Anti-inflammatory Effect of L. Fruit Methanolic Extract on Lipopolysaccharide-treated RAW 264.7 Murine Macrophages

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Feb 26

PMID 38404825

Authors

Uyen Thi Tu Phan

Hai Dang Nguyen

Thi Kieu Oanh Nguyen

Tuan Hiep Tran

Thanh Huong Le

Thi Thu Phuong Tran

Affiliations

Soon will be listed here.

Abstract

Context: The species was studied several potential properties such as anti-tumor, anti-inflammatory and antioxidant activity. However, the specific anti-inflammatory activity of the extract from the fruits of L. has not been investigated.

Objectives: Our study want to examine the anti-inflammatory effects of . L. fruit methanolic extracts (PLE) on lipopolysachharide (LPS)-stimulated RAW 264.7 murine macrophages to understand the mechanism of this effect.

Method: This study examined the chemical profiling of PLE by LC-HRMS analysis and measured the presence of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the supernatant using the Griess reagent assay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA expression of IL-6, TNF-α, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the protein expression of COX-2, iNOS and the phosphorylation of MAPK family, c-Jun N-terminal kinase (JNK), p38 in protein level were observed by western blotting.

Result: PLE have detected 66 compounds which belong to different classes such as alkaloids, flavonoids, terpenoids, phenolics, lactones, and organic acids inhibited nitric oxide products with the IC = 28.5 ± 0.91 μg/mL. Moreover, PLE at 10-100 μg/mL up-regulate HO-1 protein expression from 3 to 10 folds at 3 h. It also downregulated the mRNA and protein expression of iNOS, COX-2, decreased IL-6 and TNF-α secretion by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, specifically by decreasing the phosphorylation of p38 and JNK.

Conclusion: These results shown chemical profiling of PLE and demonstrated that PLE exhibits anti-inflammatory effects by regulating the MAPK family and could be a potential candidate for the treatment of inflammatory diseases.

Citing Articles

Traditional Knowledge and Efficacy Analysis of an Emerging Medicinal Food Plant: .

Chen Q, Wang M, Hu X, Zhang J, Zhang Q, Xu C Foods. 2025; 14(1.

PMID: 39796362 PMC: 11719614. DOI: 10.3390/foods14010072.

References

Hatziieremia S, Gray A, Ferro V, Paul A, Plevin R . The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and MAP kinase and NFkappaB signalling pathways in monocytes/macrophages. Br J Pharmacol. 2006; 149(2):188-98. PMC: 2013802. DOI: 10.1038/sj.bjp.0706856. View

Enogieru A, Haylett W, Hiss D, Bardien S, Ekpo O . Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders. Oxid Med Cell Longev. 2018; 2018:6241017. PMC: 6040293. DOI: 10.1155/2018/6241017. View

Motterlini R, Foresti R, Bassi R, Green C . Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med. 2000; 28(8):1303-12. DOI: 10.1016/s0891-5849(00)00294-x. View

Nathan C, Ding A . Nonresolving inflammation. Cell. 2010; 140(6):871-82. DOI: 10.1016/j.cell.2010.02.029. View

Rios J, Recio M, Escandell J, Andujar I . Inhibition of transcription factors by plant-derived compounds and their implications in inflammation and cancer. Curr Pharm Des. 2009; 15(11):1212-37. DOI: 10.2174/138161209787846874. View

Origassa C, Camara N . Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury. World J Hepatol. 2013; 5(10):541-9. PMC: 3812456. DOI: 10.4254/wjh.v5.i10.541. View

Juan S, Cheng T, Lin H, Chu Y, Lee W . Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol. 2004; 69(1):41-8. DOI: 10.1016/j.bcp.2004.09.015. View

Rostom A, Moayyedi P, Hunt R . Canadian consensus guidelines on long-term nonsteroidal anti-inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2008; 29(5):481-96. DOI: 10.1111/j.1365-2036.2008.03905.x. View

Zhang Z, Bao M, Lu N, Weng L, Yuan B, Liu Y . The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA. Nat Immunol. 2012; 14(2):172-8. PMC: 3645272. DOI: 10.1038/ni.2492. View

10.

Qi Z, Qi S, Ling L, Lv J, Feng Z . Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus. Int Immunopharmacol. 2016; 35:265-271. DOI: 10.1016/j.intimp.2016.04.004. View

11.

Tian C, Liu X, Chang Y, Wang R, Yang M, Liu M . Rutin prevents inflammation induced by lipopolysaccharide in RAW 264.7 cells via conquering the TLR4-MyD88-TRAF6-NF-κB signalling pathway. J Pharm Pharmacol. 2021; 73(1):110-117. DOI: 10.1093/jpp/rgaa015. View

12.

Bleasel M, Peterson G . Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2. Pharmaceuticals (Basel). 2020; 13(12). PMC: 7760625. DOI: 10.3390/ph13120428. View

13.

Dosoky N, Satyal P, Barata L, da Silva J, Setzer W . Volatiles of Black Pepper Fruits ( L.). Molecules. 2019; 24(23). PMC: 6930617. DOI: 10.3390/molecules24234244. View

14.

Guo Z, Xu J, Xia J, Wu Z, Lei J, Yu J . Anti-inflammatory and antitumour activity of various extracts and compounds from the fruits of Piper longum L. J Pharm Pharmacol. 2019; 71(7):1162-1171. DOI: 10.1111/jphp.13099. View

15.

Chovatiya R, Medzhitov R . Stress, inflammation, and defense of homeostasis. Mol Cell. 2014; 54(2):281-8. PMC: 4048989. DOI: 10.1016/j.molcel.2014.03.030. View

16.

Byun E, Sung N, Byun E, Song D, Kim J, Park J . The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages. Int Immunopharmacol. 2012; 15(2):450-6. DOI: 10.1016/j.intimp.2012.11.021. View

17.

Hsu H, Chu L, Hua K, Chao L . Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes. J Cell Physiol. 2008; 215(3):603-12. DOI: 10.1002/jcp.21206. View

18.

Wan Q, Xu J, Zhu C, Liu X, Tu Y, Lei J . Alkaloids from Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells. J Agric Food Chem. 2023; 71(27):10349-10360. DOI: 10.1021/acs.jafc.3c01667. View

19.

Shi J, Xia Y, Wang H, Yi Z, Zhang R, Zhang X . Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity. Front Pharmacol. 2022; 12:818326. PMC: 8790537. DOI: 10.3389/fphar.2021.818326. View

20.

Sharma J, Al-Omran A, Parvathy S . Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2008; 15(6):252-9. DOI: 10.1007/s10787-007-0013-x. View