The aryl hydrocarbon receptor (AhR) is a pleiotropic nuclear factor that was originally recognized as a “master” of xenobiotic metabolism but demonstrated recently to be a vital regulator of many normal physiological events. Understanding of the mechanism of action of AhR-targeted compounds, as represented by polyphenols (the greatest source of xenobiotic AhR modulators in the human diet) is of critical importance for the development of polyphenol-based nutraceutical strategies or the prevention of AHR-mediated toxicity associated with polyphenol intake. In this review, based on studies conducted over the past decade, we summarized the modes of function of polyphenolic AhR modulators. Furthermore, we made a brief mechanistic synopsis of the pharmacological/therapeutic use of polyphenols as AhR antagonists, selective AhR regulators and dual AhR/ER modulators, and underscored their potential in the prevention/treatment of common human diseases/disorders. Additionally, interesting subjects for further mechanistic investigations on polyphenolic AhR modulators have been provided.

Biochanin A (BCA), the most abundant isoflavone in chickpeas, presents a wide range of biological activities, such as hypolipidaemic, anti-oxidative, anti-proliferative, and estrogen-like effects. We investigated the interaction between BCA and human serum albumin (HSA) via several techniques. UV–Vis absorption spectroscopy verified the conformational variation of HSA after BCA addition, and fluorescence spectroscopy revealed the relevant binding parameters. Circular dichroism spectroscopy was used to estimate the secondary structural changes of HSA with and without BCA. Molecular docking and dynamics simulations were then applied to study the characteristics of HSA with BCA. Energy decomposition analysis was used to prove that Trp214 in subdomain IIA of HSA is the most likely binding site of BCA. Van der Waals forces and hydrophobic interactions may play important roles during the binding process. All of our results showed that BCA presents significant binding affinity to HSA, thus confirming that the role of HSA has as an efficient transporter of biomolecules.

It was previously found that CPe-III-S, synthesized according to the chickpea peptide CPe-III (RQSHFANAQP), exhibited an antiproliferative effect. The aim of this study was to investigate the antiproliferative mechanism of CPe-III-S. CPe-III-S was treated by pepsin and trypsin in a simulated gastrointestinal digestion environment as well as in an animal experiment. With HPLC-ESI-MS analysis, three peptide fragments of Ser-His, His-Phe, and Ala-Asn-Ala-Gln were identified. Ser-His was the only common product from both in vitro and in vivo environments. The specific bindings between three peptides and p53-R273H were performed by molecular docking, and the molecular dynamic simulation between Ser-His and p53-R273H revealed the stability of the binding complex. The binding free energy of the complex was −12.56 ± 1.03 kcal/mol with a reliable hydrogen bond between the ligand and Thr284 of p53. Ser-His may restore mutant p53-R273H activity or inhibit its binding with a downstream signal. This metabolite is a potential anticancer factor for suppressing cell proliferation.Keywords: CPe-III; molecular docking; molecular dynamics simulation; p53 mutation; Ser-His;

NAC proteins comprise a large family of transcription factors that play important roles in diverse physiological processes during development. To explore the role of NAC transcription factors in the ripening of fruits, we predicted the secondary and tertiary structure as well as regulative function of the SNAC4 (SlNAC48, Accession number: NM 001279348.2) and SNAC9 (SlNAC19, Accession number: XM 004236996.2) transcription factors in tomato. We found that the tertiary structure of SNAC9 was similar to that of ATNAP, which played an important role in the fruit senescence and was required for ethylene stimulation. Likewise, the bio-function prediction results indicated that SNAC4 and SNAC9 participated in various plant hormone signaling and senescence processes. More information about SNACs was obtained by the application of VIGS (virus-induced gene silencing). The silencing of SNAC4 and SNAC9 dramatically repressed the LeACS2, LeACS4 and LeACO1 expression, which consequently led to the inhibition of the ripening process. The silencing of SNACs down-regulated the mRNA levels of the ethylene perception genes and, at the same time, suppressed the expression of ethylene signaling-related genes except for LeERF2 which was induced by the silencing of SNAC4. The expressions of LeRIN were different in two silenced fruits. In addition, the silencing of SNAC4 reduced its mRNA level, while the silencing of SNAC9 induced its expression. Furthermore, the silencing of LeACS4, LeACO1 and LeERF2 reduced the expression of SNAC4 and SNAC9, while the silencing of NR induced the expression of all of them. In particular, these results indicate that SNAC transcription factors bind to the promoter of the ethylene synthesis genes in vitro. This experimental evidence demonstrates that SNAC4 and SNAC9 could positively regulate the tomato fruit ripening process by functioning upstream of ethylene synthesis genes. These outcomes will be helpful to provide a theoretical foundation for further exploring the tomato fruit ripening and senescence mechanism.

Breast cancer is the leading cause of death among women, with approximately 1 million diagnoses annually. Triterpenoids, which have cancer preventive or anti-tumour efficacy towards various tumour cells, may play a role in breast cancer prevention. In our previous study, an acetic ether (EtOAc) fraction from the sporocarp of the edible mushroom Pleurotus eryngii (P. eryngii) exhibited significant tumour cell growth inhibition both in vitro and in vivo. In this study, three pentacyclic triterpenoid compounds (1–3) were isolated from EtOAc extracts using chromatographic separation and were identified using nuclear magnetic resonance (NMR) and mass spectrometry (MS). The compounds were 2, 3, 6, 23-tetrahydroxy-urs-12-en-28 oic acid (1), 2,3,23-trihydroxy-urs-12-en-28 oic acid (2) and lupeol (3). All three purified triterpenes showed significant inhibitory activity against breast cancer MCF-7 cell lines in vitro, with the greatest activity exhibited by compound 1, followed by compound 2 and 3. The IC50 values were 15.71, 48 and 66.89 μM, respectively. Our study may help elucidate the health benefits of P. eryngii mushroom consumption.

This study was undertaken to determine the effects of chickpea albumin hydrolysate (CAH) on antihyperlipidemic and antitumor functions. The antihyperlipidemic results showed that CAH exhibited a dose dependent ability to decrease the levels of serum total cholesterol, triglyceride, LDL cholesterol (LDL-C), while increasing HDL cholesterol (HDL-C). Additionally, the appearance of the hyperlipidemic livers was ameliorated significantly. The antitumor results showed that CAH administration significantly increased the tumor inhibition rate and decreased tumor volume. CAH was also able to increase the spleen index and promote spleen lymphocyte proliferation. In addition, CAH treatment led to a remarkable rise in the superoxide dismutase (SOD) activity, while dramatically decreasing malondialdehyde (MDA) in the liver. Most importantly, we found that the physical conditions, such as appetite, activity, and coat luster of the mice in the CAH test group were better than those in the tumor control (TC) and positive control (PC) groups. These results taken together indicate that CAH warrants being further investigated and developed as an adjunctive element for hepatic lipid control, as well as antitumor and hypolipidemic therapies.

Fruit ripening is a complex process and is regulated by many factors. Ethylene and polygalacturonase (PG), lipoxygenase(LOX), expansin(EXP) are all critical regulating factors in fruit ripening and softening process. With antisense ACS tomato, Nr mutant tomato and cultivated tomato as materials, Northern blot hybridization showed that PG, LeEXP1 and LOX expressed differently in different parts of cultivated tomato fruit during ripening, which was related to fruit ripening. The ripening process of columella and radial pericarp was faster than pericarp. In both Nr mutant and antisense ACS transgenic tomato fruit, expression levels of PG, LeEXP1 and LOX were generally lower than those in cultivated fruit but still related to fruit ripening. The expression levels of PG, LeEXP1 and LOX increased in the mature green tomato fruits after 0.5 h treatment with ethylene (100 μL/L). These results indicate that gene expression of PG, LeEXP1 and LOX were positively regulated by ethylene. The time and cumulative effect of the concentration exists in the expression of PG regulated by ethylene. The regulation of LOX expression mainly depended on the fruit development after great amount of ethylene was produced. PG played a major role in ripening and softening of tomato fruit, and cooperated with the regulation of EXP and LOX.