Current Status of Herbal Drug Standards in the Indian Pharmacopoeia.

The benefits of herbal drugs were well understood way back. They have been used for the promotion of health and medical purposes - in disease conditions. It is a conventional belief that herbal drugs have no side effects, are cheaper and locally available. Among Indian systems of medicines, herbs/herbal formulations are used to a larger extent. The quality control of the marketed herbs/herbal formulations is important for acquiring optimum therapeutic benefit as well as for expanding global outreach. Therefore, herbal drug standards are important. Reference standards, the Indian Pharmacopoeia Reference Substances especially the botanical reference substances and the phytochemical reference substances are required for comparison of quality of herbal drugs. The Indian Pharmacopoeia Commission has initiated the process of providing Indian Pharmacopoeia Reference Substances to the stakeholders. Therefore, this article provides an overview of the history and the status of herbal drug standards in the current and forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have been made for the harmonization of standards with international counterparts wherever possible. Copyright © 2017 John Wiley & Sons, Ltd.

Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms.

PURPOSE: Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes. METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels. RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group. CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.

Cardioprotective effects of rutin via alteration in TNF-α, CRP, and BNP levels coupled with antioxidant effect in STZ-induced diabetic rats.

Diabetic cardiomyopathy (DCM) is a dreadful complication of diabetes responsible for 80 % mortality in diabetic patients, but unfortunately its pharmacotherapy is still incomplete. Rutin is a naturally occurring flavonoid having a long history of use in nutritional supplements for its action against oxidative stress, inflammation, and hyperglycemia, the key players involved in the progression of DCM, but remains unexplored for its role in DCM. This study was conducted to address this lacuna. It was performed in 4-week-old Streptozotocin-induced (45 mg/kg) diabetic rats for a period of 24 weeks to mimic the cardiotoxic effect of chronic hyperglycemia in diabetic patient's heart and to investigate the effect of rutin (50 mg/kg/day) in ameliorating these effects. Heart of the diabetic rats showed altered ECG parameters, reduced total antioxidant capacity, increased inflammatory assault, and degenerative changes. Interestingly, rutin treatment significantly ameliorated these changes with decrease in blood glucose level (p > 0.001), % HbA1c (p > 0.001) and reduced expression of TNF-α (p < 0.001), CRP (p < 0.001), and BNP (p < 0.01) compared to diabetic control rats. In addition, rutin provided significant protection against diabetes associated oxidative stress (p < 0.05), prevented degenerative changes in heart, and improved ECG parameters compared to diabetic control rats. The heart-to-body weight ratio was significantly reduced in rutin treatment group compared to diabetic control rats (p < 0.001). In conclusion, this study implicates that oxidative stress and inflammation are the central players involved in the progression of DCM and rutin ameliorates DCM through its antioxidant and anti-inflammatory actions on heart.

Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats.

The present study was undertaken to evaluate the protective effects of genistein against cardiac inflammation and oxidative stress in streptozotocin (STZ) (45 mg/kg body weight)-induced diabetic rats. genistein (300 mg/kg/day) was administered orally for 24 weeks to STZ-induced diabetic rats. The effects of genistein on blood glucose, % glycosylated hemoglobin (HbA1c), C-reactive protein, tumor necrosis factor (TNF- α), transforming growth factor (TGF-ß1), and total antioxidant were studied. Ultrastructural and histopathological assessment of injury were also undertaken using transmission electron microscope. STZ-induced diabetes resulted in significant increase in the levels of blood glucose, HbA1c, C-reactive protein, TNF- α and TGF-ß1, and a decline in total antioxidant reserve of the myocardium. Administration of genistein to diabetic rats resulted in a decrease in blood glucose (p < 0.001), % HbA1c (p < 0.0001), C-reactive protein (p < 0.001), and expression of TNF- α (p < 0.001) and TGF-ß1 (p < 0.0001) proteins. In addition, genistein treatment results in augmentation of total antioxidant (p < 0.01) reserve of the hearts. The above findings were supported by histological as well as immunohistochemical localization of NF-κB (p65) in the heart. Genistein treatment ameliorated the ultrastructural degenerative changes in the cardiac tissues as compared to the diabetic control. The result demonstrates that genistein restored the integrity of the diabetic myocardium by virtue of its anti-inflammatory and antioxidant effects.

Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate the effects of Quercetin (Qctn), a plant based flavonol, on retinal oxidative stress, neuroinflammation and apoptosis in streptozotocin-induced diabetic rats. Qctn treatment (25- and 50 mg/kg body weight) was given orally for six months in diabetic rats. Retinal glutathione (GSH) and antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] were estimated using commercially available assays, and inflammatory cytokines levels [tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß)] were estimated by ELISA method. Immunofluorescence and western blot studies were performed for nuclear factor kappa B (NF-kB), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) expressions. Structural changes were evaluated by light microscopy. In the present study, retinal GSH levels and antioxidant enzyme (SOD and CAT) activities were significantly decreased in diabetic group as compared to normal group. However, in Qctn-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of antioxidant enzyme activities was observed. Diabetic retinas showed significantly increased expression of pro-inflammatory cytokines (TNF-α and IL-1ß) as compared to that in normal retinas, while Qctn-treated retinas showed significantly lower levels of cytokines as compared to diabetic retinas. Light microscopy showed significantly increased number of ganglion cell death and decreased retinal thickness in diabetic group compared to those in normal retina; however, protective effect of Qctn was seen. Increased apoptosis in diabetic retina is proposed to be mediated by overexpression of NF-kB and caspase-3. However, Qctn showed inhibitory effects on NF-kB and caspase-3 expression. Microglia showed upregulated GFAP expression, and inflammation of Müller cells resulted in edema in their endfeet and around perivascular space in nerve fiber layer in diabetic retina, as observed through AQP4 expression. However, Qctn treatments inhibited diabetes-induced increases in GFAP and AQP4 expression. Based on these findings, it can be concluded that bioflavonoids, such as Qctn can be effective for protection of diabetes induced retinal neurodegeneration and oxidative stress.

Effects of Trigonella foenum-graecum (L.) on retinal oxidative stress, and proinflammatory and angiogenic molecular biomarkers in streptozotocin-induced diabetic rats.

The aim of the present study was to investigate the protective effects of Trigonella foenum-graecum Linn. (fenugreek) in Streptozotocin-induced diabetic rat retina. Fenugreek (100 and 200 mg/kg body weights) treatment was carried out for 24 weeks and evaluated for inflammatory [tumor necrosis factor (TNF)-α and interleukin (IL)-1ß] and angiogenic [vascular endothelial growth factor (VEGF) and protein kinase C (PKC)-ß] molecular biomarkers. Retinal oxidative stress was evaluated by estimating antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Fluorescein angiography was performed to detect retinal vascular leakage. Electron microscopy was performed to determine basement membrane thickness. In the present study, significant rises in the expressions of retinal inflammatory (TNF-α and IL-1ß) and angiogenic (VEGF and PKC-ß) molecular biomarkers were observed in diabetic retinae compared with normal retinae. However, fenugreek-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic molecular biomarkers. Moreover, results from the present study showed positive modulatory effects of fenugreek on retinal oxidative stress. Fluorescein angiograms and fundus photographs obtained from diabetic retinae showed retinal vascular leakage. On the other hand, fenugreek-treated retinae did not show vascular leakage. Further, thickened BM was recorded in diabetic retina compared with normal retinae. However, fenugreek-treated retinae showed relatively lesser thickening of capillary BM. In conclusion, it may be postulated that fenugreek has great potential in preventing diabetes-induced retinal degeneration in humans after regular consumption in the specified dosage.

Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats.

The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100 mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-α, IL-1ß), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-α and IL-1ß) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy.

Topically applied standardized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced uveal inflammation in rats.

Aqueous extract of C. longa when administered 4 h after induction of E. coli lipopolysaccharide-induced uveitis in rats showed significantly suppressed inflammation with a significantly lower mean clinical grade, histopathological grade and aqueous humor (AH) protein level compared to vehicle treated group. Although, prednisolone group showed significantly lower clinical grade, histopathological grades and AH protein levels compared to C. longa group, TNF-alpha levels did not differ significantly. Moreover, when the aqueous extract was administered starting from 3 days before induction of uveitis, the mean clinical and histopathological grade as well as AH protein and TNF-alpha levels were comparable to C. longa group when treatment was administered 4 h after induction of uveitis. It is concluded that topically applied standardized aqueous extract of C. longa suppresses endotoxin-induced uveitis in rats by reducing TNF-alpha activity.

Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats.

PURPOSE: Our objective was to investigate the effect of green tea (GT) on diabetes-induced retinal oxidative stress and proinflammatory parameters in rats. METHODS: Treatment (200 mg/kg body weight) was carried out for a period of 16 weeks in streptozotocin-induced diabetic rats and was evaluated for hypoglycemic, antioxidant [reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] and anti-inflammatory [tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF)] activity. Histological changes were evaluated by transmission electron microscopy. RESULTS: Retinal GSH levels were 1.5-fold lower in diabetic rats as compared to normal rats (p < 0.05). However, in GT-treated rats, retinal GSH levels were restored close to those of the normal group. The antioxidant enzymes SOD and CAT showed a more than 2-fold decrease in activity in diabetic retinae as compared to normal retinae (p < 0.05). Both SOD and CAT enzymatic activities were restored close to normal in the GT-treated group. Expression of proinflammatory parameters (TNF-α and VEGF) was significantly inhibited in GT-treated retinae as compared to diabetic retinae (p < 0.05). Moreover, GT treatment prevented retinal capillary basement membrane thickness. CONCLUSION: The beneficial effects of GT suggest its potential role in the prevention and treatment of diabetic retinopathy in human subjects.

Postmarketing Safety of Biosimilars: Current Status, Challenges, and Opportunities in the Spontaneous Reporting System.

Recombinant drug products successfully treat many life-threatening and chronic diseases. The high cost of these drugs makes them inaccessible to the patients particularly in developing countries. Patent expiration of innovator recombinant drug products has led to the development of biosimilars or similar biologics by several manufacturers. Unlike generics, these are not identical to their innovator products because of the differences in the manufacturing process; however, they are similar in quality characteristics, biological activity, safety, and efficacy. The regulatory procedures used for generic drugs cannot be applied for biosimilars as they are large complex structures produced from living cells and can produce potential risk of immune-based adverse reactions. Out of several safety issues related to biosimilars, two main safety concerns are variable potency and immunogenicity, for which a robust long-term pharmacovigilance system is needed. Various guidelines have been issued for the regulatory approval and pharmacovigilance of biosimilars by USFDA, EU, and pharma-emerging countries like China and India. The article includes the pharmacovigilance plan of biosimilars in these countries, discusses the challenges and opportunities in pharmacovigilance through spontaneous reporting systems, and suggests amendments in the existing suspected adverse event reporting form of the Pharmacovigilance Programme of India.

Intraocular pressure-lowering activity of topical application of Aegle marmelos fruit extract in experimental animal models.

AIM: The present study was designed to evaluate the intraocular pressure (IOP)-lowering activity of topical application of the aqueous extract of Aegle marmelos fruit in experimental animal models. MATERIALS AND METHODS: New Zealand white rabbits with normal and experimentally elevated IOP using water loading and steroid-induced models were included in this study. The IOP-lowering effect of A. marmelos fruit extract in rabbits with experimentally elevated IOP was also compared with that of timolol 0.25%. RESULTS: In rabbits with normal IOP, the A. marmelos fruit extract at a concentration of 1% showed the maximum IOP-lowering effect with 22.81% reduction from baseline IOP. The maximum IOP reduction achieved in water loading and steroid-induced models with the same concentration of A. marmelos was 27.57 and 28.41% from baseline, respectively. The efficacy was comparable to that of timolol after 45 min of water loading in the water loading model, and during the first 2 h of treatment in the steroid-induced model. CONCLUSION: A. marmelos fruit extract showed significant IOP-lowering activity in experimental animal models.

Pharmacovigilance in India: Present Scenario and Future Challenges.

Pharmacovigilance in India was initiated way back in 1986 with a formal adverse drug reaction (ADR) monitoring system, under supervision of the drug controller of India. India joined the World Health Organization (WHO) Programme for International Drug Monitoring in 1998, but was not successful. Later, the National Programme of Pharmacovigilance was launched in 2005, and was renamed as the Pharmacovigilance Programme of India (PvPI) in 2010. In consideration of having a robust pharmacovigilance system in India, steps were taken. The National Coordination Centre was shifted from New Delhi to the Indian Pharmacopoeia Commission (IPC) in Ghaziabad. The PvPI works to safeguard the health of the Indian population by ensuring that the benefit of medicines outweighs the risks associated with their use. The culture of reporting of ADRs has achieved remarkable success, with 250 PvPI-established adverse drug monitoring centres all over India and provision of training to healthcare professionals. The programme is striving hard to build trust between the physician and the patient, thereby increasing patient safety and the confidence of people in the country's health system, in addition to the detection of substandard medicines and prescribing, dispensing and administration errors. The IPC-PvPI has now become a WHO Collaborating Centre for Pharmacovigilance in Public Health Programmes and Regulatory Services. In spite of these achievements, several challenges are faced by the PvPI, like the monitoring of generic drugs, biosimilars, and disease-specific ADRs of antidiabetic, cardiovascular and antipsychotic drugs and, above all, creating awareness, which is a continual process. At the same time, the PvPI is trying to address other challenges like counterfeit drugs, antimicrobial resistance, and surveillance during mass vaccinations and other national programmes.

Postmarketing Safety of Biosimilars: Current Status, Challenges, and Opportunities in the Spontaneous Reporting System.

Recombinant drug products successfully treat many life-threatening and chronic diseases. The high cost of these drugs makes them inaccessible to the patients particularly in developing countries. Patent expiration of innovator recombinant drug products has led to the development of biosimilars or similar biologics by several manufacturers. Unlike generics, these are not identical to their innovator products because of the differences in the manufacturing process; however, they are similar in quality characteristics, biological activity, safety, and efficacy. The regulatory procedures used for generic drugs cannot be applied for biosimilars as they are large complex structures produced from living cells and can produce potential risk of immune-based adverse reactions. Out of several safety issues related to biosimilars, two main safety concerns are variable potency and immunogenicity, for which a robust long-term pharmacovigilance system is needed. Various guidelines have been issued for the regulatory approval and pharmacovigilance of biosimilars by USFDA, EU, and pharma-emerging countries like China and India. The article includes the pharmacovigilance plan of biosimilars in these countries, discusses the challenges and opportunities in pharmacovigilance through spontaneous reporting systems, and suggests amendments in the existing suspected adverse event reporting form of the Pharmacovigilance Programme of India.

Lowering of intraocular pressure by topical application of Daucus carota seed extract in rabbits.

In normotensive rabbits topical application of Daucus carota seed extract at the concentration of 0.3, 0.6 and 1.2% resulted in mean IOP reduction of 19.33. 23.20 and 25.61% respectively from baseline. As no significant difference was observed between the change in IOP in 0.6 and 1.2% extract treated groups, 0.6% concentration was chosen for further evaluation in rabbits with experimentally elevated IOP. In water loaded rabbits, maximum mean IOP reduction with 0.6% extract was 29.39%, which was comparable to pilocarpine. In steroid pretreated rabbits, maximum mean IOP reduction was 30.27% from baseline, which was significantly higher than pilocarpine. The extract showed a comparatively slower onset of action however, the duration of action was comparable to pilocarpine in all the experimental models.

Oculohypotensive effects of foeniculum vulgare in experimental models of glaucoma.

PURPOSE: Evaluation of oculohypotensive activity of single drop application of aqueous extract of Foeniculum vulgare in experimental models of glaucoma. METHODS: The evaluation of oculohypotensive activity of Foeniculum vulgare was done in rabbits with normal intraocular pressure (IOP) and with experimentally elevated IOP. The experimental increase in IOP was achieved using water loading and steroid induced glaucoma models. RESULTS: The aqueous seed extract of Foeniculum vulgare exhibited 17.49, 21.16 and 22.03% reduction of intraocular pressure (IOP) in normotensive rabbits at 0.3%, 0.6% and 1.2% (w/v) concentrations respectively. The 0.6% concentration was further evaluated in acute and chronic models of glaucoma. A maximum mean difference of 31.20% was observed between vehicle treated and extract treated eyes in water loading model while a maximum mean IOP lowering of 31.29% was observed in steroid induced model of glaucoma. CONCLUSIONS: The aqueous extract of Foeniculum vulgare possesses significant oculohypotensive activity, which was found to be comparable to that of timolol. Further investigations into the mechanism of action, possible toxicity and human clinical trials are warranted before the Foeniculum vulgare finds place in the arsenal of antiglaucoma drugs prescribed by physicians.

Ocimum sanctum modulates selenite-induced cataractogenic changes and prevents rat lens opacification.

PURPOSE: To study the effect of Ocimum sanctum (OS) on selenite-induced morphological and biochemical changes in isolated rat lenses as well as on cataract incidence in rat pups. METHODS: Transparent rat lenses were divided into normal, selenite-only, and four treated groups. Selenite-only and treated group lenses were subjected to oxidative stress in vitro by incorporating sodium selenite (100 microM) in the culture medium. The effect of OS (70, 140, 280, and 560 microg/ml) was studied on the levels of reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS) in selenite-challenged lenses. The lowest concentration of OS offering significant modulation on these two parameters was determined. Subsequently, the effect of prior and cotreatment with the lowest effective concentration of OS was studied on TBARS, GSH, and on lens antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), and glutathione-S-transferase (GST). Changes in lens protein profiles under different incubation conditions were analyzed by SDS gel-electrophoresis. In vivo, cataract was induced by a single subcutaneous injection of sodium selenite (25 micromole/kg b.w.) to 9-day-old rat pups. The anticataract effect of OS (5 and 10 mg/kg b.w.) injected intraperitoneally 4 hr prior to selenite challenge was evaluated by the presence of lens nuclear opacity in rat pups on the 16th postnatal day. Insolubilization of lens proteins post-selenite injection was monitored for 4 days. RESULTS: The lenses in the selenite-only group developed cortical opacities in 24 hr. OS showed different degrees of positive modulation in selenite-induced morphological as well as biochemical changes. The lowest effective dose of OS that significantly modulated glutathione and thiobarbituric acid reacting substances was found to be 140 microg/ml. At this dose, a significant increase in antioxidant enzyme levels and preservation of normal lens protein profile was observed. OS at the dose of 70 microg/ml did not show any significant protection with respect to either morphology or biochemistry of lenses. In vivo, 5 and 10 mg/kg of OS reduced the incidence of selenite cataract by 20% and 60%, respectively, and prevented protein insolubilization as well. CONCLUSIONS: Aqueous extract of OS possesses potential anticataract activity against selenite-induced experimental cataractogenesis. The protective effect was supported by restoration of the antioxidant defense system and inhibition of protein insolubilization of rat lenses as well.

Lycopene attenuates oxidative stress induced experimental cataract development: an in vitro and in vivo study.

OBJECTIVES: Lycopene, a nutritional antioxidant, was evaluated for its anticataract potential to further establish its role in cataract prevention. METHODS: The ability of lycopene to modulate the biochemical parameters was investigated by in vitro studies. Enucleated rat lenses were maintained in organ culture containing Dulbecco's Modified Eagles Medium alone or in addition with 100 microM selenite and served as the normal and control groups, respectively. For the test group, the control medium was supplemented with 10 microM lycopene. The lenses were incubated for 24 h at 37 degrees C. At the end of the incubation period, the lenses were examined for morphologic variation, and biochemical parameters such as reduced glutathione, the lipid peroxidation product malondialdehyde, and the antioxidant enzymes glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase were estimated. In vivo selenite cataract was induced in 9-d-old rats by subcutaneous injection of sodium selenite (25 micromoles/kg of body weight). The rats in the test group were injected with lycopene (200 microg/kg body weight, intraperitoneally) 4 h before the selenite challenge. The incidence of cataract was observed when the rats first opened their eyes. Galactose cataract was induced in rats by feeding 30% galactose in the diet. Rats in the test group were fed orally with 200 microg/kg of lycopene daily, and rats in the control group received only vehicle. Cataract stages were graded at regular intervals. RESULTS: A fall (25%) in the glutathione level and a rise (32%) in the malondialdehyde content were observed in control as opposed to normal lenses. Lycopene supplementation in the medium significantly (P < 0.001) restored glutathione and malondialdehyde levels. A significant decrease in the activity of antioxidant enzymes also was observed in the control lenses. A significant restoration in the activities of superoxide dismutase (P < 0.05) and catalase and glutathione S-transferase (P < 0.01), with no effect on glutathione peroxidase, was observed in the lycopene-supplemented group. Lycopene also reduced the incidence of selenite cataract. Only 9% of the eyes in the test group developed dense nuclear opacity as opposed to 83% in the control group. A significant delay in the onset and progression of galactose cataract was observed with oral feeding of lycopene. Only 35% of the eyes developed mature cataract as opposed to 100% in the control group. CONCLUSIONS: Lycopene protects against experimental cataract development by virtue of its antioxidant properties, and it may be useful for prophylaxis or therapy against cataracts.

Validation of traditional claim of Tulsi, Ocimum sanctum Linn. as a medicinal plant.

In several ancient systems of medicine including Ayurveda, Greek, Roman, Siddha and Unani, Ocimum sanctum has vast number of therapeutic applications such as in cardiopathy, haemopathy, leucoderma, asthma, bronchitis, catarrhal fever, otalgia, hepatopathy, vomiting, lumbago, hiccups, ophthalmia, gastropathy, genitourinary disorders, ringworm, verminosis and skin diseases etc. The present review incorporates the description of O. sanctum plant, its chemical constituents, and various pharmacological activities.

Retinoprotective effects of Moringa oleifera via antioxidant, anti-inflammatory, and anti-angiogenic mechanisms in streptozotocin-induced diabetic rats.

PURPOSE: The present study was aimed to evaluate the retinoprotective effects of Moringa oleifera (MO) in Streptozotocin-induced diabetic rats. METHODS: The study was continued for 24 weeks and evaluated for inflammatory (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß, angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-ß) and antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Retinal leakage was checked by Fluorescein angiography (FA) and fundus photographs were evaluated for retinal vessel caliber (arteriolar and venular). Transmission electron microscopy was done to determine basement membrane (BM) thickness. RESULTS: The results of the present study showed potential hypoglycemic and retinal antioxidant effects of MO. In the present study, a significant rise in the expression of retinal inflammatory (TNF-α and IL-1ß) and angiogenic (VEGF and PKC-ß) parameters was observed in diabetic retinae as compared to normal retinae. However, MO-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic parameters. Further, in the present study, diabetic retinae showed dilated retinal vessels as compared to normal. However, MO-treated retinae showed marked prevention in the dilatation of retinal vessels. Fluorescein angiograms obtained from diabetic retinae showed leaky and diffused retinal vasculature. On the other hand, MO-treated retinae showed intact retinal vasculature. Further, results of the transmission electron microscopy study showed thickened capillary BM in the diabetic retina as compared to normal retinae. However, treatment with MO prevented thickening of capillary BM. CONCLUSION: Our result suggests that MO may be useful in preventing diabetes induced retinal dysfunction.

Prevention and management of diabetic retinopathy in STZ diabetic rats by Tinospora cordifolia and its molecular mechanisms.

We investigated the potential of Tinospora cordifolia (TC) in treatment of diabetic retinopathy in STZ-induced rats due to its antihyperglycemic, angiogenic, antiinflammatory and antioxidant effects. The diabetic rats, treated for 24 weeks with TC extract (250 mg/kg), were evaluated for lenticular and fundus changes. Biochemical parameters were estimated and histopathological studies performed. TC significantly reduced blood glucose and glycated hemoglobin in treated rats. It prevented cataract development in treated group. Angiogenic markers VEGF and PKC increased in diabetic retina, which reduced significantly with TC. Anti-inflammatory parameters TNF-α and IL-1ß elevated in diabetic group unlike that in treated group. TC also provided defense against depletion of antioxidant enzymes- glutathione and catalase. Histopathological studies revealed thickening of basement membrane of the retinal and glomerular vasculature of diabetic rat, but no basement membrane widening was seen in treated animals. Destruction of pancreatic islet structure was observed in diabetic group, but not in treated. Thus, TC reduces blood glucose and inhibits overexpression of angiogenic and inflammatory mediators, which are distinct markers of diabetic retinopathy. It also prevents retinal oxidative stress and restores antioxidant enzyme levels. These data provide evidence for the safety and potential effect of TC in the management of experimental diabetic retinopathy.