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Background Trimethylamine- N -oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. Methods Five groups of male Apolipoprotein E knock-out (ApoE −/− ) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. Results Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. Conclusions The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice. Graphic abstract

Hawthorn fruit has long been used as a folk medicine with many medicinal benefits. HPLC analysis revealed that hawthorn fruit extract (HFE) contained 19.86% procyanidin B2, 15.27% epicatechin, 3.10% chlorogenic acid, 2.91% hyperoside, and 1.34% isoquercitrin. Antioxidants are essential for protection of the bodies against the damaging action of free radicals. And we hypothesized that HFE could enhance antioxidant defenses and improve antioxidant status in aged mice. To test this hypothesis, senescence-accelerated mice (SAM) used as an aging animal model were treated with HFE to evaluate the antioxidant effects of HFE in vivo. We found that the activities of antioxidant enzymes, namely, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in serum, liver, and brain of SAM mice increased upon HFE treatment, meanwhile the malondialdehyde (MDA) content declined. Concurrently, the gene expression levels of SOD, CAT, and GSH-Px were up-regulated in liver. Furthermore, the antioxidant potential of HFE was also investigated with different systems such as superoxide anion radical scavenging and reducing power. The results showed that HFE indicated a concentration-dependent antioxidant activity in vitro.

Hawthorn (Crataegus monogyna Jacq.) is a wild edible fruit tree of the genus Crataegus, one of the most interesting genera of the Rosaceae family. This review is the first to consider, all together, the pharmaceutical, phytochemical, functional and therapeutic properties of C. monogyna based on numerous valuable secondary metabolites, including flavonoids, vitamin C, glycoside, anthocyanin, saponin, tannin and antioxidants. Previous reviews dealt with the properties of all species of the entire genera. We highlight the multi-therapeutic role that C. monogyna extracts could have in the treatment of different chronic and degenerative diseases, mainly focusing on flavonoids. In the first part of this comprehensive review, we describe the main botanical characteristics and summarize the studies which have been performed on the morphological and genetic characterization of the C. monogyna germplasm. In the second part, the key metabolites and their nutritional and pharmaceutical properties are described. This work could be an essential resource for promoting future therapeutic formulations based on this natural and potent bioactive plant extract.

Designing new forms of food, food additives, and nutraceuticals is necessary due to the growing needs of consumers, as well as the inflammation of civilization diseases, the prevention and treatment of which can be significantly supported by dietary intervention. For this reason, this study aimed to obtain highly bioactive preparations in the form of powders from the fruits, leaves, and flowers of six species of hawthorn (Crataegus L.) using solid phase extraction (SPE). Ultra-performance liquid chromatography analysis (UPLC-PDA-MS/MS) showed a high concentration of phenolic compounds (in the range from 31.50 to 66.06 mg/g), including the highest concentration in hawthorn fruit preparations. Fruit preparations also showed the highest antioxidant activity (through scavenging of O2˙− and OH˙ radicals), antidiabetic activity (inhibition of α-amylase and α-glucosidase), and anticancer activity, mainly against colon cancer cells (Caco-2). At the same time, hawthorn flower preparations showed the highest biocompatibility against normal colon cells (CCD841CoN) and anti-inflammatory activity (trypsin inhibition). Correlation and principal component analysis (PCA) showed that the health-promoting potential was most influenced by the content of falavan-3-ols. The above findings provide a basis for the industrial use of the developed preparations, which is in line with the current trend in food technology related to the search for new sources of bioactive compounds and the design of highly bioactive food.

Medicinal plants, many of which are wild, have recently been under the spotlight worldwide due to growing requests for natural and sustainable eco-compatible remedies for pathological conditions with beneficial health effects that are able to support/supplement a daily diet or to support and/or replace conventional pharmacological therapy. The main requests for these products are: safety, minimum adverse unwanted effects, better efficacy, greater bioavailability, and lower cost when compared with synthetic medications available on the market. One of these popular herbs is hawthorn (Crataegus spp.), belonging to the Rosaceae family, with about 280 species present in Europe, North Africa, West Asia, and North America. Various parts of this herb, including the berries, flowers, and leaves, are rich in nutrients and beneficial bioactive compounds. Its chemical composition has been reported to have many health benefits, including medicinal and nutraceutical properties. Accordingly, the present review gives a snapshot of the in vitro and in vivo therapeutic potential of this herb on human health.

Anthocyanins constitute the primary pigment components in hawthorn (Crataegus pinnatifida) peel, yet their specific composition and concentration profiles remain poorly characterized. This study employed ultra-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics to systematically compare anthocyanin profiles between red-peel (CPR) and yellow-peel (CPY) hawthorn cultivars. Our analysis identified 26 anthocyanin metabolites in CPR and 24 in CPY, with cyanidin-3-O-galactoside and cyanidin-3-O-arabinoside being the predominant compounds in both. Multivariate analysis revealed seven significantly differential metabolites, including cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, pelargonidin-3-O-galactoside, pelargonidin-3-O-glucoside, pelargonidin-3-O-arabinoside, and peonidin-3-O-galactoside. Notably, all the differential metabolites exhibited reductions in CPY compared to CPR. Chromatic analysis demonstrated that CPR possessed highly significantly lower hue angle values (hab) than CPY (47.7093 ± 4.1706, 83.6427 ± 1.4604, p < 0.01), showing strong negative correlations with key anthocyanins. These findings enhance the scientific understanding of anthocyanin biosynthesis in hawthorn peel and provide a certain reference for the development and utilization of anthocyanins in hawthorn peel.

Hawthorn (Crataegus monogyna Jacq.) is a medicinal and nutritional plant widely recognized for its rich phytochemical composition and diverse health-promoting properties. The fruit, leaves, and flowers contain significant amounts of polyphenols, flavonoids, flavonols, phenolic acids and dye compounds with antioxidant properties that contribute to its strong antioxidant capacity. Numerous studies have demonstrated hawthorn’s beneficial effects on cardiovascular health, including regulation of blood pressure, lipid metabolism, and cardiac function. Additionally, hawthorn exhibits anti-inflammatory, antimicrobial, hypolipidemic, and antidiabetic properties, supporting its role in the prevention and management of chronic diseases. Its potential as a functional food ingredient and natural health supplement is increasingly recognized. However, further clinical trials and standardization of bioactive components are needed to confirm its efficacy, safety, and optimal dosage. Overall, hawthorn represents a valuable natural resource for promoting human health and well-being through diet and phytotherapy. Therefore, the aim of this study is to present—based on the scientific literature—the antioxidant properties of hawthorn and to assess the possibility of using this plant as a functional ingredient.

Crataegus products for food, nutritional, and pharmaceutical uses are available over the counter in the global market. The aerial parts are enriched with biochemicals and are used to treat cardiovascular, respiratory, and liver disorders and cancer. Detailed study to understand the chemical composition and different levels within medicinally important plant tissues needs hours, such as plant response for metabolite flux and quality control purposes. Therefore, comprehensive metabolite profiling (qualitatively and quantitatively) of different tissues [leaves, flowers, stems, fruits (without seeds), and seeds; n = 5] of Crataegus rhipidophylla Gand. was performed by NMR techniques in one session. Fifty-eight compounds of different classes were unambiguously identified with the use of 1D and 2D NMR techniques (1H, 13C, distortionless enhancement by polarization transfer with 135° angle, correlation spectroscopy, heteronuclear single quantum coherence, heteronuclear multiple bond correlation) and quantified by a relative quantification method. Chemical compounds such as amygdalin (seeds), rutin (flowers), isovitexin (fruits), shikimic acid (leaves), and epicatechin (stems) were identified as authentication as well as discrimination markers for the respective C. rhipidophylla tissues. The fruits contain a significant mixture of important metabolites, followed by flowers and leaves. Trends of metabolite levels, upregulation, and downregulation in plant tissues were found, which highlights the responses of plant tissues in a specific time. NMR-based comprehensive metabolite information was used to develop the chemical signature, quality control chemical markers, and strategies to understand the chemical diversity of C. rhipidophylla. This chemical information from different aerial tissues will provide guidance for the extensive utilization of Crataegus.

Hyperglycemia has deleterious effects on pancreatic β-cells, causing dysfunction and insulin resistance that lead to diabetes mellitus (DM). The possible causes of injury can be caused by glucose- or fructose-induced oxidative and endoplasmic reticulum (ER) stress. Hawthorn (Crataegus pinnatifida) fruit has been widely used as a hypolipidemic agent in traditional herbal medicine. The study aimed to investigate whether high fructose-induced pancreatic β-cell dysfunction could be reversed through amelioration of ER stress by the treatment of polyphenol-enriched extract (PEHE) from hawthorn fruit. The extract was partitioned using ethyl acetate as a solvent from crude water extract (WE) of hawthorn fruits, followed by column fractionation. The results showed that the contents of total polyphenols, flavonoids and triterpenoids in PEHE could be enhanced by 2.2-, 7.7- and 1.1-fold, respectively, in comparison to the original obtained WE from hawthorn fruit. In ER stress studies, a sharp increase in the inhibitory activity on the gene expression levels of GRP79, ATF6, IRE1α and CHOP involved in ER stress was evident when dosages of PEHE at 50–100 μg/mL were used against high-fructose (150 mM)-treated cells. HPLC–MS/MS analysis showed that polyphenols and flavonoids collectively accounted for 87.03% of the total content of PEHE.

The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p < 0.05). The serum total and low-density lipoprotein (LDL) cholesterol levels were significantly elevated in the OVX group, whereas the hawthorn groups showed a significant decrease in these levels (p < 0.05). The hepatic triglyceride (TG) and malondialdehyde (MDA) levels were significantly reduced in the hawthorn groups compared with the OVX group (p < 0.05). The mRNA expression of nuclear factor erythroid 2–related factor (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase (GPx) were significantly decreased in the OVX group, whereas the hawthorn groups exhibited a significant increase in expression (p < 0.05). The protein expressions of Nrf2, HO-1, and GPx were lower in the OVX group than the Sham group (p < 0.05). The oral administration of hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system.