Extract Containing -Inositol Suppresses TNF--Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3 and NF-B Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. (kiwiberry) is an edible fruit that contains various bioactive components. While extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified.

Pennogenin 3--β-Chacotrioside Attenuates Hypertrophied Lipid Accumulation by Enhancing Mitochondrial Oxidative Capacity.

Excessive lipid accumulation in adipocytes is a primary contributor to the development of metabolic disorders, including obesity. The consumption of bioactive compounds derived from natural sources has been recognized as being safe and effective in preventing and alleviating obesity. Therefore, we aimed to explore the antilipidemic effects of pennogenin 3--β-chacotrioside (P3C), a steroid glycoside, on hypertrophied 3T3-L1 adipocytes.

Schisandrin A in Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks.

Water Extract of Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases.

Patulin alleviates hepatic lipid accumulation by regulating lipogenesis and mitochondrial respiration.

Aims: The aim of this study is to evaluate the effects of patulin on hepatic lipid metabolism and mitochondrial oxidative function and elucidate the underlying molecular mechanisms.

Main Methods: The effects of patulin on hepatic lipid accumulation were evaluated in free fatty acid-treated AML12 or HepG2 cells through oil red O staining, triglyceride assay, real-time polymerase chain reaction, and western blotting. Alteration of mitochondrial oxidative capacity by patulin treatment was determined using Seahorse analysis to measure the oxygen consumption rate.

Role of Mitochondrial Stress Response in Cancer Progression.

Mitochondria are subcellular organelles that are a hub for key biological processes, such as bioenergetic, biosynthetic, and signaling functions. Mitochondria are implicated in all oncogenic processes, from malignant transformation to metastasis and resistance to chemotherapeutics. The harsh tumor environment constantly exposes cancer cells to cytotoxic stressors, such as nutrient starvation, low oxygen, and oxidative stress.

Phospholipase Cγ1 represses colorectal cancer growth by inhibiting the Wnt/β-catenin signaling axis.

As essential phospholipid signaling regulators, phospholipase C (PLC)s are activated by various extracellular ligands and mediate intracellular signal transduction. PLCγ1 is involved in regulating various cancer cell functions. However, the precise in vivo link between PLCγ1 and cancer behavior remains undefined.

SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice.

A metabolic imbalance between lipid synthesis and degradation can lead to hepatic lipid accumulation, a characteristic of patients with non-alcoholic fatty liver disease (NAFLD). Here, we report that high-fat-diet-induced sterol regulatory element-binding protein (SREBP)-1c, a key transcription factor that regulates lipid biosynthesis, impairs autophagic lipid catabolism via altered HS signaling. SREBP-1c reduced cystathionine gamma-lyase (CSE) via miR-216a, which in turn decreased hepatic HS levels and sulfhydration-dependent activation of Unc-51-like autophagy-activating kinase 1 (ULK1).

LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival.

Mitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival.

GDC-0980 (apitolisib) treatment with gemcitabine and/or cisplatin synergistically reduces cholangiocarcinoma cell growth by suppressing the PI3K/Akt/mTOR pathway.

Since conventional chemotherapy (gemcitabine and cisplatin) has marginal survival benefit in patients with advanced cholangiocarcinoma (CCA), an effective targeted therapeutic agent is urgently required. Activation of the PI3K/Akt/mTOR signaling pathway is frequently observed in CCA, and thus, PI3K and mTOR are promising therapeutic targets in CCA. Recently a new dual PI3K/mTOR inhibitor GDC-0980 (apitolisib) was introduced.

Modulation of the Autophagy-lysosomal Pathway in Hepatocellular Carcinoma Using Small Molecules.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer; it is the third most frequent cause of cancer-related death worldwide. In early-stage disease, surgical resection and liver transplantation are considered curative treatments. However, the majority of HCC patients present with advanced-stage disease that is treated using palliative systemic therapy.

Androgen-induced expression of DRP1 regulates mitochondrial metabolic reprogramming in prostate cancer.

Androgen receptor (AR) signaling plays a central role in metabolic reprogramming for prostate cancer (PCa) growth and progression. Mitochondria are metabolic powerhouses of the cell and support several hallmarks of cancer. However, the molecular links between AR signaling and the mitochondria that support the metabolic demands of PCa cells are poorly understood.

MFF Regulation of Mitochondrial Cell Death Is a Therapeutic Target in Cancer.

The regulators of mitochondrial cell death in cancer have remained elusive, hampering the development of new therapies. Here, we showed that protein isoforms of mitochondrial fission factor (MFF1 and MFF2), a molecule that controls mitochondrial size and shape, that is, mitochondrial dynamics, were overexpressed in patients with non-small cell lung cancer and formed homo- and heterodimeric complexes with the voltage-dependent anion channel-1 (VDAC1), a key regulator of mitochondrial outer membrane permeability. MFF inserted into the interior hole of the VDAC1 ring using Arg225, Arg236, and Gln241 as key contact sites.

Mitochondrial fission factor is a novel Myc-dependent regulator of mitochondrial permeability in cancer.

Background: Mitochondrial functions are exploited in cancer and provide a validated therapeutic target. However, how this process is regulated has remained mostly elusive and the identification of new pathways that control mitochondrial integrity in cancer is an urgent priority.

Methods: We studied clinically-annotated patient series of primary and metastatic prostate cancer, representative cases of multiple myeloma (MM) and publicly available genetic databases.

Phenolics and eudesmanolide from aged common sage exudate with sugar.

Nineteen compounds including one new flavanone were isolated from the juice of aged common sage exudate with sugar (ACSE). The isolated compounds were identified by NMR and MS analyses as levodopa methyl ester (), 3,4-dihydroxybenzoic acid (), ()-8-hydroxy-4-hydroxy-phenylpropanoic acid (), 4-hydroxybenzoic acid ethyl ester (), -caffeic acid (), -caffeic acid (), esculetin (), ()-8-hydroxy-3,4-dihydroxy-phenylpropanoic acid ethyl ester (), -rosmarinic acid (), -rosmarinic acid (), -rosmarinic acid methyl ester (), 6-methoxy-7,8,3',5'-tetrahydroxyflavanone (), nepetin (), -caffeic acid ethyl ester (), luteolin (), -caffeic acid ethyl ester (), 6-methoxynaringenin (), 1α-acetoxy-2-oxo-eudesman-3,7(11)-dien-8β,12-olide (), and hispidulin (). Compound was isolated for the first time from nature and seven compounds (, , , , , , and ) were newly identified from common sage.

Isolation of five proanthocyanidins from pear ( Nakai) fruit peels.

Five proanthocyanidins, two B-type dimers and three A-type trimers, were purified and isolated from the fruit peels of Nakai cv. Chuhwangbae. The isolated compounds were identified as (-)-epicatechin gallate-(4β → 8)-(-)-epicatechin (Hahashi et al.

3-Decylcatechol induces autophagy-mediated cell death through the IRE1α/JNK/p62 in hepatocellular carcinoma cells.

The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation.

Protocatechuic Acid from Pear Inhibits Melanogenesis in Melanoma Cells.

Despite the critical role of melanin in the protection of skin against UV radiation, excess production of melanin can lead to hyperpigmentation and skin cancer. Pear fruits are often used in traditional medicine for the treatment of melasma; therefore, we investigated the effects of pear extract (PE) and its component, protocatechuic acid (PCA), on melanogenesis in mouse melanoma cells. We found that PE and PCA significantly suppressed melanin content and cellular tyrosinase activity through a decrease in the expression of melanogenic enzymes and microphthalmia-associated transcription factor () in α-melanocyte stimulating hormone-stimulated mouse melanoma cells.

Glu-Phe from onion (Allium Cepa L.) attenuates lipogenesis in hepatocytes.

A Glu-Phe (EF) was isolated from onion (Allium cepa L. cv. Sunpower).

Sesquiterpene lactones and scopoletins from Waldst. & Kit. and their angiotensin I-converting enzyme inhibitory activities.

Ten compounds, including a new guaiane-type sesquiterpene lactone, were isolated from the aerial parts of . The structure of the new compound was determined to be 5-hydroxyguaia-3(4),11(13),10(14)-trien-6α,12-olide, named scoparanolide. Six known sesquiterpene lactones [estafiatone, 3β,4α-dihydroxyguaia-11(13),10(14)-dien-6α,12-olide, estafiatin, preeupatundin, 3β-hydroxycostunolide, and ludovicin B] and three known coumarin derivatives (scopoletin, scoparone, and isofraxidin) were identified by nuclear magnetic resonance and electrospray ionization mass spectroscopy.

Phenolics, acyl galactopyranosyl glycerol, and lignan amides from (Pall.) Kuntze.

Eleven antioxidative compounds, including five lignin amides, were isolated from the aerial part of (New Zealand spinach) using 1,1-diphenyl-2-picrylhydrazyl radicalscavenging assay-guided purification. The structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy. These compounds were identified as methyl linoleate (), methyl coumarate (), methyl ferulate (), 1-O-stearoyl-3-O-β-D-galactopyranosyl-sn-glycerol (), 1-O-caffeoyl-β-D-glucopyranoside (), N-trans-caffeoyltyramine (), cannabisin B (), cannabisin A (), Ntrans-feruloyltyramine (), N-cis-feruloyltyramine (), and N-trans-sinapoyltyramine ().

Furan, phenolic, and heptelidic acid derivatives produced by .

Eleven compounds, including a new sesquiterpene, were isolated from the culture medium of incubated with capsaicin. The structure of the new compound was determined to be 1,3,5a,6,7,8,9,9a-octahydro-9-hydroxy-9-(hydroxymethyl)-6-isopropyl-1-oxobenzo[c]oxepine-4- carboxylic acid, a heptelidic acid derivative. In addition, 10 known compounds were identified, namely 5-(hydroxymethyl)-3-furancarboxylic acid (flufuran), 3-hydroxypropanoic acid, 5-(hydroxymethyl)-2- furancarboxylic acid, 2-(4-hydroxyphenyl)-ethanol, 4-hydroxybenzoic acid, vanillic acid, 3,4-dihydroxybenzoic acid, 2-furanol, hydroheptelidic acid, and trichoderonic acid A, using spectroscopic data from nuclear magnetic resonance and electrospray ionization-mass spectroscopy.