Open Access

Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway

  • Authors:
    • Besse Hardianti
    • Lin Umeyama
    • Feng Li
    • Satoru Yokoyama
    • Yoshihiro Hayakawa
  • View Affiliations

  • Published online on: October 20, 2020
  • Pages: 5385-5391
  • Copyright: © Hardianti et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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


Accumulating evidence suggests that inflammation is linked to multiple pathological processes and induces cellular and molecular damage through the activation of inflammatory signaling pathways, including the NF‑κB pathway. The aim of the present study was to identify natural anti‑inflammatory products that can target NF‑κB activity, in order to establish a novel therapeutic approach for inflammatory diseases. Using a 4T1 breast cancer cell line that expresses the firefly luciferase gene under the control of an NF‑κB response element, 112 natural products were tested for their anti‑inflammatory properties. Sohakuhi (Morus alba Linn. bark) extract was observed to strongly suppress NF‑κB activity without affecting cell viability. To further examine the anti‑inflammatory effect of Sohakuhi, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced cellular damage of human HaCaT keratinocytes was evaluated. While TRAIL triggered the phosphorylation of the p65 subunit of NF‑κB, leading to cellular damage in HaCaT cells, treatment with Sohakuhi extract protected HaCaT cells against TRAIL‑induced cellular damage. Moreover, Sohakuhi treatment also upregulated the anti‑apoptotic proteins Bcl‑xL and Bcl‑2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were confirmed to mediate its anti‑inflammatory effects. Collectively, the present results indicated that Sohakuhi and moracin may represent potential candidates for the development of novel anti‑inflammatory drugs.


Inflammation occurs in response to a variety of stimuli, such as tissue damage, infection, or cancer (13). While acute inflammation is of short duration and represents an early body reaction that resolves quickly, chronic inflammation is defined as a prolonged process whereby tissue destruction and inflammation occur simultaneously (4). In the early stages of inflammation, the vascular endothelium is activated by cytokines, leading to adhesion and transmigration of leukocytes into the site of inflammation. Some of the pro-inflammatory processes acquired at the endothelium and leukocytes are mediated by the transcription factor NF-κb (5). Failure to treat inflammation can lead to various diseases associated with chronic inflammation, including arthritis, atherosclerosis, and even cancer (6). For most of these conditions, no satisfactory treatment has been established.

NF-κB is a transcription factor that plays an important role in cellular stress responses, including the DNA damage response (7). NF-κB activation induces the expression of >200 genes that regulate inflammation, as well as cell death/apoptosis (8). The DNA damage response is known to play a pivotal role in ageing and carcinogenesis. It consists of a signal transduction cascade that is initiated by DNA double-strand breaks and leads to DNA repair, cell cycle arrest or programmed cell death (9). Evidence strongly suggests that inflammation is linked to multiple pathologies, such as cancer and obesity (10), by inducing cellular and molecular damage through the activation of several signaling pathways, including the NF-κB pathway.

The aim of the present study was to identify natural products with anti-inflammatory effects on NF-κB activity and further characterize active compounds from plant products for drug discovery. By screening 112 natural products for their anti-inflammatory properties, it was identified that Sohakuhi (Morus alba Linn. bark) extract markedly suppressed NF-κB-dependent luciferase reporter activity in murine 4T1 cells without affecting cell viability. The anti-inflammatory effect of Sohakuhi on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cellular damage was evaluated in human HaCaT keratinocytes. TRAIL triggered the phosphorylation of p65, a subunit of NF-κB, leading to cellular damage in HaCaT cells. However, treatment with Sohakuhi extract protected HaCaT cells against TRAIL-induced damage. Moreover, Sohakuhi also upregulated the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were determined to mediate its anti-inflammatory effect.

Materials and methods

Cells and reagents

The murine B16F10 and 4T1 cell lines were obtained from the American Type Culture Collection and maintained at 37°C in Eagle's minimal essential medium or RPMI-1640 medium (Nissui Pharmaceutical Co., Ltd.) containing 10% FBS (Nichirei Biosciences, Inc.), respectively. Human HaCaT keratinocytes (provided by Dr Takeda, Juntendo University, Tokyo, Japan) were maintained at 37°C in culture medium consisting of DMEM (Nissui Pharmaceutical Co., Ltd.) supplemented with 10% FBS, 100 U/l penicillin G and 100 mg/l streptomycin at 37°C with 5% CO2. Human recombinant TRAIL (rTRAIL) was purchased from PeproTech, Inc.

In vitro NF-κB luciferase reporter assay

B16F10NFκB and 4T1NFκB cells expressing firefly luciferase under the control of an NF-κB response element were established as previously described (11,12) and maintained at 37°C in RPMI-1640 medium containing 10% FBS. Briefly, B16F10NFκB and 4T1NFκB cells were generated by transfecting the B16F10 and 4T1 cell lines with pGL4.32-luc2P/NF-κB-RE/Hygro vector (Promega Corporation) using Lipofectamine® 2000 (Invitrogen; Thermo Fisher Scientific, Inc.). The cells were selected on hygromycin B and cloned by limiting dilution.

B16F10NFκB cells and 4T1NFκB cells in the exponential growth phase were seeded at a final concentration of 4×104 cells/well in a 96-well plate. After 3-h incubation, the cells were co-cultured with 50 µg/ml extract from 112 natural products (Table SI) for 24 h. At the end of the assay, 900 µg/ml D-luciferin was added, and the plates were incubated for another 30 min. Luciferase activity was measured by the GloMax®-Multi Detection System (Promega Corporation).

Cell viability assay

Cell viability was quantified using the WST-1 cell proliferation reagent (Dojindo Molecular Technologies, Inc.). B16F10NFκB or 4T1NFκB cells were seeded on a 96-well plate and co-cultured with extracts from 112 natural products (Table SI) at 50 µg/ml for 24 h. In a separate experiment, HaCaT cells were seeded on a 96-well plate at a density of 104 cells/well and pre-treated with 20 ng/ml rTRAIL for 1 h. The cells were then cultured with or without Sohakuhi extract (6.25 to 50 µg/ml) for 24 h. After incubation, WST-1 solution was added and used according to the manufacturer's instructions, and absorbance was measured at 450 nm using a microplate reader. Cell viability was calculated as a percentage of the control.

Caspase-3 and −7 activity assay

For measurement of the activities of caspase-3 and −7, the Caspase-Glo® 3/7 assay system (Promega Corporation) was used according to the manufacturer's instructions. Briefly, HaCaT cells (5×103 cells/well in a 96-well plate) were pre-treated with 20 ng/ml rTRAIL for 1 h. The cells were then cultured with Sohakuhi extract for 24 h, and the Caspase-Glo® 3/7 reagent was then added. After 30-min incubation, caspase-3 and −7 activities were measured using the GloMax®-Multi Detection System (Promega Corporation).

Identification of the active components of Sohakuhi extract

To identify the bioactive components of Sohakuhi extract, 200 g root bark of Morus alba Linn. was decocted in 1 l water for 50 min. The water extract was fractionated by water-methanol gradient reverse-phase medium-pressure liquid chromatography (RP-MPLC) fractionation. Mass spectrometry and 1H-nuclear magnetic resonance (NMR) analysis were used to identify compounds in the isolated fractions. Extraction and isolation of Sohakuhi was conducted using a water-methanol gradient MPLC fractionation system and high-performance liquid chromatography (Accela™ HPLC system; Thermo Fisher Scientific, Inc.) profiles of water extracts of Sohakuhi were determined at 254-nm ultraviolet wavelength. A Capcell Pak C18 MG III S-5 (4.5×250 mm, 5 µm; Shiseido Co., Ltd.) column was used for HPLC analysis at a flow rate of 1 ml/min at 40°C. A gradient elution system composed of 5% CH3CN (v/v) (A) and H2O was used as follows: 0–4 min, 5% A; 4–8 min, 5–10% B; 8–12 min, 10–15% B; 12–15 min, 15–20% B; 15–18 min, 20–25% B; 18–21 min, 25–30% B; 21–25 min, 30–35% B; 25 min, 40% B. The active fraction was further analyzed using a CHCl3-MeOH gradient RP-MPLC fractionation system with mass spectrometry and 1H-NMR analysis to identify the active compounds of Sohakuhi. The MS conditions were set as follows: Negative ESI mode, spray voltage 4.5 kV, capillary voltage 40.0 kV, tube lens 150 V, capillary temperature 270°C, sheath gas flow rate 50 units, aux gas flow rate 10 units, and scan range m/z 50–2,000. A polytyrosine solution was used for instrument calibration before each experiment.

Western blot analysis

HaCaT cells were seeded at a density of 5×105 cells/well and cultured for 24 h in a 6-well plate. After treatment, the cells were washed in cold PBS, scraped and lysed in whole-cell lysis buffer (25 mmol/l HEPES, pH 7.7; 300 mmol/l NaCl; 1.5 mmol/l MgCl2; 0.2 mmol/l EDTA; 0.1% Triton X-100; 20 mmol/l β-glycerophosphate; 1 mmol/l Na3VO4; 1 mmol/l phenylmethylsulfonylfluoride; 1 mmol/l dithiothreitol; 10 mg/ml aprotinin; 10 mg/ml leupeptin). Cell lysates (10 µl/lane) were resolved by SDS-PAGE on 7.5–15% gels, then transferred to an Immobilon-P nylon membrane (EMD Millipore). The membranes were treated with Block Ace (Dainippon Sumimoto Pharma Co., Ltd.) for at least 2 h at room temperature, then probed with primary antibodies at 4°C overnight, followed by horseradish peroxidase-conjugated secondary antibodies (1:2,000; cat. nos. P0448 and P0260; Dako; Agilent Technologies, Inc.). Bands were visualized using ECL reagents (Amersham; Cytiva). The primary antibodies used were specific for Bcl-2 (clone no. D55G8; cat. no. 4223), Bcl-xL (clone no. 54H6; cat. no. 2764), p65 (clone no. L8F6; cat. no. 6956), phosphorylated-p65, (clone no. 93H1; cat. no. 3033; all Cell Signaling Technology, Inc.) and β-actin (clone no. C4; cat. no. sc-47778; Santa Cruz Biotechnology, Inc.). All primary antibodies were used at 1:1,000 dilution.

Statistical analysis

All data are presented as the mean ± SEM of three independent experiments. SPSS versions 23 and 25 software (IBM Corp.) were used to analyze data. Statistical analysis was carried out using one-way ANOVA followed by Bonferroni correction. P<0.05 was considered to indicate a statistically significant difference.


Sohakuhi suppresses NF-κB activity in murine cancer cell lines

To identify novel anti-inflammatory agents in plant products, 112 medicinal plant extracts (Table SI) were screened for their effect on NF-κB activity using cell lines that express luciferase under the control of an NF-κB response element. Among the tested extracts, Sohakuhi markedly suppressed NF-κB activity without affecting the viability of 4T1 cells (Fig. 1A). Furthermore, NF-κB activity was suppressed by Sohakuhi extract in 4T1 cells and B16F10 cells in a dose-dependent manner (Fig. 1B). However, Sohakuhi extract did not display any cytotoxic effect, even at doses reaching 50 µg/ml (Fig. 1C).

Cytoprotective effect of Sohakuhi extract on TRAIL-induced cellular damage in human keratinocytes

To examine the biological utility of Sohakuhi extract, human HaCaT keratinocytes were incubated with rTRAIL as an inflammatory stimulus to induce NF-κB activation and cytotoxicity. Compared with the control, rTRAIL treatment induced significant cytotoxicity in HaCaT cells. However, pre-treatment with Sohakuhi extract significantly protected HaCaT cells from TRAIL-induced cytotoxicity in a dose-dependent manner (Fig. 2A). The cytoprotective effect of Sohakuhi extract was evident from microscopic observation of cell morphology (Fig. 2B). These results indicated the cytoprotective effect of Sohakuhi extract against TRAIL-induced cellular damage in human keratinocytes.

Anti-apoptotic effect of Sohakuhi extract on HaCaT cells

To confirm whether Sohakuhi extract affects NF-κB activation in HaCaT cells, the expression of the p65 subunit of NF-κB and its phosphorylation status following rTRAIL stimulation was assessed in the presence or absence of Sohakuhi extract (Fig. 3A). Phosphorylation of p65 was detectable in HaCaT cells following rTRAIL stimulation, but suppressed in the presence of Sohakuhi extract. While Sohakuhi extract treatment reduced total p65 expression in rTRAIL-stimulated HaCaT cells, there was almost no effect on the basal expression of p65 in unstimulated HaCaT cells, suggesting that the effect of Sohakuhi extract might be specific to TRAIL-induced NF-κB activity. Treatment with the Sohakuhi extract also showed an inhibitory effect on TRAIL-induced apoptosis, as seen in the suppression of caspase-3/7 activation (Fig. 3B). Importantly, the anti-apoptotic proteins Bcl-xL and Bcl-2 were upregulated in Sohakuhi extract-treated HaCaT cells following TRAIL stimulation (Fig. 3C). These results indicated that the cytoprotective effect of Sohakuhi extract might result from inhibition of TRAIL-induced apoptosis and regulation of anti-apoptotic proteins.

Identification of the active component of Sohakuhi extract to inhibit NF-κB activation

As Sohakuhi extract significantly inhibited NF-κB activity and displayed a cytoprotective effect against inflammation-associated cellular damage of human keratinocytes, the bioactive components of Sohakuhi extract were then analyzed. A total of 8 yield fractions were isolated from a Sohakuhi water extract using RP-MPLC with methanol-water gradient (Fig. 4A). The preparative HPLC data for these 8 yield fractions are presented in Fig. 4B. Amongst those fractions, fraction 8 effectively and exclusively inhibited NF-κB activity (Fig. 4C). Considering that fraction 8 was eluted with 100% methanol in the water-methanol gradient, the methanol extract of Sohakuhi was then fractionated into hexane, ethyl acetate, n-butanol and a residual water layer (Fig. 5A) to test the activity of each layer with respect to NF-κB inhibition. Amongst those layers, the ethyl acetate layer displayed very potent inhibition of NF-κB activity in 4T1 cells, even at the lowest dose tested, 5 µg/ml (Fig. 5B). These results indicated that the active component of Sohakuhi was fractionated into an ethyl acetate layer from the methanol extract.

Isolation of moracin O and P as active compounds of Sohakuhi

Using a CHCl3-MeOH gradient RP-MPLC fractionation system with mass spectrometry and 1H-NMR analysis, two major compounds, moracin O and P, were identified in the ethyl acetate layer of Sohakuhi methanol extract (Fig. 6A). Importantly, both moracin O and P significantly inhibited NF-κB activity in 4T1 cells, starting at a dose of 3 nM (Fig. 6B). Additionally, both moracin O and P showed significant cytoprotective effects against TRAIL-induced cellular damage in HaCaT cells (Fig. 6C). Thus, moracin O and P were identified as active compounds of Sohakuhi that suppressed NF-κB activity and exerted a cytoprotective effect against TRAIL-induced damage in HaCaT cells.


The aim of the present study was to identify a novel anti-inflammatory drug candidate that can target NF-κB activation. A total of 112 plant extracts were screened, identifying Sohakuhi as a promising anti-inflammatory compound. The white mulberry tree (Morus alba Linn.) is a deciduous tree originating from Asia, especially China, but currently cultivated in subtropical, tropical and mild environmental conditions (13,14). Morus alba Linn. tree bark, fruits and leaves contain proteins, carbohydrates, calcium, iron, ascorbic acid, thiamine, folic acid and vitamin D (15). It has been used in conventional and natural medicine to treat diabetes, atherosclerosis, hyperlipidemia, hypertension, neurodegenerative disease and cancer (13). Phytochemical studies have reported that alkaloids, flavonoids, flavones, flavanones, stilbenes, benzophenones, coumarin derivatives, terpenoid stilbenes, oxyresveratrol and resveratrol were present in Morus species (1618). Moreover, oxyresveratrol can suppress inflammation by inhibiting nitric oxide (NO) production, inducible NO synthase expression, prostaglandin E2 production and NF-κB activation in macrophages (19). Moracin R, C, O, P and D belong to the 2-arylbenzofuran group, and display inhibitory activity against the differentiation of 3T3-L1 adipocytes and NO production in RAW264.7 cells (20). The 2-arylbenzofurans of Morus species, moracin O and P, markedly suppress hypoxia-inducible factor-1 (HIF-1) activity in the human Hep3B hepatocellular carcinoma cell line (2123). Moracin-M-3′-O-β-D-glucopyranoside has been reported to suppress 12-O-tetradecanoylphorbol-13-acetate-induced tumor progression in mouse skin, and the underlying mechanism may involve the inhibition of leukocyte infiltration, epidermal hyper-proliferation, oxidative stress, and the endogenous tumor promoter TNF (24).

NF-κB plays a central role in inflammation, immunity and several other cellular responses (2527). A variety of ligands and receptors can activate the NF-κB signaling pathway, including TNF and TNF receptor superfamily molecules that are key to inflammatory responses (24,28). Amongst these TNF superfamily members, TRAIL is known to be a potent inducer of apoptosis through activation of inflammatory signaling pathways (29,30). In the present study, TRAIL induced cellular damage of HaCaT keratinocytes through NF-κB activation. Moreover, both moracin O and P significantly protected HaCaT cells against TRAIL-induced cytotoxicity, possibly through the inhibition of apoptosis. Considering that NF-κB-mediated inflammation has been implicated in the regulation of cellular damage by balancing anti- and pro-apoptotic protein expression (3134), moracin O and P may protect against HaCaT cell damage through their anti-inflammatory activity by targeting the NF-κB pathway. In the present study, moracin O and P as novel anti-inflammatory compounds inhibiting cellular damage induced by NF-κB activation.

The aforementioned effects of Sohakuhi extract and its active components, moracin O and P, suggested that these compounds may prove beneficial for the treatment of inflammatory diseases. Although the exact mechanism of action remains to be determined, the present study demonstrated that both moracin O and P represent promising phytochemicals that may act as novel anti-inflammatory or cytoprotective agents through the suppression of the NF-κB pathway.

Supplementary Material

Supporting Data


The authors are grateful to Dr Kei Takahashi (University of Tokyo) for her technical support.


The present study was partly supported by The Ronpaku Program of Japan Science and Promotion of Science (grant no. R11815), The Research Grant from The Research Foundation of First Bank of Toyama, The Grant-in-Aid for Scientific Research on Innovative Areas (grant no. 17H06398), The Ministry of Education, Culture, Sports, Science and Technology of Japan, and The Cooperative Research Project from The Institute of Natural Medicine, University of Toyama.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

BH, LU and FL performed the experiments and analyzed the data. SY and YH analyzed and interpreted the data. BH and YH wrote the manuscript and YH designed the study. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.





tumor necrosis factor-related apoptosis-inducing ligand



Fachrudin N, Waltenberger B, Cabaracdic M, Atanasov AG, Malainer C, Schachner D, Heiss EH, Liu R, Noha SM, Grzywacz AM, et al: Identification of plumericin as apotent new inhibitor of the NF-kB pathway with anti-inflammatory activity in vitro and vivo. Br J Pharmacol. 171:1676–1686. 2014.PubMed/NCBI


Weis U: Inflammation. Nature. 454:4272008.PubMed/NCBI


Tabas I and Glass CK: Anti-Inflammatory therapy in chronic disease: Challenenges and opportunities. Science. 339:166–172. 2013.PubMed/NCBI


Patel M, Murugananthan and Gowda KPS: In vivo animal models in preclinical evaluation of anti inflammatory activity - A review. Int J Pharm Res Allied Sci. 1:01–05. 2012.


Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 1:a0016512009.PubMed/NCBI


Yuan Q, Zhang X, Liu Z, Song S, Xue P, Wang J and Ruan J: Ethanol extract of adiantum capillus-veneris L. Suppress the production of inflammatory mediator by inhibiting NF-kB activation. J Ethnopharmacol. 147:603–611. 2013.PubMed/NCBI


Giuliani C, Bucci I and Napolitano G: The role of the transcription factor nuclear factor-kappa B in thyroid autoimmunity and cancer. Front Endocrinol (Lausanne). 9:4712018.PubMed/NCBI


Aggarwal BB and Shishodia S: Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 71:1397–1421. 2006.PubMed/NCBI


De Bont R and van Larebeke N: Endogenous DNA damage in humans: A review of quantitative data. Mutagenesis. 19:169–185. 2004.PubMed/NCBI


Deng T, Lyon CJ, Bergin S, Caligiuri MA and Hsueh WA: Obesity, inflammation, and cancer. Annu Rev Pathol. 11:421–449. 2016.PubMed/NCBI


Takahashi K, Takeda K, Saiki I, Irimura T and Hayakawa Y: Functional roles of tumor necrosis factor-related apoptosis-inducing ligand-DR5 interaction in B16F10 cells by activating the nuclear factor-κB pathway to induce metastatic potential. Cancer Sci. 104:558–562. 2013.PubMed/NCBI


Takhashi K, Nagai N, Ogura K, Tsuneyama K, Saiki I, Irimura T and Hayakawa Y: Mammary tissue microenvironment determines T cell-dependent breast cancer-associated inflammation. Cancer Sci. 106:867–874. 2015.PubMed/NCBI


Flaczyk E, Kobus-Cisowska J, Przeor M, Korczak J, Remiszewski M, Korbas E and Buchowski M: Chemical characterization and antioxidative properties of polish variety of Morus alba L, leaf aqueous extracts from the laboratory and pilot-scale processes. Agriculture Sci. 4:141–147. 2013.


Amarowicz R, Pegg RB and Bautista DA: Antibacterial activity of green tea polyphenols against escherichia coli K 12. Nahrung. 44:60–62. 2000.PubMed/NCBI


Butt MS, Nazir A, Sultan MT and Schoen K: Morus alba L.Nature's functioning tonic. Trends Food SciTechnol. 19:505–512. 2008.


Fukai T, Hano Y, Hirakura K, Nomura T, Uzawa J and Fukushima K: Structures of two natural hypotensive Diels-Alder type adducts, mulberrofuran F and G, from the cultivated mulberry tree (Morus lhou KOIDZ). Chem Pharm Bull (Tokyo). 33:3195–3204. 1985.PubMed/NCBI


Ueda S, Matsumoto J and Nomura T: Four new natural diels-alder type adducts, Mulberrofuran E, Kuwanon Q, R, and V from callus culture of Morus Alba, L. Chem Pharm Bull. 32:350–353. 1984.


Fukai T, Hano Y, Hirakura K, Nomura T and Uzawa J: Structure of mulberrofuran H, A Novel 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus lhou (Ser.) Koidz). Chem Pharm Bull. 32:808–811. 1984.


Chung KO, Kim BY, Lee MH, Kim YR, Chung HY, Park JH and Moon JO: In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from morus alba L. J Pharm Pharmacol. 55:1695–1700. 2003.PubMed/NCBI


Yang ZG, Matsuzaki K, Takamatsu S and Kitanaka S: Inhibitory effects of constituents from Morus alba var. multicaulis on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells. Molecules. 16:6010–6022. 2011.PubMed/NCBI


Kaur N, Xia Y, Jin Y, Dat NT, Gajulapati K, Choi Y, Hong YS, Lee JJ and Lee K: The first total synthesis of moracin O and moracin P, and establishment of the absolute configuration of moracin O. Chem Commun (Camb). 14:1879–1881. 2009.


Dat NT, Jin X, Lee K, Hong YS, Kim YH and Lee JJ: Hypoxia-inducible factor-1 inhibitory benzofurans and chalcone-derived diels-alder adducts from Morus species. J Nat Prod. 72:39–43. 2009.PubMed/NCBI


Xia Y, Jin Y, Kaur N, Choi Y and Lee K: HIF-1α inhib-itors: Synthesis and biological evaluation of novel moracin O and P analogs. Eur J Med Chem. 46:2386–2396. 2011.PubMed/NCBI


Khyade VB, Khyade VV, Khyade SV and Moser MB: Influence of Moracin on DMBA-TPA induced skin tumerigenesis in the mouse. Int J Bioassays. 3:3509–3516. 2014.


Baldwing AS Jr: The NF-kappaB and I kappa B proteins: New discoveries and insights. Annu Rev Immunol. 14:649–683. 1996.PubMed/NCBI


Pahl HL: Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 18:6853–6866. 1999.PubMed/NCBI


Harper N, Farrow SN, Kaptein A, Cohen GM and MacFarlane M: Modulation of tumor necrosis factor apoptosis-inducing ligand-induced NF-kappaB activation by inhibition of apical caspases. J Biol Chem. 276:34743–34752. 2001.PubMed/NCBI


Hu WH, Johnson H and Shu HB: Tumor necrosis factor-related apoptosis inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways. J Biol Chem. 274:30603–30610. 1999.PubMed/NCBI


Jeremias I and Debatin KM: TRAIL induces apoptosis and activation of NF-kappaB. Eur Cytokine Netw. 9:687–688. 1998.PubMed/NCBI


Keane MM, Rubinstein Y, Cuello M, Ettenberg SA, Banerjee P, Nau MM and Lipkowitz S: Inhibition of NF-kappaB activity enhances TRAIL mediated apoptosis in breast cancer cell lines. Breast Cancer Res Treat. 64:211–219. 2000.PubMed/NCBI


Kim YS, Schwabe RF, Qian T, Lemasters JJ and Brenner DA: TRAIL mediated apoptosis requires NF-kappaB inhibition and the mitochondrial permeability transition in human hepatoma cells. Hepatology. 36:1498–1508. 2002.PubMed/NCBI


Oya M, Ohtsubo M, Takayanagi A, Tachibana M, Shimizu N and Murai M: Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells. Oncogene. 20:3888–3896. 2001.PubMed/NCBI


Southall MD, Isenberg JS, Nakshatri H, Yi Q, Pei Y, Spandau DF and Travers JB: The platelet-activating factor receptor protects epidermal cells from tumor necrosis factor (TNF) alpha and TNF-related apoptosis-inducing ligand-induced apoptosis through an NF-kappa B-dependent process. J Biol Chem. 276:45548–45554. 2001.PubMed/NCBI


Wang P, Du B, Yin W, Wang X and Zhu W: Resveratrol attenuates CoCl2-induced cochlear hair cell damage through upregulation of sirtuin1 and NF-κB deacetylation. PLoS One. 8:e808542013.PubMed/NCBI

Related Articles

Journal Cover

Volume 22 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
Spandidos Publications style
Hardianti B, Umeyama L, Li F, Yokoyama S and Hayakawa Y: Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway. Mol Med Rep 22: 5385-5391, 2020
Hardianti, B., Umeyama, L., Li, F., Yokoyama, S., & Hayakawa, Y. (2020). Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway. Molecular Medicine Reports, 22, 5385-5391.
Hardianti, B., Umeyama, L., Li, F., Yokoyama, S., Hayakawa, Y."Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway". Molecular Medicine Reports 22.6 (2020): 5385-5391.
Hardianti, B., Umeyama, L., Li, F., Yokoyama, S., Hayakawa, Y."Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway". Molecular Medicine Reports 22, no. 6 (2020): 5385-5391.