• biological activities
• gut microbiota
• molecular simulation
• nanodelivery systems
• production and synthesis

• 241111110600 Henan Province Key Research and Development
• 19008024075 Beijing High-level Talent

• inflammation
• liver fibrosis
• natural products
• precision‐cut liver slices

• Animals
• Flavanones/pharmacology
• Humans
• Male
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Mice
• Pentacyclic Triterpenes/pharmacology
• Flavonoids/pharmacology
• Collagen Type I/metabolism
• Collagen Type I/genetics
• Antifibrotic Agents/pharmacology
• Antifibrotic Agents/therapeutic use
• Mice, Inbred C57BL
• Collagen Type I, alpha 1 Chain/metabolism
• Collagen Type I, alpha 1 Chain/genetics

• Antioxidant
• Nanoformulation
• Nanotechnology
• Naringenin
• Oxidative stress
• Redox mechanisms

• GK
• LEPR
• NFH4a
• golden tomato
• lipid homeostasis
• nonalcoholic fatty liver disease
• red tomato
• steatosis

• Breast cancer
• Extracellular vesicles-associated TGF-β1
• Protein kinase C zeta
• Radiotherapy resistance
• Regulatory T cells
• Tumor microenvironment

• 81773288 Fayun Zhang
• 81773288 Fayun Zhang
• 81773288 Fayun Zhang

• Transforming Growth Factor beta/metabolism
• Smad Proteins/metabolism
• Cell Line
• Signal Transduction
• Phosphorylation
• Smad3 Protein/genetics
• Smad2 Protein/genetics
• Smad2 Protein/metabolism

Liver cirrhosis is a late-stage liver disease characterized by excessive fibrous deposition triggering portal-hypertension (PH); the prime restrainer for cirrhosis-related complications. Remedies that can dually oppose hepatic fibrosis and lower PH, may prevent progression into decompensated-cirrhosis. Different Astragalus-species members have shown antifibrotic and diuretic actions with possible subsequent PH reduction. However, A.spinosus and A.trigonus were poorly tested for eliciting these actions. Herein, A.spinosus and A.trigonus roots and aerial parts extracts were subjected to comprehensive metabolic-fingerprinting using UHPLC-MS/MS resulting in 56 identified phytoconstituents, followed by chemometric untargeted analysis that revealed variable metabolic profiles exemplified by different species and organ types. Consequently, tested extracts were in-vivo evaluated for potential antifibrotic/anticirrhotic activity by assessing specific markers. The mechanistic prospective to induce diuresis was investigated by analyzing plasma aldosterone and renal-transporters gene-expression. Serum apelin and dimethylarginine-dimethylaminohydrolase-1 were measured to indicate the overall effect on PH. All extracts amended cirrhosis and PH to varying extents and induced diuresis via different mechanisms. Further, An OPLS model was built to generate a comprehensive metabolic-profiling of A.spinosus and A.trigonus secondary-metabolites providing a chemical-based evidence for their efficacious consistency. In conclusion, A.spinosus and A.trigonus organs comprised myriad pharmacologically-active constituents that act synergistically to ameliorate cirrhosis and associated PH.

• SMAD3 signaling
• chorioallantoic membrane xenograft assay
• invadopodia
• metastasis
• transforming growth factor β

• Antioxidant
• Bangladeshi medicinal plants
• Bioactive compounds
• Ethnomedicine
• Hepatic disorders
• Hepatoprotective activity

• Bangladesh
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/metabolism
• Ethnopharmacology/methods
• Ethnopharmacology/trends
• Humans
• Phytochemicals/pharmacology
• Protective Agents/pharmacology

In recent years, there has been an increasing interest in natural therapies to prevent or treat female diseases. In particular, many studies have focused on searching natural compounds with less side effects than standard hormonal therapies. While phytoestrogen-based therapies have been extensively studied, treatments with phytoprogestins reported in the literature are very rare. In this review, we focused on compounds of natural origin, which have progestin effects and that could be good candidates for preventing and treating female diseases. We identified the following phytoprogestins: kaempferol, apigenin, luteolin, and naringenin. In vitro studies showed promising results such as the antitumoral effects of kaempferol, apigenin and luteolin, and the anti-fibrotic effects of naringenin. Although limited data are available, it seems that phytoprogestins could be a promising tool for preventing and treating hormone-dependent diseases.

• female disease
• phytochemical compounds
• phytoprogestins
• progesterone

• Female
• Genital Diseases, Female/drug therapy
• Genital Diseases, Female/prevention & control
• Humans
• Phytotherapy
• Plant Preparations/pharmacology
• Progestins/pharmacology

Fibrosis is the final common pathology of most chronic diseases as seen in the heart, liver, lung, kidney, and skin and contributes to nearly half of death in the developed countries. Fibrosis, or scarring, is mainly characterized by the transdifferentiation of fibroblasts into myofibroblasts and the excessive accumulation of extracellular matrix (ECM) secreted by myofibroblasts. Despite immense efforts made in the field of organ fibrosis over the past decades and considerable understanding of the occurrence and development of fibrosis gained, there is still lack of an effective treatment for fibrotic diseases. Therefore, identifying a new therapeutic strategy against organ fibrosis is an unmet clinical need. Naringenin, a flavonoid that occurs naturally in citrus fruits, has been found to confer a wide range of pharmacological effects including antioxidant, anti-inflammatory, and anticancer benefits and thus potentially exerting preventive and curative effects on numerous diseases. In addition, emerging evidence has revealed that naringenin can prevent the pathogenesis of fibrosis in vivo and in vitro via the regulation of various pathways that involved signaling molecules such as transforming growth factor-β1/small mother against decapentaplegic protein 3 (TGF-β1/Smad3), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), sirtuin1 (SIRT1), nuclear factor-kappa B (NF-κB), or reactive oxygen species (ROS). Targeting these profibrotic pathways by naringenin could potentially become a novel therapeutic approach for the management of fibrotic disorders. In this review, we present a comprehensive summary of the antifibrotic roles of naringenin in vivo and in vitro and their underlying mechanisms of action. As a food derived compound, naringenin may serve as a promising drug candidate for the treatment of fibrotic disorders.

• Acute kidney injury
• Cisplatin
• Inflammation
• Nox4
• Programmed cell death
• Smad3

• Conjugates
• Diabetes
• Lipid nanoparticles
• Liposomes
• Liver fibrosis
• Liver targeting
• NAFLD
• NASH
• NLCs
• SLNs

• Antiparasitic chemotherapy
• Experimental pathology
• Parasitology
• Schistosomiasis

End-stage liver fibrosis is common to all chronic liver diseases. Since liver transplantation has several limitations, including lack of donors, immunological rejection, and high medical costs, therapeutic alternatives are needed. The administration of mesenchymal stromal cells (MSCs) has been proven effective in tissue regeneration after damage. However, the risk of uncontrolled side effects, such as cellular rejection and tumorigenesis, should be taken into consideration. A safer alternative to MSC transplantation is represented by the MSC secretome, which retains the same beneficial effect of the cell of origin, without showing any considerable side effect. The paracrine effect of MSCs is mainly carried out by secreted particles in the nanometer range, known as extracellular vesicles (EVs) that play a fundamental role in intercellular communication. In this review, we discuss the current literature on MSCs and MSC-EVs, focusing on their potential therapeutic action in liver fibrosis and on their molecular content (proteins and RNA), which contributes in reverting fibrosis and prompting tissue regeneration.

• collagen
• exosomes
• fibrosis
• hepatic stellate cell
• inflammation
• mesenchymal stem cell
• microvesicles
• α-SMA

Liver fibrosis resulting from continuous long-term hepatic damage represents a heavy burden worldwide. Liver fibrosis is recognized as a complicated pathogenic mechanism with extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation. A series of drugs demonstrate significant antifibrotic activity in vitro and in vivo. No specific agents with ideally clinical efficacy for liver fibrosis treatment have been developed. In this review, we summarized the antifibrotic effects and molecular mechanisms of 29 kinds of common natural products. The mechanism of these compounds is correlated with anti-inflammatory, antiapoptotic, and antifibrotic activities. Moreover, parenchymal hepatic cell survival, HSC deactivation, and ECM degradation by interfering with multiple targets and signaling pathways are also involved in the antifibrotic effects of these compounds. However, there remain two bottlenecks for clinical breakthroughs. The low bioavailability of natural products should be improved, and the combined application of two or more compounds should be investigated for more prominent pharmacological effects. In summary, exploration on natural products against liver fibrosis is becoming increasingly extensive. Therefore, natural products are potential resources for the development of agents to treat liver fibrosis.

• SIS3
• Smad3 inhibitor
• treatment
• type 2 diabetes mellitus

• FXR
• SREBP-1c
• Smad-3
• high-fat diet
• kidney
• trans-chalcone

A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid‐derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF‐κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.

• Tregs
• cardiotonic steroids
• polyphenolics
• polysaccharides
• terpenoids
• tumor immunotherapy

• Chemoprevention
• Marine-based agents
• Natural products
• Phytochemical
• Therapeutic targeting
• Tumor microenvironment

• Hepatic stellate cell
• Kupffer cell
• PDGF
• TGF-β
• anti-fibrotics
• liver cirrhosis
• liver myofibroblast

• Animals
• Apoptosis
• Gastrointestinal Microbiome
• Humans
• Liver Cirrhosis/immunology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/pathology
• Liver Cirrhosis/therapy
• Models, Biological
• Oxidative Stress
• Signal Transduction

• 671231 European Research Council
• 862551 European Research Council
• R01 CA233794 NCI NIH HHS
• R21 CA209940 NCI NIH HHS

• Activated HSCs targeted
• Hepatic fibrosis
• Liposomes
• Naringenin
• SPARC

• ECM
• Fibrosis
• HSC
• JNK
• NF-κB
• Smad3
• TGF-β

• diabetes
• erectile dysfunction
• naringenin
• oxidative stress
• streptozotocin

Alcoholic liver disease (ALD) has become one of the major global health problems, with augmented morbidity and mortality. Evidence indicates that flavonoids can reduce the risk of ALD owing to their biological properties. However, the effect of structurally different flavonoid subclasses on alleviating alcohol-induced liver damage in a same model has never been studied. In this study, mice were supplemented with five kinds of flavonoid subgroups, apigenin (flavone), quercetin (flavonol), naringenin (flavanone), (-)-epigallocatechin gallate (flavanol), and genistein (isoflavone), in the same dose (0.3 mmol kg⁻¹ body weight) and then given 50% alcohol by gastric perfusion for five consecutive weeks. The results demonstrated that genistein and naringenin had greater benefits in terms of mitigating fibrosis and apoptosis, respectively, in the liver. Lipid deposition, partial inflammatory-related factors (nuclear factor kappa B p65, cyclooxygenase-2, and interleukin-6 levels), and hepatic histopathological alterations were similarly attenuated by five kinds of flavonoids. All the flavonoids also showed different degrees of influence on protecting against alcoholic liver injury on other aspects, such as serum biochemistry makers, hepatic lipid accumulation, lipid peroxidation, antioxidant capacities, and inflammation.

• (-)-epigallocatechin gallate
• apigenin
• genistein
• liver injury
• naringenin
• quercetin

Disrupted balance in the lineages of CD4⁺ T cell subsets, including pro-inflammatory T helper (Th) cells and anti-inflammatory regulatory T cells (Treg), is a primary pathogenic factor for developing autoimmunity. We have found that this immunomodulatory effect of naringenin on effector T cells and T-cell mediated experimental autoimmune encephalomyelitis (EAE). We therefore explored the effects of naringenin on the development of different effector CD4⁺ T cells. Naïve CD4⁺ T cells were differentiated under respective Th1, Th2, Th17, and Treg polarizing conditions with naringenin. Percent populations of each differentiated CD4⁺ T cell subsets were determined and the corresponding regulating pathways were investigated as underlying mechanisms. Naringenin mainly inhibited CD4⁺ T cell proliferation and differentiation to Th1 and Th17, but did not affect Th2 cells. Impeded Th1 polarization was associated with inhibition of its specific regulator proteins T-bet, p-STAT1, and p-STAT4 by naringenin. Likewise, Th17 regulator proteins RORγt, p-STAT3, and Ac-STAT3 were also inhibited by naringenin. In addition, naringenin promoted Treg polarization and also prevented IL-6-induced suppression of Treg development via down-regulation of p-Smad2/3 as well as inhibition of IL-6 signaling, and the latter was further supported by the in vivo results showing lower soluble IL-6R but higher soluble gp130 levels in plasma of naringenin-fed compared to the control EAE mice. Naringenin impacts CD4⁺ T cell differentiation in a manner that would explain its beneficial effect in preventing/mitigating T cell-mediated autoimmunity.

• CD4+ T cells
• Naringenin
• T cell subsets
• autoimmune diseases
• cell differentiation

• Apigenin
• Citrus flavonoids
• Inflammation
• Naringenin

• Animals
• Female
• Flavanones/pharmacology
• Flavanones/therapeutic use
• Homeostasis/drug effects
• Inflammation Mediators/metabolism
• Interleukin-1beta/metabolism
• Lung Injury/drug therapy
• Lung Injury/metabolism
• Mice
• Mice, Inbred C57BL
• Radiation Injuries, Experimental/drug therapy
• Radiation Injuries, Experimental/metabolism

• NK cell immunity
• anti-cancer immunotherapy
• rebalancing Smad3/Smad7 signaling

• TGF-β/Smad signaling pathway
• quantitative analysis
• single-molecule force spectroscopy
• single-molecule imaging and tracking

• Animals
• Cell Membrane/metabolism
• Humans
• Microscopy/methods
• Protein Binding
• Receptors, Transforming Growth Factor beta/metabolism
• Signal Transduction
• Smad Proteins/metabolism
• Transforming Growth Factor beta/metabolism

• Fetal-like phenotype
• Fibromodulin
• Scar reduction
• Transforming growth factor β1
• Wound healing

• R43 AR063558 NIAMS NIH HHS
• R44 DE026080 NIDCR NIH HHS
• T32 DE007296 NIDCR NIH HHS
• R43 AR064126 NIAMS NIH HHS
• R44 AR064126 NIAMS NIH HHS
• R44 DE024692 NIDCR NIH HHS

To study the molecular mechanisms involved in the hepatoprotective effects of naringenin (NAR) on carbon tetrachloride (CCl₄)-induced liver fibrosis.

Thirty-two male Wistar rats (120-150 g) were randomly divided into four groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose (NAR vehicle) 1 mL/daily p.o.; (2) a CCl₄ group (n = 8) that received 400 mg of CCl₄/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl₄ + NAR (n = 8) group that received 400 mg of CCl₄/kg body weight i.p. 3 times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.; and (4) an NAR group (n = 8) that received 100 mg of NAR/kg body weight daily for 8 wk p.o. After the experimental period, animals were sacrificed under ketamine and xylazine anesthesia. Liver damage markers such as alanine aminotransferase (ALT), alkaline phosphatase (AP), γ-glutamyl transpeptidase (γ-GTP), reduced glutathione (GSH), glycogen content, lipid peroxidation (LPO) and collagen content were measured. The enzymatic activity of glutathione peroxidase (GPx) was assessed. Liver histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin stains. Zymography assays for MMP-9 and MMP-2 were carried out. Hepatic TGF-β, α-SMA, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, Smad3, pSmad3 and pJNK proteins were detected via western blot.

NAR administration prevented increases in ALT, AP, γ-GTP, and GPx enzymatic activity; depletion of GSH and glycogen; and increases in LPO and collagen produced by chronic CCl₄ intoxication (P < 0.05). Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl₄. Although zymography assays showed that CCl₄ produced an increase in MMP-9 and MMP-2 gelatinase activity; interestingly, NAR administration was associated with normal MMP-9 and MMP-2 activity (P < 0.05). The anti-inflammatory, antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10 (P < 0.05). NAR completely prevented the increase in TGF-β, α-SMA, CTGF, Col-1, and MMP-13 proteins compared with the CCl₄-treated group (P < 0.05). NAR prevented Smad3 phosphorylation in the linker region by JNK since this flavonoid blocked this kinase (P < 0.05).

NAR prevents CCl₄ induced liver inflammation, necrosis and fibrosis, due to its antioxidant capacity as a free radical inhibitor and by inhibiting the NF-κB, TGF-β-Smad3 and JNK-Smad3 pathways.

• Fibrosis
• Transforming growth factor-β
• Naringenin
• pSmad3
• Smad3
• JNK
• Nuclear factor kappa
• Carbon tetrachloride

• Alanine Transaminase/blood
• Alkaline Phosphatase/blood
• Animals
• Carbon Tetrachloride/toxicity
• Flavanones/pharmacology
• Flavanones/therapeutic use
• Glutathione/blood
• JNK Mitogen-Activated Protein Kinases/metabolism
• Lipid Peroxidation/drug effects
• Liver/drug effects
• Liver/enzymology
• Liver/pathology
• Liver Cirrhosis, Experimental/blood
• Liver Cirrhosis, Experimental/chemically induced
• Liver Cirrhosis, Experimental/prevention & control
• Male
• Metalloendopeptidases/metabolism
• NF-kappa B/metabolism
• Necrosis/prevention & control
• Oxidative Stress/drug effects
• Rats
• Rats, Wistar
• Signal Transduction/drug effects
• Smad3 Protein/metabolism
• Transforming Growth Factor beta/metabolism
• gamma-Glutamyltransferase/blood

• Hepatic stellate cells (HSCs)
• Homeodomain-interacting protein kinase 2 (HIPK2)
• Liver fibrosis
• TGF-β1/Smad pathway

To study the beneficial effects of ivabradine in dilated cardiomyopathy (DCM) mice, which evolved from coxsackievirus B3-induced chronic viral myocarditis. Four-to-five-week-old male balb/c mice were inoculated intraperitoneally with coxsackievirus B3 (Strain Nancy) on days 1, 14, and 28. The day of the first virus inoculation was defined as day 1. Thirty-five days later, the surviving chronic viral myocarditis mice were divided randomly into two groups, a treatment group and an untreated group. Ivabradine was administered by gavage for 30 consecutive days in the treatment group, and the untreated group was administered normal saline. Masson’s trichrome stain was used to evaluate the fibrosis degree in myocardial tissue. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), collagen I, collagen III and p38-MAPK signaling pathway proteins were detected by Western blot. Electrocardiogram was used to investigate the heart rate and rhythm. The thickness of the ventricular septum and left ventricular posterior wall, left ventricular end diastolic dimension, left ventricular end systolic dimension, left ventricular ejection fractions and fractional shortening were studied by echocardiography. Compared with the untreated chronic viral myocarditis mice, ivabradine significantly increased the survival rate, attenuated the myocardial lesions and fibrosis, improved the impairment of the left ventricular function, diminished the heart dimension, decreased the production of collagen I and collagen III, reduced the expression of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, and lowered the production of phospho-p38 MAPK. The findings indicate the therapeutic effect of ivabradine in preventing the progression from viral myocarditis to DCM in mice with chronic viral myocarditis induced by coxsackievirus B3, is associated with inhibition of the p38 MAPK pathway, downregulated inflammatory responses and decreased collagen expression. Ivabradine appears a promising approach for the treatment of patients with viral myocarditis.

• chronic viral myocarditis
• cytokines
• fibrosis
• ivabradine
• p38 MAPK

• Breast cancer metastasis
• Naringenin
• PKC activation
• TGF-β1 secretion

Hepatic fibrosis and cirrhosis cause strong human suffering and necessitate a monetary burden worldwide. Therefore, there is an urgent need for the development of therapies. Pre-clinical animal models are indispensable in the drug discovery and development of new anti-fibrotic compounds and are immensely valuable for understanding and proofing the mode of their proposed action. In fibrosis research, inbreed mice and rats are by far the most used species for testing drug efficacy. During the last decades, several hundred or even a thousand different drugs that reproducibly evolve beneficial effects on liver health in respective disease models were identified. However, there are only a few compounds (e.g., GR-MD-02, GM-CT-01) that were translated from bench to bedside. In contrast, the large number of drugs successfully tested in animal studies is repeatedly tested over and over engender findings with similar or identical outcome. This circumstance undermines the 3R (Replacement, Refinement, Reduction) principle of Russell and Burch that was introduced to minimize the suffering of laboratory animals. This ethical framework, however, represents the basis of the new animal welfare regulations in the member states of the European Union. Consequently, the legal authorities in the different countries are halted to foreclose testing of drugs in animals that were successfully tested before. This review provides a synopsis on anti-fibrotic compounds that were tested in classical rodent models. Their mode of action, potential sources and the observed beneficial effects on liver health are discussed. This review attempts to provide a reference compilation for all those involved in the testing of drugs or in the design of new clinical trials targeting hepatic fibrosis.

• 3R principle
• animal experimentation
• clinical trials
• collagen
• hepatic fibrosis
• therapy
• translational medicine
• α-smooth muscle actin

• NASH
• fibrosis
• nutraceuticals
• oxidative stress
• polyphenols

• Animals
• Blood Glucose
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Experimental/metabolism
• Diabetic Nephropathies/drug therapy
• Diabetic Nephropathies/metabolism
• Flavanones/pharmacology
• Flavanones/therapeutic use
• Kidney/drug effects
• Male
• MicroRNAs/metabolism
• Protein Serine-Threonine Kinases/metabolism
• Rats
• Rats, Sprague-Dawley
• Receptor, Transforming Growth Factor-beta Type I
• Receptors, Transforming Growth Factor beta/metabolism
• Signal Transduction/drug effects

• Cancer biology
• Cancer prevention
• Cancer therapy
• Tumor microenvironment

• Antineoplastic Agents/therapeutic use
• Carcinogenesis/drug effects
• Carcinogenesis/genetics
• Cell Proliferation/drug effects
• Humans
• Molecular Targeted Therapy
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/prevention & control
• Neovascularization, Pathologic/drug therapy
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/prevention & control
• Signal Transduction
• Tumor Microenvironment/drug effects
• Tumor Microenvironment/genetics

• R21CA169964 NCI NIH HHS
• R21 CA169964 NCI NIH HHS
• R01 CA170378 NCI NIH HHS
• P01 CA034233 NCI NIH HHS
• R01 CA089305 NCI NIH HHS
• U54CA149145 NCI NIH HHS
• F32 CA177139 NCI NIH HHS
• F32CA177139 NCI NIH HHS
• U54 CA149145 NCI NIH HHS
• R01CA184384 NCI NIH HHS
• R01CA128704 NCI NIH HHS
• P50CA114747 NCI NIH HHS
• R15 CA137499 NCI NIH HHS
• C301/A14762 Cancer Research UK
• R01CA170378 NCI NIH HHS
• U01 CA188383 NCI NIH HHS
• R01 CA105102 NCI NIH HHS
• Intramural NIH HHS
• R15 CA137499-01 NCI NIH HHS
• R01 CA184384 NCI NIH HHS
• P50 CA114747 NCI NIH HHS

• Pathology Section
• TGF-β/Smads
• asiatic acid
• naringenin
• treatment for fibrosis

• Animals
• Blotting, Western
• Drug Therapy, Combination
• Estrogen Antagonists/pharmacology
• Fibrosis/drug therapy
• Fibrosis/metabolism
• Fibrosis/pathology
• Flavanones/pharmacology
• Gene Expression Regulation/drug effects
• Immunoenzyme Techniques
• Kidney Diseases/drug therapy
• Kidney Diseases/metabolism
• Kidney Diseases/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Pentacyclic Triterpenes/pharmacology
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Smad3 Protein/genetics
• Smad3 Protein/metabolism
• Transforming Growth Factor beta/genetics
• Transforming Growth Factor beta/metabolism

• Chemopreventive
• Hepatic fibrosis
• Hepatic steatosis
• Hepatoprotection
• Liver inflammation
• Phytochemicals