Development and application of survey-based artificial intelligence for clinical decision support in managing infectious diseases: A pilot study on a hospital in central Vietnam.

Introduction: In this study, we developed a simplified artificial intelligence to support the clinical decision-making of medical personnel in a resource-limited setting. Methods: We selected seven infectious disease categories that impose a heavy disease burden in the central Vietnam region: mosquito-borne disease, acute gastroenteritis, respiratory tract infection, pulmonary tuberculosis, sepsis, primary nervous system infection, and viral hepatitis. We developed a set of questionnaires to collect information on the current symptoms and history of patients suspected to have infectious diseases. We used data collected from 1,129 patients to develop and test a diagnostic model. We used XGBoost, LightGBM, and CatBoost algorithms to create artificial intelligence for clinical decision support. We used a 4-fold cross-validation method to validate the artificial intelligence model. After 4-fold cross-validation, we tested artificial intelligence models on a separate test dataset and estimated diagnostic accuracy for each model. Results: We recruited 1,129 patients for final analyses. Artificial intelligence developed by the CatBoost algorithm showed the best performance, with 87.61% accuracy and an F1-score of 87.71. The F1-score of the CatBoost model by disease entity ranged from 0.80 to 0.97. Diagnostic accuracy was the lowest for sepsis and the highest for central nervous system infection. Conclusion: Simplified artificial intelligence could be helpful in clinical decision support in settings with limited resources.

Virtual reality-based monitoring test for MCI: A multicenter feasibility study.

Objectives: As the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI. Methods: The VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis. Results: According to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups (F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group (F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total (R 2 = 0.082, p = 0.01) and attention scores (R 2 = 0.086, p = 0.009). Conclusion: The VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI.

Normal versus anomalous self-diffusion in two-dimensional fluids: memory function approach and generalized asymptotic Einstein relation.

Based on the generalized Langevin equation for the momentum of a Brownian particle a generalized asymptotic Einstein relation is derived. It agrees with the well-known Einstein relation in the case of normal diffusion but continues to hold for sub- and super-diffusive spreading of the Brownian particle's mean square displacement. The generalized asymptotic Einstein relation is used to analyze data obtained from molecular dynamics simulations of a two-dimensional soft disk fluid. We mainly concentrated on medium densities for which we found super-diffusive behavior of a tagged fluid particle. At higher densities a range of normal diffusion can be identified. The motion presumably changes to sub-diffusion for even higher densities.

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Selectively hydrogenated soybean oil exerts strong anti-prostate cancer activities.

Prostate cancer is the second leading cause of male deaths due to cancer in the United States. Hydrogenated vegetable oils have been suspected of inducing adverse health effects, including atherosclerosis and cancer. Here we report that a selectively hydrogenated soybean oil (SHSO) containing a high quantity of conjugated linoleic acids showed remarkably strong anticarcinogenic activity against prostate cancer in the rat model (Copenhagen rats with MAT-LyLu syngeneic rat prostate cancer cells) study in vivo and human prostate carcinoma cell lines studies in vitro, as compared with native soybean oil. A 5% dietary supplementation with SHSO inhibited the growth of prostate cancer by 80% in vivo. The TUNEL method and immunohistochemical staining assays of bax, bcl-2, and survivin clearly showed that SHSO induced prostate cancer cell apoptosis in the tested rats. DNA fragmentation analysis in vitro further confirmed the apoptotic activity of SHSO on the MAT-LyLu prostate cancer cells. The SHSO also showed strong cytotoxicity on human prostate cancer cells (DU145 and PC3). This represents the first report demonstrating the significant anticancer activities of hydrogenated vegetable oils at low levels of dietary supplementation.

Rapid identification and preparative isolation of antioxidant components in licorice.

This study employed the online HPLC-2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation (ABTS(+*)) bioassay to rapidly determine antioxidant compounds occurring in the licorice extract of Glycyrrhiza uralensis. The negative peaks of the ABTS(+*) radical scavenging detection system, which indicated the presence of antioxidant activity, were monitored by measuring the decrease in absorbance at 734 nm. The ABTS(+)-based antioxidant activity profile showed that three peaks exhibited antioxidant activity, and then the high-speed counter-current chromatography technique of preparative scale was successfully applied to separate the three peaks I-III in one step from the licorice extract. The high-speed counter-current chromatography was performed using a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (6.5:5.5:6:4, v/v). Yields of the three peaks, dehydroglyasperin C (I, 95.1% purity), dehydroglyasperin D (II, 96.2% purity), and isoangustone A (III, 99.5% purity), obtained were 10.33, 10.43, and 6.7% respectively. Chemical structures of the purified dehydroglyasperin C (I), dehydroglyasperin D (II), and isoangustone A (III) were identified by ESI-MS and (1)H- and (13)C-NMR analysis.

The anti-inflammatory effects of a methanolic extract from Radix Isatidis in murine macrophages and mice.

Radix Isatidis is the dried root of the plant Isatidis indigotica Fort (family Cruciferae) and traditionally used as an anti-viral, anti-bacterial, anti-endotoxic, and immune regulatory agent in the folk medicine of Korea and China. The aim of the present study was to determine the anti-inflammatory effects of methanolic extracts of Radix Isatidis (RIME) in lipopolysaccharide (LPS)-stimulated murine macrophages and in a TPA-induced ear edema animal model. Anti-inflammatory effects of RIME were examined in LPS-stimulated RAW 264.7 macrophages. In order to investigate the effects of RIME in vivo, activation of myeloperoxidase, and histological assessment were examined in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema model. RIME significantly inhibited the release from macrophages of inflammatory mediators such as nitric oxide, prostaglandin E(2), and pro-inflammatory cytokines. Topical administration of RIME at 1-5 mg/ear resulted in reduction of ear inflammation in mice. Thus, our results indicate that the anti-inflammatory effects of RIME involve decreased production of inflammatory mediators, which suggests that RIME may have therapeutic potential in a variety of inflammation-related diseases.

Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer.

3,3'-diindolylmethane attenuates colonic inflammation and tumorigenesis in mice.

BACKGROUND: 3,3-Diindolylmethane (DIM) is a major in vivo product of acid-catalyzed oligomerization of indole-3-carbinol (I3C) derived from Brassica food plants. Although DIM is known as a chemopreventive and chemotherapeutic phytochemical, the effects of DIM on inflammation in vivo are still unknown. In the present study we investigated the antiinflammatory effects of DIM on experimental colitis and colitis-associated colorectal carcinogenesis. METHODS: To determine if DIM has an antiinflammatory effect in vivo, we examined the therapeutic effects of DIM in dextran sodium sulfate (DSS)-induced experimental colitis and colitis-associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in BALB/c mice. RESULTS: Treatment with DIM significantly attenuated loss of body weight, shortening of the colon, and severe clinical signs in a colitis model. This was associated with a remarkable amelioration of the disruption of the colonic architecture and a significant reduction in colonic myeloperoxidase activity and production of prostaglandin E(2), nitric oxide, and proinflammatory cytokines. Further, DIM administration dramatically decreased the number of colon tumors in AOM/DSS mice. CONCLUSIONS: These results suggest that DIM-mediated antiinflammatory action at colorectal sites may be therapeutic in the setting of inflammatory bowel disease and colitis-associated colon cancer.

The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages.

Methylsulfonylmethane (MSM), also known as dimethyl sulfone and methyl sulfone, is an organic sulfur-containing compound that occurs naturally in a variety of fruits, vegetables, grains, and animals, including humans. In the present study, we demonstrated the anti-inflammatory effects of MSM in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. MSM significantly inhibited the release of nitric oxide and prostaglandin E(2) by alleviating the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW264.7 cells. Furthermore, the levels of interleukin-6 and tumor necrosis factor-alpha were decreased by MSM treatment in cell culture supernatants. Further study indicated that the translocation of the p65 subunit of nuclear factor (NF)-kappaB to the nucleus was inhibited by MSM treatment in LPS-stimulated RAW264.7 cells, in which it helped block degradation of inhibitor of NF-kappaB. In addition, in vivo studies demonstrated that topical administration of MSM at 500-1250 microg/ear resulted in similar inhibitory activities in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Collectively, theses results indicate that MSM inhibits LPS-induced release of pro-inflammatory mediators in murine macrophages through downregulation of NF-kappaB signaling.

Cuscuta chinensis extract promotes osteoblast differentiation and mineralization in human osteoblast-like MG-63 cells.

The aim of the present study was to investigate whether the aqueous extract of To-Sa-Za (TSZ-AE), the seed of Cuscuta chinensis Lam., which is a traditional medicinal herb commonly used in Korea and other oriental countries, could induce osteogenic activity in human osteoblast-like MG-63 cells. TSZ-AE treatment mildly promoted the proliferation of MG-63 cells at doses of 500 and 1,000 microg/mL in the 24-hour culture period. Dose-dependent increases in alkaline phosphatase (ALP) activity and collagen synthesis were shown at 48 and 72 hours of incubation. The release of bone morphogenetic protein (BMP)-2 but not osteocalcin in the MG-63 cells was induced by TSZ-AE at 72 hours (100-1,000 microg/mL). In addition, TSZ-AE markedly increased mRNA expression of ALP, collagen, and BMP-2 in the MG-63 cells in a dose-dependent manner. Mineralization in the culture of MG-63 cells was significantly induced at 500 and 1,000 microg/mL TSZ-AE treatment. In conclusion, this study shows that TSZ-AE enhanced ALP activity, collagen synthesis, BMP-2 expression, and mineralization in MG-63 cells. These results strongly suggest that C. chinensis can play an important role in osteoblastic bone formation and may possibly lead to the development of bone-forming drugs.

Chrysin, a natural flavone, improves murine inflammatory bowel diseases.

Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants. It has previously been shown to be an anti-tumor agent. In this study, we investigated whether chrysin could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice and whether chrysin has an inhibitory effect on nuclear factor (NF)-kappaB activation in vitro. A significant blunting of weight loss and clinical signs was observed in DSS-exposed, chrysin-treated mice when compared to vehicle-treated mice. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines. In addition, chrysin inhibited tumor necrosis factor (TNF)-alpha-induced activation of NF-kappaB in IEC-6 cells. These findings suggest that chrysin exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of NF-kappaB activation.

Apoptosis of DU145 human prostate cancer cells induced by dehydrocostus lactone isolated from the root of Saussurea lappa.

Saussurea lappa (SL) is a plant regularly utilized in traditional herbal medicine, and in vitro cell culture studies have demonstrated that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. In order to explore the possibility that SL exerts chemopreventive effects in androgen-independent prostate cancer, we attempted to determine whether the hexane extract of SL (HESL) induces apoptosis of DU145 cells, as well as the mechanisms underlying this effect. HESL substantially reduced the number of viable cells and induced apoptosis in DU145 cells in a dose-dependent manner. HESL-induced the cleavage of poly (ADP-ribose) polymerase (PARP) and caspases 8, 9, 7, and 3. HESL increased the protein levels of Bax, Bak, Bok, Bik, truncated Bid (t-Bid), and Bmf with a concomitant increase in the permeability of the mitochondrial membrane and in the release of cytochrome c from the mitochondria. The active fraction of HESL was isolated by column chromatography and the structure of the active compound dehydrocostus lactone (DHCL) was identified via (1)H NMR and (13)C NMR. DHCL promoted apoptosis with increased activation of caspases 8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid. We have demonstrated that HESL and its active principle, DHCL, inhibit cell growth and induce apoptosis in DU145 cells.

Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice.

Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, exhibits various biological properties, including chemopreventive, anti-bacterial, and anti-spasmodic activity. We report that LicA inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. Our in vitro experiments showed that LicA suppressed not only the generation of nitric oxide (NO) and prostaglandin (PG)E(2), but also the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, LicA inhibited the production of inflammatory cytokines induced by LPS in RAW264.7 cells, including IL-1 beta and IL-6. In an animal model, LicA protected BALB/c mice from LPS-induced endotoxin shock, possibly through inhibiting the production of inflammatory cytokines and NO. Collectively, LicA inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.

Protein glycation inhibitors from the fruiting body of Phellinus linteus.

To characterize active principles for prevention and treatment of diabetic complications, the isolation of protein glycation inhibitors from the fruiting body of Phellinus linteus was conducted in vitro using the model systems of hemoglobin-delta-gluconolactone (early stage), bovine serum albumin-methylglyoxal (middle stage), and N(alpha)-acetyl-glycyl-lysine methyl ester-D-ribose (last stage) assays. Nine compounds were isolated from the active ethylacetate fraction of the fruiting body and identified as protocatechuic acid (1), protocatechualdehyde (2), caffeic acid (3), ellagic acid (4), hispidin (5), davallialactone (6), hypholomine B (7), interfungins A (8), and inoscavin A (9) by spectroscopic analyses. At the early stage of protein glycation, compounds 6, 8, and 9 exhibited inhibitory activity on hemoglobin A(1C) formation. For the middle stage, compounds 2, 6, and 9 showed a significant inhibitory effect on methylglyoxal-medicated protein modification and their IC(50) values were 144.28, 213.15, and 158.66 muM, respectively. At the last stage of glycation, compound 8 was found to be a potent inhibitor of the cross-linking of proteins, which was more effective than that of aminoguanidine, a well-known inhibitor for advanced glycation end products. Consequently, compound 8 showed the most potent inhibitory effects at each stage of protein glycation. This mechanism may help to provide a protective effect against hyperglycemia-mediated protein damage.

Inhibitory constituents of aldose reductase in the fruiting body of Phellinus linteus.

In an effort to characterize active principles for diabetic complication from medicinal mushroom, aldose reductase inhibitors were isolated from the fruiting body of Phellinus linteus and identified as hispidin (5), phelligridimer A (6), davallialactone (7), methyldavallialactone (8), hypholomine B (9), interfungins A (10), and inoscavin A (11), together with protocatechuic acid (1), protocatechualdehyde (2), caffeic acid (3), and ellagic acid (4). Their structures were elucidated by spectroscopic analyses. Among them, davallialactone (7), hypholomine B (9), and ellagic acid (4) exhibited potent rat lens aldose reductase and human recombinant aldose reductase inhibitory activity with IC50 values of 0.33, 0.82, 0.63 microM and 0.56, 1.28, 1.37 microM, respectively.

Antiinflammatory activities of Rubus coreanus depend on the degree of fruit ripening.

The dried unripe fruit of Rubus coreanus, which is well-known in Korea and referred to as 'Bok-bun-ja', has been employed as a traditional medicine for centuries. This crude drug is utilized in Korea for the management of impotence, spermatorrhea, enuresis, asthma and allergic diseases. The principal objective of the present study was to conduct a comparison of the antiinflammatory effects of ethanol extracts of the unripe (URCE), half-ripened (HRCE) and ripe fruits (RCE) of Rubus coreanus. URCE and HRCE were found to reduce the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as pro-inflammatory cytokines, in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. However, RCE exerted no inhibitory effects against the production of NO and IL-6. The results of the study show that the degree of fruit ripening of Rubus coreanus affects the production of inflammatory mediators such as NO, PGE2 and inflammatory cytokines.

Induction of apoptosis in HT-29 colon cancer cells by phloretin.

Phloretin, which is present in apples and pears, has been found to inhibit the growth of several cancer cells and induce apoptosis of B16 melanoma and HL60 human leukemia cells. The present study examined whether and how phloretin induces apoptosis of HT-29 human colon cancer cells. Phloretin (0-100 micromol/L) substantially decreased viable cell number and induced apoptosis of HT-29 cells in a dose-dependent manner. Western blot analysis of total cell lysates revealed that phloretin increased the protein levels of Bax but had no effect on Bcl-2. In addition, phloretin induced cleavage of caspase-8, -9, -7, and -3 and poly(ADP-ribose) polymerase. Furthermore, phloretin increased the levels of cytochrome c and Smac/Diablo in the cytosol. The present results indicate that phloretin inhibits HT-29 cell growth by inducing apoptosis, which may be mediated through changes in mitochondrial membrane permeability and activation of the caspase pathways.

Activation of caspase-8 contributes to 3,3'-Diindolylmethane-induced apoptosis in colon cancer cells.

3,3'-Diindolylmethane (DIM) is the major in vivo product of acid-catalyzed oligomerization of indole-3-carbinol, which is a promising anticancer agent present in cruciferous vegetables and has itself been reported to have anticarcinogenic properties. This study examined DIM-mediated regulation of apoptosis in the HCT116 (wild-type p53) and HT-29 (mutant p53) human colon cancer cell lines. DIM (0-30 micromol/L) substantially decreased the number of viable cells and induced apoptosis of HCT116 and HT-29 cells in a concentration-dependent manner. Western-blot analyses of total cell lysates revealed that DIM increased the activation of caspase-3, -7, -8, and -9 and enhanced poly(ADP-ribose) polymerase cleavage in both HCT116 and HT-29 cells. In addition, DIM increased the translocation of cytochrome c and Smac/Diablo from the mitochondria to the cytoplasm. In concert with the caspase-8 activation by DIM, increased levels of Fas and truncated Bid were observed. DIM did not affect the protein levels of p53, Bcl-2, Bax, or Fas ligand (FasL) in HCT116 cells. In HT-29 cells, however, DIM decreased Bcl-2 levels, although the protein levels of Bax or FasL were not affected. The caspase-8 inhibitor Z-IETD-FMK attenuated the DIM-induced apoptosis, indicating that increased activation of this enzyme contributed to the increase in p53-independent apoptosis that was observed in colon cancer cells. We have demonstrated that DIM induces apoptosis in colon cancer cells, providing insights into the mechanisms underlying its antitumorigenic activities.

Induction of heme oxygenase-1 mediates the anti-inflammatory effects of the ethanol extract of Rubus coreanus in murine macrophages.

Foods of plant origin, especially fruits and vegetables, draw increased attention because of their potential benefits to human health. The aim of the present study was to determine in vitro anti-inflammatory activity of four different extracts obtained from the fruits of Rubus coreanus (aqueous and ethanol extracts of unripe and ripe fruits). Among the four extracts, the ethanol extract of unripe fruits of R. coreanus (URCE) suppressed nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. We also demonstrated that URCE by itself is a potent inducer of heme oxygenase-1 (HO-1). Inhibition of HO-1 activity by tin protoporphyrin, a specific HO-1 inhibitor, suppressed the URCE-induced reductions in the production of NO and PGE(2) as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Our data suggest that URCE exerts anti-inflammatory effects in macrophages via activation of the HO-1 pathway and helps to elucidate the mechanism underlying the potential therapeutic value of R. coreanus extracts.