Sajal Kumar Saha

Analgesic and Anti-inflammatory Activities of Flower Extracts of Punica granatum Linn. (Punicaceae)

Punica granatum has been used for centuries to confer health benefits in a number of inflammatory diseases. Based on its usage in Ayurvedic and Unani medicine, dietary supplements containing pomegranate extract are becoming popular for the treatment and prevention of arthritis and other inflammatory diseases. Pet-ether, dichloromethane and methanol fractions of flower part were chosen for pharmacological screening and analgesic and anti-inflammatory activities in animal model. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model. The analgesic effect was measured in mice using the acetic acid-induced writhing test. In the acetic acid-induced writhing test in mice, pet-ether, dichloromethane and methanol fractions at 200 mg/kg doses level showed 75.77% (p<0.001), 68.56% (p<0.001), 54.64% (p<0.001) inhibition of writhing, respectively. In rat paw edema model induced by carrageenan, pet-ether, dichloromethane and methanol fractions were found to reduce significantly (p<0.001) the formation of edema at the 100 mg/kg dose level and showed 26.92% (p<0.001), 27.97%(p<0.001), 21.85%(p<0.001) inhibition respectively of edema volume at the end of 4 h. Punica granatum possesses evident analgesic and anti-inflammatory activities. The results signify the traditional uses of Punica granatum for inflammation and pain.

Synthesis, Characterization and Comparison of Local Analgesic, Anti-Inflammatory, Anti-Ulcerogenic Activity of Copper and Zinc Complexes of Indomethacin

BACKGROUND Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback. OBJECTIVE The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes. METHOD The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively. RESULTS 0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 µg/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage. CONCLUSION In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.

Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice

Abstract Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.

A comprehensive in vitro biological investigation of metal complexes of tolfenamic acid

Abstract Objective The inquisitive objective of the study was to observe the antimicrobial, cytotoxicity, and antioxidant activities of some newly synthesized metal complexes of tolfenamic acid. Methods While antimicrobial activity was studied by disk diffusion method, cytotoxicity was studied by performing brine shrimp lethality bioassay. Moreover, DPPH radical scavenging potential was observed to determine the antioxidant property of the complexes. Results From the disk diffusion antimicrobial screening of tolfenamic acid and its metal complexes, it was found out that considerable antimicrobial activity in terms of zone of inhibition against the tested organisms had been demonstrated by Cu and Zn complex of tolfenamic acid. In addition, the brine shrimp lethality bioassay corroborated that tolfenamic acid and Cu, Co, Zn complexes of the parent NSAID exhibited cytotoxicity with LC50 values 1.23 ± 0.91 μg/ml, 1.12 ± 0.12 μg/ml, 1.17 ± 0.56 μg/ml, 1.35 ± 0.24 μg/ml respectively, compared to the vincristine sulfate had LC50 value of 0.82 ± 0.09 μg/ml. Furthermore, 1,1-diphenyl-2-picrylhydrazyl assay revealed that in comparison with standard BHT had IC50 of 11.84 ± 0.65, Cu and Co complex of tolfenamic acid exhibited significant antioxidant or radical-scavenging properties with IC50 values 13.61 ± 0.58 μg/ml and 15.38 ± 0.09 μg/ml, respectively. Conclusion It can be postulated that metal complexes of tolfenamic acid have auspicious pharmacological effects: antimicrobial, cytotoxicity, and antioxidant potency. Hence, these complexes might have better therapeutic responses in future; notwithstanding, it needs further detailed analysis in other pharmacological perspectives.

Synthesis and characterization of cobalt and manganese complexes of indomethacin and comparative study of local analgesic, anti-inflammatory, and anti-ulcerogenic properties

The aim of the study was to synthesize cobalt and manganese complexes of indomethacin and their biological activity screening to uncover. The structures of metal complexes were elucidated by FT-IR, UV-Vis and atomic absorption spectroscopy, X-ray diffraction and calorimetric DSC. Heat radiant tail-flick test for local analgesic activity of cobalt complex of indomethacin in the doses of 50 and 100 μg/mL demonstrated potent local analgesic response. Manganese complex of indomethacin exhibited similar potent of activity at the dose of 100 μg/mL. Anti-inflammatory study of the indomethacin-manganese and indomethacin-cobalt complexes demonstrated their activity (paw edema inhibition of 71.67% at 20 mg/kg dose in the 1 h and 83.33% at 10 mg/kg dose in the 4 h) comparable with the standard diclofenac sodium. Gastrointestinal efficacy of cobalt and manganese complexes was close to that of indomethacin.

Biochemical alterations and liver toxicity analysis with pioglitazone in healthy subjects.

Pioglitazone, a member of the thiazolidinediones, is a potent, highly selective agonist for peroxisome proliferator-activated receptor gamma and is an excellent insulin sensitizer used in treating type 2 diabetes mellitus. The present study investigated the effect of pioglitazone on glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol, total proteins, albumin (ALB), alanine transaminase (ALT), and aspartate transaminase (AST) levels in 20 healthy Bengali male volunteers in a randomized, placebo-controlled study. Blood samples were collected before and 0.5–24.0 hours after a single oral dose of a 30 mg pioglitazone tablet. Plasma pioglitazone level was determined using a validated method of reverse-phase binary high-performance liquid chromatography. Blood lipid profile and levels of glucose, ALT, and AST were estimated using enzyme assay kits, plasma protein level was estimated by the biuret method, and plasma ALB level was determined colorimetrically. No significant change in blood glucose, total proteins, total cholesterol, triglyceride, HDL, and LDL levels was observed over the 24-hour assessment period, indicating no plasma biochemical alterations. There were no significant differences between baseline and 24-hour values of ALB, ALT, and AST levels, indicating a lack of liver toxicity. Our results indicate that a single dose of 30 mg of pioglitazone has no hypoglycemic or hypolipidemic effect or liver toxicity within 24 hours of treatment among healthy Bengali males.

Comparative physicochemical, anti-inflammatory, and analgesic activity assay of synthesized chromium and nickel complexes of indomethacin

Abstract Objectives: Complexation of non-steroidal anti-inflammatory drugs (NSAIDs) with transition metals—chromium and nickel is a unique approach of masking the inherent side effect of gastrointestinal hemorrhage and ulceration of NSAID along with imparting beneficial pharmacological effects. Methods: Chromium and nickel complexes of indomethacin were synthesized followed by characterization of these complexes by FT-IR spectroscopy, UV–Visible spectroscopy, atomic absorption spectroscopy, calorimetric DSC analysis, and melting point analysis. For screening of biological activities to uncover potentially interesting pharmacological properties, the metal complexes were assayed for peripheral analgesic, central analgesic, and anti-inflammatory activity. Results: Nickel-indomethacin complex at dose of 20 mg/kg showed peripheral analgesia of 67.03% by inhibiting writhing and at its dose of 20 mg/kg showed potent central analgesic action at 60 min (92% elongation of tail flicking time). In anti-inflammatory study, nickel-indomethacin and chromium indomethacin complex at its 15 mg/kg dose in the 2 h showed inhibition of paw edema of 78.35 and 73.23%, respectively, which is comparable to the standard indomethacin. Conclusion: Based upon the results, it can be predicted that chromium and nickel complex of indomethacin may show promising pharmacological effects which can be revealed by extensive analysis using pharmacokinetic and pharmacodynamic test model.

Comparative in vitro-in vivo correlation analysis with pioglitazone tablets

Objective To assess the in vitro-in vivo correlation of immediate release formulation of pioglitazone 30 mg film coated tablet.