Pharmacological Potential of Kaempferol, a Flavonoid in the Management of Pathogenesis via Modulation of Inflammation and Other Biological Activities.

Natural products and their bioactive compounds have been used for centuries to prevent and treat numerous diseases. Kaempferol, a flavonoid found in vegetables, fruits, and spices, is recognized for its various beneficial properties, including its antioxidant and anti-inflammatory potential. This molecule has been identified as a potential means of managing different pathogenesis due to its capability to manage various biological activities. Moreover, this compound has a wide range of health-promoting benefits, such as cardioprotective, neuroprotective, hepatoprotective, and anti-diabetic, and has a role in maintaining eye, skin, and respiratory system health. Furthermore, it can also inhibit tumor growth and modulate various cell-signaling pathways. In vivo and in vitro studies have demonstrated that this compound has been shown to increase efficacy when combined with other natural products or drugs. In addition, kaempferol-based nano-formulations are more effective than kaempferol treatment alone. This review aims to provide detailed information about the sources of this compound, its bioavailability, and its role in various pathogenesis. Although there is promising evidence for its ability to manage diseases, it is crucial to conduct further investigations to know its toxicity, safety aspects, and mechanism of action in health management.

Uncovering the molecular mechanism of Mume Fructus in treatment of Sjögren's syndrome.

BACKGROUND: Modern medicine has no cure for the xerostomia caused by the early onset of Sjögren's syndrome. Mume Fructus is a common Chinese herbal medicine used to relieve xerostomia. However, the molecular mechanisms of the effects of Mume Fructus are unknown. In this study, network pharmacology and molecular docking were used to investigate the mechanisms of action of Mume Fructus on Sjögren's syndrome. MATERIALS AND METHOD: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to identify the active components and targets of Mume Fructus, and the UniProt database was used to identify the genes encoding these targets. SS-related targets were also identified from the GeneCards and OMIM databases. By finding the intersection of the targets of the compounds and the targets of Sjögren's syndrome, the predicted targets of Mume Fructus in the treatment of Sjögren's syndrome were obtained. Further investigation of the active compounds and their targets was carried out by constructing a network of "medicine-candidate compound-target-disease" using Cytoscape 3.7.2, the Protein-Protein Interaction network using the STRING database and Cytoscape 3.7.2, and key targets were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on R software. Finally, molecular docking was used to verify the affinity of the candidate compounds to the key targets. RESULTS: Quercetin, beta-sitosterol, and kaempferol in Mume Fructus interact with AKT1, IL-6, IL-1B, JUN, CASP3, and MAPK8. These results suggest that Mume Fructus exerts its therapeutic effects on the peripheral gland injury of Sjögren's syndrome and its secondary cardiovascular disease and tumorigenesis through anti-inflammatory, anti-oxidant, and anti-tumor pathways. CONCLUSION: With network pharmacology, this study systematically identified the main active components, targets, and specific mechanisms of the therapeutic effects of Mume Fructus on Sjögren's syndrome, providing both a theoretical basis and research direction for further investigations on Mume Fructus.

Fuzhengjiedu San inhibits porcine reproductive and respiratory syndrome virus by activating the PI3K/AKT pathway.

BACKGROUND: Traditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear. METHODS: In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis. RESULTS: Network pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway. CONCLUSION: We conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.

Triple Sensing Modes for Triggered ß-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases.

Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms underlying their inhibitory effect on platelet activation remain poorly understood. In this study, we applied flow cytometry to analyze the effects of six flavonoid aglycones (luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin) on platelet activation, phosphatidylserine externalization, formation of reactive oxygen species, and intracellular esterase activity. We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets. The tested aglycones did not affect platelet viability, apoptosis induction, or procoagulant platelet formation. Notably, luteolin, myricetin, quercetin, and apigenin increased thrombin-induced thromboxane synthase activity, which was analyzed by a spectrofluorimetric method. Our results obtained from Western blot analysis and liquid chromatography-tandem mass spectrometry demonstrated that the antiplatelet properties of the studied phytochemicals are mediated by activation of cyclic nucleotide-dependent signaling pathways. Specifically, we established by using Förster resonance energy transfer that the molecular mechanisms are, at least partly, associated with the inhibition of phosphodiesterases 2 and/or 5. These findings underscore the therapeutic potential of flavonoid aglycones for clinical application as antiplatelet agents.

Mulberry Leaf Compounds and Gut Microbiota in Alzheimer's Disease and Diabetes: A Study Using Network Pharmacology, Molecular Dynamics Simulation, and Cellular Assays.

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer's disease (AD). Mulberry leaves, serving as both a traditional medicinal herb and a food source, exhibit significant hypoglycemic and antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms and providing neuroprotection. However, the mechanisms of this effect have not been fully elucidated. This investigation aimed to investigate the combined effects of specific mulberry leaf flavonoids (kaempferol, quercetin, rhamnocitrin, tetramethoxyluteolin, and norartocarpetin) on both type 2 diabetes mellitus (T2DM) and AD. Additionally, the role of the gut microbiota in these two diseases' treatment was studied. Using network pharmacology, we investigated the potential mechanisms of flavonoids in mulberry leaves, combined with gut microbiota, in combating AD and T2DM. In addition, we identified protein tyrosine phosphatase 1B (PTP1B) as a key target for kaempferol in these two diseases. Molecular docking and molecular dynamics simulations showed that kaempferol has the potential to inhibit PTP1B for indirect treatment of AD, which was proven by measuring the IC50 of kaempferol (279.23 µM). The cell experiment also confirmed the dose-dependent effect of kaempferol on the phosphorylation of total cellular protein in HepG2 cells. This research supports the concept of food-medicine homology and broadens the range of medical treatments for diabetes and AD, highlighting the prospect of integrating traditional herbal remedies with modern medical research.

Kaempferol as an Alternative Cryosupplement for Bovine Spermatozoa: Cytoprotective and Membrane-Stabilizing Effects.

Kaempferol (KAE) is a natural flavonoid with powerful reactive oxygen species (ROS) scavenging properties and beneficial effects on ex vivo sperm functionality. In this paper, we studied the ability of KAE to prevent or ameliorate structural, functional or oxidative damage to frozen-thawed bovine spermatozoa. The analysis focused on conventional sperm quality characteristics prior to or following thermoresistance tests, namely the oxidative profile of semen alongside sperm capacitation patterns, and the levels of key proteins involved in capacitation signaling. Semen samples obtained from 30 stud bulls were frozen in the presence of 12.5, 25 or 50 µM KAE and compared to native ejaculates (negative control-CtrlN) as well as semen samples cryopreserved in the absence of KAE (positive control-CtrlC). A significant post-thermoresistance test maintenance of the sperm motility (p < 0.001), membrane (p < 0.001) and acrosome integrity (p < 0.001), mitochondrial activity (p < 0.001) and DNA integrity (p < 0.001) was observed following supplementation with all KAE doses in comparison to CtrlC. Experimental groups supplemented with all KAE doses presented a significantly lower proportion of prematurely capacitated spermatozoa (p < 0.001) when compared with CtrlC. A significant decrease in the levels of the superoxide radical was recorded following administration of 12.5 (p < 0.05) and 25 µM KAE (p < 0.01). At the same time, supplementation with 25 µM KAE in the cryopreservation medium led to a significant stabilization of the activity of Mg2+-ATPase (p < 0.05) and Na+/K+-ATPase (p < 0.0001) in comparison to CtrlC. Western blot analysis revealed that supplementation with 25 µM KAE in the cryopreservation medium prevented the loss of the protein kinase A (PKA) and protein kinase C (PKC), which are intricately involved in the process of sperm activation. In conclusion, we may speculate that KAE is particularly efficient in the protection of sperm metabolism during the cryopreservation process through its ability to promote energy synthesis while quenching excessive ROS and to protect enzymes involved in the process of sperm capacitation and hyperactivation. These properties may provide supplementary protection to spermatozoa undergoing the freeze-thaw process.

The mitochondria-targeted Kaempferol nanoparticle ameliorates severe acute pancreatitis.

Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.

Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK/NF-κB signaling pathway.

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.

Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model.

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.

Immunomodulatory effects of Kaempferol on microglial and Macrophage cells during the progression of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) stands as a prevalent secondary complication of diabetes, notably Type 1 Diabetes Mellitus (T1D), characterized by immune system involvement potentially impacting the retinal immune response mediated by microglia. Early stages of DR witness blood-retinal barrier permeabilization, facilitating peripheral immune cell interaction with the retinal immune system. Kaempferol (Kae), known for its potent anti-inflammatory activity, presents a promising avenue in DR treatment by targeting the immune mechanisms underlying its onset and progression. Our investigation delves into the molecular intricacies of innate immune cell interaction during DR progression and the attenuation of inflammatory processes pivotal to its pathology. METHODS: Employing in vitro studies, we exposed HAPI microglial and J774.A1 macrophage cells to pro-inflammatory stimuli in the presence or absence of Kae. Ex vivo and in vivo experiments utilized BB rats, a T1D animal model. Retinal explants from BB rats were cultured with Kae, while intraperitoneal Kae injections were administered to BB rats for 15 days. Quantitative PCR, Western blotting, immunofluorescence, and Spectral Domain - Optical Coherence Tomography (SD-OCT) facilitated survival assessment, cellular signaling analysis, and inflammatory marker determination. RESULTS: Results demonstrate Kae significantly mitigates inflammatory processes across in vitro, ex vivo, and in vivo DR models, primarily targeting immune cell responses. Kae administration notably inhibits proinflammatory responses during DR progression while promoting an anti-inflammatory milieu, chiefly through microglia-mediated synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). In vivo, Kae administration effectively preserves retinal integrity amid DR progression. CONCLUSIONS: Our findings elucidate the interplay between retinal and systemic immune cells in DR progression, underscoring a differential treatment response predominantly orchestrated by microglia's anti-inflammatory action. Kae treatment induces a phenotypic and functional shift in immune cells, delaying DR progression, thereby spotlighting microglial cells as a promising therapeutic target in DR management.

Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice.

OBJECTIVE AND DESIGN: Mast cells (MCs), as the fastest immune responders, play a critical role in the progression of neuroinflammation-related diseases, especially in depression. Quercetin (Que) and kaempferol (Kae), as two major diet-derived flavonoids, inhibit MC activation and exhibit significant antidepressant effect due to their anti-inflammatory capacity. The study aimed to explore the mechanisms of inhibitory effect of Que and Kae on MC activation, and whether Que and Kae suppress hippocampal mast cell activation in LPS-induced depressive mice. SUBJECTS AND TREATMENT: In vitro assays, human mast cells (HMC-1) were pretreated with Que or Kae for 1 h, then stimulated by phorbol 12-myristate 13-acetate (PMA) and 2,5-di-t-butyl-1,4-benzohydroquinone (tBHQ) for 3 h or 12 h. In vivo assays, Que or Kae was administered by oral gavage once daily for 14 days and then lipopolysaccharide (LPS) intraperitoneally injection to induce depressive behaviors. METHODS: The secretion and expression of TNF-α were determined by ELISA and Western blotting. The nuclear factor of activated T cells (NFAT) transcriptional activity was measured in HMC-1 stably expressing NFAT luciferase reporter gene. Nuclear translocation of NFATc2 was detected by nuclear protein extraction and also was fluorescently detected in HMC-1 stably expressing eGFP-NFATc2. We used Ca2+ imaging to evaluate changes of store-operated calcium entry (SOCE) in HMC-1 stably expressing fluorescent Ca2+ indicator jGCamP7s. Molecular docking was used to assess interaction between the Que or Kae and calcium release-activated calcium modulator (ORAI). The  hippocampal mast cell accumulation and activation  were detected by toluidine blue staining and immunohistochemistry with ß-tryptase. RESULTS: In vitro assays of HMC-1 activated by PtBHQ (PMA and tBHQ), Que and Kae significantly decreased expression and secretion of TNF-α. Moreover, NFAT transcriptional activity and nuclear translocation of NFATc2 were remarkably inhibited by Que and Kae. In addition, the Ca2+ influx mediated by SOCE was suppressed by Que, Kae and the YM58483 (ORAI inhibitor), respectively. Importantly, the combination of YM58483 with Que or Kae had no additive effect on the inhibition of SOCE. The molecular docking also showed that Que and Kae both exhibit high binding affinities with ORAI at the same binding site as YM58483. In vivo assays, Que and Kae significantly reversed LPS-induced depression-like behaviors in mice, and inhibited hippocampal mast cell activation  in LPS-induced depressive mice. CONCLUSIONS: Our results indicated that suppression of SOCE/NFATc2 pathway-mediated by ORAI channels may be the mechanism of inhibitory effect of Que and Kae on MC activation, and also suggested Que and Kae may exert the antidepressant effect through suppressing hippocampal mast cell activation.

Transcriptomic and targeted metabolomic analyses provide insights into the flavonoids biosynthesis in the flowers of Lonicera macranthoides.

BACKGROUND: Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. RESULTS: In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3'H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6''-O-acetyl)-glucoside, cosmosiin and apigenin-4'-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. CONCLUSION: The findings are helpful for genetic improvement of varieties in L.macranthoides.

Research Progress on Anti-Inflammatory Effects and Related Mechanisms of Astragalin.

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.

Development and optimization of kaempferol loaded ethosomes using Box-Behnken statistical design: In vitro and ex-vivo assessments.

Kaempferol (KMP) belong to flavonoid class have developed in ethosomal formulation and were evaluated for their potential to treat diabetic foot ulcers. Even though ethosomes are highly deformable, they can pass through human skin intact. KMP ethosomes were formulated using the cold method and optimized by Box-Behnken design (BBD) (three-factor, three-level (33 )). The formulation variables used for optimization are drug concentration of KMP, soylecithin content, and ethanol percentage. The optimized formulation was examined using transmission electronic microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, in-vitro release, ex-vivo permeation studies, and storage stability. The optimized KMP ethosomes was found to have vesicle size (VS) of 283 ± 0.3 nm and zeta potential (ZP) of -29.67 ± 0.3 mV, polydispersity index (PDI) of 0.36, % entrapment efficiency (%EE) of 91.02 ± 0.21%, drug loading (%) of 46.23 ± 2.5% followed by good storage stability at 4°C/60 ± 5% RH. In vitro drug release of optimized KMP ethosomes was 88.2 ± 2.75%, which was approximately double when compared with pure KMP release, that is 49.9 ± 1.89%. The release kinetics for optimized KMP ethosomes follows the Korsmeyer-Peppas model. An apparent permeation coefficient of 356.25 ± 0.5 µg/cm2 was determined and compared with pure KMP (118.46 ± 0.3 µg/cm2 ) for 24 h. According to the study, ethosomes can be a cutting-edge strategy that offers a new delivery method for prolonged and targeted distribution of KMP in a variety of dosage forms including oral, topical, transdermal, and so forth.

Pulp or Peel? Comparative Analysis of the Phytochemical Content and Selected Cosmetic-Related Properties of Annona cherimola L., Diospyros kaki Thumb., Cydonia oblonga Mill. and Fortunella margarita Swingle Pulp and Peel Extracts.

Fruit peels might be a valuable source of active ingredients for cosmetics, leading to more sustainable usage of plant by-products. The aim of the study was to evaluate the phytochemical content and selected biological properties of hydroglycolic extracts from peels and pulps of Annona cherimola, Diospyros kaki, Cydonia oblonga, and Fortunella margarita as potential cosmetic ingredients. Peel and pulp extracts were compared for their antiradical activity (using DPPH and ABTS radical scavenging assays), skin-lightening potential (tyrosinase inhibitory assay), sun protection factor (SPF), and cytotoxicity toward human fibroblast, keratinocyte, and melanoma cell lines. The total content of polyphenols and/or flavonoids was significantly higher in peel than in pulp extracts, and the composition of particular active compounds was also markedly different. The HPLC-MS fingerprinting revealed the presence of catechin, epicatechin and rutoside in the peel of D. kaki, whereas kaempferol glucoside and procyanidin A were present only in the pulp. In A. cherimola, catechin, epicatechin and rutoside were identified only in the peel of the fruit, whereas procyanidins were traced only in the pulp extracts. Quercetin and luteolinidin were found to be characteristic compounds of F. margarita peel extract. Naringenin and hesperidin were found only in the pulp of F. margarita. The most significant compositional variety between the peel and pulp extracts was observed for C. oblonga: Peel extracts contained a higher number of active components (e.g., vicenin-2, kaempferol rutinoside, or kaempferol galactoside) than pulp extract. The radical scavenging potential of peel extracts was higher than of the pulp extracts. D. kaki and F. margarita peel and pulp extracts inhibited mushroom and murine tyrosinases at comparable levels. The C. oblonga pulp extract was a more potent mushroom tyrosinase inhibitor than the peel extract. Peel extract of A. cherimola inhibited mushroom tyrosinase but activated the murine enzyme. F. margarita pulp and peel extracts showed the highest in vitro SPF. A. cherimola, D. kaki, and F. margarita extracts were not cytotoxic for fibroblasts and keratinocytes up to a concentration of 2% (v/v) and the peel extracts were cytotoxic for A375 melanoma cells. To summarize, peel extracts from all analyzed fruit showed comparable or better cosmetic-related properties than pulp extracts and might be considered multifunctional active ingredients of skin lightening, anti-aging, and protective cosmetics.

SAR, Molecular Docking and Molecular Dynamic Simulation of Natural Inhibitors against SARS-CoV-2 Mpro Spike Protein.

The SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found to be likely candidates for the synthesis of novel therapeutic drug. In the past, proteins were capable of engaging in interaction with a wide variety of ligands, including both manmade and plant-derived small molecules. Pyrus communis L., Ginko bibola, Carica papaya, Syrian rue, and Pimenta dioica were some of the plant species that were studied for their tendency to interact with SARS-CoV-2 main protease (Mpro) in this research project (6LU7). This scenario investigates the geometry, electronic, and thermodynamic properties computationally. Assessing the intermolecular forces of phytochemicals with the targets of the SARS-CoV-2 Mpro spike protein (SP) resulted in the recognition of a compound, kaempferol, as the most potent binding ligand, -7.7 kcal mol-1. Kaempferol interacted with ASP-187, CYS-145, SER-144, LEU 141, MET-165, and GLU-166 residues. Through additional molecular dynamic simulations, the stability of ligand-protein interactions was assessed for 100 ns. GLU-166 remained intact with 33% contact strength with phenolic OH group. We noted a change in torsional conformation, and the molecular dynamics simulation showed a potential variation in the range from 3.36 to 7.44 against a 45-50-degree angle rotation. SAR, pharmacokinetics, and drug-likeness characteristic investigations showed that kaempferol may be the suitable candidate to serve as a model for designing and developing new anti-COVID-19 medicines.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.

OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis. MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.

Comparative Analysis of Fluorescence Emission in Myricetin, Kaempferol, and Quercetin Powders and Solutions.

Myricetin is a flavonol with high antioxidant properties. In this research, the fluorescence emission of myricetin powder and its solutions in different solvents were measured and analyzed by comparing with the results of calculations. Comparison of the calculated and measured characteristic wavelengths allowed the identification of all the spectral features in the fluorescence spectra of myricetin powder and solutions with different concentrations. The computation was based on modeling the process of the excited state intermolecular proton transfer, which predicts the formation of tautomeric forms of the flavonol molecule. Characteristic emission wavelengths were obtained using TDDFT/M06-2X/6-31++G(d,p). To understand the influence of the hydroxyl groups in the B-ring of the flavonol molecule on the emission spectrum, we also compared the fluorescence spectra of myricetin with those of kaempferol and quercetin. Moreover, based on the analysis of the changes in the shape of the FL spectra with the concentration of the solution, a criterion for the complete dissolution of the flavonol powders was established, which is important for bioavailability of flavonoids.

Therapeutic potential of traditional Chinese medicine in the prevention and treatment of digestive inflammatory cancer transformation: Portulaca oleracea L. as a promising drug.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. AIM OF STUDY: In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. METHODS: The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. RESULTS: Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. CONCLUSION: The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.