In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

Attenuation of CFA-induced chronic inflammation by a bicyclic monoterpene fenchone targeting inducible nitric oxide, prostaglandins, C-reactive protein and urea.

Fenchone (a bicyclic monoterpene) is present in the essential oils of plant species like Foeniculum vulgare and Peumus boldus and is used to treat GIT disorders. Research reports have indicated its strong anti-inflammatory, antioxidant, and anti-nociceptive properties. The present study was designed to investigate fenchone's anti-arthritic effects in a rat model of chronic joint inflammation (Complete Freud's Adjuvant-mediated inflammation [CFA]). Molecular docking analysis revealed a high binding interaction of fenchone with inducible nitric oxide synthase (iNOS), Interleukin-17, Prostaglandin E Receptor EP4, and Cycloxygenase-2 (COX-2), indicating its anti-inflammatory efficacy using computational tests. Fenchone treatment at 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly enhanced the tail-flick latency when compared with the solvent-treated group. Correspondingly, the raised mRNA values of iNOS, IL-17, IL-1ß, IL-6, TNF-α, and COX-2 in solvent-treated group were significantly reduced following treatment with fenchone. Moreover, fenchone significantly lowered spleen and thymus indices, Nitric oxide (NO) and PGE2 values as compared to solvent-treated group. Hence, the results of the present study indicated that fenchone has a potent anti-inflammatory effect by inhibiting pro-inflammatory markers and thus may have therapeutic potential for chronic joint inflammation as well as chronic inflammatory disorders.

Nerolidol: a potential approach in rheumatoid arthritis through reduction of TNF-α, IL-1ß, IL-6, NF-kB, COX-2 and antioxidant effect in CFA-induced arthritic model.

Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1 mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800 mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1ß were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1ß, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration.

Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of ß-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-ß production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer's disease.

Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB, COX-2, Prostaglandin-E2 in rheumatic rats.

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats.

Pharmacological evaluation of cardioprotective potential of Berberis orthobotrys Bien.ex Aitch.

The resurgence of scrutiny in plant-based medicine is mainly due to the current widespread belief that "green medicine" is safe and more dependable than the expensive synthetic drugs. The current study was focused to evaluate the anti-myocardial ischemic potential of Berberis orthobotrys Bien ex Aitch against chemically induced myocardial ischemia in animal models. Myocardial ischemia was instigated in Sprague Dawley rats of either sex (250-450g) by administration of Isoproterenol (ISO) and doxorubicin (DOX) at doses of 25mg/kg b.w and 15mg/kg b.w. respectively. The protective effect of the plant extract was explored by pretreating a group of animals with aqueous methanolic extract of Berberis orthobotrys roots at a dose of 50mg/kg b.w. (orally) for 10 days in ISO-ischemic model while for doxorubicin ischemic model; the study was conducted for 14 days. The findings of the study revealed that serum levels of cardiac marker enzymes were significantly increased (p<0.0001) followed by the administration of Isoproterenol and doxorubicin whereas the pretreatment with aqueous methanolic plant extract had significantly (p<0.0001) prevented the rise in the same, as compared to both intoxicated groups. The statistical analysis of the study led to the conclusion that Berberis orthobotrys possesses cardio protective potential against chemically induced myocardial ischemia.

Pharmacological exploration of anti-arthritic potential of terbutaline through in-vitro and in-vivo experimental models.

Terbutaline have been reported to have anti-inflammatory activity. Present study aimed to check the anti-arthritic activity of terbutaline. The drug was tested using in vitro models (bovine serum albumin denaturation, egg albumin denaturation and HRBC membrane stabilization) and in vivo (formaldehyde induced arthritis). Results of bovine serum albumin denaturation assay illustrated that terbutaline inhibited 89.54±0.46% denaturation at 6400µg/ml concentration. Terbutaline resulted in dose dependent impediment of protein denaturation in egg albumin denaturation assay with 74.40±0.72% inhibition at concentration of 6400µg/ml. Terbutaline also showed protection of HRBC membrane against hypotonic stress in a dose dependent manner, with maximum 76.45±0.62% prevention at 6400µg/ml concentration. Results of formaldehyde induced arthritis model showed that paw volume was significantly declined by terbutaline with maximum percentage inhibition at 10th day of study period which implies immune inhibitory potential of terbutaline. Findings of present study concluded that terbutaline has arthritis reducing potential possible through inhibitory effects on synthesis and release of inflammatory mediators as well as limiting the formation of autoantigen. Thus, terbutaline might be the potential candidate for use in treatment of arthritis.

Cardioprotective potential of Thymus linearis Benth.

In developing countries, myocardial ischemia and the resulting impairments in heart function are the leading cause of illness and mortality. Thymus linearis Benth has been used as an antibiotic, antioxidant, and antihypertensive agent for centuries. The goal of this investigation was to see if Thymus linearis could protect isoproterenol and doxorubicin-induced myocardial ischemia in vivo at doses of 25 mg/kg s.c. and 15 mg/kg i.p., respectively. The level of cardiac enzymes (CK-MB, LDH, and AST) in the serum isolated from the experimental animal's blood was used to determine myocardial ischemia. The anti-ischemic potential was assessed by comparing the levels of the aforementioned cardiac biomarkers in the intoxicated and treated animal groups. The study found substantial increase (p0.0001) in the serum levels of CK-MB, LDH, AST when compared to intoxicated groups, while pretreatment of animals with crude extract of Thymus linearis significantly reduced the rise in serum cardiac indicators. The findings of the study indicated that the aqueous methanolic Thymus linearis crude extract has cardioprotective potential against Isoproterenol and Doxorubicin-induced cardiac necrosis in rats.

Anti-rheumatic activity of pseudoephedrine (a substituted phenethylamine) in complete Freund's adjuvant-induced arthritic rats by down regulating IL-1ß, IL-6 and TNF-α as well as upregulating IL-4 and IL-10.

Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1ß and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.

Venlafaxine demonstrated anti-arthritic activity possibly through down regulation of TNF-α, IL-6, IL-1ß, and COX-2.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory activities through the suppression of pro-inflammatory cytokines. Present research aimed to explore its anti-arthritic potential. Different in-vitro assays including egg albumin, bovine serum albumin denaturation and human red blood cell (RBC) membrane stabilization assays along with in-vivo models of formaldehyde and complete Freund's adjuvant-induced arthritis were used to study its anti-arthritic effect. Venlafaxine inhibited egg albumin and bovine serum albumin denaturation and preserve the integrity of red blood cells membrane in concentration-dependent manner. In formaldehyde-induced arthritis venlafaxine significantly (p < 0.001) reduced the paw edema on treatment for 10 days. Chronic administration of venlafaxine for 28 days in Freund's adjuvant-induced arthritis model decreased the paw volume (p < 0.001), arthritic index (p < 0.01), flexion pain score (p < 0.05), mobility score (p < 0.05), and improved the stance score (p < 0.05). Venlafaxine also significantly declined the rheumatoid factor (p < 0.01) and C-reactive protein (p < 0.05) levels and increased the RBC count (p < 0.01) and Hb value (p < 0.001). Upon PCR analysis venlafaxine remarkably turndown the mRNA expression of TNF-α, IL-6, IL-1ß, and COX-2. Taken together it is inferred from current findings that venlafaxine possesses the significant anti-arthritic activity and could be a potential therapeutic option for the treatment of rheumatoid arthritis.

Toxicity studies and anti-arthritic effect of mandelic acid (2-hydroxy -2-phenyl acetic acid) using in vitro and in vivo techniques.

The major concern to search for new anti-arthritic drugs is primarily to prevent systemic complications and to maintain quality of life. As these drugs are prescribed for long duration so the objective is to ensure their safety in terms of toxicity. By keeping in view this concept, the present study was investigated to determine new anti-arthritic potential using in-vitro and in-vivo methods. The in-vitro tests comprised of protein denaturation (BSA and egg albumin) and Human Red Blood cell (HRBC) membrane stabilization assays at 50-6400µg/mL, for in-vivo testing, formaldehyde-induced arthritic rats were treated with 40, 80 and 160mg/kg mandelic acid. Mandelic acid (MA) inhibited the protein denaturation and stabilized the membrane of HRBC in a concentration dependent manner. Likewise, mandelic acid exhibited dose dependent reduction in paw volume induced by formaldehyde. For acute and sub-acute treatment, MA did not show any sign of toxicity and mortality in each rat and LD50 might be greater than 2000mg/kg. In addition, histopathological assessment presented slight increased interstitial spaces in the kidney, disorganization of glomerulus, dilated sinusoids at highest dose 800mg/kg which were not observed in sub-chronic therapy. Hence, these results conclude that mandelic acid has the potential to treat rheumatoid arthritis with observed no significant signs of toxicity and should be tested further to determine anti-arthritic mechanism of drug action at cellular level.

Evaluation of phytochemical, anti-oxidant and cardiac depressant effect of Rumex dentatus by using Langendorff's isolated heart apparatus.

Rumex dentatus has been used traditionally for ailment of cardiovascular diseases. The aim of the present study was to assess cardiovascular effects in isolated perfused rabbit heart. Aqueous and n-butanolic fractions were assessed for their effect on perfusion pressure (PP), force of contraction (FC) and heart rate (HR) of rabbit heart using Langendorff's method. The possible mechanisms of action of extracts/fraction were assessed with and without application of different agonist/antagonist. Phytochemical, toxicity and anti-oxidant activities were also determined. Both extracts at 1mg/mL dose produced a highly significant decrease in FC and HR but PP remained unchanged. Moreover, aqueous fraction of Rumex dentatus at 0.001mg/mL dose produced a highly significant decrease in FC and HR but no significant change in PP was observed. Atropine 10-5 M did not inhibit the cardiac depressant response of both fractions. Furthermore, both fractions blocked the positive ionotropic and chronotropic effects of adrenaline and calcium chloride. Phytochemical studies have shown the presence of some phytochemicals. Acute and sub-chronic toxicity studies demonstrated that test extracts are safe and produced no significant changes in haematological and biochemical parameters. Crude extract showed significant antioxidant activity like ascorbic acid. This study revealed that this plant have good cardiac depressant effect.

Endothelium independent calcium channel blocking pathways mediate antihypertensive effect of morus nigra.

Present study was conducted to validate the folkloric claims of morus nigra l. (moraceae) using invasive blood pressure measuring and ex vivo vasorelaxant experimental techniques. Intravenous administration of mn. Aq in 0.01-30 mg/kg doses caused significant decrease in mean arterial pressure and heart rate in fructose-induced hypertensive rats. It also showed relaxation in high k+ [80 mm] and pe (1µm) mediated aortic contraction with ec50 1.25 and 3.72mg/ml values, respectively. Vaso-relaxant effect of mn.aq was partially blocked in presence of l-name with ec50, 5.32mg/ml value, but showed concentration dependent significant inhibition of ligand gated and voltage gated ca+2 channels and intracellular ca+2 release, similar to verapamil. Findings of current study designate that aqueous fraction of m. Nigra possesses antihypertensive activity with concentration-dependent vaso-relaxant effect predominantly mediated through endothelial-independent calcium channel blocking pathways accompanied by partial involvement of endothelium-dependent nos mediated relaxation.

Therapeutic appraisal of ephedrine against rheumatoid arthritis: A new indication.

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.

Correction to: Appraisal of disease-modifying potential of amlodipine as an anti-arthritic agent: new indication for an old drug.

Unfortunately, the 4th author name was incorrectly published in the original publication.

Appraisal of disease-modifying potential of amlodipine as an anti-arthritic agent: new indication for an old drug.

Amlodipine, a second-generation calcium channel blocker, exhibits documented anti-inflammatory potential. Thereby, present investigation was accomplished with an aim to explore anti-arthritic potential of amlodipine, giving a second chance to an existing drug. For validation of anti-arthritic potential of amlodipine, some in vitro models comprised of bovine serum albumin- and egg albumin-induced protein denaturation along with membrane stabilization of red blood cell was being conducted. In vivo models comprised of formaldehyde-provoked acute arthritis and CFA-instigated chronic arthritic. Paw edema, arthritic index, body weight alterations, biochemical and hematological parameters, and ankle joint histological and radiographic investigations were appraised. Moreover, RT-PCR was conducted to evaluate the levels of several inflammatory markers. Molecular docking was being conducted targeting TNF-α, IL-1ß and IL-6 to establish the correlation between experimental and theoretical results. Amlodipine provides significant protection against denaturation being provoked by heating egg albumin and BSA along with stabilizing membrane of red blood cell, thereby proving in vitro anti-arthritic effect. A significant (p < 0.001) reduction in paw swelling was being observed with amlodipine in case of formaldehyde-instigated arthritis especially at the dose of 20 mg/kg. In case of CFA-provoked arthritis, reduction in paw volume and arthritic score while preservation of body weight loss and normal hematological and biochemical parameters in comparison to arthritic control were being manifested by amlodipine at the dose of 20 mg/kg. Gene expression level of TNF-α, IL-6 and IL-1ß was significantly reduced by amlodipine while an increase in expression level of IL-4 and IL-10 was evident in animals treated with piroxicam and amlodipine. Molecular docking analysis demonstrated strong binding interaction of amlodipine with TNF-α, IL-6 and IL-1ß thus providing a good correlation between experimental and theoretical results. Thus, current study is suggestive that amlodipine exhibits strong anti-arthritic potential and thus can be considered as a candidate for drug repurposing as anti-arthritic agent.

Blood pressure lowering effects of Ranunculus scleratus Linn. in normal and fructose induced hypertensive rats and estimation of underlying mechanisms.

Ranunculus scleratus Linn. is used in folk medicine to treat hypertension. This study was aimed at providing validation to its traditional use and to explore underlying mechanisms of action. Effects of hydro-ethanolic crude extract of the plant and its fractions on blood pressure was evaluated using direct surgical method in normotensive and in fructose induced hypertensive rats. Various doses of crude extract, RSC, (5, 10, 20, 30mg/kg) and all fractions (3, 5, 10, 20mg/kg) were studied. Results suggested that aqueous fraction of R. scleratus (RSA) produced most pronounced effects at 10mg/kg in normotensive and at 20mg/kg in hypertensive animals. Underlying mechanisms, using various pharmacological antagonists were also elucidated. Results suggested the involvement of muscarinic receptor, angiotensin converting enzyme (ACE) inhibition, ganglionic block and nitric oxide (NO) release in presenting hypotensive response.

Evaluation of effect of Acacia jacquemontii Benth. on blood pressure in normotensive and fructose induced hypertensive sprague dawley rats: An ethnopharmacological approach.

Acacia jacquemontii Benth. is used traditionally to treat hypertension but no scientific literature supports this claim. So, this study was aimed at validating this claim. This was done by injecting various doses of crude extract of Acacia jacquemontii, AJC (5, 10, 20, 30mg/kg) and all fractions (hexane, ethyl acetate, n-butanol and aqueous) (3, 5, 10, 20mg/kg) intravenously in anaesthetized rat. Based on the results, butanol fraction (AJB) at 20mg/kg was found to be the most potent, so it was selected for exploring mechanisms of action. For this purpose, different groups were injected with various pharmacological inhibitors (L-NAME, atropine, captopril, propranolol and hexamethonium) prior to AJB administration. Also, AJB at 20mg/kg was evaluated for prolonged hypotensive effect for the period of 40 min. Results showed a significant dose dependent reduction in BP in normotensive and in hypertensive rats. AJC and AJB produced a decline in SBP, DBP and MAP with p<0.05 - p<0.001 and p<0.001 respectively in normotensive animals. Whereas in hypertensive animals, AJC showed significant reduction at 5mg/kg with p<0.01 and at 10, 20 and 30 mg/kg with p<0.001. AJB produced a decline in hypertensive animals at all tested doses with p<0.001. AJB resulted in hypotensive effect mediated by ß receptors, ganglionic block operating central sympathetic neural responses and renin angiotensin aldosterone system (RAAS). This study supports the ethnomedicinal claim of Acacia jacquemontii Benth. in treating hypertension.

Evaluation of anti-inflammatory and analgesic activities of aqueous methanolic extract of Ranunculus muricatus in albino mice.

Ranunculus muricatus (Ranunculaceae) is commonly used by inhabitants of Pakistan for the treatment of gout and rheumatism, both of which are inflammatory disorders. The present study attempts to evaluate the anti-inflammatory and analgesic activities of aqueous methanolic extract of R. muricatus in mice. The plant extract at doses of 50, 100 and 150 mg/kg was tested for anti-inflammatory activity against carrageenan and egg albumin induced paw edema in mice and analgesic activity was appraised against acetic acid induced writhing and formalin induced paw licking in mice models. The results designate that extract at the highest dose of 150 mg/kg significantly (p<0.001) and dose dependently inhibited carrageenan induced and egg albumin induced paw edema. Similarly, extract at the same dose of 150 mg/kg showed potent and dose dependent (p<0.001) suppression of formalin induced paw licking and abdominal constrictions / stretching of hind limbs induced by acetic acid. The anti-inflammatory and analgesic activity of plant extract was comparable to standard drug ibuprofen in all models. This study thus supports the use of R. muricatus in traditional medicine for conditions associated with inflammation and analgesia which might be attributed to its previously proven high alkaloid, flavonoids, phenol, tannins content and free radical scavenging activity.

Study on vascular mechanisms underlying the hypotensive effect of Sorghum halepense (L.) Pers.

Sorghum halepense L (Poaceae), ordinarily it is known as Johnson grass and locally as baru. This study was designed to find the vascular mechanisms underlying the hypotensive activity of S. halepense. In this study, effect of S. halepense seed extract/fractions on various blood pressure parameters were evaluated in normal and fructose induced hypertensive rats by invasive technique. Possible underlying hypotensive mechanism of active fraction was determined by using various pharmacological inhibitors. S. halepense extract/fractions vasorelaxant effect were also evaluated on rat aorta rings in organ bath and various intracellular signaling pathway inhibitors were used for determination of underlying mechanisms. S. halepense extract/fractions produced blood pressure lowering effect with most significant effect by its aqueous soluble fraction at dose of 10mg/kg. This effect was attenuated by pretreatment of atropine. Aqueous soluble fraction produced endothelium dependent vasorelaxation in rat aortic rings that was inhibited by pretreatment of atropine after phenylephrine induced contraction. The vasorelaxant effect of aqueous soluble fraction was attenuated by potassium channel blockers and also produced inhibitory effect on calcium entry through calcium channels. It also suppressed phenylephrine induced contraction like verapamil. By HPLC analysis found vanillic acid and naringinin in it. In conclusion, aqueous soluble fraction of S.halepense possess phytoconstituents which may be responsible for hypotensive and vasorelaxant effect of Sorghum halepense.