Preparation of an efficient and safe polymeric-magnetic nanoparticle delivery system for sorafenib in hepatocellular carcinoma.

AIMS: Superparamagnetic iron oxide nanoparticles (SPIONs), as drug delivery vehicles, offer to eliminate the concerns associated with hydrophobic anti-cancer agents. The current study was intended to fabricate a SPION based delivery system for sorafenib that can simultaneously enable targeted delivery of sorafenib and expand its therapeutic index against hepatocellular carcinoma (HCC). MAIN METHODS: Co-precipitation and physical entrapment methods were employed for the synthesis of sorafenib loaded PVA coated SPIONs. Physicochemical characterizations were done using TEM, XRD, FTIR, Raman spectra and VSM measurements. The superior activity of nanoconjugate was demonstrated by AO/EB staining, FACS, immunofluorescence and Western blot. The safety of the sorafenib conjugated nanoparticles were verified in Wistar rats. KEY FINDINGS: The synthesized nanoparticles were in the size range of 5-15 nm. The adsorption of PVA to the SPIONs and the conjugation of sorafenib to the nanocarrier were confirmed by XRD, FTIR and Raman spectra analyses. VSM study ascertained the superparamagnetic nature of the nanoconjugate. Cellular uptake studies suggested its efficient entrapment in HepG2 cells. MTT assay showed that the cytotoxicity of sorafenib loaded PVA/SPIONs was comparable or higher than free sorafenib. The activation of apoptosis and autophagy pathways in HepG2 by the nanoconjugate was evidenced. Acute toxicity testing in Wistar rats supported the safe administration of the nanoconjugate and established its localization in animal tissues by Perl's Prussian Blue reaction. SIGNIFICANCE: The novel combination of sorafenib with PVA/SPIONs showed better anticancer efficiency than free sorafenib demonstrative of its potential in cancer chemotherapy.

Glycopentalone, a novel compound from Glycosmis pentaphylla (Retz.) Correa with potent anti-hepatocellular carcinoma activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycosmis pentaphylla (Retz.) Correa is used in Indian traditional medicine against various liver ailments, including cancer. AIM OF THE STUDY: Isolation and characterization of the most active anti-hepatocellular carcinoma (HCC) compound from the alcohol extract of G. pentaphylla. MATERIALS AND METHODS: Different chromatographic (HPLC, TLC and column chromatography) and methods like IR, LCMS and NMR were used for the isolation and structural identification of the active anti-HCC compound from G. pentaphylla. Cytotoxic and apoptosis inducing effect of the active compound were assessed in Hep3 B, RAW264.7 and HEK293 cell lines by MTT assay, morphological studies, Hoechst staining and Annexin V FITC assay. RESULTS: The most active compound was isolated as yellow needle shaped crystals. The structure of the compound was identified by IR, LCMS and NMR methods. The structural details show that the isolated compound is a novel chemical and have structural similarity with chalcone. MTT assay, physiological and FACS analysis proved the anti-HCC efficacy of the isolated compound in vitro. CONCLUSION: The study confirmed that the most active anti-HCC compound present in the alcohol extract of G. pentaphylla is a chalcone derivative. This compound showed specific cytotoxicity against Hep3 B with minor cytotoxicity against non HCC cell lines, RAW264.7 and HEK293. The present study, therefore, supports the folklore knowledge for the utility of G. pentaphylla and provides a scientific basis for their traditional usage against liver cancer.

A new fluorescent based screening system for high throughput screening of drugs targeting HBV-core and HBsAg interaction.

The existing screening systems for anti-hepatitis B virus (anti-HBV) drug discovery is time-consuming mainly due to the laborious detection system it is using. A new fluorescence based screening system for high throughput anti-HBV drug discovery was created by tagging hepatitis B surface antigen (HBsAg) with monomeric red fluorescent protein and hepatitis B virus (HBV) core protein with enhanced green fluorescent protein. The two constructs were co-transfected on to Hep3B cells and the transfection was stabilized by fluorescent activated cell sorter (FACS). The fusion proteins expressed through the secretory protein pathway as evidenced by localization with ER-Tracker and tubulin tracker. The new system has given analogues results like that of conventional enzyme-linked immunosorbent assay (ELISA). Hence it can be of very high potential for large scale drug screening systems.

Anti-HBV activity of the different extracts from Phyllanthus rheedei Wight in cell culture based assay systems.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthusrheedei Wight is a plant used by Muthuvan tribes of Kerala for treating liver related diseases. MATERIALS AND METHODS: The different extracts of Phyllanthus rheedei were analysed on cell lines were viz, PLC/PRF, Hep3B, FLCII10 and HepG2215 for its anti-HBV property. The analysis was done through ELISA, SQRT-PCR and immuno blotting. The most active extract was then divided in to fractions using HPTLC and the most active fraction was further identified. RESULTS: From the screening experiments it was shown that the ethanol extract of this plant has the maximum activity in lowering the viral markers like HBsAg, HBV Core and HBV X protein and whole virions with comparatively lesser cytotoxicity. The dose responses of this particular extract were further established. CONCLUSIONS: This study concluded that the ethanol extract of Phyllanthusrheedei is very much effective in preventing the multiplication of HBV at the cellular level. This study scientifically validated the tribal claim of the use of this plant for severe liver disorders.

The apoptosis inducing effect of Glycosmis pentaphylla (Retz.) Correa and its influence on gene expression in hepatocellular carcinoma cell line, Hep3 B.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycosmis pentaphylla (Retz.) Correa is used in Indian traditional medicine against jaundice and other liver disorders. AIM OF THE STUDY: The study aims to determine the in vitro anticancer and apoptosis inducing activity of Glycosmis pentaphylla in hepatocellular carcinoma cell line, Hep3 B. MATERIALS AND METHODS: The cytotoxic and apoptosis inducing activity of the crude extract and active fractions were estimated on Hep3 B and RAW264.7 cell lines by MTT assay, Hoechst staining, DNA fragmentation, morphological studies, reverse transcription polymerase chain reaction and anti-poly-(ADP-ribose)-polymerase assays. The phytochemical profiling of active extract was done by TLC and HPTLC methods. RESULTS: Ethanol extract of Glycosmis pentaphylla was more effective than other extracts in reducing the proliferation of Hep3 B cells. As revealed by the results from DNA fragmentation, Hoechst staining, morphological studies, RT-PCR, PARP cleavage and gene expression studies, active extract induced apoptosis on Hep3 B cell line in concentration and time dependent manner with increase in the Bax/Bcl2 gene expression ratio. Chemo profiling data revealed the presence of flavonoid in the active fraction. CONCLUSIONS: The study showed that major active component in the ethanol extract of Glycosmis pentaphylla is a flavonoid which induces apoptosis on cancer cell line, Hep3 B, by increasing the expression ratio of Bax/Bcl2 genes in a time and dose dependent manner.

Protection of immunocompromised mice from fungal infection with a thymus growth-stimulatory component from Selaginella involvens, a fern.

CONTEXT: Recent studies have shown that the water extract of Selaginella involvens (Sw.) Spring, a wild fern, exhibits thymus growth-stimulatory activity in adult mice (reversal of involution of thymus) and remarkable anti-lipid peroxidation activity. Follow-up studies were carried out in the present study. MATERIALS AND METHODS: Activity-guided isolation of the active component (AC) was carried out. The effect of AC on immune function was studied using fungal (Aspergillus fumigatus) challenge in cortisone-treated mice. The in vitro antifungal activity of AC was assayed using disc diffusion assay. In vitro and in vivo effect of AC on DNA synthesis in thymus was studied using (3)H-thymidine incorporation. In in vitro anti-lipid peroxidation, hydroxyl radical scavenging and inhibition of superoxide production were assayed. RESULTS: The active principle/component (AC) was isolated in a chromatographically pure form from the water extract of S. involvens. AC showed positive reaction to glycosides. AC possessed both thymus growth-stimulatory and antioxidant properties. It protected cortisone-treated mice from A. fumigatus challenge. It did not exhibit in vitro antifungal activity. Increased (3)H-thymidine incorporation was observed in the reticuloepithelium of thymus obtained from AC-treated mice. However, in vitro AC treatment to thymus for 5 h did not result in an increase in (3)H-thymidine incorporation. DISCUSSION AND CONCLUSION: AC (named as Selagin), from S. involvens, could reverse involution of thymus to a large extent, exhibit remarkable antioxidant activity, and protect immunocompromised mice from fungal infection. Therefore, it is very promising for the development of a drug to ameliorate old age-related health problems and prolong lifespan.

In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb.

AIM OF THE STUDY: To determine anti-inflammatory and anti-cancer activities of Cuscuta reflexa in cell lines (in vitro). MATERIALS AND METHODS: Anti-inflammatory activity of the water extract was analysed in vitro using lipopolysaccharide (LPS) induced inflammatory reactions in murine macrophage cell line RAW264.7. The expression of COX-2 and TNF-α genes involved in inflammation was analysed by SQ RT-PCR. EMSA was conducted to analyse the influence of the extract on NF-κB signalling. Anti-cancer activity was analysed on Hep3B cells by MTT assay, DAPI staining, annexin V staining and SQ-RT PCR analysis of BAX, Bcl-2, p53 and survivin. RESULTS: The extract down regulated LPS induced over expression of TNF-α and COX-2 in RAW264.7 cells; blocked NF-κB binding to its motifs and induced apoptosis in Hep3B cells as evidenced from MTT, DAPI staining and annexin V staining assays. The extract up regulated pro-apoptotic factors BAX and p53, and down regulated anti-apoptotic factors Bcl-2 and survivin. CONCLUSIONS: The study showed that Cuscuta reflexa inhibits LPS induced inflammatory responses in RAW264.7 cells through interplay of TNF-α, COX-2 and NF-κB signalling. It induced apoptosis in Hep3B cells through the up regulation of p53, BAX and down regulation of Bcl-2 and survivin.

Cytotoxic and apoptotic activity of Cheilanthes farinosa (Forsk.) Kaulf. against human hepatoma, Hep3B cells.

AIM OF THE STUDY: Cheilanthes farinosa (Forsk.) Kaulf., family: Adianthaceae, is a fern of immense medicinal properties used in ethno-medicine. The Gaddis tribe of Himachal Pradesh, India, has been using this fern to treat liver damage. Aim of the current study was to determine the apoptosis inducing and cytotoxic activity, if any, of this fern towards hepatic cancer cells. MATERIALS AND METHODS: Water extract of the plant was used in the study. MTT assay was performed in hepatocellular carcinoma cell line, Hep3B as well as murine macrophage cell line, RAW264.7 to analyze the cytotoxic activity of the plant. Further, the apoptosis inducing action of water extract of the plant was evaluated using comet assay, DNA fragmentation analysis, DAPI staining of chromatin and Annexin V-FITC staining. RESULTS: This plant was found to produce considerable cytotoxicity in hepatoma cell line, Hep3B without inducing substantial damage to non-cancerous cell line RAW264.7. In addition, this plant was found to induce apoptosis in Hep3B cells. This was substantiated by comet assay, DNA fragmentation analysis, DAPI staining of chromatin and Annexin V-FITC staining for detecting early stage of apoptosis. CONCLUSIONS: This investigation shows that the water extract of Cheilanthes farinosa has antiproliferative and apoptotic activity in human liver cancer cells and is not deleterious towards non-cancerous macrophage cell line.

Cardiospermum halicacabum ethanol extract inhibits LPS induced COX-2, TNF-alpha and iNOS expression, which is mediated by NF-kappaB regulation, in RAW264.7 cells.

AIM OF THIS STUDY: Cardiospermum halicacabum L. is well known for its anti-inflammatory, analgesic and antipyretic activities. It has been used in Ayurveda and folk medicine for the treatment of rheumatism, fever and earache. But its mechanism of anti-inflammatory and analgesic action is still unclear, hence in this context, the objective of our study is to reveal the mechanism of anti-inflammatory and analgesic activity of Cardiospermum halicacabum L. which would form an additional proof to the traditional knowledge of Cardiospermum halicacabum L. MATERIALS AND METHODS: In this study the ethanolic extract of the whole plant was used to evaluate the anti-inflammatory action in mouse macrophage cell line RAW264.7 cells. The expression levels of cyclooxygenase (COX)-1, COX-2, tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and COX-2 protein expression by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot and nuclear factor kappa-B (NF-kappaB) binding activity by electrophoretic mobility shift assay (EMSA). RESULTS: We found that the ethanol extract dose dependently inhibit mRNA expression of COX-2, TNF-alpha, iNOS and COX-2 protein expression. But the extract did not affect the expression of COX-1 mRNA expression. Furthermore, Cardiospermum halicacabum L. ethanol extract inhibited the TNF-alpha induced DNA binding activity of NF-kappaB, which was associated with decreased p65 protein level in the nucleus in Jurkat cells. CONCLUSION: These results enabled to understand the mechanisms behind the anti-inflammatory and analgesic activity of Cardiospermum halicacabum L.

Chemopreventive action of Lygodium flexuosum extract in human hepatoma PLC/PRF/5 and Hep 3B cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Lygodium flexuosum (Lygodiaceae), a medicinal fern used in Indian traditional medicine against liver disorders. AIM OF THE STUDY: The rationale of the study was to examine whether the n-hexane extract from plant Lygodium flexuosum affects apoptosis on human hepatoma PLC/PRF/5 and Hep 3B cells. MATERIALS AND METHODS: Chemopreventive activity of the Lygodium flexuosum extract was determined by MTT assay, annexin-V FITC binding to phosphatidyl serine and cleavage of PARP. Subdiploid condition of cells treated with Lygodium flexuosum was analyzed by flow cytometry. Further, used transiently transfected NF-kappaB reporter in PLC/PRF/5 cells to evaluate the inhibitive effect of Lygodium flexuosum extract. RESULTS: Lygodium flexuosum extract inhibited the cell viability and induced apoptosis in hepatoma cells in a concentration dependent manner as evidenced by apoptotic changes such as flipping of phosphatidyl serine, cleavage of PARP. Cell cycle analysis showed the subG1 apoptotic population in cells treated with higher concentrations of the extract. When activated with exogenous TNF-alpha in transfected hepatoma cells it was observed that NF-kappaB dependent gene expression was inhibited by treatment with Lygodium flexuosum extract in PLC/PRF/5 cells dose-dependently. CONCLUSIONS: This investigation suggests that the Lygodium flexuosum extract has antiproliferative and apoptotic activity in both cancer cells and has inhibitive role in TNF-alpha induced NF-kappaB activation in PLC/PRF/5 cells confirms the potential of the extract as a chemopreventive agent.

Gastroprotective effect of Dodonaea viscosa on various experimental ulcer models.

AIM OF THE STUDY: Dodonaea viscosa Linn. (Sapindaceae) is used as a medicinal herb by the tribes of Shola forest regions of Western Ghats. It is used for headaches, backaches, stomach pain, piles and simple ulcers. The present study was performed to evaluate the gastroprotective effect and acute toxicity of this plant in various experimental models. MATERIALS AND METHODS: Studies were performed in two different models (ethanol and indomethacin induced gastric ulcer) in wistar rats. Gastric protection was evaluated by measuring the ulcer index, gastric glutathione assay, alkaline phosphate assay and histopathological studies. Gastric secretion studies were done by pyloric ligation experiment. RESULTS AND CONCLUSIONS: Water and ethanol extract (500 mg/kg body weight) showed moderate activity compared to hexane extract. Hexane extract of Dodonaea viscosa dose dependently inhibited ethanol induced gastric lesions, causing 90% protection at 500 mg/kg, 81% protection at 250 mg/kg, and 70% protection at 125 mg/kg and it also dose dependently inhibited indomethacin induced gastric lesions, causing 92% protection at 500 mg/kg, 77% protection at 250 mg/kg, and 52% protection at 125 mg/kg. The various degrees of inhibition were statistically significant (p

Preventive effect of ethanol extract of Phyllanthus rheedii Wight. on D-galactosamine induced hepatic damage in Wistar rats.

AIM OF THE STUDY: Phyllanthus rheedii Wight. (Euphorbiaceae) has been used by Muthuvan tribes of Kerala for curing liver diseases. The present study was conducted to assess the hepatoprotective activity of this plant. The ethanol extract of Phyllanthus rheedii was pharmacologically analysed for its preventive effect in d-galactosamine (d-GalN) induced liver damage in rats. MATERIAL AND METHODS: The levels of hepatotoxicity in various groups were quantified by different parameters of liver damage viz. serum levels of ALT, AST, LDH, GGT, ALP and total bilirubin. The effect of extract on the expression levels of pro-inflammatory cytokines like TNF-alpha, and TGF-beta were analysed by RT-PCR. Histological changes in the liver were evaluated by hematoxylin and eosin staining of paraffin processed liver sections. The antioxidant and choleretic activity of the extract were also analysed. RESULTS: Comparison of serum values of control and extract treated groups have revealed that the d-GalN induced alterations in the serum and liver markers were normalized in extract treatment groups showing hepatoprotective activity of the extract. The extract also prevented the toxin induced histological changes in liver. The mRNA levels of TGF-beta and TNF-alpha in the liver were up regulated by the hepatotoxin. The extract treatment has normalized this change, giving light to the probable mechanism of action of the extract. It has showed marked antioxidant and choleretic activity. Preliminary phytochemical screening has revealed the presence of tannins, flavanoids and phenolics as major components. CONCLUSIONS: This study concluded the ethanol extract of P. rheedii could be a promissory candidate for drug development and validated the tribal claim.

Hepatoprotection of Phyllanthus maderaspatensis against experimentally induced liver injury in rats.

The hexane extract of Phyllanthus maderaspatensis (200 and 100 mg/kg) showed significant hepatoprotection on carbon tetrachloride and thioacetamide induced liver damage in rats. The protective effect was evident from serum biochemical parameters and histopathological analysis. Rats treated with P. maderaspatensis remarkably prevented the elevation of serum AST, ALT and LDH and liver lipid peroxides in CCl(4) and thioacetamide treated rats. Hepatic glutathione levels significantly increased by the treatment with the extracts. Histopathological changes induced by CCl(4) and thioacetamide were also significantly reduced by the extract treatment. The activity of hexane extracts of P. maderaspatensis was comparable to that of silymarin, the reference hepatoprotective drug.

Preliminary studies on antihepatotoxic effect of Physalis peruviana Linn. (Solanaceae) against carbon tetrachloride induced acute liver injury in rats.

Physalis peruviana is a medicinal herb used by Muthuvan tribes and Tamilian native who reside in the shola forest regions of Kerala, India against jaundice. It was evaluated for its antihepatotoxic, phytochemical analysis and the acute toxicity of the most promising extract in rats. Water, ethanol and hexane extracts of Physalis peruviana (500mg/kg body weight) showed antihepatotoxic activities against CCl(4) induced hepatotoxicity. The ethanol and hexane extracts showed moderate activity compared to water extract, which showed activity at a low dose of 125mg/kg. The results were judged from the serum marker enzymes. Histopathological changes induced by CCl(4) were also significantly reduced by the extract. Further, the extract administration to rats resulted in an increase in hepatic GSH and decrease in MDA. Preliminary phytochemical analysis revealed the presence of various components in the crude aqueous extract. The extract was found to be devoid of any conspicuous acute toxicity in rats.

Protective mechanism of Lygodium flexuosum extract in treating and preventing carbon tetrachloride induced hepatic fibrosis in rats.

The protective effect of Lygodium flexuosum extract in preventive and curative treatments of CCl(4) induced fibrosis was quantified. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100 gm rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of L. flexuosum n-hexane extract (200 mg/kg, p.o) were administered for 10 weeks. In curative treatment L. flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with the n-hexane extract (200 mg/kg) reduced the mRNA levels of proinflammatory cytokines, growth factors and other signaling molecules, which are involved in hepatic fibrosis. The expression levels of tumor necrosis factor-alpha, interleukin-1beta, transforming growth factor-beta1, procollagen-I, procollagen-III and tissue inhibitor of metalloproteinase-1 were elevated during carbon tetrachloride administration and reduced the levels to normal by the treatment with the extract treatment. The increased levels of matrix metalloproteinase-13 in extract treated rats were indicative of the protective action of L. flexuosum n-hexane extract. In conclusion, L. flexuosum n-hexane extract functions as a potent fibrosuppresant, effectively reverses carbon tetrachloride-induced hepatic fibrosis in curative treatment and reduces the effects of ongoing toxic liver injury in preventive treatment by promoting extracellular matrix degradation in the fibrotic liver.

Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced hepatotoxicity in rats.

The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA intoxication and continued for 20 weeks. In curative animals, NDEA was administered for 20 weeks followed by treatment with the n-hexane extract of L. flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST, ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor Tie-2 mRNA. L. flexuosum extract treatment significantly (p

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats.

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.

Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D-galactosamine induced liver injury in rats.

The protective effect of Lygodium flexuosum n-hexane extract against D-galactosamine was evaluated in Wistar rats. In preventive groups extract was administered at 48, 24 and 2h before D-galactosamine intoxication whereas in post-treatment groups extract were administered 2, 24 and 48 h after D-galactosamine intoxication. Rats pre-treated with n-hexane extract at a dose of 200 and 100 mg/kg of Lygodium flexuosum showed a significant prevention of elevated AST, ALT, LDH levels and hepatic malondialdehyde in D-galactosamine treated rats. Hepatic glutathione levels significantly upregulated by the extract treatment in D-galactosamine treated rats. Quantification of histopathological sections supported the preventive action of n-hexane extract of Lygodium flexuosum. Rats treated with the extract at a dose of 200 and 100 mg/kg Lygodium flexuosum after the establishment of D-galactosamine induced liver injury showed complete protection of liver as evidenced from normal AST, ALT and LDH levels, hepatic GSH and MDA levels and also by normal histological index of liver in treated rats. Rats treated with n-hexane extract of Lygodium flexuosum were comparable to that of Silymarin, the standard hepatoprotective drug.

Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon tetrachloride induced hepatic fibrosis in rats.

The preventive and curative effect of Lygodium flexuosum on experimentally induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with CCl(4) caused a significant decrease in body and liver weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in body and liver weight. Treatment with the extract prevented or restored the elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment remarkably prevented or reversed an increase in liver hydroxyproline content in chronically treated rats. Histopathological changes of hepatic lesions induced by CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium flexuosum. These results support that Lygodium flexuosum exerts effective protection in carbon tetrachloride induced hepatic fibrosis in rats.

Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats.

Ethanol extract of Cardiospermum halicacabum Linn. (Sapindaceae), in a concentration dependant manner (200-600mg/kg) inhibited gastric ulcers induced by oral administration of absolute ethanol. Further, the extract administration to rats resulted in an increase in levels of gastric glutathione and a decrease in alkaline phosphatase activity. The extract also exhibited potent in vitro hydroxyl radical scavenging and inhibition of lipid peroxidation activities. The extract was found to be devoid of any conspicuous acute and short-term toxicity in rats.