Effects of curcumin on non-alcoholic fatty liver disease: A scientific metrogy study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases encountered in clinical practice. Curcumin can alleviate insulin resistance, inhibit oxidative stress response, reduce inflammation, reduce liver fat deposition, and effectively improve NAFLD through various modalities, inhibiting the progression into cirrhosis and fibrosis. PURPOSE: To explore the current status, hot spots, and developing trends of curcumin in NAFLD treatment through quantitative scientific analysis to serve as a reference for subsequent studies. STUDY DESIGN: A comprehensive analysis of the mechanism of action of curcumin in the treatment of NAFLD and methods to increase curcumin bioavailability using bibliometric analysis and literature review. METHODS: This study used VOSviewer software to analyze the literature related to curcumin treatment of NAFLD in the Web of Science (WOS) core set database. A comprehensive and in-depth review was conducted based on the results of scientific econometric research and literature review. RESULTS: The review observed that curcumin can activate various signaling pathways such as AMPK and NF-κB to inhibit oxidative stress and apoptosis, thereby reflecting its pharmacological effects: lowering lipid, anti-inflammatory, reducing insulin resistance, and anti-fibrosis. These mechanisms improve or even reverse the complex pathological features of lipid metabolism disorders associated with NAFLD. Curcumin also can potentially serve as a primary regulatory target for treating hepatic steatosis using gut microbiota. However, these pharmacological effects of curcumin were limited owing to its low bioavailability. CONCLUSION: This review discusses NAFLD treatment with curcumin, analyzes the reasons for its low bioavailability, and introduces models for studying and methods for improving curcumin bioavailability. As research on NAFLD grows, future research should capture the trend of basic research, pay attention to clinical research, and continuously explore the therapeutic potential of curcumin.

UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Lamiophlomis Herba against hepatic fibrosis.

BACKGROUND: Lamiophlomis Herba (LH) is a valuable traditional medicinal plant found on the Qinghai-Tibetan Plateau that promotes blood circulation, removes blood stasis, and has antibacterial and anti-inflammatory properties. The main components of LH are iridoid glycosides, phenethyl alcohol glycosides, flavonoids, and polysaccharides. PURPOSE: To investigate the mechanism of the anti-liver fibrosis effects of LH and screen for its bioactive compounds. STUDY DESIGN: Screening LH marker components and validating the LH anti-liver fibrosis mechanism. METHODS: The active ingredients of LH were identified using UPLC-Q-TOF-MS, and HotMap combined with principal components analysis (PCA) was used to screen for marker components. Network pharmacology and molecular docking techniques were used to predict the potential anti-fibrotic targets of LH. Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting were used for experimental validation and mechanistic studies. RESULTS: Fifteen compounds that actively contributed to the cluster were identified as marker compounds. Acteoside, 8-O-acetyl shanzhiside methyl ester (8-O-ASME), Luteolin, Shanzhiside Methyl ester (SME), Loganin, Loganate were the main active components. Network pharmacology and molecular docking studies have shown that LH might improve liver fibrosis, inflammation, and oxidative stress, which might be related to key targets such as PTGS2, MAPK, EGFR, AKT1, SRC, Fn1, Col3a1, Col1a1, and PC-III. The results of ELISA, RT-PCR and western blot experiments showed that Acteoside, 8-O-ASME, Luteolin, SME, Loganin, Loganate, and the LH group could reduce the levels of fibronectin, Col1a1, Col3a1, α-SMA, Col-Ⅳ, LN, and PC-Ⅲ. CONCLUSION: LH improves liver fibrosis induced by HSC-T6 cells and inhibits the deposition of extracellular matrix (ECM) in hepatocytes, resulting in a decrease in the degree of liver fibrosis and a good anti-liver fibrosis effect.

Mechanisms of theaflavins against gout and strategies for improving the bioavailability.

BACKGROUND: Gout is a crystal related arthropathy caused by monosodium urate deposition. At present, the identification of appropriate treatments and new drugs to reduce serum uric acid levels and gout risk is a major research area. PURPOSE: Theaflavins are naturally occurring compounds characterized by a benzodiazepine skeleton. The significant benefits of theaflavins have been well documented. A large number of studies have been carried out and excellent anti-gout results have been achieved in recent years. STUDY DESIGN: A comprehensive analysis of the mechanism of the anti-gout effect of theaflavins is presented through a literature review and network pharmacology prediction, and strategies for increasing the bioavailability of theaflavins are summarized. METHODS: In this review, the active components and pharmacological mechanisms of theaflavins in the treatment of gout were summarized, and the relationship between theaflavins and gout, the relevant components, and the potential mechanisms of anti-gout action were clarified by reviewing the literature on the anti-gout effects of theaflavins and network pharmacology. RESULTS: Theaflavins exert anti-gout effects by down regulating the gene and protein expression of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1), while upregulating the mRNA expression levels of organic anion transporter 1 (OAT1), organic cation transporter N1 (OCTN1), organic cation transporters 1/2 (Oct1/2), and organic anion transporter 2 (OAT2). Network pharmacology prediction indicate that theaflavins can regulate the AGE-RAGE and cancer signaling pathways through ATP-binding cassette subfamily B member 1 (ABCB1), recombinant mitogen activated protein kinase 14 (MAPK14), telomerase reverse tranase (TERT), signal transducer and activator of transcription 1 (STAT1), matrix metalloproteinase 2 (MMP2), B-cell lymphoma-2 (BCL2), and matrix metalloproteinase 14 (MMP14) targets for anti-gout effects. CONCLUSION: This review presents the mechanisms of anti-gout action of theaflavins and strategies for improving the bioavailability of theaflavins, as well as providing research strategies for anti-gout treatment measures and the development of novel anti-gout drugs.

Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension.

Eucommiae Folium (EF), a traditional Chinese medicine, has been used to treat secondary hypertension, including renal hypertension and salt-sensitive hypertension, as well as hypertension caused by thoracic aortic endothelial dysfunction, a high-fat diet, and oxidized low-density lipoprotein. The antihypertensive components of EF are divided into four categories: flavonoids, iridoids, lignans, and phenylpropanoids, such as chlorogenic acid, geniposide acid and pinoresinol diglucoside. EF regulates the occurrence and development of hypertension by regulating biological processes, such as inhibiting inflammation, regulating the nitric oxide synthase pathway, reducing oxidative stress levels, regulating endothelial vasoactive factors, and lowering blood pressure. However, its molecular antihypertensive mechanisms are still unclear and require further investigation. In this review, by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology, we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension, the related components, and underlying mechanisms. The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component, multi-target and multi-pathway mechanism. In particular, we discussed the role of EF targets in the treatment of hypertension, including epithelial sodium channel, heat shock protein70, rho-associated protein kinase 1, catalase, and superoxide dismutase. The relevant signal transduction pathways, the ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/eNOS/NO/Ca2+ pathways, are also discussed.

Clinical metabolomic analysis of Danlou tablets with antioxidant effects for treating stable angina pectoris.

The Danlou tablets (DLT) is a patented Chinese medicine that can effectively ameliorate coronary heart disease- and angina pectoris-related chest congestion and pain. However, the mechanism underlying the therapeutic effects of DLT in the context of stable angina pectoris (SAP) has not been clearly elucidated. In this study, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze serum samples from patients with SAP before and after DLT administration. The results of metabolomic analyses were verified biologically, and the mechanisms of action of DLT with respect to treating SAP were elucidated. Nineteen biomarkers were identified. Among these biomarkers, the levels of 15 reverted to those corresponding to a healthy state following DLT treatment. The main metabolic pathways associated with the functions of DLT in SAP were energy metabolism, purine metabolism, glycerophospholipid metabolism and amino acid metabolism, all of which are related to oxidative stress. Biological verification revealed that DLT decreased the expression of the oxidative stress indicators, xanthine oxidase (XOD) and malondialdehyde (MDA), and increased heme oxygenase-1 (HO-1) expression and superoxide dismutase (SOD) activity. Taken together, we revealed that DLT effectively ameliorates SAP by adjusting the oxidative stress status. This study provided an objective index for evaluating the efficacy of DLT for treating SAP.

UPLC-MS analysis and network pharmacology-based investigation into the active ingredients and molecular mechanisms of anti-fatigue of male flowers with Eucommia ulmoides Oliv.

The male flowers of Eucommia ulmoides Oliv. (MFEU) was a natural product that could alleviate fatigue and accelerate fatigue alleviation. Nonetheless, the active ingredients and underlying pharmacological mechanisms remain unknown. This study aimed to decode the active ingredients and potential action mechanisms of MFEU in the therapy of anti-fatigue using an integrated UPLC-MS analysis, network pharmacology approach, and cell experiments. Characterizations of chemical constituents of MFEU extract were identified by UPLC-Q-TOF-MS. The corresponding drug targets were retrieved from the drug target database and used to construct the "composite-target-pathway" network. The Cytoscape was used to identify potential protein targets of these MFEU components, indicating that 24 anti-fatigue compounds in MFEU regulate 18 anti-fatigue-related targets in 10 signaling pathways. The 16 components of MFEU were verified at the cellular level. The results of cell experiments showed that MFEU extract (0.361 µg/ml), Caffeic acid, Deacetylasperulosidic acid, Naringenin, Acanthoside B, Geniposidic acid, Rutin, and Quercetin could promote testosterone secretion on Leydig cells at 50 µM. The MFEU extract and seven compounds in MFEU might play a role in anti-fatigue by participating in the regulation of testosterone secretion. Finally, the results of PCR analysis showed that MFEU promotes the secretion of testosterone, which is related to CYPIIa1 and 17ß-HSD, STAR in the signal pathway of testosterone synthesis. This study provides a basis for further exploring the anti-fatigue mechanism of MFEU, adopting the method of multi-compound and multi-target.

Network pharmacology, molecular docking technology integrated with pharmacodynamic study to reveal the potential targets of Schisandrol A in drug-induced liver injury by acetaminophen.

Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine for protecting liver. However, underlying therapeutic mechanisms of these bioactive lignans from SCF similar hepatoprotective effects against drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of Schisandrol A in the treatment of DILI by APAP. The integrated UPLC-Q-TOF/MS, pharmacodynamic study, histopathological combination with network pharmacology and molecular docking technology were used to explore the potential mechanisms. The results showed that Schisandrol A reduced the level of AST, ALT, MDA, PNP, TNF-α and IL-1ß, increased the levels of the GSH against acute liver failure. Additionally, Schisandrol A could improve the morphological characteristics of DILI by APAP in mice with liver tissue. Molecular docking results had showed that Schisandrol A with high scores when docking with COX-2, ALOX5, CYP2E1, CYP2C9, CYP2C19, EGFR SRC, Nrf2, MAPK14 and MAPK8. The study demonstrated that Schisandrol A could play critical roles in DILI by APAP via regulating TNF signaling pathway, inhibiting oxidative stress, inflammation and inhibiting the activities of cytochrome P450 enzymes, which contributed to searching for leading compounds and the development of new drugs for DILI by APAP.

Evaluation of Biological Mechanisms of Eucommiae Folium in Hypertensive Kidney Injury by Integration of Untargeted Metabolomics and Network Pharmacology.

Hypertensive kidney injury (Hki) is one of the most common complications of hypertension. Early prevention and treatment of renal injury in patients with hypertension is great significance. The study, which used an integrated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis, network pharmacology approach, and plasma metabolomics, aimed to discover the active ingredients and therapeutic mechanisms of Eucommiae folium (Ef) in treating Hki. The chemical components of Ef were analyzed by UPLC-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), and the "compound-target-disease" network was constructed by screening the closely related drug targets from the drug-target database, then the signaling pathways related to Hki were analyzed. Finally, the enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction were used to test and verify the key targets in the common pathways of metabolomics and network pharmacology. The results indicated that Eucommiae folium might play an excellent role in treating Hki, likely through regulating the vascular endothelial growth factor signaling pathway, hypoxia inducible factor 1 (HIF-1) signaling pathway, and glycerophospholipid metabolism pathway, which were validated by increasing levels of nitric oxide, endothelial nitric oxide synthase and reducing levels of endothelin 1, angiotensin II, renin, cyclic guanosine monophosphate, blood urea nitrogen, and serum creatinine, as well as the reduced gene expression of Ache, Ddah2, Egfr, Lcat, Pla2g2a, Stat3 and Vegfa. The study systematically explored the protective mechanisms of Ef against Hki and also provided the practical treatment strategies of Hki from the Chinese herb.

A network pharmacology-integrated metabolomics strategy for clarifying the action mechanisms of Schisandrae Chinensis Fructus for treating drug-induced liver injury by acetaminophen.

Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine (TCM) for protecting liver. However, underlying therapeutic mechanisms of SCF for drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of SCF in the treatment of DILI by APAP using the integrated network pharmacology, plasma metabolomics profiling with UPLC-Q-TOF-MS approach. The key targets in the shared pathways of network pharmacology and metabolomics were screened and experimentally validated by Quantitative Real-time PCR analysis. The results showed that SCF could exert excellent effects on DILI by APAP probably through regulating ErbB signaling pathway and Arachidonic acid metabolism pathway, which was reflected by the reduced gene expression of TNF-α, IL-6, IL-1ß, COX-2 and EGFR, as well as the increased gene expression of Nrf2, HO-1, MDM2, MAPK8, SRC, PLD1, CYP2E1, CYP1A2, CYP3A1. This study systematically explored the pharmacological mechanisms of SCF in the treatment of DILI, meanwhile, metabolomics combine with network pharmacology approach might be a useful strategy for early diagnosis of DILI by APAP.

Network pharmacology based investigation into the bioactive compounds and molecular mechanisms of Schisandrae Chinensis Fructus against drug-induced liver injury.

OBJECTIVE: To investigate the against Drug-induced liver injury ingredients and their functional mechanisms in S. Chinensis Fructus. METHODS: Liquid chromatograph-mass spectrometry analysis was performed on S. Chinensis Fructus extrac. The "Components-Target-Disease" network model was constructed by network pharmacology-based approaches. String analysis was performed to reveal enrichment of these target proteins, protein-protein interactions, pathways and related diseases. And experiment of APAP-induced drug-induced liver injury was to be verified. RESULTS: Cytoscape was used to determine the potential protein targets for these components in S. Chinensis Fructus, indicating that 17 against Drug-induced liver injury compounds in S. Chinensis Fructus regulate 52 diabetes-related proteins in 15 signal pathways and involve 14 core key targets. Verification experiment results that S. Chinensis Fructus prevented the elevation of serum biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), purine nucleoside phosphorylase (PNP) and alkaline phosphatase (ALP) against acute liver failure. Additionally, S. Chinensis Fructus reduced the content of malondialdehyde (MDA), increased the levels of the Superoxide dismutase (SOD) and Glutathione (GSH), and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. CONCLUSION: The mechanisms of S. Chinensis Fructus against Drug-induced liver injury were involved in the regulation of multiple targets, especially affecting the ErbB signaling pathways. The active ingredients of S. Chinensis Fructus may play a role against Drug-induced liver injury by participating in the regulation of inflammatory factors, oxidative stress.

Identification of the constituents and metabolites in rats after oral administration of Zi Shen Formula by UPLC-Q-TOF/MS combined pattern recognition analysis.

An ultra-high-performance liquid chromatography mass spectrometry method was established to detect and identify the chemical constituents of Zi Shen Formula (ZSF) and its metabolites in serum, urine and feces, after oral administration to rats. A total of 68 compounds were characterized in ZSF extracts. In vivo, 38 prototype components and 32 metabolites of ZSF were tentatively identified in rat serum, urine and feces. Seven metabolic pathways including demethylation, hydroxylation, oxidation, sulfation, glucuronidation, methylation and de-caffeoyl were proposed to be involved in the generation of these metabolites. It was found that glucuronidation, methylation and demethylation were the major metabolic processes of alkaloids, while demethylation, methylation, sulfation and de-caffeoyl were the major metabolic pathways of phenylethanoid glycosides. The main metabolic pathways of steroidal saponins were oxidation and isotype reactions. These findings are significant for our understanding of the metabolism of ZSF. The proposed metabolic pathways of bioactive components might be crucial for further studies of the mechanisms of action and pharmacokinetic evaluations of ZSF.

[Molecular characters of Schisandra chinensis with white fruit by RAPD and ISSR makers].

OBJECTIVE: The characters of Schisandra chinensis with white fruit were represented at molecular levels and the genetic diversity were investigated using RAPD and ISSR. METHODS: 12 primers of RAPD randomized markers and 8 primers of ISSR markers were used to test 21 samples of white fruit Schisandra chinensis, and POPGENE 32 software were used to analyze the results. RESULTS: One or more unique bands were produced to distinguish white fruit Schisandra chinensis from normal Schisandra chinensis using the primers of S83, S180 and S300. RAPD:66 discernible DNA fragments were generated with 52 (78.79%) polymorphic fragments; ISSR: 42 discernible DNA fragments were generated with 25 (59.52%) polymorphic fragments. The genetic variation of white fruit Schisandra chinensis was more unstable than normal Schisandra chinensis, but the genetic distance of them was small at the species level. CONCLUSION: RAPD and ISSR markers can be used to put up the characteristics of Schisandra chinensis with white fruit at molecular levels. Also they can indicate the genetic relationship of the Schisandra chinensis germplasm resource.

[Identification of Schisandra chinensis with white fruits based on ITS2 sequences].

OBJECTIVE: To analyse a special kind of Schisandra chinensis with the white fruit using ITS2 barcode at molecular levels. METHOD: ITS2 regions were sequenced bidirectionally. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner, MEGA 5.0 software was used to align the sequences. The ITS2 secondary structure was predicted using ITS2 web server, BLAST 1 method was used to identify the S. chinensis with the white fruit. RESULT: The length of the ITS2 sequence was 231 bp. And the sample was identified as S. chinensis using the method of BLAST 1. Their mean interspecific genetic distance (K2P distance) among the populations of the S. chinensis with the white fruit and S. chinensis was far lower than the mean interspecific genetic distance between the S. chinensis and S. sphenanthera. CONCLUSION: By using ITS2 the S. chinensis with the white fruit was identified as S. chinensis, and the ITS2 barcode could be used to identify S. chinensis and S. sphenanthera.

[Changes of fingerprints with crude and processed cassiae semen in xuezhiling tablets].

OBJECTIVE: To establish an effective and convenient method for HPLC fingerprints of Xuezhiling tablets and new Xuezhiling tablets, and to observe the changes of fingerprint with crude and processed Cassiae Semen in Xuezhiling tablets. METHODS: The HPLC with Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) column was used for the gradient elution of acetonitrile-0.1% phosphoric acid solution, at the flow rate of 1.0 mL/min. Detection wavelength was set at 284 nm and the column temperature was 30 degrees C. RESULTS: Ten batches of Xuezhiling tablets and new Xuezhiling tablets were tested and gained HPLC fingerprint containing 20 common peaks, respectively. CONCLUSION: This method is stable and reliable. The number of common peaks of fingerprint had little change after the crude and processed Cassiae Semen in Xuezhiling tablets interchangeably, but the contents of some components had significant changes.