Cornus officinalis var. koreana Kitam extracts alleviate cadmium-induced renal fibrosis by targeting matrix metallopeptidase 9.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis var. koreana Kitam (Cornus officinalis) is a commonly used Chinese herbal medicine and has a good clinical efficacy in kidney and liver diseases. Recent years, a number of studies reported the significant effects of Cornus officinalis on renal fibrosis. However, it is still unclear about the underlying specific mechanism, the bioactive ingredients, and the target gene regulatory network. AIM OF THE STUDY: We investigated the impact of Cornus officinalis extract on cadmium-induced renal fibrosis, screened the bioactive ingredients of Cornus officinalis using a pharmacological sub-network analysis, and explored the regulatory effects of Cornus officinalis extracts on target gene matrix metallopeptidase 9 (MMP9). METHODS: Male C57BL/6N mice were treated with single or combinatorial agents such as saline, cadmium chloride, Cornus officinalis, Isoginkgetin and FSL-1. Isoginkgetin is a compound with anti-MMP9 activity. FSL-1 can induce MMP9 expression. Masson staining and Western blot and immunohistochemistry analyses were used for assessing renal fibrosis. In addition, wound healing model was established using BUMPT (Boston university mouse proximal tubular) cells to investigate how Cornus officinalis affected cadmium-induced cell migration. The main Cornus officinalis bioactive compounds were identified by UHPLC-MS (Ultra-high-performance liquid chromatography - mass spectrometry). The MMP9 target for Cornus officinalis active ingredients were confirmed through a pharmacological sub-network analysis. RESULTS: Aqueous extracts of Cornus officinalis protected from renal dysfunction and kidney fibrosis induced by cadmium chloride in mice. In vitro experiments validated that Cornus officinalis extracts inhibited cell migration ability especially in cadmium chloride condition. The sub-network analysis and chemical components profiling technique revealed the active compounds of Cornus officinalis. Cellular thermal shift assay verified the binding abilities of three active components Daidzein, N-Acetyl-L-tyrosine or Swertisin with matrix metalloproteinase-9. Gelatin zymography assay revealed that the activity of MMP9 was inhibited by the three active components. We further confirmed that MMP9 was involved in the process of Cornus officinalis extracts reducing renal fibrosis. Cornus officinalis attenuated the cadmium-induced renal fibrosis was correlated with decreased expression of MMP9, collagen I, α-SMA (alpha-smooth muscle actin) and vimentin. CONCLUSIONS: This study demonstrated that Cornus officinalis extracts could alleviate the cadmium chloride-induced renal fibrosis by targeting MMP9, and might provide new insights into the mechanism of treating renal fibrosis by Cornus officinalis.

Evaluation of the Biological Activity of Hydrogel with Cornus mas L. Extract and Its Potential Use in Dermatology and Cosmetology.

Due to the growing popularity of herbal extract-loaded hydrogels, this study assessed the biological activity of extracts and hydrogels containing three types (water (WE), water-ethanol (EE) and water-glycerin (GE)) of Cornus mas L. (dogwood) extracts. The content of biologically active compounds in the extracts was assessed using the UPLC-DAD-MS technique. Antioxidant properties were assessed by using DPPH and ABTS radicals and measuring the intracellular level of reactive oxygen species. Alamar Blue and Neutral Red tests were used to measure the cytotoxicity of the tested samples on skin cells-fibroblasts and keratinocytes. Cell migration and the anti-aging activity of the tested extracts and hydrogels were assessed. Transepidermal water loss and skin hydration after applying the hydrogels to the skin were also determined. A chromatographic analysis revealed that the extracts contained polyphenols, including gallic, caftaric, protocatechuic, chlorogenic, ellagic and p-coumaroylquinic acids, as well as iridoids, with loganic acid as the predominant component. Additionally, they contained cyanidin 3-O-galactoside, pelargonidin 3-O-glucoside and quinic acid. The obtained results show that the tested extracts and hydrogels had strong antioxidant properties and had a positive effect on the viability of skin cells in vitro. Additionally, it was shown that they stimulated the migration of these cells and had the ability to inhibit the activity of collagenase and elastase. Moreover, the tested hydrogels increased skin hydration and prevented transepidermal water loss. The obtained results indicate that the developed hydrogels may be effective delivery systems for phytochemicals contained in dogwood extracts.

The Nephroprotective Effect of Cornelian Cherry (Cornus mas L.) and Rowanberry (Sorbus aucuparia L.) in Gentamicin-Induced Nephrotoxicity on Wistar Rats with Emphasis on the Evaluation of Novel Renal Biomarkers and the Antioxidant Capacity in Correlation with Nitro-Oxidative Stress.

In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries.

Iridoid- and flavonoid-enriched fractions of Cornus sanguinea and Cornus mas exert antioxidant and anti-inflammatory effects and inhibit key enzymes in the treatment of metabolic disorders.

Background: Berry fruits are recognized as a "superfood" due to their high content of bioactive compounds and health benefits. Scope and approach: Herein, extracts of Cornus sanguinea and Cornus mas fresh and dried fruits obtained by different extraction procedures (ethanolic and hydroalcoholic maceration, ultrasound-assisted extraction, and Soxhlet apparatus) were analysed using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and compared to identify the main healthy compounds and their impact on the inhibition of key enzymes (pancreatic lipase, α-glucosidase, and α-amylase) associated with metabolic disorders. The antioxidant activity and inhibition of nitric oxide (NO) and NF-κB pathway were also investigated. Key findings and conclusions: Flavonoids, iridoids, and phenolic acids were the main classes of identified compounds. Herein, kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin, quercetin 3-O-xyloside, and myricetin 3-O-galactoside were detected for the first time in C. sanguinea. Remarkable antioxidant effects and promising α-glucosidase and lipase inhibitory activity were observed with extracts obtained by hydroalcoholic maceration of both Cornus dried fruits. Consequently, these extracts were subjected to fractionation using Amberlite XAD-16 resin. The most promising biological activities, which are attributed to the presence of some flavonoids and iridoids, were detected with the C. sanguinea fractions, in particular SD2(II). The results of this study offer new insights into the potential development of functional foods, nutraceuticals, and food supplements using the Cornus species.

A systematic review on anti-diabetic action of 7-O-galloyl-D-sedoheptulose, a polyphenol from Corni Fructus, in type 2 diabetic mice with hepatic and pancreatic damage.

Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22phox. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-ß1, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.

New Type of Tannins Identified from the Seeds of Cornus officinalis Sieb. et Zucc. by HPLC-ESI-MS/MS.

There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis. More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.

Two unusual novel iridoid glycosides from Cornus officinalis fruit and their biological activities.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

A Comparison of the Antiosteoporotic Effects of Cornelian Cherry (Cornus mas L.) Extracts from Red and Yellow Fruits Containing Different Constituents of Polyphenols and Iridoids in Osteoblasts and Osteoclasts.

Methods: Polyphenolic and iridoid constituents of extracts were analyzed qualitatively and quantitatively using the ultraperformance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry. Primary cultured osteoblasts isolated from mouse calvarias and osteoclast-lineage primary cultured monocytes isolated from mouse bone marrow were used for the assessment of osteoblast and osteoclast differentiation. In the osteoblast culture, cellular viability, alkaline phosphatase (ALP) activity, ALP staining, and mRNA expression of Alpl and Runx2 were examined. In the osteoclast culture, the examined parameters were cellular viability, tartrate-resistant acid phosphatase (TRAP) activity and staining, and mRNA expression of Nfatc1, Ctsk, and Acp. Results: A total of 41 main compounds of iridoids, anthocyanins, hydrolysable tannins, phenolic acids, and flavonols were identified in the three extracts. RED EXT1 contained most of the tested polyphenols and iridoids and was the only extract containing anthocyanins. YL EXT2 contained only one iridoid, loganic acid and gallic acid. YL EXT3 comprised a mixture of iridoids and polyphenols. RED EXT1, YL EXT 2, and to a lesser extent YL EXT3 promoted osteoblast differentiation increasing significantly ALP activity and the amount of ALP-positive stained cells. All extracts upregulated mRNA expression of Alpl and Runx2. RED EXT1 caused the most significant decrease in TRAP activity and the numbers of TRAP-positive multinucleated cells. RED EXT1 caused also the most significant downregulation of mRNA expression of osteoclast related genes Nfatc1, Ctsk, and Acp5. Extracts from yellow fruits, mostly YL EXT2 caused lower, but still significant inhibitory effect on TRAP and osteoclast related genes. Conclusions: The main conclusion of our study is that all three extracts, especially RED EXT1 from red cornelian cherry fruits, possess the antiosteoporotic potential and may be a promising phytomedicine candidate for the prevention and treatment of osteoporosis.

Cornelian Cherry (Cornus mas L.) Extracts Exert Cytotoxicity in Two Selected Melanoma Cell Lines-A Factorial Analysis of Time-Dependent Alterations in Values Obtained with SRB and MTT Assays.

Despite the fact that phytochemicals of Cornaceae species have long been discussed as possible auxiliary agents in contemporary treatment, the insights on their properties remain relatively scarce. This study focuses on Cornus mas L. (Cornelian cherry), the extracts of which are reported to exert a pleiotropic effect shown in both in vivo and in vitro studies. This study aimed to explore the cytotoxic effect of extracts from fruits of red (Cornus mas L. 'Podolski') and yellow (Cornus mas L. 'Yantarnyi' and 'Flava') Cornelian cherries on two melanoma cell lines (A375 and MeWo). The extracts were characterized in the context of the concentration of bioactive compounds of antioxidative properties. Cytotoxicity was investigated with the use of the following two assays: SRB and MTT. An additional, alternative protocol for the SRB assay was used in this study so as to account for possible bias. Cytotoxicity was assessed as a difference in the whole time series of cell viability, instead of analyzing differences in raw values (often found in the literature). Both extracts from Cornus mas L. induced cytotoxicity in both A375 and MeWo cell lines, although the response of these cells was different. Moreover, based on this study, there is no evidence for claiming a different magnitude of cytotoxicity between these two extracts.

Genoprotective effect of cornelian cherry (Cornus mas L.) phytochemicals, electrochemical and ab initio interaction study.

Cornelian cherry (Cornus mas L.) has broad and multidimensional potential in preventing civilisational diseases. Part of these diseases results from DNA oxidative mutations. Thus, the paper aimed to predict how phenolics present in C. mas may interact with dsDNA in ab initio experiment and to check the effect of different cornelian cherry extracts on DNA structure and DNA oxidation. A special research model was designed using biosensor with a carbonpaste electrode. We resulted in various effects observed for phenolics and the extracts. Flavonoids, but of vitexin interacted with declining energy of the DNA models and liability of DNA oxidation. However, for 8-oxoguaniosine the trend was the opposite. Among the evaluated extracts, water-ethanolic extracts caused decline in adenine and guanine signals after dsDNA exposition on the extract. Principal component analysis showed that alcoholic extracts of cv. Szafer and Slowianin, which were rich in apigenin and kaempferol exhibit mild genoprotective effect.

Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: A comprehensive review.

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

Ultrasound assisted aqueous two-phase extraction of polysaccharides from Cornus officinalis fruit: Modeling, optimization, purification, and characterization.

Ultrasound assisted aqueous two-phase extraction of polysaccharides from Cornus officinalis fruit was modeled by response surface methodology (RSM) and artificial neural network (ANN), and optimized using genetic algorithm coupled with ANN (GA-ANN). Statistical analysis showed that the models obtained by RSM and ANN could accurately predict the Cornus officinalis polysaccharides (COPs) yield. However, ANN prediction was more accurate than RSM. The optimum extraction parameters to achieve the highest COPs yield (7.85 ± 0.09)% was obtained at the ultrasound power of 350 W, extraction temperature of 51 ℃, liquid-to-solid ratio of 17 mL/g, and extraction time of 38 min. Subsequently, the crude COPs were further purified via DEAE-52 and Sephadex G-100 chromatography to obtain a homogenous fraction (COPs-4-SG, 33.64 kDa) that contained galacturonic acid, arabinose, mannose, glucose, and galactose in a molar ratio of 34.82:14.19:6.75:13.48:12.26. The structure of COPs-4-SG was also characterized with UV-vis, fourier-transform infrared spectroscopy (FT-IR), atomic force microscopy (AFM), scanning electron microscopy (SEM), Congo-red test, and circular dichroism (CD). The findings provide a feasible way for the extraction, purification, and optimization of polysaccharides from plant resources.

Preparation and Evaluation of Antioxidant Activities of Bioactive Peptides Obtained from Cornus officinalis.

The present study is a preparation of bioactive peptides from Cornus officinalis proteins by the compound enzymatic hydrolysis method. Response surface methodology (RSM) coupled with Box-Behnken design (BBD) is used to optimize the preparation process of Cornus officinalis peptides. The effects of independent variables, such as the amount of enzyme, pH value, time, extraction times and the ratio of material to liquid on the yield of peptides, are also investigated. The analysis results of the RSM model show that the optimum conditions for the extraction of Cornus officinalis peptides were a pH value of 6.76, temperature of 48.84 °C and the amount of enzyme of 0.19%. Under optimal conditions, the yield of peptides was 36.18 ± 0.26 %, which was close to the predicted yield by the RSM model. Additionally, the prepared Cornus officinalis peptides showed significant antioxidant activity; the scavenging rates of the peptides for DPPH and ·OH were 48.47% and 29.41%, respectively. The results of the cell proliferation assay revealed that the prepared Cornus officinalis peptides could promote embryo fibroblast cells proliferation and repair oxidative damage cells. These results have a practical application value in the design of novel functional food formulations by using Cornus officinalis.

Ultrasound-assisted enzymatic extraction of Corni Fructus alpha-glucosidase inhibitors improves insulin resistance in HepG2 cells.

Corni Fructus (CF) is a traditional medicine and beneficial food with multifaceted protective effects against diabetes and its complications. Since alpha-glucosidase inhibitors (GIs) are promising first-choice oral antihyperglycemic drugs for diabetes, we examined whether GIs from CF (GICF) are useful for diabetes treatment. Therefore, GICF was extracted by ultrasound-assisted enzymatic extraction (UAEE) that is optimized by a three-level, four-factor Box-Behnken design and determined by ultra-performance liquid chromatography. Compared to 36.31 mg g-1 without enzyme treatment, the GICF yield increased to 70.44 mg g-1via UAEE under optimum conditions (0.5% compound enzyme extracted in 23 min at 46 °C and pH 4.8). The activity (91.99%) of GICF was as predicted (93.28%). When GICF was used in an insulin-resistant HepG2 cell model, it significantly ameliorated the glucose metabolism in a dose-dependent manner. Our findings indicate that UAEE may be an innovative method for functional food extraction and a potential strategy for high-quality food ingredient (such as GI) production with high efficiency and productivity.

A systematic approach to decode the mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC).

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.

Secoiridoids from Dogwood (Cornus officinalis) Potentiate Progesterone Signaling.

The use of botanical dietary supplements for the alleviation of conditions such as hot flashes, premenstrual syndrome, and fertility is prolific worldwide. Estrogen and progesterone receptors (ER and PR) and their corresponding steroid hormones are critical for the relief of hot flashes and the treatment of patients who develop endometriosis, and these pathways can influence the development of endometrial, ovarian, and breast cancers. However, few studies have investigated or identified the natural product components in herbal supplements that act on the PR. In the current study, a new secoiridoid, demethoxy-cornuside (1), along with six known secoiridoids (2-7) were isolated from the twigs of dogwood (Cornus officinalis) by bioassay-guided isolation with a progesterone response element (PRE)/luciferase (Luc) reporter assay in Ishikawa cells. Four phytoprogestins (1, 2, 6, 7) potentiated the effect of progesterone in the PRE/Luc assay. This study demonstrates that C. officinalis components might potentiate progesterone signaling in the presence of progesterone, which could modify progesterone receptor action in hormone-responsive tissues such as the uterus and mammary gland.

Inhibitory Activities of Dimeric Ellagitannins Isolated from Cornus alba on Benign Prostatic Hypertrophy.

Benign prostatic hypertrophy (BPH) is an intractable chronic inflammatory disease. We studied the efficacy of two ellagitannins, namely camptothin B (1) and cornusiin A (2) that were isolated from Cornus alba (CA) for the treatment of BPH, which is a common health issue in older men. The ellagitannins (1 and 2) were evaluated on its inhibitory activities of the enzyme 5α-reductase and tumor necrosis factor (TNF)-α, its interleukin (IL)-1ß, IL-6, and IL-8 production, and its anti-proliferation and apoptosis induction in prostate cells that show hypertrophy (RWPE-1 cell). In inhibition of 5α-reductase, the ellagitannins (1 and 2) showed potential effects, compared to the positive control, finasteride. In the case of IL-1ß, IL-6, IL-8, and TNF-α, 1 and 2 showed good inhibitory effects as compared to the control group treated with LPS. The ellagitannins (1 and 2) were also shown to inhibit proliferation of, and induce apoptosis in, the RWPE-1 cell. These results suggest that the ellagitannins (1 and 2) may be good candidates for the treatment of BPH.

Iridoids, Flavonoids, and Antioxidant Capacity of Cornus mas, C. officinalis, and C. mas × C. officinalis Fruits.

The fruits of Cornus mas and Cornus officinalis have been known and appreciated in folk medicine for years and have a high biological value, which is mainly connected with their polyphenols and iridoids content. However, hybrids of C. mas × C. officinalis have not been investigated. The aim of this study was to evaluate the iridoids, anthocyanins, and flavonols content, and antioxidant capacity of Cornus mas, Cornus officinalis, and C. mas × C. officinalis. Iridoids and flavonoids were quantified by the High-Performance Liquid Chromatography (HPLC) method. Antioxidant capacity (AC) was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid (ABTS•+), and ferric reducing antioxidant power (FRAP) tests. Total phenolic content (TPC) was evaluated using the Folin-Ciocalteu reagent. Among the C. mas cultivars and C. officinalis genotypes, there was considerable variation in the content of iridoids, flavonoids, and AC. Interspecific hybrids C. mas × C. officinalis contained more iridoids than C. mas and more anthocyanins than C. officinalis and additionally had higher AC and TPC than C. officinalis and most C. mas. AC, TPC, and the presence of iridoids, anthocyanins, and flavonols in hybrids C. mas × C. officinalis are reported for the first time. The Cornus species deserve special attention due to their highly biologically active substances, as well as useful medicinal properties.

The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial.

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.

Can cornelian cherry mask bitter taste of probiotic chocolate? Human TAS2R receptors and a sensory study with comprehensive characterisation of new functional product.

Cornelian cherry (Cornus mas L.) fruits are a valuable source of bioactive compounds that are responsible for the perception of bitter taste of chocolate products. The aim of the study was to validate the inhibitory effect of Cornus mas on the TAS2R3 and TAS2R13 bitter taste receptors and to assess the effect of masking the bitter taste of dark chocolate with the help of the sensory panel. Dark chocolate was prepared with an addition of 5% of freeze-dried cornelian cherry fruits and 108 CFU/g of Bacillus coagulans probiotic strains. Effect on the TAS2R receptors was evaluated in specially transfected HEK293T cells, and the inhibition ratio was measured using the calcium release test. Moreover, the total polyphenol content, antioxidant activity and simulated intestinal in vitro digestion were determined for the samples. The tested chocolate products were rich in chlorogenic, caffeic and sinapic acids. The addition of cornelian cherry positively affected the antioxidant activity. The phytochemicals of Cornus mas decreased the TAS2R13 activity by 132% after a 2-minute interaction and, % at the same time, inhibited the TAS2R3 activity by 11.5. Meanwhile, chocolate with the addition of fruit was less bitter according to the sensory panel.