Anti-inflammatory and antipyretic activities of the ethanolic extract of Shorea robusta Gaertn. f. resin.

Shorea robusta Gaertn. f. (Sal) is one of the most important traditional Indian medicinal plants. The resin of the plant has been used in the treatment of inflammation in folklore medicine. In the present study, ethanolic extract (70%) of S. robusta resin (SRE) was investigated for its anti-inflammatory and antipyretic activities. Acute inflammation was produced by carrageenan-induced hind paw edema and sub-acute by cotton pellet-induced granuloma in male Wistar rats. The antipyretic activity of SRE was studied using Brewer’s yeast-induced pyrexia in rats. The rats were divided into five groups with five animals in each group. Group I was treated with vehicle i.e. 1% v/v Tween-80 and served as control. Groups II to IV were treated with three different doses of SRE (30, 100 and 300 mg/kg orally). Group V was treated with standard drug etoricoxib (10 mg/kg orally). The anti-inflammatory activity of SRE was assessed by per cent reduction in edema volume of carrageenan-induced hind paw edema and by per cent decrease in granuloma formation in cotton pellet-induced granuloma test. SRE (100 and 300 mg/kg) produced a significant reduction in edema volume and decrease in granulation tissue formation in rats. Significant reduction in pyrexia was observed at all the dose levels of SRE i.e. 30, 100 and 300 mg/kg. The results of the present study demonstrated anti-inflammatory and antipyretic activities of S. robusta resin and supported its traditional therapeutic use in painful inflammatory conditions and fever.

Wound healing activity of ethanolic extract of Shorea robusta Gaertn. f. resin.

The ethanolic extract of S. robusta resin (10 and 30 % w/w applied locally in excised and incised wounds) produced a dose-dependent acceleration in wound contraction and increased hydroxyproline content and tensile strength of wounds in rats. The results demonstrate wound healing activity of ethanolic extract of S. robusta resin.

Inhibitory role of Syzygium cumini on autacoid-induced inflammation in rats.

The ethanolic extract of Syzygium cumini bark has been reported to possess anti-inflammatory activity in our previous studies. The present study is an attempt to elucidate the anti-inflammatory activity of S. Cumini bark against inflammation induced by individual autacoid insult. Histamine (1 mg/ml), 5-HT (1 mg/ml), bradykinin (0.02 mg/ml) and PGE2 (0.001 mg/ml) were used as inflammogens. One of these agents (0.1 ml) was injected s.c. into the right hind paw of each rat. The ethanolic extract of S. cumini bark was tested at the doses of 100, 300 and 1000 mg/kg, p.o. The results indicated the anti-inflammatory activity of S. cumini bark in histamine, 5-HT and PGE2-induced rat paw oedema. However, there was no such significant inhibition of oedema volume observed in bradykinin-induced rat paw oedema at any dose level. Thus, it is concluded that S. cumini exhibits inhibitory role on inflammatory response to histamine, 5-HT and PGE2.

Effect of centrally administered nitric oxide modulators in Brewer's yeast-induced nociception in rats.

Possible modulation of Brewer's yeast-induced nociception by centrally (icv) administered nitric oxide (NO) modulators, viz., NO synthase (NOS) inhibitors, NO precursor, donors, scavengers and co-administration of NO donor (SIN-1) with NOS inhibitor (L-NAME) and NO scavenger (Hb) was investigated in rats. Administration of NOS inhibitors and NO scavenger Hb increased the pain threshold capacity significantly, whereas NO donors SIN-1, SNP and NO precursor L-arginine were found to be hyperalgesic. D-arginine, the inactive isomer of L-arginine and methylene blue, inhibitor of soluble guanylate cyclase failed to alter the nociceptive behaviour in rats. Co-administration of SIN-1 with L-NAME and Hb found to increase the nociceptive threshold. The results indicate, that centrally administered NO modulators alter the nociceptive transmission induced by Brewer's yeast in rats.

Evaluation of the activity of receptor-operated Ca2+ channels in rat portal vein in induced hyperthyroidism.

The activity of receptor-operated Ca2+ channels (ROCCs) was studied in rat portal vein in L-thyroxine-induced experimental hyperthyroidism. The following parameters were evaluated: 1. NE-stimulated 45Ca influx. 2. CaCl2-induced contractile responses in Ca2+ free NE-stimulated tissues to calculate EC50 value of CaCl2. The NE (10(-6)mol) stimulated 45Ca influx and the mean EC50 value of CaCl2 did not differ significantly in portal veins isolated from hyperthyroid rats as compared to those of euthyroid control rats. The study revealed no significant change in the functional status of ROCCs in experimental hyperthyroidism.

Effect of pinacidil on the contractile response of cyclophosphamide-treated rat vas deferens.

Effect of pinacidil, a K+ channel opener, was studied on contractility of cyclophosphamide-treated rat vas deferens. The mean IC50 value of pinacidil against 1 mmol barium chloride induced rhythmic contractions and 40 mmol potassium chloride induced tonic contractions was significantly (P < 0.01 and P < 0.001, respectively) increased in the cyclophosphamide treated group as compared to the control. The mean EC50 value of norepinephrine (NE) in the presence of pinacidil (10(-6) mol) was significantly (P < 0.001) increased in the cyclophosphamide treated group. These findings indicate that the responsiveness of rat vas deferens smooth muscle to pinacidil is reduced following cyclophosphamide treatment.

Central modulation of formalin-induced acute peripheral inflammation & pain by some putative amino acid neurotransmitters in rats.

Possible central modulation of acute peripheral inflammation by putative amino acid neurotransmitters was investigated in rats by adopting formalin induced pedal inflammation as an experimental model. Out of five amino acids (GABA, glycine, DL-alanine, L-glutamic acid and L-aspartic acid) tested, intracerebroventricular (icv) administration of GABA and L-aspartic acid produced significant alteration in acute inflammation. GABA showed a significant attenuation of paw oedema and nociception whereas, L-aspartic acid produced significant increase in oedema volume along with marked hyperalgesia. In conclusion, the study confirms that CNS is capable of modulating peripheral inflammation.

Central noradrenergic & dopaminergic modulation of brewer's yeast-induced inflammation & nociception in rats.

The possibility of central noradrenergic and dopaminergic modulation of Brewer's yeast-induced peripheral inflammation was investigated in rats. Centrally administered noradrenaline (NA), amphetamine, which liberates NA and dopamine in the central nervous system and L-dopa, the precursor of dopamine significantly suppressed paw oedema. Conversely, the beta-adrenoceptor blocker, propranolol, catecholaminergic neuron degenerator, 6-hydroxydopamine (6-OHDA), dopaminergic antagonist, haloperidol and dopamine synthesis inhibitor, alpha-methyl para tyrosine (AMPT) augmented paw oedema. In addition, 6-OHDA and haloperidol produced significant reduction in pain threshold. The results of this study indicate that central NA and dopamine exert inhibitory effects on Brewer's yeast-induced peripheral inflammation.

Central modulation of Brewer's yeast-induced peripheral inflammation by neuropeptides bradykinin and substance P.

Possible modulation of the Brewer's yeast-induced peripheral inflammation by two central neuropeptides, bradykinin and substance P (SP), was investigated in rats. Centrally administered bradykinin significantly increased pedal oedema and pain threshold whereas, SP produced significant augmentation of oedema volume and nociception. The results of the present study indicate that central bradykinin exerts pro-inflammatory and analgesic effects whereas, central SP exerts pro-inflammatory and pro-nociceptive effects on Brewer's yeast-induced peripheral inflammation.

Central serotonergic and histaminergic modulation of peripheral inflammation and nociception in rats.

Possible central serotonergic and histaminergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced acute pedal inflammation as an experimental model. Intracerebroventricular (icv) administration of central inhibitory neurotransmitter, serotonin and its precursor, 5-hydroxytryptophan (5-HTP) attenuated the oedema volume and exudate protein content alongwith augmentation in pain threshold. On the contrary, cyproheptadine, a 5-HT-receptor antagonist and selective serotonin synthesis inhibitor, parachlorophenylalanine (PCPA) produced oedema augmenting and pro-nociceptive effects besides elevating the protein content of the exudate. Centrally administered histamine attenuated pedal oedema, nociception as well as protein concentration in oedema fluid. Cimetidine, an H2 histaminergic receptor blocker did not produce any significant effect on inflammation.

Central noradrenergic and cholinergic modulation of formaldehyde-induced pedal inflammation and nociception in rats.

Possible central noradrenergic and cholinergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced pedal inflammation as the experimental model. Intracerebroventricularly (icv) administered noradrenaline (NA), alpha-adrenoceptor agonist, L-phenylephrine, alpha-2 adrenoceptor agonist, clonidine and non-selective beta-adrenoceptor blocker, propranolol, suppressed formaldehyde-induced inflammation producing a decrease in oedema volume and increase in pain threshold. Conversely, both noradrenergic neuron degenerator, 6-hydroxydopamine (6-OHDA) and non-selective alpha-adrenoceptor antagonist, phenoxybenzamine produced an increase in paw oedema along with an augmentation of pain. Significant oedema augmenting effects were also produced by central excitatory neurotransmitter, acetylcholine (ACh) on icv administration. ACh also produced pro-nociceptive action. An ACh antagonist, scopolamine and ACh synthesis inhibitor, hemicholinium-3 (HC) reduced pedal oedema and produced analgesia. The results of this study indicate that central NA exerts an inhibitory effect on peripheral oedema and pain whereas, ACh has an augmenting effect on formaldehyde-induced peripheral inflammation.