Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Optimization of Pressurized Liquid Extraction (PLE) Parameters for Extraction of Bioactive Compounds from Moringa oleifera Leaves and Bioactivity Assessment.

Moringa oleifera leaves are rich sources of bioactive compounds with potential health benefits, including antioxidants and anti-inflammatory agents. Pressurized liquid extraction (PLE) stands out as a promising technique for effectively extracting valuable compounds from natural sources. In this study, we aimed to optimize PLE parameters, such as temperature, extraction duration, and pressure, to maximize bioactive compound (polyphenols, flavonoids, and ascorbic acid) yield from M. oleifera leaves and evaluate their antioxidant and anti-inflammatory activities. According to the outcomes of this research, the maximum achieved total polyphenol content was 24.10 mg gallic acid equivalents (GAE)/g of dry weight (dw), and the total flavonoid content was increased up to 19.89 mg rutin equivalents (RtE)/g dw. Moreover, after HPLC-DAD analysis, neochlorogenic and chlorogenic acids, catechin and epicatechin, rutin, and narirutin were identified and quantified. As far as the optimum ascorbic acid content is concerned, it was found to be 4.77 mg/g dw. The antioxidant activity was evaluated by three different methods: ferric reducing antioxidant power (FRAP), the DPPH method, and the anti-hydrogen peroxide activity (AHPA) method, resulting in 124.29 µmol ascorbic acid equivalent (AAE)/g dw, 131.28 µmol AAE/g dw, and 229.38 µmol AAE/g dw values, respectively. Lastly, the albumin denaturation inhibition was found to be 37.54%. These findings underscore the potential of PLE as an efficient extraction method for preparing extracts from M. oleifera leaves with the maximum content of bioactive compounds.

Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity.

Labdanum resin or "gum" can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45-70 µg/mL, for Caco-2; IC50 = 60-80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.

Wighteone, a prenylated flavonoid from licorice, inhibits growth of SW480 colorectal cancer cells by allosteric inhibition of Akt.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.

Isoprenoid flavonoids isolated from Sophora davidii and their activities induces apoptosis and autophagy in HT29 cells.

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

A Flavonoid Glycoside Compound from Siraitia grosvenorii with Anti-Inflammatory and Hepatoprotective Effects In Vitro.

Inflammation is a pivotal factor in the development and advancement of conditions like NAFLD and asthma. Diet can affect several phases of inflammation and significantly influence multiple inflammatory disorders. Siraitia grosvenorii, a traditional Chinese edible and medicinal plant, is considered beneficial to health. Flavonoids can suppress inflammatory cytokines, which play a crucial role in regulating inflammation. In the present experiments, kaempferol 3-O-α-L-rhamnoside-7-O-ß-D-xylosyl(1→2)-O-α-L-rhamnoside (SGPF) is a flavonoid glycoside that was first isolated from S. grosvenorii. A series of experimental investigations were carried out to investigate whether the flavonoid component has anti-inflammatory and hepatoprotective effects in this plant. The researchers showed that SGPF has a stronger modulation of protein expression in LPS-induced macrophages (MH-S) and OA-induced HepG2 cells. The drug was dose-dependent on cells, and in the TLR4/NF-κB/MyD88 pathway and Nrf2/HO-1 pathway, SGPF regulated all protein expression. SGPF has a clear anti-inflammatory and hepatoprotective function in inflammatory conditions.

Metabolites from Aerial Parts of Glycyrrhiza foetida as Modulators of Targets Related to Metabolic Syndrome.

A detailed phytochemical investigation has been carried out on the aerial parts of G. foetida leading to the isolation of 29 pure compounds, mainly belonging to the amorfrutin and polyphenol classes. Among them, the new amorfrutin N (5) and exiguaflavone L (21) were isolated and their structures elucidated by means of HR-ESIMS and NMR. All the isolated compounds were investigated for modulation of mitochondrial activity and stimulation of glucose uptake via GLUT transporters, two metabolic processes involved in intracellular glucose homeostasis, which, therefore, correlate with the incidence of metabolic syndrome. These experiments revealed that amorfrutins were active on both targets, with amorfrutin M (17) and decarboxyamorfrutin A (2) emerging as mitochondrial stimulators, and amorfrutin 2 (12) as a glucose uptake promoter. However, members of the rich chalcone/flavonoid fraction also proved to contribute to this activity.

Underutilized fruit lasoda (Cordia myxa L.): Review on bioactive compounds, antioxidant potentiality and applications in health bioactivities and food.

Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.

Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT-eNOS Pathway.

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.

Inhibition of hepatocellular carcinoma cell proliferation through regulation of the Cell Cycle, AGE-RAGE, and Leptin signaling pathways by a compound formulation comprised of andrographolide, wogonin, and oroxylin A derived from Andrographis Paniculata(Burm.f.) Nees.

ETHNOPHARMACOLOGICAL RELEVANCE: In 2020, liver cancer contributed to approximately 0.9 million new cases and 0.83 million deaths, making it the third leading cause of mortality worldwide. Andrographis paniculata (Burm.f.) Nees(APN), a traditional Chinese or ethnic medicine extensively utilized in Asia, has been historically employed for treating hepatitis and liver cancer. However, the precise molecular mechanism responsible for its therapeutic efficacy remains unclear. AIM OF THE STUDY: To identify and replace the active components of APN on liver cancer, which is investigate the potential of a Multi-Component Chinese Medicine derived from Andrographis paniculata (Burm.f.) Nees(APN-MCCN) for the treatment of liver cancer. MATERIALS AND METHODS: Firstly, the TCMSP database and two liver cancer disease databases were utilized to optimize the chemical constituents of APN and the disease-related targets of liver cancer. The network was constructed using Cytoscape to visualize the relationships between them. Subsequently, the optimal combination of components in APN-MCCN for the treatment of liver cancer was determined using the contribution index method. HPLC analysis was performed to measure the content of each component. Pathway enrichment and gene annotation were conducted using the ClueGo plugin. In vivo efficacy was evaluated by transplanting S180 and H22 tumor-bearing mouse models. In vitro efficacy was determined through MTT assay, morphological observations, flow cytometry analysis, and scratch tests. Western blotting was used to validate the protein expression. The transfection techniques were employed to knockdown the expressions of key protein in different pathway. RESULTS: We obtained 24 effective compounds, with andrographolide contributing 20.78%, wogonin contributing 41.85%, and oroxylin A contributing 30.26% to the overall composition. Based on the predicted enrichment degree and correlation with liver cancer, we identified a total of 27 pathways, among which the Leptin signaling pathway, AGE-RAGE signaling pathway, and Cell Cycle signaling pathway were selected for further investigation. The content of andrographolide, oroxylin A, and wogonin in APN was found to be 0.104%, 0.0024%, and 0.0052%, respectively. In vivo experiments demonstrated that APN-MCCM significantly reduced tumor weight in S180 tumor-bearing mice and prolonged the survival time of H22 liver cancer-bearing mice. APN-MCCM exhibited inhibitory effects on the proliferation, apoptosis, and migration of liver cancer cells while arresting them in the G2/M phase. Furthermore, APN-MCCM down-regulated the protein expression of NCOA1, PTPN1, and GSK3B in the Leptin signaling pathway, NOS2 and NOS3 in the AGE-RAGE signaling pathway, CCNA2, CDK1, CDK2, and CDK7 in the Cell Cycle signaling pathway. Additionally, it upregulated the protein phosphorylation of p-P38 and p-JUN in the AGE-RAGE signaling pathway. Knockout experiments revealed that the inhibitory effect of APN-MCCM on liver cancer cell migration was prevented when the MAPK or NCOA1 genes were knocked out. Similarly, knocking out the CDK7 gene blocked the G2/M phase arrest induced by APN-MCCM in liver cancer cells. CONCLUSIONS: APN-MCCM, consisting of andrographolide, wogonin, and oroxylin A, exhibits inhibitory effects on the cell proliferation of liver cancer cells by targeting the cell cycle pathway. Additionally, it suppresses the migration of liver cancer cells through the AGE-RAGE and Leptin signaling pathways.

Bioactive neolignan, iridoid and flavonoid glycosides from the leaves of Vaccinium bracteatum.

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 - 9) and nine flavonoid glycosides (10 - 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.

Extraction and Study of Hypoglycemic Constituents from Myrica rubra Pomace.

Myrica rubra pomace accounts for 20% of the fruit's weight that is not utilized when it is juiced. The pomace contains bioactive phenolic substances such as anthocyanins and flavonoids. To improve the utilization value of Myrica rubra pomace, an optimized extraction method for the residual polyphenols was developed using response surface methodology (RSM). The resulting extract was analyzed by high performance liquid chromatography (HPLC), and the in vitro hypoglycemic activity and antioxidant activity of the polyphenolic compounds obtained were also investigated. The optimum extraction conditions (yielding 24.37 mg·g-1 total polyphenols content) were: extraction temperature 60 °C, ultrasonic power 270 W, ethanol concentration 53%, extraction time 57 min, and solid to liquid ratio 1:34. Four polyphenolic compounds were identified in the pomace extract by HPLC: myricitrin, cyanidin-O-glucoside, hyperoside, and quercitrin. DPPH and hydroxyl radical scavenging tests showed that the Myrica rubra polyphenols extract had strong antioxidant abilities. It is evident that the residual polyphenols present in Myrica rubra pomace have strong hypoglycemic activity and the juiced fruits can be further exploited for medicinal purposes.

Identification of galangin as the bioactive compound from Alpinia calcarata (Haw.) Roscoe rhizomes to inhibit IRAK-1/ MAPK/ NF-κB p65 and JAK-1 signaling in LPS stimulated RAW 264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia calcarata (Haw.) Roscoe rhizomes are used to treat diabetes, rheumatism, gastrointestinal problems, inflammatory diseases, cough and respiratory problems in traditional practices. The primary objective of the study is to identify and isolate anti-inflammatory bioactive compounds from A.calcarata rhizomes and to assess its molecular mechanism. MATERIALS AND METHODS: The bioassay-guided fractionation of methanolic extract of A. calcarata rhizomes yielded chloroform fraction as the effective fraction and galangin as the bioactive compound identified by NMR studies. The anti-inflammatory action of galangin was evaluated by determining NO and cytokine production in LPS stimulated RAW264.7 cells. Further, its mechanism was studied on the expression levels of mRNA and protein targets by qPCR and Western blot analysis. RESULTS: Based on the MTT assay, the concentration of 3.1-25 µM of galangin was selected for further studies. Galangin reduced the levels of NO and proinflammatory cytokines (TNF-α, IL-1ß and IL-6) production in LPS induced RAW 264.7 cells in a dose-dependent manner. In addition, the qPCR analysis revealed a reduction in the mRNA expression levels of COX-2, IRAK 1 and JAK 1 in galangin treated LPS stimulated RAW 264.7 cells in a dose-dependent manner. Western blot analysis implicated that galangin has markedly reduced the protein expression levels of cell signaling regulators (JAK-1, IRAK-1, MyD88, MAPK (p38 and ERK) and NF-κB p65). CONCLUSION: From the results, it is evident that the inhibition of these cell signaling regulators has contributed to the anti-inflammatory effects of galangin. To our knowledge, we are the first to report IRAK-1 and JAK-1 as therapeutic targets of galangin for its anti-inflammatory effect.

Flavonoids derived from Anemarrhenae Rhizoma ameliorate inflammation of benign prostatic hyperplasia via modulating COX/LOX pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Flavonoids are the main components of the traditional Chinese medicine Anemarrhenae Rhizoma (dried rhizome of Anemarrhena asphodeloides Bge.), which has been reported to possess activity against inflammation and tumor. AIM OF STUDY: Regulation of the arachidonic acid (AA) cascade through cyclooxygenase (COX) and lipoxygenase (LOX) represent the two major pathways to treat inflammatory of benign prostatic hyperplasia (BPH). In this study, Anemarrhenae Rhizoma flavonoids and its main compounds (mangiferin, neomangiferin and isomangiferin) were investigated for effects on AA metabolism. METHODS: Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to monitor AA metabolites in BPH rats and in PC-3 cells. COX-2 and 5-LOX protein and mRNA levels were measured by Western blot and qPCR, respectively, along with histopathological assessment of prostate tissues. RESULTS: Treatment with flavonoids significantly ameliorated BPH-associated prostate inflammation and inhibited the expression of COX-2 and 5-LOX at the protein and mRNA levels. Quantitative metabolomic analysis of blood plasma showed flavonoids treatment decreased AA levels and its metabolites associated with the COX and LOX pathways. Further exploration of the flavonoid compounds mangiferin, neomangiferin and isomangiferin showed they inhibited AA metabolism to varying degrees in PC-3 cell cultures. CONCLUSION: Anemarrhenae Rhizoma flavonoids act to inhibit BPH-related inflammation in vivo and in vitro by targeting AA metabolism and interfering with COX and LOX pathways. The identification of mangiferin, neomangiferin and isomangiferin as anti-inflammatory components suggests flavonoids interventions represent a promising therapeutic approach for BPH.

Therapeutic effect of baicalin on inflammatory bowel disease: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalin (BI) is an important biologically active flavonoid isolated from the root of Scutellaria radix (Huang Qin). Traditionally Scutellaria radix was the common drug of dysentery. As the main flavonoid compound, there is a distribution tendency of baicalin to the intestinal tract and it has a protective effect on the gastrointestinal tract. AIM OF THE REVIEW: This review aims to compile up-to-date and comprehensive information on the efficacy of baicalin in vitro and in vivo, about treating inflammatory bowel disease. Relevant information on the therapeutic potential of baicalin against inflammatory bowel disease was collected from the Web of Science, Pubmed and so on. Additionally, a few books and magazines were also consulted to get the important information. RESULTS: The mechanisms of baicalin against inflammatory bowel disease mainly include anti-inflammation, antioxidant, immune regulation, maintenance of intestinal barrier, maintenance of intestinal flora balance. Also, BI can relieve parts of extraintestinal manifestations (EIMs), and prevent colorectal cancer. CONCLUSION: Baicalin determined the promising therapeutic prospects as potential supplementary medicines for the treatment of IBD.

Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. AIM OF THE STUDY: This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. MATERIALS AND METHODS: The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-κB signaling pathway in GLUTag cells. RESULTS: Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-κB pathway. Notably, isoquercitrin exhibited more pronounced anti-diabetic efficacy. CONCLUSIONS: The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-κB pathway.

Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin.

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC50 = 4.38 µM) and FBPase (IC50 = 3.62 µM) dual inhibitory activity, which were 75-fold higher than acarbose (IC50 = 330.10 µM) and comparable with AMP (IC50 = 2.92 µM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study.

Effect of the natural polymethoxylated flavone artemetin on lipid oxidation and its impact on cancer cell viability and lipids.

The biochemical class of the polymethoxylated flavonoids represents uncommon phenolic compounds in plants presenting a more marked lipophilic behavior due to the alkylation of its hydroxylic groups. As a polymethoxylated flavone, which concerns a different bioavailability, artemetin (ART) has been examined in vitro against lipid oxidation and its impact on cancer cells has been explored. Despite this flavone only exerted a slight protection against in vitro fatty acid and cholesterol oxidative degradation, ART significantly reduced viability and modulated lipid profile in cancer Hela cells at the dose range 10-50 µM after 72 h of incubation. It induced marked changes in the monounsaturated/saturated phospholipid class, significant decreased the levels of palmitic, oleic and palmitoleic acids, maybe involving an inhibitory effect on de novo lipogenesis and desaturation in cancer cells. Moreover, ART compromised normal mitochondrial function, inducing a noteworthy mitochondrial membrane polarization in cancer cells. A dose-dependent absorption of ART was evidenced in HeLa cell pellets (15.2% of the applied amount at 50 µM), coupled to a marked increase in membrane fluidity, as indicate by the dose-dependent fluorescent Nile Red staining (red emissions). Our results validate the ART role as modulatory agent on cancer cell physiology, especially impacting viability, lipid metabolism, cell fluidity, and mitochondrial potential.

Disclosing targets and pharmacological mechanisms of total bioflavonoids extracted from Selaginella doederleinii against non-small cell lung cancer by combination of network pharmacology and proteomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Previously, the total bioflavonoids extract from Selaginella doederleinii (SDTBE) presented favorable in vitro and in vivo activities against non-small cell lung cancer (NSCLC), hinting at its medicinal potential. However, up to nowadays, targets and integrative action mechanisms of SDTBE are still not very clear, which presents an obstacle to the development of herbal medicine. AIM OF THE STUDY: The present study aimed to disclose the potential targets and integrative action mechanism of SDTBE against NSCLC. MATERIALS AND METHODS: A system pharmacology-based strategy including target fishing, network pharmacology analysis and molecular docking were applied to predict the potential targets and pathways for the seven main active ingredients in SDTBE. A proteomics study was subsequently performed for validating the affected pathways and possible targets. Western blot assay, mouse xenograft tumor model and immunofluorescence assays were used to further confirm the key targets and integrative action mechanisms of SDTBE against NSCLC. RESULTS: By system pharmacology, it was inferred that SDTBE could mainly act on mitogen-activated protein kinase (MAPK) and PI3K-AKT signaling pathways by targeting epidermal growth factor receptor (EGFR), protein kinase B (AKT) and mitogen-activated or extracellular signal-regulated protein kinase (MEK), which was validated by proteomics results, and further confirmed in vitro and in vivo by Western blot and immunofluorescence assays. CONCLUSION: SDTBE targeting multi-targets including EGFR, AKT and MEK could exert its anti-NSCLC effect mainly via MAPK and PI3K-AKT signaling pathways.

Impact of Drying Methods on Phenolic Components and Antioxidant Activity of Sea Buckthorn (Hippophae rhamnoides L.) Berries from Different Varieties in China.

Sea buckthorn berries are rich in bioactive compounds and can be used for medicine and food. The variety and drying method used have an important influence on quality. In this study, different sea buckthorn varieties from China were selected and dried with four common drying methods. The total phenolic content (TPC), total flavonoids content (TFC), contents of 12 phenolic compounds and antioxidant capacity in vitro were analyzed. The results showed that the TPC, TFC and antioxidant activity of two wild sea buckthorn berries were higher than those of three cultivated berries, and for the same varieties, measured chemical contents and antioxidant activity of the freeze-dried fruit were significantly higher than those obtained with three conventional drying methods. In addition, forty-one compounds in sea buckthorn berry were identified by UPLC-PDA-Q/TOF-MS, most of which were isorhamnetin derivatives. Multivariate statistical analysis revealed narcissin and isorhamnetin-3-O-glucoside varied significantly in sea buckthorn berries of different varieties and with different drying methods; they were potential quality markers. Strong correlations were found between TPC, gallic acid and antioxidant capacity (p < 0.05). The results revealed how components and antioxidant activity varied in different sea buckthorn, which provides a valuable reference for quality control and further development and utilization of sea buckthorn.