Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation.

BACKGROUND: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. METHODS: Cytoscape was used to construct a network of compound-disease targets and protein-protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. RESULTS: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA's significant potential as a prospective agent for the therapy of cancer.

Porous Pure MXene Fibrous Network for Highly Sensitive Pressure Sensors.

Wearable and elastic pressure sensors have caused widespread concern due to the popularity of smart terminals and human health monitoring. To obtain a flexible pressure sensor with a wide detection region and outstanding sensitivity, exploring new materials and novel structures has become the first choice for the research. Here, a wearable and flexible MXene fibrous network pressure sensor (MFNS) with a high sensitivity and wide detection region is reported. The holistic fiber network is composed of pure MXene fibers; among them, MXene fibers were prepared by wet-spinning of MXene nanosheets. The MFNS exhibits a high sensitivity in a wide detection region (51 kPa-1 for 14.7 kPa and 427 kPa-1 within the 14.7-19.9 kPa range), a low detection limit (8 Pa), a robust durability (10,000 cycles), and a prompt response (95 ms). Due to the superior performance of MFNS, it also proves prospective applications for human motion signal detection (such as swallowing, pulse beat, and joint motion) and measuring pressure distribution. This work provides an effective way to fabricate a high-performance pressure sensor for human-machine interactions, personal healthcare monitoring, and multitouch devices.

Effects of Constituent Compounds of Smilax china on Nicotine-Induced Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells.

This study investigated the effects of compounds isolated from 70% ethanol (EtOH) extraction of Smilax china L. (SCE), a plant belonging to the family Smilacaceae on nicotine-induced endothelial dysfunction (ED) in human umbilical vein endothelial cells. We isolated 10 compounds from ethyl acetate (EtOAc) fraction of 70% EtOH extract of SCE and investigated their inhibitory effect on nicotine-induced ED in endothelial cells. Kaempferol, kaempferol 7-O-α-L-rhamnopyranoside, puerarin and ferulic acid showed strong inhibition of nicotine-induced vascular cell adhesion molecule (VCAM-1) expression while kaempferol, kaempferin, and caffeic acid attenuated intercellular adhesion molecule (ICAM-1) expression. Lepidoside, caffeic acid and methylsuccinic acid caused the highest up-regulated expression of endothelial nitric oxide synthase at the protein level with caffeic acid and ferulic acid showing strong inhibitory effects on inducible nitric oxide synthase (iNOS) expression. In addition, ferulic acid and kaempferol showed inhibition against interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) expression while ferulic acid and caffeic acid showed comparatively higher inhibition of ED associated tumor necrosis factor-α (TNF-α) expression. These results show the potential of the aforementioned compounds to reverse the toxic effects of nicotine on the endothelium.

Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa.

CONTEXT: Despite phytochemical studies of Agrimonia pilosa Ledeb. (Rosaceae), the antidiabetic effects of this plant are unknown. OBJECTIVE: This study characterizes the isolated compounds from the aerial parts of A. pilosa and evaluates their PTP1B and α-glucosidase inhibitory properties. MATERIALS AND METHODS: Ethanol extract of A. pilosa was found to inhibit 64% PTP1B activity at 30 µg/mL. The ethanol extract was partitioned with methylene chloride, ethyl acetate, n-butanol, and water fractions. Among these, the ethyl acetate fraction displayed the most potent PTP1B activity. The ethyl acetate extract was separated by chromatographic methods to obtain flavonoids and triterpenoids (1-11); which were evaluated for their inhibitory effects on PTP1B activity with p-nitrophenyl phosphate (p-NPP) as a substrate, and also α-glucosidase enzyme. RESULTS: Compounds 1-11 were identified as apigenin-7-O-ß-d-glucuronide-6″-methyl ester, triliroside, quercetin-7-O-ß-d-glycoside, quercetin-3-O-ß-d-glycoside, kaempferol, kaempferol-3-O-α-l-rhamnoside, ß-sitosterol, ursolic acid, tormentic acid, methyl 2-hydroxyl tricosanoate, and palmitic acid. Compounds 8, 9, and 11 displayed inhibitory effects on PTP1B activity with IC50 values of 3.47 ± 0.02, 0.50 ± 0.06, and 0.10 ± 0.03 µM, respectively. Compounds 3, 4, 6, and 9 exhibited inhibition of the α-glucosidase activity with IC50 values of 11.2 ± 0.2, 29.6 ± 0.9, 28.5 ± 0.1, and 23.8 ± 0.4 µM, respectively. DISCUSSION AND CONCLUSION: As major ingredients of A. pilosa, compounds 1, 6, 8, and 9 showed the greatest inhibitory potency on PTP1B activity. Compounds 3, 6, 8, and 9 also showed potent inhibitory effects on α-glucosidase enzyme. This result suggested the potential of these compounds for developing antidiabetic agents.

Chemical Constituents of Euonymus alatus (Thunb.) Sieb. and Their PTP1B and α-Glucosidase Inhibitory Activities.

Phytochemical study on the corks of Euonymus alatus resulted in the isolation of a novel 3-hydroxycoumarinflavanol (23), along with ten triterpenoids (1-10), ten phenolic derivatives (11-20), and two flavonoid glycosides (21 and 22). Their structures were determined by extensive 1D and 2D-nuclear magnetic resonance spectroscopic and mass spectrometry data analysis. Furthermore, their inhibitory effects against the protein tyrosine phosphatases 1B (PTP1B) and α-glucosidase enzyme activity were evaluated. Compounds 6, 7, 9, 15, 19, and 23 were non-competitive inhibitors, exhibiting most potency with IC50 values ranging from 5.6 ± 0.9 to 18.4 ± 0.3 µm, against PTP1B. Compound 3 (competitive), compounds 5 and 15 (mixed-competitive) displayed potent inhibition with IC50 values of 15.1 ± 0.7, 23.6 ± 0.6 and 14.8 ± 0.9 µm, respectively. Moreover, compounds 15, 20, and 23 exhibited potent inhibition on α-glucosidase with IC50 values of 10.5 ± 0.8, 9.5 ± 0.6, and 9.1 ± 0.5 µm, respectively. Thus, these active ingredients may have value as new lead compounds for the development of new antidiabetic agents.

Insulin-mimetic selaginellins from Selaginella tamariscina with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity.

As part of an ongoing search for new antidiabetic agents from medicinal plants, three new (2, 4, and 5) and two known selaginellin derivatives (1 and 3) were isolated from a methanol extract of Selaginella tamariscina. The structures of the new compounds were determined by spectroscopic data analysis. All isolates showed strong glucose uptake stimulatory effects in 3T3-L1 adipocyte cells at a concentration of 5 µM. Furthermore, these compounds were found to possess inhibitory effects on PTP1B enzyme activity with IC50 values ranging from 4.6 ± 0.1 to 21.6 ± 1.5 µM. Compound 2 showed the greatest potency, with an IC50 value of 4.6 ± 0.1 µM, when compared with the positive control (ursolic acid, IC50 = 3.5 ± 0.1 µM). Therefore, these selaginellin derivatives may have value as new lead compounds for the development of agents against type 2 diabetes.

Constituents with DNA topoisomerases I and II inhibitory activity and cytotoxicity from the roots of Rubia cordifolia.

Activity-directed isolation of the ethyl acetate fraction from the roots of Rubia cordifolia resulted in the identification of a new anthraquinone, 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone-3- O- α- L-rhamnopyranosyl-(1 → 2)- ß-D-(6'-O-acetyl)-glucopyranoside (1), two new dihydronaphtoquinones, 1,4-dihydroxy-2-carbomethoxy-3-prenylnaphthalene-1-O- ß-D-glucopyranoside (2) and mollugin-1-O- ß- D-glucopyranoside (3), and a new monoterpenoid, 3 R,3a S,4 R,6a R-3,4,6-tris(hydroxymethyl)-3,3a,4,6a-tetrahydro-2 H-cyclopenta[ B]furan-2-one (4), together with nine known compounds (5-13). The structures of these compounds were elucidated on the basis of spectroscopic evidence. In addition, their DNA topoisomerases I and II inhibitory activity and cytotoxicity were measured.