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Research article
Inhibitory Effects of Compounds Isolated from Morinda citrifolia L. (Noni) Seeds against Particulate Matter-Induced Injury
1Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea
2Department of Integrative Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
3School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
4Research Institute of Tailored Food Technology, Kyungpook National University, Daegu 41566, Republic of Korea
J. Microbiol. Biotechnol. 2025. 35: e2407062
Published January 24, 2025 https://doi.org/10.4014/jmb.2407.07062
Copyright © The Korean Society for Microbiology and Biotechnology.
Abstract
Keywords
Graphical Abstract

Introduction
Besides, being a major issue for the global community, air pollution has affected the human immune system, causing chronic and acute respiratory disease, lung cancer, chronic bronchitis, and heart diseases. Especially, airborne particulate matter (PM) is one of the most important air pollutants. PM consists of particles characterized in coarse (PM10), fine (PM2.5), and ultrafine (PM0.1) for aerodynamic diameter smaller than 10, 2.5, and 0.1 μm, respectively [14]. On inhalation, PM10 is retained in the nasal cavities and upper airways, whereas PM2.5 and PM0.1 may penetrate deeper into the lung [15]. Fine PM has been widely reported to stimulate an inflammatory response in macrophages through activation of toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), and NF-κB signaling [16]. Additionally, airway chronic inflammation is related to structural changes in the airway wall and parenchyma. During inflammation, airway epithelial cells, as well as macrophages and neutrophils, release interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein (MCP)-1, which can cause airway damage [17]. Hence, inhaled PM easily affects the respiratory health, then may cause pulmonary, cardiovascular diseases, inflammation, and lung injury as well as diabetic symptoms [18]. In recent years, natural products have been rich sources of therapeutic agents for chronic inflammation including inflammatory responses related to PM-induced [19, 20]. Phenolic compounds are considered to alleviate PM-induced inflammatory reactions
In this study, our continued efforts to study anti-inflammatory compounds isolated from food products led to the isolation eight of compounds (1‒8) from noni seeds. Their chemical structures were elucidated based on extensive spectroscopic analysis as well as the comparison with those reported in the literature. The isolated lignans were then evaluated for their anti-inflammatory activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphynyltetrazolium bromide (MTT) assay in human bronchial epithelium BEAS-2B cells stimulated by 1-nitropyrene (1-NP).
Materials and Methods
General Experimental Procedures
Acetonitrile (ACN, reagent grade), water (H2O, reagent grade), and methanol (MeOH, reagent grade) were purchased from J.T.Baker (USA). Trifluoroacetic acid (TFA) was purchased from Sigma-Aldrich (USA). Organic solvents such as
Plant Material
The seeds of
Extraction and Isolation
The dried noni seeds (672.83 g) were ground and extracted with 10 L of CH2Cl2-MeOH (1:1, v/v) at room temperature. The extract was evaporated to dryness, resulting in a crude extract (88.51 g). The crude extract was then suspended in water and partitioned with
Vanillic acid (2) ‒ Light yellow powder; 1H NMR (500 MHz, methanol-
Caffeic acid (4) ‒ Yellow solid; 1H NMR (500 MHz, methanol-
Morindolin (5) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
-
Fig. 1. Isolation scheme of
M. citrifolia seeds.
(‒)-3,4,3',4'-Tetrahydroxy-9,7'
3,3'-Bisdemethylpinoresinol (7) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
Americanoic acid A (8) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
MTT Assay
BEAS-2B cells, human bronchial epithelium, were seeded (3 × 104 cells/ml) on a 96-well plate and allowed to reach 70-80% confluency [23]. The medium was changed with
Results and Discussion
Chemical Structure Identification of the Isolated Compounds
From the ethyl acetate soluble fraction, eight phenolics (1‒8) were isolated by efficient chromatographic separation techniques. Their chemical structures were elucidated as
-
Fig. 2. Chemical structures of compounds (1‒8) isolated from
M. citrifolia seeds.
Compound 1 was obtained as a white powder and exhibited a molecular ion peak at [M-H]-
Compound 2 was isolated as a light-yellow powder and revealed a molecular ion peak at [M-H]-
Compound 3 was obtained as a white solid and exhibited a molecular ion peak at [M-H]-
Compound 4 was obtained as a yellow solid and displayed a molecular ion peak at [M-H]-
Compound 5 was obtained as a pale-yellow amorphous powder and exhibited a molecular ion peak at [M-H]-
Compound 6 was obtained as a brown amorphous powder and revealed a molecular ion peak at [M-H]-
Compound 7 was collected as a pale-yellow amorphous powder and displayed a molecular ion peak at [M-H]-
Compound 8 was isolated as a pale-yellow amorphous powder and exhibited a molecular ion peak at [M-H]-
Effects of Isolated Lignans on PM2.5-Induced Lung Damage
Polycyclic aromatic hydrocarbons (PAHs), associated with the toxic substances absorbed on PM, mainly originate from incomplete combustion processes including biomass burning, coal combustion, and vehicle exhaust, and are ubiquitous environmental contaminants. PAHs could increase health risks to be higher than currently accepted due to the production of more toxic derivatives from a series of chemical reactions in the atmosphere [28]. 1-NP is an important subgroup of PAHs present in urban air pollutants and was reported to cause damage to BEAS-2B cells [29]. In addition, lignans are widely present in a range of plant kingdoms including edible plants and represent an enormous class of bioactive compounds [30, 31]. They are one of the common secondary metabolite classes in noni, distinguished depending on the pattern of additional bridging between two phenylpropanoid C6-C3 units at carbons
In the present study, to identify the bioactive components from noni seeds, the cytotoxicity of isolated lignans (5‒8) on BEAS-2B cells stimulated by 1-NP was evaluated. As results in Fig. 3, all the isolated lignans displayed cell viability percentages of over 60%. Among them, compound 5 showed the most effect with over 100% cell viability. Previous studies revealed that
-
Fig. 3. The effects of isolated lignans (5‒8) on cell viability. BEAS-2B cells were incubated to reach 70-80% confluency. Cell viability was determined using a MTT assay. The cells were pretreated for 1 h with isolated lignans and stimulated for 24 h with 1-NP. Bars represent means ± standard deviation of three independent experiments. ***
p < 0.001 compared with 1-NP-treated group.
To the best of our knowledge, the present work is the first investigation on the potential effects of noni lignans on PM2.5-induced lung injury until now. These results proved the potential effects on the anti-inflammatory activity of lignans isolated from noni seeds, thereby suggesting the promising role of noni seeds in the development of biomaterials and lignans are their active composites. Also, these findings provide the direction of research and application of the discarded noni seeds therefore alleviating pressure on industrial waste treatments in general and on the environment in particular.
Acknowledgments
This work was technically supported by Korea Basic Science Institute (National Research Facilities and Equipment center) funded by the Ministry of Education (2021R1A6C101A416). Authors (H.E., H.K., and H.Y.K.) were supported by Biological Materials-Specialized Graduate Program through Korea Environmental Industry & Technology Institute (KEITI) funded by the Ministry of Environment (MOE).
Funding
This study was carried out with the support of “Cooperative Research Program for Agriculture Science and Technology Development (project no. RS-2022-RD009982)” Rural Development Administration, Republic of Korea.
References
- Chan-Blanco Y, Vaillant F, Perez AM, Reynes M, Brillouet JM, Brat P. 2006. The noni fruit (
Morinda citrifolia L.): a review of agricultural research, nutritional and therapeutic properties.J. Food Compos. Anal. 19 : 645-654. - Bui AKT, Bacic A, Pettolino F. 2006. Polysaccharide composition of the fruit juice of
Morinda citrifolia (Noni).Phytochemistry 67 : 1271-1275. - Motshakeri M, Ghazali HM. 2015. Nutritional, phytochemical and commercial quality of noni fruit: a multi-beneficial gift from nature.
Trends Food Sci. Technol. 45 : 118-129. - Liu WJ, Chen YJ, Chen DN, Wu YP, Gao YJ, Li J,
et al . 2018. A new pair of enantiomeric lignans from the fruits ofMorinda citrifolia and their absolute configuration.Nat. Prod. Res. 32 : 933-938. - Dussossoy E, Brat P, Bony E, Boudard F, Poucheret P, Mertz C,
et al . 2011. Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.).J. Ethnopharmacol. 133 : 108-115. - Lee D, Yu JS, Huang P, Qader M, Manavalan A, Wu X,
et al . 2020. Identification of anti-inflammatory compounds from Hawaiian noni (Morinda citrifolia L.) fruit juice.Molecules 25 : 4968. - Sousa SG, Oliveira LA, Magalhães DA, Vieira de Brito T, Batista JA, Pereira CMC,
et al . 2018. Chemical structure and antiinflammatory effect of polysaccharide extracted fromMorinda citrifolia Linn (Noni).Carbohydr. Polym. 197 : 515-523. - Huang HL, Ko CH, Yan YY, Wang CK. 2014. Antiadhesion and anti-inflammation effects of noni (
Morinda citrifolia ) fruit extracts on AGS cells duringHelicobacter pylori infection.J. Agric. Food Chem. 62 : 2374-2383. - West BJ, Jensen CJ, Westendorf J. 2008. A new vegetable oil from noni (
Morinda citrifolia ) seeds.Int. J. Food Sci. 43 : 1988-1992. - Singh DR, Singh S. 2013. Phytochemicals in plant parts of noni (
Morinda citrifolia L.) with special reference to fatty acid profiles of seeds.Proc. Natl. Acad. Sci. India Sect. B Biol. Sci. 83 : 471-478. - Yang XL, Jiang MY, Hsieh KL, Liu JK. 2009. Chemical constituents from the seeds of
Morinda citrifolia .Chin. J. Nat. Med. 7 : 119-122. - Pazos DC, Jiménez FE, Garduño L, López VE, Cruz MC. 2011. Hypolipidemic effect of seed oil of noni (
Morinda citrifolia ).Nat. Prod. Commun. 6 : 1005-1008. - Campos DCO, Costa AS, Lima ADR, Silva FDA, Lobo MDP, Monteiro-Moreira ACO,
et al . 2016. First isolation and antinociceptive activity of a lipid transfer protein from noni (Morinda citrifolia ) seeds.Int. J. Biol. Macromol. 86 : 71-79. - Kampa M, Castanas E. 2008. Human health effects of air pollution.
Environ. Pollut. 151 : 362-367. - Mannucci PM, Harari S, Martinelli I, Franchini M. 2015. Effects on health of air pollution: a narrative review.
Intern. Emerg. Med. 10 : 657-662. - Fu H, Liu X, Li W, Zu Y, Zhou F, Shou Q,
et al . 2020. PM2.5 exposure induces inflammatory response in macrophagesvia the TLR4/COX-2/NF-κB pathway.Inflammation 43 : 1948-1958. - Zhang P, Mak JCW, Man RYK, Leung SWS. 2019. Flavonoids reduces lipopolysaccharide-induced release of inflammatory mediators in human bronchial epithelial cells: structure-activity relationship.
Eur. J. Pharmcol. 865 : 172731. - Lee J, Ree J, Kim HJ, Kim HJ, Kim WJ, Choi TG,
et al . 2022. Anti-apoptotic and anti-inflammatory effects of an ethanolic extract ofLycium chinense root against particulate matter 10-induced cell death and inflammation in RBL-2H3 basophil cells and BALB/c mice.Plants 11 : 2485. - Cao TQ, Phong NV, Kim JH, Gao D, Anh HLT, Ngo VD,
et al . 2021. Inhibitory effects of cucurbitane-type triterpenoids fromMomordica charantia fruit on lipopolysaccharide-stimulated pro-inflammatory cytokine production in bone marrow-derived dendrictic cells.Molecules 26 : 4444. - Diao P, He H, Tang J. 2021. Natural compounds protect the skin from airborn particulate matter by attenuating oxidative stress.
Biomed. Pharmacother. 138 : 111534. - Lee W, Hahn D, Sim H, Choo S, Lee S, Lee T,
et al . 2020. Inhibitory functions of cardamonin against particulate matter-induced lung injury through TLR-2,4-mTOR-autophagy pathways.Fitoterapia 146 : 104724. - Lee W, Jeong SY, Gu MJ, Lim JS, Park EK, Baek MC,
et al . 2019. Inhibitory effects of compounds isolated fromDioscorea batatas Decne peel on particulate matter-induced pulmonary injury in mice.J. Toxicol. Environ. Health Part A. 82 : 727-740. - Han X, Na T, Wu T, Yuan BZ. 2020. Human lung epithelial BEAS-2B cells exhibit characteristics of mesenchymal stem cells.
PLoS One 15 : e0227174. - Cho JY, Moon JH, Seong KY, Park KH. 1998. Antimicrobial activity of 4-hydroxybenzoic acid and
trans 4-hydroxycinamic acid isolated and identified from rice hull.Biosci. Biotechnol. Biochem. 62 : 2273-2276. - López-Martínez LM, Santacruz-Ortega H, Navarro RE, Sotelo-Mundo RR, González-Aguilar GA. 2015. A 1H NMR investigation of the interaction between phenolic acids found in mango (
Manguifera indica cv Ataulfo ) and papaya (Carica papaya cv Maradol ) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals.PLoS One 10 : e0140242. - Kamiya K, Tanaka Y, Endang H, Umar M, Satake T. 2004. Chemical constituents of
Morinda citrifolia fruits inhibit copper-induced low-density lipoprotein oxidation.J. Agric. Food Chem. 52 : 5843-5848. - Nguyen PH, Yang JL, Uddin MN, Park SL, Lim SI, Jung DW,
et al . 2013. Protein tyrosine phosphatase 1B (PTP1B) inhibitors fromMorinda citrifolia (Noni) and their insulin mimetic activity.J. Nat. Prod. 76 : 2080-2087. - Ma Y, Cheng Y, Qiu X, Lin Y, Cao J, Hu D. 2016. A quantitative assessment of source contributions to fine particulate matter (PM2.5)-bound polycyclic aromatic hydrocarbons (PAHs) and their nitrated and hydroxylated derivatives in Hong Kong.
Environ. Pollut. 219 : 742-749. - Park EJ, Park K. 2009. Induction of pro-inflammatory signals by 1-nitropyrene in cultured BEAS-2B cells.
Toxicol. Lett. 184 : 126-133. - Rodríguez-García C, Sánchez-Quesada C, Toledo E, Delgado-Rodríguez M, J.Gaforio J. 2019. Naturally lignan-rich foods: a dietary tool for health promotion?
Molecules 27 : 917. - Durazzo A, Lucarini M, Camilli E, Marconi S, Gabrielli P, Lisciani S,
et al . 2018. Dietary lignans: definition, description and research trends in databases development.Molecules 23 : 3251. - Cao TQ, Vu NK, Woo MH, Min BS. 2020. New polyacetylene and other compounds from
Bupleurum chinense and their chemotaxonomic significance.Biochem. Syst. Ecol. 92 : 104090. - Han HJ, Li M, Son JK, Seo CS, Song SW, Kwak SH,
et al . 2013. Sauchinone, a lignan fromSaururus chinensis , attenuates neutrophil pro-inflammatory activity and acute lung injury.Int. Immunopharmacol. 17 : 471-477. - Lee SU, Ryu HW, Lee S, Shin IS, Choi JH, Lee JW,
et al . 2018. Lignans isolated from flower buds ofMagnolia fargesii attenuate airway inflammation induced by cigarette smokein vitro andin vivo .Front. Pharmacol. 9 : 970. - Ren J, Li X, Zhu S, Yin B, Guo Z, Cui Q,
et al . 2022. Sesamin ameliorates fine particulate matter (PM2.5)-induced lung injuryvia suppression of apoptosis and autophagy in rats.J .Agric. Food Chem. 70 : 9489-9498. - West BJ, Deng S, Jensen CJ. 2020. Lignans from
Morinda citrifolia (Noni) fruit inhibit fatty acid amide hydrolase and monoacylglycerol lipase in vitro.J. Biosci. Med. 8 : 143-152. - Kim JW, Yang H, Kim HW, Kim HP, Sung SH. 2017. Lignans from
Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.Biosci. Biotechnol. Biochem. 81 : 181-183. - Masuda M, Itoh K, Murata K, Naruto S, Uwaya A, Isami F,
et al . 2012. Inhibitory effects ofMorinda citrifolia extract and its constituents on melanogenesis in murine B16 melanoma cells.Biol. Pharm. Bull. 35 : 78-83. - Chen G, Zhao W, Li Y, Zhou D, Ding J, Lin B,
et al . 2020. Bioactive chemical constituents from the seed testa ofVernicia fordii as potential neuroinflammatory inhibitors.Phytochemistry 171 : 112233.
Related articles in JMB

Article
Research article
J. Microbiol. Biotechnol. 2025; 35():
Published online January 24, 2025 https://doi.org/10.4014/jmb.2407.07062
Copyright © The Korean Society for Microbiology and Biotechnology.
Inhibitory Effects of Compounds Isolated from Morinda citrifolia L. (Noni) Seeds against Particulate Matter-Induced Injury
Thao Quyen Cao1†, Hyeongjin Eom2†, Hyukjin Kim2, Ha Yeong Kang3, Young Min Park4, Sung Keun Jung3,4*, and Dongyup Hahn1,2,3,4*
1Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea
2Department of Integrative Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
3School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
4Research Institute of Tailored Food Technology, Kyungpook National University, Daegu 41566, Republic of Korea
Correspondence to:Sung Keun Jung, skjung04@knu.ac.kr
Dongyup Hahn, dohahn@knu.ac.kr
†These authors contributed equally to this work.
Abstract
Morinda citrifolia L. (noni) is native to the tropical and semitropical areas and has been commercially available in health food stores and chain grocery stores specializing in natural foods, recently. Noni seeds are discarded as waste products through the industrial production of noni juice even though their bioactivity components might be a potential source of functional foods. Not many studies of phytochemistry and biological activity have been investigated on noni seeds until now. In this study, the phytochemical investigation of M. citrifolia seeds led to the isolation of eight compounds (1-8) including four lignans (5-8). Their chemical structures were elucidated based on extensive spectroscopic analysis as well as the comparison with those reported in the literature. The isolated lignans were then evaluated for their anti-inflammatory activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphynyltetrazolium bromide (MTT) assay in human bronchial epithelium BEAS-2B cells stimulated by 1-nitropyrene. As results, both four isolated lignans displayed high effects on the viability of BEAS-2B cells, indicating promising anti-inflammatory role in the airway disease.
Keywords: Morinda citrifolia, noni, inflammation, particulate matter, lignans, BEAS-2B cells
Introduction
Besides, being a major issue for the global community, air pollution has affected the human immune system, causing chronic and acute respiratory disease, lung cancer, chronic bronchitis, and heart diseases. Especially, airborne particulate matter (PM) is one of the most important air pollutants. PM consists of particles characterized in coarse (PM10), fine (PM2.5), and ultrafine (PM0.1) for aerodynamic diameter smaller than 10, 2.5, and 0.1 μm, respectively [14]. On inhalation, PM10 is retained in the nasal cavities and upper airways, whereas PM2.5 and PM0.1 may penetrate deeper into the lung [15]. Fine PM has been widely reported to stimulate an inflammatory response in macrophages through activation of toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), and NF-κB signaling [16]. Additionally, airway chronic inflammation is related to structural changes in the airway wall and parenchyma. During inflammation, airway epithelial cells, as well as macrophages and neutrophils, release interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein (MCP)-1, which can cause airway damage [17]. Hence, inhaled PM easily affects the respiratory health, then may cause pulmonary, cardiovascular diseases, inflammation, and lung injury as well as diabetic symptoms [18]. In recent years, natural products have been rich sources of therapeutic agents for chronic inflammation including inflammatory responses related to PM-induced [19, 20]. Phenolic compounds are considered to alleviate PM-induced inflammatory reactions
In this study, our continued efforts to study anti-inflammatory compounds isolated from food products led to the isolation eight of compounds (1‒8) from noni seeds. Their chemical structures were elucidated based on extensive spectroscopic analysis as well as the comparison with those reported in the literature. The isolated lignans were then evaluated for their anti-inflammatory activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphynyltetrazolium bromide (MTT) assay in human bronchial epithelium BEAS-2B cells stimulated by 1-nitropyrene (1-NP).
Materials and Methods
General Experimental Procedures
Acetonitrile (ACN, reagent grade), water (H2O, reagent grade), and methanol (MeOH, reagent grade) were purchased from J.T.Baker (USA). Trifluoroacetic acid (TFA) was purchased from Sigma-Aldrich (USA). Organic solvents such as
Plant Material
The seeds of
Extraction and Isolation
The dried noni seeds (672.83 g) were ground and extracted with 10 L of CH2Cl2-MeOH (1:1, v/v) at room temperature. The extract was evaporated to dryness, resulting in a crude extract (88.51 g). The crude extract was then suspended in water and partitioned with
Vanillic acid (2) ‒ Light yellow powder; 1H NMR (500 MHz, methanol-
Caffeic acid (4) ‒ Yellow solid; 1H NMR (500 MHz, methanol-
Morindolin (5) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
-
Figure 1. Isolation scheme of
M. citrifolia seeds.
(‒)-3,4,3',4'-Tetrahydroxy-9,7'
3,3'-Bisdemethylpinoresinol (7) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
Americanoic acid A (8) ‒ Pale yellow amorphous powder; 1H NMR (500 MHz, methanol-
MTT Assay
BEAS-2B cells, human bronchial epithelium, were seeded (3 × 104 cells/ml) on a 96-well plate and allowed to reach 70-80% confluency [23]. The medium was changed with
Results and Discussion
Chemical Structure Identification of the Isolated Compounds
From the ethyl acetate soluble fraction, eight phenolics (1‒8) were isolated by efficient chromatographic separation techniques. Their chemical structures were elucidated as
-
Figure 2. Chemical structures of compounds (1‒8) isolated from
M. citrifolia seeds.
Compound 1 was obtained as a white powder and exhibited a molecular ion peak at [M-H]-
Compound 2 was isolated as a light-yellow powder and revealed a molecular ion peak at [M-H]-
Compound 3 was obtained as a white solid and exhibited a molecular ion peak at [M-H]-
Compound 4 was obtained as a yellow solid and displayed a molecular ion peak at [M-H]-
Compound 5 was obtained as a pale-yellow amorphous powder and exhibited a molecular ion peak at [M-H]-
Compound 6 was obtained as a brown amorphous powder and revealed a molecular ion peak at [M-H]-
Compound 7 was collected as a pale-yellow amorphous powder and displayed a molecular ion peak at [M-H]-
Compound 8 was isolated as a pale-yellow amorphous powder and exhibited a molecular ion peak at [M-H]-
Effects of Isolated Lignans on PM2.5-Induced Lung Damage
Polycyclic aromatic hydrocarbons (PAHs), associated with the toxic substances absorbed on PM, mainly originate from incomplete combustion processes including biomass burning, coal combustion, and vehicle exhaust, and are ubiquitous environmental contaminants. PAHs could increase health risks to be higher than currently accepted due to the production of more toxic derivatives from a series of chemical reactions in the atmosphere [28]. 1-NP is an important subgroup of PAHs present in urban air pollutants and was reported to cause damage to BEAS-2B cells [29]. In addition, lignans are widely present in a range of plant kingdoms including edible plants and represent an enormous class of bioactive compounds [30, 31]. They are one of the common secondary metabolite classes in noni, distinguished depending on the pattern of additional bridging between two phenylpropanoid C6-C3 units at carbons
In the present study, to identify the bioactive components from noni seeds, the cytotoxicity of isolated lignans (5‒8) on BEAS-2B cells stimulated by 1-NP was evaluated. As results in Fig. 3, all the isolated lignans displayed cell viability percentages of over 60%. Among them, compound 5 showed the most effect with over 100% cell viability. Previous studies revealed that
-
Figure 3. The effects of isolated lignans (5‒8) on cell viability. BEAS-2B cells were incubated to reach 70-80% confluency. Cell viability was determined using a MTT assay. The cells were pretreated for 1 h with isolated lignans and stimulated for 24 h with 1-NP. Bars represent means ± standard deviation of three independent experiments. ***
p < 0.001 compared with 1-NP-treated group.
To the best of our knowledge, the present work is the first investigation on the potential effects of noni lignans on PM2.5-induced lung injury until now. These results proved the potential effects on the anti-inflammatory activity of lignans isolated from noni seeds, thereby suggesting the promising role of noni seeds in the development of biomaterials and lignans are their active composites. Also, these findings provide the direction of research and application of the discarded noni seeds therefore alleviating pressure on industrial waste treatments in general and on the environment in particular.
Acknowledgments
This work was technically supported by Korea Basic Science Institute (National Research Facilities and Equipment center) funded by the Ministry of Education (2021R1A6C101A416). Authors (H.E., H.K., and H.Y.K.) were supported by Biological Materials-Specialized Graduate Program through Korea Environmental Industry & Technology Institute (KEITI) funded by the Ministry of Environment (MOE).
Funding
This study was carried out with the support of “Cooperative Research Program for Agriculture Science and Technology Development (project no. RS-2022-RD009982)” Rural Development Administration, Republic of Korea.
Fig 1.

Fig 2.

Fig 3.

References
- Chan-Blanco Y, Vaillant F, Perez AM, Reynes M, Brillouet JM, Brat P. 2006. The noni fruit (
Morinda citrifolia L.): a review of agricultural research, nutritional and therapeutic properties.J. Food Compos. Anal. 19 : 645-654. - Bui AKT, Bacic A, Pettolino F. 2006. Polysaccharide composition of the fruit juice of
Morinda citrifolia (Noni).Phytochemistry 67 : 1271-1275. - Motshakeri M, Ghazali HM. 2015. Nutritional, phytochemical and commercial quality of noni fruit: a multi-beneficial gift from nature.
Trends Food Sci. Technol. 45 : 118-129. - Liu WJ, Chen YJ, Chen DN, Wu YP, Gao YJ, Li J,
et al . 2018. A new pair of enantiomeric lignans from the fruits ofMorinda citrifolia and their absolute configuration.Nat. Prod. Res. 32 : 933-938. - Dussossoy E, Brat P, Bony E, Boudard F, Poucheret P, Mertz C,
et al . 2011. Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.).J. Ethnopharmacol. 133 : 108-115. - Lee D, Yu JS, Huang P, Qader M, Manavalan A, Wu X,
et al . 2020. Identification of anti-inflammatory compounds from Hawaiian noni (Morinda citrifolia L.) fruit juice.Molecules 25 : 4968. - Sousa SG, Oliveira LA, Magalhães DA, Vieira de Brito T, Batista JA, Pereira CMC,
et al . 2018. Chemical structure and antiinflammatory effect of polysaccharide extracted fromMorinda citrifolia Linn (Noni).Carbohydr. Polym. 197 : 515-523. - Huang HL, Ko CH, Yan YY, Wang CK. 2014. Antiadhesion and anti-inflammation effects of noni (
Morinda citrifolia ) fruit extracts on AGS cells duringHelicobacter pylori infection.J. Agric. Food Chem. 62 : 2374-2383. - West BJ, Jensen CJ, Westendorf J. 2008. A new vegetable oil from noni (
Morinda citrifolia ) seeds.Int. J. Food Sci. 43 : 1988-1992. - Singh DR, Singh S. 2013. Phytochemicals in plant parts of noni (
Morinda citrifolia L.) with special reference to fatty acid profiles of seeds.Proc. Natl. Acad. Sci. India Sect. B Biol. Sci. 83 : 471-478. - Yang XL, Jiang MY, Hsieh KL, Liu JK. 2009. Chemical constituents from the seeds of
Morinda citrifolia .Chin. J. Nat. Med. 7 : 119-122. - Pazos DC, Jiménez FE, Garduño L, López VE, Cruz MC. 2011. Hypolipidemic effect of seed oil of noni (
Morinda citrifolia ).Nat. Prod. Commun. 6 : 1005-1008. - Campos DCO, Costa AS, Lima ADR, Silva FDA, Lobo MDP, Monteiro-Moreira ACO,
et al . 2016. First isolation and antinociceptive activity of a lipid transfer protein from noni (Morinda citrifolia ) seeds.Int. J. Biol. Macromol. 86 : 71-79. - Kampa M, Castanas E. 2008. Human health effects of air pollution.
Environ. Pollut. 151 : 362-367. - Mannucci PM, Harari S, Martinelli I, Franchini M. 2015. Effects on health of air pollution: a narrative review.
Intern. Emerg. Med. 10 : 657-662. - Fu H, Liu X, Li W, Zu Y, Zhou F, Shou Q,
et al . 2020. PM2.5 exposure induces inflammatory response in macrophagesvia the TLR4/COX-2/NF-κB pathway.Inflammation 43 : 1948-1958. - Zhang P, Mak JCW, Man RYK, Leung SWS. 2019. Flavonoids reduces lipopolysaccharide-induced release of inflammatory mediators in human bronchial epithelial cells: structure-activity relationship.
Eur. J. Pharmcol. 865 : 172731. - Lee J, Ree J, Kim HJ, Kim HJ, Kim WJ, Choi TG,
et al . 2022. Anti-apoptotic and anti-inflammatory effects of an ethanolic extract ofLycium chinense root against particulate matter 10-induced cell death and inflammation in RBL-2H3 basophil cells and BALB/c mice.Plants 11 : 2485. - Cao TQ, Phong NV, Kim JH, Gao D, Anh HLT, Ngo VD,
et al . 2021. Inhibitory effects of cucurbitane-type triterpenoids fromMomordica charantia fruit on lipopolysaccharide-stimulated pro-inflammatory cytokine production in bone marrow-derived dendrictic cells.Molecules 26 : 4444. - Diao P, He H, Tang J. 2021. Natural compounds protect the skin from airborn particulate matter by attenuating oxidative stress.
Biomed. Pharmacother. 138 : 111534. - Lee W, Hahn D, Sim H, Choo S, Lee S, Lee T,
et al . 2020. Inhibitory functions of cardamonin against particulate matter-induced lung injury through TLR-2,4-mTOR-autophagy pathways.Fitoterapia 146 : 104724. - Lee W, Jeong SY, Gu MJ, Lim JS, Park EK, Baek MC,
et al . 2019. Inhibitory effects of compounds isolated fromDioscorea batatas Decne peel on particulate matter-induced pulmonary injury in mice.J. Toxicol. Environ. Health Part A. 82 : 727-740. - Han X, Na T, Wu T, Yuan BZ. 2020. Human lung epithelial BEAS-2B cells exhibit characteristics of mesenchymal stem cells.
PLoS One 15 : e0227174. - Cho JY, Moon JH, Seong KY, Park KH. 1998. Antimicrobial activity of 4-hydroxybenzoic acid and
trans 4-hydroxycinamic acid isolated and identified from rice hull.Biosci. Biotechnol. Biochem. 62 : 2273-2276. - López-Martínez LM, Santacruz-Ortega H, Navarro RE, Sotelo-Mundo RR, González-Aguilar GA. 2015. A 1H NMR investigation of the interaction between phenolic acids found in mango (
Manguifera indica cv Ataulfo ) and papaya (Carica papaya cv Maradol ) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals.PLoS One 10 : e0140242. - Kamiya K, Tanaka Y, Endang H, Umar M, Satake T. 2004. Chemical constituents of
Morinda citrifolia fruits inhibit copper-induced low-density lipoprotein oxidation.J. Agric. Food Chem. 52 : 5843-5848. - Nguyen PH, Yang JL, Uddin MN, Park SL, Lim SI, Jung DW,
et al . 2013. Protein tyrosine phosphatase 1B (PTP1B) inhibitors fromMorinda citrifolia (Noni) and their insulin mimetic activity.J. Nat. Prod. 76 : 2080-2087. - Ma Y, Cheng Y, Qiu X, Lin Y, Cao J, Hu D. 2016. A quantitative assessment of source contributions to fine particulate matter (PM2.5)-bound polycyclic aromatic hydrocarbons (PAHs) and their nitrated and hydroxylated derivatives in Hong Kong.
Environ. Pollut. 219 : 742-749. - Park EJ, Park K. 2009. Induction of pro-inflammatory signals by 1-nitropyrene in cultured BEAS-2B cells.
Toxicol. Lett. 184 : 126-133. - Rodríguez-García C, Sánchez-Quesada C, Toledo E, Delgado-Rodríguez M, J.Gaforio J. 2019. Naturally lignan-rich foods: a dietary tool for health promotion?
Molecules 27 : 917. - Durazzo A, Lucarini M, Camilli E, Marconi S, Gabrielli P, Lisciani S,
et al . 2018. Dietary lignans: definition, description and research trends in databases development.Molecules 23 : 3251. - Cao TQ, Vu NK, Woo MH, Min BS. 2020. New polyacetylene and other compounds from
Bupleurum chinense and their chemotaxonomic significance.Biochem. Syst. Ecol. 92 : 104090. - Han HJ, Li M, Son JK, Seo CS, Song SW, Kwak SH,
et al . 2013. Sauchinone, a lignan fromSaururus chinensis , attenuates neutrophil pro-inflammatory activity and acute lung injury.Int. Immunopharmacol. 17 : 471-477. - Lee SU, Ryu HW, Lee S, Shin IS, Choi JH, Lee JW,
et al . 2018. Lignans isolated from flower buds ofMagnolia fargesii attenuate airway inflammation induced by cigarette smokein vitro andin vivo .Front. Pharmacol. 9 : 970. - Ren J, Li X, Zhu S, Yin B, Guo Z, Cui Q,
et al . 2022. Sesamin ameliorates fine particulate matter (PM2.5)-induced lung injuryvia suppression of apoptosis and autophagy in rats.J .Agric. Food Chem. 70 : 9489-9498. - West BJ, Deng S, Jensen CJ. 2020. Lignans from
Morinda citrifolia (Noni) fruit inhibit fatty acid amide hydrolase and monoacylglycerol lipase in vitro.J. Biosci. Med. 8 : 143-152. - Kim JW, Yang H, Kim HW, Kim HP, Sung SH. 2017. Lignans from
Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.Biosci. Biotechnol. Biochem. 81 : 181-183. - Masuda M, Itoh K, Murata K, Naruto S, Uwaya A, Isami F,
et al . 2012. Inhibitory effects ofMorinda citrifolia extract and its constituents on melanogenesis in murine B16 melanoma cells.Biol. Pharm. Bull. 35 : 78-83. - Chen G, Zhao W, Li Y, Zhou D, Ding J, Lin B,
et al . 2020. Bioactive chemical constituents from the seed testa ofVernicia fordii as potential neuroinflammatory inhibitors.Phytochemistry 171 : 112233.