Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

l-valine supplementation disturbs vital molecular pathways and induces apoptosis in mouse testes.

The branched-chain amino acids (BCAAs: leucine, isoleucine and valine) are essential for animal growth and metabolic health. However, the effect of valine on male reproduction and its underlying molecular mechanism remain largely unknown. Here, we showed that l-valine supplementation (0.30% or 0.45%, water drinking for 3 weeks) did not change body and testis weights, but significantly altered morphology of sertoli cells and germ cells within seminiferous tubule, and enlarged the space between seminiferous tubules within mouse testis. l-valine treatment (0.45%) increased significantly the Caspase3/9 mRNA levels and CASPASE9 protein levels, therefore induced apoptosis of mouse testis. Moreover, gene expression levels related to autophagy (Atg5 and Lamb3), DNA 5 mC methylation (Dnmt1, Dnmt3a, Tet2 and Tet3), RNA m6A methylation (Mettl14, Alkbh5 and Fto), and m6A methylation binding proteins (Ythdf1/2/3 and Igf2bp1/2) were significantly reduced. Protein abundances of ALKBH5, FTO and YTHDF3 were also significantly reduced, but not for ATG5 and TET2. Testis transcriptome sequencing detected 537 differentially expressed genes (DEGs, 26 up-regulated and 511 down-regulated), involved in multiple important signaling pathways. RT-qPCR validated 8 of 9 DEGs (Cd36, Scd1, Insl3, Anxa5, Lcn2, Hsd17b3, Cyp11a1, Cyp17a1 and Agt) to be decreased significantly, consistent with RNA-seq results. Taken together, l-valine treatment could disturb multiple signaling pathways (autophagy and RNA methylation etc.), and induce apoptosis to destroy the tissue structure of mouse testis.

Sensory-guided isolation and identification of new sweet-tasting dammarane-type saponins from Jiaogulan (Gynostemma pentaphyllum) herbal tea.

The purpose of this study was to elucidate the chemical basis for the sweet property produced by Gynostemma pentaphyllum and find new natural high-potency (HP) sweeteners. Sixteen new compounds (gypenosides YN 1-16) were obtained by sensory-guided isolation and identification, in which fifteen of them were sweet-tasting constituents with sweetness intensities 10-100 times higher than that of sucrose evaluated by human sensory panel test. Their structures were established by 1D and 2D nuclear magnetic resonance spectra, mass spectroscopy, infrared spectroscopy, UV-visible spectroscopy, and chemical method. Gypenoside YN 4 was the sweetest compound with a concentration of 15.504 ± 1.343 mg/kg, while gypenoside YN 12 has the highest concentration (1397.674 ± 12.948 mg/kg), as shown by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Structure-activity relationship analysis implied that the compounds' sweetness intensity was associated with side-chain substitutions at C-20 or the number of glucosyl groups at C-3. These new plant-derived natural products may be potential natural sweeteners.

Comparative study on the main active components of Baoyuan decoction in plasma and urine of normal and heart failure rats.

The global morbidity and mortality of heart failure has been increasing in recent years. Traditional Chinese medicine (TCM) was increasingly used to treat cardiovascular diseases. Baoyuan decoction (BYD) was a famous classical prescription in China. Modern pharmacological studies showed that it had obvious therapeutic effects on cardiovascular diseases, but its pathological pharmacokinetic studies were unclear. In this research, the absorption of 16 bioactive components in plasma and the excretion of 9 representative components in urine of control rats and isoproterenol (ISO)-induced heart failure rats were studied using the large-volume direct-injection LC-MS method established by our research group. The results indicated that flavonoid constituents exhibited quicker absorption and elimination than saponin constituents after oral administration of BYD. The half-life period of some bioactive compounds in the model group was increased, which contributed to the longer therapeutic effect. The cumulative excretion rate of major flavonoid components of BYD decreased significantly in the ISO-induced heart failure rats.

Melatonin mitigates Chloroquine-induced defects in porcine immature Sertoli cells.

Chloroquine (CQ) could function as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway, and is widely used on malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here we showed that CQ could reduce iSC viability in a dose-dependent manner. CQ treatment (20 µM) on iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis, which could be partially rescued by melatonin (MT) (10 nM). Transcriptome profiling identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20 µM CQ vs. DMSO), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, only 467 (224 up- and 243 down-regulated) DEGs (CQ + MT vs. DMSO) could be found after MT (10 nM) addition, enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction pathways. Therefore, the partial rescue effects of MT on CQ treatment were confirmed by multiple assays (cell viability, ROS level, mitochondrial function, apoptosis, and mRNA levels of selected genes). Collectively, CQ treatment could impair porcine iSC viability by deranging the signaling pathways related to apoptosis and autophagy, which could be partially rescued by MT supplementation.

Improvement of Skin Barrier Dysfunction by Phenolic-containing Extracts of Lycium barbarum via Nrf2/HO-1 Regulation.

Lycium barbarum have received an increasing popularity due to its powerful biological activity and medicinal use. However, the effect of Lycium barbarum on skin remains largely uncharacterized. The general purpose of this paper was to characterize the phenolic compounds in Lycium barbarum extract (LBE) using LC-HRMS/QTOF method and to investigate whether topical administration of LBE can repair skin barrier dysfunction in mice. Our data demonstrated that LBE could not only decrease ROS level and matrix metalloproteinase expression, but also strengthen intrinsic antioxidant defense system including SOD, GSH-Px and CAT, thereby resulting in increased skin collagen content and an improvement of UV-induced skin erythema, thickness and wrinkles. Improved skin barrier functions were highly correlated with increased expression of filaggrin, involucrin and loricrin as well as antioxidant proteins such as Nrf2 and HO-1 in UV-irradiated mice, suggesting that LBE may be promising natural products at a lower cost for the topical application in the treatment of skin diseases with defective barrier function.

Comparison of Murraya exotica and Murraya paniculata by fingerprint analysis coupled with chemometrics and network pharmacology methods.

There are two source plants for the traditional Chinese medicine Murrayae Folium et Cacumen (MFC) in Chinese Pharmacopoeia, i.e. Murraya exotica L. and M. paniculata (L.) Jack. Herein, a chemical comparison of M. exotica and M. paniculata by high performance liquid chromatography (HPLC) fingerprint analysis coupled with chemometrics and network pharmacology was performed. The main peaks in the fingerprints were identified by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) and authenticated by references. The chemometrics results showed that the HPLC fingerprints of these two species were clearly divided into two categories using hierarchical cluster analysis (HCA) and principal component analysis (PCA), and a total of 13 significantly differentiated markers were screened out by orthogonal partial least squares-discriminant analysis (OPLS-DA). However, the following network pharmacology analysis showed that these discriminated markers were found to act via many common targets and metabolic pathways, indicating the possibly similar pharmacological effects and mechanisms for M. exotica and M. paniculata. The above results provide valuable evidence for the equivalent use of these two plants in clinical settings. Moreover, the chromatographic fingerprint analysis coupled with chemometrics and network pharmacology supplies an efficient approach for the comparative analysis of multi-source TCMs like MFC.

Repellent, larvicidal and adulticidal activities of essential oil from Dai medicinal plant Zingiber cassumunar against Aedes albopictus.

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm2). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (-)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm2). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC50 (50% lethal concentration) of 44.9 µg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC50 of 5.44%, while (-)-terpinen-4-ol showed significant adulticidal activity with a LC50 of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (-)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (-)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.

Evaluation of the effects of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS) on the activities of cytochrome P450 enzymes using a cocktail method in rats.

Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.

CoQ10 improves meiotic maturation of pig oocytes through enhancing mitochondrial function and suppressing oxidative stress.

Coenzyme Q10 (CoQ10) is essential to many fundamental biological processes. However, the effect of CoQ10 on meiotic maturation of pig oocytes still remains elusive. In the present study we aimed to understand the effects of CoQ10 on porcine oocyte maturation, by supplementing different concentrations of CoQ10 (25, 50 and 100 µM) into the maturation medium. We showed that CoQ10 at 50 µM had better capacity to promote the nuclear maturation of pig oocytes derived from both small and large antral follicles. Though the cleavage and blastocyst rates of parthenotes stayed stable, 50 µM CoQ10 treatment could accelerate the development of parthenotes to blastocyst stage, and increase the average cell number of blastocyst. For cumulus-oocyte complexes from large antral follicles categorized by the brilliant cresyl blue (BCB) test, 50 µM CoQ10 treatment could specifically promote the nuclear maturation of poor-quality oocytes in the BCB-negative group. Mitochondrial function of oocytes treated by 50 µM CoQ10 could be boosted, through increasing the levels of mitochondrial membrane potential, ATP production and CoQ6, and changing the pattern of mitochondrial distribution as well. Moreover, 50 µM CoQ10 treatment suppressed the level of reactive oxygen species and reduced the percentage of oocytes with early apoptosis signal. Taken together, CoQ10 could improve the meiotic maturation of pig oocytes, especially for poor-quality oocytes, mainly through enhancing mitochondrial function and suppressing oxidative stress to reduce apoptosis.

Ascorbic acid promotes the reproductive function of porcine immature Sertoli cells through transcriptome reprogramming.

Vitamin C (ascorbic acid, AA) can regulate antioxidation and affect many cellular processes. However, the effect of AA on the reproduction of male animals remains less explored. Here, we showed that by supplementing exogenous AA to porcine immature Sertoli cells (iSCs), AA could promote the proliferation, suppress apoptosis, and decrease the global nucleic acid methylation (5 mC and m6A) levels of iSCs. After we profiled mRNA and long non-coding RNA (lncRNA) expression by transcriptome sequencing on iSCs (treated by 250 µM AA for 36 h), 1232 mRNAs and 937 lncRNAs were identified to be differentially expressed (DE). Gene enrichment analysis found multiple significantly enriched biological pathways, including oxidoreductase activity, cell proliferation and apoptosis, regulation of hormone level, regulation of catalytic activity, developmental process, ATP metabolism and reproductive process. Specifically, for the reproductive process, 49 up- and 36 down-regulated DE mRNAs (including highly expressed genes, such as Tfcp2l1, Hmgcs1, Mmp7, Fndc3a, and Zfp36l1) are involved. Moreover, AA supplementation could promote the secretion of anti-müllerian hormone, inhibin B and lactate, and enhance the activity of lactate dehydrogenase as well. Taken together, AA could promote the reproductive function of pig iSCs, potentially through reprogramming the global transcriptome, and elevating hormone secretion and metabolite production.

Single cell RNA-seq reveals molecular pathways altered by 7, 12-dimethylbenz[a]anthracene treatment on pig oocytes.

Oocytes of better quality and developmental competence are highly demanded, which is affected by many intrinsic and external factors, including environmental pollutants. We have previously demonstrated that 7, 12-dimethylbenz [a]anthracene (DMBA) reduces the developmental competence of porcine oocytes, by desynchronizing nuclear and ooplasmic maturation. However, the underlying molecular mechanism remains obscure. Here we performed single cell RNA-seq to study the transcriptome changes in DMBA-treated porcine MII oocytes, and identified 19 protein-coding genes and 156 novel long non-coding RNAs (lncRNAs) with abundance to be significantly different (P < 0.05), which enriched in signaling pathways such as glycosphingolipid biosynthesis, nicotine addiction, basal transcription factors and nucleotide excision repair. RT-qPCR on oocyte pools confirmed ornithine aminotransferase (Oat) and serine/arginine-rich splicing factor 4 (Srsf4) to be significantly up- and down-regulated, respectively (P < 0.05). Treating porcine COCs with MAPK and PLC pathway inhibitors suppressed DMBA's effects on increasing PB1 extrusion rate. In addition, DMBA co-incubation with 250 µM vitamin C derivative (l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) and 100 µM co-enzyme Q10 (CoQ10) could significantly reduce the DMBA-induced high ROS level, and partially alleviate the DMBA-induced high PB1 rate, whereas the cleavage and blastocyst rates of parthenotes derived from treated mature oocytes remained to be low. Collectively, our findings indicate that single cell RNA-seq can help reveal the dynamics of molecular signaling pathways for porcine oocytes treated by DMBA, and supplement of anti-oxidative reagents could not sufficiently rescue DMBA-induced defects of porcine oocytes.

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 µg/mL) and 25-hydroxycholesterol (2 µg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 µM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

Near-Infrared Activated Black Phosphorus as a Nontoxic Photo-Oxidant for Alzheimer's Amyloid-ß Peptide.

The inhibition of amyloid-ß (Aß) aggregation by photo-oxygenation has become an effective way of treating Alzheimer's disease (AD). New near-infrared (NIR) activated treatment agents, which not only possess high photo-oxygenation efficiency, but also show low biotoxicity, are urgently needed. Herein, for the first time, it is demonstrated that NIR activated black phosphorus (BP) could serve as an effective nontoxic photo-oxidant for amyloid-ß peptide in vitro and in vivo. The nanoplatform BP@BTA (BTA: one of thioflavin-T derivatives) possesses high affinity to the Aß peptide due to specific amyloid selectivity of BTA. Importantly, under NIR light, BP@BTA can significantly generate a high quantum yield of singlet oxygen (1 O2 ) to oxygenate Aß, thereby resulting in inhibiting the aggregation and attenuating Aß-induced cytotoxicity. In addition, BP could finally degrade into nontoxic phosphate, which guarantees the biosafety. Using transgenic Caenorhabditis elegans CL2006 as AD model, the results demonstrate that the 1 O2 -generation system could dramatically promote life-span extension of CL2006 strain by decreasing the neurotoxicity of Aß.

Chirality-Selected Chemical Modulation of Amyloid Aggregation.

Due to the composed α-helical/ß-strand structures, ß-amyloid peptide (Aß) is sensitive to chiral environments. The orientation and chirality of the Aß strand strongly influence its aggregation. Aß-formed fibrils have a cascade of chirality. Therefore, for selectively targeting amyloid aggregates, chirality preference can be one key issue. Inspired by the natural stereoselectivity and the ß-sheet structure, herein, we synthesized a series of d- and l-amino acid-modified polyoxometalate (POM) derivatives, including positively charged amino acids (d-His and l-His) and negatively charged (d-Glu and l-Glu) and hydrophobic amino acids (d-Leu, l-Leu, d-Phe, and l-Phe), to modulate Aß aggregation. Intriguingly, Phe-modified POMs showed a stronger inhibition effect than other amino acid-modified POMs, as evidenced by multiple biophysical and spectral assays, including fluorescence, circular dichroism, NMR, molecular dynamic simulations, and isothermal titration calorimetry. More importantly, d-Phe-modified POM had an 8-fold stronger inhibition effect than l-Phe-modified POM, indicating high enantioselectivity. Furthermore, in vivo studies demonstrated that the chiral POM derivatives crossed the blood-brain barrier, extended the life span of AD transgenic Caenorhabditis elegans CL2006 strain, and had low cytotoxicity, even at a high dosage.

Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS/MS with a large-volume direct injection method.

BACKGROUND: Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD. METHODS: The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3 ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM). RESULTS: The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats. CONCLUSION: The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM.

Complementary iTRAQ Proteomic and Transcriptomic Analyses of Leaves in Tea Plant ( Camellia sinensis L.) with Different Maturity and Regulatory Network of Flavonoid Biosynthesis.

The quality of tea is highly related with the maturity of the fresh tea leaves at harvest. The present study investigated the proteomic and transcriptomic profiles of tea leaves with different maturity, using iTRAQ and RNA-seq technologies. A total of 4455 proteins and 27 930 unigenes were identified, with functional enrichment analyses of GO categorization and KEGG annotation. The compositions of flavonoids (catechins and flavonols) in tea leaves were determined. The total content of flavonoids decreased with leaf maturity, in accordance with the protein regulation patterns of shikimate, phenylpropanoid, and flavonoid pathways. The abundance of ANR had a positive correlation with epi-catechin content, while LAR abundance was positively related with catechin content ( P < 0.05). The biosynthetic network of flavonoid biosynthesis was discussed in combination with photosynthesis, primary metabolism, and transcription factors. Bud had the lowest activities of photosynthesis and carbon fixation but the highest flavonoid biosynthesis ability in opposite to mature leaf. SUS-INV switch might be an important joint for carbon flow shifting into the follow-up biochemical syntheses. This work provided a comprehensive overview on the functional protein profile changes of tea leaves at different growing stages and also proposed a research direction regarding the correlations between primary metabolism and flavonoid biosynthesis.

Aromatic-turmerone ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c mice.

Psoriasis is a usual immune-mediated inflammatory skin disease with undefined pathogenesis. Aromatic-turmerone (ATM) is a mainly constituent of essential oil from Curcuma longa L. It has been shown to exhibit strong anti-oxidant, anti-tumor activities and anti-inflammatory effects. In this study, we investigated the effects of ATM on imiquimod (IMQ)-induced psoriasis-like BALB/c mice and its molecular mechanisms for anti-inflammatory effect. ATM showed inhibition of the transfer of CD8+ T cells in epidermis, and reduced expression of NF-κB and COX-2 as well as phosphorylation of p38 MAPK. It also decreased the level of TNF-α and IL-6, and down-regulates IL-17 IL-22 and IL-23 mRNA synthesis. Notably, we demonstrated that topically applied ATM alleviated skin inflammation in IMQ-induced mice. These results indicate that ATM, a natural active compound exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.

New Sweet-Tasting C21 Pregnane Glycosides from the Roots of Myriopteron extensum.

To investigate the sweet-tasting components in the roots of Myriopteron extensum, the phytochemical study of its roots was conducted, which led to the discovery of 12 new C21 pregnane glycosides (extensumside M-X, 1-12) and two known ones (extensumside C and extensumside E, 13-14). Their chemical structure elucidation was accomplished by means of spectroscopic methods: IR, UV, ESI-MS, and NMR (1H NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, HSQC-TOCSY, and ROESY), as well as the chemical evidence. Sensory analysis of these compounds revealed that nine of them (1, 3, 4, 5, 6, 7, 8, 13, and 14) are highly sweet-tasting compounds. Their sweetness intensities are 25 to 400 times greater than that of sucrose. Analysis of the structure-activity relationship (SAR) indicated that the sweet intensities of the isolated compounds are closely related to the aglycone 3ß,16α-dihydroxy-pregn-5-en-20-one, the number and type of the monosaccharide in the sugar chain linked to C-3 and C-16 and the position of the mBe group.

Effects of Baoyuan decoction, a traditional Chinese medicine formula, on the activities and mRNA expression of seven CYP isozymes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan decoction (BYD), a traditional Chinese medicine (TCM) formula, is composed of four herbs and widely used with western drugs to treat coronary heart disease, aplastic anemia and chronic renal failure in clinic. However, no study of the effect of BYD on the cytochrome P450 (CYP) activities has been reported. AIM OF THE STUDY: The purpose of the present study was to evaluate the potential influences of BYD on the activities of seven CYP isozymes (CYP1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in rats. MATERIALS AND METHODS: A sensitive and selective UPLC-MS/MS method for simultaneous determination of seven probe drugs and internal standard (IS) in rat plasma was developed and validated. The influence of BYD on the activities of CYP isozymes and mRNA expression levels were carried out by comparing plasma pharmacokinetics and real-time reverse transcription-polymerase chain reaction (RT-PCR) of probe drugs between control and BYD treatment groups respectively. RESULTS: The calibration curve were linear, with correlation coefficient (r) > 0.99 for seven probe drugs. The intra and inter-assay accuracy and precision of the method were within ±â€¯14.9% and the recoveries ranged from 83.2% to 106.1%. Compared with control group, BYD at low (1.46 g/kg) and high (7.30 g/kg) dosages could significantly increase Cmax and AUC0-t of chlorzoxazone and testosterone, while decrease AUC0-t of phenacetin at high dosage and increase AUC0-t of tolbutamide and metoprolol. Additionally, BYD had increased AUC0-t of bupropion at low dosage and decreased it at high dosage. The mRNA expression results were in accordance with those of pharmacokinetic. CONCLUSION: BYD exhibited inhibitory effects on CYP2C9, CYP2E1, and CYP3A4. Moreover, BYD had induction effects on CYP1A2, and CYP2D6 activities. However, no significant change in CYP2C19 activity was observed. It would be useful for the safe and effective usage of BYD in clinic.