Chondroprotective Effects of Ulva prolifera on Osteoarthritis through MAPKs Signaling Inhibition

이슬아,한슬희,장지윤,박보람,김춘성 한국식품영양과학회 2023 Preventive Nutrition and Food Science Vol.28 No.1

Osteoarthritis (OA) is a typical degenerative disease that mainly appears in the elderly aged 65 and over. OA is characterized by inflammation and decomposition of the cartilage matrix due to irreversible wear and tear. Ulva prolifera, a green macroalgae species, contains polysaccharides, amino acids, polyunsaturated fatty acids, and polyphenols, which are major active components responsible for anti-inflammatory and antioxidant effects. This study evaluated the chondroprotective effect of 30% prethanol extract of U. prolifera (30% PeUP). Rat primary chondrocytes were pre-treated with 30% PeUP for 1 h before interleukin-1β (10 ng/mL) stimulation. The production of nitrite, prostaglandin E2 (PGE2), collagen type II (Col II), and aggrecan (ACAN) were detected by Griess reagent and enzyme-linked immunosorbent assay. The protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin (ADAMTS)-4, ADAMTS-5, and mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38) were assessed by western blot. Thirty percent of PeUP significantly inhibited the expression of nitrite, iNOS, PGE2, COX- 2, MMP-1, MMP-3, MMP-13, ADMATS-4, and ADMATS-5 in interleukin (IL)-1β-stimulated chondrocytes. Moreover, 30% PeUP decreased the IL-1β-induced degradation of Col II and ACAN. Additionally, 30% of PeUP suppressed IL-1β-induced phosphorylation of MAPKs. Therefore, 30% PeUP is a potential therapeutic agent to mitigate OA progression.

Hypocholesterolemic effects of Curcuma longa L. with Nelumbo nucifera leaf in an in vitro model and a high cholesterol diet-induced hypercholesterolemic mouse model

정명아,이선영,한슬희,홍지애,나주련,이준열,김영재,김선오 한국통합생물학회 2015 Animal cells and systems Vol.19 No.2

Hypercholesterolemia is one of the well-established risk factors for cardiovascular mortality and morbidity in coronary heart disease. The present study was designed to investigate the effects of different types of extracts (aqueous, 20%-, and 80% ethanol) of Nelumbo nucifera leaf (NL) and Curcuma Longa L. (CL) on hypercholesterolemia in in vitro and in vivo models. Our results in in vitro experiments showed that treatment with various extracts of both NL and CL dose-dependently inhibited lipid accumulation and total cholesterol content. The 20% ethanol extract of NL (NL20E) and the aqueous extract of CL (CLW) showed the highest activity. The in vivo experimental group was fed a high cholesterol diet (HCD) with oral administration of NL20E, CLW, or a mixture of NL20E with CLW(NC; mixed equal ratio) for 8 weeks. The oral administration of NL20E, CLW, and NC (100 or 300 mg/kg/day) resulted in the suppression of the levels of serum total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, liver lipid level, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), atherogenic index (AI), cardiac risk factor (CRF), cholesteryl ester transfer protein (CETP), HMG-CoA reductase, and thiobarbituric acid-reactive substances (TBARS). Similarly, the NL20E, CLW, and NC extracts elevated high-density lipoprotein (HDL) cholesterol levels and lecithin cholesterol acyltransferase (LCAT) activity. Furthermore, NC showed a remarkable hypocholesterolemic effect by decreasing the levels of hepatic TC, AI, LDL cholesterol, HMG-CoA reductase, and CRE and by increasing the levels of HDL cholesterol. Thus, the results of this study indicate that the NC has combined hypocholesterolemic effects that block lipid accumulation, thus preventing hypercholesterolemia.

Antistress Effects of Rosa rugosa Thunb. on Total Sleep Deprivation–Induced Anxiety-Like Behavior and Cognitive Dysfunction in Rat: Possible Mechanism of Action of 5-HT6 Receptor Antagonist

나주련,오둘리,한슬희,김유진,최은진,배동혁,오동환,이유현,김선오,전우진 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.9

Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation–induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 receptor and resulting inhibition of cAMP activity.

In Vivo and In Vitro Anti-Inflammatory Effects of Aqueous Extract of Anthriscus sylvestris Leaves

이슬아,문성민,한슬희,황은주,홍준호,박보람,최미석,안훈,김재성,김흥중,전홍성,김도경,김춘성 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.6

Anthriscus sylvestris (L.) Hoffm. is a common perennial herb that is widely distributed in Europe, Korea, and New Zealand. The root of A. sylvestris has been used in Korean traditional medicine as an antitussive and cough remedy. However, the physiologically active function of A. sylvestris leaves is not yet known. In this study, we evaluated the anti-inflammatory effects, as well as the underlying molecular mechanisms of an aqueous extract of A. sylvestris leaves (AE-ASL) in vitro and in vivo. Our results indicated that pretreatment with AE-ASL significantly inhibited the lipopolysaccharide (LPS)-induced secretion of nitric oxide (NO) and prostaglandin E2 in RAW264.7 cells, without showing cytotoxicity. In addition, the LPS-induced mRNA and protein expression of inducible NO synthase, cyclooxygenase-2, and inflammatory mediators such as tumor necrosis factor alpha interleukin (IL)-1β, and IL-6 was attenuated by pretreatment with AE-ASL in a dose-dependent manner. Therefore, we investigated the activation of nuclear factor (NF)-κB, a transcription factor regulating the expression of inflammation-related genes. AE-ASL inhibited the nuclear translocation of the NF-κB p65 subunit by suppressing the phosphorylation and degradation of the inhibitor of NF-κB (IκBα). Further, AE-ASL inhibited the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells. Orally administered AE-ASL (50, 100, and 200 mg/kg of body weight [BW]) suppressed the development of carrageenan-induced rat paw edema by 15%, 31%, and 40%, respectively, after 4 h. Altogether, our results suggest that AE-ASL possesses anti-inflammatory activity, based on the suppression of NF-κB and MAPK pathways in vitro and inhibition of the carrageenan-induced paw edema in vivo.

Water Extracts of Anthriscus sylvestris Leaf induces Apoptosis in FaDu Human Hypopharynx Squamous Carcinoma Cells

양정은,이슬아,문성민,한슬희,최윤희,김수관,김도경,박보람,김춘성 대한구강생물학회 2017 International Journal of Oral Biology Vol.42 No.2

Anthriscus sylvestris (L.) Hoffm. is a perennial herb found widely distributed in various regions of Korea, Europe, and New Zealand. The root of A. sylvestris have been extensively used in the treatment for antitussive, antipyretic, cough remedy in Oriental medicine, but the physiologically active function of the leaf of A. sylvestris is as yet unknown. In this study, we investigated the anti-cancer activity and the mechanism of cell death of water extracts of leaf of Anthriscus sylvestris (WELAS), on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that WELAS treatment inhibited cell viability in a concentration- and time-dependent manner. In addition, the treatment of WELAS markedly induced apoptosis in FaDu cells, as determined by the viability assay, DAPI stain and FACS analysis. WELAS also increased the proteolytic cleavage of procaspase-3, -9 and PARP (poly(ADP-ribose) polymerase). In addition, exposure to WELAS decreased the expression of Bcl-2 (an anti-apoptotic factor), but increased the expression of Bax (a pro-apoptotic factor), suggesting that mitochondria-dependent apoptotic pathways are mediated in WELAS-induced apoptosis. Taken together, these results indicate that water extracts of leaf of A. sylvestris inhibits cell growth and induces apoptosis via the mitochondrial-dependent apoptotic pathway in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, we propose that the water extracts of leaf of A. sylvestris is a novel chemotherapeutic drug, having growth inhibitory properties and induction of apoptosis in human oral cancer cells.

Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells

신보수,이슬아,문성민,한슬희,황은주,김수관,김도경,김진수,박보람,김춘성 대한구강생물학회 2017 International Journal of Oral Biology Vol.42 No.4

Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.