Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely ¹H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a ¹H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Polygonum orientale L. (Polygonaceae) fruits have various medicinal uses, but their hepatoprotective effects have not yet been studied. This study investigated the hepatoprotective activity of the ethanolic extract of P. orientale (POE) fruits against carbon tetrachloride (CCl4)-induced acute liver injury (ALI). Mice were pretreated with POE (0.1, 0.5, and 1.0 g/kg) or silymarin (0.2 g/kg) for 5 consecutive days and administered a dose of 0.175% CCl4 (ip) on the 5th day to induce ALI. Blood and liver samples were collected to measure antioxidative activity and cytokines. The bioactive components of POE were identified through high-performance liquid chromatography (HPLC). Acute toxicity testing indicated that the LD50 of POE exceeded 10 g/kg in mice. Mice pretreated with POE (0.5, 1.0 g/kg) experienced a significant reduction in their serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and reduction in the extent of liver lesions. POE reduced the malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels, and increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in liver. HPLC revealed peaks at 11.28, 19.55, and 39.40 min for protocatechuic acid, taxifolin, and quercetin, respectively. In summary, the hepatoprotective effect of POE against CCl4-induced ALI was seemingly associated with its antioxidant and anti-proinflammatory activities.

Plectranthus amboinicus(Lour.) Spreng. is a native Labiatae plant of Taiwan. The plants are commonly used in Chinese folk medicine for the treatment of cough, fever, sore throats, mumps, and mosquito bite. The aim of this study was to investigate the analgesic and antiinflammatory properties of the aqueous extract fromPlectranthus amboinicus(PA)in vivoandin vitro. PA inhibited pain induced by acetic acid and formalin, and inflammation induced by carrageenan. The anti-inflammatory effect of PA was related to modulating antioxidant enzymes' activities in the liver and decreasing the Malondialdehyde (MDA) level and the production of tumor necrosis factor alpha (TNF-α), and cyclooxygenase2 (COX-2) in edema-paw tissue in mice.In vitrostudies show that PA inhibited the proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). PA blocked the degradation of IκB-αand nuclear translocation of NF-κB p65 subunit. Finally, the amount of carvacrol in the aqueous extract of PA was 1.88 mg/g extract. Our findings suggest that PA has analgesic and anti-inflammatory activities. These effects were mediated by inhibiting the proinflammatory mediators through blocking NF-κB activation. Meanwhile, the effects observed in this study provide evidence for folkloric uses ofPlectranthus amboinicus(Lour.) Spreng. in relieving pain and inflammation.

Background: The present study was undertaken to evaluate the anti-depressive activity of turmerone after one-week administration by using a mouse forced swimming test (FST) and tail suspension test (TST). Methods: Animals were divided into four groups (n = 10 /group): control (0.9% saline), the three doses of turmerone (1.25, 2.5, 5.0 mg/kg) for one-week treatment. To assess the effect of turmerone on locomotor activity, mice were evaluated in the open-field paradigm. Forced swimming test (FST) and Tail suspension test (TST) were used to take as a measure of antidepressant activity. The probable mechanisms of action of the anti-depressive effect of turmerone was also investigated by measuring the activity of monoamine oxidase-A and corticosterone levels in the blood and the levels of monoamines in the cortex, striatum, hippocampus and hypothalamus of the mice. Results: Turmerone (2.5, 5.0 mg/kg, p.o.) significantly reduced the immobility time of mice in both the FST and TST, but it did not significantly affect the ambulatory and total movements of mice. However, hyperactivity might explain the results. In addition, turmerone decreased the corticosterone level in the blood while it increased the levels of 5-HT in cortex, striatum, hippocampus, and hypothalamus, the level of NE in striatum and hippocampus, the levels of MHPG and DOPAC in hypothalamus, the level of 5-HIAA in striatum, and the level of DA in striatum, hippocampus, and hypothalamus. Turmerone (2.5, 5.0 mg/kg) decreased the activity of MAO-A in the frontal cortex and hippocampus of mouse brain. Conclusions: After one-week administration, turmerone produced antidepressant-like effects. The mechanisms of action of anti-depressive effect of turmerone seemed to involve an increase of the monoamines level decreasing the MAO-A activity and the stress of mice.