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Celastrus and Tripterygium species, which are used in traditional Chinese medicine, have attracted much attention due to their anti-tumor promoting and neuroprotective activities, in addition to their applications in autoimmune disorders. However, systematic relationships between them and among species are unclear, and it may disturb their further medicinal utilization. In the present study, the molecular analysis of combined chloroplast and nuclear markers of all Chinese Celastrus and Tripterygium was performed, and clear inter- and intra-genus relationships were presented. The result suggests that Tripterygium constitute a natural monophyletic clade within Celastrus with strong support value. Fruit and seed type are better than inflorescence in subgeneric classification. Chinese Celastrus are classified for three sections: Sect. Sempervirentes (Maxim.) CY Cheng & TC Kao, Sect. Lunatus XY Mu & ZX Zhang, sect. nov., and Sect. Ellipticus XY Mu & ZX Zhang, sect. nov. The phylogenetic data was consistent with their chemical components reported previously. Owing to the close relationship, several evergreen Celastrus species are recommended for chemical and pharmacological studies. Our results also provide reference for molecular identification of Chinese Celastrus and Tripterygium.

Main Conclusion A BAHD terpene alcohol acyltransferase, CaAT20, was identified from Celastrus angulatus Maxim, expressed in E. coli and functionally characterized. S405A mutant of CaAT20 increased the enzyme activity. Acylation is a diversely physiological process in the biosynthesis of plant secondary metabolites. Plant BAHD acyltransferases play an important role in the modification of volatile esters with biological activities. In this research, a BAHD acyltransferase (CaAT20) was identified from Celastrus angulatus Maxim and the function of this enzyme was characterized. CaAT20 could convert geraniol to geranyl esters by using benzoyl-CoA and acetyl-CoA as the acyl donors respectively. Furthermore, the catalytic activity of CaAT20 for benzoyl-CoA was higher than that of acetyl-CoA. Site-directed mutation of CaAT20 was carried out based on the results of molecular simulation. In vitro site-directed mutant S405A of CaAT20 increased the volume of binding cavity so as to facilitate the entry of geraniol, indicating a more efficient acylation for geraniol and benzoyl-CoA. Our research provides new insight for the catalytic functions of CaAT20.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease globally, characterized by the accumulation of lipids, oxidative stress, and mitochondrial dysfunction in the liver. Thunb. (COT) and its active compound celastrol (CEL) have demonstrated antioxidant and anti-inflammatory properties. Our prior research has shown the beneficial effects of COT in mitigating NAFLD induced by a high-fat diet (HFD) in guinea pigs by reducing hepatic lipid levels and inhibiting oxidative stress. This study further assessed the effects of COT on NAFLD and explored its underlying mitochondria-related mechanisms. COT extract or CEL was administered as an intervention in C57BL/6J mice fed a HFD or in HepG2 cells treated with sodium oleate. Oral glucose tolerance test, biochemical parameters including liver enzymes, blood lipid, and pro-inflammatory factors, and steatosis were evaluated. Meanwhile, mitochondrial ultrastructure and indicators related to oxidative stress were tested. Furthermore, regulators of mitochondrial function were measured using RT-qPCR and Western blot. The findings demonstrated significant reductions in hepatic steatosis, oxidative stress, and inflammation associated with NAFLD in both experimental models following treatment with COT extract or CEL. Additionally, improvements were observed in mitochondrial structure, ATP content, and ATPase activity. This improvement can be attributed to the significant upregulation of mRNA and protein expression levels of key regulators including FGF21, AMPK, PGC-1α, PPARγ, and SIRT3. These findings suggest that COT may enhance mitochondrial function by activating the FGF21/AMPK/PGC-1α signaling pathway to mitigate NAFLD, which indicated that COT has the potential to target mitochondria and serve as a novel therapeutic option for NAFLD.

Efficient drug delivery is crucial for the creation of effective pharmaceutical treatments, and polyethylene glycol (PEG) carriers have been emerged as promising candidates for this purpose due to their bio-compatibility, enhancement of drug solubility, and stability. In this study, we utilized molecular simulations to examine the interactions between PEG carriers and selected drug molecules extracted from Celastrus hindsii : Hindsiilactone A, Hindsiiquinoflavan B, Maytenfolone A, and Celasdin B. The simulations provided detailed insights into the binding affinity, stability, and structural properties of these drug molecules when complexed with PEG carriers. A multi-scale approach combining density functional theory (DFT), extended tight-binding (xTB), and molecular dynamics (MD) simulations was conducted to investigate both unbound and bound states of PEG/drug systems. The results from DFT and xTB calculations revealed that the unbound complex has an unfavorable binding free energy, primarily due to negative contributions of delta solvation free energy and entropy. The MD simulations provided more detailed insights into the interactions between PEG and drug molecules in water solutions. By integrating the findings from the multi-scale simulations, a comprehensive picture of the unbound and bound states of PEG and drug systems were obtained. This information is valuable for understanding the molecular mechanisms governing the binding of drugs in PEG-based delivery platforms, and it contributes to the rational design and optimization of these systems.

Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-β/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-β/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-β/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics.

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

Herbal material is both a medicine and a commodity. Accurate identification of herbal materials is necessary to ensure the safety and effectiveness of medication. With this work, we initiated an identification method to investigate the species authenticity for herbal products of Celastrus orbiculatus and Tripterygum wilfordii utilizing DNA barcoding technology. An ITS2 (internal transcribed spacer two) barcode database including 59 sequences was successfully established to estimate the reliability of species-level identification for Celastrus and Tripterygium. Our findings showed that ITS2 can effectively and clearly distinguish C. orbiculatus, T. wilfordii and its congeners. Then, we investigated the proportions and varieties of adulterant species in the herbal markets. The data from ITS2 region indicated that 13 (62%) of the 21 samples labeled as “Nan-she-teng” and eight (31%) of the 26 samples labeled as “Lei-gong-teng” were authentic; the remaining were adulterants. Of the 47 herbal products, approximately 55% of the product identity were not in accordance with the label. In summary, we support the efficacy of the ITS2 barcode for the traceability of C. orbiculatus and T. wilfordii, and the present study provides one method and reference for the identification of the herbal materials and adulterants in the medicinal markets.

Celastrus hindsii is a potential source of flavonoids with biological activities. This study aimed to develop an ultrasound-assisted technique for extracting flavonoids from leaves of C. hindsii. Response surface methodology was employed to optimize the extraction conditions for maximizing the total flavonoid content (TFC). A maximum TFC of 23.6 mg QE/g was obtained under the extraction conditions of ultrasonic power of 130 W, extraction temperature of 40°C, extraction time of 29 min, and ethanol concentration of 65%. The flavonoid-rich extracts were then studied for their antioxidant and anticancer activities. The results showed that the C. hindsii leaf extract exhibited potent radical scavenging activities against DPPH (IC50 of 164.85 μg/mL) and ABTS (IC50 of 89.05 μg/mL). The extract also significantly inhibited the growth of 3 cancer cell lines MCF7, A549, and HeLa with the IC50 values of 88.1 μg/mL, 120.4 μg/mL, and 118.4 μg/mL, respectively. Notably, the extract had no cytotoxicity effect on HK2 normal kidney cell line. This study suggests that flavonoid-rich extract is a promising antioxidant and anticancer agent and that ultrasound-assisted extraction is an efficient method for extracting flavonoids from C. hindsii leaves.

Neuroinflammation mediated by astrocyte–microglia interactions plays a critical role in the progression of neurodegenerative disorders. Celastrus paniculatus (CP) seeds have long been associated with cognitive benefits; however, the chemical composition and anti-inflammatory potential of their high-polarity fractions remain poorly characterized. In this study, thin-layer chromatography (TLC)-derived high-polarity fractions (F6 and F7) from CP seeds were analyzed using untargeted LC–MS/MS metabolite profiling. After quality filtering, 99 metabolites were retained for classification, with enrichment of alkaloids and terpenoid-related compounds, including 41 structurally complex metabolites. To evaluate biological relevance, BV2 microglia were exposed to astrocyte-conditioned medium derived from H2O2-treated astrocytes (ACM-H), modeling sterile inflammatory signaling. ACM-H stimulation induced microglial activation characterized by morphological transformation, increased CD40 and inducible nitric oxide synthase (iNOS) expression, and elevated production of pro-inflammatory cytokines TNF-α and IL-6. Co-treatment with CP fractions attenuated ACM-H-induced inflammatory responses, with fraction F7 showing stronger effects than F6. Fraction F7 showed stronger inhibitory effects on CD40 and iNOS expression, suppressed TNF-α and IL-6 production, and partially restored ramified microglial morphology, whereas F6 exhibited comparable anti-inflammatory activity and showed a stronger effect on microglial phagocytic responses. Metabolomic analysis further indicated a higher relative abundance of terpenoid-related metabolites in F7. Collectively, these findings indicate that CP seed fractions, particularly F7, attenuate astrocyte-driven microglial activation in an in vitro sterile neuroinflammatory model.

Invasive plants have the potential to interfere with native species’ reproductive success through a number of mechanisms, including heterospecific pollination and hybridization. This study investigated reproductive interactions between a native North American woody vine (American bittersweet, Celastrus scandens ) and an introduced congener (oriental bittersweet, C . orbiculatus ). The decline of C . scandens in the eastern portion of its range is coincident with the introduction and spread of C . orbiculatus , and the two species are known to hybridize. The relationship between proximity and floral production of conspecific and heterospecific males on fertilization and hybridization rates was measured at a field site in northwestern Indiana, USA where both species occur and reproduce. We found that the invasive vine had an extreme advantage in both male and female floral production, producing nearly 200 times more flowers per staminate plant and 65 times more flowers per pistillate plant than the native. Using nuclear microsatellite DNA markers we found that hybridization rates were asymmetric; 39% of the C . scandens seeds tested were hybrids, compared to only 1.6% of C . orbiculatus seeds. The asymmetric hybridization rates were likely not solely due to greater abundance of C . orbiculatus pollen because experimental hand crosses revealed that C . scandens had a higher rate (41%) of heterospecific fertilization than C . orbiculatus (2.4%). We previously reported that few hybrids were observed in the wild, and hybrids had greatly reduced fecundity. Thus, in our system, the threat posed by heterospecific pollen is not replacement by hybrids or introgression, but rather asymmetric reproductive interference. Reproductive interference extended to distances as great as 100 meters, thus, efforts to conserve the native species must reduce its exposure to C . orbiculatus over a relatively large spatial scale.