In vivo study of Rasa Bhasma on CCL4 induced Hepato-toxicity in Albino rats

India stands 27th in rank with 25.8% of death rate due to Liver diseases in 2016. In spite of scientific advancement in the field of Hepatology, Bio-medical science is clueless in finding out an effective drug against Hepatic Disorders. Detailed description on liver disorders and their management are given by all the three prominent Acharyas of Ayurveda. Rasa Bhasma is one such preparation that can be used to treat Hepatic Disorders. In present work an attempt has been made to evaluate the efficacy of Rasa Bhasma in the management of liver disorders. 24 animals were allocated into 4 groups having six animals in each group namely Group I (Normal/Control), Group II (Intoxicated Control) Toxicated Group, Group III (lower dose of Rasa Bhasma) and Group IV (Higher dose of Rasa Bhasma). All the four group were assessed for various biochemical Parameters viz. Alkaline phosphatase, SGOT (Serum glutamate oxalacetate transaminase)/AST, SGPT (Serum glutamate pyruvate transaminase)/ALT, Total Bilirubin, Direct Bilirubin and Total Proteins. Finally, the animals from all the four groups were sacrificed for Histo-pathological studies. The results were expressed as mean ± SE and One way ANOVA by using statistical software SPSS version 16.0. Results revealed that the values of Group 4 are closer to the Normal Group1 than Group 3 meaning Rasa Bhasma in Higher dose is more effective than that in lower dose. Therefore, it can be concluded that Rasa Bhasma is a potent Herbo-mineral formulation for protection of hepatic cells.

HEPATOPROTECTIVE ACTIVITY OF THE WHOLE PLANT OF NEPTUNIA PROSTRATA L. IN CARBON TETRACHLORIDE INDUCED RATS

Objective: The aim of this study is to investigate the hepatoprotective activity of the whole plant of Neptunia Prostrata L. Methods: The whole plant was collected and identified as Neptunia Prostrata L. The collected plants were shade dried and pulverized to fine powdered of particle size (#) 40. It was then defatted with petroleum ether for 24 hour and soaked with methanol and ethanol, respectively. The extracts was filtered and distilled off using a rotary evaporator. The phytochemical screening of the extracts was carried out and thin layer chromatography study was also done. Acute toxicity study and in vivo hepatoprotective activity of the methanolic extract using CCL4 (carbon tetra chloride) induced model was investigated. Results: The phytochemical screening revealed the presence of alkaloids, glycosides (saponins), flavonoids, tannins, carbohydrates, proteins, phenolic, steroids and terpenoids. Thin-layer chromatography of the methanolic and ethanolic extracts with their fractions using different solvents were performed by taking petroleum ether and ethyl acetate (2:8) as mobile phase system and were able to observe the presence of many spots. Oral administration of methanolic extract of Neptunia prostrata at doses till 2000 mg/kg was found safe and shows good hepatoprotective activity by showing decreased levels of serum SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase) and ALP (alkaline phosphatase) when compared with the standard drug silymarin. Conclusion: The preliminary phytochemical screening of the methanol and ethanolic extract shows phytoconstituents such as flavonoids, triterpenoids, tannins, saponins, alkaloids and chromatographic studies indicates the presence of several components in varying abundance. The decrease of serum bilirubin level by the methanolic extract of the plant shows hepatoprotective activity. It has confirmed the traditional claim for its use in the treatment of jaundice.

Hepatoprotective Effect of Pancha Lavana Dravagam Against Paracetamol induced Hepatotoxicity in Wistar Albino Rats - An in-Vivo Study

Objective: To evaluate the liver protective effect of Pancha Lavana Dravagam (PLD) against Paracetamol induced hepatotoxicity in wistar albino rat models. Methods: The hepatoprotective activity of PLD was evaluated using paracetamol induced liver damage in rats. Wistar albino rats were divided into five groups of six animals each. Paracetamol 1gm/kg bw, p.o. was given to produce liver toxicity. The normal control was given the vehicle (water 1ml/kg bw, p.o). Two test groups with PLD 1ml/kg, 2ml/kg bw, p.o. were tested for hepatoprotective potential. Silymarin 50mg/kg bw, p.o. was given as standard drug. All these drugs were administered for 7 days. On 8th day, the animals were sacrificed and blood was collected from retro-orbital plexus and analyzed for serum enzymes like Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Alanine Phosphate (ALP), Total Bilirubin, Total Proteins and liver was excised for histopathological analysis. Results: In toxicant control group, paracetamol produced liver toxicity due to decrease in glutathione (GSH) by oxidative stress and mitochondrial dysfunction of hepatic cells. It resulted in an increase of serum liver enzymes like SGPT, SGOT, ALP and Total Bilirubin. This increased serum liver enzymes were reduced significantly in the test drug PLD treated groups and Standard group. The histology of liver tissues was also improved in PLD treated groups when compared to the toxicant group. Conclusion: Since, no scientific evidence is available to claim the hepatoprotective effect of PLD, in vivo studies were conducted. It demonstrated that it has a potent hepatoprotective effect against the paracetamol induced hepatotoxicity by suppression of the reactive oxygen species and increasing the anti-oxidant glutathione in liver cells.

Effect of meloxicam coadministration on the anaesthetic potency of thiopental sodium in a chick model

Few studies have dealt with thiopental sodium-induced anaesthetic action and the effect of combining meloxicam (a high plasma protein-bound) in 10–15 day old chicks. First, the analgesic median effective dose (ED50) was determined as 35.85 mg/kg, IM by up-and-down routine, while the hypnotic ED50 value was 34.40 mg/kg, IM in the chick model. A thiopental sodium injection (18, 36 and 72 mg/kg, IM) produces a significant dose-responsive hypnotic effect in chicks, determined by the beginning of the lack of a righting reflex, duration and recovery time. Thiopental sodium and meloxicam (72 and 1 mg/kg, IM) in combination shortened the beginning of hypnosis, and significantly extended its duration, with a significant increase in recovery time from the hypnotic effect when compared to the group receiving only thiopental sodium. The same combination also elicited a significant increase in the analgesic percentage and efficacy, and significant increase in the voltage current estimated via using electrical stimulation to induce the ache feeling. No significant changes were found in the concentrations of serum glutamate pyruvate trans-aminase (GPT), glutamate oxalo-acetate trans-aminase (GOT) with body temperature between the two groups, with the exception of a significant change in respiratory rate. The outcomes of this study support the prospect of using thiopental sodium as an anaesthetic agent for veterinary surgical procedures in the chicks, in combination with meloxicam, to produce worthy, consistent, and proficient anaesthesia.

Acanthaster planci Inhibits PCSK9 and Lowers Cholesterol Levels in Rats

Atherosclerosis is the main cause of cardiovascular diseases which in turn, lead to the highest number of mortalities globally. This pathophysiological condition is developed due to a constant elevated level of plasma cholesterols. Statin is currently the widely used treatment in reducing the level of cholesterols, however, it may cause adverse side effects. Therefore, there is an urgent need to search for new alternative treatment. PCSK9 is an enzyme responsible in directing LDL-receptor (LDL-R)/LDL-cholesterols (LDL-C) complex to lysosomal degradation, preventing the receptor from recycling back to the surface of liver cells. Therefore, PCSK9 offers a potential target to search for small molecule inhibitors which inhibit the function of this enzyme. In this study, a marine invertebrate Acanthaster planci, was used to investigate its potential in inhibiting PCSK9 and lowering the levels of cholesterols. Cytotoxicity activity of A. planci on human liver HepG2 cells was carried out using the MTS assay. It was found that methanolic extract and fractions did not exhibit cytotoxicity effect on HepG2 cell line with IC50 values of more than 30 µg/mL. A compound deoxythymidine also did not exert any cytotoxicity activity with IC50 value of more than 4 µg/mL. Transient transfection and luciferase assay were conducted to determine the effects of A. planci on the transcriptional activity of PCSK9 promoter. Methanolic extract and Fraction 2 (EF2) produced the lowest reduction in PCSK9 promoter activity to 70 and 20% of control at 12.5 and 6.25 μg/mL, respectively. In addition, deoxythymidine also decreased PCSK9 promoter activity to the lowest level of 60% control at 3.13 μM. An in vivo study using Sprague Dawley rats demonstrated that 50 and 100 mg/kg of A. planci methanolic extract reduced the total cholesterols and LDL-C levels to almost similar levels of untreated controls. The level of serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) showed that the administration of the extract did not produce any toxicity effect and cause any damage to rat liver. The results strongly indicate that A. planci produced a significant inhibitory activity on PCSK9 gene expression in HepG2 cells which may be responsible for inducing the uptake of cholesterols by liver, thus, reducing the circulating levels of total cholesterols and LDL-C. Interestingly, A. planci also did show any adverse hepato-cytotoxicity and toxic effects on liver. Thus, this study strongly suggests that A. planci has a vast potential to be further developed as a new class of therapeutic agent in lowering the blood cholesterols and reducing the progression of atherosclerosis.

Hepatoprotective Potential of Mimusops elengi L leaf Extracts against Paracetamol Induced Hepatotoxicity in Rats

Many traditional systems of medicines employ herbal drugs for the hepatoprotection. The aim of the study is to investigate the hepatoprotective activity of Mimusopselengi L leaf extracts extracts against paracetamol induced hepatotoxicity. However, herbal plants are the windfall for the humankind providing solution for most of the wellness breakdowns. Mimusopselengi L is one of such plants with enormous therapeutic and nutraceutical potencies. The main aspiration of the current investigation is to evaluate the hepatoprotective ability of methanolic and aqueous extract of Mimusopselengi L leaves against paracetamol induced hepatotoxicity using wistar rats through biochemical parameters and histopathological findings. The phytochemical screening was carried on the leaves extracts of Mimusopselengi L revealed the presence of some active ingredients such as Alkaloids, Tannins, Sponginess, Phenols, glycosides, steroids, terpenoids and flavonoids. Leaves of Mimusopselengi L was successively ethylacetate fraction with methanolic and aqueous extract against paracetamol (2 ml/kg.p.o) induced hepatotoxicity using Standard drug Liv 52 (5 ml/kg). There was a significant changes in biochemical parameters (increases in serum glutamate pyruvate transaminase (SGPT), Serum glutamate oxaloacetate transaminase (SGOT), alanine phosphatase (ALP), serum bilirubin in paracetamol treated rats, which were restored towards normalization in Mimusopselengi L methanolic and aqueous extract (200 mg/kg and 200 mg/kg) treated animals. Thus, the present study ascertains that the leaf extract of Mimusopselengi L possesses significant hepatoprotective activity.

Characterization of a Temporal Profile of Biomarkers as an Index for Ischemic Stroke Onset Definition

Background and purpose: Stroke is a dynamic process in terms of molecular mechanisms, with prominent glutamate-mediated excitotoxicity at the onset of symptoms followed by IL-6-mediated inflammation. Our aim was to study a serum glutamate/IL-6 ratio as an index for stroke onset definition. Methods: A total of 4408 ischemic stroke patients were recruited and then subdivided into four quartiles according to latency time in minutes (0–121, 121–185, 185–277 and >277). Latency time is defined as the time between stroke onset and treatment at the neurological unit. The primary endpoint of the study was the association of early latency times with different clinical aspects and serum markers. Serum glutamate and interleukin-6 (IL-6) levels at admission were selected as the main markers for excitotoxicity and inflammation, respectively. Results: Glutamate serum levels were significantly higher in the earlier latency time compared with the higher latency times (p < 0.0001). IL-6 levels were lower in early latency times (p < 0.0001). Patients with a glutamate/IL-6 index on admission of >5 were associated with a latency time of <121 min from the onset of symptoms with a sensitivity of 88% and a specificity of 80%. Conclusions: The glutamate/IL-6 index allows the development of a ratio for an easy, non-invasive early identification of the onset of ischemic stroke symptoms, thus offering a new tool for selecting early stroke patient candidates for reperfusion therapies.

Evaluation of Hepatoprotective activity of Ethanolic Extract of Garuga pinnata Roxburgh leaves against Carbon tetrachloride induced Hepatotoxicity in rats.

In this study we investigated the in vivo Hepatoprotective activity of ethanolic extract of Garuga pinnata (EEGP) leaves in Carbon tetrachloride (CCl4) induced hepatotoxicity using wistar rats of either sex as model. Hepatotoxicity was induced by the administration of CCl4 intraperitoneally (0.125ml CCl4 in liquid paraffin (1:1) per 100g body weight). Garuga pinnata leaves extract at different dose levels (200 and 400mg/kg, p.o.) showed the dose dependant hepatoprotective effect and was compared with well known standard hepatoprotective Silymarain (100mg/kg). When groups were treated with CCl4, significant increase in serum biochemical parameters such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline phosphate (ALP), Acid Phosphate (ACP), Creatinine and alteration of tissue biochemical parameters such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and the total proteins were observed. The histopathological examination of the CCl4 treated groups showed sinusoidal congestion, centrilobular necrosis, marked vacuolations and congestion. However, pretreatment with extract of leaves of Garuga pinnata significantly reduced the increased serum levels of biochemical parameters and restored antioxidant defense enzymes level to its normal. Moreover, histopathology of leaves extract treated groups showed normal architecture with minimal sinusoidal congestion. Taken together, our study concludes that EEGP to be a more potential agent for caring liver from CCl4 induced damage.