BACKGROUND: Malaria, characterised by inflammation and multi-organ complications, needs novel chemotherapeutics due to the rise of drug-resistant malaria parasites, which is a serious health issue. Naringin (NGN), a flavanone glycoside (naringenin 7-O-neohesperidose), has a broad spectrum of pharmacological activities but its effect against malaria, alone and in combination, was not deeply investigated.
OBJECTIVE: To assess the pharmacological efficacy of NGN alone and in combination with chloroquine (CQ) against a Plasmodium strain resistant to CQ and to elucidate its potential mode of action.
METHODS: The anti-inflammatory potential of NGN was assessed in mouse microglial cells stimulated with hemozoin by analyzing inflammatory cytokines production. The anti-plasmodial potential of NGN was subsequently tested alone and in combination with CQ against the K1 strain of Plasmodium using the fixed ratio combination method. Further, we evaluated NGN\'s antimalarial efficacy against the CQ-resistant Plasmodium yoelii nigeriensis N67 strain (P. yoelii), both alone and in combination with CQ, by measuring parasitemia and survival rates. To comprehend the impact of NGN on malaria-induced inflammation in mice, we measured pro-inflammatory cytokines elevated by activated NF-кB signalling. These findings were supported by mRNA and immunohistochemical analyses of malaria-infected mice\'s liver and brain tissues.
RESULTS: Our study demonstrated that NGN displayed anti-plasmodial activity, which was further augmented when combined with CQ. At 50 µM, NGN significantly reduced the elevation of pro-inflammatory cytokines in synthetic hemozoin-stimulated microglial cells. Compared to P. yoelii-infected mice, NGN (12.5 mg kg-1) significantly reduced parasitemia in mice, resulting in a survival period of up to 13 days. Survival improved by up to 20 days when NGN and CQ were given in combination. NGN, as revealed by immunohistochemical examination of brain and liver tissues, interfered with the NF-кB pathway, potentially reducing the elevation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-18, IFN-γ, and IL-6). This was supported by the overexpression of inflammation-regulatory genes (TGFβ, Nrf2, HO-1, and iNOS) and the downregulation of inflammation-stimulating genes (NF-κB, NLRP3, and caspase-1). Histopathological analysis demonstrated the potential of NGN to restore liver and brain tissues to normal. The substantial decrease in the expression and production of ICAM-1 protein in the brain tissue implies the beneficial effects of NGN, pointing towards its potential for mitigating brain pathology.
CONCLUSIONS: The findings of this study revealed NGN as a promising drug-like candidate for the management of CQ-resistant parasite-induced malaria pathogenesis for adjunctive therapy in combination with standard antimalarial drugs through its modulation of the NF-κB-mediated inflammation.

Nonalcoholic fatty liver disease (NAFLD) is an alarming ailment that leads to severe liver damage and increases the risk of serious health conditions. The prevalence of NAFLD due to oxidative stress could be mitigated by plant-derived antioxidants. This study aims to investigate the effects of syringic acid (SA) on NAFLD in a high-fat diet (HFD) rat model. Twenty-four rats were randomly divided into four groups (n = 6): normal control, HFD, SA-administered HFD, and positive control SA on a normal diet. Rats in the normal control and positive control groups received a normal diet, and the remaining groups received an HFD for 8 weeks. SA (20 mg/kg b.w.) was orally (gavage) administered for 8 weeks. Lipid profiles were controlled by SA against HFD-fed rats (p < 0.05). SA reduced the serum aspartate aminotransferase and alanine aminotransferase levels by 70%-190%. SA also suppressed pro-inflammatory cytokines and attenuated histopathological and immunohistochemical changes against HFD-fed rats. SA reversed oxidative stress by suppressing the malondialdehyde formation by 82% and replenished the nonenzymatic and enzymatic antioxidant activities (p < 0.05). Gene expressions of nuclear factor-erythroid 2-related factor/heme oxygenase 1 (Nrf2/HO-1) were elevated in SA-treated rats. Ameliorative effects of SA on NAFLD induced by an HFD in rats were prominent through the reversal of oxidative stress and inflammation, regulated by an intrinsic mechanism of defense against oxidative stress, the Nrf2/HO-1 pathway.

The purification of flavonoids using the macroporous polymer resin method has gained attention in recent years due to its simplicity, precision, cost-effectiveness, and the ability to separate flavonoids from other constituents. Several studies have been conducted to investigate the efficiency and effectiveness of macroporous polymer resin in purifying flavonoids from various plant sources. This review aims to evaluate the existing literature on macroporous polymer resin purification of flavonoids and provide a comprehensive analysis of the current research trends and advancements in this field. It also highlights the importance of optimizing the adsorption parameters and conditions such as resin type, resin concentration, pH, and temperature for efficient purification of flavonoids using macroporous polymer resin. The key findings of this review reveal that macroporous resins with weak polarity, large surface areas, and pore diameters have a stronger adsorption capacity for flavonoids compared to polar resins. Furthermore, ultrasonic-solvent assisted extraction often combines with macroporous resin for effective the extraction and purification of flavonoids.

Fenamiphos (FNP) is an organophospate pesticide that causes many potential toxicities in non-target organisms. Naringenin (NAR) has protective properties against oxidative stress. In this study, FNP (0.76 mg/kg bw) toxicity and the effect of NAR (50 mg/kg bw) on the liver and kidney of rats were investigated via biochemical, oxidative stress, immunohistochemical, cytopathological and histopathologically. As a result of biochemical studies, FNP caused oxidative stress in tissues with a change in total antioxidant/oxidant status. After treatment with FNP, hepatic and renal levels of AChE were significantly reduced while 8-OHdG and IL-17 levels, caspase-3 and TNF-α immunoreactivity increased compared to the control group. It also changed in serum biochemical markers such as ALT, AST, BUN, creatinine. Exposure to FNP significantly induced cytopathological, histopathological and immunohistochemical changes through tissue damage. NAR treatment restored biochemical parameters, renal/hepatic AChE, ultrastructural, histopathological and immunohistochemical changes modulated and blocked the increasing effect of FNP on tissues caspase-3 and TNF-α expressions, 8-OHdG and IL-17 levels. In electron microscopy studies, swelling was observed in the mitochondria of the cells in both tissues of the FNP-treated rats, while less ultrastructural changes in the FNP plus NAR-treated rats.

Unicellular protozoan parasite Leishmania donovani is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme Leishmania donovani DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 μM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.

UNASSIGNED: The increasing influence of overactive bladder (OAB) on physical as well as mental health of individuals is becoming more pronounced annually, as evidenced by the urge urinary incontinence and nocturia. Symptoms in OAB patients may be influenced by inflammation and oxidative stress. Flavonoids are recognized as significant anti-inflammatory and antioxidant agents, which are commonly available in fruits, tea, vegetables, etc. Previous research has demonstrated the therapeutic potential of flavonoids and their subclasses in treating inflammation, and oxidative stress. Despite this, there remains a paucity of research exploring the potential correlation between flavonoid consumption, specifically within distinct subclasses, and OAB. Thus, our study aims to investigate the relationship between flavonoid intake and OAB to identify possible dietary interventions for OAB management.
UNASSIGNED: We utilized the survey data from the National Health and Nutrition Examination Survey (NHANES) and the USDA Food and Nutrient Database for Dietary Studies (FNDDS) to investigate the relationship between dietary intake of total and subclass flavonoids and the risk of OAB based on 13,063 qualified American adults. The dietary flavonoid intake was estimated from two 24-h dietary recalls. Weighted multivariate logistic regression model, quantile-based g-computation, restricted cubic spline model, and stratified analysis were used to explore the association between flavonoid intake and OAB, respectively.
UNASSIGNED: The participants diagnosed with OAB exhibited a higher percentage of being female, older, Non-Hispanic Black, unmarried, former drinkers, having a lower annual household income, lower poverty to income ratio, lower educational attainment, and a higher likelihood of being obese and smokers. Upon adjusting for confounding factors, the weighted logistic regression models revealed that the third quartile of consumption of anthocyanidin and the second quartile of consumption of flavone were significantly associated with the reduced odds of OAB, while total flavonoid consumption did not show a significant correlation with the risk of OAB. The quantile-based g-computation model indicated that flavone, anthocyanidin and flavonol were the primary contributors to the observed negative correlation. Furthermore, the restricted cubic spline models demonstrated a J-shaped non-linear exposure-response association between anthocyanidin intake and the risk of OAB (P nonlinear = 0.00164). The stratified and interaction analyses revealed that the relationship between anthocyanidin intake and the risk of OAB was significantly influenced by age (P interaction = 0.01) and education level (P interaction = 0.01), while the relationship between flavone intake and the risk of OAB was found to vary by race (P interaction = 0.02) and duration of physical activity (P interaction = 0.05).
UNASSIGNED: Our research suggests that consuming a diet rich in flavonoid subclass anthocyanidin and flavone is associated with a reduced risk of OAB, potentially offering clinical significance in the prevention of OAB development. This underscores the importance of dietary adjustments in the management of OAB symptoms.

Eggs are recognized for their rich nutrient profile, providing essential proteins and lipids with notable functional properties. This study examines the effects of incorporating Water Extract of Ampelopsis grossedentata (WEA) into poultry feed on egg quality, focusing on lipid content, choline, L-carnitine levels, and flavonoid compound deposition. Our results show significant increases in essential amino acids, flavonoids, and other bioactive compounds in eggs from WEA-treated hens, suggesting enhanced cardiovascular, antioxidant, and anti-inflammatory benefits. Additionally, we observed elevated levels of choline and betaine in egg yolks, alongside increased L-carnitine content, which may contribute to improved lipid metabolism and reduced cardiovascular disease risk. KEGG pathway analysis revealed upregulation of metabolites involved in critical metabolic pathways, enhancing the nutritional profile of eggs. Flavonoid compounds, traditionally associated with plant-based foods, were also significantly increased, with notable levels of 7, 4\'-dihydroxyflavone, daidzein, and glycitein identified in WEA-treated eggs, indicating potential health benefits. These findings suggest that WEA supplementation can produce functional eggs with improved nutritional quality, offering a novel approach to enhancing egg production and meeting the growing demand for functional foods. Further research is needed to fully understand the bioavailability and health impacts of these enriched compounds.

The microbial genome remains a huge treasure trove for the discovery of diverse natural products. Saccharopolyspora erythraea NRRL23338, the industry producer of erythromycin, has a dozen of biosynthetic gene clusters whose encoding products are unidentified. Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid. Meanwhile, two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites. Their structures were identified by comprehensive analysis of MS and NMR experiments. Putative functions of genes within the pks7 BGC were also discussed.

The study investigated total phenolic-flavonoid content, antioxidant activity, and phytochemical compounds across various parts (bulb, stem, leaf, and flower) of the endemic Bellevalia sasonii, commonly known as hyacinth, belonging to the Asparagaceae family. Phenolic content was highest in bulb extracts (117.28 μg GAE) and lowest in stems (45.11 μg GAE). Conversely, leaf extracts exhibited the highest flavonoid content (79.44 μg QEs), while stems showed the lowest (22.77 μg QEs). When the antioxidant activities were compared, by DPPH method leaf = flower > bulb > stem; in ABTS and CUPRAC methods bulb > flower > leaf > stem, respectively. Considering the results in general, it was revealed that bulbs and flowers displayed higher activity, while stem exhibited lower activity compared to other parts. The phytochemical analysis identified 53 active substances, with 27 absent in any extract and 15 detected across all extracts. The distribution of phytochemicals varied among parts, with bulbs, stems, flowers, and leaves also different numbers. The LC-MS/MS analysis revealed prominent metabolites including fumaric acid in leaves, caffeic acid in bulbs, and cosmosiin and quinic acid in flowers. This study provides foundational insights into B. sasonii, an important endemic plant in Türkiye, laying the groundwork for future research on its medicinal and ecological roles.