PMID- 36816283 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230224 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 2 DP - 2023 Feb TI - Supplementation of syringic acid-rich Phrynium pubinerve leaves imparts protection against allergic inflammatory responses by downregulating iNOS, COX-2, and NF-kappaB expressions. PG - e13343 LID - 10.1016/j.heliyon.2023.e13343 [doi] LID - e13343 AB - BACKGROUND: The present study was designed to characterize the role of ethanolic leaf extract of Phrynium pubinerve Blume (EPP) supplement in attenuating allergic inflammation, encouraged by the presence of syringic acid in it, as this phenolic acid is reportedly promising in suppressing serum immunoglobulin E (IgE) and inflammatory cytokine levels. MATERIALS AND METHODS: HPLC-DAD dereplication analysis was performed to determine the presence of the vital polyphenolic metabolites. The efficacy of EPP against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells was evaluated by measuring its inhibitory effects on NO and ROS/RNS production. The expressions of major inflammation-associated molecules (iNOS, COX-2, NF-kappaB, IL-6, and TNF-alpha) in RAW 264.7 cells were assessed through Western blot. Physiological and behavioral changes, BMI, and different biochemical parameters in mice blood serum were investigated in the toxicological assays. Formaldehyde-induced paw edema test in mice was conducted using established animal model. TDI-induced allergic model in mice was carried out to determine different allergy-like symptoms, and differential white blood cell (WBC) counts in blood and bronchoalveolar lavage (BAL) fluid. The intermolecular interaction analysis of the identified major metabolite of EPP with H1R and iNOS was studied by molecular docking. RESULTS: HPLC-DAD analysis showed the presence of syringic acid (89.19 mg/100 g EPP) and a few other compounds. LPS-induced NO generation was reduced by EPP in a concentration-dependent manner, showing IC(50) of 28.20 +/- 0.27 mug/mL. EPP exhibited a similar inhibitory effect on ROS/RNS production with IC(50) of 29.47 +/- 2.19 mug/mL. Western blotting revealed that EPP significantly downregulated the expressions of iNOS, COX-2, NF-kappaB, IL-6, and TNF-alpha in RAW 264.7 cells when challenged with LPS. The toxicological assays confirmed the dosage and organ-specific safety of EPP. In the formaldehyde-induced paw edema test, EPP caused a 66.41% reduction in mice paw volume at 500 mg/kg dose. It ameliorated TDI-induced allergy-like symptoms and decreased different inflammatory WBCs in mice's blood and BAL fluid in a dose-dependent manner. Finally, syringic acid demonstrated mentionable intermolecular binding affinity towards H1R (-6.6 Kcal/moL) and iNOS (-6.7 Kcal/moL). CONCLUSIONS: Collectively, considerable scientific reasoning was obtained in favor of the suppressive potential of EPP against allergic inflammatory responses that are proposed to be exerted via the downregulation of iNOS, COX-2, and NF-kappaB expressions, H1R antagonism and suppression of cytokines, such as IL-6, and TNF-alpha. CI - (c) 2023 The Authors. FAU - Islam, Md Arman AU - Islam MA AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. FAU - Huq Atanu, Md Samiul AU - Huq Atanu MS AD - Department of Pharmacy, Gono Bishwabidyalay, Savar, Dhaka 1344, Bangladesh. FAU - Siraj, Md Afjalus AU - Siraj MA AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. AD - Department of Pharmacy, Gono Bishwabidyalay, Savar, Dhaka 1344, Bangladesh. FAU - Acharyya, Rabindra Nath AU - Acharyya RN AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. FAU - Ahmed, Khondoker Shahin AU - Ahmed KS AD - Chemical Research Division, BCSIR Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka 1205, Bangladesh. FAU - Dev, Shrabanti AU - Dev S AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. FAU - Uddin, Shaikh Jamal AU - Uddin SJ AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. FAU - Das, Asish Kumar AU - Das AK AD - Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh. LA - eng PT - Journal Article DEP - 20230202 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC9932742 OTO - NOTNLM OT - Allergic inflammation OT - COX-2 OT - IL-6 OT - NF-kappaB OT - Phrynium pubinerve OT - Syringic acid OT - TNF- alpha OT - iNOS COIS- The authors have declared that they have no competing financial interest or personal relationship that could appear to influence the work outlined in this article. EDAT- 2023/02/24 06:00 MHDA- 2023/02/24 06:01 PMCR- 2023/02/02 CRDT- 2023/02/23 09:19 PHST- 2022/06/18 00:00 [received] PHST- 2022/12/24 00:00 [revised] PHST- 2023/01/25 00:00 [accepted] PHST- 2023/02/23 09:19 [entrez] PHST- 2023/02/24 06:00 [pubmed] PHST- 2023/02/24 06:01 [medline] PHST- 2023/02/02 00:00 [pmc-release] AID - S2405-8440(23)00550-9 [pii] AID - e13343 [pii] AID - 10.1016/j.heliyon.2023.e13343 [doi] PST - epublish SO - Heliyon. 2023 Feb 2;9(2):e13343. doi: 10.1016/j.heliyon.2023.e13343. eCollection 2023 Feb.