Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food ... more Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in...
Stress is a state that seriously disturbs psychological or physiological homeostasis of the body ... more Stress is a state that seriously disturbs psychological or physiological homeostasis of the body and subsequently affects the morphology and function of the hippocampus. Currently available anti-stress medications provide limited benefits with cost of severe adverse effects. In the present study, effect of Rosa moschata extract was evaluated using acute restraint model in mice. The stress suppressant activity of Rosa moschata was evaluated by using elevated plus maze test (EPM), dark light box test and open field test (OFT) following restraint stress protocol. Results showed that the Rosa moschata extract significantly enhanced the number of transitions and the time spent in the open arm in the EPM, increased the number of transitions and time spent in the light compartment of the dark light box, and also enhanced the locomotor activity in OFT, as compared to the stress group. In addition, LD50 of the plant extract is greater than 5000mg/Kg. Thus the findings of our studies show tha...
Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin ... more Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits’ intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit’s aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as nega...
Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little... more Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10μg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5μg/mL and 1.11±0.2μg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3μM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.
The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro antich... more The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC50 values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.
Extract of Rosa moschata (RM) fruits was evaluated for the anti-schizophrenic and antidepressant ... more Extract of Rosa moschata (RM) fruits was evaluated for the anti-schizophrenic and antidepressant activities. We first determined the neurotoxic effect of hydro-methanolic extract of RM using inverted-screen test. Further, the extract was tested in the ketamine-induced schizophrenia model and its antidepressant effect was assessed by tail suspension and forced swim test in mice. Different doses of extract were administered once/day to the animals for 14 consecutive days. Behavioral parameters were investigated 24h after last administration of drug/extract by performing Y-maze test, forced swim test and open field test. Results showed that TD50 of the extract was ~1000mg/Kg. Moreover, extract significantly increased % alternations in YMT, reduced immobility time in FST and enhanced locomotion in OFT compared to saline group. Similarly, RM extract decreased time of immobility in FST and TST significantly showed antidepressant effect. Thus, it was concluded that extract of RM has antipsychotic and antidepressant properties.
Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory l... more Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inh...
Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic ... more Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequen...
Diarrhea is a major health problem and despite of interventions, it remains a substantial cause o... more Diarrhea is a major health problem and despite of interventions, it remains a substantial cause of mortality and morbidity. In this study, a flavonoids-rich Vitex negundo extract was mechanistically evaluated for its effectiveness in diarrheal diseases. The Vitex negundo ethanolic extract was subjected to extraction for isolation of total flavonoids and qualitative phytochemical analysis. The acute toxicity of flavonoids-extract was done in mice to assess its safety and tolerability. The anti-diarrhoeal activity was determined using the castor oil induced diarrhea mouse model at doses of 10, 30 and 100 mg/kg in relation to loperamide (10 mg/kg, oral). The antispasmodic profile was determined by using cut pieces of rabbit’s jejunum in Tyrode’s solutions, employing acetylcholine (0.03μM) as a tissue stabilizer and verapamil, as a calcium channel blocker. The preliminary qualitative analysis of extract revealed different phytochemicals, in addition to flavonoids. The acute toxicity pro...
OBJECTIVES: To isolate total flavonoids from Achillea Wilhelmsii andTeucrium Stocksianum and scre... more OBJECTIVES: To isolate total flavonoids from Achillea Wilhelmsii andTeucrium Stocksianum and screen them for possible analgesic activityand to determine the safe dose range of total flavonoids for preclinicalstudies in mice.METHODS: Acute toxicity studies were performed in mice to determineits safe dose range for total flavonoids of Achillea wilhelmsii and Teucriumstocksianum. Writhing tests were performed in mice for possibleanalgesic activity. Tail immersion method was used in rats for possibleanalgesic activity.RESULTS: Respective LD50 for crude flavonoids of Achillea wilhelmsii(CFA) and crude flavonoids of Teucrium stocksianum (CFT) are1312±12.76 mg/kg and 1248 ±29.6 mg/kg. In acetic acid inducedwrithing, analgesic effect of CFA and CFT in dose 10 mg/kg is almostcomparable with standard acetylsalicylic acid (p≤0.05). Similarly, in tailimmersion method, reaction time was significantly prolonged in testdoses of 5 and 10 mg/kg (both for CFA and CFT) suggesting supraspinalanalgesic ...
Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentr... more Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have signif...
Background and Objectives: We have recently reported that stains have calcium channel blocking ac... more Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits’ aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hy...
Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food ... more Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in...
Stress is a state that seriously disturbs psychological or physiological homeostasis of the body ... more Stress is a state that seriously disturbs psychological or physiological homeostasis of the body and subsequently affects the morphology and function of the hippocampus. Currently available anti-stress medications provide limited benefits with cost of severe adverse effects. In the present study, effect of Rosa moschata extract was evaluated using acute restraint model in mice. The stress suppressant activity of Rosa moschata was evaluated by using elevated plus maze test (EPM), dark light box test and open field test (OFT) following restraint stress protocol. Results showed that the Rosa moschata extract significantly enhanced the number of transitions and the time spent in the open arm in the EPM, increased the number of transitions and time spent in the light compartment of the dark light box, and also enhanced the locomotor activity in OFT, as compared to the stress group. In addition, LD50 of the plant extract is greater than 5000mg/Kg. Thus the findings of our studies show tha...
Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin ... more Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits’ intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit’s aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as nega...
Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little... more Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10μg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5μg/mL and 1.11±0.2μg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3μM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.
The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro antich... more The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC50 values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.
Extract of Rosa moschata (RM) fruits was evaluated for the anti-schizophrenic and antidepressant ... more Extract of Rosa moschata (RM) fruits was evaluated for the anti-schizophrenic and antidepressant activities. We first determined the neurotoxic effect of hydro-methanolic extract of RM using inverted-screen test. Further, the extract was tested in the ketamine-induced schizophrenia model and its antidepressant effect was assessed by tail suspension and forced swim test in mice. Different doses of extract were administered once/day to the animals for 14 consecutive days. Behavioral parameters were investigated 24h after last administration of drug/extract by performing Y-maze test, forced swim test and open field test. Results showed that TD50 of the extract was ~1000mg/Kg. Moreover, extract significantly increased % alternations in YMT, reduced immobility time in FST and enhanced locomotion in OFT compared to saline group. Similarly, RM extract decreased time of immobility in FST and TST significantly showed antidepressant effect. Thus, it was concluded that extract of RM has antipsychotic and antidepressant properties.
Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory l... more Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inh...
Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic ... more Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequen...
Diarrhea is a major health problem and despite of interventions, it remains a substantial cause o... more Diarrhea is a major health problem and despite of interventions, it remains a substantial cause of mortality and morbidity. In this study, a flavonoids-rich Vitex negundo extract was mechanistically evaluated for its effectiveness in diarrheal diseases. The Vitex negundo ethanolic extract was subjected to extraction for isolation of total flavonoids and qualitative phytochemical analysis. The acute toxicity of flavonoids-extract was done in mice to assess its safety and tolerability. The anti-diarrhoeal activity was determined using the castor oil induced diarrhea mouse model at doses of 10, 30 and 100 mg/kg in relation to loperamide (10 mg/kg, oral). The antispasmodic profile was determined by using cut pieces of rabbit’s jejunum in Tyrode’s solutions, employing acetylcholine (0.03μM) as a tissue stabilizer and verapamil, as a calcium channel blocker. The preliminary qualitative analysis of extract revealed different phytochemicals, in addition to flavonoids. The acute toxicity pro...
OBJECTIVES: To isolate total flavonoids from Achillea Wilhelmsii andTeucrium Stocksianum and scre... more OBJECTIVES: To isolate total flavonoids from Achillea Wilhelmsii andTeucrium Stocksianum and screen them for possible analgesic activityand to determine the safe dose range of total flavonoids for preclinicalstudies in mice.METHODS: Acute toxicity studies were performed in mice to determineits safe dose range for total flavonoids of Achillea wilhelmsii and Teucriumstocksianum. Writhing tests were performed in mice for possibleanalgesic activity. Tail immersion method was used in rats for possibleanalgesic activity.RESULTS: Respective LD50 for crude flavonoids of Achillea wilhelmsii(CFA) and crude flavonoids of Teucrium stocksianum (CFT) are1312±12.76 mg/kg and 1248 ±29.6 mg/kg. In acetic acid inducedwrithing, analgesic effect of CFA and CFT in dose 10 mg/kg is almostcomparable with standard acetylsalicylic acid (p≤0.05). Similarly, in tailimmersion method, reaction time was significantly prolonged in testdoses of 5 and 10 mg/kg (both for CFA and CFT) suggesting supraspinalanalgesic ...
Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentr... more Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have signif...
Background and Objectives: We have recently reported that stains have calcium channel blocking ac... more Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits’ aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hy...
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