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Macrophages are key regulatory cells of fibrogenesis. They can have pro- or antifibrotic activity due to their plasticity and heterogeneity. Some studies have shown the antifibrotic effect of macrophages on dermal fibroblasts, but the effect of macrophages on the lung fibroblast functions remains unexplored. Therefore, the purpose of this study was to examine the influence of conditioned media of human macrophage differentiated by M-CSF/GM-CSF and further dexamethasone polarized/unpolarized on the TGF-β-induced lung fibroblast differentiation. Macrophages were derived from peripheral blood monocytes of healthy donors. Monocytes were differentiated by M-CSF or GM-CSF for 7 days. On day 5, dexamethasone was added to generation of polarized macrophages M-M(Dex) and GM-M(Dex). Polarized macrophages were compared with non-polarized M-M0 and GM-M0, to which dexamethasone was not added. Next, the conditioned medium of these macrophage subtypes was collected and tested for inhibition the lung fibroblast differentiation (HLF210 cell line). To do this, TGF-β (inducing differentiation factor) and conditioned macrophage medium were added to fibroblast cultures. Effectiveness of differentiation was estimated by the expression of the myofibroblast marker, α-smooth muscle actin (α-SMA), and the production of extracellular matrix protein, collagen I. The expression of α-SMA was determined using flow cytometry. The concentration of collagen I was measured by ELISA. Since our data indicates that spontaneous activation of fibroblasts occurs during standard cultivation, the α-SMA expression was investigated in 3D culture of fibroblasts. Notably, the content of α-SMA-positive cells in 3D cultures was significantly reduced, indicating more physiological growth cells. Regardless of the differentiation stimulus, the conditioned media of dexamethasone-polarized macrophages do not affect the level of collagen I production or the α-SMA expression. On the contrary, M-M0 showed a strong inhibitory effect that reduced the amount of collagen I in the fibroblast cultures and the expression of marker myofibroblasts by fibroblasts. Interesting, GM-M0 had no such effect and did not prevent lung fibroblast differentiation like polarized cells. Taken together, the findings suggest that M-M0 macrophages may have antifibrotic properties. Furthermore, the lack of this effect in GM-M0 macrophages indicates that the differentiation factor plays a significant role in the development of the antifibrotic macrophage phenotype.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides. [ABSTRACT FROM AUTHOR]

Asmaa A Ashour,1 Amal H El-Kamel,1 Doaa A Abdelmonsif,2,3 Hoda M Khalifa,4 Alyaa A Ramadan1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; 2Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, 21131, Egypt; 3Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21131, Egypt; 4Department of Histology, Faculty of Medicine, Alexandria University, Alexandria, 21131, EgyptCorrespondence: Amal H El-KamelDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Messalla Post Office PO Box 21521, Alexandria, EgyptTel +20 10-0508-0510Fax +20 3 4873273Email amalelkamel@yahoo.comIntroduction: Liver fibrosis represents a serious global disease with no approved treatment. Tanshinone IIA (TSIIA) is a phytomedicine with documented activity in treating many hepatic disorders. TSIIA has been reported to have potent anti-inflammatory and antioxidant properties. It can also induce apoptosis for activated hepatic stellate cells, and is thereby considered as a promising herbal remedy for treating fibrotic liver. However, its poor aqueous solubility, short half-life, exposure to the first-pass effect, and low concentration reaching targeted cells constitute the major barriers hindering its effective therapeutic potential. Therefore, this work aimed at enhancing TSIIA systemic bioavailability together with achieving active targeting potential to fibrotic liver via its incorporation into novel modified lipid nanocapsules (LNCs).Methods: Blank and TSIIA-loaded LNCs modified with either hyaluronate sodium or phosphatidyl serine were successfully prepared, optimized, and characterized both in vitro and in vivo.Results: The developed LNCs showed good colloidal properties (size ≤ 100 nm and PDI ≤ 0.2), high drug-entrapment efficiency (> 97%) with sustained-release profile for 24 hours, high storage stability up to 6 months, and good in vitro serum stability. After a single intraperitoneal injection, the administered LNCs exhibited a 2.4-fold significant increase in AUC0–∞ compared with the TSIIA suspension (p≤ 0.01). Biodistribution-study results proved the liver-targeting ability of the prepared modified LNCs, with a significant ∼ 1.5-fold increase in hepatic accumulation compared with the unmodified formulation (p≤ 0.05). Moreover, the modified formulations had an improved antifibrotic effect compared with both unmodified LNCs and TSIIA suspension, as evidenced by the results of biochemical and histopathological evaluation.Conclusion: The modified TSIIA-LNCs could be regarded as promising novel targeted nanomedicines for effective management of liver fibrosis.Keywords: phytomedicine, hyaluronic acid, phosphatidyl serine, antifibrotic activity

Three new alkaloids (1 – 3) with antifibrotic activity were obtained from the roots of Heterosmilax yunnanensis. Compound 1 is an unprecedented benzannulated spiroketal composed of four biogenetic building blocks: catechin, glucose, tryptophan and malonic acid. Pharmacological research found that compounds 1 and 2 strongly inhibited the proliferation, migration, and activation of HSCs by suppressing the activity of RhoA. [Display omitted] • Three new alkaloids (heteryunine A, heterpyrazine A, B) were isolated from the roots of Heterosmilax yunnanensis. • Heteryunine A is an unprecedented benzannulated spiroketal composed of four biogenetic building blocks. • The attachment of methylene in spiroketal to an additional fragment via a C C bond was the first to be discovered. • The absolute configuration of Heteryunine A was determined by ROESY, specific rotation and quantum chemical calculations. • Heteryunine A and heterpyrazine A showed significant anti-fibrotic effect by suppressing the activity of RhoA. An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1 , containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a C C bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA). [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Vocal fold (VF) fibroblasts are the central target for developing new strategies for the treatment of VF scarring and fibrosis. Asiatic acid (AA) is a triterpenoid derivate with antifibrotic properties. However, the effect of AA in VF scarring is poorly understood. The objective of this study was to investigate the potential application of AA as a therapeutic treatment in VF scarring. Study Design: Xxxxx. Methods: The functional expression of SMAD7 was knocked down with recombinant adenoviruses and adeno‐associated viruses carrying shRNAs in the in vitro and in vivo models, which were constructed to investigate AA's antifibrotic function. The expression of collagens and SMADs in cultured human and rabbit cell lines and animal models was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry labeling, respectively. Cell migration capacity and contraction in VF fibroblast cell lines were also evaluated. Results: AA downregulated the downstream fibrotic activation in a dose‐dependent manner. Meanwhile, AA attenuated VF scarring/fibrosis by reducing collagen deposition. Furthermore, the antifibrotic effects of AA were associated with the upregulation of SMAD7. In contrast, knockdown of SMAD7 inhibited the effect of AA on transforming growth factor‐beta‐1 (TGF‐β1) stimulation, which suggests a central role for SMAD7 in AA‐induced antifibrotic activities during VF fibrosis. Conclusion: We concluded that AA, which is a novel therapeutic candidate for preventing VF scarring/fibrosis, might exert its antifibrotic effect via the TGF‐β1/SMAD signaling pathway. Level of Evidence: NA Laryngoscope, 132:1237–1244, 2022 [ABSTRACT FROM AUTHOR]

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria , which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3 – 6), and 19 known steroidal alkaloids (7 – 25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2 , 7 – 10 , 14 , 15 , and 17 downregulated fibrotic markers induced by transforming growth factor- β (TGF- β) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF- β -induced epithelial-mesenchymal transition in A549 cells, alleviated TGF- β -induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF- β -induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents. Six undescribed and nineteen known cevanine-type alkaloids were isolated from the bulbs of Fritillaria unibracteata var. wabuensis and eight alkaloids exhibited antifibrotic activities in vitro. [Display omitted] • 25 cevanine-type alkaloids were isolated from Fritillaria unibracteata var. wabuensis. • The antifibrotic activities of steroidal alkaloids were evaluated for the first time. • Compounds 14 and 17 inhibited TGF- β -induced EMT in A549 cells. • Compounds 14 and 17 inhibited TGF- β -induced migration and proliferation of fibroblasts. [ABSTRACT FROM AUTHOR]

Aim/Background: To assess the liver antifibrotic action of ethanolic extract of aerial parts of Solanum villosum Mill subsp. miniatum (Bernh. ex Willd.) (SVE) and correlate this activity with its high performance liquid chromatography-quadrupole time of flight (HPLC-qTOF) Electrospray Ionisation Mass Spectrometry (ESIMS) phytochemical profile. Materials and Methods: The median lethal dose of SVE was determined, and a rat model of carbon tetrachloride (CCl4)-induced liver fibrosis was used to evaluate its antifibrotic activity. Markers for hepatotoxicity, fibrosis, and oxidative stress were assessed, and histopathological features of liver tissues were examined. Metabolite profiling of SVE was achieved via HPLC-qTOF-ESIMS coupled with Photodiode array (PDA). Liver fibrosis was induced in rats by oral administration of CCl4for 6 weeks. Silymarin (positive control) and SVE (100 and 250 mg/kg) were orally administered daily for 6 weeks. Results: Compared to CCl4-intoxicated group, administration of SVE obviously ameliorated fibrosis of the hepatic capsule associated with aggregation of multiple focal fat cells formation. Both silymarin and SVE ameliorated the rise in serum markers of hepatotoxicity (alanine transaminase, aspartate transaminase, and alkaline phosphatase), markedly attenuated CCl4-induced oxidative stress. The antifibrotic activity of SVE was evidenced by inhibiting the rise in hepatic hydroxyproline content and accumulation of collagen. This was confirmed by the ability of SVE to inhibit alterations in expression of the fibrosis-related genes Collagen Iα, matrixmetalloproteinase-2 (MMP-2), tissue inhibitor matrix metalloproteinase-2, and transforming growth factor beta 1. HPLC-qTOF-ESIMS analysis of SVE revealed the presence of 47 metabolites, among which 33 were tentatively identified. Conclusion: SVE exhibited hepatoprotective and antifibrotic activities in rats by enhancing the antioxidant capacity and regulating expression of fibrogenic mediators. [ABSTRACT FROM AUTHOR]

Abstract The phenolic compound content and the beneficial effects of Capparis spinosa seed extracts (CSSE) against the toxicity induced using cisplatin and CCl 4 treatment were studied. The amounts of total phenolics, flavonoids and condensed tannins were 83 mg gallic acid equivalents, ~92 mg rutin equivalents, and 1 mg tannic acid equivalents/g d.w., respectively. Results showed that CSSE pretreatment restored the higher content of serum creatinine, urea and uric acid, and increased activities of aspartate aminotransferase, and alanine aminotransferase induced by cisplatin and CCl 4 treatment. Furthermore, CSSE pretreatment decreased the protein carbonyls and malondialdehyde, and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase. Histopathological studies confirmed that CSSE decreased the degree of tissues fibrosis. The results obtained confirmed the potential nutritional and medicinal benefits of C. spinosa and highlighted the potential use of the seeds as a source of bioantioxidants for the food and pharmaceutical industries. Highlights • Preliminary phytochemical analysis of methanol extracts of Capparis spinosa seeds. • Biochemical analysis showed nephroprotective and hepatoprotective effects. • Histopathological study suggested that the extracts protect against tissues fibrosis. [ABSTRACT FROM AUTHOR]

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenol profile of the alcohol soluble fraction of aqueous T. nilotica extract, assessing its in vivo antifibrotic activity and the possible underlying mechanism, to unravel the impact of quantitative difference of sulphated polyphenols content on the antifibrotic activity of T. nilotca grown in two different habitats. Polyphenol profiling of T. nilotica extracts was performed using HPLC-HRESI-QTOF-MS-MS. The major polyphenol components included sulphated flavonoids, phenolic acids and free aglycones. The antifibrotic activity was evaluated through carbon tetrachloride-induced liver fibrosis in rats. Biochemical evaluations revealed that both fractions ameliorated the increased levels of hepatic aminotransferases, lipid peroxidation, hydroxyproline, α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB). Moreover, both fractions reduced catalase activity (CAT) and enhanced hepatic glutathione (GSH) content. Histopathological imaging undoubtedly confirmed such results. In conclusion, the T. nilotica polyphenol-rich fraction exhibited potential antifibrotic activity in rats. Significant alterations in GSH levels were recorded based on the sulphated polyphenol metabolite content.

Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4-thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis. Comparison of SRB assays on fibroblasts and cancer cells revealed that compounds which significantly reduced the viability of fibroblasts did not possess an anticancer effect. A series of thiazolidinone derivatives as interesting candidates for further testing has been identified. Among the tested compounds 2-{3-furan-2-ylmethyl-2-[(2-methyl-3-phenylallylidene)hydrazono]-thiazolidin-4-one-5-yl}- N -(3-trifluoromethylphenyl)-acetamide ( 5 ), N -(2-methoxyphenyl)-2-[5-(4-oxothiazolidin-2-ylideneamino)-[1,3,4]thiadiazol-2-ylsulfanyl]-acetamide ( 12 ), 3-[3-allyl-4-oxo-2-(thiazol-2-ylimino)thiazolidin-5-ylidene]-1,3-dihydroindol-2-one ( 33 ), and 5( Z )-(thiophen-2-ylmethylene)-4-(4-chlorophenylamino)thiazol-2(5 H )-one ( 34 ) possessed high antifibrotic activity levels, had a similar effect as Pirfenidone, and did not scavenge superoxide radicals. Their antifibrotic potential was confirmed using the xCelligence system. [ABSTRACT FROM AUTHOR]

Aim Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) resulting from chronic liver diseases. Efficient and well-tolerated drugs for its treatment are urgently needed. This study aims to identify the active ingredients of Antrodia camphorata by a bioassay-guided fractionation approach and explore the acting mechanism by using a hepatic stellate cell (HSC) line CFSC-8B stimulated by transforming growth factor-β1 (TGF-β1). Methods The accumulation of collagens was evaluated using chromogenic precipitation reaction with picro-sirius red (PSR) dye solution and quantified by spectrophotometric analysis of the dissolved stain. MTT assay, cell migration assay, quantitative polymerase chain reaction and western blotting analysis were used to determine the cell viability, cell migration and gene expression. Results We established a rapid colorimetric assay suitable for screening of anti-hepatofibrotic reagents. Stimulation with 10 ng/mL TGF-β1 for 48 h and 200 μL PSR dye solution were optimal for the colorimetric assay in CFSC-8B cells. We used SB431542, silybin and another 11 antifibrotic reagents to verify the cellular model. Within the safe doses, they attenuated ECM production induced by TGF-β1. Bioactivity-guided fractionation led to the identification of antrodin B from A. camphorata. Antrodin B significantly ameliorated cell proliferation, cell migration, suppressed HSC activation marker α-smooth muscle actin expression and ECM components Col1, Col3 and Fn expression, and blocked the phosphorylation of Smad2/3 induced by TGF-β1 in CFSC-8B cells in a dose-dependent manner. Conclusion We developed a simple assay based on TGF-β1-induced total collagen accumulation in CFSC-8B cells and identified antrodin B which may serve as a potential candidate for treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Regardless of the etiology, cellular death of the liver parenchymal hepatocyte seems to be a primary event of hepatic fibrogenesis, which ultimately results in hepatic stellate cell (HSC) activation and the synthesis of extracellular matrix proteins. Recently it has been demonstrated that hepatic fibrosis can be a reversible process when the stimulus is properly eliminated. Apoptotic removal of active HSC is considered an essential part of the resolution. By employing the HSC cell line, HSC-T6, it was found that the methanol extract of Dendrobium nobile stem significantly inhibited the proliferation of HSC-T6 cells. Three phenanthrenes, denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene isolated from D. nobile were proven to inhibit HSC proliferation. Growth arrest of HSCs by these compounds was accompanied by cellular loss via autophagy-linked apoptosis. The maximal dose of these compounds, however, had little effect on primary cultured hepatocytes in rats. Collagen deposition in HSC-T6 cells was attenuated by these phenanthrenes. Collectively, the above results demonstrated that denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene exhibited antifibrotic activities possibly by the induction of selective cell death in HSCs but not in hepatocytes, implying that these compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Suppression of hepatic stellate cell (HSC) growth and activation have been proposed as therapeutic strategies for the treatment and prevention of liver fibrosis. In the course of screening antifibrotic activity of natural products, the methanolic extract of Alnus firma barks (Betulaceae) showed inhibitory activity of cell proliferation on HSC-T6 cells. A new triterpenoid characterized as lup-20(29) en-2,28-diol-3-yl caffeate (13) was isolated with 12 known diarylheptanoids (1–12) from the barks of A. firma using bioactivity-guided fractionation. Among these compounds, 2 and 13 significantly inhibited the proliferation of HSCs in dose- and time-dependent manners at concentrations from 10 to 100μM. Taken together, antifibrotic activities of A. firma and its active constituents might suggest the therapeutic potentials against liver fibrosis. [Copyright &y& Elsevier]

In the course of screening antifibrotic activity of natural products employing HSC-T6, a rat hepatic stellate cell line, as an in vitro assay system, the methanolic extract of aerial parts of Euscaphis japonica (Tunb.) Kantiz (Staphyleaceae) showed significant inhibitory activity on HSC proliferation. Activity-guided fractionation led to the isolation of four triterpenoids, friedeline ( 1), glut-5-en-ol ( 2), pomolic acid ( 3), and methylrotundate ( 4). Among the triterpenoids isolated, pomolic acid ( 3) significantly inhibited the proliferation of HSCs at concentrations 10 and 100 μM. [ABSTRACT FROM AUTHOR]

Abstract: Hepatic stellate cells (HSCs) have been known to play a key role in the pathogenesis of liver fibrosis. In the course of screening antifibrotic activity of natural products employing HSC-T6, a rat hepatic stellate cell line as an in vitro assay system, the methanolic extract of aerial parts of Eclipta prostrata L. showed significant inhibitory activity on HSCs proliferation. Activity-guided fractionation led to the isolation of five oleanane-type triterpenoids, echinocystic acid (1), eclalbasaponin II (2), eclalbasaponin V (3), eclalbasaponin I (4) and eclalbasaponin III (5), which are all echinocystic acid derivatives. Among the five echinocystic acid derivatives isolated, echinocystic acid (1) and eclalbasaponin II (2) significantly inhibited the proliferation of HSCs in dose- and time-dependent manners. Our present study also suggests the importance of free carboxylic acid at C-28 position in echinocystic acid derivatives for the antifibrotic activity. Taken together, antifibrotic activity of E. prostrata and its triterpenoids might suggest the therapeutic potentials against liver fibrosis. [Copyright &y& Elsevier]

The in vitro antifibrotic activity of Tinospora cordifolia (Thunb.) Miers (giloy) was assessed to explore its potential for the management of oral submucous fibrosis. Epithelial cells dissociated from the tissue obtained from histopathologically normal oral mucosa during surgical extraction of third molars were cultured and fibrosis was induced by TGF-β1 in the oral keratinocytes. Cell viability was assessed by MTT and comparative gene expression analysis was carried out in the fibrosis-induced oral keratinocytes treated with various concentrations of Tinospora cordifolia extract (TcE) for matricellular protein-related gene expression. Concentrations of 0.5 µg/mL and 1 µg/mL TcE demonstrated a significant reduction in the expression of CTGF, SERPINE1, COL1A1, FN1, MMP1, MMP2, MMP3, and TIMP2 and an increase in the expression of PLAU, COL3A1, TIMP1, and TIMP3. Although TcE was found to reduce the expression of several fibrotic genes and increase the expression of antifibrotic genes, a varied effect was found, causing increased expression of COL3A1 and decreased expression of TIMP2 on TGF-β1-induced human buccal epithelial cells. However, further studies are warranted to assess the exact mechanism of antifibrotic activity and its clinical applications. [ABSTRACT FROM AUTHOR]

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenol profile of the alcohol soluble fraction of aqueous T. nilotica extract, assessing its in vivo antifibrotic activity and the possible underlying mechanism, to unravel the impact of quantitative difference of sulphated polyphenols content on the antifibrotic activity of T. nilotca grown in two different habitats. Polyphenol profiling of T. nilotica extracts was performed using HPLC-HRESI-QTOF-MS-MS. The major polyphenol components included sulphated flavonoids, phenolic acids and free aglycones. The antifibrotic activity was evaluated through carbon tetrachloride-induced liver fibrosis in rats. Biochemical evaluations revealed that both fractions ameliorated the increased levels of hepatic aminotransferases, lipid peroxidation, hydroxyproline, α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB). Moreover, both fractions reduced catalase activity (CAT) and enhanced hepatic glutathione (GSH) content. Histopathological imaging undoubtedly confirmed such results. In conclusion, the T. nilotica polyphenol-rich fraction exhibited potential antifibrotic activity in rats. Significant alterations in GSH levels were recorded based on the sulphated polyphenol metabolite content. [ABSTRACT FROM AUTHOR]

Scope: Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated., Methods and Results: Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor β1 (TGF-β1) or platelet-derived growth factor BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-β1- or PDGF-BB-induced HSCs activation, cell migration, and extracellular matrix production; blocked TGF-β1-induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK), and protein kinase B (Akt); and downregulated PDGF-BB stimulated phosphorylation of extracellular signal-regulated kinase and Akt in HSCs in a dose-dependent manner. Meanwhile, the carbon tetrachloride (CCl 4 ) induced mouse model has been used to study antifibrosis role of myricetin in vivo. Our data demonstrated that myricetin suppressed α-smooth muscle actin and collagen type I deposition and blocked phosphorylation of Smad2, mitogen-activated protein kinases, and Akt in CCl 4 -treated mice., Conclusion: Myricetin inhibits the activation of HSCs and ameliorates CCl 4 -induced liver fibrosis in mice and may serve as a potential therapeutic agent in the treatment of liver fibrosis., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)