Effects of Curcumin Against Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitor Metalloproteinase-2 (TIMP-2) Serum Level on Rat Model of Liver Fibrosis Resolution Process

Abstract

Background: Liver fibrosis is an effect from continuous fibrogenesis and fibrolysis process. During fibrogenesis, MMP-2 and TIMP-2 that produced by hepatic stellate cell (HSC) have a role to regulate extracellular matrix (ECM) homeostastic. Otherwise, curcumin inhibits both MMP-2 and TIMP-2 expression and enhances HSC apoptosis, thus inhibit fibrogenesis. Role of curcumin, MMP-2, and TIMP-2 in a fibrolysis process has not been widely studied. This study aimed to determine the correlation between curcumin administration and the decline of MMP-2 and TIMP-2 on rat model of liver fibrosis.Method: This is an experimental study done in male Wistar rats. There are 8 groups consist of 4 rats each. Both control and intervention group were exposed to CCl4 1 cc/kgBW intraperitoneally 2 times per week for 9 consecutive weeks to form F3 fibrosis. Negative control group was injected with normal saline. After CCl4 injection, control group was given curcumin solvent as placebo while intervention groups were given curcumin 200 mg/kgBW for 2, 5, and 9 weeks. Statistical analysis then conducted in the end of study. Results: MMP-2 and TIMP-2 were remarkably increased in positive control group, but found decreased in control group 5 and 9. There are remarkable decrease of MMP-2 and TIMP-2 serum level in intervention group 2, 5, and 9, but MMP-2 and TIMP-2 level was significantly lower in intervention group 2 compared to the control group.Conclusion: MMP-2 and TIMP-2 serum level were decreased after giving of curcumin for 2 weeks. The duration of curcumin administration correlated with decrease of TIMP-2 serum level but not correlated with MMP-2 serum level in rat model of liver fibrosis.

Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis

“…MMP-13 is responsible for the turnover of major fibrillar collagens in rats and mice. A reduction in MMP-2 activity, ECM deposition, and liver fibrosis was also observed in 9-week CCl 4 -or 7-week TAA-treated male Wistar rats received curcumin treatment for 2 and 7 weeks, respectively (Ali et al, 2014;Supriono et al, 2020).…”

“…MMP‐13 is responsible for the turnover of major fibrillar collagens in rats and mice. A reduction in MMP‐2 activity, ECM deposition, and liver fibrosis was also observed in 9‐week CCl 4 ‐ or 7‐week TAA‐treated male Wistar rats received curcumin treatment for 2 and 7 weeks, respectively (Ali et al, 2014; Supriono et al, 2020). In contrast, Wang et al reported that curcumin significantly increased active MMP‐2 levels in the liver of male SD rats after induction of fibrosis by CCl 4 for 8 weeks (Wang et al, 2018).…”

Evidence-Based Management of Uterine Fibroids With Botanical Drugs-A Review

“…The ability of curcumin to down-regulate the expression of fibronectin, one of the ECM proteins, which is overexpressed in leiomyoma as compared to normal myometrium, has also been documented ( Malik et al, 2009 ). The significant inhibitory effect of curcumin on the expression of ECM receptors in non-small-cell lung cancer ( Li et al, 2017 ) and reducing the activity of MMP-2 and up-regulating TIMP activity in various cancer cells ( Mitra et al, 2006 ; Hassan and Daghestani, 2012 ; Supriono et al, 2018 ) suggest the possible mechanism of curcumin in producing anti-uterine fibroid activity via reducing the ECM production, thus further study investigating the effects of curcumin on various ECM-related receptors and proteins in leiomyoma cells may be conducted.…”

Correlation between Extracellular Matrix Metalloproteinase Inducer in Peripheral Blood and Serum MMPs in patients with Acute Coronary Syndrome

“…In patient diagnosis, coronary atheromatous plaque is determined by CT value, and the CT value is expressed by HU. When the CT value is less than 60HU, the patient is a soft plaque; When the CT value is between 60 and 130 HU, the patient is a fibrous plaque; When the CT value is greater than 130HU, the patient is calcified plaque (11,12).…”