Destabilisation of Alzheimer's amyloid-ß protofibrils by Baicalein: mechanistic insights from all-atom molecular dynamics simulations.

Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death globally. Aggregation and deposition of neurotoxic Aß fibrils in the neural tissues of the brain is a key hallmark in AD pathogenesis. Destabilisation studies of the amyloid-peptide by various natural molecules are highly relevant due to their neuroprotective and therapeutic potential for AD. We performed molecular dynamics (MD) simulation to investigate the destabilisation mechanism of amyloidogenic protofilament intermediate by Baicalein (BCL), a naturally occurring flavonoid. We found that the BCL molecule formed strong hydrophobic contacts with non-polar residues, specifically F19, A21, V24, and I32 of Chain A and B of the pentameric protofibril. Upon binding, it competed with the native hydrophobic contacts of the Aß protein. BCL loosened the tight packing of the hydrophobic core by disrupting the hydrogen bonds and the prominent D23-K28 inter-chain salt bridges of the protofibril. The decrease in the structural stability of Aß protofibrils was confirmed by the increased RMSD, radius of gyration, solvent accessible surface area (SASA), and reduced ß-sheet content. PCA indicated that the presence of the BCL molecule intensified protofibril motions, particularly affecting residues in Chain A and B regions. Our findings propose that BCL would be a potent destabiliser of Aß protofilament, and may be considered as a therapeutic agent in treating AD.

Heterocyclic Phytochemicals as Anticancer Agents.

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Dry-feed Added Quercetin Mitigates Cyclophosphamide-induced Oxidative Stress, Inflammation and Gonadal Fibrosis in Adult Male Rats.

BACKGROUND: Cyclophosphamide (CYP), a widely used cancer chemotherapeutic agent has been linked with male gonadotoxicity, resulting in infertility. The notion that potent antioxidants could be beneficial in mitigating CYP-induced gonadotoxicity necessitated this research. Therefore, we examined the effects of feed-added quercetin on CYP-induced gon-adotoxicity in male rats. METHODS: Male postpubertal rats were randomly assigned into six groups of 10 rats each. The normal control (fed standard rodent diet) and two groups fed quercetin-supplemented diet at 100 and 200 mg/kg of feed received normal saline intraperitoneally at 2 ml/kg daily. A fourth group which served as the CYP control (fed standard rodent diet) and the last two groups fed quercetin at 100 and 200 mg/kg of feed were administered CYP at 150 mg/kg/day. Rats were administered normal saline or CYP intraperitoneally on days 1 and 2, while standard diet or feed-added quercetin was administered daily for 21 days. On day 22, half of the animals were either sacrificed or paired with age-matched females for fertility assessment. Estimation of testosterone levels, antioxidant, anti-inflammatory markers, and histomorphological exami-nation of the testis and epididymis was also assessed. RESULTS: The administration of CYP was associated with weight loss, decreased food intake, decreased antioxidant capacity, increased gonadosomatic index, increased lipid peroxidation, sub-fertility, and histological evidence of gonadal injury. However, administration of querce-tin reversed CYP-induced changes. CONCLUSION: The result of this study suggests that dietary quercetin supplementation has the ability to mitigate CYP induced gonadotoxicity and mitigate subfertility in male rats. How-ever, further studies are required to assess its possible use in humans.

Carob seeds as a source of bioactive flavonoid derivatives: isolation, network pharmacology-guided anti-cancer activity, and HPLC standardization.

INTRODUCTION:  Carob, Ceratonia siliqua L. (CS), is a legume well-known for its edible pod pulp. Its seeds are used almost exclusively as a source of the food additive E410. Although a variety of metabolites have been identified by HPLC and LC-MS analysis in CS, reports concerned with their isolation are scarce.   Methodology: In this study, two flavonoid derivatives were isolated from the methanolic extract of CS seeds, namely, quercetin-3-O-rhamnoside and 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside. Network pharmacology was unusually used as a guide for estimation of the biological potential of the isolated compounds. Finally, the methanolic extract of CS seeds and its ethyl acetate fraction were standardized for their 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside content by HPLC. RESULTS:  The identified isolates displayed the ability to interfere with the activity of several target proteins associated with renal and colon cancers. Their cytotoxic effect on renal and colorectal cancer cell lines was investigated in comparison to Doxorubicin. The selectivity of the isolated compounds was evaluated on normal human fetal fibroblast cell lines. The isolated 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside showed very potent cytotoxic activity against the tested cell lines with the highest selectivity. CONCLUSION:  CS seeds can be used as a source of bioactive flavonoid derivatives that can be incorporated in pharmaceutical industries.

An Updated Review Summarizing the Pharmaceutical Efficacy of Genistein and its Nanoformulations in Ovarian Carcinoma.

Implementing lifestyle interventions as a primary prevention strategy is a cost-effective approach to reducing the occurrence of cancer, which is a significant contributor to illness and death globally. Recent advanced studies have uncovered the crucial role of nutrients in safeguarding women's health and preventing disorders. Genistein is an abundant isoflavonoid found in soybeans. Genistein functions as a chemotherapeutic drug against various forms of cancer, primarily by modifying apoptosis, the cell cycle, and angiogenesis and suppressing metastasis. Furthermore, Genistein has demonstrated diverse outcomes in women, contingent upon their physiological characteristics, such as being in the early or postmenopausal stages. The primary categories of gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar cancers. Understanding the precise mechanism by which Genistein acts on ovarian cancer could contribute to the advancement of anti-breast cancer treatments, particularly in situations where no specific targeted therapies are currently known or accessible. Additional investigation into the molecular action of Genistein has the potential to facilitate the development of a plant-derived cancer medication that has fewer harmful effects. This research could also help overcome drug resistance and prevent the occurrence of ovarian cancers.

Evaluation of the effect of dietary supplementation with Allium mongolicum regel bulb powder on the volatile compound and lipid profiles of the longissimus thoracis in Angus calves based on GC-IMS and lipidomic analysis.

The effect of A. mongolicum Regel bulb powder (AMRP) supplementation on the flavour of beef from Angus calves has not been investigated thus far. We used GC-IMS and untargeted lipidomics techniques to examine the volatile compound and lipid metabolic profiles and reveal the effects of dietary AMRP supplementation on the flavour of beef. A total of 6 characteristic volatile compounds and 30 key lipid compounds were identified in the AMRP treatment group. AMRP promoted the release of triglycerides and phosphatidylinositols from beef and accelerated the production of volatile compounds such as ethyl acetate, 1-penten-3-one, and tetrahydrofurane, and the production of these three characteristic volatile compounds was significantly correlated with the UFAs in triglycerides according to correlation analysis. In summary, dietary AMRP supplementation had a positive effect on the flavour of beef, and these findings provide a theoretical basis for the development and utilisation of AMRP as a feed additive.

GmSTOP1-3 regulates flavonoid synthesis to reduce ROS accumulation and enhance aluminum tolerance in soybean.

Aluminum (Al) toxicity is a significant limiting factor for crop production in acid soils. The functions and regulatory mechanisms of transcription factor STOP1 (Sensitive to Proton Rhizotoxicity 1) family genes in Al-tolerance have been widely studied in many plant species, except for soybean. Here, expression of GmSTOP1-3 was significantly enhanced by Al stress in soybean roots. Overexpression of GmSTOP1-3 resulted in enhanced root elongation and decreased Al content, which was accompanied by increased antioxidant capacity under Al treatment. Furthermore, RNA-seq identified 498 downstream genes of GmSTOP1-3, including genes involved in flavonoid biosynthesis. Among them, the expression of chalcone synthase (GmCHS) and isoflavone synthase (GmIFS) were highly enhanced by GmSTOP1-3 overexpression. Further quantitative flavonoid metabolome analysis showed that overexpression of GmSTOP1-3 significantly increased the content of naringenin chalcone, naringenin, and genistein in soybean roots under Al treatment, which positively correlated with the expression level of the genes relative to flavonoid biosynthesis. Notably, genistein had a significant positive correlation with the expression levels of GmIFS. Combination of Dual Luciferase Complementation (LUC) and Electrophoretic Mobility Shift Assays (EMSA) revealed that GmSTOP1-3 directly bound to the promoters of GmCHS/GmIFS and activated both genes' transcription. Taken together, these results suggest that GmSTOP1-3 enhances soybean Al tolerance partially through regulating the flavonoid synthesis.

Flavonoids, gut microbiota and cardiovascular disease: Dynamics and interplay.

Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Extensive efforts have been invested to explicate mechanisms implicated in the onset and progression of CVD. Besides the usual suspects as risk factors (obesity, diabetes, and others), the gut microbiome has emerged as a prominent and essential factor in the pathogenesis of CVD. With its endocrine-like effects, the microbiome modulates many physiologic processes. As such, it is not surprising that dysbiosis-by generating metabolites, inciting inflammation, and altering secondary bile acid signaling- could predispose to or aggravate CVD. Nevertheless, various natural and synthetic compounds have been shown to modulate the microbiome. Prime among these molecules are flavonoids, which are natural polyphenols mainly present in fruits and vegetables. Accumulating evidence supports the potential of flavonoids in attenuating the development of CVD. The ascribed mechanisms of these compounds appear to involve mitigation of inflammation, alteration of the microbiome composition, enhancement of barrier integrity, induction of reverse cholesterol transport, and activation of farnesoid X receptor signaling. In this review, we critically appraise the methods by which the gut microbiome, despite being essential to the human body, predisposes to CVD. Moreover, we dissect the mechanisms and pathways underlying the cardioprotective effects of flavonoids.

Arbuscular Mycorrhizal Fungi Ameliorate Selenium Stress and Increase Antioxidant Potential of Zea mays in Seleniferous Soil.

The indigenous arbuscular mycorrhizal fungi (AMF) spores were isolated from rhizosphere soil associated with maize plants grown in natural selenium-impacted agricultural soils present in north-eastern region of Punjab, India (32°46' N, 74°46' N), with selenium concentration ranging from 2.1 to 6.1 mg kg-1 dry weight, and their role in plant growth promotion, mitigation of selenium stress and phytochemical and antioxidant potential of host maize plants in natural seleniferous soil were examined. Soils with selenium content between 2 and 200 mg kg-1 and producing plants with 45 mg selenium kg-1 dry weight are considered seleniferous soils. AMF inoculum consisting of indigenous AMF spores multiplied in pot cultures were inoculated to maize seeds at the time of sowing alongside control maize seeds in a total of 12 plots (6 replicates) made in seleniferous agricultural fields and sampled at maturity, i.e. 3 months. A significant difference was observed in plant growth parameters between control and AMF-inoculated maize plants. AMF-inoculated plants had 24.0 cm and 101.1 cm higher root and shoot length along with 27.2 g, 119.4 g and 28.1 g higher root, shoot and maize cob biomass in comparison to control plants. Se uptake studies through measurement of the emission spectrum of piazselenol complex by fluorescence spectrometry revealed that AMF inoculation led to 6.3 µg g-1 more selenium accumulation in mycorrhizal maize roots in comparison to control roots but lesser translocation to shoots and seeds, i.e. 17.17 µg g-1 and 19.58 µg g-1 lesser. AMF increased total phenolic content by 13 µg GAE mg-1 and total flavonoid content by 13.4 µg QE mg-1 in inoculated maize plants when compared to control plants. Antioxidant studies revealed that AMF inoculation also led to significant rise in enzyme activities by a difference of 115 and 193 EU g-1 in catalase, 140 and 93 EU g-1 in superoxide dismutase, 15 and 37 EU g-1 in ascorbate peroxidase and 19.8 and 23.6% higher DPPH radical scavenging activities, respectively, in shoots and roots of plants with AMF inoculation. The findings of this study imply that AMF inoculated to maize plants in seleniferous field boost their plant growth and phytochemical and antioxidant properties, as well as minimize Se bioaccumulation in shoots and seeds of plants inoculated with AMF in comparison to control plants.

Flavonoid-Rich Fruit Intake in Midlife and Late-Life and Associations with Risk of Dementia: The Framingham Heart Study.

BACKGROUND: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults. OBJECTIVES: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia. DESIGN: Longitudinal, cohort study design. SETTING: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA. PARTICIPANTS: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams. MEASUREMENTS: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer's disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148). RESULTS: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 - 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only. CONCLUSIONS: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course.

In Vitro Antioxidant Activity and Anticonvulsant Properties on Zebrafish PTZ-Induced Seizure Model of a Tilia viridis Aqueous Extract.

Objectives: Tilia viridis (Bayer) Simonk. (Malvaceae) is widely distributed in Argentina and employed for its tranquilizing properties. Other species of the genus (Tilia europaea L., Tilia cordata Mill., Tilia platyphyllos Scop.) have been traditionally used for the treatment of epilepsy. Epilepsy affects approximately 65 million people worldwide and is characterized by an imbalance between excitatory and inhibitory processes in the brain, leading to unpredictable, unprovoked, recurrent seizures. Current pharmacological interventions often present mild to moderately severe side effects. Epilepsy has been associated with oxidative and nitrative stress as well as neuroinflammation. Herbal medicine therapies may offer new treatment options with multi-target antioxidant and anticonvulsant effects for patients whose seizures remain uncontrolled, potentially providing cost-effective solutions for individuals worldwide suffering from uncontrolled epilepsy.The aim of this study was to demonstrate the anticonvulsant activity of a standardized T. viridis aqueous extract (TE). Methods: Study of the constituents of TE, TE's antioxidant and anticonvulsant activities and toxicity, and analysis of the possible relation between the potential activities and the compounds present in the extract. In order to demonstrate TE's anticonvulsant activity a zebrafish model was used. The study also assessed TE's toxicity and antioxidant activity. To standardize the extract, total polyphenols and flavonoids were quantified and specific flavonoids were identified and quantified using HPLC-MS/MS and HPLC-UV. Results: TE exhibited anticonvulsant activity at low concentrations and demonstrated antioxidant effects by scavenging free radicals, exhibiting superoxide dismutase and peroxidase-like activities, as well as inhibiting lipoperoxidation. These actions can be attributed to the presence of polyphenols, particularly flavonoids. Conclusion: TE holds promise as a complementary herbal medicine in the treatment of epilepsy and may also offer benefits for other neuropathies associated with oxidative stress, such as Parkinson's disease and Alzheimer's disease.

Pilot study on the effect of flavonoids on arterial stiffness and oxidative stress in chronic kidney disease.

BACKGROUND: Flavonoids, the main class of polyphenols, exhibit antioxidant and antihypertensive properties. AIM: To prospectively investigate the impact of flavonoids on arterial stiffness in patients with chronic kidney disease (CKD) stages I-IV. METHODS: In this prospective, single-arm study, CKD patients with arterial hypertension and diabetes mellitus were enrolled. Baseline demographic, clinical, and laboratory variables were recorded. Patients received daily treatment with a phenol-rich dietary supplement for 3 months. Blood pressure, arterial stiffness (carotid-femoral pulse wave velocity, central pulse pressure), and oxidative stress markers (protein carbonyls, total phenolic compound, total antioxidant capacity) were measured at baseline and at study end. RESULTS: Sixteen patients (mean age: 62.5 years, 87.5% male) completed the study. Following intervention, peripheral systolic blood pressure decreased significantly by 14 mmHg (P < 0.001). Carotid-femoral pulse wave velocity decreased from 8.9 m/s (baseline) to 8.2 m/s (study end) (P < 0.001), and central pulse pressure improved from 59 mmHg to 48 mmHg (P = 0.003). Flavonoids also reduced oxidative stress markers including protein carbonyls (P < 0.001), total phenolic compound (P = 0.001), and total antioxidant capacity (P = 0.013). CONCLUSION: Flavonoid supplementation in CKD patients shows promise in improving blood pressure, arterial stiffness, and oxidative stress markers.

Bioassay-guided isolation and structure elucidation of anti-mycobacterium tuberculosis compounds from Galatella grimmii (Regel & Schmalh.) Sennikov.

BACKGROUND: Galatella is a genus in the family Asteraceae, represented by 35-45 species. Considering the high effectiveness of the ethyl acetate (EtOAc) fraction of G. grimmii against Mycobacterium tuberculosis (MIC = 0.5 µg/mL), a bioassay-directed fractionation of this extract was carried out. METHODS: The methanolic extract of the aerial parts of G. grimmii was obtained using maceration, then it was suspended in water and partitioned with petroleum ether, dichloromethane (CH2Cl2), EtOAc, and n-butanol (n-BuOH), successively. The most potent fraction (EtOAc), was selected for further isolation by Sephadex LH-20 and semi-preparative HPLC to obtain active compounds. RESULTS: Fractionation of the EtOAc solvent fraction resulted in the characterization of five compounds, among them, compounds 1 and 2 showed the highest anti-mycobacterial effects with MICs of 0.062 and 1.00 µg/mL against H37Rv M. tuberculosis, respectively, which were higher than those of rifampin (MIC of 1.25 µg/mL) and isoniazid (MIC of 0.31 µg/mL), as positive controls. Also, compound 1 ​​inhibited all tested strains of drug-resistant Mycobacterium (MDR and XDR). Notably, the isolated compounds have been reported for the first time from G. grimmii. CONCLUSION: Due to the potent anti-mycobacterial effect of isolated compounds from G. grimmii, this study could pave the way for developing a novel class of natural anti-tuberculosis compounds.

Inoculation with Jeotgalicoccus sp. improves nutritional quality and biological value of Eruca sativa by enhancing amino acid and phenolic metabolism and increasing mineral uptake, unsaturated fatty acids, vitamins, and antioxidants.

Plant growth-promoting bacteria (PGPB) are considered a promising tool for triggering the synthesis of bioactive compounds in plants and to produce healthy foods. This study aimed to demonstrate the impact of PGPB on the growth, accumulation of primary and secondary metabolites, biological activities, and nutritional qualities of Eruca sativa (arugula), a key leafy vegetable worldwide. To this end, Jeotgalicoccus sp. (JW0823), was isolated and identified by using partial 16S rDNA-based identification and phylogenetic analysis. The findings revealed that JW0823 significantly boosted plant biomass production by about 45% (P<0.05) and enhanced pigment contents by 47.5% to 83.8%. JW0823-treated plants showed remarkable improvements in their proximate composition and vitamin contents, with vitamin E levels increasing by 161.5%. JW0823 induced the accumulation of bioactive metabolites including antioxidants, vitamins, unsaturated fatty acids, and essential amino acids, thereby improving the nutritional qualities of treated plants. An increase in the amounts of amino acids was recorded, with isoleucine showing the highest increase of 270.2%. This was accompanied by increased activity of the key enzymes involved in amino acid biosynthesis, including glutamine synthase, dihydrodipicolinate synthase, cystathionine γ-synthase, and phenylalanine ammonia-lyase enzymes. Consequently, the total antioxidant and antidiabetic activities of the inoculated plants were enhanced. Additionally, JW0823 improved antimicrobial activity against several pathogenic microorganisms. Overall, the JW0823 treatment is a highly promising method for enhancing the health-promoting properties and biological characteristics of E. sativa, making it a valuable tool for improving the quality of this important leafy vegetable.

Total flavonoids of Selaginella tamariscina (P. Beauv.) Spring ameliorates diabetes-induced acute lung injury via activating Nrf2/HO-1.

Objectives: This investigation explored the mechanism by which the total flavonoids of Selaginella tamariscina (P.Beauv.) Spring (TFST) mitigate oxidative stress through the activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), thereby ameliorating acute lung injury (ALI) induced by diabetes. Materials and Methods: Male mice weighing 20-25 grams were divided into four groups: a control group, a diabetic group, a diabetic group treated with TFST, and a diabetic group treated with TFST and ML385. Various biological specimens were collected for analysis, including bronchoalveolar lavage fluid (BALF), blood, and tissue samples. These were subjected to a range of assessments covering hematological and BALF parameters tumor necrosis factor-alpha (TNF-α), interleukin-6 [IL-6]), biochemical markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione peroxidase [GSH], Nrf2, and HO-1 levels), along with histopathological evaluations. Results: Pre-treatment with TFST demonstrated a significant decrease in pulmonary tissue damage, evidenced by decreased wet-to-dry (W/D) lung ratios (P<0.001), reduced lung injury scores (P<0.0001), and lower levels of TNF-α, IL-6 (P<0.0001), as well as oxidative stress markers like MDA (P<0.05). Moreover, there was an elevation in the activity of anti-oxidative enzymes, specifically SOD and GSH (P<0.05), coupled with an enhanced expression of Nrf2 and HO-1 in the diabetic group (P<0.01). Conclusion: The study findings demonstrate that TFST can suppress oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby ameliorating diabetes-induced acute lung injury.

Inhibitory mechanism on tyrosinase activity of flavonoids from flower buds of Sophora japonica L.

The flower buds of Sophora japonica L. (FBSJ) have long been applied as Traditional Chinese Medicine (TCM) and functional food in East Asia. In this study, extracts of FBSJ from 11 different locations were analyzed using the HPLC method to establish their HPLC fingerprints. By determining the IC50 on tyrosinase activity, it was discovered that the extract from Kunming, Yunnan Province exhibited the strongest inhibitory activity. Further analysis, including partial least squares regression coefficient analysis and grey correlation analysis, regarded kaempferol, isorhamnetin, and quercetin as the compounds with significant tyrosinase inhibitory activities. To understand the inhibition mechanism of tyrosinase activity, various analytical techniques such as enzymatic kinetic analysis, fluorescence quenching, circular dichroism (CD), molecular docking, and molecular dynamics simulation were employed. The results revealed that quercetin, isorhamnetin, and kaempferol exhibited higher inhibitory activity and binding energy compared with kojic acid, indicating their potential value as natural tyrosinase inhibitors. This research provides a solid theoretical foundation for studying the application and mechanism of flavonoids against tyrosinase in FBSJ.

Phenolic compounds from the aerial parts of Rhodiola rosea in Japan, and their antioxidant activity and chemical adaptation to alpine environment.

Twelve flavonoids (1-12) including a new flavonol glycoside, hibiscetin 3-O-glucopyranoside-8-O-glucuronopyranoside, ten known galloylglucoses (13-22) and three known phenolic acids (23-25) were isolated from the aerial parts of Rhodiola rosea growing in Japan. Their chemical structures were elucidated by UV-vis spectra, LC-MS, HR-MS, acid hydrolysis, NMR, and/or HPLC, and TLC comparisons with authentic samples. Antioxidant activity of major 14 compounds was measured by H-ORAC method, and two flavonols, herbacetin 3-O-glucoside-8-O-glucuronide, and gossypetin 3-O-glucuronide-8-O-glucoside, showed the strongest activity. Moreover, chemical adaptation to severe alpine environment of R. rosea was discussed.

Targeting insulin resistance: myricetin and isorhamnetin from Hardwickia binata, and luteolin from Hedysarum alpinum enhance glucose uptake and AMPK signaling in HepG2 cells.

This study examined five plants (Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum) for their potential to address insulin resistance in type 2 diabetes. In-vitro assays showed that H. binata leaves and H. alpinum flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in H. binata (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and H. alpinum (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that H. binata, H. alpinum, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.

Flavonoids from mulberry leaves exhibit sleep-improving effects via regulating GABA and 5-HT receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaf (Folium Mori) is a dried leaf of the dicotyledonous mulberry tree and is a homologous food and medicine. Treating insomnia with it is a common practice in traditional Chinese medicine. But still, its potential sleep-improving mechanism remains to be elucidated. AIM OF REVIEW: Potential bioactive components and mechanisms of the sleep-improving effect of purified flavone from mulberry leaves (MLF) were explored through in vivo experiments, network pharmacology analysis, and molecular experimental validation. MATERIALS AND METHODS: The mice model was established by pentobarbital sodium induction to evaluate the sleep-improving effect of MLF. The MLF's chemical composition was identified through a liquid chromatograph quadrupole time-of-flight mass spectrometer (Q-TOF LC/MS) to elucidate its sleep-improving active ingredient. At last, the underlying mechanism of MLF's sleep-improving effect was elucidated through neurotransmitter detection (ELISA), network pharmacology analysis, and molecular experimental validation (quantitative real-time PCR and western blotting). RESULTS: MLF could dramatically reduce sleep latency by 35%, prolong sleep duration by 123%, and increase the sleep rate of mice through increasing γ-aminobutyric acid (GABA) and serotonin (5-HT) release in serum, hypothalamus, and hippocampus. Q-TOF LC/MS identified 16 flavonoid components in MLF. Network pharmacological analysis suggested that the key sleep-improving active ingredients in MLF might be quercetin, kaempferol, morin, and delphinidin. The key path for MLF to improve sleep might be the tryptophan metabolism and neuroactive ligand-receptor interaction, and the key targets might be gamma-aminobutyric acid type A receptor subunit alpha2 Gene (GABRA2) and serotonin 1A (5-HT1A) receptors. CONCLUSIONS: MLF has shown significant sleep-improving effects in mice and may take effect through regulating the GABA and 5-HT receptors.

Antibacterial Activity of Glycosylated Flavonoids Isolated from Ocotea notata Leaves.

Research into natural products has led to the discovery of new drugs. This work shows relevant data on the antibacterial activity of Ocotea notata leaves. Dichloromethane fraction (DF) from leaves of O. notata showed antibacterial activity at the concentration of 512 µg/mL against strains of Staphylococcus. The DF was fractionated to investigate bioactive compounds and yielded six subfractions (DF1-DF6). The DF3, DF5, and DF6 showed bacteriostatic activity and DF4 showed bactericidal activity at the concentration of 2048 µg/mL and additive effect when combined with the antibiotic oxacillin. The flavonoids miquelianin (1), isoquercitrin (2), reynoutrin (3), guaijaverin (4), and afzelin (5) were isolated from the DF4 and characterized via NMR and HPLC-DAD-MS/MS analyses.  Flavonoids 1-5, especially reynoutrin (3), seem to be responsible for the DF4 antibacterial activity. Reynoutrin showed activity against Staphylococcus epidermidis ATCC 12228 and S. aureus methicillin-resistant ATCC 33591. This is the first report regarding the reynoutrin antibacterial activity and the first description of the flavonoid guaijaverin for O. notata.