Chandragouda R. Patil

Anti-Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa Roxb. (Lecythidaceae)

The fruits of Barringtonia racemosa are prescribed in the ayurvedic literature for the treatment of pain, inflammation and rheumatic conditions. In present investigation, activity guided isolation of bartogenic acid (BA) and its evaluation in the Complete Freunds Adjuvant (CFA)-induced arthritis in rats is reported. Among the various extracts and fractions investigated preliminarily for carrageenan-induced acute inflammation in rats, the ethyl acetate fraction displayed potent anti-inflammatory activity. Large-scale isolation and characterization using chromatography and spectral study confirmed that the constituent responsible for the observed pharmacological effects was BA. Subsequently the BA was evaluated for effectiveness against CFA-induced arthritis in rats. The results indicate that at doses of 2, 5, and 10u2009mgu2009kg−1u2009day−1, p.o., BA protects rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations induced by CFA. The serum markers of inflammation and arthritis, such as C-reactive protein and rheumatoid factor, were also reduced in the BA-treated arthritic rats. The overall severity of arthritis as determined by radiological analysis and pain scores indicated that BA exerts a potent protective effect against adjuvant-induced arthritis in rats. In conclusion, the present study validates the ethnomedicinal use of fruits of B. racemosa in the treatment of pain and inflammatory conditions. It further establishes the potent anti-arthritic effects of BA. However, additional clinical investigations are needed to prove the efficacy of BA in the treatment of various immuno-inflammatory disorders.

Anticonvulsant activity of aqueous root extract of Ficus religiosa

ETHNOPHARMACOLOGICAL RELEVANCEnFicus religiosa Linn is frequently used for the treatment of nervous disorders among Pawara tribe of the Satpuda range, India.nnnAIM OF THE STUDYnThis study aimed to investigate the anticonvulsant activity of the aqueous aerial root extract of Ficus religiosa in chemoconvulsant-induced seizures in mice.nnnMATERIALS AND METHODSnThe anticonvulsant activity of the extract (25, 50 and 100 mg/kg, p.o.) was investigated in strychnine-, pentylenetetrazole-, picrotoxin- and isoniazid-induced seizures in mice. Rat ileum and fundus strip preparations were used to study the effect of the extract on acetylcholine (Ach)- and serotonin (5-HT)-induced contractions, respectively.nnnRESULTSnThe extract showed no toxicity and protected the animals in the strychnine and pentylenetetrazole tests in a dose-dependent manner. Its effect in the picrotoxin and isoniazid tests, however, was less potent. The extract also exhibited dose-dependent potentiation of Ach in rat ileum but failed to potentiate the effect of 5-HT in rat fundus strip preparation.nnnCONCLUSIONSnThe results suggest that an orally administered aqueous root extract of Ficus religiosa has dose-dependent and potent anticonvulsant activities against strychnine- and pentylenetetrazole-induced seizures. The observed activities may be ascribed to the appreciable content of zinc and magnesium in the extract.

Dual effect of Toxicodendron pubescens on Carrageenan induced paw edema in rats

BACKGROUNDnToxicodendron pubescens is the current botanical name of homeopathic Rhus toxicodendron (Rhus tox). Rhus tox drug is widely used in homeopathically diluted form in the treatment of inflammatory and edematous conditions. We studied the effect of crude form of this plant, after single and multiple doses in Carrageenan induced paw inflammation in rats.nnnMETHODnWe evaluated effects of single dose and multiple doses of orally administered Rhus tox on Carrageenan induced paw inflammation in rats. We tested 10 mg/kg, 20 mg/kg and 40 mg/kg doses of Rhus tox. In the single dose study, Rhus tox was administered 1 h prior to the subplantar injection of Carrageenan. In the multiple dose study, Rhus tox was administered twice daily for three days and Carrageenan was injected 1 h after the last dose. Paw volume was measured using a digital plethysmometer.nnnRESULTSnAdministration of a single dose of Rhus tox 1h prior to injection of Carrageenan significantly reduced the paw inflammation in a dose dependent manner. Administration of multiple doses of Rhus tox increased the intensity of inflammation induced by Carrageenan, but this was not statistically significant.nnnCONCLUSIONnRhus tox, in crude form, exerts anti-inflammatory effects after a single dose and proinflammatory effect after multiple doses in Carrageenan induced paw inflammation in rats. Further study is needed to explain this dual effect.

Modulation of arthritis in rats by Toxicodendron pubescens and its homeopathic dilutions

BACKGROUNDnToxicodendron pubescens P. Mill (Anacardiaceae) known in homeopathy as Rhus toxicodendron (Rhus tox) is used as an anti-inflammatory medicine in homeopathic practice. In this study, Rhus tox in its crude form and homeopathic dilutions (3cH, 6cH, 30cH, 200cH) was evaluated for effects on Complete Freunds Adjuvant (CFA) induced arthritis in rats.nnnMETHODnWe assessed the severity of arthritis through observations including inflammatory lesions, body and organ weight and hematological parameters including C-reactive protein (CRP). Blinded radiological analysis of the affected joints and pain intensity determination was also carried out.nnnRESULTSnRhus tox protected rats from CFA-induced inflammatory lesions, body weight changes and hematological alterations. Rhus tox protected against radiological joint alterations due to arthritis. Arthritic pain scores were also favorably affected by Rhus tox. All the dilutions of Rhus tox including crude form showed anti-arthritic activity. The maximum protective effect was evident in the crude form at 10mg/kg/day, by mouth.nnnCONCLUSIONnThis study supports claims in the homeopathic literature on the role of Rhus tox and its ultra dilutions in the treatment of arthritis and associated pain. Further study is needed to explain this anti-arthritic effect of Rhus tox.

Toxicodendron pubescens retains its anti-arthritic efficacy at 1M, 10M and CM homeopathic dilutions.

BACKGROUNDnOur previous studies of Toxicodendron pubescens (Rhus tox) in homeopathic dilutions have shown anti-inflammatory activity in line with the principle of similia. The present study aimed to evaluate its anti-inflammatory activity in 1M, 10M and CM dilutions in rats.nnnMETHODnArthritis was induced by subplantar injection of 0.1 ml of Complete Freunds Adjuvant (CFA) in the right hind paws of rats. The severity of inflammatory lesions was measured plethysmometrically on 21st day post CFA injection. The intensity of pain was measured using digital Von Frey apparatus. Other estimations included serum C-reactive protein (CRP), hematological parameters, body weight changes, arthritic pain score and radiological analysis of the arthritic paws.nnnRESULTnThe 1M, 10M and CM homeopathic dilutions of Rhus tox reduced primary and secondary arthritic lesions, improved body weight gain and protected rats against CFA-induced hematological and radiological perturbations. A significant reduction in the serum levels of CRP and an improvement in pain threshold of injected paws was observed in the groups treated with the Rhus tox dilutions.nnnCONCLUSIONnThe anti-arthritic potential of Rhus tox is retained at 1M, 10M and CM dilutions.

Immunomodulatory activity of Toxicodendron pubescens in experimental models

BACKGROUNDnToxicodendron pubescens is a botanical name of Rhus toxicodendron (Rhus tox). This plant is widely used in its homeopathically diluted form in the treatment of inflammatory and edematous conditions. In this study, various dilutions of Rhus tox including its crude form have been evaluated for their effects on immune response in the in vivo and in vitro experimental models.nnnMETHODSnRhus tox in the form of mother tincture, 6cH, 30cH, 200cH and 1000cH dilutions was tested through in vivo models including sheep red blood cells (SRBCs) induced cellular and humoral immune response in C57/BL6 mice. The effects of Rhus tox dilutions were also evaluated in vitro on the functions of human polymorphonuclear (PMN) cells such as phagocytosis and intracellular killing of Candida albicans, chemotaxis, and reduction of nitroblue tetrazolium (NBT) dye.nnnRESULTSnRhus tox was found to intensify SRBCs induced antibody titer and delayed type hypersensitivity response in mice. Even higher dilutions such as 200cH and 1000cH were found to affect the immune response; however, the crude form, mother tincture, 6cH and 30cH dilutions revealed more potent effects than the 200cH and 1000cH dilutions. In in vitro assays, all the dilutions exerted stimulation of phagocytosis, candidacidal activity and chemotaxis of human PMN cells. The NBT dye reduction assay revealed that oxidative processes in the PMN cells are accelerated in the presence of Rhus tox. This study shows that Rhus tox possesses immunostimulatory activity in its crude form as well as in homeopathically diluted forms. These effects appeared to be concentration dependent as higher dilutions had less potent effects.

Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats.

Objective: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Materials and Methods: Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). Result: As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. Conclusion: These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.

Role of 5-HT2 receptors in diabetes: Swertiamarin seco-iridoid glycoside might be a possible 5-HT2 receptor modulator

In the present review, we are focusing on modulators of 5-HT2 receptors, swertiamarin and their role in diabetes. These drugs possess both central and peripheral actions in various animal models of depression, diabetes and obesity. Swertiamarin and 5-HT2 antagonist are reported antidepressant, hypolipidemic and beneficial in peripheral vasculopathy. In contrast to this, 5-HT2C selective agonist decreases hyperglycemia, hyperlipidemia and insulin secretogogue by action. Selective serotonin reuptake inhibitors (SSRIs) are known antidepressant having weight gain as an adverse effect. Swertiamarin has similar pharmacological actions as 5-HT2 antagonist and 5-HT2C selective agonist. This warrants that swertiamarin might modulate 5-HT2 receptors rather than affecting the uptake of serotonin. In the light of present investigation, the mechanism of these drugs can correlate the role of central and peripheral 5-HT2 receptors in diabetes.

Evaluation of separate role of intestine and liver in first pass metabolism of budesonide in rat

Abstract 1. Budesonide, a potent topical corticosteroid, reported to have low oral bioavailability in mice, rat, dog and human due to rapid first pass metabolism. However, there is insufficient information available in literature regarding the role of intestine and or liver responsible for the first pass metabolism of budesonide. 2. Current study in rats investigates the role of intestine and liver in first pass metabolism of budesonide using two in vivo models. Additionally, budesonide was also evaluated in in vitro assays such as thermodynamic solubility, permeability in Caco-2 cells and stability in simulated gastric (SGF), intestinal fluids (SIF) to understand the underlaying cause for low oral bioavailability. 3. Budesonide showed low oral, intra-duodenal and high intra-portal bioavailability in rat. In a dual vein cannulated rat model, intestinal and hepatic extraction ratios calculated based upon intestinal availability (Fa·Fg) and hepatic availability (Fh), suggests hepatic extraction of budesonide is minimal compared to intestinal. 4. In vitro results suggest, solubility and permeability may not be a barrier for the observed low oral bioavailability in rats. 5. Correlating the in vitro and in vivo data together, it can be concluded that, intestine might be playing major role in first pass metabolism of budesonide.