Therapeutic Management and New Upcoming Approaches for Age Related Macular Degeneration.

Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.

Intranasal delivery: An attractive route for the administration of nucleic acid based therapeutics for CNS disorders.

The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.

Gasdermins: Pore-forming Proteins as a Potential Therapeutic Target.

Gasdermins are novel pore forming proteins that comprise Gasdermin A, Gasdermin B, Gasdermin C, Gasdermin D, Gasdermin E and Pejvakin (DFNB59). Recently, pyroptosis has been redefined as "Gasdermin mediated necrosis", as gasdermins are key regulators of apoptosis, necrosis, and pyroptosis. The discovery of the gasdermin family has broadened the field of pyroptosis studies. Studies have correlated gasdermins with several diseases. This review summarizes the physiological roles and signal transduction of gasdermins. It further highlights the role of gasdermins in pathological conditions like autoimmune disease, kidney diseases, and central nervous system diseases.

Triphala churna ameliorates retinopathy in diabetic rats.

Diabetic retinopathy is one of the most prevalent complications of diabetes affecting a large number of people worldwide. Triphala churna - an Ayurvedic formulation consisting of powder of three fruits, Emblica officinalis, Terminalia bellirica and Terminalia chebula has potent antioxidant and anti-diabetic properties. Hence, the study was designed to evaluate the effect of Triphala churna in diabetic retinopathy. Diabetes was induced in rats with streptozotocin (55 mg/kg, i.p.). After four weeks of induction, animals were treated with Triphala churna powder mixed in a vehicle at a dose of 250, 500, and 1000 mg/kg for the next four weeks. At the end of the study, plasma glucose, lactate dehydrogenase levels were determined. Sorbitol dehydrogenase, aldose reductase, and oxidative stress parameters were determined in lens tissues. Electroretinography was carried out. Histopathology study of the retina was studied at the end of the study. Triphala churna significantly reduced plasma glucose and lactate dehydrogenase levels. Triphala significantly reduced sorbitol dehydrogenase, aldose reductase, and oxidative stress in lens tissues. Furthermore, Triphala significantly increased 'a' wave and 'b' wave amplitude with a reduction in the latencies. The retinal thickness was significantly reduced in Triphala-treated animals. From the results, it can be concluded that Triphala churna delays the progression of retinopathy in diabetic rats.

Narirutin-rich fraction from grape fruit peel protects against transient cerebral ischemia reperfusion injury in rats.

Objective: Ischemic stroke is one of the leading causes of disability in adults worldwide. The present study was aimed to evaluate the efficacy of Narirutin-rich fraction (NRF), obtained from grape fruit peel, on cerebral ischemia/reperfusion injury in rats.Methods: Male Wistar rats (180-200 g) were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to induce cerebral ischemia/reperfusion injury. NRF (150, 300 mg/kg, oral) was administered for 7 days continuously before animals were subjected to ischemia/reperfusion injury. Various behavioral tests (for measurement of motor coordination, locomotor activity, and spatial memory), biochemical parameters (lipid peroxidation, superoxide dismutase, and catalase activity), and histopathological alterations were assessed.Results: Seven-day NRF (150 and 300 mg/kg) pretreatment significantly improved neurobehavioral alterations and histological findings as compared to the disease control group. Further NRF treatment significantly reduced oxidative damage as indicated by improved lipid peroxidation, superoxide dismutase, and catalase activity as compared to disease control animals.Conclusion: The present study demonstrated the protective effect of NRF against cerebral ischemia/reperfusion injury in rats. The results suggest that NRF can be a potential pretreatment option against cerebral ischemia/reperfusion injury.

Triphala Churna-A Traditional Formulation in Ayurveda Mitigates Diabetic Neuropathy in Rats.

Neuropathy is a common complication of diabetes affecting a large number of people worldwide. Triphala churna is a formulation mentioned in Ayurveda-a traditional system of medicine. It is a simple powder formulation consisting of powders of three fruits, Emblica officinalis L., Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Individual components of Triphala churna have anti-diabetic and antioxidant activities. Hence, this study was designed to evaluate the effect of Triphala churna on diabetic neuropathy. Diabetes was induced with streptozotocin (STZ, 55 mg/kg, i. p.) in rats. Animals were grouped and treated orally with Triphala churna at a dose of 250, 500, and 1,000 mg/kg after 6 weeks of diabetes induction for the next 4 weeks. At the end of study, parameters such as body weight, plasma glucose level, motor nerve conduction velocity were determined. The effect of Triphala churna on thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia was also determined at the end of study. The plasma cytokine levels like TGF-ß1, TNF-α, and IL-1ß were determined by ELISA assay. Histopathology study of the sciatic nerve was studied. Western blotting was performed to study the expression of neuronal growth factor.Treatment with Triphala churna showed a significant reduction in plasma glucose and a significant rise in body weight. Triphala treatment significantly increased the motor nerve conduction velocity and decreased the thermal and mechanical hyperalgesia, as well as mechanical allodynia. The treatment significantly inhibited levels of circulatory cytokines like TGF-ß1, TNF-α, and IL-1ß. Histopathology study confirmed the neuroprotective effect of Triphala churna. The expression of NGF was significantly increased in sciatic nerves after treatment with Triphala churna. From the results, it can be concluded that Triphala churna delays the progression of neuropathy in diabetic rats.

Delivery systems for improving iron uptake in anemia.

Anemia poses a threat to a broad population globally as depleted hemoglobin leads to a plethora of conditions, and the most common cause includes iron deficiency. Iron is an essential element important for erythropoiesis, DNA synthesis, protection of the immune system, energy production, and cognitive function and hence should be maintained at appropriate levels. Various proteins are involved in transporting and absorption of iron, activation of heme synthesis, and RBC production that could be possible targets to improve iron delivery. Oral supplementation of iron either from dietary or synthetic sources has been the frontline therapy for treating iron deficiency in anemia. At the same time, intravenous administration is provided in chronic anemia, such as chronic kidney diseases (CKD). This review focuses on the strategies developed to overcome the disadvantages of available iron therapies and increase iron absorption and uptake in the body to restore iron content. Nanotechnology combined with the food fortification processes gained attention as they help develop new delivery systems to improve iron uptake by enterocytes. Furthermore, naturally obtained products such as polysaccharides, peptides, proteins, and new synthetic molecules have been used in fabrication of iron-carrier systems. The establishment of transdermal iron delivery systems such as microneedle arrays or iontophoresis, or the discovery of new molecules also proved to be an effective way for delivering iron in patients non-compliant to oral therapy.

Garcinol enriched fraction from the fruit rind of Garcinia indica ameliorates atherosclerotic risk factor in diet induced hyperlipidemic C57BL/6 mice.

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Triphala Ameliorates Nephropathy via Inhibition of TGF-ß1 and Oxidative Stress in Diabetic Rats.

INTRODUCTION: Advanced glycation end products, oxidative stress, and TGF-ß expression play a crucial role in pathophysiology of diabetic nephropathy. Inhibition of oxidative stress and TGF-ß expression by natural traditional medicines may give an economic and safe alternative treatment option. Triphala churna, a traditional medicine, has been proved to have potent antioxidant activity, and individual components of it have shown significant antidiabetic activity. Hence, the present study was designed to study the effect of Triphala churna in diabetic nephropathy in rats. METHODS: Diabetes was induced in rats by administration of streptozotocin (55 mg/kg i.p.). Four weeks after induction of diabetes, the animals were treated with Triphala churna at the doses of 250, 500, and 1,000 mg/kg for next 4 weeks. Various biochemical and urine parameters such as glucose, creatinine, blood urea nitrogen (BUN), total protein, and albumin were assessed at the end of study. Creatinine clearance, BUN clearance, and glomerular filtration rate were determined. Oxidative stress parameters such as malondialdehyde, catalase, reduced glutathione, and superoxide dismutase were determined in kidney tissues. TGF-ß1 expression was measured with ELISA, immunohistochemistry, and western blot techniques. Histopathology study was carried out with haemotoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining to determine histological changes. RESULTS: Treatment with Triphala churna significantly improved urine parameters. Triphala churna treatment also improved plasma proteins, albumin, creatinine, and BUN levels. The oxidative stress was reduced in the kidney with the treatment of Triphala churna. Histopathological studies revealed that Triphala churna reduced kidney damage. Immunohistochemistry, ELISA, and western blotting study revealed that treatment with Triphala decreased the expression of TGF-ß in kidney tissues. CONCLUSION: From the results, it can be concluded that Triphala churna has a significant nephroprotective effect because of its capability of inhibiting oxidative stress and TGF-ß in diabetes.

Gut microbiome a promising target for management of respiratory diseases.

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer's Disease.

BACKGROUND: The only conclusive way to diagnose Alzheimer's is to carry out brain autopsy of the patient's brain tissue and ascertain whether the subject had Alzheimer's or any other form of dementia. However, due to the non-feasibility of such methods, to diagnose and conclude the conditions, medical practitioners use tests that examine a patient's mental ability. OBJECTIVE: Accurate diagnosis at an early stage is the need of the hour for initiation of therapy. The cause for most Alzheimer's cases still remains unknown except where genetic distinctions have been observed. Thus, a standard drug regimen ensues in every Alzheimer's patient, irrespective of the cause, which may not always be beneficial in halting or reversing the disease progression. To provide a better life to such patients by suppressing existing symptoms, early diagnosis, curative therapy, site-specific delivery of drugs, and application of hyphenated methods like artificial intelligence need to be brought into the main field of Alzheimer's therapeutics. METHODS: In this review, we have compiled existing hypotheses to explain the cause of the disease, and highlighted gene therapy, immunotherapy, peptidomimetics, metal chelators, probiotics and quantum dots as advancements in the existing strategies to manage Alzheimer's. CONCLUSION: Biomarkers, brain-imaging, and theranostics, along with artificial intelligence, are understood to be the future of the management of Alzheimer's.

Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel drug delivery approach.

BACKGROUND: Ginger and castor oil, both are used in traditional medicine to treat arthritis, the latter is also commonly used as a vehicle in these systems of medicine. The study was designed to prepare a nanostructured lipid carrier (NLC) of ginger extract using castor oil as a novel liquid lipid and evaluate its safety and efficacy in rheumatoid arthritis in experimental animals. METHODS: Ginger extract was standardized using High performance liquid chromatography (HPLC). The optimized NLC formulation was characterized and its therapeutic efficacy was evaluated in Chronic Freund's adjuvant (CFA) induced arthritis in experimental animals. RESULTS: Ginger extract contained 38.76 ± 3.01%w/w of 6-gingerol. The optimized NLC formulation showed a particle size of around 205 nm, a zeta potential of -33.7 and %entrapment efficiency of 76.59 ± 0.83%. Reduction in primary inflammation was significantly higher with NLC when compared with ginger extract and castor oil alone (p<0.001). The formulation also improved hyperalgesia in rats. CONCLUSION: Castor oil can be used as a novel lipid in the preparation of NLC. The NLC effectively enhanced the therapeutic value of poorly bioavailable ginger extract.

Current trends in theranostics for rheumatoid arthritis.

The very complexity of Rheumatoid Arthritis (RA) makes its prognosis and management challenging. The manifestations pertaining to RA emerge in the late stage of the disease when the damage to bone and cartilage has already occurred. Therefore early diagnosis of RA becomes critical in order to avoid further complications and disabilities. In such a scenario, theranostics can be an ideal solution to tackle the barriers to disease management in RA patients. Nanotechnology has paved the way for emerging theranostics to achieve better targetability and high performance. The shortcomings of current diagnostic techniques and pharmacological treatment are addressed in this review. The article also summarizes the laboratory studies that have reported promising theranostic entities for RA diagnosis, treatment and discusses the outcomes of each. Novel platforms combined with newer techniques have found application in the theranostics of RA. These platforms include gold nanorods, nanoshells, nanowhiskers, magnetic nanoparticles, solid and mesoporous silica nanoparticles, etc. Photodynamic, chemo-photo responsive, magnetic field based imaging and simultaneous stimulation have been reported for the release of therapeutic moieties from these nanoplatform. Theranostics can also assist clinicians in determining the respondents and non-respondents to biological response modifiers and other treatments available for RA. This not only plays an important role in selecting the suitable therapy for every patient but also in monitoring the progress of treatment in the patient. The advantages of theranostics over current diagnosis and treatment for RA are tremendous. Hence it holds great opportunities for progress and enhancement of RA disease management.

Recent Patents and Discovery of Anti-inflammatory Agents from Marine Source.

BACKGROUND: Inflammation has become pathology in the majority of the prevalent diseases such as diabetes, atherosclerosis, epilepsy and neurodegenerative disorders. Anti-inflammatory drugs work wonder in all these conditions, where the patient has become refractory to standard treatment. However, available anti-inflammatory agents have side effects associated with chronic use, thus if we could develop safe and efficacious molecules, quality of health care provided will improve. Since plant sources have been extensively explored, the focus needs to be shifted on the alternative natural sources of anti-inflammatory agents. Water bodies especially the sea and ocean are under investigation to find agents which can tackle inflammation. OBJECTIVE: This article reviews anti-inflammatory agents obtained from five types of marine organisms namely microalgae, sea cucumber, mussels, sponges and corals. METHODS: A literature search was conducted using PubMed/Science Direct with keywords marine organisms, inflammation, marine sponges, sea cucumber, mussels, corals and microalgae. Patents were searched using the key terms inflammation, marine agents from www.google.com/patents, www.uspto.gov, http://espacenet.com, www.freepatentsonline.com, www.wipo.int/pctdb/en/searchsimp. jsp and www.freshpatents.com. RESULTS: Literature and current patents have revealed applications of anti-inflammatory agents from marine organisms in pharmaceuticals and cosmeceuticals. These agents are used to treat inflammatory disorders ranging from minor allergy to chronic conditions like rheumatoid arthritis. Marine waste is also a valuable resource for nutraceuticals and anti-inflammatory agents. CONCLUSION: The findings reveal that marine organisms could be a promising source of novel antiinflammatory agents. However, further investigations are suggested for the isolation and identification of bioactive, exploring the mechanism of action and evaluating the efficacy in various inflammatory conditions.

Attenuation of isoproterenol-induced cardiotoxicity in rats by Narirutin rich fraction from grape fruit.

BACKGROUND: Oxidative stress is one of the major mechanism involved in pathogenesis of myocardial infarction. Use of natural products as therapeutic approach for ischemic myocardial injury is gaining attention worldwide. PURPOSE: This study was designed to investigate efficacy of Narirutin rich fraction (NRF), obtained from grape fruit peel, in the treatment of isoproterenol induced myocardial infarction in rats. METHODS: After 3-days pretreatment with NRF (100  mg/kg and 200  mg/kg, p.o.) myocardial injury was induced by subcutaneous administration of isoproterenol (85  mg/kg) for 2 days. Hemodynamic parameters, biochemical parameters, histological and ultrastructural changes were observed. RESULTS: Isoproterenol induced myocardial injury was evidenced by significant alterations in ECG, mean arterial pressure and left ventricular functions. Myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level were reduced while MDE levels were increased. Histological findings also showed severe changes. Treatment with NRF significantly attenuated these parameters in dose dependent manner. CONCLUSION: Thus, present study provides evidences for efficacy of NRF against isoproterenol induced myocardial infarction in rats.

Anticonvulsant effect of Sphaeranthus flower extracts in mice.

Sphaeranthus indicus whole herb is included as a Rasayana drug in Ayurveda and is reported for the treatment of epilepsy. S. indicus flowers have anxiolytic, hypotensive, peripheral vasodilatory and cathartic activity. The objective of this study was to evaluate the anticonvulsant activity of the extract of flowers of S. indicus in various animal models of epilepsy. The anti-epileptic activity of Methanolic extract (ME) and Acetone extract (AE) of the flowers was evaluated using Maximal electro shock (MES) seizures, Pentyelenetetrazole (PTZ) induced convulsions and Picrotoxin induced convulsions. ME (50 mg/kg and 100 mg/kg) and AE (100 and 200 mg/kg respectively) protected animals against PTZ and Picrotoxin induced convulsion but did not have any effect against MES induced convulsion. In conclusion, the results of this study suggest that both the ME and AE possess promising anticonvulsant activity. It is further suggested that the flavonoids in the extract by the virtue of their effect on benzodiazepine site of GABA receptor, might be responsible for the effect, although no study is undertaken to prove this aspect. Nevertheless, the study provides pharmacological credibility to the anti-epileptic use of S. indicus suggested in Ayurveda.

Anti-Arthritic Effect of Garcinol Enriched Fraction Against Adjuvant Induced Arthritis.

BACKGROUND: Garcinia indica also known as kokum is used in traditional system of medicine for relieving inflammation and rheumatic pain. Garcinol, a benzophenone obtained from its fruit rind is reported to have anti-inflammatory effect via modulating arachidonic acid metabolism, suppressing iNOS expression, NF-κB activation and COX-2 expression. It has also been studied for antioxidant and anticancer activity. Apart from these, few patents claim that garcinol also has anti-obesity and hepatoprotective effect and has a potential to be used for the treatment of renal disorders, endometriosis and cardiac dysfunction. OBJECTIVE: Garcinol Enriched Fraction (GEF) from the fruit rind of Garcinia indica should be effective in the treatment of arthritis, one of the chronic inflammatory disorder owing to its anti-inflammatory property as indicated by earlier experiments. METHODS: GEF was prepared from the fruit rind of Garcinia indica and quantified using LC-MS/MS. It was found to contain 89.4% w/w of garcinol. GEF was evaluated at the dose of 10mg/kg for its efficacy against Complete Freund's Adjuvant (CFA) induced arthritis in Wistar albino rats. Paw volumes of both sides were measured by Plethysmometer and body weight was recorded on 0, 1, 5, 12 and 21st day. The hyperalgesic response was also measured by motility test and stair climbing test. RESULTS: GEF showed a significant reduction in paw swelling (p < 0.0001) and arthritis index (p < 0.0001) exhibiting anti-inflammatory potential. It also improves the motility and stair climbing ability of experimental animals (p < 0.05), thus reducing hyperalgesia. CONCLUSION: Garcinol enriched fraction shows anti-arthritic activity in experimental animals.

In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats.

BACKGROUND: Terminalia arjuna Wight & Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. T. arjuna bark extract has been reported to play a significant role as a cardiac stimulant for its beneficial effects in angina. Herb - drug interactions (HDI) are one of the most important clinical concerns in the concomitant consumption of herbs and prescription drugs. Our study was to investigate the in vitro CYP2D inhibition potential of Terminalia arjuna (T. arjuna) extracts in rat liver microsomes and to study the influence of aqueous bark extract of T. arjuna on the oral pharmacokinetics and pharmacodynamics of metoprolol succinate in rats. METHODS: The CYP2D inhibition potential of herbal extracts of T. arjuna was investigated in rat liver microsomes. Pharmacokinetic-pharmacodynamic interaction of aqueous extract of T. arjuna with metoprolol succinate was investigated in rats. RESULTS: The ethyl acetate, alcoholic & aqueous bark extracts of T. arjuna showed potent reversible non-competitive inhibition CYP2D enzyme in rat liver microsomes with IC50 values less than 40 µg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP2D enzyme in rat liver microsomes. Pharmacokinetic studies showed that aqueous bark extract of T. arjuna led to a significant reduction (P < 0.05) in AUC0-24h and Cmax of metoprolol succinate in rats, when co-administered. Pharmacodynamic studies reveal a significant reduction in therapeutic activity of metoprolol succinate on co-administration with aqueous bark extract of T. arjuna. CONCLUSION: Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with T. arjuna extracts should be done with caution.

Does copper enhance the antihypertensive effect of Elaeocarpus ganitrus in experimentally induced hypertensive rats?

Ayurveda, one of the traditional systems of medicine of India, reports that the seeds of Elaeocarpus ganitrus Linn. (Tilaceae) can be used for the treatment of hypertension. The main aim is to evaluate the antihypertensive effect of Elaeocarpus ganitrus (Rudraksha) seeds. Powdered seeds were extracted by maceration, overnight, using water, in copper (E1) and glass vessel (E2) and analyzed for antihypertensive activity in cadmium chloride (1 mg/kg intraperitoneally, for a period of 15 days) induced hypertensive male Wistar rats at three dose levels. E1 was administered at the dose of 5, 10, and 15 mg/kg and E2 at dose of 10, 20, and 30 mg/kg. All the data were analyzed using one way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. E1 and E2 did not show any toxicity at the dose of 5 g/kg in rats. It was found that 15 mg/kg of E1 and 30 mg/kg of E2 decreases the blood pressure by 30.20 mmHg and 28.96 mmHg, respectively, in hypertensive rats. Thus, it can be said that 15 mg/kg of E1 produced similar decrease in blood pressure as was observed with 30 mg/kg of E2. Copper ions in E1 might be additively affecting the reduction in blood pressure with the usage of Elaeocarpus ganitrus extracts.

Synthesis and evaluation of novel marine bromopyrrole alkaloid-based derivatives as potential antidepressant agents.

Herein, we report synthesis and screening of a series of twenty derivatives of bromopyrrole alkaloids with aroyl hydrazone feature for antidepressant activity by forced swim test (FST), tail suspension test (TST), and actophotometer method. The molecules were further evaluated for in vitro human MAO's inhibitory activities. The tested compounds exhibited moderate to good antidepressant activity compared with standard fluoxetine. Among these, most promising antidepressant derivatives 5b (%DID = 60.48), 5e (%DID = 59), and 5j (%DID = 74.86) reduced immobility duration of 50-70% at 30 mg/kg dose levels in FST. Further, derivative 5b, 5e, and 5j displayed good antidepressant activity with %DID value of 47.50, 46.62, and 52.49, respectively, in TST compared with standard fluoxetine (66.56% DID). Compound 5b showed high in vitro MAO-A potency and selectivity (Ki MAO-A (µM) = 2.4 ± 0.99, SI = 0.06) with promising pharmacological activity recognizing its potential as antidepressant lead candidate for further drug development. Study revealed that the presence of halogen atoms such as chlorine and fluorine at ortho- and/or para-position of phenyl ring and N-alkylation of pyrrole core is favored features for antidepressant activity.