chrysin and baicalin

The aim of this study was to investigate the effects of baicalin, chrysin and their combinations against emamectin benzoate-induced toxicity in rats. For this purpose, sixty four rats were divided into evenly 8 groups with 6-8-week-old male Wistar albino rats, weighing 180-250 g, in each group. While the first group was kept as a control (corn oil), the remaining 7 groups were administered with emamectin benzoate (10 mg/kg bw), baicalin (50 mg/kg bw) and chrysin (50 mg/kg bw) alone or together for 28 days. Oxidative stress parameters, serum biochemical parameters and blood/tissue (liver, kidney, brain, testis and heart) and tissue histopathology were investigated. Compared to the control group, the emamectin benzoate-intoxicated rats had significantly higher tissue/plasma concentrations of nitric oxide (NO) and malondialdehyde (MDA), as well as lower tissue glutathione (GSH) concentrations and antioxidant enzyme activity (glutathione peroxidase/GSH-Px, glutathione reductase/GR, glutathione-S-transferase/GST, superoxide dismutase/SOD, catalase/CAT). Biochemical analysis showed that emamectin benzoate administration significantly increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities, as well as triglyceride, cholesterol, creatinine, uric acid and urea levels, and decreased serum total protein and albumin levels. The histopathological examination of the liver, kidney, brain, heart and testis tissues of the emamectin benzoate-intoxicated rats demonstrated necrotic changes. Baicalin and/or chrysin reversed the biochemical and histopathological alterations induced by emamectin benzoate on these tested organs. Therefore, baicalin and chrysin (alone or in combination) could offer protection against emamectin benzoate-induced toxicity.

Topics: Animals; Antioxidants; Glutathione; Kidney; Liver; Male; Oxidative Stress; Rats; Rats, Wistar

Chaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects.. Toll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation.. The main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 μg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages.. The main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins.. CQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects.

Topics: Acinar Cells; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ceruletide; Drugs, Chinese Herbal; Emodin; Flavonoids; Inflammasomes; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreatitis; RAW 264.7 Cells; Toll-Like Receptor 3

Protective effect of mixture of flavonoids baicalin and chrysin (BCH) was studied against methylglyoxal (MG, a precursor of AGEs) induced cytotoxicity in NRK 52E kidney epithelial cells. Flow cytometry and microscopic analysis showed increased ROS generation, compromised antioxidant status, depolarization of mitochondria and apoptosis in MG stressed cells which were significantly transformed (p≤0.01) during BCH co-treatment. In vivo studies in streptozotocin induced diabetic rats increased protein levels of iNOS, protein kinase C (PKC) and decreased IκB which was modulated by oral BCH treatment (75mg baicalin and 10mg chrysin/kg b.wt.). Increased levels of AGEs and their receptor proteins (RAGE) in diabetic rats were reduced significantly (p≤0.01) in BCH treated group. Renal tubular injuries and deranged kidney function were significantly improved in BCH treated animals. The results indicate that the protection accorded by BCH through its antioxidant and anti-inflammatory effects can be explored for management of diabetic nephropathy.

Topics: Animals; Apoptosis; Cell Line; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Drug Therapy, Combination; Epithelial Cells; Flavonoids; Glycation End Products, Advanced; Male; Mitochondria; Oxidative Stress; Pyruvaldehyde; Rats; Reactive Oxygen Species; Streptozocin

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Flavonoids; Humans

Wogonin and baicalein are bioactive flavones in the popular Chinese herbal remedy Huang-Qin (Scutellaria baicalensis Georgi). These specialized flavones lack a 4'-hydroxyl group on the B ring (4'-deoxyflavones) and induce apoptosis in a wide spectrum of human tumor cells in vitro and inhibit tumor growth in vivo in different mouse tumor models. Root-specific flavones (RSFs) from Scutellaria have a variety of reported additional beneficial effects including antioxidant and antiviral properties. We describe the characterization of a new pathway for the synthesis of these compounds, in which pinocembrin (a 4'-deoxyflavanone) serves as a key intermediate. Although two genes encoding flavone synthase II (FNSII) are expressed in the roots of S. baicalensis, FNSII-1 has broad specificity for flavanones as substrates, whereas FNSII-2 is specific for pinocembrin. FNSII-2 is responsible for the synthesis of 4'-deoxyRSFs, such as chrysin and wogonin, wogonoside, baicalein, and baicalin, which are synthesized from chrysin. A gene encoding a cinnamic acid-specific coenzyme A ligase (SbCLL-7), which is highly expressed in roots, is required for the synthesis of RSFs by FNSII-2, as demonstrated by gene silencing. A specific isoform of chalcone synthase (SbCHS-2) that is highly expressed in roots producing RSFs is also required for the synthesis of chrysin. Our studies reveal a recently evolved pathway for biosynthesis of specific, bioactive 4'-deoxyflavones in the roots of S. baicalensis.

Topics: Acyltransferases; Animals; Antioxidants; Apoptosis; Biosynthetic Pathways; Cell Line, Tumor; Cytochrome P-450 Enzyme System; Flavanones; Flavones; Flavonoids; Gene Expression Regulation, Plant; Humans; Mice; Plant Extracts; Plants, Medicinal; Scutellaria baicalensis

A simple and effective neuraminidase-immobilized capillary microreactor was fabricated by glutaraldehyde cross-linking technology for screening the neuraminidase inhibitors from traditional Chinese medicines. The substrate and product were separated by CE in short-end injection mode within 2 min. Dual-wavelength ultraviolet detection was employed to eliminate the interference from the screened compounds. The parameters relating to the separation efficiency and the activity of immobilized neuraminidase were systematically evaluated. The activity of the immobilized neuraminidase remained 90% after 30 days storage at 4°C. The immobilized NA microreactor could be continuously used for more than 200 runs. The Michaelis-Menten constant of neuraminidase was determined by the microreactor as 136.6 ± 10.8 μM. In addition, six in eighteen natural products were found as potent inhibitors and the inhibition potentials were ranked in the following order: bavachinin>bavachin>baicalein>baicalin>chrysin and vitexin. The half-maximal inhibitory concentrations were 59.52 ± 4.12, 65.28 ± 1.07, 44.79 ± 1.21 and 31.62 ± 2.04 for baicalein, baicalin, bavachin and bavachinin, respectively. The results demonstrated that the neuraminidase-immobilized capillary microreactor was a very effective tool for screening neuraminidase inhibitors from traditional Chinese medicines.

Topics: Drugs, Chinese Herbal; Electrophoresis, Capillary; Enzyme Inhibitors; Enzymes, Immobilized; Flavanones; Flavonoids; Neuraminidase

A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin in rat plasma, using naringin as an internal standard. After acidifying with HCl, plasma samples were pretreated by liquid-liquid extraction with acetone. Chromatographic separation was accomplished on a Hypersil Gold-C(18) analytical column (2.1×150 mm, 5 μm) utilizing a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. All analytes showed good linearity over the investigated concentration range (r>0.9900). The lower limit of quantification was 0.5 ng/ml for baicalin, wogonoside, wogonin and oroxylin A, and 1.0 ng/ml for baicalein and chrysin. Intra-day and inter-day precisions (RSD%) were less than 15% and accuracy (RE%) ranged from -6.7% to 5.8%. The validated method was successfully applied to investigate the pharmacokinetics of the major flavonoids of Radix scutellariae extract after oral administration to rats.

Topics: Administration, Oral; Animals; Area Under Curve; Chromatography, Liquid; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucosides; Half-Life; Limit of Detection; Male; Metabolic Clearance Rate; Plant Extracts; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Scutellaria baicalensis; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

In this study, the effectiveness of both classical and novel polymeric sorbents used in solid-phase extraction (SPE) for isolation of pharmacologically active flavones (baicalin, luteolin, apigenin, wogonin and chrysin) from aerial parts of 13 species of Scutellaria L. (Skullcap) genus was assessed. The highest recoveries of hydrophilic (baicalin, luteolin) flavones for Oasis HLB were obtained, whereas for medium hydrophobic (apigenin) and hydrophobic (wogonin, chrysin) flavones better quantitative results for BakerBond phenyl cartridges were stated. Eluates were analysed using reversed-phase high-performance liquid chromatography with diode array detection (RP-HPLC-DAD). For the five target compounds the determined concentrations ranged from approximately 4 to approximately 15,500 microg/g dry wt. Very good linearities (r(2)>0.9995) of calibration curves were achieved for each flavone. The accuracy was below 5% for most compounds examined. This is the first method reported that enabled simultaneous qualification and quantitation of five flavones (being chemotaxonomic markers) in 13 species of Scutellaria L. genus.

Topics: Apigenin; Chemotactic Factors; Chromatography, High Pressure Liquid; Flavones; Flavonoids; Luteolin; Molecular Structure; Plant Extracts; Polymers; Scutellaria; Silicon Dioxide