Hepatoprotective effect of the ethanol extract of Polygonum orientale on carbon tetrachloride-induced acute liver injury in 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-1ß (IL-1ß), 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.

Hepatoprotective effect of Coreopsis tinctoria flowers against carbon tetrachloride-induced liver damage in mice.

BACKGROUND: Coreopsis tinctoria is a traditional remedy for the management of various diseases including hepatitis. The hepatoprotective role of the plant is not scientifically explored till now. This study was designed to investigate the hepatoprotective potentials of the ethanol extract from C. tinctoria (CTEtOH) using an animal model of carbon tetrachloride (CCl4)-induced acute liver injury. METHODS: CTEtOH (0.5 and 1.0 g/kg) and silymarin (200 mg/kg) were administered to the experimental mice for 7 days followed by 0.2% CCl4 (10 mL/kg of body weight (bw), ip), then all mice were sacrificed after 24 h. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Histological analysis of liver was performed. The tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nitric oxide (NO), malondialdehyde (MDA), and antioxidant enzymatic activities were also measured.. RESULTS: The results revealed that the serum ALT and AST levels significantly decreased after treatment with CTEtOH. Moreover, histological analyses indicated that CTEtOH (0.5 and 1.0 g/kg) and silymarin reduced the extent of CCl4-induced liver lesions. CTEtOH (0.5 and 1.0 g/kg) reduced the levels of malondialdehyde, nitric oxide, and proinflammatory cytokines (TNF-α and IL-1ß). Furthermore, CTEtOH (1.0 g/kg) reduced the level of IL-6. The activities of antioxidant enzymes, namely superoxide dismutase and glutathione reductase, significantly increased after treatment with CTEtOH (0.5 and 1.0 g/kg) and that of glutathione peroxidase increased after treatment with 1.0 g/kg of CTEtOH. CONCLUSIONS: These results demonstrate the hepatoprotective effect of CTEtOH against CCl4-induced acute liver injury in mice, and the underlying hepatoprotective mechanisms are associated with antioxidant and antiproinflammatory activities.

Antioxidant and anti-inflammatory properties of Taiwanese yam (Dioscorea japonica Thunb. var. pseudojaponica (Hayata) Yamam.) and its reference compounds.

Dioscorea japonica Thunb. var. pseudojaponica (DP) is consumed as food and widely used in traditional Chinese medicine in Taiwan. The aims of this study are to investigate the antioxidant and anti-inflammatory effects of ethanol extract of DP (EDP) and its reference compounds. Fingerprint chromatogram from HPLC indicated that EDP contains gallic acid and vanillic acid. EDP was evaluated for its antioxidant effects and LPS-induced nitrite oxide (NO) production in RAW264.7 cells. EDP decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. In-vivo anti-inflammatory activities of EDP were assessed in mouse paw oedema induced by λ-carrageenan (Carr). We investigated the antioxidant mechanism of EDP via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the oedematous paw. The results showed that EDP might be a natural antioxidant and anti-inflammatory agent.

Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima.

ETHNOPHARMACOLOGICAL RELEVANCE: Centipeda minima (L.) is traditionally used in Chinese folk medicine for the treatments of rhinitis, sinusitis, relieving pain, reducing swelling, and treating cancer for a long history in Taiwan. However, there is no scientific evidence which supports the use in the literature. AIM OF THE STUDY: The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of the aqueous extract of Centipeda minima (ACM). MATERIALS AND METHODS: The following activities were investigated: antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), DPPH (1,1-diphenyl-2-picrylhydrazyl)], and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigated the anti-inflammatory mechanism of ACM via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) were also measured in vivo. In HPLC analysis, the fingerprint chromatogram of ACM was established. RESULTS: ACM showed the highest TEAC and DPPH radical scavenging activities, respectively. ACM also had highest contents of polyphenol and flavonoid contents. We evaluated that ACM and the reference compound of protocatechualdehyde and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Administration of ACM showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ACM could be via NO, TNF-α, and IL-1ß suppressions and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ACM decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. CONCLUSIONS: Anti-inflammatory mechanisms of ACM might be correlated to the decrease in the level of Malondialdehyde (MDA), iNOS, and COX-2 via increasing the activities of CAT, SOD, and GPx in the edema paw. Overall, the results showed that ACM demonstrated antioxidant and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.

Chemical compositions, anti-inflammatory, antiproliferative and radical-scavenging activities of Actinidia callosa var. ephippioides.

Oxidative stress and inflammation are related to several chronic diseases including cancer. Actinidia callosa var. ephippioides (ACE) is a special folk medicinal plant from Taiwan. The aim of this study is to evaluate the antioxidant, anti-inflammatory, and antiproliferative activities of the methanol extract and fractions from the stem of ACE. Trolox Equivalent Antioxidant Capacity (TEAC), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, total phenolic content, flavonoid content, inhibition on nitric oxide (NO) productions by LPS-induced RAW264.7 cell, and on lung cancer cell proliferation were employed. Among all fractions, ethyl-acetate fraction (EA-ACE) showed higher TEAC, DPPH radical scavenging activities, polyphenol and flavonoid contents, respectively. EA-ACE also decreased the LPS-induced NO production and expressions of inducible nitric-oxide synthase (iNOS) in RAW264.7 cells. EA-ACE had the highest antiproliferative activity with an IC(50) (The concentrations required for inhibition of 50% of cell viability) of 469.17 ± 3.59 µg/mL. Catechin also had good effects in the antioxidant and anti-inflammatory activities. Catechin might be an important bioactive compound in the stem of ACE. The above experimental data indicated that the stem of ACE is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds.

Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis.

Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.

Anti-Inflammatory Activities of Cinnamomum cassia Constituents In Vitro and In Vivo.

We have investigated the anti-inflammatory effects of Cinnamomum cassia constituents (cinnamic aldehyde, cinnamic alcohol, cinnamic acid, and coumarin) using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with cinnamic aldehyde together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that cinnamic aldehyde blocked protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-κB), and IκBα, significantly. In the anti-inflammatory test, cinnamic aldehyde decreased the paw edema after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated cinnamic aldehyde attenuated the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in the edema paw after Carr injection. Cinnamic aldehyde decreased the NO, TNF-α, and PGE(2) levels on the serum level after Carr injection. Western blotting revealed that cinnamic aldehyde decreased Carr-induced iNOS, COX-2, and NF-κB expressions in the edema paw. These findings demonstrated that cinnamic aldehyde has excellent anti-inflammatory activities and thus has great potential to be used as a source for natural health products.

Hispolon Protects against Acute Liver Damage in the Rat by Inhibiting Lipid Peroxidation, Proinflammatory Cytokine, and Oxidative Stress and Downregulating the Expressions of iNOS, COX-2, and MMP-9.

The hepatoprotective potential of hispolon against carbon tetrachloride (CCl(4))-induced liver damage was evaluated in preventive models in rats. Male rats were intraperitoneally treated with hispolon or silymarin once daily for 7 consecutive days. One hour after the final hispolon or silymarin treatment, the rats were injected with CCl(4). Administration with hispolon or silymarin significantly decreased the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum and increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione (GSH) content and decreased the malondialdehyde (MDA) content in liver compared with CCl(4)-treated group. Liver histopathology also showed that hispolon reduced the incidence of liver lesions induced by CCl(4). In addition, hispolon decreased nitric oxide (NO) production and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) activation in CCl(4)-treated rats. We also examined the involvement of matrix metalloproteinase (MMP)-9 in the development of CCl(4)-induced liver damage in rats. Hispolon inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl(4)-induced rat liver damage. Therefore, we speculate that hispolon protects rats from liver damage through their prophylactic redox balancing ability and anti-inflammation capacity.

Analgesic and Antiinflammatory Activities of the Aqueous Extract from Plectranthus amboinicus (Lour.) Spreng. Both In Vitro and In Vivo.

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 from Plectranthus amboinicus (PA) in vivo and in 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 vitro studies show that PA inhibited the proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). PA blocked the degradation of IκB-α and 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 of Plectranthus amboinicus (Lour.) Spreng. in relieving pain and inflammation.

Anti-inflammatory activities of aqueous extract of Mesona procumbens in experimental mice.

BACKGROUND: Mesona procumbens is consumed as a herbal drink and jelly-type dessert in Taiwan. The aim of this study was to determine the mechanism of anti-inflammatory activities of the aqueous extract of M. procumbens (AMP) using the λ-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint chromatogram of AMP was obtained by high-performance liquid chromatography (HPLC) analysis. To investigate the anti-inflammatory mechanism of AMP, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in paw oedema were monitored. Serum nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also evaluated. RESULTS: The fingerprint chromatogram from HPLC indicated that AMP contained protocatechuic acid, chlorogenic acid, vanillic acid and caffeic acid. In the anti-inflammatory test, AMP decreased paw oedema after Carr administration and increased the CAT, SOD and GPx activities and decreased the MDA level in paw oedema at 5 h after Carr injection. AMP also affected the serum NO, TNF-α and IL-1ß levels at 5 h after Carr injection. Western blotting revealed that AMP decreased the expression of Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). CONCLUSION: Mesona procumbens has the potential to provide a therapeutic approach to inflammation-associated disorders.

Esculetin ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats.

Esculetin (ESC) is a coumarin that is present in several plants such as Fraxinus rhynchophylla and Artemisia capillaris. Our previous study found that FR ethanol extract (FR(EtOH)) significantly ameliorated rats' liver function. This study was intended to investigate the protective mechanism of ESC in hepatic apoptosis in rats induced by carbon tetrachloride. Rat hepatic apoptosis was induced by oral administration of CCl(4). All rats were administered orally with CCl(4) (20%, 0.5 mL/rat) twice a week for 8 weeks. Rats in the ESC groups were treated daily with ESC, and silymarin group were treated daily with silymarin. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the activities of the anti-oxidative enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase in the liver were measured. In addition, expression of liver apoptosis proteins and anti-apoptotic proteins were detected. ESC (100, 500 mg/kg) significantly reduced the elevated activities of serum ALT and AST caused by CCl(4) and significantly increased the activities of catalase, GPx and SOD. Furthermore, ESC (100, 500 mg/kg) significantly decreased the levels of the proapoptotic proteins (t-Bid, Bak and Bad) and significantly increased the levels of the anti-apoptotic proteins (Bcl-2 and Bcl-xL). ESC inhibited the release of cytochrome c from mitochondria. In addition, the levels of activated caspase-9 and activated caspase-3 were significantly decreased in rats treated with ESC than those in rats treated with CCl(4) alone. ESC significantly reduced CCl(4)-induced hepatic apoptosis in rats.

Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

Antinociceptive activities and the mechanisms of anti-inflammation of asiatic Acid in mice.

Asiatic acid (AA), a pentacyclic triterpene compound in the medicinal plant Centella asiatica, was evaluated for antinociceptive and anti-inflammatory effects. Treatment of male ICR mice with AA significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, AA decreased the paw edema at the 4th and 5th h after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. AA decreased the nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels on serum level at the 5th h after Carr injection. Western blotting revealed that AA decreased Carr-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor-κB (NF-κB) expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with AA also diminished neutrophil infiltration into sites of inflammation as did indomethacin (Indo). The anti-inflammatory mechanisms of AA might be related to the decrease in the level of MDA, iNOS, COX-2, and NF-κB in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver.

Antioxidant, antinociceptive, and anti-inflammatory activities of Xanthii Fructus extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthii seeds commonly called Cang-Erzi were used as a traditional Chinese medicine for treating sinusitis, headache due to rheumatism and skin pruritus. AIM OF THE STUDY: In order to evaluate the actions of this plant, studies were performed on antioxidant, antinociceptive, and anti-inflammatory activities. MATERIALS AND METHODS: The aqueous extract of Xanthii Fructus (AXF) was evaluated in mice for anti-inflammatory activity using carrageenan-induced hind paw edema model. The antinociceptive activity of AXF was evaluated by writhing and formalin tests. Antioxidant properties were assayed in terms of antioxidant activity by scavenging abilities on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS), reducing activity and liposome protection. In addition, the total phenolic content was determined with spectrophotometric method. RESULTS: AXF exhibited significant radical scavenging and reducing activity. And oral treatment with AXF elicited inhibitory activity on acetic acid effect and reduced the formalin effect at the late-phase. In the anti-inflammatory test, AXF inhibited the development of paw edema induced by λ-carrageenan (Carr). AXF decreased the paw edema at the fifth hour after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue and decreased the malondialdehyde (MDA) level in the edema paw. AXF decreased the level of serum nitric oxide (NO) and tumor necrosis factor (TNF)-α after Carr injection and AXF decreased the levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in paw edema at the fifth hour. CONCLUSIONS: AXF shows antioxidant, antinociceptive, and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.

Neuroprotective effect of luteolin on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons.

The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid beta (Abeta) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 muM Abeta (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 microM) significantly protected cortical cell cultures against Abeta (25-35)-induced toxicity. Luteolin (1, 10 microM) showed a concentration-dependent inhibition on 10 muM Abeta (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Abeta (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Abeta (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations.

Yam (Dioscorea pseudojaponica Yamamoto) ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of yam (Dioscorea pseudojaponica Yamamoto) on the senescent mice induced by D-gal. The mice in the experiments were administered orally with yam (20, 100 or 500 mg/kg for 4 weeks, from the sixth week). The learning and memory abilities of the mice in Morris water maze test and the mechanisms involved in the neuroprotective effect of yam on the mice brain tissue were investigated. The content of diosgenin in the yam was also detected by using HPLC. Mice treated with yam were found to significantly improve their learning and memory abilities in Morris water maze test compared to those treated with D-gal (200 mg/kg for 10 weeks). In addition, yam was also found to increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decrease the malondialdehyde (MDA) level on the brains of D-gal treated mice. Finally, the amount of diosgenin in the yam was 5.49 mg/g extract. To sum up, these results indicate that yam had the potential to be a useful treatment for cognitive impairment in TCM. Its beneficial effect may be partly mediated via enhancing endogenous antioxidant enzymatic activities.