We determined the therapeutic efficacy of atractylenolide I (ATR), extracted from largehead atractylodes rhizome, in managing gastric cancer cachexia (GCC), and interpreted its probable pharmacological mechanism via investigating tumor necrosis factor alpha (TNF-a), interleukin-1 (IL-1), interleukin-6 (IL-6) and proteolysis-inducing factor (PIF). This was a randomized but not-blinded pilot. The study group (n ¼ 11) received 1.32 g per day of atractylenolide I (ATR) and the control group (n ¼ 11) received 3.6 g per day of fish-oil-enriched nutritional supplementation (FOE) for 7 weeks. Conservative therapy was similar in both groups. Clinical [appetite, body weight, mid-arm muscle circumference (MAMC), Karnofsky performance status (KPS) status], biomarker (TNF-a, IL-1, IL-6 and PIF) were evaluated in the basal state, at the third and seventh weeks. To analyze changes of cytokines, an immumohistochemistry technique was adopted. Base line characteristics were similar in both groups. Effects on MAMC and body weight increase, TNF-a increase and IL-1 decreases of serum level were significant in both groups (P50.05). ATR was significantly more effective than FOE in improving appetite and KPS status, and decreasing PIF positive rate (P50.05). Slight nausea (3/11) and dry mouth (1/11) were shown in intervention groups but did not interrupt treatment. These preliminary findings suggest that ATR might be beneficial in alleviating symptoms, in modulating cytokine and in inhibiting PIF proteolysis of gastric cancer cachexia. Further research using a randomized controlled design is necessary to confirm these pilot study findings.
It has been previously demonstrated that Astragalus and Paeoniae radix rubra extract (APE) had a protective effect against liver fibrosis in mice. The present study aimed to investigate the hepatoprotective effect of APE on CCl4-induced hepatic fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII), hydroxyproline (Hyp), glutathione (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD) and transforming growth factor β1 (TGF-β1) levels were measured in rats with hepatic fibrosis. Histopathological changes in affected livers were studied using hematoxylin-eosin and Masson’s trichrome staining. The expression of transforming growth factor-β/Smad pathway proteins, α-smooth muscle actin (α-SMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. The present study observed significant reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APE-treated (2.6 and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE. Furthermore, the depletion of GSH-Px and SOD, in addition to the accumulation of MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological assessment of CCl4-induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF-β1, α-SMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGF-β1 inhibitor Smad7. These results suggested that APE may protect against liver damage and inhibit the progression of CCl4-induced hepatic fibrosis. The mechanism of action of APE is hypothesized to proceed via scavenging free radicals, decreasing TGF-β1 levels and blocking of the TGF-β/Smad signaling pathway.
Previous studies have shown that Astragalus and Paeoniae Radix Rubra extract (APE) is capable of protecting against liver fibrosis in rats. The hypothesis of the present study was that APE exerts its anti-fibrotic effect by mediating the transforming growth factor β (TGF-β)/Smad signaling pathway. In order to investigate this hypothesis, a series of assays were designed to detect the effects of APE on cell proliferation, cell invasion and the activation of hepatic stellate cells (HSCs). In addition, the effects of APE on the TGF-β/Smad signaling pathway were explored, with the aim of elucidating the underlying mechanisms. HSCs were initially isolated from normal rat liver. A number of assays were then employed in order to evaluate the effects of APE on the function of these cells. Cell proliferation was investigated using an MTT assay and cell invasion was observed with the use of transwell invasion chambers. Collagen synthesis was measured with a 3H-proline incorporation assay and expression of α-smooth muscle actin was used to determine the extent of HSC activation. Protein expression induced by TGF-β1 in HSCs was investigated by western blot and immunofluorescence analyses. Plasminogen activator inhibitor type1 (PAI-1) and urokinase-type plasminogen activator (uPA) transcriptional activity was measured using reverse transcription polymerase chain reaction. The results demonstrated that APE (5–80 μg/ml) significantly inhibited fetal bovine serum-induced cell proliferation in a dose-dependent manner. Cell invasion and activation of HSCs induced by TGF-β1 were disrupted by treatment with APE in a dose-dependent manner. TGF-β1 was observed to increase the phosphorylation of Smad2/3, while APE administered at higher doses produced inhibitory effects on Smad2/3 phosphorylation. In addition, administration of APE abrogated the TGF-β1-induced reduction in Smad-7 expression in a dose-dependent manner. The results further indicated that APE treatment not only reduced PAI-1 expression, but also increased uPA expression in a dose-dependent manner. In conclusion, APE exerted inhibitory effects on cell proliferation, invasion and activation of HSCs, and the mechanisms underlying these effects may involve the TGF-β1/Smad pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.