Anti‑inflammatory action of ambuic acid, a natural product isolated from the solid culture of Pestalotiopsis neglecta, through blocking ERK/JNK mitogen‑activated protein kinase signaling pathway

Zhang,Qian; Luan,Ruiling; Li,Huixiang; Liu,Yanan; Liu,Pan; Wang,Liying; Li,Danna; Wang,Mengdi; Zou,Qiang; Liu,Hongwei; Matsuzaki,Keiichi; Zhao,Feng

doi:10.3892/etm.2018.6294

Anti‑inflammatory action of ambuic acid, a natural product isolated from the solid culture of Pestalotiopsis neglecta, through blocking ERK/JNK mitogen‑activated protein kinase signaling pathway

Authors:
- Qian Zhang
- Ruiling Luan
- Huixiang Li
- Yanan Liu
- Pan Liu
- Liying Wang
- Danna Li
- Mengdi Wang
- Qiang Zou
- Hongwei Liu
- Keiichi Matsuzaki
- Feng Zhao
View Affiliations

Affiliations: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, P.R. China, Pharmacy Dispensing Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Yantai Branch of Shandong Technology Transfer Center, Chinese Academy of Sciences, Yantai, Shandong 264003, P.R. China, State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China, School of Pharmacy, Nihon University, Funabashi, Chiba 274‑8555, Japan
Published online on: June 12, 2018 https://doi.org/10.3892/etm.2018.6294
Pages: 1538-1546

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ambuic acid is an organic acid isolated from the solid culture of Pestalotiopsis neglecta, which is an endophytic fungus that widely exists in many species of plants. Ambuic acid has been reported to exert antimicrobial activity against Gram‑positive bacterium. The aim of the present study was to investigate the inhibitory effect of ambuic acid on lipopolysaccharide (LPS)‑induced inflammation in RAW264.7 macrophages. The results demonstrated that ambuic acid significantly suppressed the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) in a dose‑dependent manner. Furthermore, ambuic acid also inhibited the release of the proinflammatory cytokine interleukin‑6 (IL‑6) however, no inhibition of the release of tumor necrosis factor‑α (TNF‑α) was observed. Further investigations indicated that ambuic acid downregulated the LPS‑induced high expression of inducible NO synthase (iNOS) and cyclooxygenase‑2 (COX‑2) proteins, as well as inhibited the enzymatic activity of iNOS and COX‑2. In addition, ambuic acid suppressed the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK 1/2) and c‑Jun N‑terminal kinase (JNK) induced by LPS. However, ambuic acid did not inhibit the phosphorylation of p38 mitogen‑activated protein kinase (MAPK), the degradation of IκB‑α protein or the nuclear translocation of nuclear transcription factor‑κB (NF‑κB) p65 subunit. These results suggested that ambuic acid may exert anti‑inflammatory action by blocking the activation of the ERK/JNK MAPK signaling pathway, without the involvement of the p38 MAPK or NF‑κB signaling pathways.

View Figures

View References

1	Liu Y, Yang MH, Wang XB, Li TX and Kong LY: Caryophyllene sesquiterpenoids from the endophytic fungus, Pestalotiopsis sp. Fitoterapia. 109:119–124. 2016. View Article : Google Scholar : PubMed/NCBI
2	Deyrup ST, Swenson DC, Gloer JB and Wicklow DT: Caryophyllene sesquiterpenoids from a fungicolous isolate of Pestalotiopsis disseminata. J Nat Prod. 69:608–611. 2006. View Article : Google Scholar : PubMed/NCBI
3	Hwang IH, Swenson DC, Gloer JB and Wicklow DT: Disseminins and spiciferone analogues: Polyketide-derived metabolites from a fungicolous isolate of Pestalotiopsis disseminate. J Nat Prod. 79:523–530. 2016. View Article : Google Scholar : PubMed/NCBI
4	Yang XL, Awakawa T, Wakimoto T and Abe I: Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acaciae. Tetrahedron Lett. 54:5814–5817. 2013. View Article : Google Scholar
5	Klaiklay S, Rukachaisirikul V, Tadpetch K, Sukpondma Y, Phongpaichit S, Buatong J and Sakayaroj J: Chlorinated chromone and diphenyl ether derivatives from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69. Tetrahedron. 68:2299–2305. 2012. View Article : Google Scholar
6	Li J, Li L, Si Y, Jiang X, Guo L and Che Y: Virgatolides A-C, benzannulated spiroketals from the plant endophytic funfus Pestalotiopsis virgatula. Org Lett. 13:2670–2673. 2011. View Article : Google Scholar : PubMed/NCBI
7	Xu J, Kjer J, Sendker J, Wray V, Guan H, Edrada R, Lin W, Wu J and Proksch P: Chromones from the endophytic fungus Pestalotiopsis sp. isolated from the chinese mangrove plant Rhizophora mucronata. J Nat Prod. 72:662–665. 2009. View Article : Google Scholar : PubMed/NCBI
8	Harper JK, Arif AM, Ford EJ, Strobel GA, Porco JA Jr, Tomer DP, Oneill KL, Heider WM and Grant DM: Pestacin: A 1,3-dihydro isobenzofuran from Pestaliopsis microspora possessing antioxidant and antimycotic activities. Tetrahedron. 59:2471–2474. 2003. View Article : Google Scholar
9	Akone SH, Amrani ME, Lin W, Lai D and Proksch P: Cytosporins F-K, new epoxyquinols from the endophytic fungus Pestalotiopsis theae. Tetrahedron Lett. 54:6751–6754. 2013. View Article : Google Scholar
10	Xu J, Aly AH, Wray V and Proksch P: Polyketide derivatives of endophytic fungus Pestalotiopsis sp. isolated from the Chinese mangrove plant Rhizophora mucronata. Tetrahedron Lett. 52:21–25. 2010. View Article : Google Scholar
11	Strobel G, Yang X, Sears J, Kramer R, Sidhu RS and Hess WM: Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology. 142:435–440. 1996. View Article : Google Scholar : PubMed/NCBI
12	Kumaran RS, Kim HJ and Hur BK: Taxol-producing [corrected] fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata. J Biosci Bioeng. 110:541–546. 2010. View Article : Google Scholar : PubMed/NCBI
13	Tan RX and Zou WX: Endophytes: A rich source of functional metabolites. Nat Prod Rep. 18:448–459. 2001. View Article : Google Scholar : PubMed/NCBI
14	Ding G, Liu S, Guo L, Zhou Y and Che Y: Antifungal metabolites from the plant endophytic fungus Pestalotiopsis foedan. J Nat Prod. 71:615–618. 2008. View Article : Google Scholar : PubMed/NCBI
15	Wei MY, Li D, Shao CL, Deng DS and Wang CY: (±)-Pestalachloride D, an antibacterial racemate of chlorinated benzophenone derivative from a soft coral-derived fungus Pestalotiopsis sp. Mar Drugs. 11:1050–1060. 2013. View Article : Google Scholar : PubMed/NCBI
16	Xu D, Zhang BY and Yang XL: Antifungal monoterpene derivatives from the plant endophytic fungus Pestalotiopsis foedan. Chem Biodivers. 13:1422–1425. 2016. View Article : Google Scholar : PubMed/NCBI
17	Jia YL, Wei MY, Chen HY, Guan FF, Wang CY and Shao CL: (+)- and (−)-pestaloxazine A, a pair of antiviral enantiomeric alkaloid dimers with a symmetric spiro[oxazinane-piperazinedione] skeleton from Pestalotiopsis sp. Org Lett. 17:4216–4219. 2015. View Article : Google Scholar : PubMed/NCBI
18	Chen L, Zhang QY, Jia M, Ming QL, Yue W, Rahman K, Qin LP and Han T: Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds. Crit Rev Microbiol. 42:454–473. 2016.PubMed/NCBI
19	Kiho T, Itahashi S, Sakushima M, Matsunaga T, Usui S, Ukai S, Mori H, Sakamoto H and Ishiguro Y: Polysaccharides in fungi. XXXVIII. Anti-diabetic activity and structural feature of a galactomannan elaborated by Pestalotiopsis species. Biol Pharm Bull. 20:118–121. 1997. View Article : Google Scholar : PubMed/NCBI
20	Kumar DS, Lau CS, Wan JM, Yang D and Hyde KD: Immunomodulatory compounds from Pestalotiopsis leucothës, an endophytic fungus from Tripterygium wilfordii. Life Sci. 78:147–156. 2005. View Article : Google Scholar : PubMed/NCBI
21	Verma VC, Gangwar M, Yashpal M and Nath G: Anticestodal activity of endophytic Pestalotiopsis sp. on protoscoleces of hydatid cyst Echinococcus granulosus. Biomed Res Int. 2013:3085152013. View Article : Google Scholar : PubMed/NCBI
22	Tejesvi MV, Kini KR, Prakash HS, Subbiah V and Shetty HS: Antioxidant, antihypertensive, and antibacterial properties of endophytic Pestalotiopsis species from medicinal plants. Can J Microbiol. 54:769–780. 2008. View Article : Google Scholar : PubMed/NCBI
23	Xia X, Kim S, Liu C and Shim SH: Secondary metabolites produced by an endophytic fungus Pestalotiopsis sydowiana and their 20S proteasome inhibitory activities. Molecules. 21:pii: E944. 2016. View Article : Google Scholar
24	Li JY, Harper JK, Grant DM, Tombe BO, Bashyal B, Hess WM and Strobel GA: Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp. Phytochemistry. 56:463–468. 2001. View Article : Google Scholar : PubMed/NCBI
25	Harper JK, Barich DH, Hu JZ, Strobel GA and Grant DM: Stereochemical analysis by solid-state NMR: Structural predictions in ambuic acid. J Org Chem. 68:4609–4614. 2003. View Article : Google Scholar : PubMed/NCBI
26	Ding G, Li Y, Fu S, Liu S, Wei J and Che Y: Ambuic acid and torreyanin acid derivatives from the endolichenic fungus Pestalotiopsis sp. J Nat Prod. 72:182–186. 2009. View Article : Google Scholar : PubMed/NCBI
27	Nakayama J, Uemura Y, Nishiguchi K, Yoshimura N, Igarashi Y and Sonomoto K: Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria. Antimicrob Agents Chemother. 53:580–586. 2009. View Article : Google Scholar : PubMed/NCBI
28	Qi QY, Li EW, Han JJ, Pei YF, Ma K, Bao L, Huang Y, Zhao F and Liu HW: New ambuic acid derivatives from the solid culture of Pestalotiopsis neglecta and their nitric oxide inhibitory activity. Sci Rep. 5:99582015. View Article : Google Scholar : PubMed/NCBI
29	Ali AM, Habeeb RA, El-Azizi NO, Khattab DA, Abo-Shady RA and Elkabarity RH: Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients. Rev Bras Reumatol. 54:446–451. 2014.(In Portuguese). View Article : Google Scholar : PubMed/NCBI
30	Coulter JA, McCarthy HO, Xiang J, Roedl W, Wagner E, Robson T and Hirst DG: Nitric oxide-a novel therapeutic for cancer. Nitric Oxide. 19:192–198. 2008. View Article : Google Scholar : PubMed/NCBI
31	Husain K, Hernandez W, Ansari RA and Ferder L: Inflammation, oxidative stress and rennin angiotensin system in atherosclerosis. World J Biol Chem. 6:209–217. 2015. View Article : Google Scholar : PubMed/NCBI
32	Beyazit Y, Efe C, Tanoglu A, Purnak T, Sayilir A, Taskıran I, Kekilli M, Turhan T, Ozaslan E and Wahlin S: Nitric oxide is a potential mediator of hepatic inflammation and fibrogenesis in autoimmune hepatitis. Scand J Gastroenterol. 50:204–210. 2015. View Article : Google Scholar : PubMed/NCBI
33	Muscará MN and Wallace JL: Nitric Oxide. V. therapeutic potential of nitric oxide donors and inhibitors. Am J Physiol. 276:G1313–G1316. 1999.PubMed/NCBI
34	Denizot F and Lang R: Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 89:271–277. 1986. View Article : Google Scholar : PubMed/NCBI
35	Zhao F, Chen L, Zhang M, Bi C, Li L, Zhang Q, Shi C, Li M, Zhou S and Kong L: Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by indole alkaloid, 3-(hydroxy-methyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one, via NF-κB inactivation in RAW 264.7 macrophages. Planta Med. 79:782–787. 2013. View Article : Google Scholar : PubMed/NCBI
36	Wohlmuth H, Deseo MA, Brushett DJ, Thompson DR, Macfarlane G, Stevenson LM and Leach DN: Diarylheptanoid from Pleuranthodium racemigerum with in vitro prostaglandin E(2) inhibitory and cytotoxic activity. J Nat Prod. 73:743–746. 2010. View Article : Google Scholar : PubMed/NCBI
37	Zhao F, Xu H, He EQ, Jiang YT and Liu K: Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-alpha release in LPS-activated macrophages. J Asian Nat Prod Res. 10:1045–1053. 2008. View Article : Google Scholar : PubMed/NCBI
38	Zhao F, Wang L and Liu K: In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway. J Ethnopharmacol. 122:457–462. 2009. View Article : Google Scholar : PubMed/NCBI
39	Murshid A, Gong J, Prince T, Borges TJ and Calderwood SK: Scavenger receptor SREC-I mediated entry of TLR4 into Lipid microdomains and triggered inflammatory cytokine release in RAW 264.7 Cells upon LPS activation. PLoS One. 10:e01225292015. View Article : Google Scholar : PubMed/NCBI
40	Liu Y, Shepherd EG and Nelin LD: MAPK phosphatases-regulating the immune response. Nat Rev Immunol. 7:202–212. 2007. View Article : Google Scholar : PubMed/NCBI
41	Arthur JS and Ley SC: Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 13:679–692. 2013. View Article : Google Scholar : PubMed/NCBI
42	Rao KM: MAP kinase activation in macrophages. J Leukoc Biol. 69:3–10. 2001.PubMed/NCBI
43	Kaminska B: MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta. 1754:253–262. 2005. View Article : Google Scholar : PubMed/NCBI
44	Baeuerle PA and Baltimore D: I kappa B: A specific inhibitor of the NF-kappa B transcription factor. Science. 242:540–546. 1988. View Article : Google Scholar : PubMed/NCBI
45	Beg AA and Baldwin AS Jr: The I kappa B proteins: Multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 7:2064–2070. 1993. View Article : Google Scholar : PubMed/NCBI