF-α stimulation and hence this particular extract was further evaluated in stress aggravated DSS-induced ulcerative colitis model in C57BL/6 mice. Treatment of ZAHA for two weeks at a dose of 200 mg/kg significantly ameliorated the stress aggravated DSS-induced colitis in mice. Histological alterations, infiltration of inflammatory cells, and the levels of IL-1ß, IL-6, TNF-α in colon tissue and serum samples were significantly decreased in ZAHA treatment groups compared to the stress aggravated DSS induced colitis animals. Moreover, the protein expressions of p-NF-κB, p-IκBα, p-STAT3, COX-2, and TNF-α were significantly reduced in colon tissues of ZAHA treated groups and also increased anti-oxidant markers like SOD-1, Nrf2 significantly when compared with disease control group. Characterization of the extract further by LC-MS/MS revealed the presence of several active compounds which could be responsible for its anti-inflammatory activity. CONCLUSIONS: Thus from the above findings it can be concluded that ZAHA ameliorates stress aggravated DSS-induced ulcerative colitis due to its anti-inflammatory and anti-oxidant activity.

Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach.

Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP's bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.