Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AIM: The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. METHODS: Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. RESULTS: The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20ß-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20ß-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. CONCLUSION: T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.

Mechanism insights of curcumin and its analogues in cancer: An update.

Cancer is the world's second leading cause of mortality and one of the major public health problems. Cancer incidence and mortality rates remain high despite the great advancements in existing therapeutic, diagnostic, and preventive approaches. Therefore, a quest for less toxic and more efficient anti-cancer strategies is still at the forefront of the current research. Traditionally important, curcumin commonly known as a wonder molecule has received considerable attention as an anti-cancer, anti-inflammatory, and antioxidant candidate. However, limited water solubility and low bioavailability restrict its extensive utility in different pathological states. The investigators are making consistent efforts to develop newer strategies to overcome its limitations by designing different analogues with better pharmacokinetic and pharmacodynamic properties. The present review highlights the recent updates on curcumin and its analogues with special emphasis on various mechanistic pathways involved in anti-cancer activity. In addition, the structure-activity relationship of curcumin analogues has also been precisely discussed. This article will also provide key information for the design and development of newer curcumin analogues with desired pharmacokinetic and pharmacodynamic profiles and will provide in depth understanding of molecular pathways involved in the anti-cancer activities.

Comparative impact of yoga and ayurveda practice in insomnia: A randomized controlled trial.

BACKGROUND: Insomnia is connected with a lifted hazard for neurocognitive dysfunction and psychiatric disarranges. Clinical observations of psychosomatic patients indicate that their distorted somatopsychic functioning necessitates their practice of yoga-like therapy. Sleep and its modifications and management have also been explained well in ayurveda. This study aimed to compare the effectiveness of Yoga and Nasya Karma on the sleep quality, stress, cognitive function, and quality of life of people suffering from acute insomnia. MATERIAL AND METHODS: It was an open-label, randomized controlled trial. A total of 120 participants were randomly (computer-generated randomization) equally allocated to three groups, yoga group (G-1), ayurveda group (G-2), and control group (G-3). All the groups were assessed on the first day before the start of the yoga regime and the 48th day. Participants in the study were included in the age group of 18 to 45 years, fulfilling DSM-V criteria for insomnia, physically fit for the yoga module, and Nasya procedure. Outcomes were measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Perceived Stress Scale (PSS), cognitive failure questionnaire, and WHO Quality of Life Scale-Brief (WHOQOL-Brief). Proportions and frequencies were described for categorical variables and compared using the Chi-square test. ANOVA (one-way) and post hoc analysis, Bonferroni test, were performed for multiple comparisons in groups at a significance level of P < 0.05 using SPSS (23 version). RESULTS: A total of 112 participants were analyzed as per protocol analysis. All groups have observed significant mean differences for stress (<0.05) and sleep quality (<0.05). All five aspects of quality of life - general health (<0.05), physical health (<0.01), psychological health (<0.05), social health (<0.05), and environmental health (<0.05) - had a significant mean difference in all three groups. All three aspects of cognitive failure, forgetfulness (<0.05), distractibility (<0.05), and false triggers (<0.01) had a significant mean difference in scores for all three groups. CONCLUSION: Yoga practice was effective, followed by ayurveda and the control group in reducing stress and improving sleep, cognitive function, and quality of life.

Effects of Yoga on Psychological Health and Sleep Quality of Patients With Acute Insomnia: A Preliminary Study.

Context: Insomnia or poor sleep quality is associated with impaired physical, psychological, and mental functions that individuals require for health and well-being. Objective: The study aimed to evaluate the effects of yoga practice in managing insomnia and its related complications, such as cognitive failure, stress, and impaired quality of life (QoL), for individuals suffering from acute insomnia. Design: The research team designed a randomized controlled trial. Setting: The study took place at OPD of Dept. of Panchkarma Uttarakhand Ayurveda University in Uttarakhand, India. Participants: Participants were 24 patients at the hospital with acute insomnia between September 1 and September 30, 2021. Intervention: The research team randomly allocated 12 participants to the yoga group, the intervention group, and 12 to the control group. The yoga group participated in yoga practice for 60 minutes per day including Jala Neti- thrice in a week, Yoga Nidra- once in a week for 30 days, in addition to three days for an orientation program. The control group received conventional treatment. Outcome Measures: At baseline and postintervention on day 30, the research team measured outcomes using the Perceived stress scale (PSS), Cognitive Failure Questionnaire (CFQ), Pittsburgh Sleep Quality Index (PSQI), and the World Health Organization Quality of Life Abbreviated (WHO-QOL-BREF). The team assessed the data for normality and applied the paired t test and an independent t test. Results: Postintervention, the decrease in the yoga group's stress and sleep quality were significantly greater, except for cognitive failure, than those of the control group. For the yoga group, three aspects of QOL-physical, psychological, and social-showed significant improvements but environmental health didn't. Conclusions: Yoga may be helpful in the management of insomnia and other sleep-related disorders in conjunction with pharmacotherapies and psychological interventions. Yoga can enhance QOL by improving overall mental health status and sleep quality and decreasing stress.

Chickpea Peptide: A Nutraceutical Molecule Corroborating Neurodegenerative and ACE-I Inhibition.

Chickpea seeds are the source of proteins in human nutrition and attribute some nutraceutical properties. Herein, we report the effects of chickpea seed bioactive peptide on albumin, insulin, lactoglobulin and lysozyme amyloid fibril formation. Employing thioflavin T (ThT) assays and circular dichroism (CD), amyloid structural binding transition was experimented to analyze the inhibition of amyloid fibril formation. The purified active peptide with a molecular mass of 934.53 Da was evaluated in vitro for its ACE-I inhibitory, antibacterial, antifungal and antidiabetic activities. Further, in vivo animal studies were carried out in wistar rats for blood pressure lowering action. In hypertensive rats, chickpea peptide decreased 131 ± 3.57 mm of Hg for systolic blood pressure and 86 ± 1.5 mm of Hg for diastolic blood pressure after 8 h intraperitoneal administration. Additionally, the peptide suppressed the fibrillation of amyloid and destabilized the preformed mature fibrils. Data emphasize efficacy of chickpea peptide vis-a-vis ACE-Inhibitory, antibacterial, antifungal, antidiabetic and anti-amyloidogenic activities, allowing us to propose this novel peptide as a suitable candidate for nutraceutical-based drugs and seems the first kind of its nature.

Hibiscus sabdariffa Extract Protects HaCaT Cells against Phenanthrene-Induced Toxicity through the Regulation of Constitutive Androstane Receptor/Pregnane X Receptor Pathway.

Phenanthrene (Phe) exposure is associated with skin ageing, cardiotoxicity and developmental defects. Here, we investigated the mode of Phe toxicity in human keratinocytes (HaCaT cells) and the attenuation of toxicity on pre-treatment (6 h) with ethanol extract of Hibiscus sabdariffa calyxes (HS). Cell viability, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔΨm) alteration, changes in the transcriptional activity of selected genes involved in phase I and II metabolism, antioxidant response and gluconeogenesis, western blot and docking studies were performed to determine the protective effect of HS against Phe. Phe (250 µM) induced cytotoxicity in HaCaT cells through AhR-independent, CAR/PXR/RXR-mediated activation of CYP1A1 and the subsequent alterations in phase I and II metabolism genes. Further, CYP1A1 activation by Phe induced ROS generation, reduced ΔΨm and modulated antioxidant response, phase II metabolism and gluconeogenesis-related gene expression. However, pre-treatment with HS extract restored the pathological changes observed upon Phe exposure through CYP1A1 inhibition. Docking studies showed the site-specific activation of PXR and CAR by Phe and inhibition of CYP1A1 and CYP3A4 by the bioactive compounds of HS similar to that of the positive controls tested. Our results conclude that HS extract can attenuate Phe-induced toxicity in HaCaT cells through CAR/PXR/RXR mediated inhibition of CYP1A1.

The Impact of Complementary and Alternative Medicine on Insomnia: A Systematic Review.

Insomnia is characterized by difficulty in maintaining sleep and early morning awakenings. Although pharmacotherapies and psychological interventions remain essential for conventional treatment, motivational factors and interest in using complementary and alternative therapies for insomnia have developed over the last two decades. This review aims to comprehensively explore the effects of complementary and alternative medicine (CAM) on improving sleep quality to guide evidence-based clinical decision-making and inform future research. Several electronic databases such as MEDLINE, PubMed, Scopus, EMBASE, Clinical key, Cochrane, and Research gate were explored to search the relevant articles. For the systematic review, CAM studies were classified under "manual practices," "natural practices," and "mind-body practices." A total of 35 clinical trials were selected for inclusion in the systematic review, comprising adult samples. The systematic review revealed 11 RCTs with manual practice, 12 with mind-body practice, and 12 with natural medicine practice. The methodological quality of the RCTs was measured using the modified Jadad scale, a scientific quality index of ≥ 5/10 (on the augmented Jadad scale). Effect sizes (Cohen's d) were calculated and reported in all placebo-controlled studies with the available data. Regardless of systematic reviews, and randomized controlled trials on CAM, acupuncture, acupressure, herbal medicine, yoga, and tai chi, for insomnia, most of the RCTs did not agree with the findings. Further RCT for insomnia should be developed by considering the current advanced studies in the field of CAM.

Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.

Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-ß/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.

Antidepressant activity of Spathodea campanulata in mice and predictive affinity of spatheosides towards type A monoamine oxidase.

The antidepressant activity of Spathodea campanulata flowers was evaluated in mice and in silico. When tested at doses of 200 and 400 mg/kg, the methanol extract of S. campanulata (MESC) showed dose-dependent antidepressant activity in the force swim test (FST), tail suspension test (TST), lithium chloride-induced twitches test and the open field test. In FST and TST, animals treated with MESC demonstrated a significant decrease in the immobility period compared to the control group. The lithium chloride-induced head twitches were significantly reduced following administration of MESC. The latter, at the dose of 400 mg/kg, also significantly reduced locomotor activity. Following administration of MESC, changes in the levels of serum corticosterone, and of norepinephrine, dopamine, serotonin, 4-hydroxy-3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in different brain regions using HPLC. The presence of spatheoside A (m/z 541) and spatheoside B (m/z 559) in MESC was detected using HPLC/ESI-MS. These two iridoids demonstrated a high predictive binding affinity for the active site of the type A monoamine oxidase (MAO-A) enzyme with scores of 99.40 and 93.54, respectively.  These data suggest that S. campanulata flowers warrants further investigation as a source of novel templates for antidepressive drugs.

Antibacterial and antidiarrheal activity of Butea Monospermea bark extract against waterborne enterobacter Cloacae in rodents: In-vitro, Ex-vivo and In-Vivo evidences.

ETHNOPHARMACOLOGICAL RELEVANCE: Butea monosperma (Lam.) Taub. (family Leguminosae), popularly known as 'Palash' possess numerous medicinal properties since ancient times. According to the Wealth of India, stem bark of this plant exhibits various therapeutic properties like antimicrobial, astringent, styptic, aphrodisiac, and anti-inflammatory. AIM OF THE STUDY: The purpose of the present study was to investigate antibacterial and antidiarrheal effect of B. monosperma bark against newly isolated gram negative pathogenic bacterial strain Enterobacter cloacae. MATERIALS AND METHODS: Aqueous extract of B. monosperma bark (BMAqE) was subjected to LC-MS/MS analysis for determination of bioactive components. Antibacterial study of BMAqE was assessed using bacterial growth kinetic study, fluorescence spectroscopy, outer and inner membrane permeability assay, dehydrogenase inhibitory assay and protein leakage assay followed by field emission scanning electron microscope (FE-SEM) study. Antidiarrheal activity was studied using castor oil induced diarrhea model in albino rats followed by histopathology studies of rat ileum. RESULTS: LC-MS/MS analysis of BMAqE revealed presence of twenty-two different active phytoconstituents out of which most of the constituents belong to flavonoid and polyphenol family. BMAqE showed MIC and MBC (IC90) value of 5 and 200 µg/mL against targeted bacterial strain. BMAqE exhibited potent and dose dependent bactericidal effect via disruption of integrity of bacterial cell membrane, enzymatic degradation, leakage of intracellular protein and ruptured bacterial cell. In castor oil induced diarrhea model, BMAqE (200 mg/kg; orally) caused marked reduction (75.66%) in the frequency of defecation and mean weight of faeces (0.54 ±â€¯0.04) when compared to control group (2.26 ±â€¯0.25). Histopathology study revealed marked restoration of cellular architecture of rat ileum tissue. Four known flavonoids were isolated from BMAqE using column chromatography. In ex-vivo study, BMAqE (0.0002, 0.0004 and 0.0006 g/L) and isolated flavonoids i.e. rhamnetin, quercetin, kaempferol and catechin (0.5, 5 & 50 µm) produced a significant (p < 0.001) change in EC50 and indicated competitive phenomena via rightward shift of acetylcholine CRC with pA2 of 3.78, 8.0, 7.1, 7.0 and 6.9 respectively. CONCLUSION: BMAqE exhibits impressive antibacterial and anti-diarrheal activity and can be effectively used to eradicate water borne diseases.

Applicability of Tanaka-Johnston, Moyers, and Bernabé and Flores-Mir Mixed Dentition Analyses in School-going Children of Sri Ganganagar City, Rajasthan (India): A Cross-sectional Study.

BACKGROUND: The orthodontic diagnosis and treatment planning are the fundamental goals during the mixed dentition period. Numerous methods have been proposed till date such as Nance method, Moyer's method, Staley-Kerber and Tanaka-Johnston's method, and Bernabé and Flores-Mir method. AIM: The aim of the study is to determine the mesiodistal widths of the lower permanent canines and premolars from Tanaka-Johnston, Moyers, and Bernabé E and Flores-Mir C mixed dentition analysis and to determine the correlation coefficients and the new prediction equation for Sri Ganganagar population. SETTING AND DESIGN: A total of 3572 children were clinically examined from the contemporary population of Sri Ganganagar city and Outpatient Department of Pediatric and Preventive Dentistry in Sri Ganganagar, Rajasthan. A total of 150 individuals were randomly selected for the study based on the inclusion and exclusion criteria and were designated as "study samples. MATERIALS AND METHODS: A total of 150 children aged 11-16 years of Sri Ganganagar city were randomly selected. The mesiodistal width of permanent incisors, canines, premolars, and molars was measured with the help of digital vernier caliper with an accuracy of ±0.01 mm. The measurements of canines and premolars were summed up and compared with those derived from Tanaka and Johnston equations, Moyers probability tables, and Bernabé and Flores-Mir equations. STATISTICAL ANALYSIS: The data obtained were subjected to statistical analysis using IBM SPSS Statistics Windows version "20.0" using Student's t-test, Pearson correlation coefficient, and Kruskal-Wallis test. RESULTS: All the three methods overestimated the actual sum of permanent canine and premolars in both the arches in our population. The correlation coefficients and the new regression equations were derived for both maxilla and mandible in males and females for Sri Ganganagar population. CONCLUSION: The predicted values obtained from all the three methods overestimated the actual values.

Exploring ß-Tubulin Inhibitors from Plant Origin using Computational Approach.

INTRODUCTION: ß-Tubulin is an important target for the binding of anti-cancer drugs, in particular, paclitaxel (taxol), vinblastine and epothilone. However, mutations in ß-tubulin structure give resistance to chemotherapeutic agents. Notably, mutations at R306C, F270 V, L217R, L228F, A185T and A248V positions in ß-tubulin give high resistance for paclitaxel binding. OBJECTIVE: To discover novel inhibitors of ß-tubulin from natural sources, particularly alkaloids, using a virtual screening approach. METHODOLOGY: A virtual screening approach was employed to find potent lead molecules from the Naturally-occurring Plant-based Anti-cancer Compound-activity Target (NPACT) database. Alkaloids have great potential to be anti-cancer agents. Therefore, we have screened all alkaloids from a total of 1574 molecules from the NPACT database for our study. Initially, Molinspiration and DataWarrior programs were utilised to calculate pharmacokinetics and toxicity risks of the alkaloids, respectively. Subsequently, AutoDock algorithm was employed to understand the binding efficiency of alkaloids against ß-tubulin. The binding affinity of the docked complex was confirmed by means of an intermolecular interaction study. Moreover, oral toxicity was predicted by using ProTox program. Further, metabolising capacity of drugs was studied by using SmartCYP software. Additionally, scaffold analysis was done with the help of scaffold trees and dendrograms, providing knowledge about the building blocks for parent-compound synthesis. RESULTS: Overall, the results of our computational analysis indicate that isostrychnine, obtained from Strychnosnux-vomica, satisfies pharmacokinetic and bioavailability properties, binds efficiently with ß-tubulin. Thus, it could be a promising lead for the treatment of paclitaxel resistant cancer types. CONCLUSION: This is the first observation of inhibitory activity of isostrychnine against ß-tubulin and warrants further experimental investigation. Copyright © 2016 John Wiley & Sons, Ltd.