Hepatoprotective Lignan Glycosides from the Leaves and Stems of Symplocos cochinchinensis (Lour.) S. Moore.

This study investigates Symplocos cochinchinensis (Lour.) S. Moore leaves and stems, commonly known as Symplocos, a plant indigenous to Asia renowned for its traditional use in holistic medicine.

Symplosaponins A-D: New acylated oleanane-type triterpene saponins from Symplocos cochinchinensis and their hepatoprotective effect.

Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), and 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-β-D-glucopyranoside (9).

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, 18β-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), N -methylisoajimaline (11), N -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-β-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-β-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-β-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.

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).

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.

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 , 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.

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 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 (M), suggesting the possibility of designing potential inhibitors based on shikonin derivatives. The present study aimed to identify potential shikonin derivatives targeting the M of COVID-19 by using molecular docking and molecular dynamics simulations.

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 β-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.

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.

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.

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 Ca-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.

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.

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.

Dihydrostilbene glycosides from var. assamica and their cytotoxic activity.

Three undescribed dihydrostilbene glycosides, 3,5-dihydroxyldihydrostilbene 4'--[6''--(4'''-hydroxylbenzoyl)]--D-glucopyranoside (), 3,5-dihydroxyldihydrostilbene 4'--(6''--galloyl)--D-glucopyranoside (), and 3,5-dihydroxyldihydrostilbene 4'--[6''--(3''',4'''-dimethoxyl)galloyl]--D-glucopyranoside (), and seven known compounds, kaempferol 3---D-glucopyranoside (), isoquercitrin (), kaempferol 3--L-rhamnoside (), quercitrin (, (6,9)-roseoside (), (-)-epicatechin 3--gallate (), and (-)-epigallocatechin 3--gallate () have been isolated from the methanol extract of the leaves of var. (J.W.

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.

Novel ANO1 Inhibitor from Extract Exerts Anticancer Activity through Downregulation of ANO1.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds ( and ) and four known compounds (-) from These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells.

Four new sucrose diesters of substituted truxinic acids from Trigonostemon honbaensis with their anoctamin-1 inhibitory activity.

Truxinic acid sucrose diesters analogs possess interesting chemical structure by the presence of cyclobutane-ring and macrocyclic sucrose diesters moieties which are rarely found from natural sources. This paper describes the isolation and structural elucidation of four new sucrose diesters of substituted truxinic acids, trigohonbanosides A-D (1-4), from the leaves of Trigonostemon honbaensis. Their chemical structures were elucidated by HR-ESI-MS, NMR, and CD spectroscopic methods.

Domino [4 + 2] Annulation Access to Quinone-Indolizine Hybrids: Anticancer -Fused Polycycles.

A highly efficient synthetic route to new quinone-indolizine hybrids was accomplished from quinones and -substituted pyrrole-2-carboxaldehydes via a domino Michael addition-aldol condensation-aromatization sequence through which the central pyridine ring was constructed in atom-economical and environment-friendly manner. Post modification of the resulting products was also demonstrated, enabling further expansion of this heterocyclic chemical space. Biological evaluation of the quinone-indolizine hybrids revealed potent anticancer effects in human prostate adenocarcinoma cells (PC-3) and oral adenosquamous carcinoma cells (CAL-27).

Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2.

Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN.

Diversity-oriented generation and biological evaluation of new chemical scaffolds bearing a 2,2-dimethyl-2H-chromene unit: Discovery of novel potent ANO1 inhibitors.

Chemical territory bearing a 2,2-dimethyl-2H-chromene motif was expanded by utilizing an o-hydroxy aldehyde group of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde as a synthetic handle to install distinctive morphology and functionality of each scaffold. Cell based assays and in silico docking analysis led us to discover that these new compounds exhibit inhibitory effect on anoctamin1 (ANO1). ANO1 is amplified and highly expressed in various carcinomas including prostate cancer, esophageal cancer, breast cancer, and pancreatic cancer.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells.

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl and HCO is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors.

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

Two new norlignans, pouzolignan N () and pouzolignan O (), together with five known norlignans, pouzolignan F (), pouzolignan G (), pouzolignan H (), pouzolignan L (), and gnetifolin F () were isolated from the aerial parts of (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.