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Pharmacological Relevance: Caesalpinia pulcherrima L. is used in Indian Traditional Medicinal system to treat Diabetes., Aim: This study was carried out to evaluate the standardized alcoholic extract of Caesalpinia pulcherrima seed (CPS) in Streptozotocin (STZ)-induced diabetic neuropathic and cardiac complications in rodents., Materials and Methods: HPLC finger printing profile of CPS was performed to identify the bioactive molecules. Two doses of CPS (100 & 200 mg/kg b.w.) was orally administered daily once for six weeks to streptozotocin (50 mg/kg, i.v.)-induced diabetic rats. Every week intervals hot & cold immersion tests were carried to know the effect of CPS on peripheral neuropathy. In addition, blood glucose, body weight, food and water intake were also monitored. At the end of the study, sciatic nerve conduction velocity, diabetic cardiomyopathy and diabetic cognitive parameters were evaluated. Furthermore, histopathological studies of sciatic nerve and aortic strip were also carried out., Results: HPLC finger print experiment showed the presence of gallic acid and protocatechuic acid. Administration of CPS for six weeks significantly prevented the development of diabetic peripheral neuropathy (DPN), cardiomyopathy and cognitive dysfunction in diabetic rats. The CPS treated rats displayed prominent (P < 0.001) improvement in motor coordination, muscle grip, locomotor activity and memory in diabetic rats. CPS treatment restored elevated systolic, diastolic, mean arterial blood pressure (MABP), and heart rate to near normal in diabetic condition. These observed beneficial effects were well correlated and justified with histopathological studies. In addition, CPS treatment also exhibited significant (P < 0.001) reduction of loss in body weight, and reduce the water and feed intake throughout the study., Conclusion: Taken together, the present study provided a good insight in the therapeutic efficacy of Caesalpinia pulcherrima seed extract in dealing with diabetic complications. The study also scientifically justifies the ethnomedicinal/traditional claims of the title plant., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To develop and validate a rapid, accurate, economical, effective and greenery RP-HPLC method for the determination of Zolmitriptan in tablet dosage form., Material and Method: RP-HPLC method was developed using Luna (C 18 ) (4.6×250mm, 5μm) column and Sodium phosphate buffer (pH 4.7): Methanol [75: 25, v/v] was used as mobile phase at a flow rate of 1.0mL/min. The detection was carried out at 227nm. Further, eco-friendliness, productivity and performance of the optimized analytical method were assessed by green and white tools., Results: The retention time of Zolmitriptan was found to be 3.25min with acceptable chromatographic parameters. The optimized RP-HPLC method was more eco-friendly, efficient, throughput and practicable than the reported methods as confirmed by AES, AGREE, GAPI and RGB tools. Further, the proposed analytical method showed all the validation parameters within the acceptance limit of ICH Q 2 R 1 guidelines. The linear regression analysis indicated a good linear response in the 10 to 120μg/mL concentration range with R 2 of 0.99998. The percentage content and percentage assay of Zolmitriptan in Zomig-5mg tablet was found to be 103.36±0.356% and 97.86±0.693%., Conclusion: The developed and validated method has several advantages compared to the reported HPLC methods and is useful in the systematic analysis of Zolmitriptan in its dosage form., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Brain damage is a severe and common pathology that leads to life-threatening diseases. Despite development in the research, the medical evidence of the effectiveness of potential neuroprotective medicines is insufficient. As a result, there is an immense and urgent demand for promising medication. For millennia, herbal remedies were a fundamental aspect of medical treatments. Combretum micranthum (CM), a plant of the family Combretaceae in sub-Saharan Africa, has been utilized in folklore medicine to cure diverse human ailments. In order to develop a neuroprotective phytomedicine, the current research was undertaken to explore the antioxidant, anti-inflammatory, anticholinesterase and neuroprotective potential of CM extract ., Methods: Colorimetric methods were used to determine CM antioxidant activity, in-vitro protein denaturation and membrane destabilization assays were used to evaluate its anti-inflammatory capacity, anticholinesterase activity was carried out using Ellman's method, and neuroprotective potential was assessed on brain homogenate stressed with ferric chloride and ascorbic acid (FeCl 2 -AA) by assessing the lipoperoxidation biomarker malondialdehyde (MDA)., Results: In Ferric Reducing Antioxidant Power (IC 50 = 27.15 ± 0.06 µg/mL) and Total Antioxidant Capacity (IC 50 = 31.13 ± 0.02 µg/mL), CM extract demonstrated strong antioxidant activity. Anti-inflammatory effect were improved in heat-induced Egg albumin and BSA denaturation (IC 50 = 46.35 ± 1.53 and 23.94 ± 1.10 µg/mL) as well as heat and hypotonia induced membrane destabilization (IC 50 = 20.96 ± 0.11 and 16.75 ± 0.94 µg/mL).CM extract showed strong anticholinesterase activity (IC 50 = 59.85 ± 0.91 µg/mL). In an ex-vivo neuroprotective model, CM extract showed substantial inhibition (p < 0.001) of oxidative damage caused by FeCl 2 -AA in brain tissue., Conclusion: C. micranthum may be a good candidate for its probable neuroprotective potential. Its neuroprotective benefits might be attributed to its antioxidant, anti-inflammatory and anticholinesterase effects., (© 2022 The Authors.)

Ethnopharmacological Relevance: Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders., Aim of the Study: To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ., Material and Methods: Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg 2+ ), calcium (Ca 2+ ), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1 C ) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed., Results: At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein., Conclusions: Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inflammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported., Aim of the Study: The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats., Materials and Methods: During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds., Results: The absence of absorbance peaks between the 2220-2260 cm -1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations., Conclusion: The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD 50 ) of the extract was estimated to be more than 5000 mg/kg., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Nephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (HEK)-293 cells and in-vivo experiments. Further, in-silico molecular docking and dynamic experiments were carried out with bioactive compounds of the title plant against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Incubation of HEK-293 cells with cisplatin resulted in a significant increase in cell death with changes in normal cellular morphology. Co-treatment of HEK-293 cells with CP and CM extract at varying concentrations resulted in significant enhancement of cell growth compared to CP treatment indicating the cytoprotective activity of CM with an EC 50 8.136 μg/mL. In vivo nephroprotective activity was evaluated by administering CM (200 and 400 mg/kg, p.o) to rats for 10 days followed by single intraperitonial injection of CP (7.5 mg/kg) on the 5th day of the experiment. Nephrotoxicity induced by CP was apparent by elevated levels of serum and urine kidney function markers, transaminases, oxidative stress markers and histopathological alterations in kidney. Pre-treatment with CM normalized the renal function at both the doses by ameliorating the CP-induced renal damage markers, oxidative stress and histopathological variations. In-silico studies showed that, out of the thirty bioactive compounds, isovitexin and gallic acid exhibited a higher docking score of -22.467, -21.167 kcal/mol against NF-κB. Cianidanol and epicatechin exhibited a higher docking score of -14.234, -14.209 kcal/mol against sEH. The protective effect of CM extract in CP-induced nephrotoxicity might be attributed to its antioxidant, anti-inflammatory activity by inhibiting NF-κB and sEH upregulation., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Management of chronic renal failure is exceedingly expensive. Despite of encouraging experimental outcomes, there is a lack of potent nephroprotective drugable molecules in a clinics or market. To develop a nephroprotective phytomedicine, the present study was designed to do a literature survey on reported phytochemical and biological analysis of Combretum micranthum and to carry out chemoprofiling, in-vitro antioxidant and ex-vivo nephroprotective capacity of the title plant. The phytochemical and biological activity survey of C. micranthum has reveals the presence of many bioactive compounds such as flavonoids, terpenoids, steroids and alkaloids with many biological activities. Phytochemical investigation re-confirmed the presence of these compounds. Hydroalcoholic extract of C. micranthum (CM extract) showed a strong antioxidant activity by scavenging AAPH, DPPH, nitric oxide, hydrogen peroxide and chelating metal ions. CM extract exhibited significant ( P < 0.001) dose dependent inhibition of ferric chloride-ascorbic acid induced lipid peroxidation. Diabetic nephropathy is a serious and common complication leading to end stage renal disease. Therefore, in the present study, glucose-induced toxicity was also studied in human embryonic kidney cells (HEK-293) as an in vitro model for diabetic nephropathy. The results showed that exposure of cells to high glucose (100 mM) for 72 h significantly reduced the cell viability resulting in morphological changes such as cell shrinkage, rounded cell shape and cytoplasmic vacuolation. Treatment with CM extract at 10 and 25 μg/mL resulted in significant improvement in cell viability from 10 to 23% compared to the high glucose control. This study demonstrated the potential antioxidant and nephroprotective properties of C. micranthum , justifying its traditional use in the treatment of various diseases.

The present study aimed to evaluate the protective effect of fresh fruit juice of Opuntia dillenii Haw. (FJOD) on acetic acid-induced ulcerative colitis in rats. Fresh FJOD (2.5 and 5 ml/kg) and sulfasalazine (100 mg/kg) were given orally for seven consecutive days prior to colitis induction on the eighth day by intrarectal acetic acid (4% v/v) administration. Macroscopic, clinical activity scoring, biochemical, and histopathological examinations of colon were used to assess colonic damage. FJOD and sulfasalazine treatment significantly attenuated the macroscopic damage, clinical activity score, and wet weight of the colon when compared to disease control and further showed significantly reduced levels of myeloperoxidase, malondialdehyde, and serum lactate dehydrogenase and enhanced colonic levels of reduced glutathione. The protective effect of FJOD may be attributed to its antioxidant and anti-inflammatory activities in ulcerative colitis. The observed effects may be due to the presence of phenolics, flavonoids, and betalains in the fruit juice of Opuntia dillenii .

Sickness behaviour, fever, anxiety, anorexia and depression are interrelated phenomena. The citrus fruit peels offering significant low-cost nutritional dietary supplements due to its rejuvenating biological activities. The present study was undertaken to explore the beneficial effect of enriched phenolic fraction of peel (PFMC) in lipopolysaccharide (LPS)-induced sickness behaviour and anorexia in mice. Further, the HPTLC estimation of hesperidin, total phenolic and flavonoid content in PFMC were carried out. In silico molecular docking and dynamic studies of bioactive compounds against NF-κB (1NFK) were also performed. The amount of hesperidin was found to be 55.33 mg/g of PFCM as per the proposed HPTLC method. Total phenolic and flavonoid content was found to be 71 mg of gallic acid/g and 58.1 mg of quercetin/g of PFCM. The single dose of LPS (400 μg/kg, i.p) treatment exhibited significant reduction in food, water intake and behavioural tests and tissue GSH, whereas significantly higher levels of tissue LPO and plasma IL-6 levels compared to normal control. Pre-treatment of PFCM (100 and 200 mg/kg, i.p) and dexamethasone (1 mg/kg, i.p) showed significantly altered the LPS-induced behavioural, anorexia and biochemical parameters. The bioactive compounds such as hesperidin, naringenine, naringin and dexamethasone showed docking score of -22.49, -21.99, -16.43 and -11.12 respectively against NF-κB (1NFK). Among tested bioactive compounds, naringin clearly exhibited higher inhibiting property on target protein structure. The protective effect of PFCM in LPS-induced anorexia and sickness behaviour is due to its antioxidant, anti-inflammatory and appetizing activities, inhibiting IL-6 and NF-κB., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Embelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats., Methods: Two doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine. On the concluding day of pre-treatment, after apomorphine-injection, the rodents were assessed for climbing and stereotyped behaviours according to the published scoring system. Thereafter, neurotransmitters (dopamine, noradrenaline and serotonin) levels were estimated in rodent brains., Results: Embelin pre-treatment significantly inhibited apomorphine-induced climbing and stereotyped behaviours in mice and rats, respectively. Further, embelin also statistically reversed elevated levels of dopamine, noradrenaline and serotonin neurotransmitters in the brain of mice and rats. Embelin showed more significant results at high dose (10mg/kg) than low dose (5mg/kg) in both the tested models., Conclusion: Considering the present pharmacological profile of embelin, it is suggested that embelin possesses antipsychotic activity in the treatment of psychotic disorders. However, further research is warranted for evaluating its exact mechanism of action., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Present study was designed to evaluate the effect of chromium-d-phenylalanine complex (Cr (d-phe) 3 ) on indomethacin-induced inflammatory bowel disease (IBD) in rats. Adult Wistar rats were pretreated with vehicle/Cr (d-phe) 3 (30, 60 and 90μg/kg, p.o.) for 11days. On day 8 and 9, after one h of the above mentioned treatment, indomethacin (7.5mg/kg/day,s.c.) was administered to induce IBD. On day 12, blood samples were collected from animals for lactate dehydrogenase (LDH) estimation and ileum was isolated for macroscopic scoring, biochemical estimation (lipid peroxidation, reduced glutathione and myeloperoxidase activity) and histopathological study. Administration of indomethacin significantly altered the serum LDH, macroscopic and microscopic appearance and biochemical parameters in ileum tissue. Cr (d-phe) 3 , at all the tested doses, caused a significant reversal of changes induced by indomethacin. Present study demonstrates the protective effect of Cr (d-phe) 3 against indomethacin-induced IBD in rats. The observed protective effect might be attributed to the antioxidant and anti-inflammatory properties of Cr (d-phe) 3 ., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Traditionally Cassia glauca (CG) has been used to treat diabetes., Aim of the Study: The study was undertaken to evaluate anti-diabetic and antioxidant activity of polyphenolic enriched extract of CG in standardized streptozotocin (STZ)-induced diabetic rats., Materials and Methods: The effect of ethanol (CGE) and water (CGW) extracts of CG (200 and 400mg/kg) treatment were evaluated in STZ (50mg/kg, iv) induced diabetic rats. On 10 th day, oral glucose tolerance test and degree of insulin resistance was calculated. On 13 th day, insulin tolerance test was performed to know the peripheral utilization of glucose. On 15 th day, blood glucose, lipid profiles and endogenous antioxidant levels were estimated. In addition, the effects on oral glucose/sucrose tolerance test in normal rats. Further, HPLC fingerprinting profile of CGE and simultaneous quantification of biomarkers were carried out., Results: Supplementation with CGE and CGW significantly reduced STZ-induced deleterious effects and improved glucose tolerance, and insulin tolerance. In addition, supplementation also decreased oxidative stress by improving endogenous antioxidant levels. Furthermore, administration significantly improves sucrose tolerance suggesting that extract possess inhibition of α-glucosidase enzyme. Further, HPLC studies revealed that CGE contains three bioactive polyphenolic compounds viz., rutin (0.10±0.01mg/g), luteolin-7-glucoside (0.06±0.01mg/g) and isorhoifolin (0.7±0.05mg/g)., Conclusion: Observed beneficial outcome of CG might be attributed to the presence of polyphenolic compounds and mediated by interacting with multiple targets of diabetes and oxidative stress. Taken together, this study provided the scientific evidence for the traditional use of CG., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Embelia ribes (ER) has been documented in Ayurveda for treating various diseases, including diabetes mellitus (DM). The present systematic review and meta-analysis evaluated the efficacy and safety of ER and its active bio-marker, embelin and its derivatives in the treatment of DM. Literature search was performed in PubMed/MEDLINE, EMBASE, Scopus, ScienceDirect, Scifinder, and Google Scholar. Using Review Manager, meta-analysis of ER/embelin/derivatives of embelin versus diabetic control was performed with inverse-variance model, providing mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was determined by I 2 statistic. A total of 13 studies were included in the systematic review and meta-analysis, and were conducted in experimental rats. ER and embelin significantly (P≤0.01) resorted blood glucose (MD, -231.30; CI, -256.79, -205.82; and MD, -154.70; CI, -168.65, -140.74) and glycosylated haemoglobin (MD, -6.36; CI, -8.33, -4.39; and MD,-4.68; CI, -7.76, -1.60), respectively. Meta-analysis findings also reported considerable restoration of insulin, lipid profile, haemodynamic parameters, serum and oxidative stress markers. The derivatives of embelin, 6-bromoembelin and vilangin, also improved diabetic condition. In addition, treatments also ameliorated body weight changes due to diabetes. The present systematic review and meta-analysis supports scientific evidence for the antidiabetic activity of ER/embelin/derivatives of embelin. However, further research is warranted in clinical trials to validate the present findings., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Sickness behaviour is a coordinated set of adaptive behavioural changes that develop in ill individuals during the course of an infection. It is relevant to understanding depression and some aspects of the suffering that in cancer. Embelin has been reported to possess antiinflammatory, neuroprotective and anxiolytic assets and has been shown to inhibit nuclear factor κB pathway and cytokine production. The present study was undertaken to investigate the effect of embelin isolated from Embelia ribes Burm in lipopolysaccharide (LPS)-induced sickness behaviour in mice. Adult male Swiss albino mice were pre-treated with embelin (10 and 20 mg/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) for 3 days and then challenged with LPS (400 µg/kg, i.p.). At different time intervals of post-LPS challenge, sickness behaviour was evaluated in the animals by battery of behavioural tests (plus maze, open field, light-dark box, forced swim, social behaviour assessment, sucrose preference and food and water intake). Levels of oxidative stress makers (reduced glutathione and lipid peroxidation) in mice brain were also analysed. LPS induced behavioural alterations, anhedonia and anorexia, in mice. Pre-treatment with embelin attenuated behavioural changes induced by LPS. In addition, embelin prevented anhedonia, anorexia and ameliorated brain oxidative stress markers. The experimental outcomes of the present study demonstrated protective effect of embelin in LPS-induced sickness behaviour in mice. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

3-Nitropropionic acid (3-NP) causes severe neurotoxicity in animals, which depicts Huntington's disease (HD) in humans. Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, mainly anti-inflammatory, antioxidant, anticonvulsant and neuroprotective. The aim of the present study was to evaluate the neuroprotective effect of embelin against 3-NP induced experimental HD in rats. Adult Wistar rats were pretreated with vehicle/embelin (10 and 20mg/kg p.o.) for 7 days. From 8th day onwards, embelin was co-treated with 3-NP (15mg/kg, i.p.) for 7 days. At the end of the treatment schedule, animals were evaluated for behavioral alterations and brain homogenates were used for estimation of oxidative stress parameters (lipid peroxidation, reduced glutathione, catalase and glutathione-S-transferase). 2,3,5-Triphenyl tetrazolium chloride (TTC) stained brain slices were used for lesion size measurement. Administration of 3-NP significantly altered the behavioral and neuronal antioxidant status and caused significant neuronal damage in striatal region. Embelin, at both the tested doses, caused a significant reversal of behavioral and antioxidant status alterations and reversed the striatal neuronal damage induced by 3-NP. These findings suggest the neuroprotective effect of embelin against HD. The observed protective effect might be attributed to the antioxidant properties of embelin., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Traditionally Blumea lacera DC is used to treat inflammation and bowel ailments. Lack of specific, curative treatment for IBD enticed us to investigate the therapeutic efficacy of ethanolic extract of aerial parts of Blumea lacera DC (EEBL) against indomethacin-induced enterocolitis. Male Wistar rats were divided into six groups (n = 5) and different doses of EEBL (100 and 200 mg/kg, p.o) and sulphasalazine (100 mg/kg, p.o) were administered for seven days. Enterocolitis was induced by two subsequent doses of indomethacin (7.5 mg/kg, s.c) on 7th and 8th day. Treatments were continued up to 12th day and sacrificed. The protective effect was assessed on the basis of macroscopic scores of ileum strips, changes in biochemical parameters such as serum lactate dehydrogenase (LDH), tissue myeloperoxidase (MPO), lipid peroxidation (LPO), and total thiols (TT). Further, activity was ascertained by histopathological evaluations. HPLC fingerprinting profiling of EEBL was also carried out. Pre-treatment with EEBL or sulphasalazine significantly attenuated the indomethacin-induced proximal ileal damage, elevated levels of serum LDH, tissue MPO, LPO and lower levels of TT. Further, observed activity of EEBL was well correlated with histopathological alterations. The results revealed the protective action of the title plant against the indomethacin-induced enterocolitis in rats, which might be attributed by its antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing properties.

Background: Śilājatu (Shilajit; SJ) is claimed in traditional Indian medical practice to be useful in the treatment of nervous disorders, epilepsy and as antistress., Aim: To investigate whether SJ possesses antiepileptic and antipsychotic activities in rodents., Materials and Methods: Isonicotinyl hydrazine (INH), pentylenetetrazole (PTZ), apomorphine, phenytoin, diazepam, haloperidol and other chemicals of analytical grade were procured from standard companies. The antiepileptic activity of SJ was assessed using maximal electro shock (MES)-induced seizures in rats, INH and PTZ-induced seizures in mice. The antipsychotic effect of SJ was evaluated using apomorphine-induced climbing and stereotyped behaviours respectively, in mice and rats., Settings and Designs: SJ (25 and 50 mg/kg, p.o.) was given orally once daily for 15 days in all the rodent models. On the test day, SJ was administered 1 h prior to electric shock or chemical inducers (INH/PTZ/apomorphine) in experimental animals; the animals were then observed for different phases of seizures and psychotic behaviours. In addition, gamma-aminobutyric acid (GABA) content in the brain of rats and mice was estimated in seizure models., Statistical Analysis: The data were expressed as mean ± standard error of mean. Statistical comparisons were performed by one-way ANOVA followed by Tukey's post-test using Graph Pad Prism version 5.0, USA. A P < 0.05 was considered significant., Results and Conclusions: SJ pretreatment significantly inhibited the seizures induced by MES, INH and PTZ in a dose dependent manner. Further, SJ augmented brain GABA levels to normal, decreased by INH and PTZ in mice brain. SJ pretreatment also significantly inhibited the climbing and stereotyped behaviours induced by apomorphine. The present data seems to confirm the antiepileptic activity of SJ which may be because of enhancing the GABAergic system. The antipsychotic activity observed may be due to anti-dopaminergic and/or GABA-mimetic actions.

A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4-oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4thh, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC50 values., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

Monosodium glutamate (MSG) is a popular flavour enhancer used in food industries; however, excess MSG is neurotoxic. Oxidative stress is well documented in MSG induced neurotoxicity. The compounds having antioxidant and anti-inflammatory properties reportedly possess beneficial effects against various neurotoxic insults. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant and anti-inflammatory activities. Hence, this present study has been designed to evaluate the neuroprotective effect of COE on MSG-induced neurotoxicity in rats. Adult Wistar rats were administered systemically for 7 days with MSG and after one h of MSG injection, rats were treated with COE (100 and 200 mg/kg) orally. At the end the treatment period, animals were assessed for locomotor activity and were sacrificed; brains were isolated for estimation of LPO, GSH, CAT, TT, GST, Nitrite and histopathological studies. MSG caused a significant alteration in animal behavior, oxidative defense (raised levels of LPO, nitrite concentration, depletion of antioxidant levels) and hippocampal neuronal histology. Treatment with COE significantly attenuated behavioral alterations, oxidative stress, and hippocampal damage in MSG-treated animals. Hence, this study demonstrates that COE protects against MSG-induced neurotoxicity in rats. The antioxidant and anti-inflammatory properties of COE may be responsible for its observed neuroprotective action.

Ethnopharmacological Relevance: Chromolaena odorata Linn., is used in traditional Indian medicine in the treatment of diabetes and eye problems., Aim of the Study: The present study was designed to investigate the effect of the ethanol extract Chromolaena odorata leaves (ACO) in streptozotocin (STZ; 45 mg/kg, i.v) induced diabetes and cataract in rats., Materials and Methods: Different doses of ACO (200 and 400mg/kg) was administered once daily for eight weeks to STZ-induced diabetic rats. To know the mechanism of action of title plant, AUC(glucose), AUC(insulin), Homeostatic Model Assessment (HOMA), insulin tolerance test (ITT) and glucose uptake by rat hemi-diaphragms were carried out. Further, cataract score was taken once in a week upto eight weeks and opacity index was measured. HPLC fingerprinting profiling of ACO was also carried out., Results: Administration of ACO exhibited significant reduction in glucose, HOMA, lipid profiles and significantly improved glucose and insulin tolerance, glycogen content, glucose uptake by skeletal muscle, serum insulin and HDL-c levels. In addition, ACO also decreased oxidative stress by improving endogenous antioxidants. Further, treatment of ACO showed significantly reduced onset and extent of cataract., Conclusion: The present data suggested that the treatment of ACO reversed the STZ-induced diabetes and cataract in rats. The observed beneficial effects may be mediated by interacting with multiple targets operating in diabetes mellitus and its complication. Taken together, this study provided the scientific evidence for the traditional use of Chromolaena odorata., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Context: Leptadenia reticulata Linn. (Asclpiadaceae) commonly known as "dodi," is an Indian medicinal plant which is known to have ethno-medical uses such as stimulant, tonic, immunostimulant and is one of the ingredient in ayurvedic formulation called as "Chawanprash," which is widely used in India to increase the strength of immune system., Objective: The aim of present study is to evaluate immunomodulatory and antioxidant activity of ethanolic extract of L. reticulata L. leaves in rodents., Methods: Haemagglutinating antibody (HA) titre, haematological profile (Hb, WBC, RBC), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), delayed type of hypersensitivity (DTH) response, neutrophil adhesion test and carbon clearance assay were determined by in vivo experiments., Results: The evaluation of immunomodulatory potential of L. reticulata (100, 200 mg/kg, p.o.) evoked a significant dose-dependent increase in antibody titre values; DTH reaction induced by SRBC and potentiated percentage neutrophil adhesion to nylon fibers as well as phagocytosis in carbon clearance assay. Also it caused significant increase in haematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed rats., Conclusion: The results obtained in this study indicate that L. reticulata possesses potential immunomodulatory and antioxidant activity and can play a major role in reducing the risk to develop immunodeficiency disorders.

N-methyl-D-aspartate (NMDA) antagonists and γ-aminobutyric acid (GABA) agonists are proven protective in various animal models of ischemic brain damage. Tramadol, a centrally acting opioid analgesic reportedly possesses NMDA antagonistic and GABA agonistic properties, with additional ion channel blocking activity. The aim of the present study was to evaluate the possible neuroprotective effect of tramadol hydrochloride in a rat model of transient forebrain ischemia. Male Wistar rats were pretreated with tramadol hydrochloride at doses of 10 and 20 mg/kg b.w. intraperitoneally for 4 days and were subjected to 30 min occlusion of bilateral common carotid arteries followed by reperfusion for 24 h. Impairment in sensorimotor functions was evaluated by beam walking task, spontaneous locomotor activity and hanging wire test. Animals were sacrificed and the brain homogenates were used for estimating the levels of lipid peroxidation, a marker for extent of oxidative stress. Ischemic rats exhibited a significant decrease in locomotion, grip strength and increase in beam walking latency. Tramadol attenuated the post ischemic motor impairment evidenced by improvement in the performance in sensorimotor tests. The extent of lipid peroxidation was significantly (p < 0.001) reduced by tramadol pretreatment which was higher in ischemic control. This study demonstrates the neuroprotective effect of tramadol against transient forebrain ischemia in rats.

The present study was designed to investigate the effects of the ethanol extract of Ficus racemosa (FRE) on biochemical parameters in type 2-like diabetes, induced by a combination of standardised high-fat diet and low-dose streptozotocin (25mgkg(-1), i.p.) in rats. To elucidate the mode of action of FRE, its effects on a battery of targets involved in glucose homeostasis was evaluated. FRE (200 and 400mgkg(-1), p.o.), in a dose-dependent manner, altered the biochemical parameters and significantly improved glucose tolerance and HDL-c levels. In different bioassays, FRE showed inhibition of PTP-1B (IC50 12.1μg/mL) and DPP-IV (42.5%). FRE exhibited 82.6% binding to PPAR-γ. Furthermore FRE exhibited stimulation of glucose uptake by skeletal muscles (hemi-diaphragm). Bergenin was quantified in bioactive-FRE by high-performance liquid chromatography (0.15%w/w). This is the first report demonstrating the effectiveness of F. racemosa stem bark in type 2 diabetes and targets involved in it., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: In the traditional Indian and Thai system of medicine, Mimusops elengi Linn., flower is used as brain tonic and to calm anxiety and panic attacks., Aim of the Study: The present study was designed to investigate the neuroprotective effect of hydroalcoholic extract of Mimusops elengi (ME) against cerebral ischemic reperfusion injury in rats., Materials and Methods: Male rats were pretreated with ME (100 and 200mg/kg) for seven days and focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) method. After 60min of MCAO and 24h of reperfusion, a battery of behavioral tests assessed the extent of neurological deficits. Infarct volume and brain edema were measured in TTC stained brain sections and the extent of blood brain barrier (BBB) disruption was observed by Evan's blue extravasation. Oxidative and nitrative stress parameters were estimated in the brain homogenates. Further, simultaneous quantification of five polyphenolic biomarkers were done using HPLC., Results: Pretreatment with ME at doses of 100 and 200mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema and extent of BBB disruption induced by ischemia reperfusion injury. It also prevented the alteration in the antioxidant status and reduced the nitrite levels when compared to ischemic animals. Further, HPLC studies revealed that ME contains five bioactive polyphenolic compounds., Conclusions: These results clearly indicate the neuroprotective effect of ME against stroke like injury. The observed protective effect might be attributed to the polyphenolic compounds and their antioxidant and anti-inflammatory property., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of whole plant of Amaranthus viridis (MEAV) in alloxan (ALX) induced diabetic rats. Diabetes was confirmed after 5 days of single intraperitoneal injection of ALX (140 mg/kg) in albino Wister rats. MEAV (200 and 400 mg/kg) and glibenclamide (10 mg/kg, p.o.) orally administered daily for 15 days, blood was withdrawn for glucose determination on 0, 1, 10 and 15 days respectively. On the 15th day, overnight fasted rats were sacrificed and blood was collected for the determination of high density lipoproteins cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), total glycerides (TG) and total proteins (TP). For in vivo antioxidant activity of MEAV, liver tissues were homogenized and the assay of lipid peroxidation and was measured as Malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and total thiols (TT) were performed in control, ALX and MEAV treated rats. MEAV at doses of 200 and 400 mg/kg showed significant reduction is blood glucose, lipid profiles and significant improvement in MDA, GSH, CAT and TT when compared to diabetic control group. In vitro α-amylase inhibition activity of MEAV was also studied. We concluded that MEAV possess antidiabetic, antihyperlipidemic and antioxidant activities., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Monosodium glutamate (MSG) is commonly used as a flavor enhancer in many countries. However, overconsumption of MSG has been reported to produce detrimental effects on several organs. It mainly affects the normal physiology and function of the brain and causes severe oxidative stress. Mimusops elengi Linn. traditionally is used in many countries as a brain tonic and to calm anxiety and panic attacks. The effect of standardized hydroalcoholic extract of M. elengi flowers (ME) was evaluated against MSG-induced oxidative stress and excitotoxicity in Wistar rats. Excitotoxicity was induced by intraperitoneal administration of MSG (2 g/kg) for 7 days, and ME (100 and 200 mg/kg) was administered for 3 days before and for 7 days with administration of MSG. Animals were evaluated for locomotor activity, and brain homogenates were estimated for the levels of antioxidants and nitrite. In animals treated with MSG, pretreatment with ME improved ambulatory behavior, reduced lipid peroxidation and nitrite levels, and restored the enzymatic and nonenzymatic antioxidant (glutathione, total thiols, glutathione-S-transferase and catalase) status to near-normal levels; these were altered in the MSG control animals. Altogether, this investigation demonstrates the neuroprotective effect of ME against excitotoxicity and oxidative stress induced by MSG, and the observed protective effect might be attributed to the potential antioxidant property of ME.

Objective: The aim of the present study was to evaluate the sedative and antiepileptic activities of ethanolic extract of Anthocephalus cadamba (ACE) bark in various experimental animal models., Materials and Methods: ACE was tested at three doses viz. 100, 200 and 400 mg/kg p.o. We used ketamine-induced sleeping time model to test the sedative property of the extract where, onset and duration of sleep were observed. A paradigm of anticonvulsant models (pentylenetetrazole, isoniazid and maximal electroshock-induced seizures) were used to evaluate its protective effect against absence and generalized types of seizures. Onset of clonic convulsions, tonic extension and time of death were observed in PTZ and INH-induced seizure models. In MES model, duration of tonic hind leg extension and onset of stupor were observed., Results: ACE showed significant increase in ketamine induced sleeping time. It also exhibited significant increase (P<0.05, 0.01 and 0.001) in latency to clonic convulsion, tonic extension and time of death in PTZ and INH models at all tested doses, whereas in the MES model, the lower dose was found to be effective when compared with the higher doses (200 and 400 mg/kg, p.o.)., Conclusion: The results of the present investigation demonstrated that ACE possesses sedative and antiepileptic activities.

Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30 min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50 mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.

The aim of the present study is to evaluate the effect of embelin isolated from Embelia ribes on acetic acid induced colitis in rats. Experimental animals received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100mg/kg, p.o.) for five consecutive days before induction of colitis by intra-rectal acetic acid (3% v/v) administration and the treatment continued up to 7 days. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Embelin treatment significantly decreased clinical activity score, gross lesion score, percent affected area and wet colon weight when compared to acetic acid induced controls. The treatment also reduced significantly the colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase and significantly increased the reduced glutathione. The histopathological studies also confirmed the foregoing findings. The protective effect may be due to its antioxidant and anti-inflammatory activities., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Methanol extract of whole plant of Amaranthus caudatus (MEAC) was screened for hepatoprotective potency against paracetamol (PCM)-induced liver damage in Wistar rats., Methods: Rats of five groups were given sodium carboxy methyl cellulose, PCM, MEAC (200 and 400 mg/kg, respectively) plus PCM, and silymarin plus PCM, respectively. Fourteen days after administration, blood samples were collected for biochemical estimation, then animals were sacrificed and liver samples were collected, weighed and subjected for histopathological studies. Liver marker enzymes such as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and serum albumin (ALB), total protein (TP), total bilirubin (TB) and direct bilirubin (DB) levels and the markers for oxidative defense namely malondialdehyde (MDA), reduced glutathione (GSH), total thiols (TT) and catalase (CAT) were measured., Results: MEAC at 200 and 400 mg/kg significantly normalized the PCM-induced biochemical changes compared with PCM-treated group (P<0.01); increased ALT, AST, TB and DB levels and decreased serum ALB were significantly reversed by the MEAC treatment (200 and 400 mg/kg). Treatment with MEAC (200 and 400 mg/kg) significantly prevented the rise of MDA and TP levels (P<0.01), and prevented the reduction of GSH, CAT and TT levels significantly compared with PCM-treated group (P<0.01). Histopathological examination of the liver sections also proved the hepatoprotective activity of MEAC., Conclusion: MEAC shows significant hepatoprotective activity against PCM-induced liver damage in rats. This finding supports the use of the plant in ethnomedicine for the treatment of liver diseases.

Anticonvulsant activity of embelin (2.5, 5 and 10mg/kg, i.p.) was studied. It showed a significant inhibition of the seizures induced by electroshock and pentylenetetrazole in a dose dependent manner and the activity was comparable to phenytoin and diazepam. Significant decrease in locomotion revealing its CNS depressant activity was observed. The findings suggest that embelin possess anticonvulsant activity against both grand mal and petit mal epilepsy., (2010 Elsevier GmbH. All rights reserved.)

Antioxidant and related properties of the plant Embelia ribes and embelin are well known. In the present study embelin was condensed with various aromatic substituted primary amines to yield ten new and one reported derivatives along with monomethyl embelin. All these compounds along with embelin were evaluated for in vitro antioxidant activity using 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and 2,2'-diphenyl-1-picryl hydrazyl (DPPH) methods. Two para-substituted embelin derivatives showed potent antioxidant activity. These compounds along with embelin were studied for analgesic and anti-inflammatory activities at 10 and 20 mg/kg doses by standard methods. Potent analgesic activity higher than the standard pentazocine was observed. Embelin and both of its derivatives almost completely abolished the acetic acid induced writhing. p-Sulfonylamine phenylamino derivative showed better anti-inflammatory activity than embelin.

Context: High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model for type 2 diabetes mellitus (T2DM) that would closely reflect the natural history and metabolic characteristics of human T2DM and is also suitable for pharmacological screening., Objective: The present study was designed to investigate the effect of the water extract (DVW) and the polar fraction of ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on biochemical parameters in type 2 diabetes induced by a standardized HFD and low dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action we evaluated its effects on a battery of targets involved in glucose homeostasis (in vitro studies)., Materials and Methods: Different doses of DVW and DVE-4 were administered once daily for two weeks to HFD + STZ diabetic rats. Quantification of biomarker quercetin was done using HPLC., Results and Discussion: Both DVW and DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model assessment (HOMA), lipid profiles, and significantly improved glucose tolerance and HDL-c levels. In addition, the extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different, bioassays, DVW and DVE-4 showed inhibition of PTP-1B and at a concentration of 10 μg/mL showed 60 and 54.2% binding to PPARγ, respectively. Both extract/fraction exhibited stimulation of glucose uptake by skeletal muscles., Conclusion: Taken together, these results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin resistance, lipid abnormalities and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.

To study the effect and mode of action of water extract (DVW) and polar fraction of ethanol extract (DVE-4) of D. viscosa in high-fructose diet induced insulin resistance in male Wistar rats. D. viscosa's effects were evaluated on a battery of targets involved in glucose homeostasis (in vitro studies). Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for six weeks. DVW and DVE4 at different doses were administered simultaneously. At the end of the study, blood glucose, oral glucose tolerance test, lipid profile and insulin were estimated and homeostatic model assessment (HOMA) levels were calculated. In addition, enzymatic and nonenzymatic liver antioxidant levels were also estimated. Quantification of biomarker quercetin was done using HPLC. Fructose diet with DVW, DVE-4 significantly reduced blood glucose, serum insulin, HOMA, lipid profiles and significantly improved glucose tolerance and HDL-c levels. In addition, these extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different bioassays, DVW and DVE-4 inhibited protein tyrosine phosphatase-1B with IC50 65.8 and 54.9 microg/ml respectively and showed partial inhibition of dipeptidyl peptidase-IV. Moreover, DVW and DVE-4, at 10 microg/ml showed 60 and 54.2% binding to peroxisome proliferator-activated receptor-gamma. Further, 2.1% (w/w) of quercetin was quantified in bioactive-DVE-4 using HPLC method. The results provide pharmacological evidence of D. viscosa in treatment of prediabetic conditions and these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity.

Ethanol extract (FRE) and water extract (FRW) of Ficus racemosa (family: Moraceae) were subjected to free radical scavenging both by steady state and time resolved methods such as nanosecond pulse radiolysis and stopped-flow spectrophotometric analyses. FRE exhibited significantly higher steady state antioxidant activity than FRW. FRE exhibited concentration dependent DPPH, ABTS(*-), hydroxyl radical and superoxide radical scavenging and inhibition of lipid peroxidation with IC(50) comparable with tested standard compounds. In vitro radioprotective potential of FRE was studied using micronucleus assay in irradiated Chinese hamster lung fibroblast cells (V79). Pretreatment with different doses of FRE 1h prior to 2 Gy gamma-radiation resulted in a significant (P < 0.001) decrease in the percentage of micronucleated binuclear V79 cells. Maximum radioprotection was observed at 20 mug/ml of FRE. The radioprotection was found to be significant (P < 0.01) when cells were treated with optimum dose of FRE (20 mug/ml) 1 h prior to 0.5, 1, 2, 3 and 4 Gy gamma-irradiation compared to the respective radiation controls. The cytokinesis-block proliferative index indicated that FRE does not alter radiation induced cell cycle delay. Based on all these results we conclude that the ethanol extract of F. racemosa acts as a potent antioxidant and a probable radioprotector.

The effect of mononuclear copper (II) complex of curcumin in 1:1 stoichiometry (hereafter referred to as complex) administered 30 min before gamma-irradiation (4.5 Gy) on alterations in antioxidant and Thiobarbituric acid reactive substances (TBARS) levels in livers was studied in comparison to curcumin at a dose of 50 mg/kg. The different antioxidants like GSH, GST, catalase, SOD, TBARS and total thiols were estimated in the liver homogenates excised at different time intervals (1, 2 and 4 h) post irradiation using colorimetric methods. There was a radiation-induced decrease in the levels of all the studied enzymes at 1 h post irradiation, while an increase was observed at later time points. Both curcumin and complex treatment in sham-irradiated mice decreased the levels of GSH and total thiols, whereas there was an increase in the levels of catalase, GST and SOD compared to normal control. Under the influence of irradiation, both curcumin and complex treatment protected the decline in the levels of GSH, GST, SOD, catalase and total thiols, and inhibited radiation-induced lipid peroxidation. Further, the complex was found to be more effective in protecting the enzymes at 1 h post irradiation compared to curcumin treated group. This may be due to the higher rate constants of the complex compared to curcumin for their reactions with various free radicals.

Anticlastogenic activity of morin was explored against whole body gamma radiation, at a dose rate of 1.66 Gy/min in Swiss albino mice pretreated intraperitoneal or orally. Pretreatment with morin 10, 25, 50, 75, 100, 125, and 150 mg/kg, i.p. delayed and reduced percentage mortality and increased mean survival times in mice irradiated with 10 Gy gamma radiation. Intraperitoneal route was found superior to oral route. An i.p. dose of 100 mg/kg was found to be the most effective dose in preventing radiation-induced weight loss, increasing the mean survival times and reducing percentage mortality. Morin (100 mg/kg) pretreatment effectively maintained spleen index (spleen weight/body weight x 100) and stimulated endogenous spleen colony forming units. Pretreatment with morin (100 mg/kg) significantly reduced dead, inflammatory, and mitotic cells in irradiated mice jejunum along with a significant increase in goblet cells and rapidly multiplying crypt cells. Morin (100 mg/kg) also maintained the villus height close to normal, prevented mucosal erosion and basement membrane damage in irradiated jejunum. Nuclear enlargement in epithelial cells of jejunum was lower in morin treated mice compared to radiation control. Morin (100 mg/kg) also significantly elevated the endogenous antioxidant enzymes viz. glutathione S transferase (GST), superoxide dismutase (SOD) and reduced glutathione (GSH), in normal mice at 2, 4 and 8 h post treatment. Drastic decrease in endogenous enzymes (GSH, GST, catalase and SOD) and total thiols was observed in irradiated mice at 2, 4 and 8 h post irradiation, while pretreatment with morin (100 mg/kg) prevented this decrease. Morin (100 mg/kg) also elevated radiation LD(50) from 9.2 to 10.1 Gy, indicating a dose modifying factor (DMF) of 1.11.

The ethanolic extract of Pilea microphylla (L.) was defatted, successively fractionated with acetone and the residue so obtained was found to be most potent when subjected to detailed free radical scavenging and in vivo radioprotection studies. The most active fraction reacts with free radicals, such as DPPH (50 microM), ABTS(.)(-) (100 microM) and (.)OH (generated by Fenton reaction) with IC(50) value of 23.15 microg/ml, 3.0 microg/ml and 310 microg/ml, respectively. The most active fraction inhibited iron-induced lipid peroxidation in phosphatidyl choline liposomes with an IC(50) of 13.74 microg/ml. The kinetics of scavenging of DPPH and ABTS(.)(-) radicals were followed at different concentrations of the fraction by employing stopped-flow studies. The observed first order decay rate constants at 200 microg/ml and 50 microg/ml of fraction with DPPH (50 microM) and ABTS(.)(-) (50 microM) were found to be 0.4s(-1) and 2.1s(-1), respectively. The fraction when screened for in vivo radioprotection in Swiss albino mice showed 80% protection at a dose of 900 mg/kg and with a DRF of about 1.12. The fraction was also found to protect livers of irradiated mice from depletion of endogenous antioxidant enzymes like glutathione, GST, SOD, catalase and thiols. The fraction also protected the villi height, increased the number of crypt cells while offering general protection to the intestine from acute radiation effects. The fraction also protected the hematopoietic system as assessed by endogenous spleen colony assay, contributing to the overall radioprotective ability.

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100mg/kg bw, administered intraperitoneally 30min prior to 9.5Gy whole-body gamma-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50mg/kg bw) in mice irradiated with 15Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25mg/kg bw.

Treatment of phenols with ninhydrin in acidic medium afforded 2-hydroxy-2-(ortho-hydroxy-phenyl/naphthyl)-1,3-dioxoindanes, which being unstable were isolated in their hemiketal forms. These synthesized compounds were subjected to TLC screening for radical scavenging and in vitro lipoxgenase and cycloxygenase enzyme inhibition assays. The best compound was identified and studied in detail for steady-state and time-resolved free radical kinetics, viz., DPPH, ABTS(-), *OH and rate constants for these reactions were evaluated. The best compound was also subjected to in vivo anti-inflammatory and analgesic activities in which the compound showed good promise for further structural optimization.

Purpose: To evaluate and optimize the radioprotective ability of the most potent fraction of an aqueous extract of Coronopus didymus in whole body gamma-irradiated Swiss albino mice and to evaluate the antioxidant status and lipid peroxidation of the livers of the surviving mice. To correlate the free radical scavenging studies with in vivo radioprotection ability., Materials and Methods: Swiss albino mice were treated with either vehicle or the different doses of extract/fraction suspension by an i.p. route, 30 min before exposure to 10 Gy gamma-irradiation and the animals were monitored twice daily for any signs of radiation toxicity and mortality. Radiation dose response (7-11 Gy), optimization of route, time of drug administration and evaluation of dose response factor (DRF) at the best dose of the fraction was studied. Endogenous antioxidant status and lipid peroxidation of the livers of the mice surviving on the 31st day was evaluated by using spectrophotometric methods., Results: The most active free radical scavenging fraction (CDF1) as assessed by competition kinetic studies using pulse radiolysis showed maximum in vivo radioprotection of 70% at a dose of 400 mg/kg body weight (bw) compared to corresponding 10 Gy irradiated control. Optimum radioprotection was observed upon i.p. administration, 30 min prior to 10 Gy irradiation and DRF at a dose of 400 mg/kg bw for 30 day survival was found to be 1.07. The levels of endogenous antioxidant enzymes and lipid peroxidation in the CDF1 treated surviving mice were found to reverse back to their normal levels., Conclusions: The optimum dose, time and route of drug administration for maximum radioprotection by CDF1 were determined. The reversal of the levels of endogenous antioxidant enzymes and lipid peroxidation indicates reduced oxidative stress in CDF1 treated surviving mice.