Anti-inflammatory effects of Passiflora foetida L. in LPS-stimulated RAW264.7 macrophages

  • Authors:
    • Ji-Won Park
    • Ok-Kyoung Kwon
    • Hyung Won Ryu
    • Jin-Hyub Paik
    • Imam Paryanto
    • Prasetyawan Yuniato
    • Sangho Choi
    • Sei-Ryang Oh
    • Kyung-Seop Ahn
  • View Affiliations

  • Published online on: March 12, 2018
  • Pages: 3709-3716
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Passiflora foetida L. (Passifloraceae), a perennial climber in general, is used for treating many ailments in conventional medicine. In this study, the anti-inflammatory effect of methanolic extracts of P. foetida L. (PFME) and the involvement of nuclear factor-κB (NF-κB) signalling in the regulation of inflammation were investigated. PFME prevented the production of prostaglandin E2 (PGE2) and the expression of inducible cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophage cells. Additionally, PFME reduced the release of pro-inflammatory cytokines. Moreover, in LPS-induced RAW264.7 cells, the phosphorylation of MAPKs (ERK1/2, p38 and JNK) was suppressed by PFME. Furthermore, PFME inhibited the NF-κB activation induced by LPS, which was associated with nuclear p65 levels with the abrogation of IκBα degradation and subsequent decreases. These results indicated that the PFME inhibited the LPS-induced inflammatory and oxidative responses. Therefore, we propose that the PFME may be therapeutic for treating inflammatory diseases.


Inflammation is a crucial physiological response of the immune system to infection, and this complex biological symptom is frequently caused by the assault of pathogens during destructive injury of human tissues (1-4). Inflammation is an acute phase that is the initial response, which involves the increased motion of plasma and inflammatory cells from the bronchial tubes to the tissue. Inflammation is described in the pathogenesis of several diseases, including metabolic disease, infection, pulmonary disease and neoplasm (5-7). Then, the lipopolysaccharides (LPS) of gram-negative bacteria activate macrophages, as indicated by the production of tumour necrosis factor-α (TNF-α), interleukins (ILs) and leukotrienes (8,9).

MAPKs and nuclear factor-κB (NF-κB) signalling pathways are major adjusters in the expression of inflammatory mediators involving cyclooxygenase-2 (COX-2) (10,11). The dimeric form of NF-κB is taken into the cytoplasm by the physical combination in unstimulated cells with an inhibitory protein, IκBα (7,12-14). With degradation of IκBα, NF-κB is translocated to the nucleus, and specific NF-κB inhibitors check COX-2 expression (15). Activation of MAPKs leads to the production of inflammatory mediators such as COX-2 in activated macrophage cells (16). In this study, as part of a continuing search to establish the anti-inflammatory mechanism of methanolic extracts of P. foetida L. (PFME), we demonstrated that PFME is a strong inhibitor of COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Moreover, the anti-inflammatory mechanism by which PFME blocks LPS-induced inflammation via NF-κB and MAPKs signalling pathways is novel.

Passiflora foetida L. (Passifloraceae) is better known as 'Wild maracuja', 'Bush Passion fruit' or 'Buah tikus' in Indonesia. The 'foetid' stinking passionflower is a species of passionflower with a stinky smell that is indigenous to tropical America in Mexico, the Southwestern United States (Arizona, Southern Texas) the Caribbean and much of South America. During the Age of Exploration, the species was introduced to Europe, India and Southeast Asia for cultivation and gardening, which was followed by naturalization in other tropical countries (17,18). The plant is a climbing herb with tendrils, and the flowers are white to pale cream and ~5-6 cm in diameter with 2-4-fold pinnatifid bracts at the base. Leaves are ovate to obovate, with 3 shallow lobes, 6-9 cm in length, with a heart-shaped base and frequently a winding and ciliate and pointed tip. Black seeds are embedded in the pulp. The woody and wiry stems are sheer, covered by yellow tacky hairs, and the 2-3 cm diameter fruit is yellowish-orange to red (when ripe). The plant is generally scattered, growing in wayside thickets and riverbeds and dried-up forest floors and is similarly found close to human settlements (18). Extracts from the leaves and fruit of P. foetida (PF) have been used to treat biliousness and asthma (19), and leaf and root extracts are used to treat hysteria, and in the case of headache, a paste of the leaf is rubbed on the head. The herb is used in lotions or poultices for skin diseases with erysipelas and inflammation in Brazil (20). Present study has focused on the pain reliever, anti-diarrhoeal and cytotoxic activities of PF (17), in addition to the antiulcer effects, antioxidant activity (21), analgesic activities, biological and pharmacological activities (17,22,23) and anti-inflammatory effects (22,23). However, the anti-inflammatory activity of PFME and the underlying mechanisms have not been closely examined. In the present study, we investigate the anti-inflammatory effects of PFME and the fundamental mechanisms in RAW264.7 macrophage cells.

Materials and methods

Preparation of Passiflora foetida L. (PF) extract

Plants were collected from the 'Pirangrung, Ujung Kulon National Park' West Java of Indonesia in 2008. The Center for Pharmaceutical and Medical Technology (PTFM, BPPT, Jawa Timur, Indonesia) collected and identified the plants, with the identifications verified by Herbarium Bogoriense (LIPI, Jakarta, Indonesia). Voucher specimens are deposited in the herbarium of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) and in the PTFM and Herbarium Bogoriense. Passiflora foetida was treated with methanol and sonicated repeatedly for 3 days at room temperature to produce the extract.

Cell culture and reagents

Murine macrophage RAW264.7 cells were purchased from the American Tissue Culture Collection (ATCC, Manassas, VA, USA). The RAW264.7 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 1% (v/v) penicillin (100 U/ml)/streptomycin (100 μg/ml) and 10% fetal bovine serum (FBS). The RAW264.7 cells were cultured three times a week, and the RAW264.7 cells were used for experimentation at 70-80% confluence. After pre-incubation of the cells for 4 h, 5, 10, 20 and 30 μg/ml of the extract was added. The cell lines were incubated under a humidified condition of 5% CO2 at 37°C. Escherichia coli LPS and the Griess reagent were purchased from Sigma (St. Louis, MO, USA). DMEM (Welgene, Gyeongsan-si, Korea), FBS (HyClone, Logan, UT, USA), and the 1% (v/v) penicillin (100 U/ml)/streptomycin (100 μg/ml) (Invitrogen, Grand Island, NY, USA) were also purchased. In another set of cultures, the cells were co-incubated with the p42/44 inhibitor, PD98059 (10 μM), the p38 inhibitor, SB203580 (10 μM), the c-Jun N-terminal kinase (JNK) inhibitor, SP600125 (10 μM), and the IκBα inhibitor (BAY11-7082) (all from Merck Millipore, Darmstadt, Germany).

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay

Briefly, the RAW264.7 cells were seeded in a 96-well plate (1×105 cells/ml) and treated with 5, 10, 20 and 30 μg/ml PFME for 24 h. The cell proliferation was analysed by MTT (Amnesco, Solon, OH, USA), using the analysis expressed previously (24). To calculate actual observance, the background levels of PFME when incubated only with MTT solution were subtracted. The optical density (OD) was measured using a multimode microplate reader (Tecan Trading AG, Mannedorf, Switzerland) at 570 nm.

Prostaglandin E2 (PGE2) assay

In the supernatant, the PGE2 concentration was verified using a commonly available PGE2 enzyme-linked immunosorbent assay (ELISA) kit (Cayman Chemical Co., Ann Arbor, MI, USA), according to the manufacturer's protocols as described previously (25).


The levels of pro-inflammatory cytokines were determined with commercial ELISA kits. IL-6, IL-1β and TNF-α were purchased from R&D Systems (Minneapolis, MN, USA). The assay procedure for each item was conducted according to manufacturer's instructions. The concentrations of mediators were determined at 450 nm using a multimode microplate reader (Tecan Trading AG).

Reverse transcription-polymerase chain reaction (RT-PCR)

RT-PCR was performed to detect the mRNA expression of COX-2 and β-actin. Briefly, after LPS (0.5 μg/ml) stimulation of the RAW264.7 cells for 6 h, the total RNA was isolated using TRIzol™ reagent (Invitrogen) as recommended by the producer, and a reverse transcription reaction was accomplished using an AMPIGENE® cDNA synthesis kit (Enzo Life Sciences, Farmingdale, NY, USA). The PCR was conducted using a premix and specific sense and antisense primers in conformity with the manufacturer's instructions (Bioneer, Daejeon, Korea). The amplification course consisted of denaturing at 94°C for 5 min, followed by 94°C for 20 sec, annealing at 60°C for 30 sec, and extension at 72°C for 45 sec, with a final extension performed at 72°C for 1 min. The primer sequences were as follow: murine COX-2, 5′-GAAGTCTTTGGTCTGGTGCCTG-3′ (sense) and 5′-GTCTGCTGGTTTGGAATAGTTGC-3′ (antisense); and murine β-actin, 5′-TGTTTGAGACCTTCAACACC-3′ (sense) and 5′-CGCTCATTGCCGATAGTGAT-3′ (antisense). β-actin was used as the housekeeping gene when indicated. PCR products were resolved on 1.5% agarose gels and stained with ethidium bromide. The images were captured by an Olympus C4000 Zoom Camera system (Olympus Corp. America, Inc., Center Valley, PA, USA).

Immunoblot analysis

Equal amounts of extracted protein (30 μg) were divided by 11% SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to polyvinylidene difluoride (PVDF) membranes. Each membrane was blocked for 1 h with 5% skim milk in TBS/T buffer (0.1% Tween-20, 0.1 M Tris-HCl, 0.9% NaCl, pH 7.4) to block non-specific binding and was then incubated with primary antibodies that recognized COX-2 (1:1,000), the total forms of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and JNK1/3 (1:1,000), the phosphorylated forms of p38 MAPK (1:1,000) (all from Santa Cruz Biotechnology, Santa Cruz, CA, USA) and the phosphorylated forms of ERK1/2 and JNK1/2 (1:1,000), in addition to those for β-actin (1:4,000) and PARP (1:1,000) (all from Cell Signaling Technology, Beverly, MA, USA). Secondary antibodies were goat anti-rabbit or anti-mouse antibodies (1:5,000; Santa Cruz Biotechnology, Inc.). The enhanced chemiluminescence reaction was performed using a Clarity™ Western ECL Substrate (Bio-Rad Laboratories, Hercules, CA, USA), and the positive bands were detected on radiographic film.

Statistical analyses

From the statistical analyses, the values are expressed as the mean ± SEM of the sample determinations. The statistical significance was determined using a two-tailed Student's t-test for independent means, with P-values of <0.05 statistically significant.


Effects of PFME on cell viability in RAW264.7 macrophages

Fig. 1 shows the effect of PFME on cell viability as determined by the MTT assay, with morphology of the cells confirmed with microscopic pictures. Cell viability did not decrease significantly at concentrations of PFME up to 30 μg/ml. Accordingly, for all ensuing experiments, the concentration range used was 0-30 μg/ml PFME.

PFME decreases the production of PGE2 by suppressing COX-2 and pro-inflammatory cytokine expression in LPS-stimulated RAW264.7 cells

Unstimulated RAW264.7 cells secreted basal levels of PGE2, whereas PGE2 production increased with LPS stimulation. We determined that PFME decreased the LPS-stimulated production of PGE2 and inhibited the expression of COX-2 in the macrophage cells. Moreover, PFME substantially decreased the LPS-stimulated PGE2 production in a concentration-dependent manner (Fig. 2A). The LPS-stimulated RAW264.7 cells overexpressed COX-2, whereas the PFME-treated cells stimulated with LPS suppressed expression of COX-2 protein (Fig. 2B). The expression of COX-2 protein was consistent with the mRNA results, and the PFME suppressed the expression of COX-2 mRNA in the LPS-stimulated RAW264.7 cells (Fig. 2C). Cytokines and pro-inflammatory mediators play significant roles in an immune reaction (26,27). Therefore, we estimated the influence of PFME on the production of cytokines, such as IL-6, TNF-α and IL-1β, and pro-inflammatory mediators in RAW264.7 macrophage cells (Fig. 2D–F). As shown in Fig. 2D–F as measured by ELISA, PFME suppressed production of IL-6, TNF-α and IL-1β in a concentration-dependent manner.

PFME inhibits the phosphorylation of the MAPKs in LPS-stimulated RAW264.7 cells

MAPKs play a vital role in the regulation of differentiation and cell growth and also control cellular responses to cytokines and stress (28). To determine the suppression of PFME on MAPKs signalling of inflammation in RAW264.7 cells, the regulation of the phosphorylation of the mediators JNK, p38 and ERK1/2 was investigated. The whole cell lysates were then examined with phospho-specific antibodies for JNK, p38 and ERK. The RAW264.7 cells treated with LPS alone showed increased phosphorylation of JNK, p38 and ERK1/2; however, PFME treatment decreased levels of phosphorylation of JNK, p38 and ERK1/2 in LPS-stimulated RAW264.7 cells in a concentration-dependent manner (Fig. 3). The level of expression of non-phosphorylated JNK, p38 and ERK1/2 did not change in cells treated with LPS or LPS and PFME. These experiments indicated that suppression of the phosphorylation of p38 and ERK1/2 kinases may explain the dramatic inhibitory effect of PFME on LPS-stimulated inflammatory mediator activation in RAW264.7 cells, although the phosphorylation of JNK was only slightly inhibited by PFME in the macrophage cells.

PFME and an inhibitor of MAPK phosphorylation inhibit the phosphorylation of the activation of MAPKs and the expression of NO and pro-inflammatory cytokines in LPS-stimulated RAW264.7 cells

To investigate the molecular mechanism of inflammatory mediator inhibition by PFME and MAPK inhibitors in LPS-stimulated RAW264.7 cells, we studied the inhibition of the phosphorylation of JNK, p38 and ERK1/2. In cells treated with LPS alone, phosphorylation of JNK, p38 and ERK1/2 increased. However, PFME, SP600125 (JNK), SB203580 (p38), and PD98059 (ERK) treatment decreased levels of phosphorylated JNK, p38 and ERK1/2 in LPS-stimulated RAW264.7 cells (Fig. 4). We further investigated the effect of the PFME, SP600125, SB203580, and PD98059 on the inhibition of the NO assay and ELISA (IL-6 and TNF-α) (Fig. 5). These results suggested that suppression of phosphorylation of JNK, p38 and ERK1/2 may be involved in the inhibitory effect of PFME, SP600125, SB203580 and PD98059 on LPS-stimulated inflammatory mediator activation in RAW264.7 cells.

PFME and an inhibitor of IκBα phosphorylation inhibits the phosphorylation of the activation of NF-κB in LPS-stimulated RAW264.7 cells

The levels of IκBα, a molecular marker in the NF-κB mechanism, were examined by immunoblot analysis. As shown in Fig. 6A, the basal level of IκBα and p65 in resting cells was high, but LPS treatment led to reduction in the translocation of p65 and IκBα degradation through the ubiq-uitin-proteasome pathway, with decreases in levels of p65 and IκBα. IκBα sequestered NF-κB in unstimulated RAW264.7 cells, but in LPS-induced cells, degradation of IκBα allowed NF-κB to translocate to the nucleus, with subsequent activation of gene expression resulting from the interaction of NF-κB and the corresponding cis-acting element. Therefore, we examined the levels of p65, the major subunit of NF-κB, in nuclear and cytoplasmic fractions, using PARP as a nuclear loading control. In this study, the inhibitor of cytokine-induced IκBα phosphorylation was BAY11-7082 (IC50, 10 μM), which was used to inhibit the NF-κB pathway as an irreversible inhibitor of IκBα phosphorylation that increases stabilization of IκBα and specifically blocks NF-κB signalling. As shown in Fig. 6B, the NF-κB p65 subunit decreased in the cytoplasm and increased in nuclear extracts after treatment with LPS. Treatment with PFME and BAY11-7082 reversed these trends in a concentration-dependent manner. We further investigated the effect of PFME and BAY11-7082 on the inhibition of NO. The LPS-stimulated translocation of the NF-κB p65 subunit from the cytosol to the nucleus in RAW264.7 cells (Fig. 6C) was inhibited by PFME. The NF-κB p65 and IκBα protein levels were significantly correlated with the reduced nuclear accumulations. Thus, we suggest that the PFME inhibited the translocation of the NF-κB p65 subunit and IκBα via the regulation of a signal transduction mechanism related to NF-κB activation.


Natural products play an important role in both drug discovery and chemical biology (29). PFME is traditionally used as an herbal medicine in several countries (21,30), although the anti-inflammatory effect of PFME is not fully understood. Therefore, we investigated the molecular mechanism and anti-inflammatory effect of PFME in LPS-stimulated RAW264.7 macrophage cells. We found that PFME decreased the release of the inflammatory mediators NO (data not shown) and PGE2 and suppressed pro-inflammatory cytokine production, including that of IL-1β, IL-6 and TNF-α (Fig. 2C-2). Additionally, iNOS (data not shown) and COX-2 protein expression in LPS-stimulated RAW264.7 cells was downregulated by PFME. We also discovered that PFME considerably inhibited inflammatory process signalling pathways, including NF-κB nuclear translocation and phosphorylation of MAPKs. Therefore, we suggest that PFME increased the anti-inflammatory effect in LPS-stimulated macrophages.

During inflammation, excess levels of PGE2, NO, and pro-inflammatory cytokines are caused by activated inflammatory cells, which result in damaging effects on tissues and cells and the activation in inflammation-associated sickness (31). Through the inflammatory pathways, iNOS and COX-2 expression remarkably increases the generation of NO and PGE2, respectively, and accordingly, the inhibition of PGE2 and NO production can be a critical marker for anti-inflammatory responses (32). The fundamental role of the NF-κB signalling pathway is regulation of the transcription factors that control expression of iNOS and COX-2. In LPS-unstimulated macrophages, NF-κB was suppressed by IκB in the cytoplasm. Then, NF-κB can freely translocate from the cytosol to the nucleus in which it promotes transcription of target genes and further induces the transcription of pro-inflammatory mediators, such as IL-6, IL-1β, TNF-α and COX-2 (9,33,34). Many anti-inflammatory agents express their potencies by suppressing NF-κB signalling (35). The molecular signalling of the extract-mediated emaciation in macrophage cells had a close relationship with the inhibition of p65 subunit translocation into the nucleus. Our results indicated that PFME downregulated the expression of COX-2 and also the production of PGE2 in LPS-stimulated cells (Fig. 2). Additionally, PFME reduced the secretions of IL-6, IL-1β and TNF-α (Fig. 2). The decrement of PFME-mediated molecular signalling in the macrophage cells was closely associated with the oppression of IκB kinase activation followed by inhibition of the translocation of NF-κB p65 subunits into the nucleus (Fig. 6). These results suggest that the PFME inhibited the expression of pro-inflammatory mediators by downregulating the NF-κB pathway in stimulated macrophage cells.

MAPKs, including p38, ERK and JNK, are a syndicate of signalling molecules that likely have an important function in inflammatory mechanisms (36). Zhang et al (37) suggested that LPSs induced MAPK cascades and the pathways leading to activation of NF-κB p65. Additionally, MAPKs are complicated by the expression of iNOS in the LPS-induced signalling pathway (38). In this study, LPS induced the phosphorylation of MAPKs. The treatment with PFME significantly inhibited the phosphorylation of LPS-induced ERK, p38 and JNK at 1 h. Consequently, these results suggest that ERK, p38 and JNK were complicated in the inhibition by PFME of LPS-stimulated NF-κB p65 binding in RAW264.7 macrophage cells. In this study, the treatment with PFME blocked the activation of ERK, p38 and JNK, which suggested that PFME suppressed LPS-induced NF-κB translocation by inhibiting the activation of these intracellular signalling cascades, leading to decreased protein levels of iNOS and COX-2 (Fig. 4).

The inhibitory activity of PFME on the MAPKs (JNK, ERK and p38) is shown in Fig. 3. The PFME showed excellent inhibitory activity of the MAPK pathway. When the major MAPK signal in the primary inflammatory response is suppressed, related diseases are affected. Regarding these effects, a comparative analysis was performed using inhibitors known to be actual inhibitors of MAPK. The importance of this experiment was to show that PFME had some influence on the inhibitory activity of each inhibitor. As confirmed in Fig. 4, the MAPK was inhibited with an inhibitor and PFME for each target. As shown in Fig. 5, the inhibitory activity of MAPK against NO, TNF-α and IL-6 was confirmed, which was the result of treating with inhibitors of MAPK and PFME, indicating that the signal-affected targets were inhibited. As a result, the activity of PFME was confirmed to be better than that of the actual MAPK inhibitors. As with the inhibitors, PFME affected the target and was more effective when using two bells simultaneously. Additionally, the NF-κB inhibitor BAY11-7082 decreased translocation of NF-κB p65 and IκBα and iNOS production in LPS-stimulated macrophages. BAY11-7082 with PFME also inhibited p65 and IκBα expression in this result. The results suggested that blocking of the MAPKs pathway was involved in the suppression of LPS-stimulated NF-κB bound by PFME in RAW264.7 cells (Fig. 6).

To conclude, PFME exhibited anti-inflammatory activities that were related to the suppression of NO, PGE2, IL-1β, IL-6 and TNF-α and reduced expression of COX-2 and iNOS via activation of the NF-κB p65 pathway in macrophage cells. The anti-inflammatory effect of PFME was particularly maximized when macrophages were pre-treated with PFME and an extract containing a mixture of ten plant-based food groups. Combined, these results suggest that PFME can help diminish the inflammation mediated by activated macrophages, which could potentially improve the response of a host to inflammation-mediated illnesses.

In conclusion, the results of this study indicated that PFME inhibited the LPS-induced inflammatory and oxidative responses, with these effects likely closely related with the suppression of NF-κB activation. Therefore, we propose PFME for possible use as a therapeutic for treating inflammatory diseases.


Not applicable.


[1] Funding

The present study was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation and funded by the Korean government (MSIT; grant no. NRF-2016K1A1A8A01939075) and from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program of the Republic of Korea (grant no. KGM1221814).

[2] Availability of data and material

The analyzed datasets generated during the study are available from the corresponding author upon reasonable request.

[3] Authors' contributions

JWP analyzed the data and wrote the manuscript. OKK, HWR, JHP, IP and PY prepared the Passiflora foetida L., and analyzed and edited the manuscript. SC, SRO and KSA designed the study and edited the manuscript. All authors critically revised the article and have approved the final version of the manuscript.

[4] Ethics approval and consent to participate

Not applicable.

[5] Consent for publication

Not applicable.

[6] Competing interests

The authors declare that they have no competing interests.



Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI


Brevetti G, Giugliano G, Brevetti L and Hiatt WR: Inflammation in peripheral artery disease. Circulation. 122:1862–1875. 2010. View Article : Google Scholar : PubMed/NCBI


Hummasti S and Hotamisligil GS: Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ Res. 107:579–591. 2010. View Article : Google Scholar : PubMed/NCBI


Kim HS, Park JW, Kwon OK, Kim JH, Oh SR, Lee HK, Bach TT, Quang BH and Ahn KS: Anti-inflammatory activity of a methanol extract from Ardisia tinctoria on mouse macrophages and paw edema. Mol Med Rep. 9:1388–1394. 2014. View Article : Google Scholar : PubMed/NCBI


Lambrecht BN and Hammad H: The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lancet. 376:835–843. 2010. View Article : Google Scholar : PubMed/NCBI


Christaki E, Opal SM, Keith JC Jr, Kessinian N, Palardy JE, Parejo NA, Lavallie E, Racie L, Mounts W, Malamas MS, et al: Estrogen receptor beta agonism increases survival in experimentally induced sepsis and ameliorates the genomic sepsis signature: A pharmacogenomic study. J Infect Dis. 201:1250–1257. 2010. View Article : Google Scholar : PubMed/NCBI


Park JW, Shin IS, Ha UH, Oh SR, Kim JH and Ahn KS: Pathophysiological changes induced by Pseudomonas aeruginosa infection are involved in MMP-12 and MMP-13 upregulation in human carcinoma epithelial cells and a pneumonia mouse model. Infect Immun. 83:4791–4799. 2015. View Article : Google Scholar : PubMed/NCBI


Corriveau CC and Danner RL: Endotoxin as a therapeutic target in septic shock. Infect Agents Dis. 2:35–43. 1993.PubMed/NCBI


Park JW, Kwon OK, Jang HY, Jeong H, Oh SR, Lee HK, Han SB and Ahn KS: A leaf methanolic extract of Wercklea insignis attenuates the lipopolysaccharide-induced inflammatory response by blocking the NF-κB signaling pathway in RAW 264.7 macrophages. Inflammation. 35:321–331. 2012. View Article : Google Scholar


Pouliot M, Baillargeon J, Lee JC, Cleland LG and James MJ: Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase. J Immunol. 158:4930–4937. 1997.PubMed/NCBI


Zhang G and Ghosh S: Toll-like receptor-mediated NF-kappaB activation: A phylogenetically conserved paradigm in innate immunity. J Clin Invest. 107:13–19. 2001. View Article : Google Scholar : PubMed/NCBI


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


Baker JR Jr and Baldwin JL: Allergy and immunology. JAMA. 275:1794–1795. 1996. View Article : Google Scholar : PubMed/NCBI


Park JW, Kwon OK, Kim JH, Oh SR, Kim JH, Paik JH, Marwoto B, Widjhati R, Juniarti F, Irawan D, et al: Rhododendron album Blume inhibits iNOS and COX-2 expression in LPS-stimulated RAW264.7 cells through the downregulation of NF-κB signaling. Int J Mol Med. 35:987–994. 2015. View Article : Google Scholar : PubMed/NCBI


Riches DW, Chan ED, Zahradka EA, Winston BW, Remigio LK and Lake FR: Cooperative signaling by tumor necrosis factor receptors CD120a (p55) and CD120b (p75) in the expression of nitric oxide and inducible nitric oxide synthase by mouse macrophages. J Biol Chem. 273:22800–22806. 1998. View Article : Google Scholar : PubMed/NCBI


Ajizian SJ, English BK and Meals EA: Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis. 179:939–944. 1999. View Article : Google Scholar : PubMed/NCBI


Asadujjaman M, Mishuk AU, Hossain MA and Karmakar UK: Medicinal potential of Passiflora foetida L. plant extracts: Biological and pharmacological activities. J Integr Med. 12:121–126. 2014. View Article : Google Scholar : PubMed/NCBI


Huang WC, Wu SJ, Tu RS, Lai YR and Liou CJ: Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells. Food Funct. 6:1960–1967. 2015. View Article : Google Scholar : PubMed/NCBI


Krishnaveni A and Thaakur SR: Pharmacognostical and preliminary phytochemical studies of Passiflora foetida. Anc Sci Life. 27:19–23. 2008.PubMed/NCBI


Nunes ES, Brown JK, Moreira AG, Watson G, Lourenção AL, Piedade SM, Rezende JA and Vieira ML: First report and differential colonization of Passiflora species by the B biotype of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in Brazil. Neotrop Entomol. 37:744–746. 2008. View Article : Google Scholar


Sathish R, Sahu A and Natarajan K: Antiulcer and antioxidant activity of ethanolic extract of Passiflora foetida L. Indian J Pharmacol. 43:336–339. 2011. View Article : Google Scholar : PubMed/NCBI


Sasikala V, Saravanan S and Parimelazhagan T: Analgesic and anti-inflammatory activities of Passiflora foetida L. Asian Pac J Trop Med. 4:600–603. 2011. View Article : Google Scholar : PubMed/NCBI


Nguyen TY, To DC, Tran MH, Lee JS, Lee JH, Kim JA, Woo MH and Min BS: Anti-inflammatory flavonoids isolated from Passiflora foetida. Nat Prod Commun. 10:929–931. 2015.PubMed/NCBI


Lee JW, Shin NR, Park JW, Park SY, Kwon OK, Lee HS, Hee Kim J, Lee HJ, Lee J, Zhang ZY, et al: Callicarpa japonica Thunb. attenuates cigarette smoke-induced neutrophil inflammation and mucus secretion. J Ethnopharmacol. 175:1–8. 2015. View Article : Google Scholar : PubMed/NCBI


Park JW, Kwon OK, Yuniato P, Marwoto B, Lee J, Oh SR, Kim JH and Ahn KS: Amelioration of an LPS-induced inflammatory response using a methanolic extract of Lagerstroemia ovalifolia to suppress the activation of NF-κB in RAW264.7 macrophages. Int J Mol Med. 38:482–490. 2016. View Article : Google Scholar : PubMed/NCBI


Shin IS, Park JW, Shin NR, Jeon CM, Kwon OK, Lee MY, Kim HS, Kim JC, Oh SR and Ahn KS: Melatonin inhibits MUC5AC production via suppression of MAPK signaling in human airway epithelial cells. J Pineal Res. 56:398–407. 2014. View Article : Google Scholar : PubMed/NCBI


Lee BH, Kushwah R, Wu J, Ng P, Palaniyar N, Grinstein S, Philpott DJ and Hu J: Adenoviral vectors stimulate innate immune responses in macrophages through cross-talk with epithelial cells. Immunol Lett. 134:93–102. 2010. View Article : Google Scholar : PubMed/NCBI


Park JW, Lee IC, Shin NR, Jeon CM, Kwon OK, Ko JW, Kim JC, Oh SR, Shin IS and Ahn KS: Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling. Nanotoxicology. 10:445–452. 2016. View Article : Google Scholar


Newman DJ and Cragg GM: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 75:311–335. 2012. View Article : Google Scholar : PubMed/NCBI


Puricelli L, Dell'Aica I, Sartor L, Garbisa S and Caniato R: Preliminary evaluation of inhibition of matrix-metalloprotease MMP-2 and MMP-9 by Passiflora edulis and P. foetida aqueous extracts. Fitoterapia. 74:302–304. 2003. View Article : Google Scholar : PubMed/NCBI


Xiao YQ, Malcolm K, Worthen GS, Gardai S, Schiemann WP, Fadok VA, Bratton DL and Henson PM: Cross-talk between ERK and p38 MAPK mediates selective suppression of pro-inflammatory cytokines by transforming growth factor-beta. J Biol Chem. 277:14884–14893. 2002. View Article : Google Scholar : PubMed/NCBI


Navarro C, Bravo ML, Carulla C and Bulbena O: Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: Modifications induced by pretreatment with zinc acexamate. Prostaglandins Leukot Essent Fatty Acids. 50:305–310. 1994. View Article : Google Scholar : PubMed/NCBI


Jung WK, Heo SJ, Jeon YJ, Lee CM, Park YM, Byun HG, Choi YH, Park SG and Choi IW: Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. J Agric Food Chem. 57:4439–4446. 2009. View Article : Google Scholar : PubMed/NCBI


Kim HG, Shrestha B, Lim SY, Yoon DH, Chang WC, Shin DJ, Han SK, Park SM, Park JH, Park HI, et al: Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol. 545:192–199. 2006. View Article : Google Scholar : PubMed/NCBI


Umezawa K and Chaicharoenpong C: Molecular design and biological activities of NF-kappaB inhibitors. Mol Cells. 14:163–167. 2002.PubMed/NCBI


An H, Xu H, Yu Y, Zhang M, Qi R, Yan X, Liu S, Wang W, Guo Z, Qin Z, et al: Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways. Immunol Lett. 81:165–169. 2002. View Article : Google Scholar : PubMed/NCBI


Zhang JS, Feng WG, Li CL, Wang XY and Chang ZL: NF-kappaB regulates the LPS-induced expression of interleukin 12 p40 in murine peritoneal macrophages: Roles of PKC, PKA, ERK, p38 MAPK, and proteasome. Cell Immunol. 204:38–45. 2000. View Article : Google Scholar : PubMed/NCBI


Cañas N, Gorina R, Planas AM, Vergés J, Montell E, García AG and López MG: Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation. Neuroscience. 167:872–879. 2010. View Article : Google Scholar : PubMed/NCBI

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Volume 41 Issue 6

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Park J, Kwon O, Ryu HW, Paik J, Paryanto I, Yuniato P, Choi S, Oh S and Ahn K: Anti-inflammatory effects of Passiflora foetida L. in LPS-stimulated RAW264.7 macrophages. Int J Mol Med 41: 3709-3716, 2018
Park, J., Kwon, O., Ryu, H.W., Paik, J., Paryanto, I., Yuniato, P. ... Ahn, K. (2018). Anti-inflammatory effects of Passiflora foetida L. in LPS-stimulated RAW264.7 macrophages. International Journal of Molecular Medicine, 41, 3709-3716.
Park, J., Kwon, O., Ryu, H. W., Paik, J., Paryanto, I., Yuniato, P., Choi, S., Oh, S., Ahn, K."Anti-inflammatory effects of Passiflora foetida L. in LPS-stimulated RAW264.7 macrophages". International Journal of Molecular Medicine 41.6 (2018): 3709-3716.
Park, J., Kwon, O., Ryu, H. W., Paik, J., Paryanto, I., Yuniato, P., Choi, S., Oh, S., Ahn, K."Anti-inflammatory effects of Passiflora foetida L. in LPS-stimulated RAW264.7 macrophages". International Journal of Molecular Medicine 41, no. 6 (2018): 3709-3716.