Acute and sub-chronic toxicity of a lyophilised aqueous extract of Centaurium erythraea in rodents

Ethnopharmacological relevance

An aqueous concoction made from centaury (Centaurium erythraea (L.) Rafn., (Gentianaceae) whole plant is used in the Moroccan traditional medicine for the treatment of diabetes, as well as a number of other diseases. No systematic study of the potential toxicity of the plant has been described.

Aim of the study

The present investigation was carried out to evaluate the safety of an aqueous extract of Centaurium erythraea whole plant (CE-extract) by determining its potential toxicity after acute and sub-chronic administration in rats and mice.

Materials and methods

For the acute study, the lyophilised CE-extract was administered to adult IOPS OFA mice in single oral doses of 1-15 g/kg given by gavage, and single intraperitoneal (i.p.) doses of 1-14 g/kg. General behavioral adverse effects, mortality, and latency of mortality were determined for up to 14 days. In the sub-chronic dose study, the CE-extract was administered orally at doses of 100, 600 and 1200 mg/kg daily for 90 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined every 30 days and at the end of 90 days of daily administration; sections of liver and kidney were examined histologically for any signs of organ damage at the end of the treatment.

Results

In the acute study in mice, there were no deaths or any signs of toxicity observed after oral administration of single doses of the CE-extract at any dose level up to the highest dose tested (15 g/kg), which was the no-observed-adverse-effect level (NOAEL). However, the mortality rate as well as the acute toxicity of the i.p. administered CE-extract increased progressively with increasing dose. The NOAEL for the i.p. dose was 6 g/kg while the lowest-observed-adverse-effect level (LOAEL) was 8 g/kg; the calculated acute toxicity (LD₅₀) of i.p. administered CE-extract in mice was 12.13 g/kg.In sub-chronic studies in rats, the CE-extract (administered orally at daily doses of 100, 600 and 1200 mg/kg for 90 days), did not cause any changes in hematological and biochemical parameters, except a small reduction of mean corpuscular volume, and a decrease in serum glucose and triglyceride levels at the higher doses. Histopathological examination of the liver and kidneys at the end of the study showed normal architecture suggesting no morphological disturbances.

Conclusions

Because of the lack of toxicity of the CE-extract given by the oral route, and relatively high NOAEL values for the i.p. dose in the acute study in mice, as well as lack of mortality or clinically significant adverse changes in the biological and hematological parameters, and the morphology of liver and kidneys in rats after 90 days of daily dosing, it may be concluded that the CE-extract is relatively non-toxic. Also, in view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Centaurium erythraea.     

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.     

Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice

Aims of study

Although Artemisia sacrorum Ledeb. (Compositae) has long been used as one kind of oriental folk medicine to treat some liver diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. This study was designed to investigate the hepatoprotective effects of 50% ethanol eluate precipitation of Artemisia sacrorum Ledeb. (EEP) on acetaminophen (APAP)-induced toxicity in mice.

Materials and methods

The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-α (TNF-α) levels in mouse sera, and glutathione (GSH), malondialdehyde (MDA) in mouse liver tissues were measured. In addition, apoptosis and necrosis were evaluated by liver histopathological analysis and DNA laddering. Moreover, caspase-3 and -8 protein expressions in mouse livers were observed by Western blot analysis.

Results

Pretreated with EEP prior to the administration of APAP significantly prevented the increases of AST, ALT, and TNF-α levels in sera, and suppressed the GSH depletion, MDA accumulation in liver tissues markedly. In addition, EEP prevented APAP-induced apoptosis and necrosis, as indicated by liver histopathological analysis, immunohistochemical analysis, and DNA laddering. Furthermore, according to the results from Western blot analysis, EEP decreased APAP-induced caspase-3 and caspase-8 protein expressions in mouse livers markedly.

Conclusion

All these results suggest that the protective effects of EEP against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-α mediated apoptosis. In a word, EEP could be a valuable candidate for further development for prevention and treatment of hepatic injury.     

The protective effect of Zizyphus jujube fruit on carbon tetrachloride-induced hepatic injury in mice by anti-oxidative activities

Aim of the study

The study was aimed to investigate the protective effect against hepatic injury induced by CCl₄ for the ethanolic extract of FZJ.

Materials and methods

The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected as biomarker in blood of hepatic injury. Product of lipid peroxidation (MDA), activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed at the degree of hepatic injury.

Results

After administrated the FZJ, the dose of 200 mg/kg significantly decreased ALT and AST, and attenuated histopathology of hepatic injury, and ameliorated the oxidative stress in hepatic tissue. Partly assayed indexes were ameliorated after administrated FZJ at the dose of 100 mg/kg.

Conclusion

These results indicated that hepatic protective effects of FZJ were very relevant to modulate the oxidative stress in hepatic injury.     

Protective effect of Smilax glabra extract against lead-induced oxidative stress in rats

Ethnopharmacological relevance

Smilax glabra Roxb. is a traditional Chinese herb, the rhizome of Smilax glabra has been used in folk medicine for the treatment of lead poisoning.

Aims of the study

The present study was conducted to investigate the protective role of Smilax glabra extract (SGE) individually or combined with meso-2,3-dimercaptosuccinic acid (DMSA) against the effects of lead acetate on oxidative stress and lead burden in rats.

Materials and methods

The biochemical parameters and enzymes in different treated rats were determined by commercial kits. The metal concentrations were measured using atomic absorption spectrophotometer.

Results

SGE (300 mg/kg) showed very low toxicity to organs in non-lead exposed rats. Administration of SGE individually had no effect on blood zinc protoporphyrin (ZPP) level but significantly enhanced the glutathione (GSH) content and δ-aminolevulinic acid dehydratase (ALAD), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in lead exposed rats. The co-treatment of SGE and DMSA had a synergism in increasing brain, liver and kidney superoxide dismutase (SOD), catalase (CAT) activities and GSH level, and decreasing oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) levels. Moreover, the co-treatment could improve the hepatic and renal histopathology changes. SGE as chelating agent showed significant efficiency in reducing blood and tissue lead burden.

Conclusions

The in vivo results suggested that SGE individually or combined with DMSA exhibited remarkable protective effects on lead-induced oxidative stress and lead burden in rats.     

Acute and sub-chronic toxicity of HPLC fingerprinted extract of Conyza sumatrensis (Retz.) E.H. Walker in rodents

Ethnopharmacological relevance

Conyza sumatrensis (CS) is an extensively used medicinal herb in the tropics for varied ailments related to pain, inflammation and malaria. Though in constant folkloric use, scientific validations are proving valuable.

Aim of the study

Evaluate the safety profile of methanol extract from CS in mice and rats through acute and sub-chronic toxicity studies respectively.

Material and methods

Acute toxicity study involved the single oral administration of CS at 1000, 2000 and 3000 mg/kg in mice, while the sub chronic toxicity was carried upon in rats at doses 250, 500 and 1000 mg/kg/day for 28 days. Besides body weight, general behaviour and mortality, serum biochemical parameters and liver histology were assessed after 7 and 28 days for acute and sub-chronic study respectively. The parameters were again checked on days 14 and 56 in order to assess the recovery from damage, if any. HPLC fingerprinting of the aqueous and methanol extract was performed through C18 column using water: acetonitrile as mobile phase with observations at 240 nm.

Results

In the acute toxicity test, single oral dose of 1000, 2000 and 3000 mg/kg of CS did not result in any behavioural changes or mortality, indicating non toxicity. In sub-chronic toxicity studies in rats, no mortality was observed at 250, 500 and 1000 mg/kg/day when administered orally for a period of 28 days. Except Serum Glutamate Pyruvate Transaminase (SGPT) level in acute study and Alkaline Phosphatase (ALP), SGPT and Serum Glutamate Oxaloacetate Transaminase (SGOT) level in sub-chronic study, all the observational, haematological and biochemical parameters studied showed non-significant changes. Histological examination of liver did not reveal any treatment-related effects in any of the studies. Moreover, haematological and biochemical changes orchestrated by CS got normalised after 14 and 56 days post-treatment in acute and sub-chronic toxicity respectively. The HPLC fingerprint could resolve 11 and 28 peaks from aqueous and methanol extracts respectively.

Conclusion

The experiments indicate the methanol extract to be safe even at high and repeated doses in pre-clinical studies even though the constituents are more than in aqueous extract.     

Hepatoprotective effect of Trichosanthes cucumerina Var cucumerina L. on carbon tetrachloride induced liver damage in rats

Ethnopharmacological relevance

Different parts of the plant Trichosanthes cucumerina Var cucumerina L. (cucurbitaceae) are used to treat liver disorders, traditionally. It is one among the constituents in various Ayurvedic formulations used for the treatment of liver disorders and other diseases.

Aims of study

The aim of the present study is to evaluate the protective effect of Trichosanthes cucumerina against experimentally induced liver injury.

Materials and methods

The methanolic extract of whole plant of Trichosanthes cucumerina (TCME) was evaluated for the hepatoprotective activity against carbon tetrachloride (CCl₄) induced hepatotoxicity in rats. Various biochemical parameters like alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), total protein (TP) and albumin (ALB) levels were estimated in serum as well as the glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Histopathological changes in the liver of different groups were also studied.

Results

The pre-treatment of TCME at dose levels of 250 and 500 mg/kg b.w.p.o. had controlled the raise of AST, ALT, ALP, TB and MDA levels and the effects were comparable with standard drug (silymarin 100 mg/kg b.w.p.o.). The GSH, TP and ALB levels were significantly increased in the animals received pre-treatment of the extract. The animals received pre-treatment of the extract shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus the histopathalogical studies also supported the protective effect of the extract.

Conclusion

This study demonstrates the hepatoprotective activity of Trichosanthes cucumerina and thus scientifically supports the usage of this plant in various Ayurvedic preparations and traditional medicine for treatment of liver disorders.     

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats

Ethnopharmacological relevance

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties.

Materials and methods

Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration.

Results

Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity.

Conclusion

The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine.     

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice

Aim of the study

Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models.

Materials and methods

We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24 h after oral administration of 250 mg/kg AAs.

Results

Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects.

Conclusions

The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo.     

In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice

Aim of the study

This study aimed to evaluate in vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. (AEAA), which has been used for the treatment of liver disorders in Traditional Uighur Medicine.

Materials and methods

Qualitative and quantitative phytochemical analysis of the AEAA was performed by means of thin layer chromatography and spectrophometric assays. Aqueous extract (50, 100 or 200 mg/kg body weight/day) was administered orally to experimental mice. Liver injury was induced chemically, by a single CCl₄ administration (0.1% in olive oil, 10 ml/kg, i.v.), or immunologically, by injection of endotoxin (LPS, 10 μg, i.v.) in BCG-primed mice. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in mouse sera, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) in mouse liver tissues were measured. The biochemical observations were supplemented by histopathological examination.

Results

Obtained results demonstrated that the pretreatment with AEAA significantly (P < 0.001) and dose-dependently prevented chemically or immunologically induced increase in serum levels of hepatic enzymes. Furthermore, AEAA significantly (P < 0.05) reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes SOD and GPx towards normal levels. In the BCG/LPS model, increase of the levels of important pro-inflammatory mediators TNF-α and IL-1 was significantly (P < 0.01) suppressed by AEAA pretreatment. Histopathology of the liver tissue showed that AEAA attenuated the hepatocellular necrosis and led to reduction of inflammatory cells infiltration. Phytochemical analyses revealed the presence of sesquiterpene lactones, flavonoids, phenolic acids and tannins in the AEAA.

Conclusions

The results of this study strongly indicate the protective efect of AEAA against acute liver injury which may be attributed to its antioxidative and/or immunomodulatory activity, and thereby scientifically support its traditional use.     

Anti-inflammatory and antioxidant effects of a hypoglycemic fructan fraction from Psacalium peltatum (H.B.K.) Cass. in streptozotocin-induced diabetes mice

Ethnopharmacological importance

Psacalium peltatum (H.B.K.) Cass. (Asteraceae) is used medicinally to treat diabetes, rheumatic pains, as well as gastrointestinal and kidney ailments. Previous pharmacological and chemical assays have demonstrated that an aqueous fraction from Psacalium peltatum (AP-fraction) contains a carbohydrate-type compound with hypoglycemic activity. Nevertheless, studies have not yet considered the hypoglycemic action of the AP-faction by sub-chronic administration nor on other healing properties, some of which might be associated with DM2 and other inflammatory processes.

Aim of study

To determine whether a hypoglycemic carbohydrate fraction (AP-fraction) from Psacalium peltatum roots has antioxidant and anti-inflammatory effects in streptozotocin-induced diabetes mice.

Material and methods

Healthy mice received either saline, the AP-fraction with a high content of fructans, or pioglitazone (a positive control) daily by gavage. After 15 days of treatment, these animals received a single intraperitoneal administration of streptozotocin and all treatments were continued for additional 33 days. The antioxidant and anti-inflammatory properties of the AP-fraction were evaluated through the quantification of biomarkers of oxidative stress (glutathione (GSH) and malondialdehyde (MDA)) and inflammation (interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10).

Results

The AP-fraction reduced glycemia and the glycated hemoglobin. Furthermore, animals treated with the AP-fraction had increased GSH, while MDA was decreased in the liver and the heart, without changes in the kidneys and the pancreas. The AP-fraction significantly reduced TNF-α serum levels but did not modify IL-6; in addition, this fraction increased IFN-γ and IL-10 levels. The increase in IL-10 levels may indicate an inhibition of the production of pro-inflammatory cytokines such as TNF-α, whereas the increase in IFN-γ might be indicative of a beneficial effect on the immune system.

Conclusions

The AP-fraction hypoglycemic fructans from Psacalium peltatum roots showed antioxidant and anti-inflammatory properties in mice with streptozotocin-induced diabetes. The Psacalium peltatum hypoglycemic fructans may be valuable in preventing insulin resistance, as well as the development and progression of diabetic complications caused by chronic inflammation.     

Antihyperglycemic,hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats

Ethnopharmacological relevance

As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has multiple pharmacological activities, including relieving rheumatism, promoting blood circulation to arrest pain, inducing diuresis to reduce edema, and antidiabetic action. It has long been used as a folk medicine for the treatment of traumatic injury, rheumatic arthralgia, nephritis, edema, hepatitis and diabetes mellitus in China.

Aim of study

To evaluate the antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis (SAT) in experimental type 2 diabetic mellitus (T2DM) rats.

Materials and methods

Acute toxicity was studied in rats to determine the safe oral dose of SAT. Then, SAT was given orally to normal and streptozotocin–nicotinamide induced T2DM rats at 80, 160 and 320 mg/kg doses for a series of 28 days to determine the antihyperglycemic activity. Glibenclamide (600 μg/kg), a standard antidiabetic drug, was used as a positive control drug. At the end of treatment, biochemical parameters and antioxidant levels were measured to evaluate the hypolipidemic and antioxidant activities of SAT.

Results

Oral administration of SAT did not exhibit toxicity and death at a dose not more than 2000 mg/kg. SAT dose-dependently improved the symptoms of polydipsia, polyuria, polyphagia and weight loss in diabetic rats. Compared with diabetic control group, administration of 320 mg/kg SAT resulted in significant (P<0.05) fall in the levels of fasting blood glucose, glycosylated hemoglobin, creatinine, urea, alanine transarninase, aspartate aminotransferase, total cholesterol, triglycerides, low density lipoprotein cholesterol and malondialdehyde, but significant (P<0.05) increase in the levels of serum insulin, superoxide dismutase and reduced glutathione. However, SAT did not have any effect on the normal rats.

Conclusions

SAT had excellent antihyperglycemic, hypolipidemic and antioxidant activities in T2DM rats and might be a promising drug in the therapy of diabetes mellitus and its complications.     

Polyprenols from Taxus chinensis var. mairei prevent the development of CCl4-induced liver fibrosis in rats

Ethnopharmacological relevance

The aim of this study was to investigate the anti-fibrotic effects and the possible underlying mechanisms of taxus polyprenols (TPs) isolated from the needles of Taxus chinensis var. mairei.

Materials and methods

The animals were randomly divided into normal control with vehicles only (olive oil), rat model given CCl₄ only, CCl₄+low TPs (48 mg/kg), CCl₄+medium TPs (120 mg/kg), CCl₄+high TPs (300 mg/kg), and CCl₄+Polyene phosphatidylcholine (PP, 120 mg/kg). The rat model of liver fibrosis was induced by subcutaneous injection of 40% (v/v) of CCl₄ diluted in olive oil (3 mL/kg body weight) twice per week for 8 weeks. Liver histopathological study was performed. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and albumin (ALB) of the serum were determined for evaluating the liver function. In order to reveal the possible mechanisms of the anti-fibrotic effects, oxidative stress level, hepatic collagen metabolism, and hepatic stellate cells (HSCs) activation were investigated. Furthermore, the mRNA expression of the fibrotic-related factors was measured by the quantitative real-time RT-PCR.

Results

TPs successfully attenuated liver injury induced by CCl₄ shown by histopathological sections of livers and improved liver function as indicated by decreased ALT, AST and ALP levels and increased ALB levels in serum of the rats. TPs significantly increased the hepatic Cu/Zn SOD and GSH-Px activities along with GSH content while a remarkable decrease in MDA content. Both immunohistochemical staining and mRNA expression levels of α-SMA indicated a profound suppression of HSCs activation. Furthermore, it significantly inhibited the mRNA expression of the pro-fibrotic cytokines Col α1(I), Col α1(Ш), MMP-2, TIMP-1, TIMP-2, PDGF-β, TGF-β1, CTGF and TNF-α and restored the hepatoprotective factor HGF.

Conclusion

These results suggest that the protective effects of TPs in chronic CCl₄-induced liver fibrosis might be related with the reduction of oxidative damage, the inhibition of HSCs activation, the down-regulation of pro-fibrogenic stimuli and the protection of hepatocytes.     

Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats

Terminalia belerica Roxb. is one of the oldest medicinal herb of India, is an ingredient of Indian Ayurvedic drug 'triphala' used for the treatment of digestion and liver disorders. Present study is aimed to evaluate the protective effect of Terminalia belerica fruit extract and its active principle, gallic acid (3,4,5-trihydroxybenzoic acid) at different doses against carbon tetrachloride intoxication. Toxicant caused significant increase in the activities of serum transaminases and serum alkaline phosphatase. Hepatic lipid peroxidation level increased significantly whereas significant depletion was observed in reduced glutathione level after carbon tetrachloride administration. A minimum elevation was found in protein content on the contrary a significant fall was observed in glycogen content of liver and kidney after toxicant exposure. Activities of adenosine triphosphatase and succinic dehydrogenase inhibited significantly in both the organs after toxicity. Treatment with TB extract (200, 400 and 800mg/kg, p.o.) and gallic acid (50, 100 and 200mg/kg, p.o.) showed dose-dependent recovery in all these biochemical parameters but the effect was more pronounced with gallic acid. Thus it may be concluded that 200mg/kg dose of gallic acid was found to be most effective against carbon tetrachloride induced liver and kidney damage.     

Effect of Cydonia oblonga Mill. leaf extract on serum lipids and liver function in a rat model of hyperlipidaemia

Ethnopharmacological relevance

Cydonia oblonga Mill. leaves are traditionally used in Uyghur medicine to treat or prevent cardiovascular disease. Beyond a demonstrated effect on thrombosis, we tested it for an effect on dyslipidemia, in a rat model of hyperlipidemia.

Methods

Seventy healthy Sprague Dawley rats were randomly divided into 6 groups: normal controls, model controls, simvastatin, and low-, medium- and high-dose Cydonia oblonga Mill. leaf extracts (COM), orally for 56 days. The normal controls were fed a normal diet, all other groups a high fat diet. Rat weights were recorded over time. Total cholesterol (TC), triglycerides (TG), low and high-density lipoproteins (LDL, HDL), as well as AST, ALT and total protein (TP) were measured in serum at the end of the study. The antioxidant capacity of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA) was measured in liver samples, along with lipoprotein lipase (LPL), and hepatic lipase (HL). Liver pathology was described.

Results

COM dose-dependently reduced TC, TG, LDL-C and MDA, inhibited the activity of ALT, AST and LPS, increased HDL-C content, increased the activity of SOD, GSH-PX, LPL and HL, and reduced liver steatosis in hyperlipidaemia rats, which was significant at medium and high doses. The effect of COM was similar to that of simvastatin except for increased LPL and HL which were reduced by COM but not by simvastatin.

Conclusion

Cydonia oblonga Mill. leaf extracts have hypolipidaemic and hepatoprotective effects, probably related to increasing antioxidant capacity and lipoprotein metabolism in the liver, and inhibition of lipogenesis.     

Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease

Ethnopharmacological relevance

In South Africa, the plant Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is traditionally used as a “tea” referred to as rooibos or redbush. This plant has been listed as a medicinal plant based mostly on anecdotal evidence.

Aims of the study

Despite a long history of traditional use in South Africa, very little scientific data are available from controlled clinical trials confirming its popular use. The aim of the present study was to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease.

Materials and methods

After a washout period of 2 weeks, 40 volunteers consumed six cups of fermented/traditional rooibos daily for 6 weeks, followed by a control period. Blood biochemical parameters indicative of antioxidant activity and content (total polyphenols), lipid peroxidation (conjugated dienes - CDs, thiobarbituric acid reactive substances - TBARS), redox status (total glutathione - tGSH, ratio of reduced to oxidized glutathione - GSH:GSSG), lipid profile (total cholesterol, low density lipoprotein - LDL and high density lipoprotein - HDL cholesterol and triacylglycerol levels) and liver and kidney function were measured at the end of each study period.

Results

Plasma antioxidant capacity was not altered, but plasma total polyphenol levels increased significantly after rooibos consumption compared with the control levels (from 79.8 ± 16.9 mg/L to 89.8 ± 14.1 mg/L). Significant decreases in plasma markers of lipid peroxidation were found after rooibos consumption, as reported by levels of CDs (167.3 ± 29.5 nmol/mL vs. 108.8 ± 20.1 nmol/mL) and TBARS (1.9 ± 0.6 μmol/L vs. 0.9 ± 0.3 μmol/L). Reduced glutathione (797 ± 238 μmol/L vs. 1082 ± 140 μmol/L) and the GSH:GSSG ratio (41 ± 14 vs. 76 ± 17) were both significantly increased after consumption of rooibos. The lipid profiles showed that rooibos consumption, compared with the control values, significantly decreased serum LDL-cholesterol (4.6 ± 1.3 mmol/L vs. 3.9 ± 0.7 mmol/L) and triacylglycerols (1.7 ± 0.8 mmol/L vs. 1.2 ± 0.7 mmol/L), while HDL-cholesterol (0.9 ± 0.1 mmol/L vs. 1.2 ± 0.2 mmol/L) was significantly increased.

Conclusion

Confirming its popular use, consumption of fermented, traditional rooibos significantly improved the lipid profile as well as redox status, both relevant to heart disease, in adults at risk for developing cardiovascular disease.     

Safety evaluation of tea (Camellia sinensis (L.) O. Kuntze) flower extract: assessment of mutagenicity, and acute and subchronic toxicity in rats

Ethnopharmacological relevance

Tea (Camellia sinensis (L.) O. Kuntze, Theaceae) flowers possess many physiological functions and have been used in traditional medicines for deodorization, skin care, cough suppressant and expectorant in China. However, there is a little information about its possible toxicity.

Aim of the study

The present investigation was carried out to evaluate the safety of tea flower extract by mutagenicity and acute and subchronic toxicity studies.

Materials and methods

Mutagenicity of tea flower extract was evaluated by the Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102 at concentrations of 0.008, 0.04, 0.2, 1.0, 5.0 mg/plate. In the acute toxicity study, Sprague-Dawley rats were administered a single dose of 12.0 g/kg of body weight by gavage, and were monitored for 14 days. In the subchronic toxicity study, tea flower extract was administered by gavage at doses of 1.0, 2.0 and 4.0 g/kg body weight daily for 13 weeks to Sprague-Dawley rats.

Results

In the Ames test, there was no mutagenic effect of tea flower extract (up to 5.0 mg/plate) towards four tested strains (TA97, TA98, TA100, TA102), with or without metabolic activation (S9). In the acute toxicity study, all animals gained weight and appeared active and normal, so the LD₅₀ value must be >12.0 g/kg body weight. In the subchronic toxicity study, no dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed.

Conclusion

These results indicate that tea flower extract does not possess mutagenic potential, and that both acute and subchronic toxicity towards animals is very low. A no-observed adverse-effect level (NOAEL) for tea flower extract is 4.0 g/kg bw/day for rats under the conditions of this study.     

Calotropis gigantiea (L.) R. Br (Apocynaceae): A phytochemical and pharmacological review

Ethnopharmacological relevance

Calotropis gigantiea (L.) R. Br (Apocynaceae) commonly called as “crown flower” or “giant milk weed” is a well-known weed to many cultures for treating various disorders related to central nervous system, skin diseases, digestive system, respiratory system, reproductive system etc. Indigenous groups made the plant as a part of their lives since they use the fruit fibre to make ropes, household items, for weaving clothes and flowers for garlands apart from usage for various indications. The study aims at far-reaching review on phytochemistry, pharmacological activities, ethnopharmacology, intellectual property transfer on pharmacological therapies, toxicity which aids to provide scientific evidence for the ethnobotanical claims and to identify gaps required to be conducted as a future research prerequisite.

Materials and methods

A systematic literature search was performed using different databases such as Scopus, Science direct, PubMed and Sciverse with no timeline limit set during the search. All the available abstracts and full text articles were included in the systematic review.

Results

Most of the folkloric uses were validated by the scientific studies such as analgesic, anti-arthritic, anti-asthmatic, anti-bacterial, anti-convulsant, anti-pyretic, central nervous system disorders, contraceptive, anti-ulcer and wound healing. In addition other studies such as anti-diabetic, anti-diarrhoeal, anti-helminthic, anti-histamine, anti-inflammatory, anti-microbial, anti-oxidant, cardio-protective studies, cytotoxicity, hepatoprotectivity, fibrinolytic, mosquitocidal, nerve muscle activity, vasodilation and skeletal muscle activities were also reported for the plant. Isolated compounds such as calotropin, frugoside and 4'-O-β-d-glucopyranosyl frugoside were tested for the cytotoxicity efficacy against both human and rat cell lines out of which calotropin showed potent activity (IC₅₀–15 ng/ml). However there were no clinical trials reported on the plant which is one of the major lacunas.

Conclusions

This review article explores the ethnopharmacological, pharmacological activities phytochemistry and intellectual rights of Cg which gives the evidence of a potent and commercial drug which up on further research leads to the most viable drug for variety of treatments. However there is further need for in-vivo studies and clinical trials on isolated phytoconstituents which will help to commercialise.