Discovery of natural AMPK activator from the fruits of Xanthium sibiricum Patr.: Xanthiumine A, protoberberine alkaloid with unique C skeleton.

Two protoberberine alkaloids with a unique C skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a.

Inhibition effect of 1-acetoxy-6α-(2-methylbutyryl)eriolanolide toward soluble epoxide hydrolase: Multispectral analysis, molecular dynamics simulation, biochemical, and in vitro cell-based studies.

Soluble epoxide hydrolase (sEH) serves as a potential target in inflammation-related diseases. Based on the bioactivity-guided separation, a new sesquiterpenoid inulajaponoid A (1) was isolated from Inula japonica with a sEH inhibitory effect, together with five known compounds, such as 1-O-acetyl-6-O-isobutyrylbritannilactone (2), 6β-hydroxytomentosin (3), 1β,8β-dihydroxyeudesma-4(15),11(13)-dien-12,6α-olide (4), (4S,6S,7S,8R)-1-O-acetyl-6-O-(3-methylvaleryloxy)-britannilactone (5), and 1-acetoxy-6α-(2-methylbutyryl)eriolanolide (6). Among them, compounds 1 and 6 were assigned as mixed and uncompetitive inhibitors, respectively.

A high-resolution α-glucosidase inhibition profiling for targeted identification of natural antidiabetic products from (L.) Pic. Serm and their inhibitory mechanism study.

The targeted identification of α-glucosidase inhibitors from the crude ethyl acetate of (L.) Pic. Serm () was guided by high-resolution inhibition profiling.

Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites.

18-Glycyrrhetinic acid (GA) is a triterpenoid possessing an anti-inflammatory activity in vivo, while the low bioavailability limits its application due to its intestinal accumulation. In order to investigate the metabolism of GA in intestinal microbes, it was incubated with human intestinal fungus RG13B1, finally leading to the isolation and identification of three new metabolites () and three known metabolites () based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite could target myeloid differentiation protein 2 (MD2) to suppress the activation of nuclear factor-kappa B (NF-κB) signaling pathway via inhibiting the nuclear translocation of p65 to downregulate its target proteins and genes in lipopolysaccharide (LPS)-mediated RAW264.

SILAC-based chemoproteomics reveals a neoligan analogue as an anti-inflammatory agent targeting IRGM to ameliorate cytokine storm.

Cytokine storm is a key feature of sepsis and severe stage of COVID-19, and the immunosuppression after excessive immune activation is a substantial hazard to human life. Both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by various pattern recognition receptors (PRRs), which lead to the immune response. A number of neolignan analogues were synthesized in this work and showed powerful anti-inflammation properties linked to the response to innate and adaptive immunity, as well as NP-7 showed considerable anti-inflammatory activity at 100 nM.

Room Temperature Engineering Crystal Facet of CuO for Photocatalytic Degradation of Methyl Orange.

Cuprous oxide (CuO) has received enormous interest for photocatalysis owing to its narrow band gap of 2.17 eV, which is beneficial for visible-light absorption. In this work, we succeeded in synthesizing CuO nanocrystals with two morphologies, cube and sphere, at room temperature via a simple wet-chemistry strategy.

Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from .

Biseuphoids A (1) and B (2), two unprecedented -abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from , along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions.

Amentoflavone from Selaginella tamariscina as a potent inhibitor of gut bacterial β-glucuronidase: Inhibition kinetics and molecular dynamics stimulation.

Gut bacterial β-glucuronidase (GUS) plays a pivotal role in the metabolism and reactivation of a vast of glucuronide conjugates of both endogenous and xenobiotic compounds in the gastrointestinal tract of human, which has been implicated in certain drug-induced gastrointestinal tract (GI) toxicity in clinic. Inhibitors of gut microbial GUS exhibited great potentials in relieving the drug-induced GI toxicity. In this study, Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) were evaluated for their inhibitory activity against Escherichia coli GUS.

Investigation of the inhibitory effect of protostanes on human carboxylesterase 2 and their interaction: Inhibition kinetics and molecular stimulations.

Carboxylesterase 2 (CES 2), plays a pivotal role in endobiotic homeostasis and xenobiotic metabolism. Protostanes, the major constituents of the genus Alisma, display a series of pharmacological activities. Despite the extensive studies of pharmacological activities, the investigation on inhibitory effects of protostanes against CES 2 is rarely reported.

An integrated approach based on phytochemistry, network pharmacology and metabolomics reveals the mechanism of action of L. for allergic rhinitis.

L. (XS) is a traditional Chinese medicine (TCM) that has been widely used in Chinese medicine prescription for allergic rhinitis (AR). However, the action mechanisms of XS on the therapeutic effects on AR remain elusive.

The inhibition effect of uncarialin A on voltage-dependent L-type calcium channel subunit alpha-1C: Inhibition potential and molecular stimulation.

Cardiovascular diseases, such as hypertension and cardiac failure, have become the most major and global cause for threatening human health in recent years. Uncaria rhynchophylla as a traditional Chinese medicine is widely used to treat hypertension for a long history, whereas its medicinal effective components and potential action mechanism are uncertain. Therefore, twenty-four alkaloids (1-24) isolated from U.

Protostane-type triterpenoids as natural soluble epoxide hydrolase inhibitors: Inhibition potentials and molecular dynamics.

The inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic approach to treat inflammation and other disorders. In our present investigation on searching for sEH inhibitors from traditional Chinese medicines, we found that Alisma orientale displayed inhibition of sEH. We constructed a small library of protostane-type triterpenoids (1-25) isolated from A.

The study of inhibitory effect of natural flavonoids toward β-glucuronidase and interaction of flavonoids with β-glucuronidase.

β-Glucuronidase plays a vital role in the metabolism of drugs and endogenous substance. Herein, we assayed the inhibitory effects of thirty-six flavonoids (1-36) toward β-glucuronidase (Escherichia coli) using the probe reaction of DDAO-glu hydrolysis. The results showed that kushenol X (6), (2S)-farrerol (10), 5,7,2'-trihydroxy-8,6'-dimethoxy flavone (20), demethylbellidifolin (31), and gentisin (32) exhibited potent inhibitory activities toward β-glucuronidase with the IC values of 2.

Berberrubine and its analog, hydroxypropyl-berberrubine, regulate LDLR and PCSK9 expression via the ERK signal pathway to exert cholesterol-lowering effects in human hepatoma HepG2 cells.

Berberine (BBR), the major isoquinoline alkaloid in Chinese herb Rhizoma coptidis, has significant lipid-lowering effect by upregulating hepatic low-density lipoprotein receptor (LDLR) expression. In a previous study, we have indicated that berberrubine (M3), a major metabolite of BBR in vivo, displays the most potential hypolipidemic effects via upregulating LDLR expression in human hepatoma (HepG2) cells compared with BBR and 3 other metabolites. Accordingly, 9 M3 analogs (A1-A9) were modified at the C9 position.

9-O-benzoyl-substituted berberine exerts a triglyceride-lowering effect through AMPK signaling pathway in human hepatoma HepG2 cells.

Berberine is an isoquinoline alkaloid extracted from Rhizoma coptidis and shows anti-hyperlipidemia effect in vivo and in vitro. We previously found that berberine could decrease the intracellular triglyceride content in human hepatoma HepG2 cells through activation of AMP-activated protein kinase (AMPK), a major regulator of lipid metabolism. Herein, to find a more effective agent, several berberine analogues (A1-A13) were isolated and synthesized, and the triglyceride-lowering effects and potential mechanisms were investigated in HepG2 cells.

Two pairs of phenylpropanoid enantiomers from the leaves of Eucommia ulmoides.

Two pairs of phenylpropanoid enantiomers, (+)-(7S,8S)-alatusol D (1a), (-)-(7R,8R)-alatusol D (1b), (-)-(7S,8R)-alatusol D (2a) and (+)-(7R,8S)-alatusol D (2b) were isolated from the leaves of Eucommia ulmoides Oliver. Among them, 1a and 2b were firstly obtained by chiral enantiomeric resolution. Their structures were elucidated based on extensive spectroscopic analysis and the induced CD (ICD) spectrum caused by adding Mo(AcO) in DMSO.

Two pairs of phenolic enantiomers from the leaves of Eucommia ulmoides Oliver.

Two pairs of new phenolic enantiomers, (+)-eucophenolic A (1a), (-)-eucophenolic B (1b), (-)-eucophenolic C (2a), (+)-eucophenolic D (2b) were isolated from the leaves of Eucommia ulmodies Oliver by chiral enantiomeric resolution. Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1a/1b and 2a/2b were determined by empirical method and the calculated ECD and OR.

Nine pairs of megastigmane enantiomers from the leaves of Eucommia ulmoides Oliver.

Nine pairs of megastigmane enantiomers (1a/1b-9a/9b), comprising two new compounds (6S,9R)-blumenol C (7b), (6S,9S)-blumenol C (8b), two pairs of enantiomers (+)-(6R)-eucomegastigmane A (1a), (-)-(6S)-eucomegastigmane A (1b), (+)-(3S,4S)-eucomegastigmane B (5a), (-)-(3R,4R)-eucomegastigmane B (5b) isolated by chiral resolution firstly, and twelve known compounds, were isolated from the leaves of Eucommia ulmoides Oliver. Their structures were elucidated based on extensive spectroscopic analysis. Absolute configurations of the megastigmane enantiomers were assigned by comparing experimental ECD and OR with calculated ECD and OR.

Megastigmane glycosides from leaves of Eucommia ulmoides Oliver with ACE inhibitory activity.

Four new megastigmane glycosides, eucomegastigsides A-D (2, 3, 5 and 7), together with three known megastigmane glycosides, (6R, 7E, 9R)-9-hydroxy-4, 7-megastigmadien-3-one-9-O-[α-l-arabinopyranosyl-(l→6)-β-d-glucopyranoside (1), foliasalacioside B (4) and eleganoside A (6), were isolated from the leaves of Eucommia ulmoides Oliver. Their anti-hypertensive effect was investigated in vitro based on the inhibition of Angiotensin Converting Enzyme (ACE) using HPLC. The results showed that the isolates (2, 3, 4, 5, 7) had moderate inhibitory effects on ACE in vitro compared with captopril.

Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells.

Berberine (BBR) is an isoquinoline alkaloid isolated from several Chinese herbal medicines, such as Coptis chinensis, Berberis aristata, and Coptis japonica. It exhibits a lipid-lowering effect by up-regulating the hepatic low density lipoprotein receptor (LDLR) expression. However, the plasma concentration of BBR is very low after oral administration for the reason that BBR is poorly absorbed and rapidly metabolized.

Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells.

Ethnopharmacological Relevance: Rhizoma coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumors. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of R.