Search

This study aimed to provide irrefutable evidence of the preventive effects of oxymatine (OMT) on a model of endotoxin induced glaucoma in Wistar rats which can be attributed to its anti‐inflammatory, antioxidant, and TNF‐α antagonistic properties. To assess the impact of OMT on uveitic glaucoma, the normal group received 100 μL distilled water topically for 15 days, while the glaucoma control group was induced with uveitic glaucoma by applying 10 μL of 10 μg/mL lipopolysaccharide (LPS) topically for 3 consecutive days. The treatment groups were then given OMT solution at a volume of 50 μL with varying doses of 0.25%, 0.5%, and 1% once a day via topical administration for 15 days. In addition, as a standard, the animals were also given 100 μL of 1% dorzolamide topically for 15 days. All ophthalmic dosing was carried out by pulling the lower eye‐lid of the experimental animals and administration of the respective solutions. The study uses cutting‐edge real‐time imaging of the retinal vasculature in anesthetized animals, postsacrifice lenticular picturization and biochemical evidence to support the changes in the retinal layers. LPS induced animals demonstrated increased IOP, disrupted antioxidant systems, massive lipid damage, enhanced TNF‐α activity and changes in intracellular ATPase and ionic activities. The damaged retinal vasculature and lenticular opacification further supported the biochemical evidence. However, using OMT at a 1% dosage effectively enhanced the antioxidant levels, regulated intracellular ion concentration and ATPases, decreased TNF‐α activity, and counteracted mechanobiological changes in the visual front and retina. Moreover, OMT can successfully normalize intraocular pressure, making it a highly beneficial treatment option for glaucoma. [ABSTRACT FROM AUTHOR]

Background and Purpose: A high-fat diet (HFD) is a common risk factor for Type 2 diabetes mellitus (T2DM) and its associated cognitive impairments. In models of diabetes, resveratrol, a modulator of SIRT1, regulates the fasting glucose and antioxidant levels, as well as the lipid profile. Resveratrol may also alleviate the cognitive dysfunctions associated with diabetes.Experimental Approach: Albino rats were fed a HFD, (60% kcal fat) after treatment with streptozotocin (45 mg·kg-1 ,i.p., single dose) to induce an experimental model of T2DM. After 14 weeks of the animals in confirmed diabetic condition, they were treated with metformin (200 mg·kg-1 ,i.p.) or resveratrol (50 or 100 mg·kg-1 ,i.p.) for 4 weeks. Levels of oxidative-nitroso-stress, SIRT1, TGF-β1, inflammation and cholinergic activity were determined in plasma, hippocampus and cerebral cortex. A battery of behavioural studies associated with learning memory were performed during and after the experimental protocol.Key Results: Treatment with resveratrol attenuated the increased glucose levels (pre- and post-prandial), impaired glucose tolerance, HbA1c, and decreased the body weights of the T2DM rats. Moreover, resveratrol ameliorated the impaired learning and memory associated with increased SIRT1 and decreased TGF-β1, TNF-α, oxidative-nitroso-stress, and cholinergic activities in the plasma and the brains of the T2DM animals.Conclusion and Implication: Our results demonstrated that SIRT1 modulation interacted with TGF-β1 signalling, and mitigated hyperglycaemia and subsequent learning-memory impairments in the T2DM animals. Our study also suggested novel therapeutic targets, including TGF-β1, which may add to our knowledge of resveratrol, when used to treat impaired memory associated with diabetes. [ABSTRACT FROM AUTHOR]

Previously, we assessed that hypertension increases cataractogenesis. In the present study, we evaluated the effect of oral and topical administration of enalapril on two kidney one clip (2K1C)-induced hypertensive cataract model by evaluating the biochemical alteration of lenticular antioxidants, ionic content, ATPase activity, protein content and careful examination of the lenticular opacity. Animals were divided into normal and hypertensive animals. Hypertensive animals were divided into hypertensive control group (0.3% CMC), enalapril (oral) treatment group (20 mg/kg/day; p.o), and enalapril (topical) treatment group (0.1% w/v on the eye cornea) for a period of twelve weeks. During experimental study blood pressure, heart rate and morphology of the eyes were monitored biweekly. After twelve weeks, lenses were photographed and various catractogenic biochemical parameters were assessed. Enalapril (oral) treatment conserved the blood pressure (systolic and diastolic), restored the level of antioxidants, restored the lipid peroxidation marker, nitrite content, ionic content, ATPase function, protein content, and thus delayed the cataract formation. While, enalapril (topical) treatment exhibited anti-cataract effect without affecting the systolic and diastolic blood pressure that could be by restoring the antioxidant level, maintaining the ionic balance, balancing the protein levels, and by inhibiting the upregulated ocular renin angiotensin system. The overall results suggest that enalapril (topical) treatment showed conspicuous effect than enalapril (oral) treatment in adjourning the cataract formation. Based on the results, it may be concluded that upregulated ocular RAS by increasing oxidative stress and by misbalancing the lenticular ionic and protein content may lead to cataract formation in hypertensive condition. [ABSTRACT FROM AUTHOR]

The present study was designed to determine protective effects of Coleus forskohlii hydroalcoholic leaf-extract along with its fractions against fructose-induced cataract rat model. The Coleus forskolii leaf extract was subjected to silica gel column chromatography and fractions were collected. A major high yielding fraction of the leaf extract, designated as fraction B6 was pharmacologically evaluated in Sprague Dawley albino rats at three doses 0.1, 1 and 10 mg/kg respectively. Compound B2; isolated from B6 fraction, identified as 'gallic acid' was also pharmacologically evaluated at three different doses. Cataract was induced by concurrent administration of fructose solution (10% w/v, per oral, dissolved in drinking water) for eight consecutive weeks. Mean arterial pressure, blood glucose level and lenticular opacity were determined. At the end of eight weeks, C. forskohlii leaf extract fraction and gallic acid reduced mean arterial pressure and glucose level in a dose dependent manner. In addition, C. forskohlii led to significant restoration of lens antioxidants enzyme level and reduced cataract formation in rats. These results showed the concentration dependent protective effect by C. forskohlii leaf extract against cataract formation due to restoration of oxidative stress markers. [ABSTRACT FROM AUTHOR]

Previously, we established several facts regarding hypertension‐associated cataractogenesis. As a follow‐on study, we evaluated the role of the renin–angiotensin system (RAS) in angiotensin‐II (Ang‐II)‐induced cataract formation in experimental hypertensive rats. Sprague–Dawley male albino rats (150–180 g) were used for the present experiment. The animals were divided into four groups, with six animals in each group. During the 12 weeks of the experimental protocol, the normal group received sterile water (1 ml/kg/day, subcutaneously (sc), and the Ang‐II control group received angiotensin (1 mg/kg/day) subcutaneously. The ARB (O) group received olmesartan (2 mg/kg/day) orally, and the ARB (T) group received two drops of olmesartan (5 mM) topically on the cornea; concurrently, both groups were treated with Ang‐II (1 mg/kg/day, sc) to induce hypertension. Biweekly, the systolic and the diastolic blood pressures were recorded, and the eyes were examined; moreover, cataractogenic parameters, such as oxidative stress markers and protein contents in the lenses, were evaluated after completion of the experimental protocol. Twelve weeks of olmesartan administered, orally or topically, significantly reduced the progression of cataract formation and restored antioxidants, lipid peroxidation, nitrite content, and protein contents in the lenses of the mice in groups O and T, respectively, as compared with those in the Ang‐II control group. On the basis of our results, we conclude that the ocular RAS exacerbates the lenticular oxidative stress that may lead to cataract formation. The results showed that the RAS has an independent and important role in cataract formation under hypertensive conditions. [ABSTRACT FROM AUTHOR]

High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract. Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol. Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective. These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract. [ABSTRACT FROM AUTHOR]

Purpose: Previously we established a strong association of systemic hypertension with cataract formation. In the present study, we investigated the role of nitric oxide (NO) in the development of cataract formation in CdCl2-induced hypertensive animals. Materials and Methods: Hypertension was induced in male albino rats by intraperitoneal administration of CdCl2 (0.5 mg/kg/day) for eight weeks. The NO modulators, 10 µM S-nitrosoglutathione (NO donor) and 1% w/v Nω-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) were applied topically once a day on the eye cornea during the experimental period. Amlodipine (3mg/kg/day) was used as a standard antihypertensive drug and administered orally. Results: In the CdCl2 control group, mean arterial pressure was significantly increased along with augmentation of lens nitrite, opacity, and oxidative stress. The control of hypertension by amlodipine substantially restored lens nitrite and cataractogenic events. Moreover, topical application of L-NAME significantly alleviated the lens nitrite, opacity, antioxidants (GSH, CAT, SOD, and GPx), MDA, proteins, and ionic (Na+ and Ca2+) contents. Whereas, S-nitrosoglutathione topical application exacerbated these cataractogenic events without affecting hypertension as compared to CdCl2 control group. The findings demonstrated that NO donor exacerbates and NOS inhibitor alleviates the cataract formation in hypertensive condition. The control of hypertension also reduces the cataract formation with reduction of lens nitrite level. Conclusion: The overall findings suggested the strong correlation between NO and hypertension associated cataract formation. The elevation of lens nitrite (NO metabolite) is one of the key factors of augmentation of lenticular oxidative stress and cataract formation in the hypertensive condition. [ABSTRACT FROM AUTHOR]

Previously we found that hypertension potentiates the risk the cataractogenesis. In the present study, we investigated the protective effects of magnesium taurate (MgT) on hypertension and associated lenticular damages against cadmium chloride (CdCl 2 )-induced hypertensive animals. Male Sprague-Dawley albino rats (150–180 g) were assigned to five experimental groups (n = 6). Among the five groups, normal group received 0.3% carboxymethyl cellulose (10 ml/kg/day, p.o.). Hypertension control group received CdCl 2 (0.5 mg/kg/day, i.p.). Tests and standard groups received MgT (3 and 6 mg/kg/day, p.o.) and amlodipine (3 mg/kg/day, p.o.) concurrently with CdCl 2 respectively , for six consecutive weeks. Blood pressure, heart rate, and eyes were examined biweekly, and pathophysiological parameters in serum and eye lenses were evaluated after six weeks of the experimental protocol. The chronic administration of MgT concurrently with CdCl 2 significantly restored the blood pressure, serum and lens antioxidants (CAT, SOD, GPx, and GSH), MDA level, and ions (Na + , K + , and Ca 2+ ). Additionally, MgT treatment led to significant increase in the lens proteins (total and soluble), Ca 2+ ATPase, and Na + K + ATPase activity as compared to hypertension control group. Ophthalmoscope observations indicated that MgT treatments delayed the progression of cataract against the hypertensive state. The study shows that MgT prevents the progression of cataractogenesis via restoration of blood pressure, lenticular oxidative damages, and lens ATPase functions in the hypertensive state. The results suggest that MgT supplement may play a beneficial role to manage hypertension and associated cataractogenesis. [ABSTRACT FROM AUTHOR]

To investigate hepatoprotective effect of ethanolic extract of Carissa carandas fruits in carbon tetrachloride intoxicated rats. Carissa carandus unripe fruits were collected, dried, powdered and subjected to extraction using ethanol as solvent. Wistar rats were divided into seven groups (n=6) and induced hepatotoxicity using carbon tetrachloride [CCl4 with Olive oil (1:1), 0.5 ml/kg, i.v.], administered for 5 days. Three different doses (100, 200 and 400mg/kg) of ethanolic extract of Carissa carandus (EECC) fruits were used to administer and improvement in liver function was observed by estimation of serum marker enzymes like aspartate amino transferase (AST), alanine amino transferase ( ALT), alkaline phosphatase (ALP), serum bilirubin (SBLN), gamma glutamyl transpeptidase (GGT), total lipids (TL), albumin etc. The normal values for AST, ALT, ALP, SBLN, GGT, TP, TL and albumin in serum were significantly altered in hepatotoxic rats. These parameters attained near normal values in EECC (100 & 200mg/kg) treated rats. [ABSTRACT FROM AUTHOR]

In the indigenous system of medicine, the Reno syrup (Ayurvedic preparation) reported to be useful in the treatment of urinary stones. In present study, we evaluated the antiurolithiatic property of Reno syrup using in vitro (homogeneous precipitation method) as well as in vivo (ethylene glycol induced hyperoxaluria model in rats) method. In vitro study was performed in glass tubes instead of collecting the precipitate over filter papers. Reno syrup at different dose (1 ml, 2ml and 4 ml) were compared with the standard Cystone syrup (1 ml). The activity of Reno syrup and Cystone syrup were evaluated by ability to inhibit the formation of calcium and phosphate precipitate in glass tubes containing 25 ml each of 25 mM CaCl2.2H2O, 25 mM Na2 HPO4.2H2 O or 25 mM Na2 C2 O4. Result of in vitro study indicates that Reno syrup (4ml) has more effective than Reno syrup (1 ml and 2 ml) and Reno syrup (4ml) showed comparable activity to the standard Cystone in terms of inhibiting the formation of calcium and phosphate precipitate. The results of in vivo study, Reno syrup significantly decreases the level of oxalate, calcium and phosphate excretion in urine of rats and significantly lowered the elevated serum levels of creatinine, uric acid, BUN and GFR at three different dose level 1 ml/kg, 2 ml/kg and 4 ml/kg. Our findings indicate that Reno syrup (4 ml/kg, p.o.) has potential antiurolithiatic activity and in future it can be prescribed in the respective treatment. [ABSTRACT FROM AUTHOR]

The Polianthes tuberose is traditionally used against snake venom poisoning in Chhattisgarh region of India. The study aimed to examine the Naja venom neutralization potential of the ethanolic extract (200, 400 and 800 mg/kg) of Polianthes tuberose (Agavacae). The ethanolic extract at 400 and 800 mg/kg oral significantly inhibited the Naja venom induced lethality, haemorrhage, necrotizing effect, oedema in rats. The observation confirmed that the ethanolic extract of Polianthes tuberose possesses snake venom neutralizing properties. [ABSTRACT FROM AUTHOR]

Diospyros peregrina, commonly known as Kalatendu, is widely used in different parts of India for the treatment of diabetes mellitus. The present study was designed to evaluate the antihyperglycemic effect of an methanolic extract of Diospyros peregrina leaves (DPLE) in alloxan diabetic rats. Hyperglycemia was induced by single intravenous injection of alloxan (70mg/kg body weight). The extract was administered orally at a dose of 100, 200 and 400 mg/kg body weight, to normal and alloxan diabetic rats. Significant reduction in glucose was observed in alloxan diabetic rats. The studies indicate that the DPLE exhibited statistically significant antihyperglycemic activities in glucose tolerance test and alloxan induced diabetic rats. [ABSTRACT FROM AUTHOR]

Morina longifolia Wall is a small genus of perennial herbs, belong to the family Dipsacaceae is traditionally used for the treatment of inflammatory conditions and other diseases in Garhwal region of India. In present study attempt has been made to study the antiarthritic activity of hydroalcoholic extract of Morina longifolia (MLE). The anti-arthritic activity was evaluated by using Freund's Complete Adjuvant (FCA) induced monoarthritic rat model. Treatment of arthritic rat with MLE had significant effect on FCA-induced rat paw edema from 1st week to 6th week of the study; the results were comparable with the standard drug indomethacin. [ABSTRACT FROM AUTHOR]

Oxidative stress‐induced toxicity plays a major role in ocular diseases such as retinal degeneration, age‐related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)‐induced age‐related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca2+ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti‐cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca2+ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs. [ABSTRACT FROM AUTHOR]

The chemical composition of the essential oil from aerial parts of A. parviflora was analysed by GC and GC-MS. Twenty-two compounds, accounting for 72.7% of the oil, were identified. The main components identified were β-caryophyllene (15.3%), germacrene D (14.7%), camphor (11.4%), artemisia ketone (7.8%), 1,8-cineole (5.8%), α-copaene (2.6%), artemisia alcohol (2.6%), terpinene-4-ol (2.3%), caryophyllene oxide (1.2%), α-pinene (1.1%), sabinyl acetate (1.1%) and α-humulene (1.1%). Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The ocular renin‐angiotensin system has become an interesting target for ocular diseases because it has been implicated in various ocular diseases such as diabetic retinopathy, glaucoma, age‐related macular degeneration, uveitis, and hypertensive cataracts. In the present study, we explored the effect of topically and orally administered losartan (an angiotensin receptor blocker) on streptozotocin‐induced diabetic cataract in albino rats. Topical treatment with losartan modulated neither the blood glucose level nor the polyol content but oral treatment with losartan decreased both. Topical and oral treatment with losartan significantly increased the antioxidants (glutathione, glutathione peroxidase, superoxide dismutase, and catalase), decreased the lipid peroxidant malondialdehyde, and restored soluble protein, and insoluble protein and various ions (Na+, K+, and Ca2+) in the lens; however, topical treatment had a better effect than oral treatment. These findings demonstrate that topical administration of losartan significantly reduces the risk of cataract formation without affecting either the blood glucose level or polyol contents. [ABSTRACT FROM AUTHOR]

Objective To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Methods Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. Results At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark. Conclusions It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases pose significant challenges to healthcare systems globally due to their complex etiology and relentless progression, often rendering conventional treatments ineffective. Recent advances have spotlighted excitatory amino acids, particularly D-amino acids, once considered as products of metabolism of the microbiota or deriving from food intake. This review explores the role of D-amino acids in mitigating excitotoxicity—a process characterized by excessive calcium influx through aberrant N-methyl-D-aspartate receptor (NMDAR) activation, which is implicated in the pathogenesis of diseases like Alzheimer's disease. By providing alternative pathways for neuronal signaling and protecting against excitotoxic damage, D-amino acids offer a novel approach to reversing neurodegenerative trajectories. Future research should focus on elucidating the detailed mechanisms of action of these compounds, evaluating their therapeutic potential through rigorous preclinical and clinical trials, and developing effective delivery systems to optimize their neuroprotective effects. This emerging field holds promise for developing innovative treatment strategies that could significantly improve outcomes for patients with neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] Despite large investments by industry and governments, no disease-modifying medications for the treatment of patients with Alzheimer's disease (AD) have been found. The failures of various clinical trials indicate the need for a more in-depth understanding of the pathophysiology of AD and for innovative therapeutic strategies for its treatment. Here, we review the rational for targeting IP3 signaling, cytosolic calcium dysregulation, phosphodiesterases (PDEs), and secondary messengers like cGMP and cAMP, as well as their correlations with the pathophysiology of AD. Various drugs targeting these signaling cascades are still in pre-clinical and clinical trials which support the ideas presented in this article. Further, we describe different molecular mechanisms and medications currently being used in various pre-clinical and clinical trials involving IP3/Ca+2 signaling. We also highlight various isoforms, as well as the functions and pharmacology of the PDEs broadly expressed in different parts of the brain and attempt to unravel the potential benefits of PDE inhibitors for use as novel medications to alleviate the pathogenesis of AD. [ABSTRACT FROM AUTHOR]