• bioavailability
• liver disease
• silibinin-C-2‘3-dihydrogen succinate
• silibinin-phosphatidylcholine complex
• silybin

• Humans
• Silybin/pharmacology
• Silybin/administration & dosage
• Silybin/chemistry
• Silybin/pharmacokinetics
• Biological Availability
• Liver Diseases/drug therapy
• Liver Diseases/metabolism
• Animals
• Antioxidants/pharmacology
• Antioxidants/chemistry
• Antioxidants/pharmacokinetics
• Antioxidants/administration & dosage
• Silybum marianum/chemistry
• Silymarin/pharmacology
• Silymarin/pharmacokinetics
• Silymarin/chemistry
• Silymarin/administration & dosage

• epigenetic
• long noncoding RNA
• lung cancer
• noncoding RNAs
• polyphenols
• therapy

• RNA, Long Noncoding/genetics
• Polyphenols/pharmacology
• Humans
• Lung Neoplasms/drug therapy
• Animals

• Bone morphogenic proteins
• ID3
• Lung cancer
• Milk thistle
• SMAD
• Silibinin

• Silybin/pharmacology
• Inhibitor of Differentiation Proteins/genetics
• Inhibitor of Differentiation Proteins/metabolism
• Humans
• Animals
• Cell Line, Tumor
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Lung Neoplasms/drug therapy
• Mice
• Mice, Nude
• Activin Receptors, Type I/metabolism
• Activin Receptors, Type I/genetics
• Silymarin/pharmacology
• Bone Morphogenetic Protein Receptors, Type II/metabolism
• Bone Morphogenetic Protein Receptors, Type II/genetics
• Xenograft Model Antitumor Assays
• Bone Morphogenetic Protein 6
• Silybum marianum/chemistry
• Bone Morphogenetic Protein Receptors, Type I/metabolism
• Bone Morphogenetic Protein Receptors, Type I/genetics
• Female
• Neoplasm Proteins

• immune checkpoint
• immunotherapy
• lung cancer
• natural product
• traditional medicine

• Humans
• Lung Neoplasms/therapy
• Lung Neoplasms/etiology
• Biological Products/therapeutic use
• Immunotherapy/adverse effects
• Medicine, Traditional

• National Natural Science Foundation of China

• Cancer
• Epigenetic
• HDAC inhibitors
• Histone acetyltransferase (HAT)
• Histone deacetylase (HDAC)
• Natural products
• Small molecules

• Humans
• Histone Deacetylase Inhibitors/pharmacology
• Histone Deacetylase Inhibitors/therapeutic use
• Histone Deacetylases/genetics
• Histone Deacetylases/metabolism
• Histone Deacetylases/therapeutic use
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/genetics
• Epigenesis, Genetic

• HSF1
• Hsp70
• apoptosis
• bladder cancer
• silibinin

• MLKL
• Silibinin
• apoptosis
• cell death
• lung cancer.
• mitochondria
• necroptosis

• Silybin/pharmacology
• Silybin/chemistry
• Humans
• Apoptosis/drug effects
• Lung Neoplasms/drug therapy
• Lung Neoplasms/pathology
• Lung Neoplasms/metabolism
• Necroptosis/drug effects
• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemistry
• Cell Proliferation/drug effects
• Mice
• Drug Screening Assays, Antitumor
• Dose-Response Relationship, Drug
• Structure-Activity Relationship
• Molecular Structure
• Tumor Cells, Cultured
• Neoplasms, Experimental/drug therapy
• Neoplasms, Experimental/pathology
• Neoplasms, Experimental/metabolism

• 5-fluorouracil
• apoptosis
• inflammation
• ovary
• oxidative stress
• silibinin

• Rats
• Animals
• Antioxidants/pharmacology
• Antioxidants/metabolism
• Silybin/pharmacology
• Caspase 3
• Tumor Necrosis Factor-alpha
• Oxidative Stress
• Oxidants/pharmacology
• Fluorouracil/toxicity
• Superoxide Dismutase/metabolism

• ageing
• bioactive compounds
• chronic diseases
• epigenetics
• metabolism

• dry-powder inhalers
• inhalation
• lung cancer
• nanomedicines
• pulmonary delivery

Lung cancer and pandemic acute respiratory disease, COVID-19, are examples of the most worldwide widespread diseases. The aim of the current study is to develop cyclodextrin based nanosponge (CD-NS) for loading the flavonoid drug, quercitrin (QCT). This is to improve its solubility in an attempt to enhance its activity against lung cancer as well as SARS-CoV-2 virus responsible for COVID-19. Preparation of CD-NS was performed by ultrasound-assisted synthesis method. Two CDs were employed, namely, β cyclodextrin (βCD) and 2-hydroxy propyl-β-cyclodextrin (2-HPβCD) that were crosslinked with diphenyl carbonate, one at a time. QCT loaded CD-NS revealed entrapment efficiency and particle size ranged between 94.17 and 99.03% and 97.10–325.90 nm, respectively. QCT loaded 2-HPβCD-NS revealed smaller particle size compared with that of QCT loaded βCD-NS. Zeta potential absolute values of the prepared formulations were >20 mV, indicating physically stable nanosystems. The selected formulations were investigated by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy which proved the formation of QCT loaded CD-NS exhibiting porous structure. QCT exhibited partial and complete amorphization in βCD-NS and 2-HPβCD-NS, respectively. In vitro release revealed an improved release of QCT from CD-NS formulations. The biological activity of free QCT and QCT loaded CD-NS was investigated against lung cancer cell line A549 as well as SARS-CoV-2 virus. The results revealed that IC₅₀ values of free QCT against lung cancer cell line A549 and SARS-CoV-2 were higher than those exhibited by QCT loaded CD-NS by 1.57–5.35 and 5.95–26.95 folds, respectively. QCT loaded 2-HPβCD-NS revealed enhanced in vitro release and superior biological activity compared with QCT loaded βCD-NS.

• A549 lung cancer cell line
• COVID-19
• Cyclodextrins
• Nanosponge
• Quercitrin
• SARS-CoV-2

• cancer therapy
• gold nanoparticles
• lung cancer
• phytochemicals
• silibinin

Plant phenolic compounds have shown the ability to cooperate with one another at low doses in producing enhanced anticancer effects. This may overcome the limitations (e.g., poor bioavailability and high-dose toxicity) in developing these agents as cancer medicines. We have previously reported that the hydroxycinnamic acid derivative (HCAD) methyl-4-hydroxycinnamate and the phenolic diterpene carnosic acid (CA) can synergistically induce massive calcium-dependent apoptosis in acute myeloid leukemia (AML) at non-cytotoxic concentrations of each agent. Here, we explored the chemical nature of the synergy between HCADs and either CA, in inducing cytotoxicity, or the active metabolite of vitamin D (calcitriol), in enhancing the differentiation of AML cells. This was done by determining the structure–activity relationship of a series of hydroxycinnamic acids and their derivatives (methyl hydroxycinnamates and hydroxybenzylideneacetones) in combination with CA or calcitriol. The HCAD/CA synergy required the following critical structural elements of an HCAD molecule: (a) the para-hydroxyl on the phenolic ring, (b) the carbon C7–C8 double bond, and (c) the methyl-esterified carboxyl. Thus, the only HCADs capable of synergizing with CA were found to be methyl-4-hydroxycinnamate and methyl ferulate, which also most potently enhanced calcitriol-induced cell differentiation. Notably, the C7–C8 double bond was the major requirement for this HCAD/calcitriol cooperation. Our findings may contribute to the rational design of novel synergistically acting AML drugs based on prototype combinations of HCADs with other agents studied here.

• acute myeloid leukemia
• carnosic acid
• hydroxycinnamates
• structure-activity relationship
• vitamin D

• Anti-angiogenesis
• Anti-metastasis
• Apoptosis
• Cell cycle arrest
• Clinical studies
• Flavonolignans
• Silibinin

• Animals
• Antineoplastic Agents, Phytogenic/pharmacology
• Humans
• Neoplasms/drug therapy
• Polyphenols/pharmacology
• Silybin/pharmacology

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.

• EGFR
• JAK2/STAT5b
• MMP2
• NSCLC
• PD-L1
• PI3K/AKT
• silibinin
• tumorsphere

• Apoptosis/drug effects
• B7-H1 Antigen/genetics
• B7-H1 Antigen/metabolism
• Carcinoma, Non-Small-Cell Lung/metabolism
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Cycle Checkpoints/drug effects
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Disease Progression
• ErbB Receptors/metabolism
• Human Umbilical Vein Endothelial Cells/drug effects
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Models, Biological
• Neoplasm Invasiveness
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Neovascularization, Physiologic/drug effects
• Promoter Regions, Genetic/genetics
• Protein Binding/drug effects
• STAT5 Transcription Factor/metabolism
• Silybin/pharmacology
• Spheroids, Cellular/drug effects
• Spheroids, Cellular/pathology

The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules.

• EMT
• STAT3
• metastasis
• non-small cell lung cancer
• silibinin
• silymarin

Lung cancer is the leading cause of cancer‐related mortality both in men and women and accounts for 18.4% of all cancer‐related deaths. Although advanced therapy methods have been developed, the prognosis of lung cancer patients remains extremely poor. Over the past few decades, clinicians and researchers have found that chemical compounds extracted from natural products may be useful for treating lung cancer. Drug formulations derived from natural compounds, such as paclitaxel, doxorubicin, and camptothecin, have been successfully used as chemotherapeutics for lung cancer. In recent years, hundreds of new natural compounds that can be used to treat lung cancer have been found through basic and sub‐clinical research. However, there has not been a corresponding increase in the number of drugs that have been used in a clinical setting. The probable reasons may include low solubility, limited absorption, unfavorable metabolism, and severe side effects. In this review, we present a summary of the natural compounds that have been proven to be effective for the treatment of lung cancer, as well as an understanding of the mechanisms underlying their pharmacological effects. We have also highlighted current controversies and have attempted to provide solutions for the clinical translation of these compounds.

• apoptosis
• chemotherapy
• lung cancer
• nanoparticles
• natural products

• Bioavailability
• Cancer therapy
• Drug delivery
• Herbal medicine
• Pharmacological effects
• Silibinin.

• Mediterranean diet
• cancer
• epigenetic
• nutraceuticals
• nutrigenomics
• review

• Antineoplastic Agents/therapeutic use
• Diet, Mediterranean
• Dietary Supplements/statistics & numerical data
• Epigenesis, Genetic
• Humans
• Neoplasms/diet therapy
• Neoplasms/genetics
• Nutrigenomics

• Epithelial–mesenchymal transition
• NSCLC
• RHBDD1
• Silibinin

• A549 Cells
• Aged
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Movement/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms/drug therapy
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Male
• Middle Aged
• Serine Endopeptidases/genetics
• Serine Endopeptidases/metabolism
• Silybin/pharmacology
• Survival Rate

• 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)
• Dopaminergic neuron
• Estrogen receptor
• Luteolin-7-O-glucoside
• Parkinson's disease

• Animals
• Behavior, Animal/drug effects
• Cell Line
• Dopaminergic Neurons/drug effects
• Estrogen Antagonists/pharmacology
• Flavones/pharmacology
• Glucosides/pharmacology
• Humans
• Hypokinesia/etiology
• Hypokinesia/prevention & control
• MAP Kinase Signaling System/drug effects
• MPTP Poisoning/pathology
• MPTP Poisoning/prevention & control
• MPTP Poisoning/psychology
• Male
• Mice
• Mice, Inbred C57BL
• Muscle Strength/drug effects
• Neuroprotective Agents/pharmacology
• Receptors, Estrogen/drug effects
• STAT3 Transcription Factor/drug effects
• Signal Transduction/drug effects
• Substantia Nigra/pathology

• in vivo
• cancer
• chemoprevention
• drug dosing

• Animals
• Anticarcinogenic Agents/toxicity
• Chemoprevention
• Drug Administration Routes
• Drug Evaluation, Preclinical/methods
• Drug-Related Side Effects and Adverse Reactions/prevention & control
• Humans
• Neoplasms/prevention & control

• Apoptosis
• Autophagy
• Cancer
• Cell cycle
• Silibinin
• microRNA

• Animals
• Apoptosis/drug effects
• Autophagy/drug effects
• Cell Cycle/drug effects
• Cell Cycle Checkpoints/drug effects
• Cell Division/drug effects
• Cell Line, Tumor
• Flavonolignans/pharmacology
• Humans
• MicroRNAs/drug effects
• Neoplasms/drug therapy
• Signal Transduction/drug effects
• Silybin/metabolism
• Silybin/pharmacology

• Adaptor Proteins, Signal Transducing/metabolism
• Apoptosis/drug effects
• Autophagy/drug effects
• Cell Line, Tumor
• Glioblastoma/drug therapy
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Humans
• Phosphoproteins/metabolism
• Silybin
• Silymarin/pharmacology
• TOR Serine-Threonine Kinases/antagonists & inhibitors
• TOR Serine-Threonine Kinases/metabolism
• Transcription Factors
• YAP-Signaling Proteins

The effect of paclitaxel combined with lobaplatin on the sensitivity of lung cancer cell line NCI-H446 through influencing the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was investigated. The sensitivity of lobaplatin to NCI-H446 and the effect of paclitaxel and PI3K inhibitor LY294002 combined with lobaplatin on the sensitivity to NCI-H446 were detected via methyl thiazolyltetrazolium (MTT) assay. The effect of paclitaxel combined with lobaplatin on cell apoptosis was detected using flow cytometry, the effect of paclitaxel combined with lobaplatin on the cell migration was detected via cell wound scratch assay, and the effect of paclitaxel combined with lobaplatin on the cell invasion was detected via Transwell assay. Finally, the effect of paclitaxel on PI3K/Akt pathway was detected via western blotting. MTT assay showed that 30 µg/ml lobaplatin could significantly inhibit the growth of NCI-H446 (p<0.01). Lobaplatin group (group L), 2 µg/ml paclitaxel combined with lobaplatin group (group LP) and lobaplatin combined with 10 µmol/ml LY294002 group (group LL) were set up. The cell survival rates in group LP and group LL were significantly lower than that in group L (p<0.01), and the cell survival rate in group LP was similar to that in group LL (p>0.05). Flow cytometry revealed that the cell apoptotic levels in group LP and group LL were obviously higher than that in group L (p<0.01), and there was no statistically significant difference in the cell apoptotic level between group LP and group LL (p>0.05). Cell wound scratch assay showed that the cell migration capacity in group LP was significantly lower than those in group L and group LL (p<0.01, p<0.05), and the cell migration capacity in group LL was lower than that in group L (p<0.05). Besides, Transwell assay revealed that the cell invasion capacity in group LP was obviously lower than those in group L and group LL (p<0.01, p<0.05), and the cell invasion capacity in group LL was lower than that in group L (p<0.01). Finally, western blotting showed that the levels of PI3K, phosphorylated-Akt (p-Akt) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β) in group LP and group LL were significantly lower than those in group L, and the differences were statistically significant (p<0.01). Paclitaxel can significantly increase the sensitivity of lobaplatin to lung cancer cell line NCI-H446. Moreover, paclitaxel can enhance the effect of lobaplatin on lung cancer cells and reduce the drug resistance through inhibiting PI3K/Akt pathway.

• PI3K/Akt
• lobaplatin
• lung cancer
• paclitaxel

Recently, genkwanin (GKA) has been shown to display in vitro antitumor activity against some cancer cells, but its poor solubility restricted the in vivo study and further investigation of its antitumor therapeutic efficacy. In this paper, genkwanin nanosuspensions (GKA-NSps) were successfully prepared using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer using the precipitation-homogenization method. The obtained GKA-NSps had an average particle size of 183.1 ± 4.4 nm, a PDI value of 0.16 ± 0.07, a zeta potential of −16.2 ± 0.1 mV, and a drug loading content of 49.36 ± 0.14%. GKA-NSps showed spherical morphology and very good stability in normal saline, phosphate buffer saline (PBS, pH 7.4), 5% glucose, artificial gastric juice, artificial intestinal juice and plasma; thus, it is suitable for both oral and intravenous administration. The resultant GKA-NSps displayed sustained drug release behavior and stronger in vitro cytotoxicity against 4T1, MCF-7, MDA-MB-453, HeLa, HepG2, BT474, and A549 cells than free GKA. The in vivo study in MCF-7 tumor-bearing nude mice indicated that GKA-NSps (60 mg/kg, i.v.) achieved similar therapeutic efficacy as PTX injection (8 mg/kg, i.v.) (62.09% vs. 61.27%), while the minimal lethal dose was more than 320 mg/kg, indicating good safety. By using nanotechnology, our study suggested that some antitumor flavonoids of low potency, such as GKA, are promising as safe but effective anticancer drugs.

• Genkwanin
• TPGS
• antitumor activity
• cytotoxicity
• nanosuspensions

• chitosan nanoparticles
• hydrophobically-modified CNP
• nanobiotechnology
• slibinin

• antitumor
• apoptosis
• cell cycle
• cell growth inhibition
• myricanol 5-fluorobenzyloxy ether

• ER stress
• ROS
• apoptosis
• choriocarcinoma
• silibinin

• Liver diseases
• Meta-analysis
• Milk thistle
• Silymarin
• Systematic review

• Alanine Transaminase/blood
• Aspartate Aminotransferases/blood
• Humans
• Liver/drug effects
• Liver Diseases/blood
• Liver Diseases/drug therapy
• Protective Agents/pharmacology
• Protective Agents/therapeutic use
• Randomized Controlled Trials as Topic
• Silymarin/pharmacology
• Silymarin/therapeutic use
• gamma-Glutamyltransferase/blood

• ACC-M cells
• adenoid cystic carcinoma
• autophagy
• microtube-related protein 1 light-chain 3
• silibinin

• Silibinin
• bladder cancer
• breast cancer
• colon cancer
• hepatocellular carcinoma
• lung cancer
• prostatic cancer

• Apoptosis
• Cytochrome-c
• Evodiamine
• Lung cancer
• Pifithrin-α
• p53

• Cancer metastasis
• Cancer therapy
• Invasion

• Antineoplastic Agents, Phytogenic/therapeutic use
• Cadherins/genetics
• Humans
• Molecular Targeted Therapy
• Neoplasm Invasiveness/genetics
• Neoplasm Metastasis
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Signal Transduction/drug effects
• Tight Junctions/drug effects
• Tight Junctions/genetics

• basal cell carcinoma
• chemoprevention
• hedgehog signaling
• inflammation
• natural products
• silibinin
• ultraviolet B

• antioxidant
• methotrexate
• pulmonary toxicity
• rat
• silibinin

• Cancer
• Legasil®
• STAT3
• Silibinin
• Siliphos
• Silybin
• Silymarin

Silibinin, a dietary cancer chemopreventive flavonoid from the seeds of milk thistle, has been reported to exhibit anti-metastatic effects on renal cell carcinoma (RCC), but the mechanism underlying this phenomenon is not fully understood. The present study aimed at examining the potential role of autophagy in regulating silibinin-induced anti-metastatic effects on RCC cells. Using RCC ACHN and 786-O cells as a model system in vitro, we found that silibinin treatment increased the expression of LC3-II, resulted in the formation of autophagolysosome vacuoles, and caused a punctate fluorescence pattern with the monomeric red fluorescence protein-enhanced green fluorescence protein-LC3 (mRFP-EGFP-LC3) protein, which all are markers for cellular autophagy. Autophagy flux was induced by silibinin in RCC cells, as determined by LC3 turnover assay. Mechanically, the adenosine 5'-monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was identified as involved in regulation of silibinin-induced autophagy. Furthermore, autophagy induction was demonstrated to positively contribute to silibinin-induced anti-metastatic effects on RCC cells in vitro. Activation of autophagy enhanced silibinin-induced inhibition of migration and invasion of RCC cells, while inhibition of autophagy attenuated it. These findings thus provide new information about the potential link between autophagy and metastasis inhibition induced by silibinin, and the induction of autophagy may shed some light into future treatment strategies for metastatic RCC.

• Adenylate Kinase/metabolism
• Antineoplastic Agents/pharmacology
• Autophagy/drug effects
• Carcinoma, Renal Cell/drug therapy
• Carcinoma, Renal Cell/secondary
• Cell Line, Tumor
• Cell Movement
• Drug Screening Assays, Antitumor
• Humans
• Kidney Neoplasms/drug therapy
• Kidney Neoplasms/pathology
• Signal Transduction
• Silybin
• Silymarin/pharmacology
• TOR Serine-Threonine Kinases/metabolism

Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO)  action of SM. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B₁₂, etc.), might have similar hepatoprotective effects as described in human nutrition.

• NF-κB
• Nrf2
• antioxidant
• gut
• silibinin
• silybin
• silymarin
• vitagenes

AIM: To assess the value of drug utilization review (DUR) and drug utilization evaluation (DUE) in the evaluation of the rationality of usage of hepatoprotective drugs at our hospital.

METHODS: DUR and DUE methods were used to analyze drug use index (DUI), medication, treatment monitoring and treatment results in hospitalized patients with hepatitis at our hospital.

RESULTS: Of the hepatoprotective drugs used in 129 hepatitis patients, two had a DUI > 1, two had a DUI < 1 and five had a DUI = 1, which accounted for 22.2%, 22.2% and 55.6% of all surveyed hepatoprotective drug varieties, respectively. The frequencies of usage of the top three drugs were Silibinin Capsules (52.78%), Reduced Glutathione Injection (21.23%) and Polyene Phosphatidylcholine Injection (21.04%), respectively. The frequencies of single, double, triple and quadruple therapies were 15.5%, 48.1%, 34.9% and 1.6%, respectively. Liver function returned to normal or showed improvement in 55%, 96.8%, 86.7% and 50% of patient receiving single, double, triple and quadruple therapies, respectively, which showed a significant difference (P < 0.01). Double therapy had the best therapeutic effect, followed by triple, single and quadruple therapies.

CONCLUSION: The usage of hepatoprotective drugs in hepatitis patients at our hospital was basically reasonable, and double therapy had the best therapeutic effect.

• Hepatoprotective drugs
• Drug utilization evaluation
• Drug use evaluation
• Drug combination
• Analysis of drug usage