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Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide

Salama SM, Ibrahim IAA, Shahzad N, Al-Ghamdi S, Ayoub N, AlRashdi AS, et al.

APMIS, 2018 Sep;126(9):710-721.
PMID: 30058214 DOI: 10.1111/apm.12878

This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra-peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT), serum platelet-derived growth factor (PDGF) and transforming growth factor (TGF-β1), and hepatic metalloproteinase enzyme (MMP-2) and its inhibitor extracellular matrix protein (TIMP-1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8-hydroxy 2- deoxyguanosine (8-OH-dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF-β1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF-β1, hepatic MMP-2 and TIMP-1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.

Matched MeSH terms: Transforming Growth Factor beta1/blood
Assessment of interleukin 17 and transforming growth factor-beta 1 in hepatitis C patients with disease progression

Elbanan WK, Fathy SA, Ibrahim RA, Hegazy MGA

Trop Biomed, 2020 Dec 01;37(4):1093-1104.
PMID: 33612761 DOI: 10.47665/tb.37.4.1093

Hepatitis C virus (HCV) infection in Egypt is the most serious health problem. Identifying HCV-positive persons at high risk of early complications can help prioritize treatment decisions. Recently, attention has been directed to non-invasive, accurate alternatives using serum biochemical markers. The transforming growth factor β 1/interleukins pathway plays an important role in the process of cell injury and inflammation. Thus, TGF-β1 and IL-17 were assessed in serum of chronic HCV patients with correlation to hepatic inflammatory and fibrotic status. The quantitative serum levels of TGF-β1 and IL-17 were analyzed among chronic hepatitis C (CHC) patients (n=75) and normal control (NC) subjects (n=15). Disease severity in patients was assessed using the Child-Pugh scores and METAVIR. Serum levels of TGF-β1 and IL-17 were significantly increased in HCV patients compared to control group. Furthermore, the levels of TGF-β1 and Il-17 were positively correlated to serum transaminases and alpha-fetoprotein and they were negatively correlated with serum albumin and platelets. Additionally, the serum levels of TGF-β1 and Il-17 were associated with inflammation grades and stages of liver fibrosis. TGF-β1 and IL-17 may be hopeful serum biomarkers concerned in the progression of liver inflammation and fibrosis accompanying chronic HCV infection. Therefore, they could be used in the future as targets for anti-fibrotic therapy of chronic HCV to ameliorate the disease progress.

Matched MeSH terms: Transforming Growth Factor beta1/blood*
Fulltext Combined assessment of TGF-beta-1 and alpha-fetoprotein values improves specificity in the diagnosis of hepatocellular carcinoma and other chronic liver diseases in Malaysia

Yasmin Anum MY, Looi ML, Nor Aini AH, Merican I, Wahidah A, Mohd Radzi AH, et al.

Med J Malaysia, 2009 Sep;64(3):223-7.
PMID: 20527273 MyJurnal

Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.

Matched MeSH terms: Transforming Growth Factor beta1/blood*
Fulltext Wound-healing potential of the fruit extract of Phaleria macrocarpa

Abood WN, Al-Henhena NA, Najim Abood A, Al-Obaidi MM, Ismail S, Abdulla MA, et al.

Bosn J Basic Med Sci, 2015 05 12;15(2):25-30.
PMID: 26042509 DOI: 10.17305/bjbms.2015.39

The wound-healing potential of Phaleria macrocarpa was evaluated by monitoring the levels of inflammatory mediators, collagen, and antioxidant enzymes. Experimentally, two-centimeter-wide full-thickness-deep skin excision wounds were created on the posterior neck area of the rats. The wounds were topically treated with gum acacia as a vehicle in the control group, intrasite gel in the reference group, and 100 and 200 mg/mL P. macrocarpa ‎fruit extract in the treatment group. Granulation tissues were excised on the 15th day and were further processed for histological and biochemical analyzes. Wound healing was evaluated by measuring the contractions and protein contents of the wounds. Cellular redistribution and collagen deposition were assessed morphologically using Masson's trichrome stain. Superoxide dismutase (SOD) and catalase (CAT) activities, along with malondialdehyde (MDA) level were determined in skin tissue homogenates of the dermal wounds. Serum levels of transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor alpha (TNF-α) were evaluated in all the animals. A significant decrease in wound area was caused by a significant increase in TGF-β1 level in the treated groups. Decrease in TNF-α level and increase in the collagen formation were also observed in the treated groups. Topical treatment with P. macrocarpa fruit extract increased the SOD and CAT activities in the healing wounds, thereby significantly increasing MDA level. The topical treatment with P. macrocarpa fruit extract showed significant healing effect on excision wounds and demonstrated an important role in the inflammation process by increasing antioxidant enzyme activities, thereby accelerating the wound healing process and reducing tissue injury.

Matched MeSH terms: Transforming Growth Factor beta1/blood
Fulltext A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Koay YY, Tan GCJ, Phang SCW, Ho JI, Chuar PF, Ho LS, et al.

Nutrients, 2021 Jan 18;13(1).
PMID: 33477404 DOI: 10.3390/nu13010258

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

Matched MeSH terms: Transforming Growth Factor beta1/blood
Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

Estai MA, Suhaimi F, Das S, Shuid AN, Mohamed Z, Soelaiman IN

Clinics (Sao Paulo), 2011;66(12):2113-9.
PMID: 22189738

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-b) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats.
METHODS: Thirty female Sprague-Dawley rats weighing 200-250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 mg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing.
RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02).
CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

Matched MeSH terms: Transforming Growth Factor beta1/blood*
Fulltext Antioxidant and pro-oxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome

Varatharajan R, Sattar MZ, Chung I, Abdulla MA, Kassim NM, Abdullah NA

BMC Complement Altern Med, 2013;13:242.
PMID: 24074026 DOI: 10.1186/1472-6882-13-242

Catechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Several polyphenolic compounds reported as antioxidants such as quercetin, catechins and gallic acid have been highlighted to have pro-oxidant activity at high doses. Therefore, the present study was conducted to investigate the antioxidant and pro-oxidant effects of chronically administering high dose of OPLE (1000 mg kg⁻¹) in an animal model of diabetic nephropathy (DN).

Matched MeSH terms: Transforming Growth Factor beta1/blood
Fulltext Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial

Chuar PF, Ng YT, Phang SCW, Koay YY, Ho JI, Ho LS, et al.

Nutrients, 2021 Oct 25;13(11).
PMID: 34836025 DOI: 10.3390/nu13113770

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

Matched MeSH terms: Transforming Growth Factor beta1/blood