Exploring the neuropharmacological properties of scopoletin-rich Evolvulus alsinoides extract using in-silico and in-vitro methods.

OBJECTIVES: This study investigates the neuropharmacologic properties of Scopoletin, a bioactive compound in Evolvulus alsinoides (EA) extract, for managing cognitive impairment using in-vitro, in-silico, and zebrafish embryo toxicity assays. METHODS: The study estimates Scopoletin concentration in EA extract using HPTLC, assesses antioxidant properties using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing ability of plasma (FRAP) assays, and uses bioinformatic tools for scopoletin targets. Zebrafish embryo toxicity (ZET) is used to assess its toxicological profile. RESULTS: 0.0076% w/w Scopoletin in the samples was quantified using HPTLC, further studies on the DPPH (0.5 mM) and FRAP gave EC50 at 440.0 µg/ml and 84.29 µg/ml respectively. Twelve common targets associated with cognitive impairment (CI) were identified, along with possible pathways and molecular interactions. Our results indicate significant binding affinities of Scopoletin with ERAP1, SCN3A, and COMT. Molecular dynamics simulations further confirm the stability of these interactions. ZET assessment demonstrated mortality after 450 µg/ml concentration of EA extract. CONCLUSION: The study verifies the presence of Scopoletin in EA, along with their targets playing a crucial role in neurogenesis and neuroplasticity. The ZET demonstrated concentration-dependent effects, emphasizing the importance of dosage considerations in developing new formulations or therapeutics. This comprehensive study contributes valuable insight into the therapeutic potential of Scopoletin from EA for cognitive impairment, paving the way for further research.

Impact of Heartfulness meditation practice on anxiety, perceived stress, well-being, and telomere length.

Objective: Exhaustion, stress, and burnout have all been found to be reduced using techniques like yoga and meditation. This study was carried out to check the effectiveness of Heartfulness practice (a form of meditation) on certain psychological and genetic variables. Methods: A total of 100 healthy individuals (aged 18-24) were recruited and randomized into two groups-Heartfulness intervention and control group. The intervention was carried out for 03 months. Participants from both groups were analysed for their cortisol levels and telomere length before and after the intervention. Psychometric measures of anxiety, perceived stress, well-being and mindfulness were carried out using Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), WHO-Well-being Index (WHO-WBI) and Five Facet Mindfulness Questionnaire (FFMQ). Results: The cortisol levels in the meditators group significantly decreased (p < 0.001) after the intervention as compared to the non-meditators group, whereas, the telomere length increased in the mediators group. This increase was not significant (p > 0.05). Anxiety and perceived stress also decreased post intervention, and well-being as well as mindfulness increased, as assessed by the questionnaire tools, although the decrease in perceived stress was statistically insignificant (p > 0.05). A negative correlation was observed between telomere length and cortisol (stress biomarker), whereas a positive correlation was found between telomere length and well-being. Conclusion: Our data provide evidence that Heartfulness meditation practice can improve our mental health. Additionally, telomere length is shown to be affected by cortisol levels, and this meditation practice can also help to increase telomere length, and thereby slow down cellular aging. However, future studies with larger sample size are required to confirm our observations.

Nanostructured gold in ancient Ayurvedic calcined drug 'swarnabhasma'.

BACKGROUND: Swarnabhasma (calcined gold) is a famous ancient Ayurvedic medicine. However, its detail characteristic investigations are very limited. OBJECTIVE: Herein, investigation of swarnabhasma is demonstrated using ancient and ultramodern techniques to understand the physicochemical nature of this drug, and to understand whether the mercury [Parada] used during preparation method marks its presence in swarnabhasma. MATERIALS AND METHODS: The investigated swarnabhasma was prepared by repeated incinerations of Au-Hg-Lemon juice amalgamation and sulphur. The bhasma was tested by all traditional tests of rasashastra. It was characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FE-SEM), Field Emission Transmission Electron Microscopy (FE-TEM), Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES), Energy Dispersive X-ray Fluorescence (EDXRF), Fourier Transform Infrared Spectroscopy (FTIR), and gravimetric analysis. RESULTS: Traditional tests of rasashastra were complied by the sample. XRD confirms that swarnabhasma consists of principally pure gold at nanoscale. FE-SEM showed agglomerated particles. FE-TEM showed that swarnabhasma contains highly crystalline nanostructured gold comprised with spherical gold nanoparticles of size, 5-20 nm. ICP-AES exhibited absolute absence of Hg and presence of Au, Si, Ag, Al, Ca, Cu, Fe, K, Mg, Mn, Na, P, Sr, Ti, and Zn. EDXRF confirmed the absence of mercury and confirmed the presence of Au, Si, Zr, Nb, S, Cl, K, Ca, Fe, and Ni. FTIR confirmed presence of water molecules adsorbed over surface of bhasma. Gravimetric analysis confirmed presence of 95% gold. CONCLUSION: Nano-structuring of gold enhances the surface area as well as activity. The present investigation shows that the entire process from rasashastra confers the unique nanostructure to gold and same is responsible for its medicinal potential. This nanomedicine is highly stable, which is specified as niruttha and apunarbhava in rasashastra.

Physicochemical Variation in Nanogold-Based Ayurved Medicine Suvarna Bhasma Produced by Various Manufacturers Lead to Different In Vivo Bioaccumulation Profiles.

Suvarna Bhasma (SB) is a gold particle-based medicine that is used in Ayurved to treat tuberculosis, arthritis and nervous diseases. Traditionally, the Ayurved preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary Ayurved processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (Cmax), half-life (t1/2) and terminal elimination slope (λz) for all the 5 SB preparations. SB-B showed the highest Cmax (8.55 µg/L), whereas SB-D showed the lowest Cmax (4.66 µg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned Ayurved references.

Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and behavioural assessment in zebrafish model.

ETHNOPHARMACOLOGICAL RELEVANCE: Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children. AIM OF THE STUDY: To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy. MATERIALS AND METHODS: Suvarna Bhasma was characterised by physicochemical characterization techniques such as scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and atomic emission spectroscopy (ICP-AES). Toxicity of Suvarna Bhasma was studied in Holtzman rats with daily oral dose from 3 mg/kg (therapeutic dose, TD) up to 30 mg/kg (10 TD) body weight for 90 days. Behavioural study, such as motor and geotactic behaviour were examined in zebrafish model to find out any sign of neurotoxicity or behavioural changes due to Suvarna Bhasma administration. RESULTS: Suvarna Bhasma has two types of gold particles, large ones (~60 µm) having irregular shapes, and nano-sized spherical particles (starting from ~10 nm), the latter coated with Fe, Si, O, P and Na. XRD study revealed that all the peaks of Suvarna Bhasma match well with pure gold (face centred cube) with crystallites size 45 ±â€¯2.8 nm. In rat studies, some change in biochemical parameters such as urea, creatinine and alanine aminotransferase (ALT) was observed mainly at the higher therapeutic dose; however, those parameters were within the normal range. There were no significant macroscopic as well as microscopic treatment-related alteration observed, in any of the organs and tissues evaluated. In zebrafish behavioural study, the motor parameters of Suvarna Bhasma treated fish showed normal behaviour analogous to the vehicle control group. Interestingly, the geotactic behaviour showed anxiolytic effects of Suvarna Bhasma as evidenced by the time spent in the upper zone, and average swimming height. The anxiolytic effects persisted for more than 30 days after withdrawing the Suvarna Bhasma treatment. CONCLUSIONS: Suvarna Bhasma contained spherical gold nanoparticles. It was nontoxic in rat model at the does tested. Suvarna Bhasma has anxiolytic effects in zebrafish behavioural model.

Preparation and Characterization of Suvarna Bhasma Parada Marit.

OBJECTIVES: The goal of this study was to characterize Suvarna Bhasma Parada Marit by using the Ayurvedic test parameters, physico-chemical tests, and various instrumentation techniques. METHODS: Suvarna Bhasma, an Ayurvedic formulation manufactured as per Bharat Bhaishajya Ratnakar 5/8357 (BBR), has been studied using various instrumentation techniques: X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), laser particle size distribution (PSD) analysis, fourier transform infrared spectroscopy (FT-IR), and atomic absorption spectroscopy (AAS), and physico-chemical parameters, such as the loss on drying (LOD), loss on ignition (LOI), and acid insoluble Ash (AIA) were determined. In addition, Ayurvedic tests, such as Rekhapurnatva (enterable in the furrows of the fingers), Varitaratwa (floatable over water), Nirdhoomta (smokeless), Dantagre Kach-Kach (gritty particle feeling between the teeth), were performed. RESULTS: The XRD study showed Suvarna Bhasma to be crystalline in nature and to contain more than 98% gold. The mean size of the gold crystallites was less than 10 microns, and the morphology was globular and irregular. Suvarna Bhasma contains gold as its single and major element, with EDAX and FT-IR spectra showing that it is more than 98% pure gold. The moisture content (LOD) is less than 0.5%, the LOI is less than 2%, and the AIA is not less than 95%. The Ayurvedic tests, as specified above, helped to confirm the quality of Suvarna bhasma prepared as per the text reference (BBR). CONCLUSION: This chemical characterization of Suvarna Bhasma performed in this study by using modern instrumentation techniques will be helpful in understanding its pharmacological actions and will help in establishing quality protocols and specifications to substantiate the safety, efficacy & quality of Suvarna Bhasma.

Effects of agomelatine in a murine model of obsessive-compulsive disorder: interaction with meta-chlorophenylpiperazine, bicuculline, and diazepam.

The anticompulsive potential of agomelatine, a potent MT1/2 receptor agonist, and its combined effect with m-chlorophenylpiperazine hydrochloride (mCPP), bicuculline, and diazepam, were investigated in male C57BLJ/6 mice using marble-burying behavior (MBB) test. Acute administration of agomelatine (30-40 mg/kg, intraperitoneal (i.p.)) significantly inhibited the MBB in mice without influencing their locomotor activity. Further, chronic (28 days) administration of lower doses of agomelatine (10 and 20 mg/kg, i.p.) dose-dependently reduced the MBB without influencing their locomotor activity. Interaction studies revealed that pretreatment with mCPP (0.5 mg/kg, i.p.), a serotonin 5HT2C agonist, partially attenuated the anticompulsive effect of agomelatine (30 mg/kg). Further, a GABAA receptor agonist (diazepam, 1.25 mg/kg, i.p.) and antagonist (bicuculline, 1 mg/kg, i.p.) had no influence on the effects of agomelatine on MBB and locomotor activity. The doses of modulators were selected on the basis of dose-response studies. The results indicate that agomelatine has a potent anticompulsive effect that can be attributed to 5HT2C antagonism and MT1/2 agonism, and is certainly not mediated via its effects on the GABAergic system. Thus, the study adds to the growing literature on the psychopharmacological effects of agomelatine, and warrants further exploration in multiple paradigms.

Antiulcer activity of Amlapitta Mishran suspension in rats: A pilot study.

CONTEXT: Amlapitta Mishran suspension is a poly herbal ayurvedic formulation, which has been traditionally used for acidity and gastric ulcers. AIM: The aim of this study is to evaluate the antiulcer activity of Amlapitta Mishran on non-steroidal anti-inflammatory drugs (NSAID's) -induced ulcers in the rat model. SUBJECTS AND METHODS: The antiulcer activity of Amlapitta Mishran was investigated on indomethacin (100 mg/kg) NSAID's induced ulcers in rats. Effect of two different doses of Amlapitta Mishran was studied by calculating the total number of ulcers, ulcer index and percentage inhibition. STATISTICAL ANALYSIS USED: Data was analyzed by the Student's t-test (P < 0.05). RESULTS: Amlapitta Mishran treated rats have shown significant (P < 0.0001) decrease in the total number of ulcers and ulcer index and significant increase in % inhibition of ulcers as compared with positive control group. CONCLUSION: The results indicate that Amlapitta Mishran has showed a dose dependent antiulcer activity in experimental animals and confirms ayurvedic use of Amlapitta Mishran in gastric ulcers.