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.

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.

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.

Modifying anti-inflammatory effect of Diclofenac with Murraya koenigii.

Murraya koenigii (Curry leaves) has been widely used in Asian countries for the treatment of some ailments such as diabetes and hypertension. In the present study, leaves of Murraya koenigii were extracted with ethanol and evaluated for anti-inflammatory activity in rats using carrageenan induced paw edema method. Ethanolic extract showed a potent anti-inflammatory activity at third hour after carrageenan administration when compared with the standard drug, Diclofenac. The percent inhibition of paw volume was found to be 84.75% for 50 mg/kg of extract whereas it was found to be 80.86% for 50 mg/kg extract in combination with Diclofenac 10 mg/kg. Thus, the present study suggests that the combination therapy potentiates the anti-inflammatory effect of diclofenac and may help in reducing the dose of the synthetic drug. Some relevant patents are also outlined in this article.

Effective detoxification of Abrus precatorius Linn. seeds by Shodhana.

Ayurveda, which is one of the traditional systems of medicine of India, reports the seeds of Abrus precatorius (family: Fabaceae) can be used therapeutically after shodhana process, which removes the toxin. The main objective was to scientifically study the shodhana process by evaluating the safety and efficacy of A. precatorius seeds. Aqueous extract (A1) and detoxified extract (A2) of the seeds were prepared by a process described in Ayurvedic pharmacopoeia. Thin-layer chromatography (TLC) method was developed for the two extracts using different solvent systems. Identical spots were obtained in A1 with reference values (Rf) 0.27, 0.47, and 0.79, whereas A2 showed the absence of spot having Rf value 0.47, which could possibly be the toxin found in the intact seed. A1 and A2 were evaluated for their safety and efficacy. The acute toxicity studies for A1 and A2 revealed that A1 was toxic, whereas A2 was safe at the dose of 2 g/kg. Absence of toxicity in the detoxified extract suggests removal of toxic material in processed seeds. The results obtained for hair growth activity of both the extracts were comparable to that of the standard. However, A2 showed better results in comparison to A1. Thus, the shodhana process described in Ayurveda helps in removing the toxin, while retaining the efficacy at the same time. The statistical analysis was done using one-way analysis of variance.

Intestinal permeability of Lamivudine using single pass intestinal perfusion.

The intestinal transport of lamivudine, a nucleotide reverse transcriptase inhibitor, was investigated using the single pass intestinal perfusion technique in male Wistar rats. Single pass intestinal perfusion was performed in small intestine at a flow rate of 0.20 ml/min. Lamivudine exhibits a high intestinal permeability over the length of the small intestine indicative of compounds that are well absorbed. The P eff of lamivudine is in the range of drugs with high intestinal permeability and high fraction of dose absorbed indicating that lamivudine readily crosses the intestine. This also suggests that lamivudine belongs to biopharmaceutics classification system class I and is a good candidate for biopharmaceutics classification system based biowaiver. The permeability values obtained from this study may be useful in models of exposure assessment.