α‑rhamnrtin‑3‑α‑rhamnoside (ARR) is the principal compound extracted from Franch. & Sav. However, its underlying pharmacological properties remain undetermined. Inflammation is a defense mechanism of the body; however, the excessive activation of the inflammatory response can result in physical injury. The present study aimed to investigate the effects of ARR on lipopolysaccharide (LPS)‑induced RAW264.7 macrophages and to determine the underlying molecular mechanism. A Cell Counting Kit‑8 assay was performed to assess cytotoxicity. Nitric oxide (NO) production was measured via a NO colorimetric kit. Levels of prostaglandin E2 (PGE) and proinflammatory cytokines, IL‑1β and IL‑6, were detected using ELISAs. Reverse transcription‑quantitative (RT‑q)PCR analysis was performed to detect the mRNA expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase‑2 (COX‑2), IL‑6 and IL‑1β in LPS‑induced RAW246.7 cells. Western blotting, immunofluorescence and immunohistochemistry analyses were performed to measure the expression levels of NF‑κB and nuclear factor‑erythroid 2‑related factor 2 (Nrf2) signaling pathway‑related proteins to elucidate the molecular mechanisms of the inflammatory response. The results of the cytotoxicity assay revealed that doses of ARR ≤200 g/ml exhibited no significant effect on the viability of RAW264.7 cells. The results of the Griess assay demonstrated that ARR inhibited the production of NO. In addition, the results of the ELISAs and RT‑qPCR analysis discovered that ARR reduced the production of the proinflammatory cytokines, IL‑1β and IL‑6, as well as the proinflammatory mediators, PGE, iNOS and COX‑2, in LPS‑induced RAW264.7 cells. Immunohistochemical analysis demonstrated that ARR inhibited LPS‑induced activation of TNF‑associated factor 6 (TRAF6) and NF‑κB p65 signaling molecules, while reversing the downregulation of the NOD‑like receptor family CARD domain containing 3 (NLRC3) signaling molecule, which was consistent with the results of the western blotting analysis. Immunofluorescence results indicated that ARR reduced the increase of NF‑κB p65 nuclear expression induced by LPS. Furthermore, the results of the western blotting experiments also revealed that ARR upregulated heme oxygenase‑1, NAD(P)H quinone dehydrogenase 1 and Nrf2 pathway molecules. In conclusion, the results of the present study suggested that ARR may exert anti‑inflammatory effects by downregulating NF‑κB and activating Nrf2‑mediated inflammatory responses, suggesting that ARR may be an attractive anti‑inflammatory candidate drug.
Acta Biomater. 2021 Aug;130:223-233
[PMID:
34087444]
Food Chem Toxicol. 2018 Mar;113:211-217
[PMID:
29407474]
J Ethnopharmacol. 2018 May 10;217:89-97
[PMID:
29432855]
Int J Mol Med. 2018 May;41(5):2771-2783
[PMID:
29436586]
Int Immunopharmacol. 2018 Nov;64:264-274
[PMID:
30218953]
Biomed Pharmacother. 2018 Apr;100:583-589
[PMID:
29500959]
Pharm Biol. 2017 Dec;55(1):837-846
[PMID:
28140744]
Arch Physiol Biochem. 2020 Apr 22;:1-17
[PMID:
32319823]
Arch Pharm Res. 2004 Jan;27(1):44-7
[PMID:
14969337]
Sci Rep. 2018 Feb 16;8(1):3176
[PMID:
29453346]
J Cell Mol Med. 2020 Jan;24(2):1541-1552
[PMID:
31793207]
Food Chem. 2021 Mar 15;340:127931
[PMID:
32871358]
Mediators Inflamm. 2020 Aug 7;2020:3164239
[PMID:
32848508]
J Med Food. 2015 Jan;18(1):83-94
[PMID:
25383596]
Int Immunopharmacol. 2018 May;58:117-124
[PMID:
29573719]
J Clin Epidemiol. 2011 Dec;64(12):1451-62
[PMID:
21530172]
Mol Cell Biochem. 2018 Aug;445(1-2):169-178
[PMID:
29368095]
Int J Biol Macromol. 2020 Apr 15;149:1042-1050
[PMID:
32035153]
Toxicol Appl Pharmacol. 2020 Jan 15;387:114846
[PMID:
31790703]
Int Immunopharmacol. 2021 Feb;91:107264
[PMID:
33340782]
Immunity. 2014 Mar 20;40(3):329-41
[PMID:
24560620]
Int Immunopharmacol. 2019 Aug;73:321-332
[PMID:
31129419]
J Ethnopharmacol. 2021 Mar 1;267:113497
[PMID:
33091492]
Food Chem Toxicol. 2019 Sep;131:110583
[PMID:
31220533]
Eur J Pharmacol. 2020 Jun 5;876:173052
[PMID:
32135124]
Hepatobiliary Pancreat Dis Int. 2020 Oct;19(5):455-460
[PMID:
32386989]
J Vet Sci. 2020 Nov;21(6):e91
[PMID:
33263238]
Chem Cent J. 2018 Feb 13;12(1):14
[PMID:
29442202]
Biochem Soc Trans. 2015 Aug;43(4):621-6
[PMID:
26551702]
J Innate Immun. 2015;7(1):25-36
[PMID:
25277106]
Nat Immunol. 2012 Sep;13(9):823-31
[PMID:
22863753]
Inflammopharmacology. 2020 Oct;28(5):1315-1326
[PMID:
32418005]
Mol Med Rep. 2020 Sep;22(3):1985-1993
[PMID:
32705181]
Redox Biol. 2020 May;32:101500
[PMID:
32193146]
Food Chem. 2021 Aug 15;353:129452
[PMID:
33714115]
Nat Commun. 2016 May 23;7:11624
[PMID:
27211851]
Biol Pharm Bull. 2013;36(8):1341-7
[PMID:
23739488]
Exp Ther Med. 2016 Mar;11(3):1116-1122
[PMID:
26998046]
Molecules. 2019 Oct 30;24(21):
[PMID:
31671623]
Molecules. 2020 Apr 12;25(8):
[PMID:
32290603]
J Nat Prod. 2014 Feb 28;77(2):258-63
[PMID:
24397781]
J Physiol Biochem. 2020 Feb;76(1):49-60
[PMID:
31900806]
Nutrients. 2020 Apr 15;12(4):
[PMID:
32326385]
J Ethnopharmacol. 2020 Jun 28;256:112785
[PMID:
32222576]
Inflammation. 2018 Jun;41(3):835-845
[PMID:
29508185]
BMB Rep. 2019 Aug;52(8):508-513
[PMID:
31383251]
Immunopharmacol Immunotoxicol. 2018 Jun;40(3):219-224
[PMID:
29355056]
Methods. 2001 Dec;25(4):402-8
[PMID:
11846609]
Int Immunopharmacol. 2018 Apr;57:62-71
[PMID:
29475097]
J Ethnopharmacol. 2021 Apr 24;270:113793
[PMID:
33421599]
BMC Complement Altern Med. 2018 Feb 01;18(1):46
[PMID:
29391009]
Biomed Pharmacother. 2018 May;101:422-429
[PMID:
29501764]
J Ethnopharmacol. 2020 Aug 10;258:112857
[PMID:
32298752]
Biochem Pharmacol. 2020 Jul;177:113949
[PMID:
32251678]
Exp Ther Med. 2017 Dec;14(6):5809-5816
[PMID:
29285125]
Molecules. 2020 Sep 07;25(18):
[PMID:
32906766]
J Ethnopharmacol. 2017 Feb 23;198:389-398
[PMID:
28119098]
Inflamm Res. 2020 Feb;69(2):233-244
[PMID:
31907559]
Inflammation. 2020 Oct;43(5):1821-1831
[PMID:
32468498]
Biomed Pharmacother. 2021 May;137:111271
[PMID:
33561643]
Int J Mol Sci. 2020 Mar 16;21(6):
[PMID:
32187984]
J Pharm Pharmacol. 2018 Jun;70(6):808-820
[PMID:
29512159]
Inflammopharmacology. 2020 Dec;28(6):1509-1524
[PMID:
32128702]
