Isoflavone Derivatives as Potential Anticancer Agents: Synthesis and Bioactivity Studies.

Isoflavones are phenolic natural compounds with a C6C3C6 framework. They possess a plethora of biological activities that are associated with putative benefits to human health. In particular, the cancer chemopreventive and chemotherapeutic potential of isoflavones has attracted the interest of researchers. Several isoflavone derivatives have been synthesised and probed for their anticancer activities. The isoflavone analogues are mainly synthesised by molecular hybridisation and other strategies that enable diversification through early or late-stage functionalisation of A-, B- and C-rings of the isoflavones. This has resulted in the discovery of isoflavone analogues with improved antiproliferative activities against several cancer cells and different mechanisms of action. In this review, the synthesis of isoflavone derivatives and their anticancer activity studies are discussed.

UV-B Radiation Exhibited Tissue-Specific Regulation of Isoflavone Biosynthesis in Soybean Cell Suspension Cultures.

Isoflavones, a class of substances with high biological activity, are abundant in soybeans. This study investigated isoflavone biosynthesis in soybean cell suspension cultures under UV-B radiation. UV-B radiation enhanced the transcription level and activity of key enzymes involved in isoflavone synthesis in cell suspension cultures. As a result, the isoflavone contents significantly increased by 19.80% and 91.21% in hypocotyl and cotyledon suspension cultures compared with the control, respectively. Meanwhile, a significant difference was observed in the composition of isoflavones between soybean hypocotyl and cotyledon suspension cultures. Genistin was only detected in hypocotyl suspension cultures, whereas glycitin, daidzein, and genistein accumulated in cotyledon suspension cultures. Therefore, UV-B radiation exhibited tissue-specific regulation of isoflavone biosynthesis in soybean cell suspension cultures. The combination of suspension cultures and abiotic stress provides a novel technological approach to isoflavone accumulation.

Impact of Lactobacillus acidophilus and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model.

Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.

Equol: a metabolite of gut microbiota with potential antitumor effects.

An increasing number of studies have shown that the consumption of soybeans and soybeans products is beneficial to human health, and the biological activity of soy products may be attributed to the presence of Soy Isoflavones (SI) in soybeans. In the intestinal tracts of humans and animals, certain specific bacteria can metabolize soy isoflavones into equol. Equol has a similar chemical structure to endogenous estradiol in the human body, which can bind with estrogen receptors and exert weak estrogen effects. Therefore, equol plays an important role in the occurrence and development of a variety of hormone-dependent malignancies such as breast cancer and prostate cancer. Despite the numerous health benefits of equol for humans, only 30-50% of the population can metabolize soy isoflavones into equol, with individual variation in gut microbiota being the main reason. This article provides an overview of the relevant gut microbiota involved in the synthesis of equol and its anti-tumor effects in various types of cancer. It also summarizes the molecular mechanisms underlying its anti-tumor properties, aiming to provide a more reliable theoretical basis for the rational utilization of equol in the field of cancer treatment.

Can Isoflavone-Rich Legume Plants Be Useful in the Chemoprevention of Hormone-Dependent Cancers?-A Systematic Review.

Plants from the Fabaceae family are widely distributed around the world, especially in Europe, Asia and North America. They are a rich source of isoflavones, compounds with estrogen-like activity, which are suspected of having a chemopreventive effect against hormone-dependent cancers. Following the PRISMA guidelines, we conducted a systematic review aimed at assessing the impact of Fabaceae plant extracts on hormone-dependent cancer cells and the content of active compounds in plant raw materials. We analyzed the results of 63 articles from in vitro and in vivo studies describing the effect of plant extracts containing isoflavones on cancer cells, along with their anti-inflammatory and antioxidant potential. In the process, we determined the research limitations and future research directions. The collected results indicate the plant species with potentially high contents of phytoestrogens and anti-inflammatory, antioxidant and cytotoxic properties. They point to the potential use of plants in the diet as a source of compounds offering cancer prevention.

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

Potential therapeutic properties of broccoli extract and soy isoflavones on improvement endometriosis and involved oxidative parameters.

OBJECTIVES: In Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity that is associated with chronic pelvic pain and subfertility. The purpose of the study was to investigate the effect of broccoli extract (BE) alone and in combination with soy isoflavones (SI) on endometrial implants in female rat. METHODS: In this study, endometriosis was induced surgically in 40 mature female rats. The rats were divided into 5 groups that were treated by oral gavage for 6 weeks with 0.5 mL of saline 0.9 %/day (control group), BE (3,000 mg/kg/day), SI (50 mg/kg/day), BE/soy isoflavones (BE 3000 mg/kg/day + soy isoflavones 50 mg/kg/day) and diphereline as a standard medication (3 mg/kg) intramuscularly. At the end of treatments, the volume and histopathology of the endometrial implants were compared among the 5 groups. The serum levels of oxidative parameters including superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) were also compared between the groups. The volume of the implants significantly decreased in diphereline group (p=0.002). RESULTS: The histopathological grade of endometrial implants in BE/SI and diphereline group were significantly decreased compared to the control group (p=0.001). The serum levels of SOD in BE group were enhanced significantly in comparison to the control group (p=0.034). CONCLUSIONS: BE in combination with SI decreased the growth and histopathologic grades of transplanted endometrial implants. These herbal compounds may have the potential therapeutic effect to be used as an alternative medication for the treatment of endometriosis.

Endometriosis happens when tissue similar to the uterus tissue grows outside of the uterus. It can be associated with severe pelvic pain and make several difficulties to get pregnant. Since the use of hormonal drugs is prohibited when planning to get pregnant and due to the common recurrence of lesions after surgery, scientists have been encouraged to study regarding the efficacies of natural products on improvement of endometriosis. In this study, it is represented that the dietary consumption of broccoli extract combined with soy isoflavones may have potential beneficial properties on clinical symptoms of endometriosis.

Mass Yields, Antioxidant and Anti-DU145 Prostate Cancer Cell Proliferation Properties of ProSoy Soymilk as Affected by Extraction Methods and Cooking.

Both the soybean variety and processing method affect the end soybean product's characteristics. This study's objective was to characterize the effects of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances and the antioxidant and anti-DU145 prostate cancer cell proliferation properties of soymilks prepared from a yellow soybean of the ProSoy variety, which is a high-protein variety. The results showed that the soymilk processing yield was the greatest using method 4, although method 2 gave the highest solid and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding method, also gave increased yields (8 and 7% for solids and proteins, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), and total isoflavone content values in both raw and cooked soymilks as compared to method 1. Cooking the soymilks reduced 14-17% of their total phenolic substances. Cooking reduced the anti-cancer capacity of the phenolic extracts from the soymilk prepared using method 4 by increasing the IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in the Prosoy soymilks using methods 2 and 4, with simultaneous increases in product and solid yields, are of significant benefit to the soymilk industry and consumer health.

Flavonoids and their relationship with the physiological quality of seeds from different soybean genotypes.

Flavonoids are compounds that result from the secondary metabolism of plants and play a crucial role in plant development and mitigating biotic and abiotic stresses. The highest levels of flavonoids are found in legumes such as soybean. Breeding programs aim to increase desirable traits, such as higher flavonoid contents and vigorous seeds. Soybeans are one of the richest sources of protein in the plant kingdom and the main source of flavonoid derivatives for human health. In view of this, the hypothesis of this study is based on the possibility that the concentration of isoflavones in soybean seeds contributes to the physiological quality of the seeds. The aim of this study was to analyze the content of flavonoids in soybean genotypes and their influence on the physiological quality of the seeds. Seeds from thirty-two soybean genotypes were obtained by carrying out a field experiment during the 2021/22 crop season. The experimental design was randomized blocks with four replications and thirty-two F3 soybean populations. The seeds obtained were subjected to germination, first germination counting, electrical conductivity and tetrazolium vigor and viability tests. After drying and milling the material from each genotype, liquid chromatography analysis was carried out to obtain flavonoids, performed at UPLC level. Data were submitted to analysis of variance and, when significant, the means were compared using the Scott-Knott test at 5% probability. The results found here show the occurrence of genotypes with higher amounts of flavonoids when compared to their peers. The flavonoid FLVD_G2 had the highest concentration and differed from the others. Thus, we can assume that the type and concentration of flavonoids does not influence the physiological quality of seeds from different soybean genotypes, but it does indirectly contribute to viability and vigor, since the genotypes with the highest FLVD_G2 levels had better FGC values. The findings indicate that there is a difference between the content of flavonoids in soybean genotypes, with a higher content of genistein. The content of flavonoids does not influence the physiological quality of seeds, but contributes to increasing viability and vigor.

Widely Targeted Metabolomics Provides New Insights into Nutritional Profiling and Reveals the Flavonoid Pathway of Pea (Pisum sativum L.).

To learn more about the nutritional composition and health benefits for human consumers of peas, we used a widely targeted metabolomics-based approach to reveal the metabolite components from three main varieties, and a total of 1095 metabolites were identified. A comparison of 487 differentially accumulated metabolites shared among three varieties of fresh and dried peas found most of the amino acids and derivatives were downregulated and most of the lipids and flavonoids were upregulated in dried peas. Furthermore, comparing the main nutrient profiles exclusively showed that there were few differences in free fatty acids, sugars, vitamins, and alkaloids between dried and fresh peas. Peas are especially enriched with B-group vitamins. Through detailed identification and classification, the flavonoid pathway of peas was revealed; a variety of glycosylated derivatives from kaempferol, quercetin, and luteolin were confirmed to be abundant in peas. It was also found that isoflavones are richer in peas than in many other plants, and putatively the isoflavone synthesis pathway originates from liquiritigenin and naringenin. Our study not only offers guidance for understanding the nutritional components of peas, but also provides the basis for healthy diet analysis of the edible value and health benefits of peas.

Effect of Origin, Seed Coat Color, and Maturity Group on Seed Isoflavones in Diverse Soybean Germplasm.

Soybeans are grown worldwide owing to their protein, oil, and beneficial bioactive compounds. Genetic and environmental factors influence soybean seed isoflavones. In the present study, we profiled the seed isoflavones in world diverse soybean germplasm grown in two locations over two years in China. Significant differences (p < 0.001) were observed between the accessions, accession origins, seed coat colors, and maturity groups for individual and total isoflavone (TIF) content. TIF content of the soybean accessions ranged from 677.25 µg g-1 to 5823.29 µg g-1, representing an 8-fold difference. USA soybean accessions showed the highest mean TIF content (3263.07 µg g-1), followed by Japan (2521.26 µg g-1). Soybean with black seed coat showed the highest (3236.08 µg g-1) TIF concentration. Furthermore, isoflavone levels were significantly higher in late-maturity groups. Correlation analysis revealed significant positive associations between individual and TIF content. Malonyldaidzin and malonylgenistin showed higher correlations with TIF content (r = 0.92 and r = 0.94, respectively). The soybean accessions identified as having high and stable TIF content can be utilized in the food and pharmaceutical industries and breeding programs to develop soybean varieties with enhanced isoflavone content.

[Soy isoflavones alleviates calcium overload in rats with cerebral ischemia-reperfusion by inhibiting the Wnt/Ca2+ signaling pathway].

OBJECTIVE: To explore the mechanism by which soybean isoflavone (SI) reduces calcium overload induced by cerebral ischemia-reperfusion (I/R). METHODS: Forty-eight SD rats were randomized into 4 groups to receive sham operation, cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion (I/R model group), or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+ signaling pathway.Calcium levels and pathological changes in the ischemic penumbra (IP) were measured using calcium chromogenic assay and HE staining, respectively.Another 72 SD randomly allocated for sham operation, I/R modeling, or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter, and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining, and ROS level, Ca2+ level, cell apoptosis, and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry; the protein expressions of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP were detected with Western blotting and immunohistochemistry. RESULTS: In rats with cerebral I/R, Frizzled-2 knockdown significantly lowered calcium concentration (P < 0.001) and the expression levels of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP area.In soy isoflavones-pretreated rats, calcium concentration, ROS and MDA levels, cell apoptosis rate, cerebral infarct volume, and expression levels of Wnt/Ca2+ signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group. CONCLUSION: Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+ signaling pathway.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults.

BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Germination time and in vitro gastrointestinal digestion impact on the isoflavone bioaccessibility and antioxidant capacities of soybean sprouts.

Soybeans' isoflavone content increases with germination; nevertheless, their bioaccessibility in the gastrointestinal system is limited. This study evaluated the influence of germination time (1, 3, 5, and 7 days) and in vitro gastrointestinal conditions on the isoflavone profile of soybean sprouts. The total isoflavones (4.07 mg/g) and the malonyl genistin (1.37 mg/g) had the highest contents on day 5 in the gastric phase. The highest isoflavone bioaccessibility was observed in daidzein, genistein, and glycitin. An increase in antioxidant capacity was found during germination (day 7 > day 5 > day 3); however, the same trend was not observed during in vitro digestion. In summary, the results indicate that soybean sprouts germinated for 5 days may be more beneficial for consumption since they have the highest and most readily absorbed levels of isoflavones. These data suggest that soybean sprouts may be a functional food that provides bioavailable antioxidants.

Protective effect of flavonoids on oxidative stress injury in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, which is mainly caused by the damage of the structure and function of the central nervous system. At present, there are many adverse reactions in market-available drugs, which can't significantly inhibit the occurrence of AD. Therefore, the current focus of research is to find safe and effective therapeutic drugs to improve the clinical treatment of AD. Oxidative stress bridges different mechanism hypotheses of AD and plays a key role in AD. Numerous studies have shown that natural flavonoids have good antioxidant effects. They can directly or indirectly resist -oxidative stress, inhibit Aß aggregation and Tau protein hyperphosphorylation by activating Nrf2 and other oxidation-antioxidation-related signals, regulating synaptic function-related pathways, promoting mitochondrial autophagy, etc., and play a neuroprotective role in AD. In this review, we summarised the mechanism of flavonoids inhibiting oxidative stress injury in AD in recent years. Moreover, because of the shortcomings of poor biofilm permeability and low bioavailability of flavonoids, the advantages and recent research progress of nano-drug delivery systems such as liposomes and solid lipid nanoparticles were highlighted. We hope this review provides a useful way to explore safe and effective AD treatments.

Dynamic changes on sensory property, nutritional quality and metabolic profiles of green kernel black beans during Eurotium cristatum-based solid-state fermentation.

Eurotium cristatum, a unique probiotic in Fu brick tea, is widely used in food processing to enhance added values. Here, green kernel black beans (GKBBs) were solid-fermented with E. cristatum and dynamic changes in flavour, chemical composition and metabolites during fermentation were investigated. As results, E. cristatum fermentation altered aroma profiles and sensory attributes of GKBBs, especially reduced sourness. After fermentation, total polyphenolic and flavonoid contents in GKBBs were elevated, while polysaccharides, soluble proteins and short-chain fatty acids contents were decreased. E. cristatum fermentation also induced biotransformation of glycosidic isoflavones into sapogenic isoflavones. During fermentation, dynamic changes in levels of 17 amino acids were observed, in which 3 branched-chain amino acids were increased. Non-targeted metabolomics identified 51 differential compounds and 10 related metabolic pathways involved in E. cristatum fermentation of GKBBs. This study lays foundation for the development of green kernel black bean-based functional food products with E. cristatum fermentation.

Urinary Equol and Equol-Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults.

BACKGROUND: The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers. METHODS AND RESULTS: In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 µg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all P<0.05), and 0.61% increase in high-density lipoprotein cholesterol (P=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; Ptrend=0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected P<0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all P<0.05). CONCLUSIONS: Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.

Preparation and Evaluation of the Biological Properties of Ethanolic Extract of Red Clover: An In Vitro Study.

INTRODUCTION: Red clover, a perennial herbaceous plant, has been demonstrated to possess blood-purifying, expectorant, and calming properties. This research endeavors to create and evaluate the antimicrobial, antioxidant characteristics, and cytotoxic effects of the ethanolic extract derived from red clover. METHODS: A water-based solution of red clover was formulated and subjected to centrifugation. Various concentrations of the extract were applied to the wells of agar plates inoculated with E. coli, Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Candida albicans and then left to incubate. The inhibition zones for each concentration were subsequently measured. The antioxidant properties were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while the cytotoxicity of the extract was assessed through the brine shrimp lethality assay. RESULTS: Initially, the extract was tested with a volume of 10 µL, which was subsequently incremented to 20 µL, 30 µL, 40 µL, and 50 µL. According to the DPPH assay, as the concentration of the extract solution increased incrementally by 10 µL, its antioxidant activity also exhibited a corresponding rise. The cytotoxicity assay indicated that the mouthwash formulated with red clover had minimal cytotoxic effects within the range of 5-20 µL. Antibacterial analysis revealed a similar zone of inhibition between the test and control groups. CONCLUSION: The ethanolic extract obtained from red clover was identified as a powerful antioxidant, antibacterial, and biocompatible substance. Hence, it can be a potential candidate for application as a mouthwash.

Chemical Compositions before and after Lactic Acid Fermentation of Isoflavone-Enriched Soybean Leaves and Their Anti-Obesity and Gut Microbiota Distribution Effects.

In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects on gut microbiota. Fermented IESLs (FIESLs) were found to be rich in nutrients, especially lauric acid, oleic acid, and linoleic acid. In addition, the concentrations of most essential free amino acids were increased compared to those of IESLs. The contents of bioactive compounds, such as total phenolic, total flavonoid, daidzein, and genistein, significantly increased as well. In addition, FIESLs administration in a high-fat diet (HFD) animal model improved the final body weight, epididymal fat, total lipid, triglyceride, total cholesterol, blood glucose, and leptin levels, as well as reverting microbiota dysbiosis. In conclusion, these findings indicate that FIESLs have the potential to inhibit obesity caused by HFDs and serve as a modulator of gut microbiota, offering the prevention of diet-induced gut dysbiosis and metabolite diseases associated with obesity.

Total Syntheses and Antibacterial Studies of Natural Isoflavones: Scandenone, Osajin, and 6,8-Diprenylgenistein.

Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (1), osajin (2), and 6,8-diprenylgenistein (3) are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate 15 was used for the synthesis of the natural isoflavones 1-3, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of 1-3 were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, 2 was the most potent one against MRSA, with a MIC value of 2 µg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and E. faecalis could be disrupted by 2. These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.