Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.

Evolutionary research trend of Polygonatum species: a comprehensive account of their transformation from traditional medicines to functional foods.

With the advances in Polygonatum research, there is a huge interest in harnessing the valuable functional ingredients of this genus with the potential for functional foods. This review emphasizes the different aspects of Ploygonatum based research starting from its bioactive compounds, their structural characterization, various extraction methods, as well as biological activities. In view of its integral use as an essential medicinal plant, our review emphasizes on its promising food applications both as an ingredient and as a whole food, and its improved health benefits with potential for agricultural and environmental relevance are also discussed. As we collated the recent research information, we present the main challenges and limitations of the current research trend in this area which can upgrade the further expansion of Polygonatum-related research that will strengthen its economic and accessible nutritional value in the food and health industries. By highlighting the need for the unattended species, this review not only fills existing research gaps, but also encourages the researchers to find new avenues for the natural production of bio-based functional materials and the development of highly functional and health-promoting foods for disease prevention and treatment.

Integrated miRNA and mRNA omics reveal dioscin suppresses migration and invasion via MEK/ERK and JNK signaling pathways in human endometrial carcinoma in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum Redouté (PS, also called Huangjing in traditional Chinese medicine), is a perennial herb as homology of medicine and food. According to the traditional Chinese medicine theory "Special Records of Famous Doctors", its functions include invigorating qi and nourishing yin, tonifying spleen and kidney. Traditionally, qi and blood therapy has been believed as most applicable to the treatment of uterine disease. The current research has focused on the effect and mechanism of dioscin, the main active component of PS, on Endometrial carcinoma (EC). AIM OF THE STUDY: To study the efficacy of dioscin on proliferation and migration of Endometrial carcinoma cell line, we conducted experiments by using xenograft model and Ishikawa cells, and explored the potential molecular mechanism. MATERIALS AND METHODS: mRNA and miRNA omics techniques were employed to investigate the regulatory mechanism of dioscin on EC Ishikawa cells. Based on in vivo and in vitro experiments, cell clone formation, cell scratching, Transwell, H&E staining, immunohistochemistry, q-PCR, and Western blot techniques were used to determine the molecular effects and mechanisms of dioscin on cell migration. RESULTS: Integrated miRNA and mRNA omics data showed that 513 significantly different genes marked enrichment in MAPK signaling pathway. The in vivo data showed that dioscin (24 mg/kg) significantly inhibited tumor growth. The in vitro proliferation and invasiveness of dioscin on Ishikawa cells showed that dioscin could significantly decrease the colony numbers, and suppress the Ishikawa cell wound healing, migration and invasion. Molecular data revealed that dioscin decreased the MMP2 and MMP9 expression in vitro and in vivo. The p-MEK, p-ERK, and p-JNK expression levels were also confirmed to be significantly reduced. Key regulators in the MAPK signaling pathway were further validated in xenograft tumors. CONCLUSION: Our data indicated that dioscin inhibited Ishikawa cell migration and invasion mediated through MEK/ERK and JNK signaling. More importantly, screened hub miRNAs and genes can be regarded as potential molecular targets for future EC treatment.

Transcriptome and proteomics conjoint analysis reveal metastasis inhibitory effect of 6-shogaol as ferroptosis activator through the PI3K/AKT pathway in human endometrial carcinoma in vitro and in vivo.

Endometrial cancer remains as one of the widespread female malignancies despite the existing treatment measures mainly surgery, radiotherapy, and chemotherapy. In recent times, studies have focused on medicinal plants such as ginger due to its multifaceted characteristics compared to conventional medicine. 6-Shogaol is regarded as the main active compound of ginger participating in pharmacological activities and combating various health disorders, especially cancer. In our study, we compared the effects of 6-gingerol, 6-paradol, and 6-shogaol on Ishikawa cells, and found 6-shogaol as a more effective ingredient against Ishikawa cell proliferation. Moreover, its promoted ferroptosis, as a result, triggered mitochondrial morphologic alternation, as well as changed iron concentration, GSH and MDA levels. Furthermore, 6-Shogaol inhibited cell metastasis by influencing cell invasion and migration. Finally, 6-shogaol could trigger PI3K/AKT signaling pathways in vitro and in vivo confirmed by western blotting assay and immunohistochemical evaluation. These findings suggest that 6-shogaol can be used as promising functional food component in health diet and in drug target methods for endometrial cancer therapy.

[Neuromodulation: Past, Present, and Future].

Neuromodulation technology is one of the medical fields currently experiencing the most rapid development, witnessing a surge in the types of modulation techniques and a constant expansion of indications. Consequently, hundreds of thousands of patients with functional neurological disorders have benefited from the advancements in the field all over the world. Nevertheless, some challenges remain, for exmaple, the lack of a thorough understanding of the mechanism of neuromodulation, the long-standing controversy over the optimal targets of neuromodulation, the lack of reliable efficacy predictors, and the cumbersome and inefficient mode of postoperative programming. We anticipate that these issues will be resolved with the continued advancement in medical technology and the gradual revelation of the neural network mechanism of brain disorders. More individualized, precise, and intelligent neuromodulation technology will be the main direction of development in the future. Herein, we reviewed and commented on the evolution of neuromodulation technology, the current status of its applications, and its prospective development.

Gut modulatory effects of flaxseed derived Maillard reaction products in Sprague-Dawley rats during sub-chronic toxicity.

Our study aimed to understand the effects of Maillard reaction products (MRPs) intake on intestinal health, in vitro digestion, and fermentation metabolites in Sprague-Dawley (SD) rats. MRPs promoted the digestion of pepsin, but was not conducive to the subsequent in vitro digestion of trypsin. MRPs ingestion increased the propionate in intestine, but it could not change the branched-chain fatty acids (BCFAs) and short-chain fatty acids (SCFAs). However, MRPs ingestion led to an increase in the Lactobacillus abundance in gut. In the high-dose groups, the abundance of genes in partial amino acid and monosaccharide metabolism increased, while in lipid metabolism decreased compared with the middle dose groups. Therefore, the absorption of MRPs was lowered than that of protein and carbohydrates. Through functional predictive analysis, our study could reveal the effects of long-term intake of MRPs on intestinal health in SD rats.

Functional and emulsification characteristics of phospholipids and derived o/w emulsions from peony seed meal.

Peony seed phospholipids (PPLs), a kind of multifunctional plant-like phospholipids were extracted from peony seed meal. We investigated the functional properties of PPLs and compared their emulsification performance in corn oil-peony seed oil o/w emulsion systems with that of soy lecithin (DPLs). The PPLs were characterized with the higher content of phosphatidylcholine (PC) (416 ± 28 mg/g) and lyso-phosphatidylcholine (LPC) (43 ± 14 mg/g) fractions, and lower content of phosphatidylethanolamine (PE) (71 ± 13 mg/g). The polyunsaturated fatty acids showed higher content (83.25%), with the highest content of linoleic acid (46.05%) in PPLs. PPLs-emulsions showed smaller average particle size and higher loaded peony seed oil content at pH 5, temperature 50 °C, and about 60% corn oil content. PPLs-emulsions imparted better hydroxyl radical scavenging efficiency and reducing power than DPLs. Our results suggest that PPLs can be used as emulsifiers with improved antioxidant properties.

Riboflavin Bioenriched Soymilk Alleviates Oxidative Stress Mediated Liver Injury, Intestinal Inflammation, and Gut Microbiota Modification in B2 Depletion-Repletion Mice.

Epidemiological evidence emphasizes that ariboflavinosis can lead to oxidative stress, which in turn may mediate the initiation and progression of liver injury and intestinal inflammation. Although vitamin B2 has gained worldwide attention for its antioxidant defense, the relationship between B2 status, oxidative stress, inflammatory response, and intestinal homeostasis remains indistinct. Herein, we developed a B2 depletion-repletion BALB/c mice model to investigate the ameliorative effects of B2 bioenriched fermented soymilk (B2FS) on ariboflavinosis, accompanied by oxidative stress, inflammation, and gut microbiota modulation in response to B2 deficiency. In vivo results revealed that the phenotypic ariboflavinosis symptoms, growth rate, EGRAC status, and hepatic function reverted to normal after B2FS supplementation. B2FS significantly elevated CAT, SOD, T-AOC, and compromised MDA levels in the serum, simultaneously up-regulated Nrf2, CAT, and SOD2, and down-regulated Keap1 gene in the colon. The histopathological characteristics revealed significant alleviation in the liver and intestinal inflammation, confirmed by the downregulation of inflammatory (IL-1ß and IL-6) and nuclear transcription (NF-κB) factors after B2FS supplementation. B2FS also increased the abundance and diversity of gut microbiota, increased the relative abundance of Prevotella and Absiella, as well as decreased Proteobacteria, Fusobacteria, Synergistetes, and Cyanobacteria in strong conjunction with antioxidant, anti-inflammatory properties, and gut homeostasis along with the remarkable increase in cecal SCFAs content. We hereby reveal that B2FS can effectively alleviate deleterious ariboflavinosis associated with oxidative stress mediated liver injury, chronic intestinal inflammation, and gut dysbiosis in the B2 depletion-repletion mice model via activation of the Nrf2 signaling pathway.

Formononetin reshapes the gut microbiota, prevents progression of obesity and improves host metabolism.

Formononetin (FMNT) is an isoflavone that has been studied for its anti-hyperglycemic and anti-diabetic effects. However, the effect of FMNT on gut dysbiosis and metabolic complications associated with western-style diet consumption has not been reported yet. This study aimed to investigate how FMNT can reshape the gut microbiota at a specific dosage and ameliorate the symptoms of obesity-related metabolic disorders in both genders. Results indicate that FMNT at 60 mg per kg bodyweight dosage can effectively control body weight, hyperglycemia, and insulin resistance, leptin levels and improve HDL to LDL ratio. FMNT treatment suppressed Porphyromonadaceae (Uncultured Alistipes) and augmented maximum genera from families Lachnospiraceae and Clostridiacea, but at species level, formononetin increased Clostridium aldenense, Clostridiaceae unclassified, Eubacterium plexicaum; acetate and butyrate-producing bacteria. Moreover, formononetin regulated the expression of specific liver miRNA involved in obesity and down-regulated mRNA expression levels of pro-inflammatory cytokines IL-6, IL-22 and TNF-α. Additionally, FMNT maintained intestinal membrane integrity by regulating the expression of Muc-2 and occludin. Our findings indicate that FMNT could be a potential prebiotic that can effectively regulate the gut microbiota, improve host metabolism and systemic inflammation, and prevent deleterious effects of a western-style diet by elevating acetate lactate and lactate butyrate producers.

Preparation and characterization of clove essential oil loaded nanoemulsion and pickering emulsion activated pullulan-gelatin based edible film.

The clove essential oil (CEO) loaded nano and pickering emulsions prepared with Tween 80 and whey protein isolate/inulin mixture, respectively were incorporated into pullulan-gelatin film base fluid at three levels (0.2%, 0.4%, and 0.6%). The droplet sizes of NE and PE loaded with CEO were 15.93 nm and 266.9 nm, respectively. The PDI of CEOs with stable NE and PE were 0.262 and 0.259, respectively. Our results showed the improved compatibility between pullulan-gelatin and essential oil-loaded nanocarriers. The active film composed of PE carrier had the structural characteristics of high density, low water content, and low permeability, thus exhibiting excellent mechanical properties, water barrier properties, and appreciable antioxidant activities. Compared with NE, it was found that the CEO-loaded PE showed slow-release profile in the film sample. The prepared active film containing PE possessed a great potential to be used as effective and natural alternatives for active food packaging.

Effect of grape seed power on the structural and physicochemical properties of wheat gluten in noodle preparation system.

Noodles were prepared using wheat flour supplemented with 1%, 3%, and 5% grape seed power (GSP). The farinograph properties of wheat flour, the textural properties of the dough, and thermal properties of the gluten were determined. The microstructure was analyzed by scanning electron and atomic force microscopy, and the effects of the addition of GSP on the physicochemical and structural properties (free sulfhydryl content, surface hydrophobic region, and secondary structure) of wheat gluten protein were analyzed. 1% GSP promoted the aggregation of gluten proteins by promoting hydrophobic interactions and hydrogen bonding, thus enhanced the noodle quality. Whereas, 3% and 5% GSP addition disrupted the disulfide bonds between gluten protein molecules and formed macromolecular aggregates linked to gluten proteins through non-covalent bonds and hydrophobic interactions, which prevented the formation of the gluten protein reticulation structure. Our study emphasized the interaction between wheat proteins and GSP in noodle making dough.

Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway.

Asparanin A (AA), a natural compound present in vegetables and medicinal herbs like Asparagus officinalis L., has been investigated extensively for its pharmacological attributes. So far, the effect of AA on endometrial cancer (EC) cell migration and invasion has not been explored. Herein, we elucidated the anti-metastasis mechanism of AA on Ishikawa cells based on miRNA-seq and mRNA-seq integrated analyses. AA treatment led to altered miRNAs expression in Ishikawa cells and inhibited the cell wound healing, cell migration and invasion. Gene Ontology and KEGG enrichment analyses showed that the target genes of different expression miRNAs were significantly enriched in Ras, Rap1 and MAPK signaling pathways. Further verification of these changes via qRT-PCR and Western blot assays in vitro and in vivo demonstrated that AA could suppress human EC cell migration and invasion through Ras/ERK/MAPK pathway. Furthermore, top two miRNAs (miR-6236-p5 and miR-12136_R+8) and top three target genes (KITLG, PDGFD, and NRAS) were identified as functional hub miRNAs and genes through miRNA-target gene network analysis. Our data presented a holistic approach to comprehend the anti-metastatic role of AA in EC after in vitro and in vivo analyses.

A recent update on the multifaceted health benefits associated with ginger and its bioactive components.

Due to recent lifestyle shifts and health discernments among consumers, synthetic drugs are facing the challenge of controlling disease development and progression. Various medicinal plants and their constituents are recognized for their imminent role in disease management via modulation of biological activities. At present, research scholars have diverted their attention on natural bioactive entities with health-boosting perception to combat the lifestyle-related disarrays. In particular, Zingiber officinale is a medicinal herb that has been commonly used in food and pharmaceutical products. Its detailed chemical composition and high value-added active components have been extensively studied. In this review, we have summarized the pharmacological potential of this well-endowed chemo preventive agent. It was revealed that its functionalities are attributed to several inherent chemical constituents, including 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 6-hydroshogaol, and oleoresin, which were established through many studies (in vitro, in vivo, and cell lines). In this review, we also focused on the therapeutic effects of ginger and its constituents for their effective antioxidant properties. Their consumption may reduce or delay the progression of related diseases, such as cancer, diabetes, and obesity, via modulation of genetic and metabolic activities. The updated data could elucidate the relationship of the extraction processes with the constituents and biological manifestations. We have collated the current knowledge (including the latest clinical data) about the bioactive compounds and bioactivities of ginger. Their detailed mechanisms, which can lay foundation for their food and medical applications are also discussed.

Antibacterial Activity and Mechanism of Ginger Essential Oil against Escherichia coli and Staphylococcus aureus.

Though essential oils exhibit antibacterial activity against food pathogens, their underlying mechanism is understudied. We extracted ginger essential oil (GEO) using supercritical CO2 and steam distillation. A chemical composition comparison by GC-MS showed that the main components of the extracted GEOs were zingiberene and α-curcumene. Their antibacterial activity and associated mechanism against Staphylococcus aureus and Escherichia coli were investigated. The diameter of inhibition zone (DIZ) of GEO against S. aureus was 17.1 mm, with a minimum inhibition concentration (MIC) of 1.0 mg/mL, and minimum bactericide concentration (MBC) of 2.0 mg/mL. For E. coli, the DIZ was 12.3 mm with MIC and MBC values of 2.0 mg/mL and 4.0 mg/mL, respectively. The SDS-PAGE analysis revealed that some of the electrophoretic bacterial cell proteins bands disappeared with the increase in GEO concentration. Consequently, the nucleic acids content of bacterial suspension was raised significantly and the metabolic activity of bacteria was markedly decreased. GEO could thus inhibit the expression of some genes linked to bacterial energy metabolism, tricarboxylic acid cycle, cell membrane-related proteins, and DNA metabolism. Our findings speculate the bactericidal effects of GEO primarily through disruption of the bacterial cell membrane indicating its suitability in food perseveration.

Treatment of coronavirus disease 2019 in Shandong, China: a cost and affordability analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs. METHODS: This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost. RESULTS: A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure. CONCLUSIONS: Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.

Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

Comparison of phenolic compounds extracted from Diaphragma juglandis fructus, walnut pellicle, and flowers of Juglans regia using methanol, ultrasonic wave, and enzyme assisted-extraction.

The phenols in Diaphragma juglandis fructus (DJF), walnut pellicle (WP), and flowers of Juglans regia (FJR) from walnut were extracted using three methods (methanolic condensation reflux extraction, ultrasonic wave extraction, and enzyme assisted-extraction), and phenolics and antioxidant capacities of different extractions were compared. Overall, 50 phenolics were identified by HPLC-MS/MS with 41 compounds in DJF, 32 in WP, and 29 in FJR. It was observed that tannins in WP was higher than those in DJF and FJR. As for PCA, more than 70% of the variance was explained with the obvious comparison between the phenolic constituents. The phenolics in walnut contributed to remarkable antioxidant effect, with the highest effect observed in WP. This study presents the analysis and comparison of the phenols can be further extended for the development of functional walnut instant foods.

Anticancerous potential of polysaccharides sequentially extracted from Polygonatum cyrtonema Hua in Human cervical cancer Hela cells.

The anticancerous effects of PCHPs (HBSS, CHSS, DASS, and CASS) were investigated on Human cervical cancer Hela cells proliferation inhibition, cytotoxicity, caspase-3 activity, cell cycle, and apoptosis. The inhibition rate was expressed as CASS > HBSS > CHSS > DASS, with the maximum inhibition of 74.453 ± 3.399%. Cell cytotoxicity was observed (CASS > CHSS > HBSS > DASS) with the maximum cell death rate of 82.472 ± 3.488%. The caspase-3 activity was induced by CASS > HBSS > DASS > CHSS, with the maximum multiple of 2.954 ± 0.103. CASS induced cell cycle block at the G2/M phase by elevating mRNA expression of CyclinD1, p21, p53 and Wee1, and lowering the expression of Survivin, CHK2, Wee1, CyclinB1, and CDK-1. CASS enhanced the mRNA expression of DR3, DR5, FasL, FADD, PARP, TNF- α, TNF- R1, TRDAA, caspases-8, caspases-10 and the protein expression of FasL and caspases-8, -10 in the death receptor pathway; while, lowered the mRNA expression of antiapoptotic genes (Bcl - 2 and Bcl-xL) and the protein expression of Bcl - 2. The mRNA expression of apoptosis genes (Bak, Cytc, Puma, and caspases-3, -7, -9) and the protein expression of caspases-3, -9 of mitochondria pathway was up regulated which led to cell apoptosis.

Asparanin A from Asparagus officinalis L. Induces G0/G1 Cell Cycle Arrest and Apoptosis in Human Endometrial Carcinoma Ishikawa Cells via Mitochondrial and PI3K/AKT Signaling Pathways.

Asparanin A (AA), a steroidal saponin from Asparagus officinalis L., has anticancer activity: however, its detailed molecular mechanisms in endometrial cancer (EC) have not been studied so far. We evaluated the anticancer activity and underlying mechanism of AA on EC cell line Ishikawa in vitro and in vivo. AA inhibited the Ishikawa cell proliferation and caused cell morphology alteration and cell cycle arrest in G0/G1 phase. Moreover, it could induce apoptosis through mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio which led to the generation of ROS, up-regulation of cytochrome c followed by decrease of Δψm, and activation of caspases, besides inhibition of the PI3K/AKT/mTOR pathway. In vivo data showed that administration of AA significantly inhibited the tumor tissue cell proliferation, reduced the tumor growth, and induced the apoptosis occurrence. AA can be a possible functional food ingredient to cure endometrial cancer followed by clinical trials.

Icariside II inhibits tumorigenesis via inhibiting AKT/Cyclin E/ CDK 2 pathway and activating mitochondria-dependent pathway.

Cervical cancer contributes largely in women cancer-related mortality. Herein, Icariside II, a flavonoid extracted from edible and pharmaceutical plant Epimedium brevicornum Maxim, exhibited significant anticancer activity on cervical cancer. At first, it was observed that Icariside II inhibited Hela cell proliferation at IC50 (9.2 µM) and the growth of Hela-originated xenografts in BALB/c nude mice. Next, we studied the underlying mechanisms of Icariside II from the aspects of cell growth and cell death. As for cell growth, Icariside II arrested cell cycle at G0/G1 phase through AKT/Cyclin E/CDK 2 from transcriptional and translational levels. As for cell death, Flow Cytometry and Immunofluorescence showed that Icariside II promoted cell death in a dose-dependet manner. And, Icariside II turned to activate the mitochondria-dependent pathway Caspase 9/Caspase 3 much more significantly than death receptor pathway Caspase 8/Caspase 3. Taken together, Icariside II presented anticancer effect on cervical cancer both in vitro and in vivo. Our study provides the evidence that Icariside II can be used as a suitable novel agent in cervical cancer treatment.