• Title/Summary/Keyword: tumor necrosis factor alpha

Search Result 1,714, Processing Time 0.03 seconds

Anti-Atopic Effects of Mixed Extracts from Date Plum, Persimmon, and Mulberry Leaves (고욤잎, 감잎 및 뽕잎 복합추출물의 항아토피 효과)

  • Cho, Byoung Ok;Yin, Hong Hua;Shin, Jae Young;Fang, Chong Zhou;Chang, Che Denis;Jang, Seon Il
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.45 no.4
    • /
    • pp.501-509
    • /
    • 2016
  • The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor $(TNF)-{\alpha}$ and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, $TNF-{\alpha}$, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

Anticancer and Immune-modulatory Activities of Extracts from Various Parts of Cornus macrophylla Wall. (곰의말채 부위별 추출물의 항암 및 면역증진 효과)

  • Jin, Ling;Han, Jae-Gun;Ha, Ji-Hye;Jeong, Hyang-Suk;Kim, Cheol-Hee;Kwon, Min-Chul;Lee, Hak-Ju;Kang, Ha-Young;Choi, Geun-Pyo;Lee, Yong-Hyeon
    • Korean Journal of Medicinal Crop Science
    • /
    • v.16 no.5
    • /
    • pp.349-355
    • /
    • 2008
  • Anticancer and immuno-modulatory activities of methanol extracts from different parts, bark, wood and leaf, of Cornus macrophylla Wall. were investigated in this study. All extracts at a concentration of 1.0mg/ml showed relativity low cytotoxicities on human normal kidney cell (HEK293) by approximately 25%. Bark extract of C. macrophylla showed the highest anticancer activity on human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) by 57.4% and 58.7%, respectively, at a concentration of 1.0mg/ml. All extracts enhanced the growth of human B and T cells, showing 38.7% and 65.9% increase compared to control, respectively, by 5 days incubation with bark extract. The secretions of interleukin 6 (IL6) and tumor necrosis factor alpha (TNF-$\alpha$) from human B and T cells were significantly increased by extracts, especially bark extract. B or T cell medium, which contains cytokines (IL 6 and TNF-$\alpha$) secreted by bark extract treatment for 5 days, time-dependently enhanced the growth of NK-92MI cells with the maximal effect at 5th day of incubation. These results suggest that C. macrophylla, especially bark, has the potential for anticancer and immuno-modulatory activities.

The Effect of Hydrogen Peroxide on Inducible Nitric Oxide Synthase Expression in Murine Macrophage RA W264.7 Cells (Murine macrophage RAW264.7에서 과산화수소가 유발형 산화질소 합성효소의 발현에 미치는 영향)

  • Ahn, Joong-Hyun;Song, Jeong-Sup
    • Tuberculosis and Respiratory Diseases
    • /
    • v.47 no.2
    • /
    • pp.172-183
    • /
    • 1999
  • Background: Nitric oxide is a short-lived effector molecule derived from L-arginine by the nitric oxide synthase(NOS). Nitric oxide plays a role in a number of physiologic and pathophysiologic functions including host defense, edema formation, and regulation of smooth muscle tone. Some kinds of cells including macrophage are known to produce large quantities of nitric oxide in response to inflammatory stimuli such as interleukin-$1\beta$(IL-$1\beta$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), interferon-$\gamma$(IFN-$\gamma$) and lipopolysaccharide(LPS). Reactive oxygen species are also known to be important in the pathogenesis of acute cell and tissue injury such as acute lung injury model Methods: Using the RA W264.7 cells, we have examined the ability of oxidant hydrogen peroxide($H_2O_2$) to stimulate nitric oxide production and inducible NOS mRNA expression. Also, we have examined the effects of NOS inhibitors and antioxidants on $H_2O_2$ induced nitric oxide production. Results: Stimulation of RAW264.7 cells with combinations of 100 ng/ml IL-$1\beta$, 100 ng/ml TNF-$\alpha$, and 100 U/ml IFN-$\gamma$ or 100 U/ml IFN-$\gamma$ and $1{\mu}g/ml$ LPS induced the synthesis of nitric oxide as measured by the oxidation products nitrite($NO_2^-$) and nitrate($NO_3^-$). Addition of $250 {\mu}M-2$ mM $H_2O_2$ to the cytokines significantly augmented the synthesis of $NO_2^-$ and $NO_3^-$(p<0.05). When cells were incubated with increasing concentrations of $H_2O_2$ in the presence of IL-$1\beta$, TNF-$\alpha$ and IFN-$\gamma$ at constant level, the synthesis of $NO_2^-$ and $NO_3^-$ was dose-dependently increased(p<0.05). $N^G$-nitro-L-arginine methyl ester(L-NAME), dose dependently, significantly inhibited the formation of $NO_2^-$ and $NO_3^-$ in cells stimulated with LPS, IFN-$\gamma$ and $H_2O_2$ at constant level(p<0.05). Catalase significantly inhibited the $H_2O_2$-induced augmentation of cytokine-induced $NO_2^-$ and $NO_3^-$ formation(p<0.05). But, boiled catalase did not produce a significant inhibition in comparison with the native enzyme. Another antioxidant 2-mercaptoethanol and orthophenanthroline dose-dependently suppressed $NO_2^-$ and $NO_3^-$ synthesis(p<0.05). Northern blotting demonstrated that H:02 synergistically stimulated the cytokine-induced iNOS mRNA expression in RA W264.7. Conclusion: These results suggest that $H_2O_2$ contributes to inflammatory process by augmenting the iNOS expression and nitric oxide synthesis induced by cytokines.

  • PDF

A Study on Pulmonary Toxic Effect of High-Dose Cisplatin Administered by Isolated Lung Perfusion in Dogs (잡견에서 분리폐관류 방법으로 투여된 고농도 cisplatin의 페독성에 관한 연구)

  • 김관민;한정호;김주현
    • Journal of Chest Surgery
    • /
    • v.33 no.9
    • /
    • pp.697-706
    • /
    • 2000
  • Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

  • PDF

Anti-inflammatory Effect of Oxya chinensis sinuosa Ethanol Extract in LPS-induced RAW 264.7 Cells (LPS로 유도된 RAW 264.7세포에 대한 벼메뚜기(Oxya chinensis sinuosa) 에탄올 추출물의 항염증 효과)

  • Yoon, Young-Il;Chung, Mi Yeon;Hwang, Jae-Sam;Goo, Tae-Won;Ahn, Mi-Young;Lee, Young-Bo;Han, Myung-Sea;Yun, Eun-Young
    • Journal of Life Science
    • /
    • v.24 no.4
    • /
    • pp.370-376
    • /
    • 2014
  • Although the grasshopper Oxya chinensis sinuosa has long been used as food in Korea, there is little data on its functional effects. In this study, we investigated the anti-inflammatory effect of O. c. sinuosa ethanol extract (OCE) in RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for induction of inflammation. First, we determined that there is no cytotoxicity at $2,000{\mu}g/ml$ or less of OCE in RAW 264.7 cells. To evaluate the anti-inflammatory effects of OCE, we investigated expression levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, and pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether OCE could inhibit translocation of NF-${\kappa}B$ p65 into the nucleus in LPS induced RAW 264.7 cells. As a result, we found that the mRNA and protein levels of TNF-${\alpha}$ and IL-6 decreased in LPS-induced RAW 264.7 cells after treatment with OCE in a dose-dependent manner. In addition, we confirmed a $2,000{\mu}g/ml$ concentration of OCE inhibited translocation of NF-${\kappa}B$ p65 by immunnostaining and Western blot analysis, and a decrease in the protein expression levels of iNOS and COX-2. Accordingly, we suppose that OCE has an anti-inflammatory effect through down-regulation of TNF-${\alpha}$, IL-6, iNOS, and COX-2 related to ${\kappa}B$ p65 inflammatory signaling pathways.

Anti-inflammatory Activity of an Ethanol Extract of Laminaria japonica Root on Lipopolysaccharide-induced Inflammatory Responses in RAW 264.7 Cells (Lipopolysaccharide로 유도된 RAW 264.7 세포에서 다시마 뿌리 에탄올 추출물의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Ahn, Na-Kyung;Choi, Yeon-Uk;Ahn, Dong-Hyun
    • Korean Journal of Food Science and Technology
    • /
    • v.46 no.6
    • /
    • pp.729-733
    • /
    • 2014
  • Laminaria japonica roots have not been used practically in Korea. In this study, in order to promote the use of these by-products, the anti-inflammatory activity of an ethanol extract of Laminaria japonica root (LJREE) was investigated using a lipopolysaccharide (LPS) to induce an inflammatory response in RAW 264.7 cells. To examine the potential anti-inflammatory effects of LJREE, levels of nitric oxide (NO) and pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interleukin-$1{\beta}$ (IL-$1{\beta}$), and cell proliferation were measured. We found that NO levels decreased in a dose-dependent manner, the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed, and the production of IL-$1{\beta}$ was inhibited over 30% after treatment with $100{\mu}g/mL$ LJREE. In conclusion, the proliferation of RAW 264.7 cells, measured by MTT assay, confirmed that LJREE may have significant effects on inflammatory factors without any cytotoxicity, making it a potential anti-inflammatory agent.

Screening of immune enhancing activities in medicinal herbs, Compositae (국화과 약용 식물의 면역증진활성 검색)

  • Lee, Mi-Kyoung;Moon, Hyoung-Chol;Lee, Jin-Ha;Kim, Jong-Dai;Yu, Chang-Yeon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.10 no.1
    • /
    • pp.51-57
    • /
    • 2002
  • The biological activities of immune modulating activities of the extracts from Echinacea purpurea, Chrysanthmum indicum L. and Circium japonicum var. ussuriense KITAMURA were compared. About 70% of the growth of human hepatocarcinoma and 80% of human gastric cancer cell was inhibited in adding 0.5mg/ml of the ethanol extracts of Echinacea purpurea, Chrysanthmum indicum L. and Circium japonicum var. ussuriense KITAMURA, respectively. The growth of human breast cancer cells was also inhibited in adding 0.5mg/ml of the extracts as well as 60% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 3, which is higher than those from the conventional herbs. The growth of both human immune B and T cells was enhanced up to 1.4 to 2.0 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 94 pg/ml in adding the Echinacea purpurea ethanol extract (0.5mg/ml). Circium japonicum var. ethanol extract also increased up to about 96 pg/ml of interleukin-6(IL-6) from B cell.

In Vitro Anti-bacterial and Anti-inflammatory Effects of Six Types of Herb Aqueous Extracts (일부 살충해독유(殺蟲解毒類) 한약의 Staphylococcus aureus에 대한 시험관 내 항균 및 항염 효과)

  • Jang, Se-Ran;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
    • /
    • v.27 no.1
    • /
    • pp.81-100
    • /
    • 2014
  • Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of six single aqueous herbal extracts-Quisqualis Fructus (QuF), Meliae Cortex (MeC), Arecae Semen (ArS), Crassirhizomae Rhizoma (CrR), Ulmi Pasta Semen(UlS), Torreyae Semen(ToS)- against Staphylococcus aureus (S. aureus) and Lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities against S. aureus of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS were detected using standard agar microdilution methods. In addition, the effects on the cell viability, prostaglandin $E_2$ ($PGE_2$), nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells were detected. The anti-bacterial and anti-inflammatory effects were respectively compared with lincomycin and piroxicam. Results: Minimal Inhibition Concentration (MIC) of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS against S. aureus was respectively detected $5.625{\pm}4.075$ (3.125~12.500), $0.332{\pm}0.273$ (0.098~0.782), $1.094{\pm}0.428$ (0.782~1.563), $2.969{\pm}2.096$ (0.782~6.250), $9.375{\pm}4.419$ (3.125~12.500)>25 mg/ml. MIC of lincomycin was detected as $0.469{\pm}0.297$ (0.195~0.782) ${\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of QuF, MeC, ArS, CrR, UlS and ToS was as follows - Cell viability: 66.370, 2.908, 1.747, 259.553, 18.150 and 34.160 mg/ml; NO production: 389.486, 0.294, 0.138, 523.060, 45.363 and 49.327 mg/ml; $PGE_2$ production: 114.271, 0.223, 0.046, 243.078, 8.829 and 28.947 mg/ml; TNF-${\alpha}$ production: 406.288, 0.343, 0.123, 9404.227, 125.406 and 140.775 mg/ml; IL-$1{\beta}$ production: 117.178, 0.135, 0.019, 237.451, 7.923 and 19.418 mg/ml; IL-6 production: 31.261, 0.105, 0.055, 128.434, 2.290 and 3.745 mg/ml. ED50 of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and $5.044{\mu}g/ml$, respectively at same conditions. Conclusions: All six single aqueous herbal extracts showed anti-bacterial effects against S. aureus, in the order of MeC, ArS, CrR, QuF and UlS aqueous extracts except for ToS; they did not showed any anti-bacterial effects (MIC>25 mg/ml). They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of ArS, MeC, UlS, ToS, QuF and CrR aqueous extracts. It means that the ArS and MeC will be showed favorable potent anti-bacterial and related anti-inflammatory effects.

The Effect of Woogakseungmatang Extract on NO Production in LPS- Stimulated RAW 264.7 Cells (우각승마탕이 LPS로 유도된 RAW 264.7 세포에서 NO 생산에 미치는 영향)

  • Jo, Na Young
    • Korean Journal of Acupuncture
    • /
    • v.35 no.4
    • /
    • pp.166-173
    • /
    • 2018
  • Objectives : Woogakseungmatang is a prescription medication mainly used to treat facial paralysis in Korean medicine. The purpose of this study is to investigate the effects of Woogakseungmatang on anti-inflammation and anti-oxidation. Methods : Woogakseungmatang was extracted using hot water. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) method; nitric oxide(NO) production and Prostaglandin $E_2$ ($PGE_2$) production in RAW cells treated with Woogakseungmatang were investigated; and the cytokine changes associated with inflammation were examined. The antioxidant capacity of Woogakseungmatang was measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Results : RAW cells treated with Woogakseungmatang showed 90% cell viability at a $100-{\mu}g/ml$ concentration. NO production was decreased by 15% at a $100-{\mu}g/ml$ concentration. $PGE_2$ production was decreased by 18% at a $100-{\mu}g/ml$ concentration. Interleukin $1{\beta}$ ($IL-1{\beta}$), interleukin 6(IL-6), and tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) were significantly reduced at $100{\mu}g/ml$ compared with those in the control group. The DPPH free radical scavenging capability was more than 50% at $100{\mu}g/ml$. Conclusions : Woogakseungmatang showed only a slight anti - inflammatory effect at $100{\mu}g/ml$ and it was difficult to confirm the concentration-dependent anti-inflammatory effect. Therefore, this study means to confirm the potential anti-inflammatory effects of Woogakseungmatang. Based on this research, more systematic and diverse studies should be conducted.

In vitro Antioxidant and Anti-Inflammatory Activities of Ethanol Extract and Sequential Fractions of Flowers of Prunus persica in LPS-Stimulated RAW 264.7 Macrophages (복숭아꽃 에탄올 추출물과 분획물의 in vitro 항산화 효과 및 RAW 264.7 대식세포에서의 항염증 효과)

  • Kwak, Chung Shil;Choi, Hye-In
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.44 no.10
    • /
    • pp.1439-1449
    • /
    • 2015
  • Prunus persica Flos (PPF) were investigated for their antioxidant and anti-inflammatory activities to find a natural functional food resource preventing degenerative diseases associated with excessive oxidative stress and chronic inflammation. PPF was extracted using ethanol (EtOH) and then sequentially fractioned by hexane (Hx), dichloromethane (DM), ethyl acetate (EA), n-butanol (BtOH), and water (DW). Contents of total phenolics and flavonoids, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production were also measured using LPS-treated RAW 264.7 macrophages. EtOH extract showed relatively high antioxidant activity with high total phenolic (78.1 mg tannic acid/g) and flavonoid contents (55.3 mg rutin/g). EA fraction contained the highest total phenolic and flavonoid contents (394.6 mg tannic acid/g, 253.7 mg rutin/g), followed by BtOH (128.3 mg tannic acid/g, 93.1 mg rutin/g). EA and BtOH fractions and EtOH extract showed higher DPPH radical and ABTS radical scavenging activities than the others (P<0.05). In LPS-treated RAW 264.7 macrophages, EtOH extract ($200{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, and TNF-${\alpha}$ production levels to 38.5%, 32.3%, and 48.9% of the control, respectively, as well as reduced iNOS and COX-2 protein expression. DM fraction ($50{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 43.5%, 13.3%, 38.7%, and 41.3% of the control, respectively, and EA fraction ($50{\mu}g/mL$) showed significantly reduced NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 44.8%, 22.4%, 45.7%, and 62.0% of the control, respectively. Taken together, EtOH extract of PPF showed potent antioxidant and anti-inflammatory activities, and EA and BtOH fractions showed comparatively stronger antioxidant activities while DM and EA fractions showed stronger anti-inflammatory activities. It can be concluded that EtOH extract of PPF and its fractions are good candidates as natural resources for the development of anti-oxidative and anti-inflammatory functional food products.