Metabolic disorders, such as obesity, type 2 diabetes mellitus, dyslipidemia and hypertension, are one of the fastest-growing health issues across the world due to insulin resistance, low-grade chronic inflammation, and disrupted energy homeostasis. The endocannabinoid system (ECS) is a crucial factor in the regulation of appetite, glucose and lipid metabolism, inflammatory signalling, and energy balance, as the cannabinoid type 1. CB1 receptor has become a major molecular mediator in the pathogenesis of metabolic diseases. Initial clinical trials showed that pharmacological inhibition of the CB1 receptor could promote body weight, glycemic and lipid profile and cardiometabolic risk factors; first-generation centrally acting CB1 antagonists, like rimonabant, were discontinued because of unacceptable neuropsychiatric adverse effects. This constraint led to a paradigm shift in the creation of the peripherally restricted CB1 receptor antagonist that maintains metabolism efficacy and limits exposure to the central nervous system (CNS). The role of the peripheral CB1 receptor in obesity, insulin resistance, dyslipidemia, and hypertension is critically discussed in this review, and the mechanisms by which CB1 blockade improves insulin sensitivity, reduces lipid accumulation, attenuates inflammation, and maintains glucose homeostasis are elucidated. The emerging technology in medicinal chemistry has resulted in the discovery of novel peripherally selective CB1 antagonists, such as RTI1092769, INV-202, BAR-1, otenabant and thioamide-based antagonists, which exhibit encouraging preclinical efficacies with reduced safety profiles. Moreover, contemporary obstacles in clinical translation, regulatory mechanisms, and prospects of using combination therapy, precision medicine, and targeting with tissue are also described. Taken together, the peripherally selective CB1 receptor blockade is a mechanistically well-founded and highly promising therapeutic approach in the treatment of metabolic disorders. Keywords: Cannabinoid type-1 receptor, Endocannabinoid system, Metabolic disorder, Type 2 diabetes mellitus, Obesity

The gut-brain axis (GBA) is an intricate, bidirectional communication network connecting the central nervous system (CNS) and gastrointestinal tract (GIT) via neural, immune, endocrine, and metabolic pathways. This dynamic interaction, modulated by the gut microbiota, influences essential physiological and cognitive functions, including mood regulation, stress response, and neuronal signaling. Dysbiosis, an imbalance in gut microbial composition, contributes to neurodegenerative disorders (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) by promoting inflammation and neuroinflammation, oxidative stress, neurotransmitter production and regulation, bloodbrain barrier integrity, protein aggregation, and misfolding. Microbial metabolites, such as short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives, play a crucial role in maintaining CNS homeostasis, whereas neurotoxic metabolites, like trimethylamine N-oxide (TMAO), exacerbate neurodegenerative pathology. Therapeutic interventions, including dietary modulation, prebiotics, probiotics, psychobiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and small-molecule modulators, represent promising approaches to restore GBA balance and delay neurodegeneration. However, challenges remain in translating preclinical evidence into human application due to interindividual microbiome variability and limited mechanistic understanding. Emerging methodologies such as organ-on-a-chip models, wearable biosensors, and artificial intelligence-driven microbiome analytics hold potential for personalized, microbiota-based therapies. Standardization of biomarkers and study protocols will be essential to further clarify the GBA’s mechanistic involvement and therapeutic potential in neurodegenerative disease management.

Background: Alcohol withdrawal (AWD) induces central nervous system hyperexcitability, leading to anxiety, depression, and motor dysfunction, primarily via dysregulation of GABAergic, glutamatergic, and monoaminergic systems. Thymol, a monoterpenoid phenol from Thymus vulgaris, possesses documented GABAA receptor modulatory, anxiolytic, antioxidant, and anti-inflammatory properties. This study evaluated thymol's protective effects against AWD-induced neurobehavioral abnormalities in mice. Material and Methods: Adult male Swiss albino mice were divided into six groups (n = 6/group): Control (CON) - vehicle-treated, Ethanol Withdrawal (EW) - 10% ethanol at 2 g/kg p.o. for 10 days, followed by abrupt withdrawal + Thymol 10 (EW-T10)- 10 mg/kg p.o. Thymol during withdrawal, EW+ Thymol 30 (EW-T30)-30 mg/kg p.o. thymol during withdrawal, Thymol 10 (T10) and Thymol 30 (T30) - Thymol only, no ethanol exposure. behavioural testing was performed 24 hours post-withdrawal using: Elevated Plus Maze (EPM), Open Field Test (OFT), and Light-Dark Test (LDT) for anxiety-like behaviour, Hole Board Test (HBT) for exploratory activity, Marble Burying Test (MBT) for compulsive/anxiety-linked behavior, Tail Suspension Test (TST) for depressive-like behavior, Stumbling and rotarod test for motor incoordination. Statistical analysis was conducted using one-way ANOVA followed by Tukey's post hoc test (p<0.05). Results: AWD significantly increased anxiety-like behavior (EPM, OFT, LDT), compulsive behavior (MBT), depressive-like behavior (TST), and motor incoordination, while reducing exploration (HBT). Thymol treatment (10 and 30 mg/kg) significantly reversed these alterations in a dose-dependent manner. The higher dose (EW-T30) showed near-complete behavioral restoration. Thymol alone caused no adverse effects. Conclusion: Conclusion: Thymol exhibits significant neuroprotective effects against alcohol withdrawal-induced anxiety, depression, and motor deficits in mice. Its likely mechanism involves positive modulation of GABA-A receptors, attenuation of oxidative stress, and restoration of neurotransmitter homeostasis. These findings support thymol's potential as a phytopharmacological agent for managing alcohol withdrawal syndrome and its neuropsychiatric sequelae.

Alcohol withdrawal is a serious condition that often leads to heightened anxiety, depressive symptoms, and problems with motor coordination, all of which can significantly affect quality of life. These effects are largely tied to chemical imbalances in the brain, particularly involving GABA and glutamate systems, as well as oxidative stress. Berberine, a natural plant alkaloid long recognized for its therapeutic potential, is known to have calming, mood-stabilizing, and neuroprotective properties. In this study, mice were exposed to repeated alcohol intake (10% v/v, 2 g/kg p.o) followed by withdrawal, which produced marked behavioral changes resembling anxiety, depression, and poor motor performance. When treated with berberine (10 or 30 mg/kg p.o.) , however, these animals showed a clear reversal of withdrawal-induced problems. At both lower and higher doses, berberine reduced anxiety-like behavior, improved exploratory activity, lessened depressive signs, and improved motor coordination, with the higher dose offering stronger benefits. Importantly, berberine by itself did not cause any harmful effects, suggesting that it is safe in this context. These findings indicate that berberine may offer meaningful protection against the emotional and motor disturbances caused by alcohol withdrawal. Its ability to ease anxiety and depression while supporting brain function makes it a promising candidate for managing alcohol withdrawal syndrome.

Mainaim of current research was to determine feasibility of developing, designing, and testing liposomal formulations loaded with Fulvestrant for purpose of targeted drug transfer in management of breast cancer. With an impressive encapsulation effectiveness of 85%, they were made utilizing the thin-film hydration approach solvent evaporation followed high pressure homogenization technique for particle size reduction..The physicochemical characterization, these liposomess were seen to be in the dimension of <150-200nm with low polydispersity index (<0.3), -25 mV of the zeta potential, and indicated stability and will also be best for an in vivo application. Ex-vivo diffusion will reveal high numbers of drugs being released as compared to free Fulvestrant and further made the release sustained over 48 hours. Cytotoxic evaluation of MCF-7 breast cancer cells was exhibited that for fulvestrant-loaded liposomes at 5 μM, there was a 50% reduction of cell viability-which is an extremely significant increase compared with free drug (30% reduction). Pharmacokinetic study did exhibit an improvement in bioavailability due to increased circulation time, fetching changes in drug accumulation into tumor tissues through enhancement of permeability and retention phenomenon. It means nearly all formulations have comparatively mild hemolytic activity less than 5%, thereby exhibiting probable safety. This study brings into light a very feasible total approach of Fulvestrant-loaded liposomes for a prolonged tumor targeting by showing diminished exposures to such drug as compared to conventional injectable therapies offering therapeutic potential enhancement with lesser side effects. The overall findings would provide good ground to conduct further in vivo testing of these formulations for clinical applicability.

This study investigates the neuroprotective and partial agonistic effects of PP-43 against rotenone-induced Parkinson’s disease using C57BL6/J mice. PP-43 Administration of PP-43 (10 mg/kg and 20 mg/kg) significantly attenuated neurotoxicity by improving behavioural performance and reducing oxidative stress markers. Treated mice exhibited reduced cataleptic behaviour, enhanced motor coordination, and increased locomotor activity. Biochemical analysis revealed that PP-43 elevated dopamine and glutathione levels while decreasing neuroinflammatory markers, including MPO, IL-1β, and IL-6. Additionally, PP-43 minimized lipid peroxidation and acetylcholine dysregulation, preserving neuronal integrity. Histopathological assessments confirmed reduced glial cell congestion and neuronal damage in PP-43-treated groups. While levodopa showed stronger neuroprotective effects, PP-43 effectively alleviated Parkinsonian symptoms and neuroinflammation. Observations of pyknotic nuclei in rotenone-treated mice further indicated dopaminergic neuronal apoptosis. These findings suggest that PP-43 holds promise as a neuroprotective agent for Parkinson’s disease, warranting further research to elucidate its precise mechanism and therapeutic potential.

The research aims to design, formulate, and assess desired SLNs for poorly soluble anticancer drug Fulvestrant. The SLNs were made up of solid dispersion by high shear mixing and high pressure homogenization to make a very fine suspension. Drug loading, entrapment efficacy, particle size, and stability are the general parameters that were considered in this case for the different formulations; hence, optimization was performed through them. A good place to prove this preparation is an investigation of the saturation solubility of the Fulvestrant in various solvents, and subsequently determining which of them is clearly shown in 0.1 N HCl. Various observations of thermal analysis, that is DSC and XRD, indicated that the nanoparticles had stable, crystalline-like structure and, at the same time, favorable thermal properties. The optimized Batch B formulation was the one showing the highest drug loading and very high entrapment efficiency of about 70.8 and 95.2%, respectively. The particles normally had 150-nm size, while zeta potential was measured to be -220 mV. Ex-vivo diffusion studies successfully verified the drug release profiles of the nanoparticles, and the findings implied that Batch B exhibited 99.1% cumulative drug release for a 12-hour period. The pharmacokinetic studies indicated that the drug was released at a controlled rate and it had caused an increase in Tmax, which implied that there was an extended action of the drug. Stability studies verify Batch B as stable in both accelerated and long-term conditions. These studies flag the much value-adding potential of these SLNs as a good vehicle capable of delivering the improved pharmaceutical characteristics noted earlier for Fulvestrant. Keywords: Solid Lipid Nanoparticles, Fulvestrant, Drug Delivery, Microemulsion Technique, Sustained Release, Cancer Treatment, Pharmacokinetics, Stability Studies

A wide range of pharmaceutical medications have been employed to facilitate the blockage of the neurohumoral system that is implicated in the pathogenesis of congestive heart failure (CHF). An often-used antiarrhythmic medication is amiodarone. Treatment for persistent ventricular tachycardia, ventricular fibrillation, and class III atrial fibrillation are indicated. There is curiosity about metoprolol, which is a selective β1-adrenergic receptor blocker. Myocardial infarction, atrial fibrillation/edema, Heart failure (HF), and hypertension are among the conditions for which the FDA has approved treatments. Among the most common reasons for adverse drug reaction (ADR) is drug exposure, and we find that polypharmacy contributes to the higher prevalence of this syndrome among the elderly. Drug interactions involving amiodarone have been documented. mostly blocks CYP2C8 and CYP3A4, with CYP1A2, CYP2C19, and CYP2D6 being slightly blocked as well. The finding that using amiodarone was linked to greater amounts of α-OH-metoprolol was unexpected. The existing literature indicates that the concentration of α-OH-metoprolol will likely decrease with moderate and strong CYP2D6 inhibitors. Cardiovascular Pharmacogenomics focuses on the development and selection of cardiovascular drugs to increase therapeutic efficacy and reduce toxicity. The purpose of this article is to investigate the pharmacogenetic and drug-drug interactions between amiodarone and metoprolol and their side effects.

[This retracts the article DOI: 10.1016/j.heliyon.2023.e16963.].

The main goal of the current investigation was to find out how ferulic acid (FA) affected the neuropathic pain that vincristine caused in rats. Rats were given vincristine to cause painful neuropathy. To measure the mechanical dynamic allodynia, cold allodynia, degree of mechanical hyperalgesia, heat hyperalgesia, and muscle relaxant rota rod, respectively. Several pain-sensitive tests, including the von frey hair test, pinprick, hot plate, and rota rod, were carried out on various weeks (0, 4 and 8 weeks) as indicators of inflammation and oxidative stress the IL-1β, IL-10, tumour necrosis factor-alpha (TNF-α), tissue parameters like Na+/K+ ATPase, Ca2+ ATPase & Mg2+ ATPase and superoxide dismutase (SOD), catalase (CAT) level, reduced glutathione (GSH), lipid peroxidase (LPO), NO level were assessed. Gabapentin (30 mg/kg i.p.) in addition to FA (50, 100, as well as 150 mg/kg orally) was given for 08 weeks. FA administration markedly decreased vincristine-induced behavioral and biochemical alterations (p < 0.05). FA also reduced the inflammation IL-10 and increased IL-1β and TNF-α. FA also reduces oxidative stress (LPO, NO level) and increases at (GSH, SOD, CAT levels) that vincristine caused. FA can alleviate the painful states brought on by vincristine-induced painful neuropathy, which might also be explained by its anti-inflammatory effects and following reduction of oxidative stress.

Developing effective therapeutics for stroke, extending beyond brain injury to overcome the post stroke complications is the need of hour. Post-stroke recovery is a primary research goal, necessitating treatments targeting multiple aspects of stroke pathology to enhance patient outcomes. Co-administration of therapies presents a promising approach to address post-stroke complications. Here, we assessed the combined effect of Metformin (MET) and Coenzyme Q10 (CoQ10) in mitigating post-stroke injury in rats. Rats underwent bilateral common carotid artery occlusion followed by reperfusion. They were divided into groups: Sham, IR (ischemic reperfusion), MET-treated, CoQ10-treated, and co-administered (MET+CoQ10). All treatments were given intramuscularly for 1–3 days post-stroke. Brain infarct size was significantly reduced in all treatment groups as compared to IR. Neurological score, % alteration, transfer latency, and discrimination ratio are ameliorated in all treatment groups. Coadministration shows a significant reduction in LPO as compared to IR and MET-treated animals. Glutathione and BBB integrity improved in all treated groups. Histology shows less pyknosis and vacuolization in treated rats’ hippocampus. MET and CoQ10 treatment for 3 days post-stroke exhibited neuroprotective effects and improved cognitive function. Co-administration demonstrated enhanced antioxidant defense compared to individual treatments, suggesting potential synergy in mitigating post-stroke complications.

: This cross-sectional study was aimed to assess the knowledge, attitudes, awareness, facilitators, and barriers associated with the uptake of influenza vaccination during pregnancy in the urban area of Pune. : The study was conducted with 500 participants: 62 pregnant women and 438 postpartum women (total 524 were approached) attending Obstetrics and Gynaecology outpatient department (OPD) in a tertiary-care municipal hospital in Pune. The study-questionnaire collected data regarding socio-demographics general knowledge about influenza, attitude towards influenza vaccination, vaccine risk awareness, and its potential risk and benefits during pregnancy. The log-binomial regression models were used to examine the factors associated with influenza vaccination. : A good uptake of the vaccine (223/500, 44.6%) was found during current pregnancy of the participant; however, only 2.7% of study-participants vaccinated with influenza vaccine in their previous pregnancies. Also, there was poor awareness among all the participants regarding the safety of the seasonal influenza vaccine during pregnancy (19%, n=95/500). 11.2% (n=31/277) study-participants were found to be against the maternal influenza vaccination. Women receiving the vaccine against influenza were more likely to be previously informed of the recommendations from health-care providers about maternal influenza vaccination with odds ratio of 0.18 (95% CI, 0.04 to 0.8; p<0.00001), received the influenza vaccine in the past OR 8.27 (95% CI, 0.94 to 72.0), Z 1.09, p=0.05 and of having knowledge on influenza and its complications has more impact on influenza vaccination during pregnancy OR 14.4 (95% CI, 5.68 to 36.53), Z 5.6, p<0.0001 respectively. : This study concludes the vital causative factors for non-vaccination were provision of incomplete information or poor awareness about influenza vaccination (68.6%). There was poor knowledge among the pregnant women regarding the safety of maternal influenza vaccines. The recommendation from healthcare professionals is the major facilitators of decision-making by pregnant women for influenza vaccination during pregnancy.

This article summarizes all aspects related to the exclusion and inclusion of pregnant women in clinical trials.Historically to date, pregnant women were observed as most excluded population from clinical research.There are various scientific as well as ethical reasons behind their exclusion.However, given the burden of various illnesses and diseases during pregnancy, there is a need to include them in clinical research.Available data regarding safety and efficacy of medicinal products were also collected from accidental exposure.But these evidences are insufficient to give results.Various ethical aspects and scientific reasons are also given proper evidences to include pregnant women in clinical trials.In this review, we have summarized data from clinicaltrials.gov.in on completed clinical trials exclusively on pregnant women and ongoing clinical trials in pregnant women to find out the current status of pregnant women in clinical research.There is a need to consider designing of clinical trials in pregnant women in such a way that fear of any harm should be overcome, such that more pregnant women can participate in clinical trials.

Diabetic neuropathy (DN) is a common complication of diabetes mellitus (DM) characterized by neuropathic pain due to persistent hyperglycemia. Recent studies have shown that phytochemicals’ antioxidant capabilities can reduce oxidative stress associated with diabetic neuropathy. Although phytochemicals with high antioxidant capacity have been discovered, this study aimed to investigate the neuroprotective effect of a combination of kudzu root extract (KRE) and maqui berry extract (MBE). We evaluated the neuroprotective effects of kudzu root extract and maqui berry extract on streptozotocin (STZ)-induced DN in rats. Male Wistar rats (180–250 g) were divided into eight groups (n = 6), with DN induced via a single intraperitoneal injection of STZ (55 mg/kg). Behavioral parameters (mechanical allodynia, cold allodynia, thermal hyperalgesia, and mechanical hyperalgesia) and biochemical parameters (blood glucose, serum markers, antioxidant levels, and ATPase activity) were assessed. Rats were treated with KRE (50 and 100 mg/kg) and MBE (50 and 100 mg/kg) alone and in combination for two weeks. The results showed that treatment with KRE and MBE significantly reduced blood glucose levels and increased body weight compared to diabetic controls. Paw withdrawal latency improved in treated groups, indicating reduced neuropathic pain. Biochemical analysis revealed increased levels of antioxidants (GSH, CAT, and SOD) and ATPase activity, with decreased levels of nitric oxide (NO) and lipid peroxidation (LPO) in the treatment groups. These findings suggest that KRE and MBE exhibit significant neuroprotective effects in STZ-induced DN due to their strong antioxidant properties. Further molecular studies are warranted to elucidate the precise mechanisms underlying their neuroprotective effects.

, commonly known as the baobab tree, founded mainly in Africa and is also found in Indiana region. It associates to the kapok tree group and this tree hold record of highest wood tree in the world. The baobab is an adaptable plant that provides protection, food, clothing, medicament and raw materials for multiple products. All eatable section including seeds, leaves, roots, flowers, pulp and bark, are shared to be beneficial. Baobab trees are over 4,000 years old. contains many phytochemicals such as vitamin C, steroids, flavonoids, epicatechin, campestral and amino acids. This large tree can growth a height of 20-25 meters and a cyclize of up to 9 meters and has been in place for centuries.It is called the "Queen of Carbon Storage" because it can absorb so much carbon from the air. The tree is known for its size, unique shape and long-life expectancy, often surviving for thousands of years. Baobab has a variety of biological properties, including antibacterial, antimalarial, antidiarrheal, antianemic, antiasthmatic, antiviral, antioxidant. Phytochemical analysis has revealed the presence of flavonoids, phytosterols, amino acids, fatty acids, vitamins, and minerals. Parts of the plant are used for treating bronchial asthma, dermatitis, sickle cell anemia, diuretic, antidiabetic, antidiarrheal, antidysenteric, laxative, and hiccups in children. This article summarizes the pharmacological, phytochemical, and pharmacological properties of the baobab tree.

The pediatric population differs from adults in various ways, including physiological factors, pharmacokinetics, pharmacodynamics, and dosage administration. However, many medications prescribed for children are formulated for adults, necessitating dose adjustments throughout childhood. This underscores the need for pediatric drug formulations and regulations worldwide. This review delves into the intricate landscape of international pediatric drug regulations to elucidate key initiatives, challenges, and advancements shaping this field. Commencing with a historical backdrop, the review outlines the evolution of regulatory frameworks across major regions, including the United States (US), Europe, Japan, and China, while underscoring the imperative for the implementation of pediatric drug regulations in India. These regulations mandate age-appropriate dosing, rigorous clinical trials, and thorough labeling to prevent misuse. They require pediatric-specific studies to understand drug effects and dosages and enforce guidelines for off-label use. Agencies such as the US Food and Drug Administration oversee these regulations, ensuring pediatric drugs meet safety standards before approval. In addition, regulations often include provisions for informed consent and parental involvement in treatment decisions, aiming to protect children from adverse effects while providing effective therapeutic options tailored to their developmental needs. In summary, this review emphasizes the importance of global cooperation and harmonized regulations in advancing pediatric drug research. It highlights recent progress while acknowledging ongoing challenges and opportunities in this critical area.