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Driving behavior has frequently been overlooked in previous road traffic crash research. Hereby, abnormal (extreme) driving behavior data transmitted by the onboard navigation systems were collected for vehicles involved in traffic crashes, including sharp-lane-change, sharp-acceleration, and sudden-braking behaviors. Using these data in conjunction with expressway crash records, multiple classification learners were trained to establish a behavior-driven risk prediction model. To further investigate the influence of driving behavior on crash risk, partial dependence plots (PDPs) were applied. Regression analyses indicate that models have a stronger effect when derivative features such as frequency of specific deviant behavior, speed, and acceleration in the behavior process are included. The behavioral RUSBoost model surpasses other models, achieving an AUC prediction metric of 0.782 and outperforming traditional traffic-flow-driven machine learning models. PDP analysis demonstrates that the sudden-braking behavior is the leading contributory factor of expressway crashes, particularly when the acceleration exceeds 0.5 G. This study confirms the potential of predicting crash risks through augmenting behavior data from navigation software; the findings lay a foundation for countermeasures. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate whether the slow component of oxygen uptake was concurrent with the recruitment of large α-motoneuron muscle fibres by using wavelet and principal component analysis (PCA) of electromyography (EMG) during heavy and severe cycling exercise. Eleven male subjects participated in the study. After establishing each subject's maximum value of oxygen uptake through an incremental test on the cycle ergometer, the subjects performed 6-min cycling tests at heavy and severe intensity. EMG signals were collected from rectus femoris, biceps femoris long head, tibialis anterior, and medial gastrocnemius and processed by combined use of wavelet and PCA analysis. The time delays to the onset of slow component occurred significantly earlier during severe (105.22 ± 5.45 s) compared with during heavy (138.78 ± 15.09 s) exercise. ANOVA with repeated measures showed that for all muscles tested, the angle θ formed by the first and second principal components decreased significantly between time windows during heavy and severe exercise. However, significant increases of EMG mean power frequency (MPF) were found only during heavy exercise. Our results show the concurrence of the oxygen uptake slow component with the additional recruitment of muscle fibres, presumably less efficient large α-motoneuron fibres. Novelty The expected rise in MPF may be offset by muscle fatigue occurring in the later time windows of the slow component during severe exercise. The gradual shift to higher EMG frequencies throughout the slow-component phase was reflected in the progressive and significant decrease of angle θ. [ABSTRACT FROM AUTHOR]

Abstract: A preparative high-speed counter-current chromatography (HSCCC) method for isolation and purification of four prenylflavanones from the crud extract after microbial biotransformation of kurarinone was developed successfully using a stepwise elution with two-phase solvent system composed n-hexane–ethyl acetate–methanol–water at the volume ratios of 1:1:0.7:1 (v/v) and 1:1:1.2:1 (v/v). A total of 7mg of 4a,5a-dihydroxy norkurarinone (1), 11mg of 7-methoxyl-4a,5a-dihydroxy norkurarinone (2), 14mg of 6a-hydroxykurarinone (3) and 10mg of norkurarinone (4) were obtained in one-step separation from 520mg of the crude biotransformation sample with purities of 94.0%, 97.8%, 99.5% and 98.7%, respectively. Among them, compounds 1–3 are novel compounds, and their chemical structures were identified on the basis of the extensive spectral methods such as UV, IR, HR-MS and NMR. [ABSTRACT FROM AUTHOR]

The biotransformation of dehydroandrographolide (1) by Cunninghamella elegans was performed and four transformed products were obtained. Based on their extensive spectral data, the structures of these metabolites were identified as 3-oxo-dehydroandrographolide (2), 3-oxo-2β-hydroxy-dehydroandrographolide (3), 3-oxo-8β,17α-epoxydehydroandrographolide (4), 3,19-dihydroxy-7,11,13-ent-labdatrien-15,16-olide (5), respectively. Among them, products 3-5 are new compounds. [ABSTRACT FROM AUTHOR]

Two new transformed sesquiterpenes of alantolactone by Mucor polymorphosporus were obtained. They were characterized as 3β-hydroxy-11βH-eudesm-5-en-8β,12-olide (2) and 3β,11α-dihydroxy-eudesm-5-en-8β,12-olide (3), on the basis of spectral methods including 2D NMR. And product 3 was an unusual hydroxylation derivative of alantolactone at C-11. [ABSTRACT FROM AUTHOR]

Abstract: Eighteen strains of filamentous fungi (from nine genera) were screened for their capabilities to transform three major bufadienolides, cinobufagin (1), bufalin (2) and resibufogenin (3), from the traditional Chinese medicine Chan Su. Penicillium aurantigriseum AS 3.4512 was found to be the most potent strain to transform these compounds into in vivo metabolites in rat. Ten transformation products were obtained with high yield and identified using chromatographic and spectral means. Among them, six products were found to be same with the in vitro metabolites transformed by rat liver microsome. Three compounds were the major in vivo metabolites of 1, 2 and 3, respectively. Compound 3a was a firstly reported metabolite of 3 in vivo. All of these suggested the bioconversion of 1, 2 and 3 by P. aurantigriseum were very similar with the metabolism of them in vivo, and these transformed products could be used as the reference standards to investigate the mammalian metabolism of bufadienolides. [Copyright &y& Elsevier]

Abstract: Twenty strains of filamentous fungi (from nine genera) and four species of bacteria were screened for their capabilities to transform bufadienolides. The highly stereo- and regiospecific isomerization and dehydrogenation of three major bufadienolides (resibufogenin, cinobufagin and bufalin) at 3-OH by Fusarium solani AS 3.1829 were reported. Three major transformed products were obtained and their structures were identified as 3-epi-resibufogenin (1a), 3-epi-bufalin (2a), 3-keto-cinobufagin (3a), respectively, on the basis of their spectral data. The reaction kinetics and the effects of pH, substrate concentration and incubation phase on the biotransformation were also investigated. [Copyright &y& Elsevier]

Abstract: Twenty strains of filamentous fungi (from nine genera) and four species of bacteria were screened for their capabilities to transform dehydrocostuslactone (1) and costunolide (10). Stereo- and region-specific hydroxylation, epoxidation and hydrogenation reactions of the substrates by Mucor polymorphosporus AS 3.3443 and Aspergillus candidus CICC 2360 were reported. Twelve transformed products were obtained and their structures were identified on the basis of their spectral data. Among them, 10α,14β-epoxy-11α,13-dihydrodehydrocostuslactone and 10α,14-dihydroxy-11α,13-dihydrodehydrocostuslactone are new compounds. The biotransformation kinetics were also investigated. [Copyright &y& Elsevier]

Abstract: Twenty strains of filamentous fungi (from nine genera) and four species of bacteria were screened for their capabilities to transform curdione (1). Site-specific hydroxylation and epoxidation of the substrate by Mucor spinosus AS 3.3450 were reported. Five compounds were obtained, and their structures were identified as 1β,10α-epoxycurdione (2), 1α,10β-epoxycurdione (3), 2β-hydroxycurdione (4), 11-hydroxycurdione (5) and 2β,11-dihydroxycurdione (6), respectively, on the basis of their spectral data. Among them, products 5 and 6 are new compounds. The biotransformation kinetics was also investigated. [Copyright &y& Elsevier]

Cryptotanshinone (1) is one of the major bioactive constituents in Salvia miltiorrhiza Bunge. Preparative-scale biotransformation of cryptotanshinone by Cunninghamella elegans (AS 3.2082) produced three new products, which were identified as (3R,15R)-3-hydroxycryptotanshinone (2), (3S,15R)-3-hydroxycryptotanshinone (3), and (4S,15R)-18-hydroxycryptotanshinone (4), respectively. The structural elucidation was based primarily on 1D and 2D NMR and HR-ESI-MS analyses. The absolute configuration of these three products was confirmed by comparison of their circular dichroism spectra with those of the known compounds. These biotransformed metabolites were used as for the comparison of in vivo metabolites in rat bile sample after intravenous administration and they are identical to three of the minor hydroxylated metabolites in vivo, which suggested that microbial biotransformation model was a useful and feasible approach for the preparation of mammalian metabolites in trace. [ABSTRACT FROM AUTHOR]

Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3 β -hydroxy-25-anhydro-alisol F (1) and 3 β -hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC 50 values of 10.06 and 30.45 μM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a K i value of 5.13 μM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1 , which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: The investigation of Morinda officinalis led to the isolation of twelve compounds (1—12), including three new iridoid glycosides morindalins A—C (1—3) and nine known compounds (4—12). Their structural identifications were conducted using HRMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. Compound 6 displayed the most significantly agonistic activity against farnesoid X receptor (FXR) with an EC50 value of 7.18 μM, and its agonistic effect was verified through the investigation of FXR downstream target genes including small heterodimer partner 1 (SHP1), bile salt export pump (BSEP), and organic solute transporter subunit alpha and beta (OSTα and OSTβ). The potential interaction of compound 6 with FXR was analyzed by molecular docking and molecular dynamics stimulation, revealing that amino acid residues Leu287, Thr288, and Ser332 played a crucial role in the activation of compound 6 towards FXR. These findings suggested that compound 6 could be regarded as a potential candidate for the development of FXR agonists. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history. After investigation of U. rhynchophylla, eleven monoterpene indole alkaloids, including four new compounds uncarialins J—M (1—4) and seven known analogues (5—11), were isolated and identified. Their structural characterization was conducted using HRESIMS, 1D and 2D NMR, electronic circular dichroism (ECD) spectra, and quantum chemical computations. Compounds 1, 2, 7, and 9—11 displayed significant agonistic effects towards 5‐HT1A receptor, and their EC50 values were 7.86, 7.32, 2.24, 1.18, 1.52, and 3.75 μmol/L, respectively. Furthermore, in vivo experimental results fully revealed that hirsuteine (7) displayed a significant antidepression effect in unpredictable chronic mild stress (UCMS)‐induced depression mice mainly via regulating 5‐HT1A signaling pathway. Molecular docking and site‐directed amino acid mutation verified that amino acid residues Asp116 and Asn386 were the binding sites of hirsuteine (7) with 5‐HT1A receptor. In addition, pre‐treatment of mice with WAY 100635 also blocked the anti‐depression effect of hirsuteine (7), which further demonstrated that 5‐HT1A receptor was a potential target of hirsuteine (7) to effectively treat depression. These findings indicated the therapeutic material basis of U. rhynchophylla and the anti‐depression underlying mechanism of hirsuteine (7), and further provided the useful guidance for the development of hirsuteine (7) as a potential antidepressant candidate. [ABSTRACT FROM AUTHOR]

As a genus of the Asteraceae, Inula is widely distributed all over the world, and several of them are being used in traditional medicines. A number of metabolites were isolated from Inula species, and some of these have shown to possess ranges of pharmacological activities. The genus Inula contains abundant sesquiterpenoids, such as eudesmanes, xanthanes, and sesquiterpenoid dimers and trimers. In addition, other types of terpenoids, flavonoids, and lignins also exist in the genus Inula. Since 2010, more than 300 new secondary metabolites, including several known natural products that were isolated for the first time from the genus Inula. Most of them exhibited potential bioactivities in various diseases. The review aimed to summarize the advance of recent researches (2010–2020) on phytochemical constituents, biosynthesis, and pharmacological properties of the genus Inula for providing a scientific basis and supporting its application and exploitation for new drug development. [ABSTRACT FROM AUTHOR]

The gut microbiota is very important in the initiation, progression, and dissemination of cancer, and the regulation of microbiota has been employed as a novel strategy to enhance the effect of immunotherapy. Adiponectin (APN), an adipocyte-derived hormone, plays a vital role in regulating the immune response of innate immune cells. The deficiency of APN inhibits rhabdomyosarcoma growth. However, whether this function is associated with regulating gut microbiota remains unknown. To investigate, we performed 16S ribosomal RNA (rRNA) gene sequencing on the fecal microbiome of APN gene knockout mice to determine whether APN deletion affects the gut microbiota. We found APN deficiency alters gut microbial functions involved in metabolism, genetic information processing, and cellular processes. In addition, a decreased abundance of Bacteroides and an increased abundance of Prevotella and Helicobacter were observed in rhabdomyosarcoma-bearing APN knockout mice; these bacteria were associated with the inhibition of rhabdomyosarcoma growth. These findings suggest that gut microbiota may be a potential target of APN deficiency against rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

The gut microbiota is very important in the initiation, progression, and dissemination of cancer, and the regulation of microbiota has been employed as a novel strategy to enhance the effect of immunotherapy. Adiponectin (APN), an adipocyte-derived hormone, plays a vital role in regulating the immune response of innate immune cells. The deficiency of APN inhibits rhabdomyosarcoma growth. However, whether this function is associated with regulating gut microbiota remains unknown. To investigate, we performed 16S ribosomal RNA (rRNA) gene sequencing on the fecal microbiome of APN gene knockout mice to determine whether APN deletion affects the gut microbiota. We found APN deficiency alters gut microbial functions involved in metabolism, genetic information processing, and cellular processes. In addition, a decreased abundance of Bacteroides and an increased abundance of Prevotella and Helicobacter were observed in rhabdomyosarcoma-bearing APN knockout mice; these bacteria were associated with the inhibition of rhabdomyosarcoma growth. These findings suggest that gut microbiota may be a potential target of APN deficiency against rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

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. rhynchophylla were assayed for their relaxant effects against phenylephrine (Phe)-induced contraction of rat mesenteric arteries. Among them, we surprisingly found that uncarialin A (21) exhibited most potent relaxation effect against Phe-induced contraction (IC 50 = 0.18 μM) in the manner of independent on endothelium-derived vasorelaxing factors and endothelium. All the experiments including measurement of Ca2+ in vascular smooth muscle cells (VSMCs) by fluorescence microscopy, whole-cell path clamp, molecular docking, and molecular dynamics, demonstrated that uncarialin A (21) could significantly inhibit L-type calcium channel subunit alpha-1C (Cav1.2) via the hydrogen bond interaction with amino acid residue Met1186, allowing the inhibition of Ca2+ inward current. Our results suggested that uncarialin A (21) could be served as a potential L-type Cav1.2 blocker in the effective treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium was isolated to obtain eight compounds, including 4 H -tomentosin (1), xanthalongin (2), linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC 50) from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. The inhibition kinetics suggested that 4 H -tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constants (K i) of 7.02 and 6.57 μM, respectively, and linoleic acid (3) was a competitive type inhibitor with a K i values of 3.52 μM. The potential interactions of 4 H -tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524. • Eight compounds were isolated from I. helenium. • Compounds 1-3 could inhibit sEH activity with IC 50 values from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. • They were all mixed-competitive type inhibitor with Ki values from 3.52 μM to 7.02 μM • Molecular docking revealed interaction of compounds 1-3 with sEH. [ABSTRACT FROM AUTHOR]

Inulae Herba (IH) is known as Jinfeicao recorded in Chinese Pharmacopoeia with effects of lowering qi and eliminating phlegm, and used for the treatment of pulmonary diseases. However, its protective mechanism on pulmonary diseases, especially acute lung injury (ALI), is still undefined. This study aimed to explore anti-inflammatory and anti-oxidation effects of IH and its underlying mechanism for treating ALI. We constructed a lipopolysaccharide (LPS)-ALI mouse model to reveal the therapeutical effect of IH. Western blot, real-time quantitative PCR, flow cytometry, small RNA interference, immunohistochemical staining, and the dual-luciferase experiment were performed to study the mechanism of IH for treating ALI. IH attenuated LPS-mediated pathological changes (e.g. pneumonedema and pulmonary congestion) through inactivation of macrophages in an ALI mouse model. The result of flow cytometry demonstrated that IH regulated the homeostasis of M1 (CD80+CD206-) and M2 (CD80+CD206+) phenotype macrophages. Furthermore, IH suppressed mRNA expressions of M1 phenotype markers, such as iNOS and IL-6 , whereas promoted mRNA expressions of M2 phenotype markers, such as ARG1 and RETNLA in LPS-mediated mice. Notably, IH targeted Keap1 to activate the Nrf2 receptor, exerting its anti-inflammatory and anti-oxidation effects proved by using immunohistochemical staining, dual-luciferase, and Keap1 knockdown technologies. These findings suggested that targeting Keap1 with IH alleviated LPS-mediated ALI, and it could serve as a herbal agent for developing anti-ALI drugs. [Display omitted] • Inulae Herba displayed an anti-ALI effect in the animal model. • Inulae Herba regulated the homeostasis of M1 and M2 phenotype macrophages. • Inulae Herba exerted anti-inflammatory and anti-oxidation effects. • Targeting Keap1 with Inulae Herba exerted an anti-ALI effect. [ABSTRACT FROM AUTHOR]

Environmental hormones have attracted more attention because of their adverse impact on the health and ecological security of human. Biodegradation is still an efficient tactics to remove environmental hormones, but human intestinal microbes remain to be elucidated in the role of their degradation. In the present work, we intended to perform the in vitro experiment for investigating the degradation of 17 β -estradiol, the main environmental estrogen, by human intestinal microflora Aspergillus niger RG13B1. Its degradation led to the production of eighteen metabolites characterized by 1H, 13C, and 2D NMR, and HRMS spectra, including nine new (1–9) and nine known metabolites (10–18). Based on their structures, the degradation pathway of 17 β -estradiol mediated by A. niger RG13B1 involved hydroxylation, oxidation, methylation, acetylation, and dehydrogenation, especially infrequent lactylation, and the key degradation enzymes were found in the gene cluster of A. niger. In addition, we found that metabolite 12 interacted with amino acid residues Lys37, Gln39, Lys93, and Asn115 of NF-κB p65 to suppress expressions of inflammatory genes or proteins, exerting its anti-inflammatory effect. This study first illustrated the role of human gut microbe in 17 β -estradiol degradation and provided new insights into its degradation mechanism by A. niger RG13B1. [Display omitted] • 17 β -Estradiol was degraded by human intestinal fungus A. niger RG13B1. • Its degradation pathway mainly involved hydroxylation, and oxidation. • The key enzymes were characterized in A. niger RG13B1. • Some metabolites displayed anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

As a part of our searching for natural human carboxylesterase 2 (human CES 2) inhibitors from traditional Chinese medicine, we found that the extract of Alisma orientale significantly inhibited human CES 2 in vitro. The investigation on A. orientale led to the isolation of a new protostane-type triterpenoid alismanin I (1). Its structure was determined according to HRESIMS, 1D and 2D NMR spectra. Alismanin I (1) displayed significantly inhibitory activity against human CES 2 with IC 50 value of 1.31 ± 0.09 μM assayed by human CES 2-mediated DDAB hydrolysis. According to its inhibition kinetic result, compound 1 was a noncompetitive type inhibitor, and its Ki was 3.65 μM. Its inhibitory effect was confirmed in living cell level through a visual manner. The potential interaction mechanism of compound 1 with human CES 2 was also analyzed by circular dichroism (CD) spectrum and molecular docking. [ABSTRACT FROM AUTHOR]

Highlights • Preparation of resveratrol esters with caprylic acid. • Hydrolysis of resveratrol esters in modeling gastrointestinal digestion. • No hydrolysis of resveratrol esters in mouth and gastric phases. • Digestibility of resveratrol esters in intestinal phase by pancreatic lipase. • Differences in hydrolysis degree between esters with various substitution degrees. Abstract Lipophenols, esterified phenols with fatty acids, have attracted increasing attention because of their better protective effects in lipid-based food matrices from oxidation. However, little is known about their digestion. In this study, the digestive stability of resveratrol (RSV) esters with caprylic acid (RCAPs) in a model gastrointestinal digestion system was evaluated. The results demonstrated that RCAPs were relatively stable without hydrolysis in mouth and gastric phases. However, in the intestinal phase, pancreatic lipase rather than phospholipase A 2 could hydrolyze monoester and diesters to free RSV. After 120 min of incubation at 37 °C, 53.68% of monoester and 11.36% of diesters were hydrolyzed. However, no hydrolysis of the triester was noticed. Obviously, the level of hydrolysis of RCAPs was negatively correlated with the degree of substitution. Therefore, it was speculated that RSV in fatty acid ester forms could partially be absorbed by intestinal lumen in the form of free RSV. [ABSTRACT FROM AUTHOR]

Air pollution represented by particulate matter 2.5 (PM2.5) is closely related to diseases of the respiratory system. Although the understanding of its mechanism is limited, pulmonary inflammation is closely correlated with PM2.5-mediated lung injury. Soluble epoxide hydrolase (sEH) and epoxy fatty acids play a vital role in the inflammation. Herein, we attempted to use the metabolomics of oxidized lipids for analyzing the relationship of oxylipins with lung injury in a PM2.5-mediated mouse model, and found that the cytochrome P450 oxidases/sEH mediated metabolic pathway was involved in lung injury. Furthermore, the sEH overexpression was revealed in lung injury mice. Interestingly, sEH genetic deletion or the selective sEH inhibitor TPPU increased levels of epoxyeicosatrienoic acids (EETs) in lung injury mice, and inactivated pulmonary macrophages based on the MAPK/NF-κB pathway, resulting in protection against PM2.5-mediated lung injury. Additionally, a natural sEH inhibitor luteolin from Inula japonica displayed a pulmonary protective effect towards lung injury mediated by PM2.5 as well. Our results are consistent with the sEH message and protein being both a marker and mechanism for PM2.5-induced inflammation, which suggest its potential as a pharmaceutical target for treating diseases of the respiratory system. [Display omitted] • PM2.5 exposure affected the AA metabolism. • PM2.5 exposure led to the increase of the sEH expression. • Genetic deletion or chemical inhibition of sEH attenuated PM2.5 mediated lung injury. • Luteolin, a sEH inhibitor from the genus Inula , displayed the protective effect in PM2.5 mediated lung injury. [ABSTRACT FROM AUTHOR]

Chemical investigation has been performed on the roots of Euphorbia fischeriana, a traditional Chinese medicine. Three diterpenoids were obtained using various chromatographic techniques, and their structures were determined by spectroscopic data including HRESIMS, 1D NMR, 2D NMR, ECD, and calculated ECD, which gave two new diterpenoids, daphnane type (1) and ent-pimarene type (3). Additionally, the isolated compounds (1-3) displayed moderate inhibitory effects against α-glucosidase in an in vitro bioassay. [ABSTRACT FROM AUTHOR]

The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 μM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE. [ABSTRACT FROM AUTHOR]

A novel 1(2), 2(18)-di seco indole diterpenoid , drechmerin H ( 1 ), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2′- epi terpendole A ( 3 ), and a known analogue, terpendole A ( 2 ). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A ( 2 ) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC 50 value of 134.91 ± 2.01 nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1–3 is also discussed in the present work. [ABSTRACT FROM AUTHOR]

Background/Aims:Uncaria rhynchophylla, known as “Gou-teng”, is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. Methods: MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson’s disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. Results: URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. Conclusions: URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment. [ABSTRACT FROM AUTHOR]

Abstract: Malignant glioma is one of the most challenging central nervous system diseases to treat and has high rates of recurrence and mortality. Current therapies often fail to control tumor progression or improve patient survival. Marinobufagenin (MBG) is an endogenous mammalian cardiotonic steroid involved in sodium pump inhibition. Currently, various studies have indicated the potential of MBG in cancer treatments; however, the precise mechanisms are poorly understood. The functions of MBG were examined using colony formation, migration, cell cycle, and apoptosis assays in glioma cells. A mitochondrial membrane potential assay was performed to determine the mitochondrial transmembrane potential change, and cytochrome c release from mitochondria was assayed by fluorescence microscopy. An immunofluorescence assay was performed, and the nuclear translocation of NF‐κB in glioma cells was confirmed by confocal microscopy. Western blotting and RT‐qPCR were used to detect the protein and gene expression levels, respectively. In addition, transfection experiment of ATP1A1‐siRNA was further carried out to confirm the role of sodium pump α1 subunit in the anticancer effect of MBG in human glioma. The apoptosis‐promoting and anti‐inflammatory effects of MBG were further investigated, and the sodium pump α1 subunit and the ERK signaling pathway were found to be involved in the anticancer effect of MBG. The in vivo anticancer efficacy of MBG was also tested in xenografts in nude mice. Thus, therapies targeting the ERK signaling‐mediated mitochondrial apoptotic pathways regulated by MBG might represent potential treatments for human glioma, and this study could accelerate the finding of newer therapeutic approaches for malignant glioma treatment. [ABSTRACT FROM AUTHOR]

A chemical investigation of the roots of Euphorbia ebracteolata identified eighteen diterpenoids and glycosides. On the basis of spectroscopic data, they were determined to be ent -kauranes, ent -atisanes, tigliane derivatives, ingenane, and ent -abietanes, among which were eleven previously undescribed diterpenoids. The inhibitory effects of the isolated compounds against human carboxylesterase 2 (hCE-2) were evaluated in vitro , which revealed moderate inhibitory effects with IC 50 values < 50 μM. Next, the inhibitory kinetics were evaluated for the putative hCE-2 inhibitor 4 β ,9 α ,16,20-tetrahydroxy-14(13 → 12)-abeo-12 α H-1,6-tigliadiene-3,13-dione (IC 50 3.88 μM), and results indicated competitive inhibition with K i 4.94 μM. Additionally, none of the diterpenoids showed cytotoxic effects against five human tumor cell lines as determined by MTT assays. [ABSTRACT FROM AUTHOR]

A pair of novel sesquiterpenoids, (8R)-alismanoid A (1a) and (8S)-alismanoid A (1b), possessing an unprecedented 1,2-seco bisabolene carbon skeleton, were isolated from rhizomes of Alisma orientale together with two new sesquiterpenoids: a 15-nor guaiane alismanoid B (2) and alismanoid C (3). Their structures were elucidated by 1D and 2D NMR, HRESIMS, electronic circular dichroism (ECD), and theoretical calculations, and a plausible biosynthetic pathway for compound 1 is discussed. Meanwhile, compounds 1–3 were investigated for their protective effects on H2O2-induced damage in human dopaminergic neuroblastoma cells (SH-SY5Y), and compounds 1b, 2, and 3 showed significantly protective activities at a certain concentration. Further, the action mechanism of compound 3 was proved to be through inhibition of H2O2-induced apoptosis in SH-SY5Y cells. Herein, these results suggest that sesquiterpenoids are potential candidate drugs for treating Parkinson's disease induced by reactive oxygen species. [ABSTRACT FROM AUTHOR]

The bioactive substance investigation of Euphorbia ebracteolata obtained 17 compounds by various chromatographic techniques. Their structures were elucidated using widely spectroscopic data, including ESI-MS, HRESI-MS, CD, 1D- and 2D-NMR, which gave 5 new phenolic glucosides and 4 new monoterpenoids. The phenolic glucosides and monoterpenoids showed the inhibitory effect against the human carboxylesterase-2 (hCE-2) using a fluorescence bioassay in vitro , with the strongest inhibitor compound 4 (IC 50 7.17 μM). The antioxidant effects of these isolated compounds were evaluated using a DPPH scavenging assay. All of the phenolic acids displayed the DPPH scavenging effect, especially that eight compounds have better effect than vitamin C, with the IC 50 values ranging from 4.52 to 7.52 μM. Additionally, compounds 1 – 17 showed no cytotoxic effect against five human cancer cell lines by MTT assay. [ABSTRACT FROM AUTHOR]

An accurate, precise, selective, and sensitive high performance liquid chromatography coupled to tandem mass spectrometry (HPLC–MS/MS) method was developed for the simultaneous determination of baicalin and its metabolite, baicalein 6- O -glucopyranuronoside, in normal and febrile rats plasma. Two analytes, along with hesperidin as an internal standard, were determined by multiple reactions monitoring (MRM) operated in the positive electrospray ionization (ESI) mode. Chromatographic separation was performed on an Agilent ZORBAX Extend-C18 column (100 mm × 2.10 mm, 3.5 μm) with a mobile phase of 0.1% formic acid solution and acetonitrile at a flow rate of 0.6 mL/min. The calibration curves showed good linearity (r ≥ 0.9974) with the concentration ranges of 2.000–2000 ng mL −1 for baicalin and baicalein 6- O -glucopyranuronoside. The inter- and intra-day accuracies (relative error, RE%) were between −6.62% and 6.75%, and the precisions (relative standard deviation, RSD%) were less than 9.09% for quality control samples (QCs). The method also possessed good selectivity, recovery and stability, and was successfully applied to a comparative pharmacokinetic study of baicalin and baicalein 6- O -glucopyranuronoside in normal and febrile rats after oral administration of baicalin and Chaiqin Qingning capsule . [ABSTRACT FROM AUTHOR]

An efficient glucosylation of alcoholic hydroxyls in the structures of protostane triterpenoids catalyzed by fungus has been developed. Four protostanes 1 – 4 as the substrates have been transformed by Syncephalastrum racemosum AS 3.264 and generated corresponding 11-OH glucosylation derivatives. The regioselective characteristics were also identified by various highly oxygenated protostane substrates. The time-courses displayed the highest yields of 1a , 3a , and 4a at > 50%, and 1a had the highest yield of 72%. All of the protostane analogues displayed hCE-2 inhibitory effects in an in vitro bioassay. This report describes a rare biocatalytic alcoholic hydroxyl glucosylation with considerable yield and regioselective characteristics. [ABSTRACT FROM AUTHOR]

Phyllodium pulchellum (P. pulchellum) is a folk medicine with a significant number of bioactivities. The aim of this study was to investigate the effects displayed by alkaloids fractions, isolated from the roots of P. pulchellum, on neurotransmitters monoamine levels and on monoamine oxidase (MAO) activity. Six alkaloids, which had indolealkylamine or β-carboline skeleton, were obtained by chromatographic technologies and identified by spectroscopic methods such as NMR and MS. After treatment with alkaloids of P. pulchellum, the reduction of DA levels (54.55%) and 5-HT levels (35.01%) in rat brain was observed by HPLC-FLD. The effect of alkaloids on the monoamines metabolism was mainly related to MAO inhibition, characterized by IC50 values of 37.35±6.41 and 126.53±5.39 μg/mL for MAO-A and MAO-B, respectively. The acute toxicity indicated that P. pulchellum extract was nontoxic. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum is a famous edible and medicinal fungus. Through a bioactive phytochemical investigation of the ethanolic extracts of the fruiting bodies of G. lucidum , twenty-nine triterpenoids, including eleven previously undescribed triterpenoids, were isolated and characterized based on spectroscopic data. The inhibitory effects of all the triterpenes against fatty acid amide hydrolase (FAAH) were found to be in the range of 30–60% at 100 μM. Methyl ganoderate A displayed the strongest inhibitory activity (61%) against FAAH. Furthermore, all compounds displayed no cytotoxicity against LOVO and MCF-7 human cancer cells. Hence, our present study provides information about G. lucidum as a functional food or pharmaceutical supplement for the treatment of neuroinflammation. Eleven previously undescribed and eighteen known triterpenoids have been isolated from Ganoderma lucidum , most of which inhibit the hydrolysis activity of FAAH. [Display omitted] • Twenty nine triterpenoids were isolated from the fruiting bodies of Ganoderma lucidum. • Structures of eleven undescribed triterpenes were determined as lanostane derivatives. • Methyl ganoderate A displayed strong inhibitory activity (61%) against FAAH. • All of these triterpenoids displayed no cytotoxicity against LOVO and MCF-7 cells. [ABSTRACT FROM AUTHOR]

1. Bufalin (BF), one of the major bioactive compounds in traditional Chinese medicine (TCM) Chansu, has been found with various pharmacological and toxicological effects. This study aims to investigate the species differences in phase I metabolism of BF in hepatic microsomes from human and five common experimental animals. 2. Metabolite profiling demonstrated that two major metabolites were formed in liver microsomes from human and animal species in NADPH-generating system. Two major metabolites were identified as 5β-hydroxyl-bufalin and 3-keto-bufalin, with the help of authentic standards. CYP3A was assigned as the main isoform involved in both 5β-hydroxylation and 3-oxidation in all studied liver microsomes. The apparent kinetic parameters including substrate affinity and catalytic efficiency for 5β-hydroxylation and 3-oxidation of BF were also determined. 3. In summary, CYP3A mediated 5β-hydroxylation and 3-oxidation were two major metabolic pathways of BF in hepatic microsomes from human and five studied animals, but kinetic analysis demonstrated that the intrinsic clearances of these two metabolic pathways were much different among various species. The qualitative and quantitative interspecies study indicated that minipig exhibited the similar metabolic profile, kinetic behaviors and intrinsic metabolic clearances of BF phase I biotransformation in comparison with that of human. [ABSTRACT FROM AUTHOR]

Schisanlactone E ( SE ) is a major triterpene obtained from the plants of genus Kadsura. The aim of this research was to investigate the transformed metabolites of SE by fungi and evaluate the bioactivities of these products. After screening 10 strains of filamentous fungi, Cunninghamella blakesleana AS 3.970 was chosen as a potent organism to be used for the biotransformation of SE . 13 metabolites were obtained and determined to be new compounds through the use of spectroscopic data, including UV, 1D-, 2D-NMR, and HR-ESIMS. Furthermore, in an in vitro bioassay, metabolites 7 and 9 showed moderate inhibitory effects on the nitric oxide production in LPS-induced macrophages with IC 50 values of 16.73, 5.91 μM, respectively; 9 could inhibit the proliferation of acetaldehyde-induced HSC-T6 cells, with the IC 50 value of 21.4 μM. Preliminary findings on the structure–activity relationships for these metabolites were also discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Unprecedented dimeric ent -abietanes were obtained from Euphorbia fischeriana. • Novel dimer 1 possesses a scaffold that incorporates a cage-like pentacyclic core. • Bislangduoid A showed cytotoxicity by apoptosis-induced effects in HepG2 cells. Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent -abietanes tethered by C-17−C-15′ bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway. [ABSTRACT FROM AUTHOR]

Three new phenolic constituents 1–3 were obtained from the 95% ethanol extract of the roots of Phyllodium pulchellum (Leguminosae). Their structures were elucidated on the basis of spectroscopic analyses, such as NMR, UV, IR, HR-ESI-MS, and CD. Furthermore, in an in vitro bioassay, all compounds were tested for inhibitory effects against the proliferation of acetaldehyde-stimulated HSC-T6 cells, and compound 3 exhibited potent inhibitory activity with the IC50 value of 7.6 μM. [ABSTRACT FROM AUTHOR]

Abstract: Herb–drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (Ki) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (Ki) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb–drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. [Copyright &y& Elsevier]

In this study, two new compounds and six known compounds were isolated from the aerial parts ofPteris semipinnata.The chemical structures of these two new compounds were elucidated as 6β,11α-dihydroxy-15-oxo-ent-kaur-16-en-19-oic acid (1) and 7α,11α-dihydroxy-15-oxo-ent-kaur-16-en-19-oic acid (2) by the extensive spectral methods including 2D NMR and HR-MS techniques. [ABSTRACT FROM PUBLISHER]

Abstract: The biotransformation of isoimperatorin (1) by Cunninghamella blakesleana AS 3.970 yielded 6 novel products, 14-hydroxyl-isoimperatorin (2), 11-carbonyl-14-hydroxyl isoimperatorin (3), 11-carbonyl-14-hydroxyl-12,13-dihydrogen-iso-imperatorin (4), 14-hydroxyl-12,13-dihydrogenisoimperatorin (5), isoimperatorin-14-O-β-d-mannoside (6) and isoimperatorin-14-O-β-d-glucoside (7), respectively. The chemical structures of these metabolites were elucidated based on extensive spectral data including 2D NMR and HRMS. The hydroxylation, hydrogenation, carbonylation and glycosylation reactions of 1 by C. blakesleana AS 3.970 were observed in the present study. In addition, anti-osteoporosis activities of substrate and all transformed products were evaluated by using MC3T3-E1 cells. Our results suggested that hydroxylation or glycosylation of C-14 would enhance anti-osteoporosis activity significantly. [Copyright &y& Elsevier]

Abstract: The metabolites and pharmacokinetics of ganoderic acid C2 (GAC2), a bioactive triterpenoid in Ganoderma lucidum in rat plasma were investigated by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI-MS/MS). Totally, ten minor phase I metabolites of GAC2 were characterized after oral administration of GAC2, on the basis of their mass fragmentation pathways or direct comparison with authentic compounds by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC–DAD–ESI-MS n ), and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC–ESI-IT-TOF/MS) methods. Moreover, a rapid and specific method for quantification of GAC2 in rat plasma after oral administration was developed by using a liquid–liquid extraction procedure and HPLC–ESI-MS/MS analysis. It is the first time to report the metabolites and pharmacokinetics of GAC2. [Copyright &y& Elsevier]

Abstract: Osthole (1) as a natural product, has the potent anti-osteoporosis activity. In the present paper, a scaled-up biotransformation of 1 by Mucor spinosus AS 3.3450 was carried out for improving its activities and water-solubility. Nine metabolites were obtained in the biotransformation process of 1, and their structures were elucidated as 4′-hydroxyl-osthole (2), osthenol (3), osthenol-7-O-β-d-glucoside (4), 5′-hydroxyl-osthole (5), 5′-hydroxyl-2′,3′-dihydro-osthole (6), 2′,3′-dihydroxyl-osthole (7), 2′-ketone-3′-hydroxyl-osthole (8), 2′-acetoxy-3′-hydroxy-osthole (9) and 2′-hydroxyl-isoothole (10), on the basis of extensive spectral data including 2D NMR and MS spectroscopy. Among them, metabolites 6 and 8 were new. The hydroxylation, dehydrogenation, demethylation and glycosylation reactions of 1 by M. spinosus AS 3.3450 were reported in the present study. And anti-osteoporosis activities of all products were also evaluated by using MC3T3-E1 cells. [Copyright &y& Elsevier]

In this paper, microbial transformation of kurarinone (1) by Cunninghamella echinulata AS 3.3400 was investigated and four transformed products were isolated and identified as 6″-hydroxykurarinone (2), 4″,5″,8″-trihydroxynorkurarinone (3), norkurarinone (4), and kurarinone-7-O-β-glucoside (5), respectively. Among them, 3 and 5 are new compounds, and the rare glycosylation in microbial transformation was observed. In addition, the cytotoxicities of transformed products (2–5) were also investigated. [ABSTRACT FROM AUTHOR]

In this paper, microbial transformation of norkurarinone (1) by Cunninghamella blakesleana AS 3.970 was investigated and seven transformed products were isolated and characterized as kurarinone (2), 4″,5″-dihydroxykurarinone (3), 6″-hydroxyl-2′-methoxyl-norkurarinone 7-O-β-d-glucoside (4), 6″-hydroxyl-norkurarinone 4′-O-β-d-glucoside (5), 4″,5″-dihydroxynorkurarinone (6), 7-methoxyl-norkurarinone (7), and 7-methoxyl-4″,5″-dihydroxynorkurarinone (8), respectively. Among them, 3–5 are new compounds, and the glycosylation reaction in microbial transformation process was reported rarely. In addition, the cytotoxicities of transformed products (1–8) were also investigated. [ABSTRACT FROM PUBLISHER]

Abstract: A strain of Arthrobacter sp. DL001 with high transglycosylation activity was successfully isolated from the Yellow Sea of China. To purify the extracellular enzyme responsible for transglycosylation, a four-step protocol was adopted and the enzyme with electrophoretical purity was obtained. The purified enzyme has a molecular mass of 210kDa and displays a narrow hydrolysis specificity towards α-1,4-glucosidic bond. Its hydrolytic activity was identified as decreasing in the order of maltotriose>panose>maltose. Only 3.61% maltose activity occurs when p-nitrophenyl α-d-glycopyranoside serves as a substrate, suggesting that this enzyme belongs to the type II α-glucosidase. In addition, the enzyme was able to transfer glucosyl groups from the donors containing α-1,4-glucosidic bond specific to glucosides, xylosides and alkyl alcohols in α-1,4- or α-1,6-manners. A decreased order of activity was observed when maltose, maltotriose, panose, β-cyclodextrin and soluble starch served as glycosyl donors, respectively. When maltose was utilized as a donor and a series of p-nitrophenyl-glycosides as acceptors, the glucosidase was capable of transferring glucosyl groups to p-nitrophenyl-glucosides and p-nitrophenyl-xylosides in α-1,4- or α-1,6-manners. The yields of p-nitrophenyl-oligosaccharides could reach 42–60% in 2h. When a series of alkyl alcohols were utilized as acceptors, the enzyme exhibited its transglycosylation activities not only to the primary alcohols but also to the secondary alcohols with carbon chain length 1–4. Therefore, all the results indicated that the purified α-glucosidase present a useful tool for the biosynthesis of oligosaccharides and alkyl glucosides. [Copyright &y& Elsevier]

Abstract: Triterpenoids are the main bioactive components of Ganoderma lucidum, a famous traditional Chinese medicine. After oral administration of total triterpenoids of G. lucidum (TTGL), the rat bile was analyzed by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC-DAD–ESI-MS n ) and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC–ESI-IT-TOF/MS). From rat bile and TTGL samples, a total of 31 triterpenoids, including seven new compounds, were identified or tentatively characterized based on their fragmentation behaviors. Among them, 22 triterpenoids were identified from TTGL and 29 triterpenoids were detected from rat bile after oral administration of TTGL. The results indicated that the majority of triterpenoids detected in TTGL extract could be excreted through rat bile. It is the first report on excretion of total triterpenoids of G. lucidum in rat bile. [Copyright &y& Elsevier]

Abstract: A series of analogues of deoxyandrographolide (1) transformed by Cunninghamella blakesleana AS 3.2004 were isolated and identified by spectral methods including 2D NMR. Among them, 3-oxo-17,19-dihydroxy-7,13-ent-labdadien-15,16-olide (9), 3-oxo-19-hydroxy-1,13-ent-labdadien-15,16-olide (16), 3-oxo-1β-hydroxy-14-deoxy-andrographolide (17) and 3-oxo-2β-hydroxy-14-deoxyandrographolide (18) are new compounds. And their structure–activity relationships (SAR) of inhibitory activity on LPS-induced NO production in RAW 264.7 macrophage cells were also discussed. [Copyright &y& Elsevier]