Thiolated Chitosan-Centella asiatica Nanocomposite: A Potential Brain Targeting Strategy Through Nasal Route.

The major challenge associated with the treatment of neurological disorders is the inefficiency of drugs to enter the Central Nervous System (CNS). Polymer-drug conjugates are now being tailored to overcome this hindrance associated with conventional drugs. The study aimed at developing polymer hybrid nasal nanocomposite for enhanced delivery of Centella to the CNS. Thiolated chitosan was complexed with Centella to form a composite using EDAC hydrochloride. The composite was characterized by FTIR, XRD, NMR, and MS. Further, this composite was converted into a nanoformulation by the ionic-gelation method, characterized, and subjected to ex vivo permeation studies. Additionally, MTT assay was performed using Human Uumbilical cord Vein Endothelial Cells (HUVECs) mimicking Blood-Brain Barrier (BBB) to establish the safety of nanocomposite. The targeting efficacy was predicted by molecular docking studies against receptors associated with BBB. The FTIR, XRD, NMR, and MS studies confirmed the chemical conjugation of thiolated chitosan with Centella. Nanocomposite characterization through SEM, AFM, and DLS confirmed the size and stability of the developed nanocomposite having a zeta potential of - 14.5 mV and PDI of 0.260. The nanocomposite showed no signs of nasal ciliotoxicity and good permeation of 89.44 ± 1.75% (mean ± SD, n = 3) at 8 h across the nasal mucosa. MTT assay showed that the nanocomposite had lesser toxicity compared to the free drug (IC50 of Centella-269.1 µg/mL and IC50 of CTC nanocomposite-485.375 µg/mL). The affinity of polymer to the BBB receptors as proved by docking studies suggests the ability of polymer-based nanocomposite to concentrate in the brain post nasal administration.

Tamarindus indica. Linn leaves ameliorates experimental induced heart failure in Wistar rats.

OBJECTIVES: Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. METHODS: In vitro cardiotonic activity was determined using Langendorff's heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5 mg/kg, i.p for seven days) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200 mg/kg, p.o), high dose (400 mg/kg, p.o) and standard drug Digoxin (100 µg/kg, p.o) for seven days. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined. Isolated hearts were subjected to histopathological studies. RESULTS: The TIEE at a concentration of 60 µg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. CONCLUSIONS: The study revealed the cardioprotective activity of T. indica leaf extract by both in vitro and in vivo methods.

Repression of Polyol Pathway Activity by Hemidesmus indicus var. pubescens R.Br. Linn Root Extract, an Aldose Reductase Inhibitor: An In Silico and Ex Vivo Study.

Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of Hemidesmus indicus var. pubescens root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between ß-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that ß-sitosterol (- 10.2 kcal/mol) and hemidesmin-2 (- 8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate - 100 µg/mL (standard) and test extract (500 and 1000 µg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that H. indicus var. pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.

Antihyperglycemic and neuroprotective effects of Wattakaka volubilis (L. f. ) Stapf root against streptozotocin induced diabetes

ABSTRACT Murva is an important drug in Ayurveda. Wattakaka volubilis is used as one of the botanical sources of Murva. The aim of this study is to evaluate the effect of the alcohol extract of W. volubilis root in streptoztocin (STZ) induced diabetes and diabetic neuropathy. Diabetes mellitus (DM) was induced by the administration of STZ (45 mg/kg, i.p). DM was induced within 72 h. Diabetic animals were treated with glimepiride (0.5 mg/kg) and ethyl alcohol extract 100 and 200 mg/kg for 21 d. After determining the changes in fasting serum glucose and lipid profile, animals were further treated for a period of 15 d to determine the protective effect of extract against diabetic neuropathy. All the alcohol extract treated animals, showed a significant decrease in serum glucose level (P<0.001), and overall decrease in the severity of diabetic neuropathy. Alcohol extract of W. volubilis root showed antihyperglycemic activity and beneficial protection against diabetic neuropathy and hence can be a promising agent for treatment and prevention of diabetic neuropathy.