Moracin E and M isolated from Morus alba Linné induced the skeletal muscle cell proliferation via PI3K-Akt-mTOR signaling pathway.

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Comparative effectiveness of a low-calorie diet combined with acupuncture, cognitive behavioral therapy, meal replacements, or exercise for obesity over different intervention periods: A systematic review and network meta-analysis.

Objective: The aim of this study was to evaluate the comparative effectiveness of a low-calorie diet (LCD) combined with acupuncture, cognitive behavioral therapy (CBT), meal replacements (MR), and exercise on weight loss. Methods: The electronic databases MEDLINE, EMBASE, CENTRAL, CNKI, RISS, and KISS were searched systematically. Randomized controlled trials (RCTs) that directly compared the effect of a low-calorie diet (LCD)-combined acupuncture, CBT, and exercise and an MR-based diet on weight loss with LCD-alone for adults with simple obesity (body mass index [BMI] > 25) published before August 2021 were included in the study. Two investigators extracted and coded the data using a template. Any disagreements between investigators were resolved through discussion. Changes in BMI or weight were transformed to Hedges' g values with a 95% CI, and network meta-analyses using a Bayesian random-effects model were conducted. Results: A total of thirty-two trials involving 3,364 patients were finally included in the study. The effect sizes of four interventions were medium, in the order of acupuncture (Hedges' g = 0.48, 95% CI = 0.25 - 0.71), CBT (Hedges' g = 0.42, 95% CI = 0.20 - 0.63), MR (Hedges' g = 0.32, 95% CI = 0.19 - 0.45), and exercise (Hedges' g = 0.27, 95% CI = 0.06 - 0.46).In terms of intervention period, acupuncture was effective in the short period (≤ 12 weeks, Hedges' g = 0.39, 95% CI = 0.12 - 0.67) and the long period (>12 weeks, Hedges' g = 0.89, 95% CI = 0.37 - 1.40), whereas CBT (Hedges' g = 0.51, 95% CI = 0.26 - 0.76) and exercise (Hedges' g = 0.37, 95% CI = 0.12 - 0.59) were effective only in the long period. MR was effective only in the short period (Hedges' g = 0.35, 95% CI = 0.18 - 0.53). Conclusions: This study suggests that acupuncture, CBT, MR, and exercise for simple obesity show a medium effect size, and their effectiveness differs according to the intervention period.

Therapeutic effects of Gambi-jung for the treatment of obesity.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

UVB protective effects of Sargassum horneri through the regulation of Nrf2 mediated antioxidant mechanism.

The present study aimed to evaluate the protective effect of a methanol extract of Sargassum horneri (SHM), which contains 6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one (HTT) and apo-9'-fucoxanthinone, against ultraviolet B (UVB)-induced cellular damage in human keratinocytes and its underlying mechanism. SHM significantly improved cell viability of UVB-exposed human keratinocytes by reducing the generation of intracellular reactive oxygen species (ROS). Moreover, SHM inhibited UVB exposure-induced apoptosis by reducing the formation of apoptotic bodies and the populations of the sub-G1 hypodiploid cells and the early apoptotic cells by modulating the expression of the anti- and pro-apoptotic molecules, Bcl-2 and Bax, respectively. Furthermore, SHM inhibited NF-κB p65 activation by inducing the activation of Nrf2/HO-1 signaling. The cytoprotective and antiapoptotic activities of SHM are abolished by the inhibition of HO-1 signaling. In further study, SHM restored the skin dryness and skin barrier disruption in UVB-exposed human keratinocytes. Based to these results, our study suggests that SHM protects the cells against UVB-induced cellular damages through the Nrf2/HO-1/NF-κB p65 signaling pathway and may be potentially useful for the prevention of UVB-induced skin damage.

Phytochemicals in Chinese Chive (Allium tuberosum) Induce the Skeletal Muscle Cell Proliferation via PI3K/Akt/mTOR and Smad Pathways in C2C12 Cells.

Chinese chive (Allium tuberosum) is a medicinal food that is cultivated and consumed mainly in Asian countries. Its various phytochemicals and physiological effects have been reported, but only a few phytochemicals are available for skeletal muscle cell proliferation. Herein, we isolated a new compound, kaempferol-3-O-(6″-feruloyl)-sophoroside (1), along with one known flavonoid glycoside (2) and six amino acid (3-8) compounds from the water-soluble fraction of the shoot of the Chinese chive. The isolated compounds were identified using extensive spectroscopic methods, including 1D and 2D NMR, and evaluated for their proliferation activity on skeletal muscle cells. Among the tested compounds, newly isolated flavonoid (1) and 5-aminouridine (7) up-regulated PI3K/Akt/mTOR pathways, which implies a positive effect on skeletal muscle growth and differentiation. In particular, compound 1 down-regulated the Smad pathways, which are negative regulators of skeletal muscle growth. Collectively, we suggest that major constituents of Chinese chive, flavonoids and amino acids, might be used in dietary supplements that aid skeletal muscle growth.

Safety of co-administration of herbal and conventional medicines on liver and kidney function in stroke patients: A single-center retrospective study.

BACKGROUND: Although herbal medicines (HMs) are widely used worldwide, information concerning their interactions with conventional medicines (CMs) is sparse. In particular, stroke affects a high proportion of elderly people with impaired hepatic and renal function. Stroke is often accompanied by various complications and is commonly treated via the co-administration of HMs and CMs in Asia. PURPOSE: We aimed to investigate the effects of co-administration of HMs and CMs on liver and kidney function in patients with stroke. We estimated the prevalence of drug-induced liver injury (DILI) or herb-induced liver injury (HILI) and drug-induced acute kidney injury (DIAKI) or herb-induced acute kidney injury (HIAKI) in patients co-administered HMs and CMs. STUDY DESIGN: This was a retrospective study that reviewed the electronic medical records of 401 patients with stroke in a single hospital. METHODS: The prevalence of DILI or HILI and types of liver injury was examined according to abnormal increases in liver tests. The probable causality between drug or herb administration and liver injury was assessed using the Roussel Uclaf Causality Assessment Method. In addition, the prevalence of DIAKI or HIAKI was estimated using the Kidney Disease Improving Global Outcomes acute kidney injury stage criteria and related medical records. RESULTS: Out of a total of 401 patients, only four (1.0%) developed liver injury. Two cases of DILI (0.5%) and two cases of HILI (0.5%) were reported. Moxifloxacin and ebastine were the CMs that caused hepatotoxicity. Chungpyesagan-tang and Yeoldahanso-tang were the HMs that caused liver toxicity. Even in cases showing severe liver damage, alkaline phosphatase levels remained less than five times the normal value, and liver function test values recovered within 14 days. There were no cases of DIAKI or HIAKI in this cohort. CONCLUSION: These results suggest that if appropriately prescribed by experts, the co-administration of CMs and HMs is safe and does not adversely affect liver and kidney function in patients with stroke. To support these results, further large-scale multicenter prospective studies and toxicological studies based on the interaction between HMs and CMs are warranted.

1-Cinnamoyltrichilinin from Melia azedarach Causes Apoptosis through the p38 MAPK Pathway in HL-60 Human Leukemia Cells.

Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating the development of novel compounds with a high therapeutic window. This study aimed to investigate the anticancer effects of several compounds derived from the fruits of Melia azedarach (a tree with medicinal properties). Among them, 1-cinnamoyltrichilinin (CT) was found to strongly suppress the viability of HL-60 human leukemia cells. CT treatment induced apoptosis and increased nuclear fragmentation and fractional DNA content in HL-60 cells in a dose-dependent manner. CT induced phosphorylation of p38 mitogen-activated protein kinases (p38), though not of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), and activated Bcl-2 family proteins towards the proapoptosis and cleavage of caspase-3 and poly (ADP-ribose) polymerase. Both CT-mediated apoptosis and apoptotic protein expression were reversed by treatment with the p38 inhibitor, thereby indicating the p38 pathway to be critical in CT-stimulated apoptosis. The results collectively indicated CT to suppress HL-60 survival by activating the p38 pathway and inducing apoptosis, hence being a novel potential therapeutic agent for AML.

Electroacupuncture for post-stroke dysphagia: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Post-stroke dysphagia (PSD) requires effective treatment as it may cause aspiration pneumonia, dehydration, or malnutritution, which can increase the length of hospital stay as well as mortality. In the field of stroke, electroacupuncture (EA) has been widely used, and a number of clinical research papers have been published regarding its effects. This systematic review aims to evaluate the effectiveness of EA for the treatment of PSD. METHODS: Randomized controlled trials evaluating the use of EA in PSD will be included in this meta-analysis. The following electronic databases will be searched from inception to July 31, 2020, using terms relating to EA and PSD: PubMed, the Cochrane Library, the Excerpta Medica Database, China National Knowledge Infrastructure, the Korean Medical Database, KoreaMed, the National Digital Science Library, and the Oriental Medicine Advanced Searching Integrated System. Two reviewers will independently search these databases, select studies for inclusion, and evaluate the quality of the studies. Methodological quality will be assessed using the Cochrane Handbook for Systematic Reviews of Interventions (version 6.0). The primary outcome will be the total effective rate; secondary outcomes will include results of other assessments of dysphagia such as the water drinking test scale and videofluoroscopic swallowing study. We will also investigate the number and severity of adverse events. The Cochrane Review Manager (RevMan) software (version 5.3.5) will be employed to assess bias risk, data integration risk, and meta-analysis risk. Mean difference and standardized mean difference will be used to represent continuous data, while risk ratios will be used for pooled binary data. RESULTS: This study will provide a comprehensive review and evaluation of the available evidence regarding the efficacy and safety of EA as a treatment for PSD. CONCLUSION: This study will clarify whether EA could be an effective and safe treatment for PSD.

Sargassum horneri (Turner) inhibit urban particulate matter-induced inflammation in MH-S lung macrophages via blocking TLRs mediated NF-κB and MAPK activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum horneri is a nutrient rich edible brown seaweed with numerous biological properties found in shallow coastal areas of Korean peninsula. S. horneri traditionally used as a medicinal ingredient to treat several disease conditions such as hyperlipidemia, hypertension, heart disease, and inflammatory diseases (furuncle). However, to utilize S. horneri as an active ingredient for functional foods and human health applications requires to conform the bioactive properties and underlying mechanisms of those activities. AIM OF THE STUDY: Here, we investigated anti-inflammatory mechanisms of commercial grade 70% ethanol extract separated from S. horneri (SHE) on inflammatory response in particulate matter (PM)-induced MH-S lung macrophages; where PM in breathable air one of the major health concern in Korea. MATERIALS AND METHODS: We compared the anti-inflammatory effects of SHE on the activity of toll-like receptors (TLR) activation, NF-κB, MAPKs, and pro-inflammatory cytokine secretion in MH-S lung macrophages exposed to PM as a lung inflammation model. RESULTS: According to the results, PM-stimulation, induced the levels of NO, PGE2, TNF-α, IL-1ß, IL-6, iNOS, and COX2 (P < 0.05) in MH-S macrophages. In addition, phosphorylation levels of NF-κB and MAPKs were also increased with the PM stimulation through the upregulated expression of TLR. However, SHE treatment significantly repressed the secretions of inflammatory cytokines and reduced protein expression such as PGE2, TNF-α, IL-6, IL-1ß, NF-κB, and MAPKs from PM-activated macrophages. Specifically, SHE inhibited the upregulated mRNA expression levels of TLR2, TLR3, TLR4, and TLR7 in PM-induced MH-S cells; known biomarkers of downstream activation of NF-κB and MAPKs. CONCLUSION: These results suggested that SHE is a potential inhibitor of PM-induced inflammatory responses in lung macrophages. Thus, SHE could inhibit PM-induced chronic inflammation in lungs via blocking TLR/NF-κB/MAPKs signal transduction. Therefore, it was concluded that SHE may be a useful substance to develop as functional product to reduce inflammation against PM-induced inflammation.

Free radical scavenging activity of the peptide from the Alcalase hydrolysate of the edible aquacultural seahorse (Hippocampus abdominalis).

Seahorses, Hippocampus abdominalis, have a long history in traditional Chinese medicine as an important healthy ingredient in foods. This study evaluated the antioxidant activity of an enzymatic hydrolysate prepared from a seahorse bred in Jeju, South Korea. Experiments were performed in vitro using electron spin resonance spectrometry (ESR) to determine the free radical scavenging activity and in vivo using a zebrafish model to determine the protective effects against 2,2-azobis hydrochloride (AAPH)-induced oxidative damage. H. abdominalis protein hydrolysate (HPH) exhibited peroxyl radical scavenging activity (IC50  = 0.58 mg/ml) generated by the water-soluble AAPH (azo initiator of peroxyl radicals). HPH reduced dose-dependently both intracellular reactive oxygen species (ROS) levels in AAPH-induced cells and cell death in AAPH-induced zebrafish embryos. The antioxidant peptide purified from HPH was identified as a tripeptide (alanine-glycine-aspartic acid) using Q-TOF ESI mass spectroscopy. Thus, this study demonstrated that HPH contains antioxidant peptides that exhibit a strong antioxidant activity. PRACTICAL APPLICATIONS: Hippocampus abdominalis is one of the largest seahorse species and cultivated in many countries. Because of its large body size compared to other seahorse species, H. abdominalis has acquired considerable consumer attraction in the global market. Owing to its biologically useful properties, it recently gained attention as the natural products obtained from H. abdominalis have varied applications in the field of medicine, health care products, and functional foods. Thus, commercial products of this particular seahorse species are popular among customers, especially in China. The purpose of this study was to evaluate the antioxidant property of H. abdominalism, cultured in a commercial seahorse farm in Jeju Island. Owing to its prominent antioxidant activity, it could be used as an ingredient in medicinal preparations, nutraceuticals, and functional foods.

Reduction of heavy metal (Pb2+) biosorption in zebrafish model using alginic acid purified from Ecklonia cava and two of its synthetic derivatives.

Heavy metal contamination has become a major problem that causes severe environmental and health issues due to their biosorption, bioaccumulation, and toxicity. This study was designed to evaluate heavy metal chelating abilities of alginic acid (AA) extracted from the brown seaweed Ecklonia cava and two of its derivatives prepared by the partial oxidation of the 2° OH groups (OAA) and partial carboxylation of the monomeric units (CAA) upon reducing the heavy metal biosorption in zebrafish (Danio rerio) modal. Metal ions were quantified using ICP-OES and biopolymers were characterized by FTIR and XRD analysis. All investigated biopolymers indicated potential ability for chelating Pb2+, Cu2+, Cd2+, As3+, and Ag+. The sorption capacities were in the order of CAA>OAA>AA. All biopolymers indicated a comparatively higher chelation towards Pb2+. AA, OAA, and CAA could effectively reduce Pb2+ induced toxicity and Pb2+ stress-induced ROS production in zebrafish embryos. Besides, they could reduce the biosorption of Pb2+ in adult zebrafish which could lead to bioaccumulation. Since alginic acid purified from E. cava and its derivatives could be utilized as seaweed derived biopolymers to purify heavy metals contaminated water and as a dietary supplement to reduce heavy metal biosorption in organisms.

Corrosion resistance and bioactivity enhancement of MAO coated Mg alloy depending on the time of hydrothermal treatment in Ca-EDTA solution.

In this study, a two-step surface treatment was developed to restrain the rapid primary degradation of a biodegradable Mg alloy and to improve their biocompatibility. Micro arc oxidation (MAO) coating was performed in alkaline electrolytes such as 1.0 M NaOH with 0.1 M glycerol and 0.1 M Na3PO4. Hydrothermal treatment was performed in 0.1 M Ca-EDTA (C10H12CaN2Na2O8) and 0.5 M NaOH solution at 90 °C for different times (6, 12, 24, and 48 h). The film morphology and chemical properties were evaluated by XRD and FE-SEM. The electrochemical and corrosion behaviors were examined in the simulated body fluid, and cytotoxicity was assessed using MC3T3-E1 cells. After MAO coating, an oxide layer containing [Formula: see text] formed on the surface. During the hydrothermal treatment in Ca-EDTA solution, calcium phosphate and Mg(OH)2 were produced via a reaction between [Formula: see text] on the surface and Ca2+ in solution. The layer with ceramics and oxides was grown on the surface with increasing hydrothermal treatment time, and improved the surface corrosion resistance. The 24 h hydrothermal-treated group showed the lowest immersion corrosion rate and high cell viability. Therefore, this treatment was the most favorable surface modification for improving the initial corrosion resistance and bioactivity of the biodegradable Mg alloy.

In vitro and in vivo antioxidant activities of polysaccharide purified from aloe vera (Aloe barbadensis) gel.

The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel by using ten digestive enzymes including five carbohydrases and five proteases. Among them, the highest yield was obtained with the Viscozyme extract and the same extract showed the best radical scavenging activity. An active polysaccharide was purified from the Viscozyme extract using ethanol-added separation and anion exchange chromatography. Purified aloe vera polysaccharide (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In addition, APS showed a protective effect against AAPH-induced oxidative stress and cell death in Vero cells as well as in the in vivo zebrafish model. In this study, it is proved that both the in vitro and in vivo antioxidant potentials of APS could be further utilized in relevant industrial applications.

Heat shock factor 1 inducers from the bark of Eucommia ulmoides as cytoprotective agents.

The barks of Eucommia ulmoides (Eucommiae Cortex, Eucommiaceae) have been used as a traditional medicine in Korea, Japan, and China to treat hypertension, reinforce the muscles and bones, and recover the damaged liver and kidney functions. Among these traditional uses, to establish the recovery effects on the damaged organs on the basis of phytochemistry, the barks of E. ulmoides have been investigated to afford three known phenolic compounds, coniferaldehyde glucoside (1), bartsioside (2), and feretoside (3), which were found in the family Eucommiaceae for the first time. The compounds 1-3 were evaluated for their inducible activities on the heat shock factor 1 (HSF1), and heat shock proteins (HSPs) 27 and 70, along with four compounds, geniposide (4), geniposidic acid (5), pinoresinol diglucoside (6), and liriodendrin (7), which were previously reported from E. ulmoides. Compounds 1-7 increased expression of HSF1 by a factor of 1.214, 1.144, 1.153, 1.114, 1.159, 1.041, and 1.167 at 3 µM, respectively. Coniferaldehyde glucoside (1) showed the most effective increase of HSF1 and induced successive expressions of HSP27 and HSP70 in a dose-dependent manner without cellular cytotoxicity, suggesting a possible application as a HSP inducer to act as cytoprotective agent.

Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells.

Considerable attention has recently been focused on identifying chemopreventive phytochemicals derived from medicinal plants. Here, we analyzed phenolic phytochemicals from red pine (RP) leaves and found epigallocatechin gallate (EGCG) and epigallocatechin (EGC), and catechin gallate (CG) as their major phenolic phytochemicals. This article also investigated whether RP leaf extract and its phenolic phytochemicals inhibit the invasion of SK-Hep-1 human hepatocellular carcinoma cells (SK-Hep-1 cells). RP suppressed the invasion and the migration of SK-Hep-1 cells. EGCG and CG also inhibited the invasion and migration, with EGC exhibiting a lower efficacy. Matrix metalloproteinases (MMPs), particularly gelatinase-A (MMP-2) and gelatinase-B (MMP-9), degrade components of the basement membrane and are strongly implicated in invasion and metastasis formation of malignant tumors. RP suppressed both MMP-2 and MMP-9 activities. EGCG and CG reduced the activities of MMP-9 and MMP-2 in a dose-dependent manner, with EGC exhibiting a lower efficacy on both MMPs. Our results suggest that RP inhibits tumor invasion and migration, which may be attributed to the effects of EGCG and CG. In particular, EGCG plays a key role in the efficacy of RP against hepatocarcinogenesis.