Bal Krishan Chandan

Boerhaavia diffusa: A study of its hepatoprotective activity

An alcoholic extract of whole plant Boerhaavia diffusa given orally exhibited hepatoprotective activity against experimentally induced carbon tetrachloride hepatotoxicity in rats and mice. The extract also produced an increase in normal bile flow in rats suggesting a strong choleretic activity. The extract does not show any signs of toxicity up to an oral dose of 2 g/kg in mice.

Hepatoprotective activity of Woodfordia fruticosa Kurz flowers against carbon tetrachloride induced hepatotoxicity

ETHNOPHARMACOLOGICAL RELEVANCE Dried flowers of Woodfordia fruticosa Kurz. Family Lythraceae are used in variety of diseases in traditional Indian system of medicine including hepatic ailments. AIMS OF STUDY The aim of present study was to validate hepatoprotective activity of flowers of Woodfordia fruticosa Kurz. MATERIALS AND METHODS Petroleum ether (WF1), chloroform (WF2), ethyl alcohol (WF3) and aqueous (WF4) extracts of the flowers of Woodfordia fruticosa were evaluated for hepatoprotective activity against carbon tetrachloride induced hepatotoxicity using biochemical markers, hexobarbitone sleep time, bromosulphalein (BSP) clearance test and effect on bile flow and bile solids. RESULTS The aqueous extract (WF4) was most potent among the four extracts studied in detail. WF4 showed significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity as evident by restoration of serum transaminases, alkaline phosphatase, bilirubin and triglycerides. The restoration of microsomal aniline hydroxylase and amidopyrine-N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. Restoration of lipid peroxidation and glutathione contents suggests the antioxidant property of WF4. The recovery in bromosulphalein clearance and stimulation of bile flow suggested the improved excretory and secretary capacity of hepatocytes. Light microscopy of the liver tissue further confirmed the reversal of damage induced by hepatotoxin. CONCLUSION Present study showed that the aqueous extract of Woodfordia fruticosa significantly restores physiological integrity of hepatocytes. WF4 did not show any sign of toxicity up to oral dose of 2g/kg in mice.

An evaluation of Lawsonia alba extract as hepatoprotective agent

The hepatoprotective activity of an ethanol-water (1:1) extract of Lawsonia alba has been studied against CCl4-induced liver toxicity. The effects of the extract on hexobarbitone-induced sleep, BSP clearance, and on certain biochemical parameters indicated its protective role. There was no effect on bile flow. The extract did not show any signs of toxicity and the minimum lethal dose was greater than 2.0 g/kg p.o. in mice.

Biodegradable polymeric system for cisplatin delivery: Development, in vitro characterization and investigation of toxicity profile ☆ ☆☆

Cisplatin is one of the most potent anticancer agent used in the treatment of various solid tumors, however, its clinical use is limited due to severe adverse effects including nephrotoxicity. In this investigation cisplatin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were developed and characterized for various in vitro characteristics including size distribution, zeta potential, drug loading and release profile. PLGA nanoparticles were successfully developed as investigated using scanning electron microscopy and exhibited average particles size and zeta potential as 284.8 nm and -15.8 mV, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated an absence of any polymer-drug interactions. Cisplatin nanoparticles exhibited in vitro anticancer activity against A549 cells comparable to that of cisplatin solution. The biodistribution study in mice indicated that the kidney cisplatin level was significantly (p<0.01) lower with cisplatin nanoparticles than cisplatin solution. Following two cycles of cisplatin treatment, a week apart, blood urea nitrogen level was found to be higher in case of cisplatin solution as compared to cisplatin nanoparticles. Further, there was a significant (p<0.01) increase in plasma creatinine level in case of cisplatin solution as compared to cisplatin nanoparticles. Histopathological examination of kidney from cisplatin nanoparticles treated group revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of cisplatin solution. The results suggest that PLGA nanoparticle based formulation could be a potential option for cisplatin delivery.

Effect of Zizyphus sativa leaves on blood glucose levels in normal and alloxan-diabetic rats.

An alcoholic extract of Zizyphus sativa leaves was tested for hypoglycemic activity in normal and alloxan-diabetic rats. Single (100-400 mg/kg) oral doses of extract to normal animals showed a dose-dependent statistically significant lowering of blood glucose 2, 4 and 6 h later. The effect was most pronounced at 6 h with blood glucose returning to control values at 24 h. In alloxan-diabetic rats, no significant effect was observed with extract and tolbutamide. The minimum lethal dose was greater than 3000 mg/kg, orally in mice.

Hepatoprotective effects of Wedelia calendulacea

The alcoholic extract of whole plant Wedelia calendulacea exhibited protective activity against carbon tetrachloride-induced liver injury in vivo. The extract also increased the bile flow in rats suggesting a stimulation of liver secretory capacity. The minimum lethal dose was greater than 200 mg/kg p.o. in mice.

Actions of some flavonoids on specific and non-specific immune mechanisms

The immunomodulatory activity of some flavonoids on antigen specific humoral and cell mediated immune responses and complement-mediated hemolysis has been investigated and compared with that of levamisole. Flavanone, 6-methoxyflavanone, 7-methoxyflavanone and bavachinin enhanced the sheep erythrocyte (SRBC), induced primary and secondary humoral immune responses in mice, and 6-hydroxyflavanone, 7-hydroxyflavanone and rutin inhibited primary response. Levamisole slighly stimulated the primary and suppressed the secondary response. All the flavonoids tested decreased the manifestation of SRBC induced delayed type hypersensitivity reaction and showed no effect on classical or alternative pathway dependent hemolysis. The studies revealed the significant immunomodulatory potential of these flavonoids, methoxy derivatives having immunostimulatory activity and hydroxy derivatives immunosuppressive properties.

Chemoprevention with Aqueous Extract of Butea monosperma Flowers Results in Normalization of Nuclear Morphometry and Inhibition of a Proliferation Marker in Liver Tumors

Butea monosperma (Lam.) (family: Fabaceae) popularly known as ‘Palas’ or ‘fire of forest’ has been used traditionally as a hepatoprotective agent. This study evaluated the hepatoprotective and antitumorigenic properties of the aqueous extract and butanol fractions of B. monosperma flowers in animal models. Dried flowers of B. monosperma were extracted with water and fractionated further using n‐butanol. The hepatoprotective activity of the aqueous extract was initially confirmed in a carbon tetrachloride‐induced liver damage model of rats. Oral administration of the aqueous extract produced a strong hepatoprotective effect similar to silymarin and normalized the serum levels of ALT, AST, bilirubin and triglyceride in rats. However, it did not affect the levels of glutathione and malondialdehyde which are oxidative stress markers in liver. Intraperitoneal administration of the aqueous extract in the X15‐myc oncomice not only maintained liver architecture and nuclear morphometry but also down‐regulated the serum VEGF levels. Immunohistochemical staining of liver sections with anti‐Ribosomal protein S27a antibody showed post‐treatment abolition of this proliferation marker from the tumor tissue. The butanol fractions, however, did not show antitumorigenic activity. Thus, the aqueous extract of B. monosperma flowers is not only hepatoprotective but also antitumorigenic by preserving the nuclear morphometry of the liver. Copyright

Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Aim:  The curative effect of emodin (1,3,8‐trihydroxy‐6‐methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl4) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats.

Reduced toxicological manifestations of cisplatin following encapsulation in folate grafted albumin nanoparticles.

AIMS Cisplatin is one of the most potent chemotherapeutic agents acting against a variety of tumors, however, its use is mainly limited due to the dose limiting toxicities and acquired resistance to cisplatin. Folate functionalized albumin nanoparticles were developed for targeted delivery of drug to limit the adverse effects of cisplatin. MAIN METHODS Cisplatin loaded nanoparticles functionalized with folate (CP-FA-BSA-NPs) were developed and characterized for various parameters. In order to investigate the targeting ability of folate conjugated nanoparticles, in vitro cellular uptake study was performed in folate receptor over expressing cells (MCF-7). Further, blood urea nitrogen (BUN) level, plasma creatinine level, body weight and kidney weight of the mice were measured followed by histopathological examination of various tissues to have an insight into the potential of developed formulation in the reduction of drug associated adverse effects. KEY FINDINGS The cellular uptake studies demonstrated higher internalization of folate conjugated nanoparticles as compared to plain counterpart (CP-BSA-NPs). Following two cycles of cisplatin treatment, a week apart, BUN and plasma creatinine level were found to be significantly higher in case of free cisplatin as compared to saline, CP-BSA-NPs and CP-FA-BSA-NPs treated groups. Body weight and kidney weight of free cisplatin treated mice were significantly reduced as compared to other group. Histopathological examination of kidney from CP-BSA-NPs and CP-FA-BSA-NPs treated groups revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of free cisplatin. SIGNIFICANCE The results demonstrated the potential of developed formulation in reducing the adverse effects of cisplatin.