Stir-bar sorptive extraction based on hydroxyl-functionalized zirconium-metal-organic framework for the detection of three quinolones in actual samples.

A novel analytical method based on stir-bar sorptive extraction was proposed for the determination of three trace quinolones in fish and shrimp samples. UiO-66-(OH)2 , a hydroxyl-functionalized zirconium metal-organic framework, has been coated on frosted glass rods by an in situ growth method. The product, UiO-66-(OH)2 modified frosted glass rods, has been characterized and key parameters have been optimized in combination with ultra-high-performance liquid chromatography. The detection limits of enoxacin, norfloxacin, and ciprofloxacin were 0.48-0.8 ng ml-1 , and the detection concentrations were in the range of 10-300 ng ml-1 , showing a good linear relationship. This method was used for the determination of three quinolones in aquatic organisms, and the recoveries in spiked fish and shrimp muscle tissue samples were 74.8%-105.4% and 82.5%-115.8%, respectively. The relative standard deviations were less than 6.9%. The established method combined stir-bar sorptive extraction based on UiO-66-(OH)2 modified frosted glass rods with ultra-high-performance liquid chromatography, has good application prospects for the detection of quinolone residues in fish and shrimp muscle samples.

Optimization of clofibrate with O-desmethyl anetholtrithione lead to a novel hypolipidemia compound with hepatoprotective effect.

Oxidative stress and inflammation were considered to be the major mechanisms in liver damage caused by clofibrate (CF). In order to obtain lipid-lowering drugs with less liver damage, the structure of clofibrate was optimized by O-desmethyl anetholtrithione and got the target compound clofibrate-O-desmethyl anetholtrithione (CF-ATT). CF-ATT significantly reduced the levels of plasma triglycerides (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR-1339. In addition, CF-ATT has a significantly protective effect on the liver compared with CF. The liver weight and liver coefficient were reduced. The hepatic function indexes were also decreased, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Histopathological examination of the liver revealed that inflammatory cell infiltration, nuclear degeneration, cytoplasmic loosening and hepatocyte necrosis were ameliorated by administration with CF-ATT. The hepatoprotective mechanism showed that CF-ATT significantly up-regulated Nrf2 and HO-1 protein expression and down-regulated p-NF-κB P65 expression in the liver. CF-ATT has obviously antioxidant and anti-inflammatory activity. These findings suggested that CF-ATT has significant hypolipidemia activity and exact hepatoprotective effect possibly through the Nrf2/NF-κB-mediated signal pathway.

1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

Design, synthesis of Cinnamyl-paeonol derivatives with 1, 3-Dioxypropyl as link arm and screening of tyrosinase inhibition activity in vitro.

This study aimed to obtain tyrosinase inhibitors for treating hyperpigmentation. A series of cinnamyl ester analogues were designed and synthesized with cinnamic acid (CA) and peaonol compounds. The safety, melanin content and inhibitory effects of all target compounds were evaluated. In the enzymatic activity test, the inhibitory rate of compounds 8, 13 and 14 had stronger inhibitory activity with the IC50 values of 20.7 µM, 13.98 µM and 15.16 µM, respectively than the positive drug kojic acid (IC50 with 30.83 µM). The cytotoxicity evaluation showed that compounds 13 and 14 have higher safety than the other compounds to the proliferation of B16F10 cells. The result of the melanocyte test supported that compound13 has stronger cellular tyrosinase inhibitory activity than kojic acid and arbutin at 100 µM and 200 µM. The enzyme kinetics mechanism revealed that compound 13 was a non-competitive inhibitor while compounds 8 and 14 were mixed inhibitors. For the experiments of melanin content and tyrosinase activity in the B16F10 melanona cells, the inhibition rates of compounds 8, 14 and 13 were with 19.62%, 20.59% and 23.83%, respectively. In addition, compound 13 revealed the highest inhibitory activity to tyrosinase in the melanocyte with inhibition rates of 23.83%, which was better than kojic acid and arbutin (19.21% and 20.45%) at the same concentration. In the anti-melanogenesis experiment, compounds 8 and 13 had better anti-melanin effects than kojic acid from 25 µM to 100 µM. In summary, the results indicated that compounds 8, 13 and 14 had better tyrosinase inhibitory activity and anti-melanogenesis activity. Especially, the compound 13 has potentiality to develop novel tyrosinase inhibitors and whitening agents. The docking studies results revealed that the functional group of compound 13 mostly depends on the phenolic hydroxyl moiety, and its hydroxyl group did not insert into the active site of tyrosinase, which was in agreement with the results of the kinetics study.

Study on the protective effects of danshen-honghua herb pair (DHHP) on myocardial ischaemia/reperfusion injury (MIRI) and potential mechanisms based on apoptosis and mitochondria.

CONTEXT: Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge (Labiatae) and honghua, the dried flower of Carthamus tinctorius L. (Compositae) as the herb pair was used to treat cardiovascular diseases (CVD). OBJECTIVE: To study the effects of DHHP on MIRI and mechanisms based on apoptosis and mitochondria. MATERIALS AND METHODS: 36 SD rats (n = 6) were randomly divided into control group (Con), the ischaemia-reperfusion group (IR), positive control (Xinning tablets, XNT, 1 g/kg/d) and DHHP (1.2, 2.4, and 4.8 g/kg/d). Except for Con, the other groups were intragastrically administrated for 5 d, the rat hearts were isolated to establish the MIRI model in vitro for evaluating the effects of DHHP on MIRI. 24 SD rats (n = 6) were randomly divided into Con, IR, DPPH2.4 (2.4 g/kg/d) and DPPH 2.4 + Atractyloside (ATR) (2.4 + 5 mg/kg/d), administered intragastrically for 5 d, then treated with ATR (5 mg/kg/d) by intraperitoneal injection in DPPH2.4 + ATR group, took rat hearts to establish MIRI model in vitro for revealing mechanism. RESULTS: Myocardial infarct sizes were, respectively, 0.35%, 40.09%, 15.84%, 30.13%, concentrations of NAD+ (nmol/gw/w) were 144, 83, 119, and 88, respectively, in Con, IR, DHHP2.4, DHHP2.4 + ATR group. Cleaved caspase-3 were 0.3, 1.6, 0.5 and 1.3% and cleaved caspase-9 were 0.2, 1.1, 0.4 and 0.8%, respectively, in Con, IR, DHHP2.4 and DHHP2.4 + ATR group. The beneficial effects of DHHP on MIRI were reversed by ATR. CONCLUSIONS: The improvement of MIRI by DHHP may be involved in inhibiting MPTP opening, decreasing oxidative damage, alleviating ischaemic injury and inhibiting cardiomyocyte apoptosis.

3,4-Dihydroxyphenethyl nitrate with nitric oxide releasing, antioxidant, hypoglycemic and hypolipidemic effects.

Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO2) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO2 significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO2 also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO2 displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO2 shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications.

Design, synthesis and evaluation of 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-Based fibrates as potential hypolipidemic and hepatoprotective agents.

Six novel target compounds 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT) based fibrates were synthesized and evaluated. All the synthesized compounds were preliminarily screened by using the Triton WR-1339-induecd hyperlipidemia model, in which T1 exhibited more potent hypolipidemic property than positive drug fenofibrate (FF). T1 also significantly decreased serum triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in methionine solution (Mets) induced hyperlipidemic mice. Moreover, hepatic transaminases (AST and ALT) were obviously ameliorated after treatment with T1 and the histological observation indicated that T1 ameliorated the injury in liver tissue and inhibited the hepatic lipid accumulation. In the livers of T1-administrated rat, the levels of PPARα related to lipids metabolism were up-regulated. Additional effects such as antioxidant, anti-inflammatory and H2S releasing action confirmed and reinforced the activity of T1 as a potential multifunctional hypolipidemic and hepatoprotective agent.

Design, synthesis and evaluation of phenylfuroxan nitric oxide-donor phenols as potential anti-diabetic agents.

Both nitric oxide (NO) dysfunction and oxidative stress have been regarded as the important factors in the development and progression of diabetes and its complications. Multifunctional compounds with hypoglycemic, NO supplementation and anti-oxidation will be the promising agents for treatment of diabetes. In this study, six phenylfuroxan nitric oxide (NO) donor phenols were synthesized, which were designed via a combination approach with phenylfuroxan NO-donor and natural phenols. These novel synthetic compounds were screened in vitro for α-glucosidase inhibition, NO releasing, anti-oxidation, anti-glycation and anti-platelet aggregation activity as well as vasodilatation effects. The results exhibited that compound T5 displayed more excellent activity than other compounds. Moreover, T5 demonstrated significant hypoglycemic activity in diabetic mice and oral glucose tolerance test (OGTT) mice. T5 also showed NO releasing and anti-oxidation in diabetic mice. Based on these results, compound T5 deserves further study as potential new multifunctional anti-diabetic agent with antioxidant, NO releasing, anti-platelet aggregation and vasodilatation properties.

Synthesis, nitric oxide release, and dipeptidyl peptidase-4 inhibition of sitagliptin derivatives as new multifunctional antidiabetic agents.

Nitric oxide (NO) dysfunction has been found to be an important factor in both the development and progression of diabetic complications due to its many roles in the vascular system. Multifunctional compounds with hypoglycemic and endothelial protective action will be promising agents for the treatment of diabetes and its complications. In this study, a series of novel NO-donating sitagliptin derivatives and relevant metabolites were synthesized and evaluated as potential multifunctional hypoglycemic agents. All of synthetic compounds shown remarkable inhibitory activity against dipeptidyl peptidase IV (DPP-IV) in vitro and demonstrated excellent hypoglycemic activities in diabetic mice, similar to the activity of sitagliptin, and compounds T1-T4 shown different extents of NO-releasing abilities and potent antioxidant abilities in vivo. By screening in DPP-4, compound T4 was recognized as a potent DPP-4 inhibitor with the IC50 value of 0.060 µM. Docking study revealed compound T4 has a favorable binding mode. Furthermore, compounds T1-T4 exhibited different extents of NO-releasing abilities and excellent anti-platelet aggregation in vitro. The overall results suggested that T4 could help to the amelioration of endothelial dysfunction by reducing blood glucose, lessening oxidative stress and raising NO levels as well as inhibiting platelet aggregation. Based on this research, compound T4 deserves further investigation as potential new multifunctional anti-diabetic agent with antioxidant, anti-platelet aggregation and endothelial protective properties.

5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates as potential hypolipidemic and hepatoprotective agents.

Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compound 6 shown more significant antidyslipidemic activity than fenofibrate (FF). The compound 6 was also found to reduce serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in HFD-induced hyperlipidemic mice. Moreover, compound 6 displayed hepatoprotective effect, a significant amelioration in hepatic indices (AST and ALT) toxicity was observed and the histological examination showed that compound 6 inhibited the development of hepatic lipid accumulation and ameliorated the damage in hepatic tissue compared to model mice. Additional effects such as the potent antioxidant and anti-inflammatory action confirmed and reinforced the efficacy of compound 6 as a new agent of dual-effect hypolipidemic and hepatoprotective activities.

A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects.

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.

Phenylsulfonylfuroxan NO-donor phenols: Synthesis and multifunctional activities evaluation.

Phenylsulfonyfuroxan nitric oxide (NO)-donor phenols were designed, synthesized and evaluated. The compounds were designed through a symbiotic approach using selected phenols and phenylsulfonylfuroxan NO-donor. The antioxidant activities of the hybrid compounds T2-T6 showed to be good in vivo. Compounds T4 and T6 revealed excellent yeast α-glucosidase inhibitory activity and anti-glycosylation activity. All of the compounds exhibited strong NO releasing activity and significant anti-platelet aggregation activity. The inhibition of platelet aggregation was more than 50% at low concentration (1.5µM) and 95% at higher concentration (15µM and 150µM). The vasodilatation experiment demonstrated that the six compounds under test exhibited definite vasodilation activity (pIC50 ranged from 5.698 to 6.383), especially compound T6 (pIC50 was 6.383) which was similar to sodium nitroprusside (pIC50 was 6.786). Both anticoagulant and vasodilatation effects were correlated with their NO releasing activities. These hybrid phenylsulfonyfuroxan-based NO-donor phenols offer a multifunctional prodrug design concept for the development of therapeutic or preventive agents for metabolic syndrome.

A collapse risk assessment method for subway foundation pit based on cloud model and improved Dempster-Shafer evidence theory.

Collapse is a major engineering hazard in open-cut foundation pit construction, and risk assessment is crucial for considerably reducing engineering hazards. This study aims to address the ambiguity problem of qualitative index quantification and the failure of high-conflict evidence fusion in risk assessment. Thus, a fast-converging and high-reliability multi-source data fusion method based on the cloud model (CM) and improved Dempster-Shafer evidence theory is proposed. The method can achieve an accurate assessment of subway pit collapse risks. First, the CM is introduced to quantify the qualitative metrics. Then, a new correction parameter is defined for improving the conflicts among evidence bodies based on conflict degree, discrepancy degree and uncertainty, while a fine-tuning term is added to reduce the subjective effect of global focal element assignment. Finally, the risk assessment result is obtained according to the maximum affiliation principle. The method is successfully applied to Luochongwei Station, where the difference between the maximum value and the second largest value of the basic probability assignment is 0.624, and the global uncertainty degree is 0.087. Both values satisfy the decision evaluation condition; however, values of other methods only satisfy one or neither condition. In addition, the proposed method requires only four cycles to reach the steady state by fusing data of the same index, which has faster convergence compared with that of other methods. The proposed method has good universality and effectiveness in subway pit collapse risk assessment.

Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway.

PURPOSE: Investigate the protective effect and mechanism of Puerarin (PU) against Dioscorea bulbifera L. (DB)-induced liver injury. MATERIALS AND METHODS: The protective effect of PU against DB-induced liver injury was evaluated by the present animal experiment, which assessed the pathological changes in the liver of mice and detected Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (AKP), as well as inflammation and oxidative stress-related indexes. Finally, the transcription and expression of related proteins were detected using western blot and quantitative reverse transcription (PCR) techniques. RESULTS: PU significantly increased body weight, reduced liver index, and attenuated pathological changes in the liver compared to the DB group. It also decreased levels of AST, ALT, AKP, tumor necrosis factor-α, interleukin-1ß, and malondialdehyde while increasing interleukin-10 levels and superoxide dismutase activity. Additionally, it upregulated inhibitor of NF-κB (IκB-α), B-cell lymphoma-2 (Bcl-2), Nuclear respiratory factor 2 (Nrf2), and Heme oxygenase 1 (HO-1) expression while down-regulating p-NF-κB p65 and bcl2-associated x (Bax) expression in the liver. Furthermore, PU upregulated protein and gene expression levels of Multidrug resistance-associated protein2, bile salt export pump, p-glycoprotein, and UDP-glucuronyltransferase 1A1 (UGT1A1) as well. CONCLUSION: PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.

UPLC-Q-TOF-MS/MS Combined with Network Pharmacology, Molecular Docking, and Animal Verification Reveals the Mechanism of Insomnia Treatment by Shen Qi Wu Wei Zi Capsules.

BACKGROUND: Shen Qi Wu Wei Zi capsules (SQWWZ) are often used to treat insomnia; however, the potential therapeutic mechanism is still unclear. OBJECTIVE: This study aimed to investigate the mechanism underlying the therapeutic effects of the Shen Qi Wu Wei Zi capsules on insomnia. METHODS: The components of SQWWZ were identified using the UPLC-Q-TOF-MS/MS technique in conjunction with relevant literature. Insomnia-related targets were searched in the Gene- Cards and DisGeNET databases, and the intersection targets were obtained using a Venn diagram. A component-target-insomnia network diagram was constructed using Cytoscape 3.7.2 software. Core targets underwent GO and KEGG enrichment analyses. Molecular docking techniques were employed to verify the key proteins involved in the pathway and their corresponding compounds. Insomnia was induced in SD rats through the intraperitoneal injection of pchlorophenylalanine (DL-4-chlorophenylalanine, PCPA). The rats were treated orally with SQWWZ, and the serum levels of 5-HT and GABA in each group were determined using ELISA. Histological analysis of hippocampal tissue sections from the rats was performed using HE staining. RESULTS: Using UPLC-Q-TOF-MS/MS and reviewing relevant literature, we identified 49 components of SQWWZ. Additionally, we obtained 1,043 drug targets and 367 insomnia-related targets. Among these, 82 targets were found to be common to both drug and insomnia targets. Following drug administration, rats in the treatment group exhibited a significant increase in the serum levels of 5-HT and GABA. Moreover, histological analysis using HE staining revealed neatly arranged hippocampal neuronal cells in the treated rats. CONCLUSION: The active components of SQWWZ had good inhibition of insomnia. This study provides a reference and guidance for the in-depth study of SQWWZ for the treatment of insomnia.

Studies on the Preparation of a Microemulsion Formulation of Matricaria Recutita Essential Oil and the Treatment of 2,4-Dinitro-Chlorobenzene- Induced Eczema in Mice by Inhibiting Inflammation.

BACKGROUND: Eczema, an inflammatory skin disease causing intense itching, is a function of a range of internal and external factors, impacting individuals of all ages and leading to economic loss. Inflammation is the most important manifestation of eczema, and Matricaria recutita essential oil (MREO) extracted from Matricaria recutita possesses excellent antibacterial and anti-inflammatory properties. METHODS: In this study, Matricaria recutita microemulsions were prepared by the trans-phase emulsification method and their stability was determined by evaluating the relevant indexes. Establishment of 2,4-dinitro-chlorobenzene-induced AD model in mice. Detection of serum indexes of IL-6, IL-17, and TNF-α, and on pathological tissue sections, the HE staining, toluidine blue staining, immunohistochemistry, and observation were performed. RESULTS: The study obtained optimal conditions for the preparation of microemulsion formulations of Matricaria recutita. Through quality evaluation, it was found that the microemulsion increased stability, reduced irritation, and retained anti-inflammatory activity and therapeutic effects on eczema compared to Matricaria recutita essential oil (MREO). Studies have demonstrated that microemulsion formulations of Matricaria recutita and Matricaria recutita significantly down regulate the proinflammatory factors TNF-α, IL-17, and IL-6. It was shown by hematoxylin-eosin (HE) staining that both Matricaria recutita essential oil (MREO) and Matricaria recutita microemulsion (MRME) improved the inflammatory status of eczematous skin tissues in mice. The number of mast cells expressed in the tissues was decreased in the surface-treated group, as shown by toluidine blue staining. Additionally, the number of mast cells expressed in the tissues in the surface-treated group was reduced, as demonstrated by immunohistochemistry. Furthermore, immunohistochemistry revealed that MREO and MRME have immunomodulatory effects on the tissues. CONCLUSION: The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

Therapeutic mechanism of Cornus Officinalis Fruit Coreon on ALI by AKT/Nrf2 pathway and gut microbiota.

BACKGROUND: Acute liver injury (ALI) often precipitates severe liver function impairment and is associated with high mortality rates. Traditional Chinese Medicine (TCM) has demonstrated efficacy in mitigating hepatic damage by exhibiting anti-inflammatory effects, enhancing antioxidant activity, and modulating gut microbiota (GM). Numerous studies have identified similar or identical bioactive compounds within the Cornus Officinalis Fruit Coreon(COFO) and its flesh. Notably, Cornus Officinalis has been shown to possess potent hepatoprotective properties. However, studies on the pharmacological effects and mechanism of action of COFO for hepatoprotection have received little attention. PURPOSE: To elucidate the mechanisms underlying the COFO effect in ALI by integrating GM gene sequencing, quantifying Short-Chain Fatty Acids (SCFAs), and examining relevant signaling pathways. MATERIALS AND METHODS: A rat model for carbon tetrachloride (CCl4)-induced ALI was established, and the best liver protective components of COFO were selected by pathological observation and biochemical determination. The therapeutic efficacy of COFO in mitigating liver injury was elucidated through an integrated approach that included network pharmacology, biochemical indexes, 16S rDNA sequencing analyses, short-chain fatty acids, Western blotting analysis of protein levels, and immunohistochemical evaluations. RESULTS: Pharmacological evaluation established that the n-butanol fraction (CNBP) provided optimal hepatoprotective effects. Firstly, the chemical constituents of CNBP were characterized, and its principal anti-ALI targets, such as ALI, AKT1, TNF, and IL-6, were identified through network pharmacology analysis. Secondly, experimental validation revealed that CNBP may enhance the genetic diversity of the GM, augmenting the diversity of the microbial community, increasing the levels of three SCFAs, and activating key proteins in the AKT/Nrf2 signaling pathway (AKT1, TNF-α, IL-6, NF-κB p65, Nrf2, and HO-1). Consequently, CNBP exhibited hepatoprotective effects, with antioxidative and anti-inflammatory properties. CONCLUSION: CNBP may mitigate GM-induced disturbances, augment the levels of three SCFAs, activate the AKT/Nrf2 signaling pathway, and exhibit antioxidant and anti-inflammatory effects, thereby conferring hepatoprotective benefits.