Xanthoceraside (XAN) is a natural-derived compound with anti-Alzheimer activity from the husks of
Xanthoceras sorbifolia
. Although its therapeutic effect had been confirmed in previous studies, the ...mechanism was still unclear due to its poor solubility and low permeability. In this study, the pharmacological effect of XAN on Alzheimer’s disease (AD) was confirmed by behavior experiments and H&E staining observation. Fecal microbiota transplantation (FMT) experiment also replicated the therapeutic effects, which indicates the potential targets of XAN on gut microbiota. The sequencing of 16S rRNA genes in fecal samples demonstrated that XAN reversed gut microbiota dysbiosis in AD animals. XAN could change the relative abundances of several phyla and genus of bacterial, particularly the ratio of
Firmicutes/Bacteroidetes
. Among them,
Clostridium IV
,
Desulfovibrio
,
Corynebacterium
, and
Enterorhabdus
had been reported to be involved in the pathologic developments of AD and other central nervous system disease. In metabolomics study, a series of host endogenous metabolites were detected, including amino acids, lysophosphatidylcholine, dihydrosphingosine, phytosphingosine, inosine, and hypoxanthine, which were all closely associated with the development of AD. Combined with the Spearman’s correlation analysis, it was confirmed that the increases of five bacterial strains and decreases of six bacterial strains were closely correlated with the increases of nine host metabolites and the decreases of another five host metabolites. Therefore, XAN can modulate the structure of gut microbiota in AD rats; the changes of gut microbiota were significantly correlated with endogenous metabolites, and symptom of AD was ultimately alleviated. Our findings suggest that XAN may be a potential therapeutic drug for AD, and the gut microbiota may be potential targeting territory of XAN
via
microbiome–gut–brain pathway.
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•Berberine (BBR) was immobilized onto MgAl monolayer hydrotalcite (MLDH) by ion-exchange method.•BBR-MgAl monolayer hydrotalcite (BBR/MLDH) could increase the solubility and ...bioavailability of BBR.•BBR/MLDH showed stronger hypoglycemic effect than free BBR in diabetic mice.
Berberine (BBR) is a potential novel agent to treat diabetes, but its oral bioavailability is restricted by the poor solubility, which greatly limits its clinical application. Here, a new drug delivery system of BBR-MgAl monolayer hydrotalcite (BBR/MLDH) was prepared to increase the solubility and bioavailability of BBR. The results showed that BBR/MLDH presented as a uniform hexagonal plate-like particle with a loading capacity of 28.61 %, a diameter of ∼70 nm and a thickness of ∼1.5 nm. The solubility and dissolution of BBR increased when loading onto MLDH. Compared with BBR, pharmacokinetics of BBR/MLDH in rats showed significant enhancement (P < 0.01) in area under the curve (AUC) and the peak plasma concentration (Cmax), suggesting the bioavailability of BBR was improved. Furthermore, BBR/MLDH showed more potent effects in reducing fasting blood glucose, ameliorating glucose tolerance and insulin resistance comparing to the equivalent dose of BBR. In a word, the solubility, oral bioavailability and hypoglycemic effect of BBR could be improved by loading onto MLDH.
•XSE showed cognitive-improving effect in AD-like rat models.•Dendritic spine density deficits were ameliorated by treatment with XSE.•BDNF was up-regulated and RhoA/ROCK2 were inhibited which were ...involved in the pharmacodynamics of XSE.
Xanthoceras sorbifolia, a traditional Chinese folk medicine with anti-inflammatory effects, has been used for a long time in China, especially in the Inner Mongolian area for the treatment of rheumatism. Inflammation is one of the main causes of Alzheimer’s disease (AD). AD is characterized by aggregation of amyloid β-peptide (Aβ) plaques, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. To investigate whether Xanthoceras sorbifolia extracts (XSE) improve cognition and protect dendritic spines, we performed behavioral tests to investigate learning and memory in an Aβ25-35-induced dementia animal model of AD as well as Golgi staining to observe dendritic spine formation in CA1 pyramidal neurons and western blots to test the expression levels of PSD95, BDNF and downstream signaling pathways. Our results indicated that oral treatment with XSE significantly reduced cognitive impairments in behavioral tests (passive avoidance test, novel object recognition test, Y-maze test and Morris water maze test). Golgi staining results revealed that XSE ameliorated dendritic spine density deficits in CA1 pyramidal neurons in the hippocampus. Western blot analysis suggested that XSE upregulated PSD95, which is the major scaffolding protein in synapses. BDNF levels and the ratio of p-TrkB/TrkB increased, and the expression of the RhoA, a member of the Rho-GTPase family, and its downstream target protein ROCK2 decreased in the dementia animal model following treatment with XSE. Therefore, the cognition-improving effects of XSE probably resulted from dendritic spine protection effects through regulation of BDNF signaling pathways.
Natural products are considered as potential sources of leading compounds and play an important role in drug discovery. The liquid chromatography-mass spectrometry (LC-MS) technique is a powerful ...tool for compound-guided isolation from natural products. In this study, a high-efficiency integrated strategy was adopted to improve the new leading compounds discovery, including offline two-dimensional (2D) LC to extend the peak capacities, target neutral loss (NL) data-dependent acquisition (DDA) for barrigenol-type triterpenoids saponins and automatic screening through predicted natural product screening (PNPS) in TraceFinder. To validate the integrated strategy, the shell of Xanthoceras sorbifolium Bunge (XSB) was taken as a case. An offline 2D-LC system was constructed with hydrophilic interaction chromatography (HILIC) and reversed phase (RP) C18 column, and orthogonality of 0.66 and peak capacity of 3494. The 2D-LC system improved chromatographic baseline separation and peak resolution. Full MS/all ion fragmentation (AIF)/NL dd-MS2 DDA was employed for the detection of the barrigenol saponins. PNPS strategy was adopted and markedly extended the screening coverage. The combined strategy showed about 5 times improvement in the screening capability. The PNPS screening process, using TraceFinder software, discovered a total of 752 barrigenol saponins from the shell of XSB, including 707 potentially new barrigenol saponins, accounting for 94.02%. The feasibility of the strategy was also confirmed by the isolation of two novel barrigenol saponins, the structures of which were unambiguously identified using nuclear magnetic resonance (NMR). Furthermore, this strategy could also be applied to rapidly discover new bioactive constituents from other herbal medicines or other natural sources, especially the barrigenol saponins constituents.
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•First comparative study of E. fischeriana and E. ebracteolate by plant metabolomics was conducted.•29 characteristic metabolites were identified by UHPLC-QE-MS analysis.•8 ...constituents were identified as potential markers for discriminating two species.•12 representative compounds were isolated from two species.•Two plants showed differences in antioxidant, antibacterial, and antitumor activities.
Background Belamcanda chinensis (L.) DC. (BC) belongs to the family of Iridaceae and is widely cultivated and used in many Chinese patent medicine and Chinese medicinal formulae. However, due to the ...high similarities in appearance such as color and shape to Iris tectorum Maxim (ITM), another plant from the same family, BC is often confused or even misused with ITM. Methods Therefore, in order to distinguish the chemical constituents, qualities and biological activities of BC and ITM, multiple technologies including plant metabolomics, digital reference standard (DRS) analyzer and biological activities assay were employed to provide a sufficient basis for their practical applications. Results In plant metabolomics, the PCA and OPLS-DA score plot indicated the obvious differences in chemical profiling between BC and ITM and 6 compounds were successfully identified to contribute to the differences. In DRS study, the fingerprints of 10 and 8 compounds in BC and ITM were developed based on DRS analyzer, respectively, involving relative retention time (RRT) method and linear calibration using two reference substances (LCTRS) technique. The DRS analyzer also accurately identified 10 and 8 compounds from BC and ITM, respectively, by using only two reference standards. In biological activities assay, BC had a better anticancer effect than ITM due to the high abundance of irigenin, while ITM showed stronger hepatoprotective activity than BC because of the high abundance of tectoridin. Conclusions Therefore, due to the significant differences of B. chinensis and I. dichotoma in chemical composition and biological activities, the current studies strongly proved that these two medicinal plants could not be mixed in industrial production and clinical medication. Keywords: Belamcanda chinensis (L.) DC, Iris tectorum Maxim, Plant metabolomics, Digital reference standard, Biological activities
Four new guaiane-type sesquiterpenes, argyin H–K (1–4), and two known analogues (5 and 6) were isolated from the leaves of
Artemisia argyi
Lévl et Vant. The new compounds were characterized by the ...basic analysis of the spectroscopic data obtained (
1
H NMR,
13
C NMR, HMBC, and NOESY experiments), and their absolute configurations were determined by empirical approaches, combined with the exciton chirality method and electronic circular dichroism calculations. To further understand the antitumor effects of
A. argyi
, the antiproliferative activities of these compounds against A549, MCF-7, and HepG2 cell lines were tested
in vitro
using CCK-8 assays. The results showed that these compounds had significant antiproliferative effects on MCF-7, with IC
50
values of 15.13–18.63 μM, which were superior to that of oxaliplatin (i.e., IC
50
22.20 μM).
Abstract
The analgesic studies on
Stauntonia brachyanthera
, a traditional Chinese folk medicine used to treat headache, pains and inflammatory diseases in local areas, showed that the EtOH extracts ...(EESB) and the characteristic ingredient YM
11
could significantly inhibit the acetic acid-induced writhing responses by 43.1% and 78.95%, and decrease the xylene-induced ear edemas by 48.9% and 21.4%, respectively. EESB could significantly increase pain threshold of mice in hot-plate test, but the effect of YM
11
was not obviously. Further study in formalin test showed the inhibitory effect of YM
11
in 2
nd
phase was more significant than that in 1
st
phase, revealed the peripheral analgesic activity of YM
11
. The ELISA and Western Blot analysis suggested that the analgesic mechanisms of YM
11
were related to the inhibitions of the expressions of TNF-α, IL-1β and IL-6, and down-regulations of Na
v
1.8 protein in the left side of L4–6 DRG regulated by MAPKs, in which the levels of p-ERK, p-JNK and p-p38 were all decreased. In addition, the electrophysiological experiments indicated YM
11
could reduce the Nav1.8 currents by 46.01% in small-diameter DRG neurons. Therefore, the analgesic activity of
S. brachyanthera
might be based on the regulation of inflammatory mediators and the directly control of the sodium channel prompt.
•The antioxidants in Stauntonia brachyanthera might confer many health protective benefits.•13 compounds isolated from S. brachyanthera were investigated for their antioxidant and cytotoxic ...activities.•Six compounds revealed strong antioxidant activities using three antioxidant assays.•Some compounds displayed qualified antioxidant and significant cytotoxicity activities.•Six new compounds were obtained from S. brachyanthera.
Stauntonia brachyanthera Hand-Mazz., known as zhuyaozi or north banana by Dong Ethnicity in the southwest of China, is widely accepted as a delicious fruit with high economic value because of the presence of health-promoting components and the delivery of new tastes. In search for antioxidant compounds, the activity-guided fractionation and purification processes were performed on the stems and roots of S. brachyanthera, which resulted in the isolation of six new compounds, brachyanin A–F (1–6), and seven known compounds (7–13). Their structures were elucidated by 1D and 2D NMR, and HR-ESI-MS. Brachyanin A (1) exhibited significant cytotoxicity against HepG2 and K562 cell lines with IC50 values of 6.93 and 7.89 µM, respectively, and possessed antioxidant activity. Six compounds presented stronger antioxidant activities than those of vitamin C and quercetin in three tests (DPPH, ABTS, and FRAP). Among them, calceolarioside B (9) exhibited strongest activity and was present in higher amounts in the plant, which could be designated as characteristic component for the pharmacognostic identification and the quality control of S. brachyanthera. These findings laid solid theoretical references for the exploration of traditional usage of S. brachyanthera.
•Natural phytochemicals from the flower tea Coreopsis tinctoria exhibited anti-neuroinflammatory and NQO1 inducing activity.•The chemical profile of the effective part was clarified.•Brief SAR was ...discussed based on anti-neuroinflammatory and NQO1 inducing activity.
Oxidative stress and neuroinflammation are critical in the pathogenesis of neurodegenerative diseases. Extract of Coreopsis tinctoria Nutt. has been shown to ameliorate neurodegenerative diseases, potentially via inducing quinone oxidoreductase 1 (NQO1) and anti-neuroinflammation. The present study aimed to characterize the chemical profile and bioactive composition of the extract to identify the effective components responsible for the effects. Chromatography and spectra analysis yielded 26 constituents, including a new chalcone (compound 8). Bioassays showed that compounds 6, 9, 15, 17, 19, 21 and 22 significantly inhibited production of nitric oxide (NO) in N9 cells induced by lipopolysaccharides (LPS). Meanwhile compounds 1, 3, 6, 11, 19 and 20 exhibited significant NQO1 inducing activities in Hepa 1c1c7 cells. These results suggest that extract of C. tinctoria Nutt. contains bioactive components attenuating the progress of neurodegenerative diseases, thus, a valuable functional food for the prevention of neurodegenerative diseases.
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