Total Syntheses, Absolute Configurations, and Cytotoxicity Evaluation of Ugonstilbenes A, B, and C from the Rhizomes of .

This study describes the first and efficient syntheses of the naturally occurring ugonstilbenes A, B, and C. The stilbene skeleton was prepared using the Horner-Wadsworth-Emmons reaction. On the basis of their specific rotations, the absolute configurations of ugonstilbenes A and C were both determined to be , while the absolute configuration of ugonstilbene B was determined as 4a,9a.

β-Lapachone, an NQO1 activator, alleviates diabetic cardiomyopathy by regulating antioxidant ability and mitochondrial function.

Background: Diabetic cardiomyopathy (DC) is one of the major lethal complications in patients with diabetes mellitus (DM); however, no specific strategy for preventing or treating DC has been identified.

Purpose: This study aimed to investigate the effects of β-lapachone (Lap), a natural compound that increases antioxidant activity in various tissues, on DC and explore the underlying mechanisms.

Study Design And Methods: As an in vivo model, C57BL/6 mice were fed with the high-fat diet (HF) for 10 weeks to induce type 2 DM.

Mitochondrial activity is the key to the protective effect of β-Lapachone, a NAD booster, in healthy cells against cisplatin cytotoxicity.

Background: Cisplatin (CDDP) is a first-line chemotherapeutic drug for treating various cancers. However, CDDP also damages normal cells and causes many side effects. Recently, CDDP has been demonstrated to kill cancer cells by targeting mitochondria.

Extract and Individual Synthesized Component Derivatives Induce Activating-Transcription-Factor-3-Mediated Anti-Obesity Effects and Attenuate Obesity-Induced Metabolic Disorder by Suppressing C/EBPα in High-Fat-Induced Obese Mice.

Pharmacological studies indicate that extract (SME) can improve cardiac and blood vessel function. However, there is limited knowledge regarding the effects (exerted through epigenetic regulation) of SME and newly derived single compounds, with the exception of tanshinone IIA and IB, on obesity-induced metabolic disorders. In this study, we administered SME or dimethyl sulfoxide (DMSO) as controls to male C57BL/J6 mice after they were fed a high-fat diet (HFD) for 4 weeks.

Characterizing the structure-activity relationships of natural products, tanshinones, reveals their mode of action in inhibiting spleen tyrosine kinase.

The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications. Here, we employed pharmacophore-based drug screening combined with biochemical assay and molecular dynamics (MD) simulations to identify and characterize inhibitors targeting SYK. The built pharmacophore model, phar-TanI, successfully identified tanshinone (TanI (IC = 1.

Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3.

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 ( ) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration.

Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation.

Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics.

Antioxidant activity and inhibition of α-glucosidase by hydroxyl-functionalized 2-arylbenzo[b]furans.

This study synthesized a series of hydroxyl-functionalized 2-arylbenzo[b]furans based on the structure of tournefolic acid A and evaluated them for antioxidant and α-glucosidase inhibitory activities. Compounds 5a, 5e, and 5n showed remarkable inhibition of α-glucosidase (IC50 values of 1.9-3.

Ring-oxidative biotransformation and drug interactions of propofol in the livers of rats.

Propofol, an intravenous anesthetic agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known.

Neobavaisoflavone stimulates osteogenesis via p38-mediated up-regulation of transcription factors and osteoid genes expression in MC3T3-E1 cells.

Neobavaisoflavone (NBIF) is an isoflavone isolated from Psoralea corylifolia L, a plant claimed to have osteogenic activity and used to treat bone fractures, osteomalacia and osteoporosis. The present results showed that NBIF concentration-dependently promoted osteogenesis in MC3T3-E1cells, demonstrated by notable enhancement of alkaline phosphatase (ALP) activity, increase of bone-specific matrix proteins expression including type I collagen (Col-I), osteocalcin (OCN) and bone sialoprotein (BSP), and formation of bone nodules. However, cell proliferation in the presence of NBIF was not affected.

Combined phytochemistry and chemotaxis assays for identification and mechanistic analysis of anti-inflammatory phytochemicals in Fallopia japonica.

Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation.

A role of ygfZ in the Escherichia coli response to plumbagin challenge.

Plumbagin is found in many herbal plants and inhibits the growth of various bacteria. Escherichia coli strains are relatively resistant to this drug. The mechanism of resistance is not clear.

Psoralidin inhibits LPS-induced iNOS expression via repressing Syk-mediated activation of PI3K-IKK-IκB signaling pathways.

Psoralidin has been reported to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production, but the mechanisms of the action remain unclear. Thus, the impact of psoralidin on signaling pathways known to be implicated in NO synthesis was explored in LPS-activated RAW264.7 macrophages by using RT-PCR and Western blotting.

A new dimeric phenylpropanoid and cytotoxic norditerpene constituents from Podocarpus nakaii.

A new dimeric phenylpropanoid namely podonaka A (1), along with the 13 known compounds including diterpenes (2 and 3), norditerpenes (4 and 5), benzenoids (6-10), steroids (11 and 12), chalcone (13), and megastigmane (14), was isolated from the EtOH extract of Podocarpus nakaii Hayata. The structure of 1 was elucidated on the basis of spectroscopic analysis including 1D and 2D NMR and MS techniques. Biological evaluation showed that norditerpenes, inumakilactone B (4), and podolactone E (5) have potent cytotoxic activities against Daoy, WiDr, KB, and HeLa tumor cell lines.

Anti-inflammatory ergostanes from the basidiomata of Antrodia salmonea.

Three new anti-oxidative ergostanes, methyl antcinate L (1), antcin M (2), and methyl antcinate K (3), together with nine additional known compounds, 3-ketodehydrosulphurenic acid, sulphurenic acid, dehydrosulphurenic acid, 3beta,15alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid, zhankuic acid A, zhankuic acid B, zhankuic acid C, antcin C, and antcin K were isolated from the basidiomata of Antrodia salmonea, a newly identified species of Antrodia (Polyporaceae) in Taiwan. These three new compounds were identified as methyl 3alpha,7alpha,12alpha-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (1), 3alpha,12alpha-dihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oic acid (2), and methyl 3alpha,4beta,7beta-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (3) by spectroscopic analysis. We studied their antioxidative potential on the production of reactive oxygen species and nitric oxide (NO) in neutrophils and microglial cells, respectively.

Cryptotanshinone inhibits macrophage migration by impeding F-actin polymerization and filopodia extension.

We evaluated the anti-inflammatory effects of cryptotanshinone and tanshinone IIA, two major tanshinones isolated from Salvia miltiorrhiza, on chemoattractant-induced cell migration in RAW264.7 macrophages. Results showed that cryptotanshinone inhibited cell migration toward complement 5a (C5a) and macrophage inflammatory protein-1alpha (MIP-1alpha) in a concentration-dependent manner.

Involvement of NO/cGMP signaling in the apoptotic and anti-angiogenic effects of beta-lapachone on endothelial cells in vitro.

Neovascularization is an essential process in tumor development, it is conceivable that anti-angiogenic treatment may block tumor growth. In angiogenesis, nitric oxide (NO) is an important factor which mediates vascular endothelial cell growth and migration. beta-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho-[1,2-b]pyran-5,6-dione), a natural product extracted from the lapacho tree (Tabebuia avellanedae), has been demonstrated to possess anti-cancer and anti-viral effects.

Synthesis and cytotoxic activities of 4,5-diarylisoxazoles.

A series of 4,5-diarylisoxazoles related to combretastatin A-4 (CA-4) were synthesized and evaluated for cytotoxicity against three human cancer cell lines. Among them, compound 6e showed better cytotoxic activity than CA-4 in HeLa and HepG2 cell lines assayed with IC(50) value as low as 0.022 and 0.

Antitumor agents. 254. Synthesis and biological evaluation of novel neo-tanshinlactone analogues as potent anti-breast cancer agents.

In our previous study, neo-tanshinlactone (1) showed potent and selective anti-breast cancer activity. To explore the SAR of 1, nine analogues (15-18, 24-28) were designed and synthesized. Together with 1 and tamoxifen (TAM), all newly synthesized compounds and some intermediates were evaluated for in vitro anticancer activity against several human tumor cell lines.

Elimination of rutaecarpine and its metabolites in rat feces and urine measured by liquid chromatography.

Rutaecarpine is an alkaloid isolated from the medicinal herb Evodia rutaecarpa. This study was to evaluate the elimination pathway of rutaecarpine in rat feces and urine. Rutaecarpine and its metabolites (3-, 10-, 11- and 12-hydroxyrutaecarpine) in urine were measured after incubation with beta-glucuronidase.

Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza.

The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the treatment of cardiovascular and cerebrovascular diseases. To assess possible herb-drug interactions, the effects of the aqueous and ethyl acetate extracts of S. miltiorrhiza on cytochrome P450 (CYP) were studied.

New lanostanes and naphthoquinones isolated from Antrodia salmonea and their antioxidative burst activity in human leukocytes.

Four new compounds were isolated from the basidiomata of the fungus Antrodia salmonea, a newly identified species of Antrodia (Aphyllophorales) in Taiwan. These new compounds are named as lanosta-8,24-diene-3beta,15alpha,21-triol (1), 24-methylenelanost-8-ene-3beta,15alpha,21-triol (2), 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (3), and 2,3-dimethoxy-6-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (4), respectively. Their structures were elucidated by spectroscopic methods.

Oxidative metabolism of the alkaloid rutaecarpine by human cytochrome P450.

Rutaecarpine is the main active alkaloid of the herbal medicine, Evodia rutaecarpa. To identify the major human cytochrome P450 (P450) participating in rutaecarpine oxidative metabolism, human liver microsomes and bacteria-expressed recombinant human P450 were studied. In liver microsomes, rutaecarpine was oxidized to 10-, 11-, 12-, and 3-hydroxyrutaecarpine.

Cytotoxic and aromatic constituents from Salvia miltiorrhiza.

As part of an ongoing study of traditional Chinese medicinal plants, the root tissue of Salvia miltiorrhiza was further investigated for its chemical constituents. Five naturally occurring products along with 13 known constituents were isolated from an ethyl acetate-soluble portion of its ethanol extract. Their structures were elucidated by means of spectroscopic methods.

Nitrogen-containing compounds from Salvia miltiorrhiza.

Five new N-containing compounds, neosalvianen (1), salvianen (2), salvianan (3), salviadione (4), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (5), were isolated from Salvia miltiorrhiza. Their structures were mainly established by spectroscopic methods. Neosalvianen (1) and its analogues (6a, 6b) were synthesized for spectroscopic data comparison.