Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential.

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

Alkaloids and Lignans from the Aerial Parts of Rauvolfia tetraphylla Inhibit NO Production in LPS-activated RAW 264.7 Cells.

Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18ß-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), Nb -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-ß-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-ß-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-ß-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56 µM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66 µM. The other isolates were inactive with IC50 values over 100 µM.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

Dopaminergic cell protection and alleviation of neuropsychiatric disease symptoms by VMAT2 expression through the class I HDAC inhibitor TC-H 106.

The importance of vesicular monoamine transporter 2 (VMAT2) in dopamine regulation, which is considered crucial for neuropsychiatric disorders, is currently being studied. Moreover, the development of disease treatments using histone deacetylase (HDAC) inhibitors (HDACi) is actively progressing in various fields. Recently, research on the possibility of regulating neuropsychiatric disorders has been conducted. In this study, we evaluated whether VMAT2 expression increased by an HDACi can fine-tune neuropsychotic behavior, such as attention deficit hyperactivity disorder (ADHD) and protect against the cell toxicity through oxidized dopamine. First, approximately 300 candidate HDACi compounds were added to the SH-SY5Y dopaminergic cell line to identify the possible changes in the VMAT2 expression levels, which were measured using quantitative polymerase chain reaction. The results demonstrated, that treatment with pimelic diphenylamide 106 (TC-H 106), a class I HDACi, increased VMAT2 expression in both the SH-SY5Y cells and mouse brain. The increased VMAT2 expression induced by TC-H 106 alleviated the cytotoxicity attributed to 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+ ) and free dopamine treatment. Moreover, dopamine concentrations, both intracellularly and in the synaptosomes, were significantly elevated by increased VMAT2 expression. These results suggest that dopamine concentration regulation by VMAT2 expression induced by TC-H 106 could alter several related behavioral aspects that was confirmed by attenuation of hyperactivity and impulsivity, which were major characteristics of animal model showing ADHD-like behaviors. These results indicate that HDACi-increased VMAT2 expression offers sufficient protections against dopaminergic cell death induced by oxidative stress. Thus, the epigenetic approach could be considered as therapeutic candidate for neuropsychiatric disease regulation.

ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers.

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.

Unveiling the Potentiality of Shikonin Derivatives Inhibiting SARS-CoV-2 Main Protease by Molecular Dynamic Simulation Studies.

Shikonin, a phytochemical present in the roots of Lithospermum erythrorhizon, is well-known for its broad-spectrum activity against cancer, oxidative stress, inflammation, viruses, and anti-COVID-19 agents. A recent report based on a crystallographic study revealed a distinct conformation of shikonin binding to the SARS-CoV-2 main protease (Mpro), suggesting the possibility of designing potential inhibitors based on shikonin derivatives. The present study aimed to identify potential shikonin derivatives targeting the Mpro of COVID-19 by using molecular docking and molecular dynamics simulations. A total of 20 shikonin derivatives were screened, of which few derivatives showed higher binding affinity than shikonin. Following the MM-GBSA binding energy calculations using the docked structures, four derivatives were retained with the highest binding energy and subjected to molecular dynamics simulation. Molecular dynamics simulation studies suggested that alpha-methyl-n-butyl shikonin, beta-hydroxyisovaleryl shikonin, and lithospermidin-B interacted with two conserved residues, His41 and Cys145, through multiple bonding in the catalytic sites. This suggests that these residues may effectively suppress SARS-CoV-2 progression by inhibiting Mpro. Taken together, the present in silico study concluded that shikonin derivatives may play an influential role in Mpro inhibition.

Two new triterpenoid glycosides from Bacopa monnieri and their cytotoxic activity.

Using combined chromatographic methods, two new triterpenoid glycosides, bacopasaponin K (1) and bacopasaponin L (2), along with eight known compounds, bacopaside IV (3), bacopaside VII (4), bacopasaponin E (5), bacoside A3 (6), bacopasaponin F (7), bacopasaponin C (8), bacopaside I (9), and bacopaside II (10) were isolated from the methanol extract of the Bacopa monnieri. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS and comparing with the NMR data reported in the literature. All these compounds were evaluated for their cytotoxic activity using the cell counting kit-8 (CCK-8) assay. Compounds 4, 6, 8, and 10 exhibited potential cytotoxic effects against human lung cancer cells (PC9) and human colon cancer cells (SW620).

GB83, an Agonist of PAR2 with a Unique Mechanism of Action Distinct from Trypsin and PAR2-AP.

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and ß-arrestin recruitment. Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been misconceived as antagonists, and this has impeded a better understanding of the pathophysiological role of PAR2. In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist of PAR2 that induces unique cellular signaling, distinct from trypsin and PAR2-activating peptide (AP). Activation of PAR2 by GB83 markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed and sustained manner compared to the rapid and transient signals induced by trypsin and PAR2-AP. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization with ß-arrestin. Moreover, the recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2. Our results revealed that GB83 is a bona fide agonist of PAR2 that uniquely modulates PAR2-mediated cellular signaling and is a useful pharmacological tool for studying the pathophysiological role of PAR2.

Anticancer effect of verteporfin on non-small cell lung cancer via downregulation of ANO1.

Anoctamin 1 (ANO1) is a calcium-activated chloride channel found in various cell types and is overexpressed in non-small cell lung cancer (NSCLC), a major cause of cancer-related mortality. With the rising interest in development of druggable compounds for NSCLC, there has been a corresponding rise in interest in ANO1, a novel drug target for NSCLC. However, as ANO1 inhibitors that have been discovered simultaneously exhibit both the functions of an inhibition of ANO1 channel as well as a reduction of ANO1 protein levels, it is unclear which of the two functions directly causes the anticancer effect. In this study, verteporfin, a chemical compound that reduces ANO1 protein levels was identified through high-throughput screening. Verteporfin did not inhibit ANO1-induced chloride secretion but reduced ANO1 protein levels in a dose-dependent manner with an IC50 value of ~300 nM. Moreover, verteporfin inhibited neither P2Y receptor-induced intracellular Ca2+ mobilization nor cystic fibrosis transmembrane conductance regulator (CFTR) channel activity, and molecular docking studies revealed that verteporfin bound to specific sites of ANO1 protein. Confirming that verteporfin reduces ANO1 protein levels, we then investigated the molecular mechanisms involved in its effect on NSCLC cells. Interestingly, verteporfin decreased ANO1 protein levels, the EGFR-STAT3 pathway as well as ANO1 mRNA expression. Verteporfin reduced the viability of ANO1-expressing cells (PC9, and gefitinib-resistant PC9) and induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage. However, it did not affect hERG channel activity. These results show that the anticancer mechanism of verteporfin is caused via the down-regulation of ANO1.

Two new norlignans from the aerial parts of Pouzolzia sanguinea (Blume) Merr.

Two new norlignans, pouzolignan N (1) and pouzolignan O (2), together with five known norlignans, pouzolignan F (3), pouzolignan G (4), pouzolignan H (5), pouzolignan L (6), and gnetifolin F (7) were isolated from the aerial parts of Pouzolzia sanguinea (Blume) Merr. Their chemical structures were elucidated via HR-ESI-MS and NMR spectroscopic methods. Absolute configurations at stereocenters were confirmed by comparisons of CD spectra with those of TD-DFT calculations. Compounds 1-6 exhibited chemical structures unique to Pouzolzia species. At a concentration of 30 µM, compounds 1-7 exhibited weak cytotoxic activity toward CAL27 and MDA-MB-231 cell lines (cell viability from 65.3 ± 0.86 to 98.8 ± 1.23%). They also inhibited anoctamin-1 activity with inhibitory rates from 8.1 ± 0.87 to 24.3 ± 1.41%.

Impact of regional anesthesia on outcomes of geriatric patients undergoing lower extremity revascularization: A propensity score-matched cohort study.

Lower extremity revascularization (LER) for peripheral artery disease in elderly patients is associated with a high risk of perioperative morbidity and mortality. This study aimed to a conduct retrospective review and propensity score matching analysis to determine whether the use of regional anesthesia (RA) instead of general anesthesia (GA) in geriatric patients undergoing LER for peripheral artery disease results in improved short-term mortality and health outcomes. We reviewed medical records of 1271 patients aged >65 years who underwent LER at our center between May 1998 and February 2016. According to the anesthesia method, patients were grouped in the GA and RA groups. The primary outcome was short-term mortality (7-day and 30-day). The secondary outcomes were 5-year survival rate, intraoperative events, postoperative morbidity, and postoperative length of stay. A propensity score-matched cohort design was used to control for potentially confounding factors including patient demographics, comorbidities, American Society of Anesthesiologists physical status, and preoperative medications. After propensity score matching, 722 patients that received LER under GA (n = 269) or RA (n = 453) were identified. Patients from the GA group showed significantly higher 7-day mortality than those from the RA group (5.6% vs 2.7% P = .048); however, there was no significant difference in 30-day mortality between the groups (GA vs RA: 6.3% vs 3.6%, P = .083). The 5-year survival rate and incidence of arterial and central venous catheter placement or intraoperative dopamine and epinephrine use were significantly higher in the GA group than in the RA group (P < .05). In addition, the frequency of immediate postoperative oxygen therapy or mechanical ventilation support was higher in the GA group (P < .05). However, there was no difference in the postoperative cardiopulmonary and cerebral complications between the 2 groups. These results suggest that RA can reduce intraoperative hemodynamic support and provide immediate postoperative respiratory intensive care. In addition, the use of RA may be associated with better short-term and 5-year survival rates in geriatric patients undergoing LER.

Dihydrostilbene glycosides from Camellia sinensis var. assamica and their cytotoxic activity.

Three undescribed dihydrostilbene glycosides, 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(4'''-hydroxylbenzoyl)]-ß-D-glucopyranoside (1), 3,5-dihydroxyldihydrostilbene 4'-O-(6''-O-galloyl)-ß-D-glucopyranoside (2), and 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(3''',4'''-dimethoxyl)galloyl]-ß-D-glucopyranoside (3), and seven known compounds, kaempferol 3-O-ß-D-glucopyranoside (4), isoquercitrin (5), kaempferol 3-O-α-L-rhamnoside (6), quercitrin (7), (6S,9R)-roseoside (8), (-)-epicatechin 3-O-gallate (9), and (-)-epigallocatechin 3-O-gallate (10) have been isolated from the methanol extract of the leaves of Camellia sinensis var. assamica (J.W.Mast.) Kitam. (synnonym of Camellia assamica (Mast.) H.T.Chang) (Theaceae). Their structures were elucidated by spectroscopic methods (1 D-, 2 D-NMR) and mass spectra. All compounds were evaluated for cytotoxic activity against human oral cancer (CAL27) and human breast cancer (MDAMB231) cell lines. Compound 10 showed significant cytotoxic activity against CAL27 and MDAMB231 cell lines with IC50 values of 9.78 ± 0.25 and 3.27 ± 0.18 µM, respectively, compared to those of positive control, capecitabine (IC50 values of 8.20 ± 0.75 and 5.20 ± 0.89 µM).

Oleanane-type triterpene saponins from Aralia armata leaves and their cytotoxic activity.

Two new, aramatosides A and B (1 and 2), together with seven known oleanane-type triterpene saponins (3-9) were isolated from the leaves of Aralia armata. Their structures were determined by combination of HR-ESI-MS, 1 D and 2 D NMR spectral data as well as comparison with the previous literature. Compounds 6-9 exhibited cytotoxic effects towards three human cancer cell lines (HT29, A2058, and A549) with IC50 values ranging from 2.01 ± 0.17 to 18.8 ± 1.17 µM. Especially, compound 7 (narcissiflorin) showed significant cytotoxic activity against HT29 and A549 cell lines with IC50 values of 2.02 ± 1.65 and 2.01 ± 0.17 µM, respectively, which are smaller than those of positive control irinotecan hydrochloride (IC50 values of 10.3 ± 1.32 and 9.89 ± 0.19 µM).

Diethylstilbestrol, a Novel ANO1 Inhibitor, Exerts an Anticancer Effect on Non-Small Cell Lung Cancer via Inhibition of ANO1.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca2+-activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent.

Urinary Metabolomic Profiling after Administration of Corydalis Tuber and Pharbitis Seed Extract in Healthy Korean Volunteers.

Pharmacometabolomics is a useful tool to identify biomarkers that can assess and predict response after drug administration. The primary purpose of pharmacometabolomics is to better understand the mechanisms and pathways of a drug by searching endogenous metabolites that have significantly changed after drug administration. DA-9701, a prokinetic agent, consists of Pharbitis seed and Corydalis tube extract and it is known to improve the gastrointestinal motility. Although the overall mechanism of action of DA-9701 remains unclear, its active ingredients, corydaline and chlorogenic acid, act as a 5-HT3 and D2 receptor antagonist and 5-HT4 receptor agonist. To determine the significant metabolites after the administration of DA-9701, a qualitative analysis was carried out using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometer followed by a multivariate analysis. Seven candidates were selected and a statistical analysis of fold change was performed over time. Our study concluded that all the seven selected metabolites were commonly involved in lipid metabolism and purine metabolism.

Novel positive allosteric modulator of protease-activated receptor 1 promotes skin wound healing in hairless mice.

BACKGROUND AND PURPOSE: Protease-activated receptor 1 (PAR1) is a GPCR expressed in several skin cell types, including keratinocyte and dermal fibroblast. PAR1 activation plays a crucial role in the process of skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated its effect on skin wound healing. EXPERIMENTAL APPROACH: The enhancement of PAR1 activity by GB83 was measured using Fluo-4 calcium assay. In silico docking analysis of GB83 in PAR1 was performed using dock ligands method (CDOCKER) with CHARMm force field. Effects of GB83 on cell viability and gene expression were observed using MTS assay and quantitative real-time PCRs, respectively. SKH-1 hairless mice were used to investigate the wound healing effect of GB83. KEY RESULTS: We demonstrated that GB83 did not activate PAR1 by itself but strongly enhanced PAR1 activation by thrombin and PAR1-activating peptide (AP). In silico docking analysis revealed that GB83 can bind to the PAR1 binding site of vorapaxar. GB83 significantly promoted PAR1-mediated cell viability and migration. In addition, the enhancement of PAR1 activity by GB83 strongly increased gene expression of TGF-ß, fibronectin and type I collagen in vitro and promoted skin wound healing in vivo. CONCLUSION AND IMPLICATIONS: Our results revealed that GB83 is the first positive allosteric modulator of PAR1 and it can be a useful pharmacological tool for studying PAR1 and a potential therapeutic agent for skin wound healing.

Relationship between hs-CRP and HbA1c in Diabetes Mellitus Patients: 2015-2017 Korean National Health and Nutrition Examination Survey.

This study aimed to examine the relationship between hemoglobin A1c (HbA1c), one of the indicators of diabetes, and high sensitivity C-reactive protein (hs-CRP), one of the indicators of inflammation. Raw data from the Korean National Health and Nutrition Examination Survey (KNHANES, 2015-2017) was analyzed. Among the patients diagnosed with diabetes, 1,479 adults were selected as subjects for our study, and their HbA1c levels, hs-CRP levels, sex, age, body mass index (BMI), waist circumference, level of triglycerides and high-density lipoprotein (HDL)-cholesterol, hypertension, receipt of diagnosis, monthly average income, education, and drinking and smoking habits were recorded. Multiple regression analysis of hs-CRP was performed by dividing hs-CRP into quartiles using HbA1c as the dependent variable. In Model 1, sex, age, and BMI were adjusted, and in Model 2, sex, age, BMI, waist circumference, level of triglycerides and HDL-cholesterol, hypertension, and receipt of diagnosis were adjusted. In Model 3, Model 2 parameters along with monthly average household income, education level, and drinking and smoking habits were adjusted. HbA1c levels increased as the hs-CRP quartile increased, that is, 2nd Quartile=0.307, p=0.003; 3rd Quartile=0.431, p=0.001; and 4th Quartile=0.550, p=0.001. Of the various factors related to diabetes, this study examined the relationship between inflammation and diabetes.

Determination of candesartan or olmesartan in hypertensive patient plasma using UPLC-MS/MS.

Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity (r > 0.99) in the concentration range of 2-500 ng/mL for candesartan and 5-2,500 ng/mL for olmesartan. Accuracies were 86.70-108.8% for candesartan and 87.87-112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans.

Triterpenoid glycosides from the rhizomes of Allium ascalonicum and their anoctamin-1 inhibitory activity.

Ten triterpenoid glycosides including two undescribed compounds (1 and 2) were isolated from the methanol extract of Allium ascalonicum rhizomes. These compounds were structurally elucidated to be 3ß-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl-19α-hydroxyolean-12-ene-28-oic acid 28-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl] ester (1), 3-O-ß-D-glucopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-α-L-arabinopyranosyl-3ß,19α-dihydroxyoleanane-12-en-28-oic acid (2), lactifoloside C (3), lactifoloside H (4), randiasaponin IV (5), kudinoside G (6), ilexkudinoside W (7), lactifoloside G (8), kudinoside D (9), and ilexkudinoside T (10) by analyzing their HR-ESI-MS, NMR spectral data and by comparison with those reported in the literature. Compounds 1-10 were evaluated for anoctamin-1 (ANO1) inhibitory activity using yellow fluorescent protein reduction assays. At the concentration of 30 µM, compounds 2 and 9 displayed moderate ANO1 inhibitory percentages of 28.9 ± 0.85% and 26.2 ± 0.65%, respectively.

Chemical constituents from Schisandra sphenanthera and their cytotoxic activity.

Extensive phytochemical investigation of Schisandra sphenanthera leaves resulted in the isolation of six highly oxygenated nortriterpenoids (1-6) and five lignans (7-11) including a new pre-schisanartane-type, schisandrathera A (1), a new dibenzocyclooctadiene glycoside, schisandrathera B (7) and two new lignans, schisandrathera C (8) and schisandrathera D (9). Their chemical structures including absolute configurations were determined extensively by means of HR-ESI-MS, NMR, and ECD spectra. In addition, all isolated compounds were tested for cytotoxic activity against PC3 (prostate cancer) and MCF7 (breast cancer) cell lines. Among these compounds, schirubrisin B (3) showed strong cytotoxic effect on both PC3 and MCF7 cell lines with IC50 values of 3.21 ± 0.68, 13.30 ± 0.68 µM, respectively, whereas ten remaining compounds were found to be less effective in the investigated models.