Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.

Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls.

3,4,5-tri-O-caffeoylquinic acid attenuates influenza A virus induced inflammation through Toll-like receptor 3/7 activated signaling pathway.

Background: 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), a natural polyphenolic acid, has been shown to be effective against influenza A virus (IAV) infection. Although it was found to inhibit the neuraminidase of IAV, it may also perturb other cellular functions, as polyphenolic acids have shown antioxidant, anti-inflammatory and other activities.

Purpose: This study aimed to investigate the effect of 3,4,5-TCQA at a cell level, which is critical for protecting host cell from IAV infection.

Berberine Reduces Lipid Accumulation in Obesity via Mediating Transcriptional Function of PPARδ.

Obesity is defined as a dampness-heat syndrome in traditional Chinese medicine. Coptidis Rhizoma is an herb used to clear heat and eliminate dampness in obesity and its complications. Berberine (BBR), the main active compound in Coptidis Rhizoma, shows anti-obesity effects.

Berberine activates PPARδ and promotes gut microbiota-derived butyric acid to suppress hepatocellular carcinoma.

Background: Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-inducible transcription factors that govern various essential metabolic activities in the liver and other organs. Recently, berberine (BBR) has been characterized as a modulator of PPARs; however, the matter of whether PPARs are involved in the inhibitory effect of BBR on hepatocellular carcinoma (HCC) is not well understood.

Purpose: This study aimed to investigate the role of PPARs in the suppressive effect of BBR on HCC and to elucidate the relative mechanism.

Pore-Forming Cardiotoxin VVA2 (Volvatoxin A2) Variant I82E/L86K Is an Atypical Duplex-Specific Nuclease.

VVA2 (volvatoxin A chain 2) is a cardiotoxic protein purified from . Its biological activities include hemolysis, writhing reaction, neurotoxicity, and ventricular systolic arresting activity. The cytotoxicity of VVA2 was mainly considered due to its pore-forming activity.

Therapeutic Efficacies of Berberine against Neurological Disorders: An Update of Pharmacological Effects and Mechanisms.

Neurological disorders are ranked as the leading cause of disability and the second leading cause of death worldwide, underscoring an urgent necessity to develop novel pharmacotherapies. Berberine (BBR) is a well-known phytochemical isolated from a number of medicinal herbs. BBR has attracted much interest for its broad range of pharmacological actions in treating and/or managing neurological disorders.

Novel mechanistic insight on the neuroprotective effect of berberine: The role of PPARδ for antioxidant action.

Cerebral ischemic stroke ranks the second leading cause of death and the third leading cause of disability in lifetime all around the world, urgently necessitating effective therapeutic interventions. Reactive oxygen species (ROS) have been implicated in stroke pathogenesis and peroxisome proliferator-activated receptors (PPARs) are prominent targets for ROS management. Although recent research has shown antioxidant effect of berberine (BBR), little is known regarding its effect upon ROS-PPARs signaling in stroke.

Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota.

The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH) as a coenzyme. Here, we show that oral berberine (BBR) might supply H through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH from dihydrobiopterin; the increased BH enhances TH activity, which accelerates the production of L-dopa by the gut bacteria.

Berberine Protects C17.2 Neural Stem Cells From Oxidative Damage Followed by Inducing Neuronal Differentiation.

Neurodegeneration is the loss of structure and/or function of neurons. Oxidative stress has been suggested as one of the common etiology in most of the neurodegenerative diseases. Previous studies have demonstrated the beneficial effects of berberine in various neurodegenerative and neuropsychiatric disorders.

Isolation of novel biflavonoids from Cardiocrinum giganteum seeds and characterization of their antitussive activities.

Ethnopharmacological Relevance: Seeds of Cardiocrinum giganteum var. yunnanense (Leichtlin ex Elwes) Stearn (Liliaceae), also known as Doulingzi, have been used as a folk substitute for conventional antitussive herb "Madouling" (Aristolochia species) to treat chronic bronchitis and pertussis. The active antitussive phytochemicals in C.

Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine.

Nitroreductases (NRs) are bacterial enzymes that reduce nitro-containing compounds. We have previously reported that NR of intestinal bacteria is a key factor promoting berberine (BBR) intestinal absorption. We show here that feeding hamsters with high fat diet (HFD) caused an increase in blood lipids and NR activity in the intestine.

In Vitro Study of the Metabolic Characteristics of Eight Isoquinoline Alkaloids from Natural Plants in Rat Gut Microbiota.

Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut microbiota and an LC/MS-IT-TOF technique was used to identify the resulting metabolites. Palmatine, tetrahydropalmatine, dauricine, and tetrandrine containing nitro-hexatomic isoquinoline rings could be easily transformed by the intestinal flora in vitro and a total of nine demethylated metabolites were detected.

Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism.

Objective: Berberine (BBR) clinically lowers blood lipid and glucose levels via multi-target mechanisms. One of the possible mechanisms is related to its effect on the short chain fatty acids (SCFAs) of the gut microbiota. The goal of this study is to investigate the therapeutic effect and mode of action of BBR working through SCFAs of the gut microbiota (especially, butyrate).

Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC-MS/MS: Rg1 excretion in rat bile, urine and feces.

Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity (>0.

In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats.

Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.

Interaction effects on cytochrome P450 both in vitro and in vivo studies by two major bioactive xanthones from Halenia elliptica D. Don.

The major components, 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1) and 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) isolated from Halenia elliptica D. Don (Gentianaceae), could cause vasodilatation in rat coronary artery with different mechanisms. In this work, high-performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMS-IT-TOF) was used to clarify the metabolic pathways, and CYP450 isoform involvement of HM-1 and HM-5 were also studied in rat.

Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters.

Background: Berberine (BBR), as a new medicine for hyperlipidemia, can reduce the blood lipids in patients. Mechanistic studies have shown that BBR activates the extracellular-signal regulated kinase pathway by stabilizing low-density-lipoprotein receptor mRNA. However, aside from inhibiting the intestinal absorption of cholesterol, the effects of BBR on other metabolic pathways of cholesterol have not been reported.

Transforming berberine into its intestine-absorbable form by the gut microbiota.

The gut microbiota is important in the pathogenesis of energy-metabolism related diseases. We focused on the interaction between intestinal bacteria and orally administered chemical drugs. Oral administration of berberine (BBR) effectively treats patients with metabolic disorders.

Biotransformation and in vitro metabolic profile of bioactive extracts from a traditional Miao-nationality herbal medicine, Polygonum capitatum.

Polygonum capitatum Buch.-Ham.ex D.

Excretion of berberine and its metabolites in oral administration in rats.

Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200 mg/kg).