With an aim to comprehend the precise regulatory mechanism of dioscin against endometrial carcinoma (EC), we firstly extracted the components from Polygonatum sibiricum followed by identification and structural characterization. The anti-EC activity of dioscin was initially determined based on the inhibition of Ishikawa cell proliferation and tumor growth. The high-throughput sequencing data indicated that dioscin not only promoted apoptosis, including decrease of poly ADP-ribose polymerase (PARP) and B-cell lymphoma-2 (Bcl-2) and increase of c-PARP and Bcl-2-associcated agonist of cell death (Bad), but also induced autophagy, including increase of autophagic lysosomes and LC3Ⅱ/LC3Ⅰ ratio. Mechanistic exploration suggested that dioscin induced autophagy and apoptosis through inhibition of PI3K/AKT/mTOR signaling pathway. Besides, the dioscin-regulated p53 pathway was mainly involved in autophagy induction. Furthermore, inhibition of Ishikawa cell autophagy was linked to dioscin-induced apoptosis. Our data suggest the immense potential of dioscin for the development of functional food for EC and related medical application.

Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by several symptoms. The pathogenesis of COPD is complex and involves multiple factors. A fantastic drug from traditional Chinese medicine (TCM), Isodon Suzhouensis (ISZ) is a perennial herb belonging to the labiaceae family. It has the functions of resolving phlegm, removing stasis, promoting blood circulation and eliminating qi stagnation. ISZ has been found to possess great potential against COPD. Present study is focused to identify microRNA (miRNA) biomarkers for COPD and to determine the role of ISZ leaves extract in regulating the disease through miRNA expression in serum exosomes. The sprague-dawley (SD) rats were randomly divided into control group, model group and drug groups. After the establishment of the model, the rats were sacrificed and the results were compared with control group. Then the total RNA, of rat serum was extracted and identified by nanoparticle tracker. Finally, high-throughput screening and sequencing were performed to screen miRNAs with significant differential expression. Then different databases were used to figure out the possible target genes and their functions were assessed by employing gene ontology (GO) as well as kyoto encyclopedia of genes and genomes (KEGG) analyses. The sequencing results were then further verified by qRT-PCR. The results pointed out that these 17 differentially expressed miRNAs may have the potential of diagnostic and prognostic biomarkers against COPD. Interestingly it was also found that ISZ leaves extract may regulate the occurrence of COPD by affecting the expression of miRNAs. This study identified the biomarkers of COPD and clarified the mechanism of the treatment of COPD by ISZ leaves extract, which is helpful to improve the level of early diagnosis and treatment of COPD.

Corona Virus Disease 2019 (COVID-19) has brought the new challenges to scientific research. Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects, which is considered as a potential treatment for COVID-19. The possibility for the treatment of COVID-19 with suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology. Network pharmacology and molecular docking were used to screen drug targets, and Lipopolysaccharide (LPS) induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification. Collectively a total of 209 possible linkages against 18 chemical components from suzhouensis and 1194 COVID-19 related targets were selected. Among these, 164 common targets were obtained from the intersection of suzhouensis and COVID-19. GO and KEGG enriched 582 function targets and 87 target proteins pathways, respectively. The results from molecular docking studies revealed that rutin, vitexin, isoquercitrin and quercetin had significant binding ability with SARS-CoV-23CLpro and ACE2. In vitro studies showed that Isodon suzhouensis extract (ISE) may inhibit the activation of PI3K/Akt pathway and the expression level of downstream pro-inflammatory factors by inhibiting the activation of EGFR in RAW264.7 cells induced by LPS. In addition, ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS. Overall, the network pharmacology and in vitro studies conclude that active components from suzhouensis have strong therapeutic potential against COVID-19 through multi-target, multi-pathway dimensions and can be a promising candidate against COVID-19.

Apigenin, a natural flavonoid has been reported against a variety of cancer types. However, it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells. There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells. We found that iron accumulation, lipid peroxidation, glutathione consumption, p62, HMOX1, and ferritin were increased, while, solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased. Ferrostatin-1, an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells. On the other hand, apigenin could promote autophagy via up-regulating Beclin 1, ULK1, ATG5, ATG13, and LC3B and down-regulating AMPK, mTOR, P70S6K, and ATG4. Furthermore, apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.

To explore the function of licochalcone A as an anticancer phytochemical on HepG2 cells and investigate its potential mechanisms, we analyzed the microRNAs (miRNAs) expression profile of HepG2 cells in response to licochalcone A (70 μmol/L) in vitro. 102 dysregulated miRNAs were detected, and SP1 was expected as the transcription factor that regulates the functions of most screened miRNAs. A sum of 431 targets, the overlap of predicted mRNAs from TargetScan, miRDB, and miRtarbase were detected as the targets for these dysregulated miRNAs. FoxO signaling pathway was the hub pathway for the targets. A protein-protein interaction network was structured on the STRING platform to discover the hub genes. Among them, PIK3R1, CDC42, ESR1, SMAD4, SUMO1, KRAS, AGO1, etc. were screened out. Afterwards, the miRNA-target networks were established to screen key dysregulated miRNAs. Two key miRNAs (hsa-miR-133b and hsa-miR-145-5p) were filtered. Finally, the miRNA-target-transcription factor networks were constructed for these key miRNAs. The networks for these key miRNAs included three and two transcription factors, respectively. These identified miRNAs, transcription factors, targets, and regulatory networks may offer hints to understand the molecular mechanism of licochalcone A as a natural anticarcinogen.

The anticancer activity of stevenleaf (SV) on the basis of cell viability, cell cycle, and apoptosis induction in HepG2 cancer cells were evaluated. SV controlled the growth of HepG2 cells with IC₅₀ of 139.82 μmol/L for 24 h, IC₅₀ of 119.12 μmol/L for 48 h and cell cycle arrested at G0/G1 phase, induced cell apoptosis and enhanced intracellular ROS generation. For cell cycle arrest, the mRNA expression levels of p21, p27 and p53 were up-regulated, while the expression levels of Cyclin A, Cyclin D1, Cyclin E and CDK1/2 were down-regulated. SV efficiently up-regulated TNF R1, TRADD1 and FADD and down-regulated Caspase8 for cell death receptors; similarly, up-regulated Bax, Bak, Cyt c, Apaf1, Caspase3 and Caspase9, and down-regulated Bcl2, Bcl xl and Bad for mitochondrial signal pathway. SV induced the mTOR-mediated cell apoptosis in HepG2 cells via activation of Akt and AMPK. The mechanistic explanation for the anticancer activity of SV as functional food can be derived from above results.