Isolation, Characterization, and Antiproliferative Activity of Terpenoids from the Tropical Plant Turraea delphinensis.

The isolation, structure determination, and biological evaluation of constituents from the organic extract of Turraea delphinensis Wahlert (Meliaceae) resulted in the isolation of 51 secondary metabolites, including 14 new terpenoids (six cycloartanes, four tirucallanes/euphanes, three limonoids, and a 7-keto sterol). Among the new compounds, 1 is the first triterpenoid with a trioxaspiro[4.4]nonane side chain, while 11-13 are the first 17-γ-lactone tetranortriterpenoids with four oxygenated functional groups at C-1, -3, -6, and -7. The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a vinblastine-resistant cell line.

Cyclic Sesquiterpene-Flavanone [4+2] Hybrids, Syzygioblanes A-C, Found in an Indonesian Traditional Medicine, "Jampu Salo" (Syzygium oblanceolatum).

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) and found for the first time in Sulawesi; it was previously reported only in the eastern Philippines and Borneo. A phytochemical study of S. oblanceolatum led to the isolation of three unprecedented meroterpenoids, syzygioblanes A-C (1-3, respectively). These compounds might be biosynthesized through [4+2] cycloaddition of various germacrane-based cyclic sesquiterpenoids with the flavone desmethoxymatteucinol to form a spiro skeleton. The unique and complex structures were elucidated by microcrystal electron diffraction analysis in addition to general analytical techniques such as high-resolution mass spectrometry, various nuclear magnetic resonance methods, and infrared spectroscopy. Synchrotron X-ray diffraction and calculations of electronic circular dichroism spectra helped to determine the absolute configurations. The newly isolated compounds exhibited collateral sensitivity to more strongly inhibit the growth of a multidrug resistant tumor cell line compared to a chemosensitive tumor cell line.

Clinical characteristics of new-onset diabetes after liver transplantation and outcomes.

Background: We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods: Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results: A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion: Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.

Exception Policy Change Increased the Simultaneous Kidney-Liver Transplant Probability of Polycystic Disease in the Centers With High Median MELD at Transplantation.

BACKGROUND: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD). METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras. RESULTS: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P  = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P  = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P  = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P  = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 ( P  = 0.006), it became comparable in Era 2 ( P  = 0.54). CONCLUSIONS: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.

Unusual Vilasinin-Class Limonoids from Trichilia rubescens.

Eight vilasinin-class limonoids, including the unusually chlorinated rubescins K-M (1-3), the 2,3-epoxylated rubescin N (4), and rubescins O-R (5-8), were newly isolated from Trichilia rubescens. The structures of the isolated compounds were determined through spectroscopic and spectrometric analyses, as well as ECD calculations. The natural occurrence of chlorinated limonoids 1-3 was confirmed by chemical methods and HPLC analysis of a roughly fractionated portion of the plant extract. Eight selected limonoids, including previously known and new compounds, were evaluated for antiproliferative activity against five human tumor cell lines. All tested limonoids, except 8, exhibited significant potency, with IC50 values of <10 µM; in particular, limonoid 14 strongly inhibited tumor cell growth, with IC50 values of 0.54-2.06 µM against all tumor cell lines, including multi-drug-resistant cells.

Improved Waitlist Outcomes in Liver Transplant Patients With Mid-MELD-Na Scores Listed in Centers Receptive to Use of Organs Donated After Circulatory Death.

BACKGROUND: Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers' receptiveness to use of DCD organs impacted patient outcomes. METHODS: Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories. RESULTS: In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51-2.11, P < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41-1.81, P < 0.001) and between groups 2 and 3 with MELD-Na 15-24 (aHR 1.19-1.20, P < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20-24: aHR, 0.71, P = 0.03; score, 25-29: aHR, 0.51, P < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20-24: aHR0.69, P = 0.02; scores 25-29: aHR 0.63, P = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead. CONCLUSIONS: We conclude that transplant centers' use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients.

Caged Xanthones and Biphenyls Isolated from the Tropical Plant Garcinia lateriflora.

Four cytotoxic heptacyclic caged-xanthones [gambogefic acids B-E (1-4)], a cytotoxic hexacyclic caged-xanthone [garcilatelic acid (5)], and four biphenyl derivatives [garcilatelibiphenyls A-D (6-9)] were newly isolated in a phytochemical study of a 50% MeOH/CH2Cl2 extract of Garcinia lateriflora (Clusiaceae). The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines including a vincristine-resistant line. The new caged-xanthones displayed potent activity with IC50 values from 0.5 to 6.7 µM against all tested tumor cell lines.

Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

Machine learning-based prediction of postoperative mortality in emergency colorectal surgery: A retrospective, multicenter cohort study using Tokushukai medical database.

Background: Although prognostic factors associated with mortality in patients with emergency colorectal surgery have been identified, an accurate mortality risk assessment is still necessary to determine the range of therapeutic resources in accordance with the severity of patients. We established machine-learning models to predict in-hospital mortality for patients who had emergency colorectal surgery using clinical data at admission and attempted to identify prognostic factors associated with in-hospital mortality. Methods: This retrospective cohort study included adult patients undergoing emergency colorectal surgery in 42 hospitals between 2012 and 2020. We employed logistic regression and three supervised machine-learning models: random forests, gradient-boosting decision trees (GBDT), and multilayer perceptron (MLP). The area under the receiver operating characteristics curve (AUROC) was calculated for each model. The Shapley additive explanations (SHAP) values are also calculated to identify the significant variables in GBDT. Results: There were 8792 patients who underwent emergency colorectal surgery. As a result, the AUROC values of 0.742, 0.782, 0.814, and 0.768 were obtained for logistic regression, random forests, GBDT, and MLP. According to SHAP values, age, colorectal cancer, use of laparoscopy, and some laboratory variables, including serum lactate dehydrogenase serum albumin, and blood urea nitrogen, were significantly associated with in-hospital mortality. Conclusion: We successfully generated a machine-learning prediction model, including GBDT, with the best prediction performance and exploited the potential for use in evaluating in-hospital mortality risk for patients who undergo emergency colorectal surgery.

Preoperative prognostic predictors and treatment strategies for surgical procedure focused on the sequential organ failure assessment score in nonocclusive mesenteric ischemia: a multicenter retrospective cohort study.

BACKGROUND: Several large-scale studies have assessed endovascular and surgical treatment methods for nonocclusive mesenteric ischemia (NOMI); however, the prognostic factors for NOMI remain unclear. Therefore, this study aimed to evaluate risk factors for in-hospital mortality among patients with NOMI who underwent laparotomy and to examine therapeutic strategies that may improve the prognosis. MATERIALS AND METHODS: In this multicenter retrospective study, the authors reviewed the electronic medical records retrieved from the inpatient database of patients with NOMI at eight district general hospitals between January 2011 and January 2021. A total of 88 patients who underwent laparotomies were divided into survivor and nonsurvivor groups, and statistical analysis was performed to determine clinical and physiological factors. RESULTS: Exploratory laparotomy based on second-look surgery was the first treatment choice. The overall mortality rate was 48.8%, with a male-to-female ratio of 1.1:1. The median Sequential Organ Failure Assessment (SOFA) score was 8 [interquartile range: 3.75-14.2], and the median SOFA scores were 5 [3-7] in the survivor group and 13 [9-17.5] in the nonsurvivor group. Univariate analysis revealed a significant difference in BMI ( P <0.001), hypoglycemia ( P =0.0012), previous cardiovascular surgery ( P =0.0019), catecholamine use ( P <0.001), SOFA score ( P <0.001), platelet count ( P =0.0023), and lactate level ( P <0.001). Logistic regression analysis using the factors with significant differences revealed that SOFA score ≥10 (odds ratio 23.3; 95% CI: 1.94-280.00; P =0.013) was an independent prognostic factor. In addition, catecholamine use was suggested as a factor with a SOFA score greater than or equal to 10. CONCLUSION: This study confirmed that a SOFA score of greater than or equal to 10 may be associated with increased mortality. While closely monitoring low blood pressure and renal dysfunction, survival rates may be improved if surgical intervention is performed before the SOFA score reaches greater than or equal to 10.

Methoxyflavones isolated from the whole plant of Scutellaria rubropunctata Hayata var. rubropunctata promote osteoblast differentiation in MC3T3-E1 cells.

In this study, we isolated two new methoxyflavones (1 and 2) and eight known methoxyflavones (3-10) from the whole plant of Scutellaria rubropunctata Hayata var. rubropunctata (SR). Based on spectroscopic analyses, the methoxyflavones were identified as 5,8,2',6'-tetramethoxy-6,7-methylenedioxyflavone (1) and 5,2',6'-trimethoxy-6,7-methylenedioxyflavone (2). We reported SR might have effects on promoting osteoblast differentiation and stimulating estrogen receptor (ER) in the previous study. Then, the effects of 1-10 on pre-osteoblast MC3T3-E1 cells were investigated, and 1, 2, and 9 were observed to promote alkaline phosphatase activity. To evaluate their effect on osteogenesis-related genes, we performed gene expression analysis using quantitative real-time PCR after treatment of MC3T3-E1 cells with these compounds. Although 2 was only effective at lower concentrations, 1 and 9 upregulated the mRNA levels of Runx2, Osterix, Osteopontin, Osteocalcin, Smad1, and Smad4. These results indicate that 1 and 9 may induce osteoblast differentiation by activating Runx2 via the BMP/Smad pathway and may play a central role in the promotion of osteoblast differentiation by SR. The ER agonist activity of 1-10 were tested using a luciferase reporter assay in HEK293 cells. However, none of the compounds exhibited remarkable activity. Thus, SR may contain other compounds that contribute to its ER agonist activity.

A New Bis-indole Alkaloid, Spermaocymine A, and an Anthraquinone from Spermacoce ocymoides.

A phytochemical study on Spermacoce ocymoides has led to the isolation of a novel bis-indole alkaloid, spermaocymine A (2), together with the known alkaloid 4-methyl-borreverine (1), as well as an anthraquinone, 8-hydroxy-2-(hydroxymethyl)-1-methoxyanthracene-9,10-dione (3). The structures of the isolated compounds were elucidated by analyzing spectroscopic and spectrometric data, including one-dimensional (1D)- and 2D-NMR and high resolution (HR)-MS. Newly isolated alkaloid 2 was a C-3,14-stereoisomer of 1, the first natural stereoisomer of related bis-indoles containing an indeno[1,2-b]indole skeleton with an epiminoethano bridge. When 1-3 were assayed against five tumor cell lines including multi-drug resistant cells, compound 1 exhibited potent antiproliferative activity with IC50 values of 6.2-11.5 µM.

Effects of the implementation of acuity circle policy on waitlist and post-transplant outcomes of liver re-transplantation.

BACKGROUND: Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n = 750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n = 556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. RESULTS: In Era 2, the probability of transplant within 90 days overall and among patients relisted > 14 days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p < .001; sHR 1.52, 95% CI 1.23-1.88, p = .001, respectively). However, there was no difference by era among patients relisted ≤14 days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p = .15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p = .004; and aHR 8.22, 95% CI 1.85-36.59, p = .005, respectively); for late relisting patients, risks for these outcomes were similar across eras. CONCLUSION: Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed > 14 days from initial transplant. However, the impact upon early relisting patients may be mixed.

17ß-neriifolin from unripe fruits of Cerbera manghas suppressed cell proliferation via the inhibition of HOXA9-dependent transcription and the induction of apoptosis in the human AML cell line THP-1.

Homeobox A9 (HOXA9) is a transcription factor that is overexpressed in acute myeloid leukemia (AML). It is associated with the pathogenesis and progression of AML, and is a factor responsible for a poor prognosis. Therefore, the development of HOXA9-targeting molecules may contribute to not only better understanding of the mechanism of HOXA9 regulation, but also the development of therapeutic applications. We constructed a reporter assay system using the promoter region of the KBTBD10 gene, to which HOXA9 directly binds and regulates transcription, in the human acute monocytic leukemia cell line THP-1. Using this luciferase gene assay, we screened 1120 plant extracts and a methanol extract of the unripe fruits of Cerbera manghas was found to suppress the reporter gene expression mediated by the KBTBD10 promoter. From the extract, five steroid-type compounds were identified as the active constituents: 7α-neriifolin (1), 17ß-neriifolin (2), 17α-digitoxigenin ß-D-glucosyl-(1 → 4)-α-L-thevetoside (3), 17ß-digitoxigenin ß-D-glucosyl-(1 → 4)-α-L-thevetoside (4), and acetylthevetin B (5). Among the five compounds, 17ß-neriifolin most potently inhibited HOXA9-dependent gene expression without affecting the HOXA9 mRNA levels, and suppressed cell proliferation by inducing apoptosis. The findings on the structure-activity relationships of the compounds from C. manghas may contribute to the development of small molecule inhibitors of HOXA9.

Essential oil composition of Curcuma species and drugs from Asia analyzed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry.

Essential oils (EOs) comprised of various bioactive compounds have been widely detected in the Curcuma species. Due to the widespread distribution and misidentification of Curcuma species and differences in processing methods, inconsistent reports on major compounds in rhizomes of the same species from different geographical regions are not uncommon. This inconsistency leads to confusion and inaccuracy in compound detection of each species and also hinders comparative study based on EO compositions. The present study aimed to characterize EO compositions of 12 Curcuma species, as well as to detect the compositional variation among different species, and between the plant specimens and their related genetically validated crude drug samples using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. The plant specimens of the same species showed similar EO patterns, regardless of introducing from different geographical sources. Based on the similarity of EO compositions, all the specimens and samples were separated into eight main groups: C. longa; C. phaeocaulis, C. aeruginosa and C. zedoaria; C. zanthorrhiza; C. aromatica and C. wenyujin; C. kwangsiensis; C. amada and C. mangga; C. petiolata; C. comosa. From EOs of all the specimens and samples, 54 major compounds were identified, and the eight groups were chemically characterized. Most of the major compounds detected in plant specimens were also observed in crude drug samples, although a few compounds converted or degraded due to processing procedures or over time. Orthogonal partial least squares-discriminant analysis allowed the marker compounds to discriminate each group or each species to be identified.

Lanceolanone A, a new biflavanone, and a chalcone glucoside from the flower heads of Coreopsis lanceolata and their aldose reductase inhibitory activity and AMPK activation.

The MeOH extract of the flower heads of Coreopsis lanceolata L. (Asteraceae) exhibited aldose reductase (AR) inhibitory activity (IC50 8.36 µg/mL). Bioassay-guided fractionation of the extract resulted in the isolation of a new biflavanone-named Lanceolanone A (1) and a chalcone glucoside (6), along with 12 known compounds (2-5 and 7-14), of which 4, 7, 9, 10, and 12 were isolated from C. lanceolata for the first time. The structures of the new compounds (1 and 6) were determined by extensive spectroscopic analysis, including two-dimensional (2D) NMR, and ECD calculation method. Compounds 2, 4, 11, 13, and 14 exhibited AR inhibitory activities with IC50 values between 2.40 and 9.99 µM. Furthermore, 8-13 at 1.0 mM activated AMPK expression in HepG2 human hepatoma cells compared to the control.

Effects of a Whole Plant Extract of Scutellaria rubropunctata var. rubropunctata on Bone Metabolism with Estrogen Receptor Activation.

We screened natural resources for estrogen receptor (ER)-activating and bone metabolism-promoting activities with the aim of finding potential treatments for osteoporosis. A screen of 1531 extracts from Ryukyu Arc plants using a luciferase reporter assay identified an 80% MeOH extract of Scutellaria rubropunctata var. rubropunctata (SRE) with dose-dependent ER transcription-promoting activity. Importantly, SRE had no proliferative effect on human breast cancer cells. SRE enhanced the ALP activity of pre-osteoblast MC3T3-E1 cells after 72 h in culture and slightly enhanced mineralization at 14 and 21 d. SRE did not significantly affect the TRAP activity of RAW264.7 cells. Gene expression analysis in MC3T3-E1 cells by quantitative real-time PCR revealed that SRE upregulated the mRNA levels of Runx2, Osterix (Osx), Osteopontin (Opn), Osteocalcin (Ocn), Smad1, Smad4, and Smad5 at 72 h, and those of Runx2, Osx, Smad1, Smad4, and Smad5 at 21 d of osteogenic induction. Analysis of the expression levels of osteogenic markers suggested that SRE may promote osteogenic differentiation by acting at the early stage of differentiation rather than at the late stage of differentiation. These results indicate that SRE activates ER and induces osteoblast differentiation by activating Runx2 and Osx through the BMP/Smad pathway, suggesting that SRE may be useful for the prevention and treatment of postmenopausal osteoporosis.

Retusone A, a Guaiane-Type Sesquiterpene Dimer from Wikstroemia retusa and Its Inhibitory Effects on Histone Acetyltransferase HBO1 Expression.

Retusone A (1), a new sesquiterpene dimer consisting of two guaiane-type sesquiterpenoids, and oleodaphnal (2) were isolated from heartwood of Wikstroemia retusa (Thymelaeaceae). The planar structure of 1 was elucidated on the basis of HRESIMS and NMR spectroscopic data, and the relative stereochemistry was established by X-ray diffraction analysis. The absolute configuration of 1 was determined by electronic circular dichroism. Compound 1 suppressed luciferase reporter gene expression driven by the HBO1 (histone acetyltransferase binding to ORC1) gene promoter in human breast cancer MCF7 cells. Compound 1 also decreased the expression of endogenous HBO1 mRNA and protein, and inhibited proliferation of the cells. These results suggest that retusone A (1), which has a unique dimeric sesquiterpenoid structure with inhibitory activity against HBO1 expression, may contribute to the development of a novel therapeutic candidate for the treatment of breast cancer.

Chemical Components in Hedera rhombea Leaves and Their Cytotoxicity.

Two novel triterpene glycosides (1 and 2), 17 known triterpene glycosides (3-19), two known flavonoid glycosides (20 and 21), and two known norsesquiterpene glucosides (22 and 23) were isolated from Hedera rhombea (Araliaceae) leaves. The structures of 1 and 2 were determined by spectroscopic analysis, including two-dimensional NMR spectroscopy, and chromatographic analysis of the hydrolyzed products. The cytotoxicity of the isolated triterpene glycosides (1-19) against HL-60 human promyelocytic leukemia cells was evaluated. Compounds 9, 10, and 11 were cytotoxic to HL-60 cells with IC50 values of 7.2, 21.9, and 32.8 µM, respectively. Other compounds isolated from the leaves were not cytotoxic at sample concentrations of 50 µM.