Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration.

Alzheimer's disease [AD] is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid ß hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid ß [Aß] and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as Punica granatum Linn, Radix Scutellariae, and Curcuma longa have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including Ginkgo biloba, Bacopa monnieri, and Withania somnifera, have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach to managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.

Quantification of Arbortristoside-A isolated from Nyctanthes arbor-tristis using HPLC: Method development and pharmaceutical applications.

Arbortristoside-A (Arbor-A) is a naturally occurring iridoid glycoside and herbal-based lead molecule with proven medicinal potential. Aiming at the development of an efficient analytical tool for the quantification of Arbor-A in pharmaceutical dosage forms, in the presented work, we developed an economical, fast, and sensitive RP-HPLC-UV method and validated the procedure as per the ICH guidelines, Q2(R1). The chromatographic separation was accomplished under the optimised experimental conditions using an HPLC system with an LC-2010 autosampler, a PDA detector, and a Phenomenex C18 column with the mobile phase composed of a 70:30 (v/v) water-acetonitrile mixture eluting isocratically at a flow rate of 1 mL/min at ambient temperature, and UV detection at 310 nm. Arbor-A showed a sharp peak at the retention time of 5.60 min and exhibited linearity (R2 = 0.9988) with LOD and LOQ of 0.50 µg/mL and 1.50 µg/mL, respectively. The accuracy of the method was 98.33-101.36 % with acceptable intra-day and inter-day precisions as well as robustness (<2% RSD). To ratify the applicability of the presented approach in emerging pharmaceuticals, a nanoformulation loaded with Arbor-A was designed and analysed utilising the provided methodology. The method has also enabled to determine the degradation kinetics of Arbor-A under stress conditions, etcetera, employing forced degradation and short term stability studies.

Fucoidan loaded PVA/Dextran blend electrospun nanofibers for the effective wound healing.

Chronic wounds have become a serious global health issue. In this study, we investigated the effect of increasing fucoidan (FD) concentration on the characteristics of nanofibers and their wound healing potential at in vitro as well as in vivo level. The results showed that increasing FD content (0.25 to 1 %) led to an significant increase in nanofiber diameter (487.7 ± 125.39 to 627.9 ± 149.78 nm), entrapment efficiency (64.26 ± 2.6 to 94.9 ± 3.1 %), and water uptake abilities (436.5 ± 1.2 to 679.7 ± 11.3 %). However, the in vitro biodegradation profile decreased with an increase in FD concentration. Water vapor transmission rate analysis showed that it was within the standard range for all FD concentrations. Nanofibers with 1 % PVA/DX/FD exhibited slow-release behavior, suggesting prolonged FD availability at the wound site. In vivo studies in rats with full-thickness wounds demonstrated that applying 1 % FD-enriched PVA/DEX nanofibers significantly (p < 0.0001) improved mean wound area closure. These findings suggest that FD-enriched nanofibers have immense potential as a wound dressing material in future if explored further.

Isolation of Arbortristoside-A from Nyctanthes arbor-tristis seeds and its structural validation by X-ray crystallographic analysis.

Aiming at confirming the chemical structure, herein, we report the crystal structure of Arbortristoside-A, isolated from the seeds of Nyctanthes arbor-tristis Linn. and investigated by single crystal X-ray crystallographic analysis. The unambiguously established structure of Arbortristoside-A not only addresses previously reported structural flaws but also encourages its chemical, computational, and physiological studies as a lead drug candidate of pharmaceutical significance.

Emerging strategies and challenges of molecular therapeutics in antileishmanial drug development.

Molecular therapy refers to targeted therapies based on molecules which have been intelligently directed towards specific biomolecular structures and include small molecule drugs, monoclonal antibodies, proteins and peptides, DNA or RNA-based strategies, targeted chemotherapy and nanomedicines. Molecular therapy is emerging as the most effective strategy to combat the present challenges of life-threatening visceral leishmaniasis, where the successful human vaccine is currently unavailable. Moreover, current chemotherapy-based strategies are associated with the issues of ineffective targeting, unavoidable toxicities, invasive therapies, prolonged treatment, high treatment costs and the development of drug-resistant strains. Thus, the rational approach to antileishmanial drug development primarily demands critical exploration and exploitation of biochemical differences between host and parasite biology, immunocharacteristics of parasite homing, and host-parasite interactions at the molecular/cellular level. Following this, the novel technology-based designing and development of host and/or parasite-targeted therapeutics having leishmanicidal and immunomodulatory activity is utmost essential to improve treatment efficacy. Thus, the present review is focused on immunological and molecular checkpoint targets in host-pathogen interaction, and molecular therapeutic prospects for Leishmania intervention, and the challenges ahead.

Identification of molecular fingerprints of natural products for the inhibition of breast cancer resistance protein (BCRP).

BACKGROUND: Extensive research over the past several decades, explored that the natural compounds contain different plant secondary metabolites and have the potential to inhibit breast cancer resistance protein (BCRP). PURPOSE: To identify crucial molecular fingerprints of some natural products for the inhibition of breast cancer resistance protein and also to screen out some potent natural BCRP inhibitors. STUDY DESIGN: Multiple modelling strategies were applied with three main mottos: (a) Generation of robust classification models to identify the linear and non-linear relationships among the natural compounds and the inhibition of BCRP, (b) Identification of important structural fingerprints that modulate BCRP inhibition and screening of natural database to find the probable hit molecules, (c) Comprehensive ligand-receptor interactions analysis of those against the putative breast cancer resistant protein through molecular docking analysis. METHODS: Monte Carlo optimization and SPCI analysis was used to identify important structural fingerprints. QSARCo. and swissADME analysis were used for screening and prediction of hits. Finally, docking analysis was performed for interaction study. RESULTS: In this study, some important structural fingerprints of BCRP inhibitors were identified. Additionally, eleven natural anti-cancer compounds were predicted to be active against the BCRP and also satisfy the different drug-likeliness properties. Among them, apigenin was found to have better binding affinities against the putative target as obtained from molecular docking analysis. CONCLUSION: This study is an attempt to understand about the molecular fingerprints of natural compounds for the inhibition of BCRP and also to dig out some novel natural inhibitors against BCRP.

Diabetes and hepatocellular carcinoma: A pathophysiological link and pharmacological management.

Both diabetes mellitus (DM) and cancer are multifarious, dissimilar, and long-lasting, fatal diseases with a remarkable influence on health worldwide. DM is not only related to cardiovascular diseases, neuropathy, nephropathy, and retinopathy, but also related to a number of liver diseases such as nonalcoholic fatty liver disease, steatohepatitis, and liver cirrhosis. Recently, it is hypothesized that DM has a greater risk for many forms of cancer, such as breast, colorectal, endometrial, pancreatic, gallbladder, renal, and liver cancer including hepatocellular carcinoma (HCC). Both DM and cancer have many common risk factors, but the association between these two is poorly stated. Several epidemiologic studies have revealed the association between pathogenic and prognostic characteristics of DM and a higher incidence of HCC, thus representing DM as an independent risk factor for HCC development. The etiological and pathophysiological relationship between DM and HCC has been presented in this review by linking hyperglycemia, hyperinsulinemia, insulin resistance, and activation of insulin-like growth factor signaling pathways and pharmacological management of HCC associated with DM.

Antiurolithiatic activity of natural constituents isolated from Aerva lanata.

BACKGROUND: Pashanabheda is used as antiurolithiatic in Ayurveda. In the present study, Aerva lanata (L) Juss. ex. Schult (Amaranthaceae) from Western Ghats of India was selected for isolation of active constituents and screening for antiurolithiatic potentials. OBJECTIVE: Screening of compounds isolated from A. lanata for antiurolithiatic potentials. MATERIALS AND METHODS: Ethylene glycol (0.75% v/v) induced urolithiasis model was used to study the antiurolithiatic activity in male Wistar albino rats. The animals were divided into five groups containing six each. Based on the LD50 of the plant extract (2000 mg/kg b.w) equivalent dose was calculated from their yield. Two isolated compounds (quercetin and betulin) of A. lanata were screened for antiurolithiatic potentials in calculi induced (ethylene glycol 0.75% v/v) male Wistar albino rats by administering 2 mg/kg b.w/day orally as test dose for 28 days. RESULTS: The urine volume was found to be significantly increased from 12.76 ± 0.10 ml to 21.35 ± 0.20 ml in the rats treated by quercetin and 21.50 ± 0.21 ml in rats treated by betulin. Urine microscopy revealed significant reduction (p < 0.001) in the size of calculi and significantly enhanced (p < 0.001) excretion of calcium, oxalate, phosphate, whereas the level of magnesium was increased. SEM of kidney sections has revealed reduction in the calculi in treated animals. Serum analysis has revealed significant reduction in the level of BUN and creatinine in treated rats. CONCLUSION: The isolated quercetin and betulin from A. lanata have shown mild diuretic effect as well as antiurolithiatic effect by significantly reducing the size of calculi in the kidneys and enhancing the excretion of calcium, phosphate, oxalate while maintaining the level of magnesium, which is reported to be one of the calculi inhibiting factors.

Efficacy of ß-sitosterol isolated from Evolvulus alsinoides L. as anti-hyperlipidemic and anti-tumor agent: Evidence from animal studies.

OBJECTIVE: To explore the anti-hyperlipidemic and anti-tumor effect of ethanolic extract of Evolvulus alsinoides, its chloroform fraction and isolated components in Triton-induced hyperlipidemic rats. METHODS: Animals were administered with intraperitoneal (i.p.) injection of Triton WR 1339 at a dose of 400 mg/kg body weight. After 24 h of Triton administration the test drugs were administered orally at a dose of 200 mg/kg body weight in rats. The ethanolic extract and stigmast-5-en-3ß-ol from Evolvulus alsinoides were further investigated for the tumor take inhibitory activity in hybrid mice (of C57BL strain + Swiss albino strain). Preventive group animals were injected daily with the extract and stigmast-5-en-3ß-ol at dose of 50 mg/kg body weight i.p. for 10 consecutive days. The animals were observed for the growth of tumor after injection of B16F10 melanoma cells into the dorsal skin of mice. RESULTS: Stigmast-5-en-3ß-ol showed a marked antihyperlipidemic potential by reducing the total cholesterol, triglycerides, low density lipoproteins level, and significantly increased high density lipoprotein level compared with other isolated component. Pretreatment with the drug showed delay tumor growth by increasing the volume doubling time and growth delay. The stigmast-5-en-3ß-ol showed better mean survival time. CONCLUSION: The supplementation of antioxidants and phytosterols rich food Evolvulus alsinoides has significant tumor take inhibitory activity.

Natural products as potential drug permeation enhancer in transdermal drug delivery system.

Permeation enhancers are defined as substances that are capable of promoting penetration of drugs into skin and transdermal therapeutic systems offers a more reliable mean of administering drug through the skin. Skin is a natural barrier so it is necessary to employ enhancement strategies to improve topical bioavailability. This review explores that natural products have got potential to enhance the permeation of the drug through skin by reversibly reducing the skin barrier resistance. The use of natural products is the most reliable means of permeation enhancement of transdermally administered drugs and permits the delivery of broader classes of drugs through the stratum corneum. They are safe, non-toxic, pharmacologically inert, non-irritating, and non-allergenic to use as permeation enhancers. The present review initially highlights the current status of natural products on the basis of SAR studies which have shown significant enhancer activities.

A survey on polypharmacy and use of inappropriate medications.

In the past, polypharmacy was referred to the mixing of many drugs in one prescription. Today polypharmacy implies to the prescription of too many medications for an individual patient, with an associated higher risk of adverse drug reactions (ADRs) and interactions. Situations certainly exist where the combination therapy or polytherapy is the used for single disease condition. Polypharmacy is a problem of substantial importance, in terms of both direct medication costs and indirect medication costs resulting from drug-related morbidity. Polypharmacy increases the risk of side effects and interactions. Moreover it is a preventable problem. A retrospective study was carried out at Bhopal district (Capital of Madhya Pradesh, India) in the year of September-November 2009 by collecting prescriptions of consultants at various levels of health care. The tendency of polypharmacy was studied and analyzed under the various heads in the survey. Available data suggests that polypharmacy is a widespread problem, and physician, clinical pharmacists and patients are all responsible. These risks can be minimized through identifying the prevalence of this potential problem in a high-risk population and by increasing awareness among patients and healthcare professionals. Physicians and clinical pharmacists have the potential to combating this problem through a variety of interventions such as reducing the number of medications taken, reducing the number of doses taken, increasing patient adherence, preventing ADRs, improving patient quality of life and decreasing facility and drug costs.

Antidiabetic activity of Cassia occidentalis (Linn) in normal and alloxan-induced diabetic rats.

OBJECTIVE: To evaluate the hypoglycemic activity of various extracts, petroleum ether, chloroform and aqueous extract of Cassia occidentalis in normal and alloxan-induced diabetic rats. MATERIALS AND METHODS: Petroleum ether, chloroform and aqueous extract of whole plant of Cassia occidentalis were orally tested at the dose of 200 mg/kg for hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract-treated diabetic rats, were compared with diabetic control and normal animals. Histopathological observations during 21 days treatment were also evaluated. RESULTS: Aqueous extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats. Apart from aqueous extract, petroleum ether extract showed activity from day 14 and chloroform extract showed activity from 7 days. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein, and changes in body weight by aqueous extract treated-diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathological studies of the pancreas of these animals showed comparable regeneration by extract which were earlier necrosed by alloxan. CONCLUSION: Aqueous extract of C. occidentalis exhibited significant antihyperglycemic activity in normal and alloxan-induced diabetic rats. They also showed improvement in parameters like body weight and serum lipid profiles as well as histopathological studies showed regeneration of ß-cells of pancreas and so might be of value in diabetes treatment.

Hypolipidemic activity of seeds of Cassia tora Linn.

Ethanolic extract of seeds of Cassia tora L. and its fractions were investigated for hypolipidemic activity on triton induced hyperlipidemic profile. Ethanolic extract and its ether soluble and water soluble fraction decreased serum level of total cholesterol by 42.07, 40.77 and 71.25%, respectively. On the other hand ethanolic extract, ether soluble fraction and water soluble fraction increased the serum HDL-cholesterol level by 6.72, 17.20 and 19.18%, respectively. Ethanolic extract, ether fraction and water fraction decreased triglyceride level by 26.84, 35.74 and 38.46%, respectively. The reduction in LDL-cholesterol level by ethanolic extract, ether soluble fraction and water soluble fraction were 69.25, 72.06 and 76.12%, respectively.