Caragana sinica (Buc'hoz) Rehd. (jin ji er) polysaccharide regulates the immune function and intestinal microbiota of cyclophosphamide (CTX) induced immunosuppressed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana sinica (Buc'hoz) Rehd. is a plant widely grown in Yunnan, China, for both medicinal and edible purposes. The "National Compilation of Chinese Herbal Medicine" describes its nature as "slightly temperate and sweet". Caragana sinica is usually medicated with whole herbs, the main function is to replenish the kidneys and stop bleeding. Caragana sinica was used in folk medicine in Chuxiong, Yunnan, to treat deficiency colds, fatigue, fever, cough, hypertension, and other diseases. AIM OF THE STUDY: This article investigates the structural characteristics of Caragana sinica polysaccharide (CSP) and explores its immune-regulatory activity and molecular biological mechanisms in cyclophosphamide-induced immunosuppressed mice, as well as its effects on intestinal bacteria. METHODS: With the water-extraction and alcohol-precipitation method, Caragana sinica polysaccharide were extracted, obtaining CSP by purification. A variety of methods and techniques have been used to analyze the chemical properties and structural characteristics of CSP. Immunosuppressive mice model was established through intraperitoneal injection of cyclophosphamide (CTX) to study the immune-regulatory effects and mechanisms of CSP. RESULTS: The data indicated that CSP is a neutral heteropolysaccharide mainly composed of arabinose and galactose. This article uses immunosuppressive mice induced by cyclophosphamide (CTX) as the model. The results showed that CSP can promote the immune function of CTX treated immunosuppressed mice and regulate the diversity and composition of intestinal microbiota. CSP can increase macrophage phagocytosis, NK cell killing activity, and lymphocyte proliferation activity. It can also repair the index and morphological damage of the thymus and spleen. And by binding to the TLR4 receptor, MyD88 was activated and interacted with TRAF6 to promote the transfer of NF-κB into the nucleus. Thereby promoting cytokine release and increasing the production of IL-1ß, IL-6, IL-10, TNF-α, IgA, and IgG in the serum. CSP also effectively alleviated the liver damage caused by CTX through antioxidant activity. Furthermore, CSP can dramatically affect the intestinal microbiota and the body's immunity by boosting the relative presence of Bacteroides and Verrucamicrobiota. CONCLUSIONS: Research results indicated that CSP can regulate the immune function of mice, providing a basis for developing CSP as a potential immune modulator and functional food.

Study on Components with Anti-Neuroinflammatory Activities from Caragana microphylla Lam.

Caragana microphylla Lam., is a perennial herb in the genus Caragana in the Fabaceae family. Two undescribed triterpenoid saponins (1-2), along with thirty-five known components (3-37) were obtained from the roots of C. microphylla Lam. These compounds were identified using physicochemical analyses and various spectroscopic methods. The anti-neuroinflammatory activities were evaluated by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compared with positive control minocycline, compounds 10, 19, and 28 exhibited significant effects with IC50 values of 14.04, 19.35 and 10.20 µM, respectively.

Hypoglycemic oligostilbenes from the stems of Caragana sinica.

Six new oligostilbenes, carastilphenols A-E (1-5) and (-)-hopeachinol B (6), with three reported oligostilbenes were obtained from the stems of Caragana sinica. The structures of compounds 1-6 were determined by comprehensive spectroscopy analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Thus, natural tetrastilbenes were determined as absolute configuration for the first time. Also, we did several pharmacological essays. In the antiviral tests, compounds 2, 4 and 6 showed moderate anti-coxsackie virus B3 type (CVB3) effect on Vero cells activities in vitro with IC50 values of 19.2 âˆ¼ 69.3 µM; and compounds 3 and 4 showed different levels of anti-respiratory syncytial virus (RSV) effect on Hep2 cells activities in vitro with IC50 values of 23.1 and 33.3 µM, respectively. As for hypoglycemic activity, compounds 6-9 (10 µM) showed the inhibition of α-glucosidase in vitro with IC50 values of 0.1 âˆ¼ 0.4 µM; and compound 7 showed significant inhibition (88.8%, 10 µM) of protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 1.1 µM in vitro.

Determining the chemical profile of Caragana jubata (Pall.) Poir. by UPLC-QTOF-MS analysis and evaluating its anti-ischemic stroke effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana jubata, belonging to the Leguminosae family, is a shrubby medicinal plant distributed in high-altitude areas of China. The red heartwood of C. jubata is the original source of 'zuomuxing', a Tibetan medicine that promotes blood circulation and removes blood stasis to treat different diseases associated with the blood. AIM OF THE STUDY: To date, research on the chemical constituents of C. jubata remains very limited. The anti-ischemic stroke (anti-IS) effects of this plant have not been studied. The aim of the present study was to analyze the chemical profile of C. jubata, establish various anti-IS models to comprehensively evaluate the anti-IS effects of C. jubata, and explore the mechanism of action. MATERIALS AND METHODS: Ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was chosen to analyze the chemical profile. A middle cerebral artery occlusion reperfusion (MCAO/R) model, zebrafish cerebral thrombosis model, and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12/BV2 cells were used to thoroughly evaluate the anti-IS effects of C. jubata. Additionally, western blotting and immunofluorescence staining were used to detect the mechanism of action. RESULTS: Fifty-three compounds were identified from a 95% ethanol extract of C. jubata (ECJ) by UPLC-QTOF-MS analysis. 17 and 7 compounds were identified from C. jubata and the genus Caragana for the first time. ECJ was found to attenuate infarct size and reduce brain edema and neurological scores in MCAO/R rats. ECJ notably reduced the zebrafish cerebral thrombosis incidence in a dose-dependent manner compared with that in the model group. Surprisingly, compared to the positive control drug aspirin, 50 µg/ml ECJ exhibited a better therapeutic effect than aspirin at 30 µg/ml. Additionally, ECJ significantly increased the viability of PC12/BV2 cells injured by OGD/R. Moreover, ECJ inhibited the protein expression of M1 markers (TNF-α, iNOS, and IL-1ß) and increased that of M2 markers (Arg-1 and CD206) in OGD/R-injured BV2 cells. ECJ significantly decreased the immunofluorescence intensity of CD16 and increased that of CD206. CONCLUSIONS: The results from UPLC-QTOF-MS analysis showed that ECJ was rich in flavonoids. The results from pharmacological experiments verified the anti-IS effects of C. jubata in vivo and in vitro for the first time. In addition, ECJ could regulate the polarization of microglia. The present study highlights the medicinal value of C. jubata, thus providing a theoretical basis for the further development of new drugs from C. jubata to treat IS.

Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways.

Caragana rosea Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of Caragana rosea (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/ß and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.

Bioactive-guided isolation and identification of oligostilbenes as anti-rheumatoid arthritis constituents from the roots of Caragana stenophylla.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Caragana stenophylla have been used as folk medicine due to the functions of activating blood, diuresis, analgesic and tonicity, especially in treating rheumatoid arthritis and hypertension. However, the anti-rheumatoid arthritis mechanisms and bioactive ingredients have not previously been fully investigated. AIM OF THE STUDY: The aim of this study was to assess the anti-rheumatoid arthritis effects of the roots of Caragana stenophylla ethanol extract (EC), elucidate its mechanism of action and identify its active substances. MATERIALS AND METHODS: Anti-rheumatoid arthritis activity of EC was assessed using type II-collagen induced arthritis in rats. Arthritis severity was evaluated by foot paw volume, arthritis index, joint swelling degree and histopathology. The serum inflammatory cytokines and matrix metalloproteinases (MMPs) were also detected by immunohistochemical analysis. In addition, the protein expression of IκB, p-IκB, iNOS and COX-2 was analyzed by western blot. RAW 264.7 macrophage cells were employed to assess the anti-inflammatory effects of fractions and compounds in vitro. UPLC-Q-TOF-MS was adopted to appraise the ingredients of the active fraction of the roots of C. stenophylla. Furthermore, various chromatographic techniques and spectroscopic methods were used for isolation and structure elucidation of compounds. RESULTS: The results showed that EC could reduce type II collagen-induced rheumatoid arthritis model arthritic score and histopathology markedly at dose of 240 mg/kg. Besides, EC could suppress the levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) and matrix metalloproteinases (MMP-3, MMP-9), and the expression levels of COX-2, p-IκB and iNOS also were declined. While, the levels of IL-10 and IκB were increased. The ethyl acetate fraction exhibited potent inhibitory effects against nitric oxide production in RAW 264.7 macrophage cells. Eleven main components including 1 flavonoid and 10 oligostilbenes from active fraction were isolated by mass directed chromatographic techniques. Their structures were determined on the basis of various spectroscopic methods and by comparison with the published NMR data. CONCLUSION: The roots of C. stenophylla attenuated arthritis severity, restored serum cytokine imbalances by regulating NF-κB signaling pathway in type II collagen-induced rheumatoid arthritis model. Oligostilbenes were essential ingredients in ethyl acetate extract of C. stenophylla roots. Stilbenes and flavonoids should be responsible for its anti-rheumatoid arthritis activities.

Inhibitory mechanism of O-methylated quercetins, highly potent ß-secretase inhibitors isolated from Caragana balchaschensis (Kom.) Pojark.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana has a standing history of implementation in Traditional Chinese Medicine (TCM). Most species of this genus have been explored for multi-functional purposes, such as promoting blood circulation and curing neuralgia, fatigue, migraine, arthritis, and vascular hypertension (Meng et al., 2009). Among them, the well-known species C. sinica showed the most promising potential to increase the expression of ADAM10 among 313 tested medicinal plants, which is one of the promising approach for the treatment of Alzheimer's disease (AD). (Schuck et al., 2015). AIM OF THIS STUDY: The aim of this work is to explore ß-secretase inhibitory activity of compounds isolated from the aerial part of endemic Caragana balchaschensis (Kom.) Pojark. We provided a full characterization of their inhibitory mechanisms, binding affinities, and binding modes. MATERIALS AND METHODS: The isolation of quercetin derivatives was accomplished by various chromatographical approaches and their structures were annotated by spectroscopic analysis. The detailed kinetic behavior of ß-secretase inhibitors was determined by estimation of kinetic parameters (Km, Vmax, KI, and KIS). Binding affinities (KSV) and binding modes of inhibitors were elucidated by fluorescence quenching and molecular docking studies, respectively. RESULTS: O-methylated quercetins (2-7) were significantly effective in ß-secretase inhibition with IC50 ranging from 1.2 to 6.5 µM. The most active one (6) was 20-fold effective than the mother skeleton, quercetin. The O-methyl motif was a critical factor in ß-secretase inhibition: tri-O-methylated (1.2 µM) > di-O-methylated (3.5 µM) > mono-O-methylated (6.5 µM) > quercetin (25.2 µM). In the kinetic study, all quercetins (1-7) showed a noncompetitive inhibition, but glucoside ones (8 and 9) were mixed type I inhibitors. The binding affinities (KSV) were agreed with inhibitory potencies. The O-methylated quercetins were annotated as the most natural abundant metabolites in the aerial part by LC-ESI-TOF/MS. Binding modes of inhibitors to enzyme were elucidated by molecular docking experiments. CONCLUSION: This study disclosed that most of the major phenolic metabolites of the aerial part of C. balchaschensis are O-methylated quercetins, which have a significant inhibitory effect on ß-secretase, which is a critical factor for AD.

Inhibition effect of Caragana sinica root extracts on Osteoarthritis through MAPKs, NF-κB signaling pathway.

Osteoarthritis (OA) is a common joint disease characterized by degradation and inflammation of cartilage extracellular matrix. We aimed to evaluate the protective effect of Caragana sinica root (CSR) on interleukin (IL)-1ß-stimulated rat chondrocytes and a monosodium iodoacetate (MIA)-induced model of OA. In vitro, cell viability of CSR-treated chondrocytes was measured by MTT assay. The mRNA expression of Matrix metallopeptidases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) and extracellular matrix (ECM) were analyzed by quantitative real-time PCR (qRT-PCR). Moreover, the protein expression of MAPK (phosphorylation of EKR, JNK, p38), inhibitory kappa B (IκBα) and nuclear factor-kappa B (NF-κB p65) was detected by western blot analysis. In vivo, the production of nitric oxide (NO) was detected by Griess reagent, while those of inflammatory mediators, MMPs and ECM were detected by ELISA. The degree of OA was evaluated by histopathological analyses, Osteoarthritis Research Society International (OARSI) score and micro-CT analysis. CSR significantly inhibited the expression of MMPs, ADAMTSs and the degradation of ECM in IL-1ß-stimulated chondrocytes. Furthermore, CSR significantly suppressed IL-1ß-stimulated of MAPKs, NF-κB signaling pathway. In vivo, CSR and Indomethacin inhibited the production of inflammatory mediators, MMPs and degradation of ECM in MIA-induced model of OA. In addition, CSR improved the severity of OA. Taken together, these results suggest CSR is a potential therapeutic active agent in the treatment of OA.

Neuraminidase Inhibitors from the Roots of Caragana sinica.

Two new oligostilbenes, caragasinins D and E, along with four known compounds, kobophenol A, α-viniferin, wistin, and 5-hydroxy-2-[(4-hydroxyphenyl)acetyl]-3-methoxybenzoic acid, were isolated from the roots of Caragana sinica. These compounds were spectroscopically analyzed for their structures and configurations and compared with existing data. The configurations of caragasinins D and E were elucidated by 1 H-NMR spectroscopy, CD spectroscopy, and time-dependent density-functional theory simulated ECD spectral data. All six compounds were evaluated for their inhibitory activity against neuraminidase (NA) from Clostridium perfringens. Among the tested compounds, 5-hydroxy-2-[(4-hydroxyphenyl)acetyl]-3-methoxybenzoic acid demonstrated statistically significant NA inhibitory activity, which was comparable to the positive control, mangiferin.

Separation of five flavonoids with similar polarity from Caragana korshinskii Kom. by preparative high speed counter-current chromatography with recycling and heart cut mode.

Five flavonoids with similar polarity were obtained from Caragana korshinskii Kom. by preparative high speed counter-current chromatography. Due to their similar polarity, it is difficult to select a suitable solvent system for one-step separation. Three fractions including one pure compound were only obtained with a relatively suitable solvent system of ethyl acetate: n-butanol:water (0.5% glacial acetic acid) (4:6:10, v:v:v). In order to improve the separation efficiency, recycling and heart cut modes were introduced. As a result, two flavonoids with separation factor value at 1.13 and the other two with separation factor value at 1.20 were successfully separated. Finally, five flavonoids with purity higher than 98% were obtained. Fortunately, a new compound named myricetin 3'-methyl ether 3-O-glucoside-7-O-rhamnoside was obtained. The results indicated that the recycling combined with heart-cut mode could be effective for the preparation of natural compounds with similar polarity.

Drought stress-induced autophagy gene expression is correlated with carbohydrate concentrations in Caragana korshinskii.

Autophagy has been reported to be an adapt function of plant cells under various stresses. In this report, autophagy-related gene expressions and carbohydrate concentrations in Caragana korshinskii leaf cells under drought stress were investigated. Leaf samples of C. korshinskii plants of an estimated 15-year-old were collected from three sites with different drought stress (annual precipitation range, 325.8 to 440.8 mm) at the Loess Plateau in northwestern China. Autophagy was observed in C. korshinskii samples from all three sites and was revealed by autophagosomes in the cytoplasm of mesophyll cells and increased chloroplasts degradation observed by transmission electron microscopy. Furthermore, with the drought stress increase, autophagy-related gene expressions were upregulated and leaf concentration of sucrose was increased, while concentrations of monosaccharide sugars such as glucose, fructose and galactose were decreased. The results suggested that drought stress induced autophagy gene expression, which may serve as a survival mechanism for nutrient remobilisation.

2,4-Dihydroxy-3'-methoxy-4'-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway.

Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3'-methoxy-4'-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 µM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 µM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 µM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 µM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.

Anti-inflammatory Chalcone-Isoflavone Dimers and Chalcone Dimers from Caragana jubata.

Two new chalcone-isoflavone dimers, caraganins A (1) and B (2), two new chalcone dimers, caraganins C (3) and D (4), and eight known compounds (5-12) were obtained from the red heartwood of the rhizomes of Caragana jubata. The structures of caraganins A-D were established by 1D and 2D NMR spectroscopy, HRMS and ECD analysis, and comparison with previously known compounds. The anti-inflammatory activities of the new compounds were evaluated by measuring the production of NO, IL-6, and TNF-α in mouse RAW 264.7 macrophages induced by lipopolysaccharide. Among these, compounds 2 and 4 showed the most potent inhibitory activities (IC50: 4.1 and 5.2 µM, respectively) on nitric oxide formation, and compounds 1 and 4 displayed the most potent inhibitory activities on the secretion of inflammatory factor TNF-α, with IC50 values of 11.4 and 14.7 µM. The possible biosynthetic pathways of the chalcone-isoflavone dimers and the chalcone dimers are proposed.

Analysis of Metabolite Accumulation Related to Pod Color Variation of Caragana intermedia.

Caragana intermedia, a leguminous shrub widely distributed in cold and arid regions, is rich in secondary metabolites and natural active substances, with high nutritional and medical values. It is interesting that the pods of C. intermedia often show different colors among individual plants. In this study, 10-, 20- and 30-day-old red and green pods of C. intermedia were used to identify and characterize important metabolites associated with pod color. A total 557 metabolites, which could be classified into 21 groups, were detected in the pod extracts using liquid chromatography coupled with ESI-triple quadrupole-linear ion trap mass spectrometer (LC-ESI-MS/MS). Metabolomics analysis revealed significant differences in 15 groups of metabolites between red and green pods, including amino acids, nucleotide derivatives, flavonoids, and phytohormones. Metabolic pathway analysis showed that the shikimic acid and the phytohormone metabolic pathways were extraordinarily active in red pods, and the difference between red and green pods was obvious. Moreover, red pods showed remarkable flavonoids, cytokinins, and auxin accumulation, and the content of total flavonoids and proanthocyanidins in 30-day-old red pods was significantly higher than that in green pods. This metabolic profile contributes to valuable insights into the metabolic regulation mechanism in different color pods.

Isolation of antioxidative peptide from the protein hydrolysate of Caragana ambigua seeds and its mechanism for retarding lipid auto-oxidation.

BACKGROUND: Peptides can act as antioxidants in emulsion, although the mechanism involved is poorly understood. Caragana ambigua seed is a potential protein source for which the commercial applications have not been explored yet. In the present study, we aimed to evaluate the bio-economic potential of C. ambigua by isolating and characterizing antioxidative peptides from the protein hydrolysate of its seeds for the purpose of protecting lipids from oxidation. RESULTS: A novel decapeptide, identified as QITEGEDGGG, was purified by high-protein liquid chromotography based on the enrichment of antioxidant fractions, and its antioxidative activity for walnut oil was evaluated in terms of its effect on oil quality, primary and secondary peroxide formation, oxidation kinetics, and structure of oil droplets. A molecular simulation involving the peptide and fatty acid was carried out aiming to understand the mechanism underlying the prevention of lipid oxidation by the peptide. The peptide effectively scavenged superoxide anions (86.46%), inhibited the rate of linoleic acid oxidation (60.37%) and delayed auto-oxidation of walnut oil. Its inhibition of lipid oxidation was attributed to the protection of phenolic compounds and polyunsaturated fatty acids of walnut oil. CONCLUSION: The findings of the present study will help in the exploitation of novel antioxidant peptides of lipids from woody seed-based protein sources such the seeds of C. ambigua trees. © 2018 Society of Chemical Industry.

Precipitation is the main factor affecting the variation of foliar nitrogen isotope composition in two leguminous shrub species of northwestern China.

An increase in foliar nitrogen isotope composition (δ15N) with decreasing precipitation has been shown to occur widely in non-N2-fixing plant species. However, similar patterns have not been identified in N2-fixing species. Here, we tested the relationships of foliar δ15N with local environmental factors and leaf properties in two leguminous shrub species (Caragana korshinskii and Caragana liouana) sampled from 30 populations. Results indicated that the mean annual precipitation (MAP) primarily accounted for the variation of foliar δ15N in the two species. Further analysis revealed strong negative correlations between foliar δ15N and MAP within and across species. These results suggest that the foliar δ15N of leguminous shrub species also shift along precipitation gradients, which augments our understanding of the relationships between foliar δ15N and climatic factors.

[Hepatoprotective activity of aqueous extract from Caragana jubata (Pall.) Poir. shoots in the model of acute hepatitis induced by acetaminophen in rats]. / Gepatoprotektornaia aktivnost' vodnogo izvlecheniia iz pobegov Caragana jubata (Pall.) Poir. na modeli ostrogo gepatita, indutsirovannogo atsetaminofenom u krys.

The aim of the study was to investigate the hepatoprotective activity of an aqueous extract of Caragana jubata (Pall.) Poir. Acute experimental hepatitis was induced by acetaminophen administration of 1000 mg/kg. Studies were conducted in white Wistar rats. The aqueous extract of C. jubata demonstrated the hepatoprotective effect, comparable to that of the reference preparation "Carcil". This was manifested by the normalization of biochemical blood parameters (ALT, AST, alkaline phosphatase, cholesterol, total bilirubin) and antioxidant activity of liver homogenates, determined by the method based on oxidation of luminol induced by 2,2¢-azo-bis-2-amidinopropane. Normalization of morphofunctional indices was also shown in a histological study of liver of rats that received aqueous extract from C. jubata.

α-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis.

Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica. Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism. Results:C. sinica or α-viniferin inhibited melanin production in α-melanocyte-stimulating hormone (α-MSH)-, histamine- or cell-permeable cAMP-activated melanocyte cultures. Moreover, topical application with C. sinica containing α-viniferin, a standard in quality control, decreased melanin index on facial melasma and freckles in patients. As a molecular basis, α-viniferin accelerated protein kinase A (PKA) inactivation via the reassociation between catalytic and regulatory subunits in cAMP-elevated melanocytes, a feedback loop in the melanogenic process. α-Viniferin resultantly inhibited cAMP/PKA-signaled phosphorylation of cAMP-responsive element-binding protein (CREB) coupled with dephosphorylation of cAMP-regulated transcriptional co-activator 1 (CRTC1), thus down-regulating expression of MITF-M or Tyro gene with decreased melanin pigmentation. Conclusion: This study assigned PKA inactivation, a feedback termination in cAMP-induced facultative melanogenesis, as a putative target of α-viniferin in the treatment of melanocyte-specific hyperpigmented disorder. Finally, C. sinica containing α-viniferin was approved as an antimelanogenic agent with topical application in skin hyperpigmentation.

Zeolitic imidazolate framework-8 for selective extraction of a highly active anti-oxidant flavonoid from Caragana Jubata.

The medicinal compositions or active components in medicinal plants are the major sources to find new drugs or lead compounds. Exploring novel sorbents with good selectivity for extraction and separation of medicinal compositions or active components from complex medicinal plants are interesting and challenging. Metal-organic frameworks (MOFs) show great potential in adsorption and extraction recently. Herein, we report our primary attempt of zeolitic imidazolate framework-8 (ZIF-8) as a model MOF for selective extraction of a flavonoid named 3,4-dihydroxy-8,9-methylenedioxypterocarpan (compound 1) from a traditional medicinal plant Caragana Jubata. The enrichment factor of ZIF-8 for compound 1 is 57.7. The recoveries of compound 1 at three spiked levels (50, 100, 150 mg L-1) in Caragana Jubata dichloromethane extract are 62.1%, 66.4%, and 75.4%, respectively, with the relative standard deviations of less than 2.9%. The compound 1 also gave good linearity (R2 of 0.999) in the concentration range of 5-1000 mg L-1. The obtained compound 1 gave highly antioxidant activity (DPPH radical scavenging rate of 79.03%, inhibitory rate on lipid peroxidation of 75.30%, which were higher than the positive controls Vitamin C and BHT) and low IC50 values (5.438 ±â€¯0.068, 20.970 ±â€¯0.083 µg mL-1 for DPPH radical scavenging activities and inhibitory effects on lipid peroxidation, respectively). These results demonstrated the feasibility of MOFs in selective extraction of medicinal compositions or active components from complex medicinal plants. The current work may open a new way of MOFs in selective extraction of pharmacological active components from medicinal plants.

[Chemical constituents from roots of Caragana stenophylla and their anti-tumor activities].

Fourteen compounds were isolated from the 80% ethanol extract of Caragana stenophylla root, by using a combination of various chromatographic approaches, including silica gel sephadex LH-20 column chromatography, and preparative HPLC. On the basis of their physical and chemical properties and spectroscopic data, their structures were elucidated as 2-(4-hydroxy-3-methoxy lphenyl)-3-methoxyl benzofuran-6-ol (1), mucodianin C (2), isopterofuran (3), formononetin (4), afromosin (5), calycosin (6), acacetin (7), 3-O-methylkaempferol (8), liquiritigenin (9), isoliquiritigenin (10), variabilin (11), resveratrol (12), zhebeiresinol (13), and 2, 3-dicarboxy-6, 7-dihydroxy-1-(3', 4'-dihydroxy)-phenyl-1, 2-dihydronaphthalen (14). Compound 1 is a new benzofuran derivative, named as mucodianin S; compounds 2, 3, 11, 13, 14 were isolated from the genus Caragana for the first time, and compounds 4-10 were firstly isolated from Caragana stenophylla. MTT assay was used to determine their cytotoxicity of the isolated compounds against human tumor cell lines, and 2 showed cytotoxicity against human hepato cellular cancer (HepG2) and human cervical (HeLa) lines, with IC50 values of (16.18±0.95), (3.75±0.08) µmol•L ⁻¹, respectively.