Notoginsenoside R1 targets PPAR-γ to inhibit hepatic stellate cell activation and ameliorates liver fibrosis.

BACKGROUND: Hepatic fibrosis, a common pathological process that occurs in end-stage liver diseases, is a serious public health problem and lacks effective therapy. Notoginsenoside R1 (NR1) is a small molecule derived from the traditional Chinese medicine Sanqi, exhibiting great potential in treating diverse metabolie disorders. Here we aimed to enquired the role of NR1 in liver fibrosis and its underlying mechanism in hepatoprotective effects. METHODS: We investigated the anti-fibrosis effect of NR1 using CCl4-induced mouse mode of liver fibrosis as well as TGF-ß1-activated JS-1, LX-2 cells and primary hepatic stellate cell. Cell samples treated by NR1 were collected for transcriptomic profiling analysis. PPAR-γ mediated TGF-ß1/Smads signaling was examined using PPAR-γ selective inhibitors and agonists intervention, immunofluorescence staining and western blot analysis. Additionally, we designed and studied the binding of NR1 to PPAR-γ using molecular docking. RESULTS: NR1 obviously attenuated liver histological damage, reduced serum ALT, AST levels, and decreased liver fibrogenesis markers in mouse mode. Mechanistically, NR1 elevated PPAR-γ and decreased TGF-ß1, p-Smad2/3 expression. The TGF-ß1/Smads signaling pathway and fibrotic phenotype were altered in JS-1 cells after using PPAR-γ selective inhibitors and agonists respectively, confirming PPAR-γ played a pivotal protection role inNR1 treating liver fibrosis. Further molecular docking indicated NR1 had a strong binding tendency to PPAR-γ with minimum free energy. CONCLUSIONS: NR1 attenuates hepatic stellate cell activation and hepatic fibrosis by elevating PPAR-γ to inhibit TGF-ß1/Smads signalling. NR1 may be a potential candidate compound for reliving liver fibrosis.

Systematic Assessment of Chinese Medicine Compounds for Mitigating Anthracycline-Induced Cardiotoxicity.

Background: Anthracycline chemotherapy is highly effective in treating various cancers but is associated with significant cardiotoxicity. Chinese herbal compounds have shown promise in mitigating this adverse effect, warranting systematic evaluation for clinical applicability. Objective: This study seeks to systematically assess the effectiveness of Chinese herbal compounds in managing anthracycline-induced cardiotoxicity via meta-analysis. The objective is to establish an evidence-based framework for their clinical use in preventing and treating this condition. Methods: This study employed a systematic review and meta-analysis design. A comprehensive search strategy was implemented across multiple databases, including CNKI, VIP, PubMed, Embase, and the Cochrane Library, to identify relevant randomized controlled trials (RCTs). Data collection involved extracting information on the efficacy of Chinese herbal compounds in treating anthracycline-induced cardiotoxicity. The primary outcome measures included left ventricular ejection fraction (LVEF), serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), creatine kinase (CK), and ST-T abnormality. The risk of bias in these studies was assessed following Cochrane Handbook guidelines. Meta-analysis of outcome indicators was conducted utilizing RevMan 5.4. Results: A total of 10 RCTs involving 748 patients met the inclusion criteria. Findings indicate that Chinese herbal compounds significantly enhance left ventricular ejection fraction (LVEF) while reducing serum levels of cTnI, CK-MB, and CK. Additionally, the compounds demonstrate a significant improvement in ST-T abnormality. Conclusions: Chinese herbal compounds exhibit promising potential in ameliorating anthracycline-induced cardiotoxicity. These findings underscore the potential utility of Chinese herbal medicine as an adjunctive therapy in managing this condition. Further research is warranted to explain the underlying mechanisms and optimize their clinical application.

Genomic insight into the origin, domestication, dispersal, diversification and human selection of Tartary buckwheat.

BACKGROUND: Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. RESULTS: Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency. CONCLUSIONS: This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.

Prevention and treatment of inflammatory arthritis with traditional Chinese medicine: Underlying mechanisms based on cell and molecular targets.

Inflammatory arthritis, primarily including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, is a group of chronic inflammatory diseases, whose general feature is joint dysfunction with chronic pain and eventually causes disability in older people. To date, both Western medicine and traditional Chinese medicine (TCM) have developed a variety of therapeutic methods for inflammatory arthritis and achieved excellent results. But there is still a long way to totally cure these diseases. TCM has been used to treat various joint diseases for thousands of years in Asia. In this review, we summarize clinical efficacies of TCM in inflammatory arthritis treatment after reviewing the results demonstrated in meta-analyses, systematic reviews, and clinical trials. We pioneered taking inflammatory arthritis-related cell targets of TCM as the entry point and further elaborated the molecular targets inside the cells of TCM, especially the signaling pathways. In addition, we also briefly discussed the relationship between gut microbiota and TCM and described the role of drug delivery systems for using TCM more accurately and safely. We provide updated and comprehensive insights into the clinical application of TCM for inflammatory arthritis treatment. We hope this review can guide and inspire researchers to further explore mechanisms of the anti-arthritis activity of TCM and make a great leap forward in comprehending the science of TCM.

BushenHuoxue decoction suppresses M1 macrophage polarization and prevents LPS induced inflammatory bone loss by activating AMPK pathway.

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1ß (39.42 ± 3.076 ng/L, p < 0.05), IL-6 (49.24 ± 1.766 mg/L, p < 0.05) and TNF-α (286.3 ± 27.12 ng/L, p < 0.05) were significantly increased. The addition of BSHXD decreased the expression levels of IL-1ß, IL-6, and TNF-α to 31.55 ± 1.296 ng/L, 37.94 ± 0.8869 mg/L, and 196.4 ± 25.25 ng/L, respectively (p < 0.05). The results of immunofluorescence staining, Western blotting (WB) and flow cytometry indicated that the proportion of M1 macrophages in RAW264.7 cells treated with BSHXD for 24 h was significantly lower than that in the LPS group (13.36% ± 0.9829% VS 24.80% ± 4.619%, p < 0.05). The evidence from in-vitro experiments showed that the immunomodulatory ability of BSHXD may be associated with the activation of AMP-dependent protein kinase (AMPK) pathway in LPS-treated macrophages. In addition, the results of micro-CT, H&E staining, immunohistochemical staining and immunofluorescence staining of mouse skull further demonstrated that BSHXD treatment significantly alleviated LPS-induced local bone loss and inflammatory damage in mouse skull model. All results indicated that BSHXD significantly inhibited inflammatory factors release and M1 polarization of macrophage through AMPK signaling pathway. Therefore, BSHXD may be a promising drug for the treatment of inflammatory bone loss.

A comprehensive study on physicochemical properties, bioactive compounds, and emulsified lipid digestion characteristics of Idesia polycarpa var. Vestita Diels fruits oil.

Idesia polycarpa var. vestita Diels fruits oil (IPO) has the potential to broaden the availability of healthy vegetable oil and relieve pressure on the edible oil supply. In this study, we compared the physicochemical, bioactivity, and digestive properties of IPO, olive oil (OO), and soybean oil (SO) to comprehensively evaluate the edible potential of IPO. The results revealed no significant differences in relative density or refractive index among the three oils. IPO was rich in ß-sitosterol (366.74 mg/100 g), ß-tocopherol (8.42 mg/100 g), and α-tocopherol (37.10 mg/100 g). The digestive properties of IPO emulsion were investigated for the first time using in vitro simulated digestion. The IPO emulsion stood out regarding its free fatty acid release (88.03 %). Finally, the IPO emulsion released mainly unsaturated fatty acids and had a higher monoacylglycerol content. This study provides new insights into IPO as a high-quality edible vegetable oil.

Optimization and comparison of nonconventional extraction techniques for soluble phenolic compounds from brocade orange (Citrus sinensis) peels.

Brocade orange (Citrus sinensis L. Osbeck) peels (BOPs) are rich in a variety of phenols with multiple and strong bioactivities. This study sought to utilize a response surface methodology to optimize the parameters of accelerated solvent extraction (ASE) to obtain phenolic extracts from BOPs. Total phenolic and flavonoid content (TPC and TFC), profiles, and antioxidant activities of extracts for free, esterified-, and glycosylated-bound phenols from ASE were compared with those derived from Soxhlet extraction (SE) (80°C, 6 h) and heat-reflux extraction (HRE) (80°C, 3 h). Maximum practical TPC and TFC under optimal ASE conditions (15 min, 108°C, 82 bar, and three cycles) were determined to be 32.82 mg gallic acid equivalents/dry weight (DW) and 10.25 mg rutin equivalents/DW, respectively. The profiles, contents, and corresponding bioactivities of the extracts significantly depended on extraction method, particularly with regard to phenolic fraction. Generally, ASE and HRE were associated with higher levels of extraction efficiency and higher quality targeted bioactive compounds with stronger antioxidant activity. More importantly, ASE represents a simple, efficient, and time-saving technique for the extraction of phenols. Furthermore, the finding that different phenolic fractions contain variable profiles and contents of phenols is useful for efforts to obtain targeted individual bioactive ingredients and make better use of biomass residues.

Determination of main alkylamides responsible for Zanthoxylum bungeanum pungency through quantitative analysis of multi-components by a single marker.

The pungency of Chinese pepper (Zanthoxylum bungeanum) is mainly attributed to the alkylamides contained therein. However, the quantitation and application of these alkylamides are hindered by the lack of commercially available standards. Herein, five alkylamides mainly responsible for the pungency of Z. bungeanum were quantified in 31 batch samples of this plant by high-performance liquid chromatography-mass spectrometry and quantitative analysis of multi-components by a single marker (QAMS) to reveal significant differences in composition distribution according to the sample source. The two methods employed for this purpose, namely an external standard method and QAMS, were shown to be consistent, as the corresponding standardized mean difference was below 5.0%. Thus, the developed QAMS method was concluded to be a promising alternative for the comprehensive and effective quality control of Z. bungeanum from different sources.

Paeoniflorin Ameliorates Hyperprolactinemia-Induced Inhibition of Osteoblastogenesis by Suppressing the NF-κB Signaling Pathway.

Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.

Deodorizing effects of rosemary extract on silver carp (Hypophthalmichthys molitrix) and determination of its deodorizing components.

Fishy odor in fish products severely influences both eating quality and commercial acceptability, and natural plant extracts, particularly spices, have recently become popular for the removal of fishy odor. This study aimed to explore the potential of rosemary extract for the deodorization of silver carp (Hypophthalmichthys molitrix), as well as to identify the deodorizing components in rosemary extract. Results showed that all of the spice extracts used in this study (ginger, garlic, angelica dahurica, fennel, rosemary, nutmeg, white cardamom, cinnamon, star anise, and bay leaf) significantly reduced the fishy odor value of silver carp, among which rosemary extract was most effective, decreasing the fishy odor value by about 58%. Gas chromatography-mass spectrometry analysis and sensory evaluation showed that the fishy odor value and concentrations of the fishy odor-active compounds were significantly reduced by the application of rosemary extract. However, the lower the total phenolic content of rosemary extract, the poorer the deodorizing effects against silver carp, suggesting that the deodorizing effect was primarily driven by polyphenols. Fourteen phenolic compounds were measured in rosemary extract, and three individual phenolic compounds (rosmarinic acid [RA], carnosic acid [CA], and carnosol [CS]) were chosen for deodorizing experiment. Sensory detection results and changes of contents of volatile showed that these three phenolic compounds are effective at removing the fishy odor. These results suggest that polyphenols are the main deodorizing components, and RA, CA, and CS are the main deodorizing active compounds in rosemary extract. PRACTICAL APPLICATION: The results of this study may provide a new way to determine the deodorizing components of spice extracts. Moreover, it can provide guidance for further research in investigating the deodorizing mechanism of sipce extracts.

Recent Advances in Functional Carbon Quantum Dots for Antitumour.

Carbon quantum dots (CQDs) are an emerging class of quasi-zero-dimensional photoluminescent nanomaterials with particle sizes less than 10 nm. Owing to their favourable water dispersion, strong chemical inertia, stable optical performance, and good biocompatibility, CQDs have become prominent in biomedical fields. CQDs can be fabricated by "top-down" and "bottom-up" methods, both of which involve oxidation, carbonization, pyrolysis and polymerization. The functions of CQDs include biological imaging, biosensing, drug delivery, gene carrying, antimicrobial performance, photothermal ablation and so on, which enable them to be utilized in antitumour applications. The purpose of this review is to summarize the research progress of CQDs in antitumour applications from preparation and characterization to application prospects. Furthermore, the challenges and opportunities of CQDs are discussed along with future perspectives for precise individual therapy of tumours.

The immunomodulatory effects of Carapax Trionycis ultrafine powder on cyclophosphamide-induced immunosuppression in Balb/c mice.

BACKGROUND: There are abundant resources of Carapax Trionycis from soft-shelled turtle processing wastes each year in China. Our preliminary work showed that Carapax Trionycis ultrafine powder (CTUP) obtained using ball-milling with a particle size of 2.24 µm (D0.025) contained more active ingredients. The CTUP D0.025 has a good bioaccessibility, but there has been no report about the immunomodulatory function of CTUP. Therefore, using a cyclophosphamide-induced immunosuppression mice model, we investigated the immunomodulatory effects of CTUP D0.025. RESULTS: The results indicated that CTUP D0.025 administration significantly improved the immune organ (bone marrow, thymus and spleen) indices, ameliorated spleen tissue morphology and increased the capacity of splenocyte proliferation and the activity of macrophage phagocytosis. CTUP D0.025 also significantly promoted the secretion of cytokines (IL-2, IL-4, IL-10, IFN-γ and TNF-α), improved the related mRNA expression levels of IL2, IFN-γ, T-bet and GATA3 in immunosuppressed mice and increased the production of serum hemolysin and the levels of IgG, IgM as well as complement C3 . Moreover, CTUP D0.025 administration enhanced the antioxidant capacity of mice, exhibited a moderating effect on the damage of bone and skeletal muscle and improved the recovery of bone mineral density and calcium metabolism. CONCLUSIONS: These findings demonstrated that CTUP D0.025 had an effective immune-enhancing function in immunosuppressive Balb/c mice and also exhibited anti-osteoporosis properties. © 2020 Society of Chemical Industry.

Qishen Huanwu capsule reduces pirarubicin-induced cardiotoxicity in rats by activating the PI3K/Akt/mTOR pathway.

BACKGROUND: One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms. METHODS: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR. RESULTS: Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed. CONCLUSIONS: QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.

Performance, mechanism and stability of nitrogen-doped sewage sludge based activated carbon supported magnetite in anaerobic degradation of coal gasification wastewater.

In current study, the UASB reactor was enhanced by nitrogen-doped sewage sludge based activated carbon supported Fe3O4 (Fe3O4/N-SBAC) for coal gasification wastewater treatment. The results showed that COD removal efficiency was increased to 64.4% with Fe3O4/N-SBAC assistance and the corresponding methane production rate achieved up to 1093.6 mL/d. Fe3O4/N-SBAC promoted microbial growth and enzymatic activity, leading to high extracellular polymeric substances and coenzyme F420 concentrations. Fe3O4/N-SBAC also facilitated the sludge granulation process with high particle size, substantial interspecific signal molecules and low diffusible signal factor. Microbial community analysis revealed that Fe3O4/N-SBAC might support direct interspecies electron transfer process, in which the enriched Geobacter was likely to communicate with Methanothrix via electrical connection, improving anaerobic degradation of coal gasification wastewater. Total phenols shock and pH impact revealed that reactor stability was enhanced in the Fe3O4/N-SBAC-supplemented system.

A comparison of a polysaccharide extracted from ginger (Zingiber officinale) stems and leaves using different methods: preparation, structure characteristics, and biological activities.

This study investigates how extraction method impacts the yield, chemical composition, structure characteristics, hypoglycemic and antioxidant activity of polysaccharides from ginger (Zingiber officinale Roscoe) stems and leaves (GSLP). Four extraction methods were employed to obtain the GSLP, including hot water extraction (HWE), ultrasound-assisted extraction (UAE), alkaline solution extraction (ASE), and enzyme-assisted extraction (EAE). The data showed that ASE produced highest extraction yield compared to the other extraction methods. Scanning electron microscopy indicated that GSLP microstructures were greatly influenced by extraction method. Moreover, in vitro hypoglycemic activity and antioxidant activity experiments demonstrated that the biological capacities of ASE-GSLP were superior to GSLPs extracted by the other methods. Taken together, these results indicate that polysaccharides from ginger stems and leaves obtained by alkali, complex enzyme, and ultrasonic-assisted extractions are imbued with different characteristic mechanisms of degradation, despite the uniformity of their main structures. In addition, ASE-GSLP displayed better biological activities probably due to its abundant uronic acid content, higher sulfate radical, and smaller molecular weight. Thus, it can be concluded that ASE has great potential as an effective strategy for obtaining polysaccharides from stems and leaves because of its higher yield and the remarkable bioactivity of its products.

Antibacterial Constituents of Hainan Morinda citrifolia (Noni) Leaves.

Noni (Morinda citrifolia L.) is an edible and medicinal plant distributed in Hainan, China. The antibacterial activities of the extracts of water (WE), petroleum ether (PEE), ethyl acetate (EAE), chloroform (CE), and n-butanol (BE) were assayed by the disk diffusion method. The results showed that the extracts from Noni leaves possessed antibacterial effects against Bacillus subtilis, Escherichia coli, Proteus vulgaris, and Staphylococcus aureus. Among 5 different extracts, the BE produced the best antibacterial activity. The samples were first extracted by ethanol, and the primary compounds in the BE fraction of ethanol extract was further isolated and identified. Six phenolic compounds, including 5, 15-dimethylmorindol, ferulic acid, p-hydroxycinamic acid, methyl 4-hydroxybenzoate, methyl ferulate, and methyl 4-hydroxycinnamate, were identifiedby NMR. The results indicated that the phenolic compounds might significantly contribute to antibacterial activities of Noni leaves.

Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts.

Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol.

Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chromatography.

The phytochemical resveratrol (trans-3,4',5-trihydroxystilbene) is a naturally occurring polyphenol with a plethora of health-beneficial properties, including a preventive role in cancer. We surmise that resveratrol may exert its diverse biological effects by interacting with specific target proteins, denoted RTPs. To test this possibility, resveratrol was immobilized on epoxy-activated agarose forming a resveratrol affinity column (RAC), which was used to detect and isolate RTPs. Distinct RTPs can be resolved on RAC by fractionation with increasing NaCl, followed by 1mM ATP, and finally, with 1-2mM resveratrol. A 22-kDa polypeptide, RTP-22, eluted with resveratrol was identified by MALDI-TOF MS and cloning/expression in Escherichia coli, as dihydronicotinamide riboside quinone reductase 2 (NQO2). The utility of RAC was additionally explored with extracts derived from different staging prostate cancer cells. NQO2 was most abundant in CWR22Rv1, a model for prostate cancer transition from androgen-dependent to the hormone-refractory state, but was marginally expressed in JCA-1 cells as representing more advanced stage prostate cancer. These results provide evidence for the existence of distinctive RTPs in mammalian cells and that RAC is a facile approach to identify and purify RTPs.