Comparative analyses of anti-inflammatory effects of Resveratrol, Pterostilbene and Curcumin: in-silico and in-vitro evidences.

Inflammation is an adaptive response that involves activation, and recruitment of cells of innate and adaptive immune cells for restoring homeostasis. To safeguard the host from the threat of inflammatory agents, microbial invasion, or damage, the immune system activates the transcription factor NF-κB and produces cytokines such as TNF-α, IL- 6, IL-1ß, and α. Sirtuin 1 (SIRT1) controls the increased amounts of proinflammatory cytokines, which in turn controls inflammation. Three phytoconstituents resveratrol (RES), pterostilbene (PTE), and curcumin (CUR) which are SIRT1- activators and that have marked anti-inflammatory effects (in-vivo), were chosen for the current study. These compounds were compared for their anti-inflammatory potential by in-silico docking studies for IL-6, TNF-α, NF-κB, and SIRT1 and in-vitro THP-1 cell line studies for IL-6, TNF-α. PTE was found to be more effective than RES and CUR in lowering the concentrations of IL-6 and TNF-α in THP-1 cell line studies, and it also showed a favorable docking profile with cytokines and SIRT1. Thus, PTE appears to be a better choice for further research and development as a drug or functional food supplement with the ability to reduce inflammation in metabolic disorders. Graphical abstract: Schematic representation of in-silico and in-vitro analysis of Resveratrol, Pterostilbene, and Curcumin.

Pterostilbene alleviates cafeteria diet-induced obesity and underlying depression in adolescent male Swiss albino mice and affects insulin resistance, inflammation, HPA axis dysfunction and SIRT1 mediated leptin-ghrelin signaling.

Cafeteria diet (CD) model for in-vivo studies mimics the western diet having imbalanced nutritional value, high caloric-density and palatability. Uncontrolled eating leads to the development of childhood obesity, poor self-esteem and depression due to its effects on brain development. Herbal supplements are novel inclusion in the management of obesity and mental well-being. Pterostilbene (PTE) found in blueberries and Pterocarpus marsupium heartwood, is known to prevent obesity in invivo models. Adolescent Swiss albino male mice were fed on CD for 70 days and the development of obesity was assessed by gain in body weight, abdominal circumference. Forced swim and tail suspension test confirmed depression in CD fed mice. Obesity induced depressed (OID) mice were treated with PTE (10, 20, 40 mg/kg), standard antiobesity drug cetilistat (10 mg/kg), antidepressant fluoxetine (10 mg/kg) for 28 days. Post treatment, PTE-treated mice showed reduction in BW and depression-like behavior analysed using paradigms such as sucrose preference, open field, marble burying, and resident intruder test in comparison to the CD group. Insulin resistance, lipid profile, antioxidant enzyme, inflammatory cytokines (NF-κB, IL-6, TNF α) and cortisol levels were mitigated by PTE. It also restored normal cellular architecture of the brain and adipose tissue and increased the Silent mating type information regulation 2 homolog1 (SIRT1), leptin and ghrelin receptors gene expression in the brain. Thus, it can be concluded that PTE might have inhibited OID like behavior in mice via inhibition of IR, modulating neuroinflammation and hypothalamic-pituitary-adrenal axis dysfunction and upregulating SIRT1 mediated leptin-ghrelin signaling.

Improved Pharmacokinetic and Pharmacodynamic Profile of Deuterium-Reinforced Tricyclic Antidepressants Doxepin, Dosulepin, and Clomipramine in Animal Models.

BACKGROUND AND OBJECTIVES: Doxepin, dosulepin, and clomipramine are tricyclic antidepressants (TCAs) that act as serotonin and noradrenaline reuptake inhibitors. The metabolites formed by N-dealkylation of these tricyclic antidepressants contribute to overall poor pharmacokinetics and efficacy. Deuteration of the methyl groups at metabolically active sites has been reported to be a useful strategy for developing more selective and potent antidepressants. This isotopic deuteration can lead to better bioavailability and overall effectiveness. The objective is to study the effect of site-selective deuteration of TCAs on their pharmacokinetic and pharmacodynamic profile by comparison with their nondeuterated counterparts. METHODS: In the current study, the pharmacokinetic profile and antidepressant behavior of deuterated TCAs were evaluated using the forced swim test (FST) and tail suspension test (TST), using male Wistar rats and male Swiss albino mice, respectively; additionally, a synaptosomal reuptake study was carried out. RESULTS: Compared with the nondeuterated parent drugs, deuterated forms showed improved efficacy in the behavior paradigm, indicating improved pharmacological activity. The pharmacokinetic parameters indicated increased maximum concentration in the plasma (Cmax), elimination half-life (t1/2), and area under the concentration-time curve (AUC)  in deuterated compounds. This can have a positive clinical impact on antidepressant treatment. Synaptosomal reuptake studies indicated marked inhibition of the reuptake mechanism of serotonin (5-HT) and norepinephrine. CONCLUSIONS: Deuterated TCAs can prove to be potentially better molecules in the treatment of neuropsychiatric disorders as compared with nondeuterated compounds. In addition, we have demonstrated a concept that metabolically active, site-selective deuteration can be beneficial for improving the pharmacokinetic and pharmacodynamic profiles of TCAs. A further toxicological study of these compounds is needed to validate their future clinical use.

Resveratrol attenuates early life stress induced depression in rats: Behavioural and neurochemical evidence.

PURPOSE: Maternal deprivation (MD), a severe naturalistic type of stress in the early postnatal days, is a well-established model of early life stress (ELS) that models juvenile adversity and may result in significant depressive disease in adults. In order to analyze the behavioural, brain monoamine level and HPA axis dysregulations caused by ELS and to determine whether Resveratrol (Res) could counteract these effects, Wistar rat pups were subjected to the MD paradigm, which simulated the consequences of depression. METHODS: The pups on their postnatal day 1-10 were divided in 5 groups (n = 8); nondeprived (ND), maternally deprived (DC), standard fluoxetine (FLX) (5 mg/kg i.p), Res (20, 40 mg/kg i.p). Excluding the ND group, other pups were separated from dam for 3hr/day from day 1 to 10th day. Treatment was initiated from 50th day and was given for 12 days. The behaviour parameters light/dark test, sucrose preference, and resident intruder test were employed. Serum cortisol levels, brain antioxidant activity, monoamine levels and neuronal morphology in the hippocampus were assessed. RESULTS: The MD rats showed altered behaviour, including more light-dark transitions, less desire for sucrose, and lower attack latencies. MD influenced the release of serum cortisol and interfered with monoamine, antioxidant levels as well as reduced Nissl bodies in the hippocampus. Treatment with Res led to improved behavioural functions also restored monoamine levels, reduced cortisol release, oxidative stress and prevented histopathological alterations in the rat hippocampus. CONCLUSION: Res showed neuroprotective effects by improving the brain antioxidants and monoamine levels and HPA axis dysregulation and thus improves MD induced depression like behaviour in Wistar rats.

Pterostilbene ameliorates type-2 diabetes mellitus - Induced depressive-like behavior by mitigating insulin resistance, inflammation and ameliorating HPA axis dysfunction in rat brain.

One of the most serious mental health comorbidities associated with diabetes mellitus is depression. The occurrence is almost double in type 2 diabetes mellitus (T2DM) compared with the general population. Pterostilbene (PTE), a dimethylated analog of resveratrol, has been reported for significant neuroprotective, anti-inflammatory, hypolipidemic, hypoglycaemic and antioxidant effects. However, its effect on diabetes-induced depression-like behavior (DID) has not been studied. The current study aimed at studying the effects of PTE on depressive-like behavior in male Wistar rats with T2DM. It was induced by single dose administration of nicotinamide (NA) and streptozotocin (STZ). On day 21, forced swim test (FST) was conducted for the confirmation of DID. Rats demonstrating depressive-like behavior were treated with PTE (10, 20 and 40 mg/kg), metformin (MET; 500 mg/kg) and fluoxetine (FLX; 10 mg/kg) for 28 days, orally. At the end of the treatment, behavioral assessment for depression, blood glucose (BG) and lipid profile, oxidative stress markers, gene expression of Sirtuin 1 (SIRT1) and histopathological parameters were investigated. PTE significantly reduced weight loss and mitigated depressive-like behavior paradigms such as sucrose preference test (SPT), resident intruder test (RIT) and open field test (OFT). It significantly restored BG, lipid and liver profile, creatinine and antioxidant level. It Improved glucose tolerance, insulin resistance (IR) and reduced cortisol level as well as inflammatory markers. It showed improved morphology of the pancreas, brain, liver and kidney. Gene expression studies revealed that, PTE significantly increased SIRT1 expression. PTE by its virtue to maintain BG, reduced IR, amelioration of the HPA axis, anti-inflammatory, antioxidant activity and improvement of SIRT1 gene expression proved to be effective in the treatment of DID-like behavior in rats.

An Overview of Chemistry, Kinetics, Toxicity and Therapeutic Potential of Boldine in Neurological Disorders.

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties. There is a dearth of information regarding its pharmacokinetics and toxicity in addition to its potential pharmacological activity. Boldine belongs to the aporphine alkaloid class and possesses lipophilic properties which enable its efficient absorption and distribution throughout the body, including the central nervous system. It exhibits potent free radical scavenging activity, thereby reducing oxidative stress and preventing neuronal damage. Through a variety of neuroprotective mechanisms, including suppression of AChE and BuChE activity, blocking of connexin-43 hemichannels, pannexin 1 channel, reduction of NF-κß mediated interleukin release, and glutamate excitotoxicity which successfully reduces neuronal damage. These results point to its probable application in reducing neuroinflammation and oxidative stress in epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Moreover, its effects on serotonergic, dopaminergic, opioid, and cholinergic receptors were further investigated in order to determine its applicability for neurobehavioral dysfunctions. The article investigates the pharmacokinetics of boldine and reveals that it has a low oral bioavailability and a short half-life, requiring regular dosage to maintain therapeutic levels. The review studies boldine's potential therapeutic uses and mode of action while summarizing its neuroprotective benefits.  Given the favorable results for boldine as a potential neurotherapeutic drug in laboratory animals, more research is required. However, in order to optimise its therapeutic potential, it must be more bioavailable with fewer detrimental side effects.

Buspirone, a 5-HT1A agonist attenuates social isolation-induced behavior deficits in rats: a comparative study with fluoxetine.

Social isolation is a potent stressor in both humans and animals that results in increased anger-like emotion, (anger in humans), aggression and suicidal ideation in humans [suicidal trait-related behavior in rats (STRB)]. The study's purpose was to compare the effects of buspirone (BUS) and fluoxetine (Flx) on social isolation-induced behavior deficits in rats. The male Wistar rats were randomized into six groups and caged individually for 14 days except for the non stress control (nSC) group. They were then divided into the following groups, stress control (SC), Flx (30), BUS (10), BUS (20) and BUS (40) and treated from day 14 to day 28. On the last day of treatment behavior parameters were recorded. Serum cortisol, blood pressure (BP) measurement, magnetic resonance imaging (MRI) of the rat's brain and brain-derived neurotrophic factor (BDNF) expression were performed. SC group showed a significant increase in anger-like emotion, aggression, irritability score, learned helplessness, increased cortisol level and reduced BDNF. These behavioral deficits were attenuated by BUS and Flx, Both were found to be equally beneficial in preventing anger-like emotions and aggression. Flx, which has been found to promote suicidal thoughts in people, did not reduce irritability in rats, showing that it did not affect it. BUS significantly improved all behavioral traits also reduced cortisol levels, significantly increased BDNF and normalized BP. Neuroimaging studies in SC brains showed a reduction in amygdala size compared to nSC, BUS treatment mitigated this reduction. Buspirone is effective in preventing social isolation induced behavioural-deficits.

Corrigendum to "Phytochemical analysis and antifertility potential of Cynodon dactylon in female Wistar rats: A herbal approach towards contraception" [Chin Herb Med 12 (2020) 281-288].

[This corrects the article DOI: 10.1016/j.chmed.2020.06.001.].

Self-microemulsifying drug delivery system (SMEDDS) of curcumin attenuates depression in olfactory bulbectomized rats.

BACKGROUND: Current therapies for depression remain limited and plagued by various side effects. Problems associated with curcumin administration include poor aqueous solubility and bioavailability issues. Hence to overcome these, curcumin self micro emulsifying drug delivery system (SMEDDS) which will result in a nanosize emulsion droplets when administered in vivo were formulated in the present study. METHODS: Depression was induced by bilateral olfactory bulbectomy and the animals were randomized into 8 groups as normal, control [(vehicle 10 ml/kg, p.o., (per oral)], pure curcumin (10, 20, 40 mg/kg, p.o.), and curcumin SMEDDS (10, 20, 40 mg/kg, p.o). After 14 days of respective treatment, behavioral parameters such as open field test (OFT), ambulation counts and passive avoidance response (PAR) were evaluated. At the end of experiments, blood was withdrawn from r.o.p (retro orbital plexus) for serum cortisol estimation. RESULTS: In OFT, increased central area frequency, peripheral area frequency, central area duration and decreased rearing and grooming were recorded with an increased ambulation counts. In PAR, significant reduction in number of trials and step down from platform was observed in the animals treated with test drug. Serum cortisol level was also found to be decreased in the test groups. CONCLUSION: Behavioral and biochemical estimations in the present study revealed the improved brain permeability and further increase in biological activity of curcumin SMEDDS.

Phytochemical analysis and antifertility potential of Cynodon dactylon in female Wistar rats: A herbal approach towards contraception.

Objective: The objective of the present study was to evaluate the antifertility activity of ether (ErCD), chloroform (CeCD) and ethyl alcohol (EyCD) extracts of the whole plant of Cynodon dactylon in female Wistar albino rats. Methods: Acute oral toxicity and an antifertility study were performed in female Wistar rats with two dose levels (200 and 400 mg/kg, orally) of EyCD. The estrogenic and progestogenic effects of EyCD were further observed by administering it to immature Wistar rats by investigations of vaginal cornification, hormonal level, uterus weight, biochemical parameters, histopathology of the uterus and deciduoma formation, respectively. Isolation of EyCD was carried out by Flash Chromatography and isolated fraction was estimated by HPLC. Results: No toxicity with any of the extract was found up to the dose of 2000 mg/kg body weight. EyCD treated rats exhibited maximum reduction in pregnancy (83.33%). Estimation of EyCD on vaginal cornification, estrogen-induced uterotrophic assay and deciduoma model demonstrated vaginal cornification, significant (P < 0.01) increase in uterine weight and uterine proliferation in histopathology and reduced deciduoma formation respectively. Hormonal and biochemical parameters confirmed the above findings indicating estrogenic potential and antiprogestogenic potential of EyCD that might be attributed to the presence of phytoestrogen (apigenin) in EyCD. Conclusion: The results suggested that extracts of C. dactylon possess significant antifertility activity, which is consistent with the literature reported in folk medicine of this plant in fertility regulation.

Ferulic acid ameliorates doxorubicin-induced cardiac toxicity in rats.

Ferulic acid (FA) is a phenolic compound with potent antioxidant activity. The objective of the study was to study the protective effects of FA on doxorubicin (Dox)-induced myocardial toxicity in rats. Wistar rats received vehicle (control) or Dox (20 mg/kg, i.p.) or telmisartan (Tel; 10 mg/kg, p.o.) or ferulic acid (20 mg/kg and 40 mg/kg, p.o.) for 7 days followed by treatment with Dox (20) on the fifth day of treatment, except the control group. On day 8, electrocardiographic parameters were recorded followed by blood withdrawal and then the animals were sacrificed for histopathology. Administration of Dox showed prolonged RR, QTc interval, and QRS complex. The levels of serum CK-MB, LDH, IL-1ß, and IL-6 were significantly increased (p < 0.01). Similarly, levels of Ca+2, Mg+2 ATPase, and Ca+2 ATPase and expression of ANP and BNP were significantly higher as compared to the control. In the FA-treated group, ECG was normal. The serum levels of CK-MB, LDH, IL-1ß, and IL-6 were not elevated. Heart tissue Ca+2, Mg+2 ATPase, and Ca+2 ATPase did not show a statistical difference compared to the control group. The FA treatment attenuated the expression of ANP and BNP. FA (20 and 40) augmented myocardial GSH and Na+/K+ ATPase. Histopathology of the heart confirmed the cardioprotective effect of FA.

Beneficial effects of Stevioside on AGEs, blood glucose, lipid profile and renal status in streptozotocin-induced diabetic rats.

The advanced glycated end products (AGEs) are formed in the diabetic patients; it is a major cause of macrovascular and microvascular complications in diabetes. Clinically there is no treatment available for the AGEs. Stveoside (Stv), a sweetener has potent anti-diabetic and anti-oxidant activity. Hence, we investigated its use in prevention of AGEs formation using in vitro and in vivo models. Diabetes was induced by streptozotocin (STZ). These rats were kept without treatment till blood HbA1c was markedly increased. They were then divided into 5 groups and treated orally with vehicle or Metformin (MET) or Stv respectively for 28 days. Every 7th day, animals were tested for body weight and blood glucose (BG). On the last day of treatment, all the groups were evaluated for physiological and biochemical parameters, histopathology and AGEs; N-carboxymethyl-lysine (CML) estimation. Stv showed inhibition of AGEs in in vitro as well as in in vivo respectively. Positive effects were seen on the BG, lipid profile and urine parameters as well it showed reduced formation of CML. It also showed antihyperglycaemic, antihyperlipedemic and nephroprotective activities. The present study provides scientific rationale for the use of Stv as a sweetener with additional benefits in diabetes.

Telmisartan attenuates diabetes induced depression in rats.

BACKGROUND: Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats. METHODS: Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). RESULTS: Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1ß (p<0.001). TMS antagonized depression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1ß (p<0.001). CONCLUSIONS: Low dose TMS and its combination with metformin normalizes depressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID.

Ameliorative effects of type-A procyanidins polyphenols from cinnamon bark in compound 48/80-induced mast cell degranulation.

Allergic diseases are a significant health concern in developing countries. Type-A procyanidin polyphenols from cinnamon (Cinnamomum zeylanicum Blume) bark (TAPP-CZ) possesses antiasthmatic and antiallergic potential. The present study was aimed at the possible anti-allergic mechanism of TAPP-CZ against the compound 48/80 (C48/80)-induced mast cell degranulation in isolated rat peritoneal mast cells (RPMCs). TAPP-CZ (1, 3, 10, and 30 µg/ml) was incubated for 3 hours with isolated, purified RPMCs. The C48/80 (1 µg/ml) was used to induce mast cell degranulation. The mast cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay whereas histamine, ß-hexosaminidase (ß-HEX), and interleukin-4 (IL-4) levels were determined in RPMCs. TAPP-CZ (3, 10, and 30 µg/ml) showed significant and dose-dependent decrease in a number of degranulated cells and levels of markers (histamine, ß-HEX, and IL-4) as compared with C48/80 control. In conclusion, TAPP-CZ stabilizes mast cell and cause inhibition of the allergic markers such as histamine, IL-4, and ß-HEX in IgE-mediated manner. The present study supports mast cell stabilization as a possible mechanism of action of TAPP-CZ against immune respiratory disorders such as asthma and allergic rhinitis.

Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors.

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 µg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 µg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.

Antiallergic effect of piperine on ovalbumin-induced allergic rhinitis in mice.

CONTEXT: Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied. OBJECTIVE: The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema. MATERIALS AND METHODS: Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40 mg/kg, p.o.), or montelukast (10 mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1ß), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action. RESULTS: PIP (10, 20, and 40 mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p < 0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p < 0.001), as well as reduced expression of IL-6, IL-1ß, and IgE (p < 0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p < 0.001). DISCUSSION AND CONCLUSION: PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.

Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice.

The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 µL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 µL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 µL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats.

OBJECTIVE: Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) is present in many Ayurveda compound formulations including Chavanaprasha and Dasamoolarishta. The whole plant is used in conditions such as inflammation, constipation and promoting conception in females. In the present study, we carried out different tests to evaluate the effect of aqueous extract of Solanum xanthocarpum (SXE) in postmenopausal syndrome. METHODS: The study was carried out in bilaterally ovariectomized one-month-old Wistar rats (40-50 g). Bilaterally ovariectomized (OVX) Wistar rats were divided into four groups (n=6) receiving different treatments, consisting of a vehicle (distilled water), aqueous extract of Solanum xanthocarpum at two different doses (200 and 400 mg/kg) administered orally daily for 90 d and standard drug ß estradiol at a dose of 1 mg/kg administered subcutaneously biweekly for 90 d. Estrogenic activity was assessed by vaginal cornification, sexual behavior, serum estradiol and uterine weight to body weight ratio. Antiosteoporotic activity was assessed on the basis of biomechanical and biochemical parameters followed by histopathological studies, and antidepressant activity was assessed by forced swim test. RESULTS: SXE showed presence of steroids. At the dose of 200 mg/kg, it significantly improved all the parameters of sexual behavior (P<0.01), caused vaginal cornification, and increased serum estradiol and uterine weight (P<0.01). It also significantly improved all the parameters of bone strength as well as depression (P<0.01). Histopathology of bones confirmed the above findings. CONCLUSION: The study indicated that SXE may provide an effective treatment in the prevention of postmenopausal symptoms.

Protective effect of hesperetin in rat model of partial sciatic nerve ligation induced painful neuropathic pain: an evidence of anti-inflammatory and anti-oxidative activity.

Behavioral, biochemical and gene expression changes were investigated in a rat model of partial sciatic nerve ligation (PSNL) after administration of hesperetin (20, 50mg/kg; p.o.), pregabalin (10mg/kg; p.o.) or vehicle (1 ml/kg, p.o.). Thirty-six animals were randomly divided into six groups. Left sciatic nerve was exposed and ligated, animals in the control and test groups were treated orally with respective drugs for fifteen days. Nociceptive threshold was assessed on 0 day and thereafter every three days. Three weeks later, sciatic nerve tissue homogenate was prepared and subjected for estimation of oxidative markers namely total protein, nitric oxide, lipid peroxidase, interleukins (IL-1ß and IL-6) and TNF-α. Administration of hesperetin resulted in a dose dependent attenuation in PSNL-induced mechanical and thermal hyperalgesia, mechanical allodynia as well as down regulation of IL-1ß, IL-6 and TNF-α, and biochemical markers. Consequently, it can be concluded that anti-hyperalgesic effect of hesperetin in rats after PSNL may be attributed to various oxidative markers as well as the pro-inflammatory mediators secreted at the injury site. Hesperetin appears to be a promising candidate for the development as a novel therapeutic for the patients suffering from the neuropathic pain.

Diuretic potential of aqueous extract of roots of Solanum xanthocarpum Schrad & Wendl, a preliminary study.

In traditional system of medicine S. xanthocarpum is used treating difficulty in urination and renal calculus. The objective of the present study was to scientifically evaluate diuretic potential of S. xanthocarpum. The study was divided into two phases of evaluation (acute and sub-acute) with administration of aqueous extract of S. xanthocarpum roots. The animals were treated with either aqueous extract of S. xanthocarpum (AqSX; 200, 400 mg/kg, po) or furosemide (25 mg/kg, po) or hydrochlorthiazide (HCTZ; 25 mg/kg, po). In acute study, the treated animals were observed for urine volume, urine pH, urine and serum electrolytes and creatinine after 6th and 24th h. While in sub-acute study observations for above mentioned parameters were done on day 1, day 7 and day 14. Diuretic index, natriuretic and saluretic potential were also calculated. The results indicated strong diuretic potential with AqSX (400 mg/kg). The diuretic prospective of AqSX was similar to furosemide without any type of toxicity based on the observations of serum electrolytes, serum creatinine and urine creatinine measurement. The findings support ethnobotanical use of S. xanthocarpum.