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Context: Screening of cocrystals of active pharmaceutical ingredients is important in the development of pharmaceutical compounds because it improves bioavailability, stability, solubility, and many other physicochemical properties. In this work, quantum chemical calculations were utilized for the computational evaluation of the cocrystal screening of benznidazole (BZN) API via hydrogen bonding with four coformers (maleic acid, malonic acid, oxalic acid, and salicylic acid), and they contain carboxylic groups. The nitrogen of the imidazole ring in benznidazole and the carboxylic group of the coformer form a hetero-synthon connected by a strong hydrogen bond. The strength of the hydrogen bonding interaction O-H…N was measured using various tools. It was found that in comparison to BZN cocrystals with malonic acid, oxalic acid, and salicylic acid, the O-H…N interaction in the BZN-maleic acid cocrystal had higher interaction energy, indicating it had stronger hydrogen bonding. The strength of the hydrogen bond O-H…N for synthons was discovered to be more beneficial than the C-H…O interaction, as confirmed by ESP analysis. The BZN-salicylic acid cocrystal was found to be more reactive and polarizable, whereas the BZN-malonic acid cocrystal was more stable. Cocrystals of benznidazole exhibited better physicochemical characteristics than API benznidazole, as indicated by electron transition properties between the most significant orbitals., Methods: The computational evaluation for the screening of benznidazole cocrystals was performed in Gaussian 16 software using density functional theory (DFT) with the hybrid functional B3LYP and the basis set 6-311 +  + G(d,p). The UV-Vis absorption spectrum in solvent water was analyzed using the TD-DFT/6-311 +  + G(d,p) method to determine the influence of the solvent in cocrystals using a polarizable continuum model. The strength of the hydrogen bonding interactions O-H…N in each of those mentioned cocrystals was used to screen the cocrystals using tools such as thermodynamic probability, ESP analysis, QTAIM analysis, and NBO analysis. The pairing energy of interaction was measured by determining H-bond donor ( α max ) and H-bond acceptor ( β max ) parameters for hydrogen bonds from maxima and minima on the ESP surface. GaussView 06 software was used to create, visualize, and plot the optimized structure of the cocrystal and HOMO-LUMO orbitals. The AIMALL (10.05.04) software package generated the molecular graph for intra- and intermolecular interactions. The RDG-scatter plot, MEP map, and ELF plot were rendered from Multiwfn 8.0 and VMD 1.9.1 software., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC 50 : 3.014 μg/ml), insignificantly different (p > 0.05) from allopurinol (IC 50 : 2.47 μg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study has been planned to evaluate the impact of seasonal variation in labdane-type diterpenoids namely isoforskolin, forskolin, 1,9-dideoxyforskolin and 1-deoxyforskolin in Coleus forskholii (roots). The plant samples were harvested in different seasons from our experimental field located at CSIR-NBRI garden, Lucknow (India) and metabolite contents were estimated through validated high performance thin layer chromatography (HPTLC) method. The HPTLC plate was developed in tertiary mobile phase of toluene-ethyl acetate-methanol (8.5-1-0.05 v/v) for separation of all the four metabolites. The metabolite content viz. isoforskolin, forskolin, 1,9-dideoxyforskolin and 1-deoxyforskolin varies from 0.0247% to 0.198%, 0.238 to 0.730%, 0.056 to 0.161% and 0.0401 to 0.332% on dry weight basis respectively. The maximum content of metabolites was recorded in winter season and was found optimum for harvesting of C. forskholii roots. Optimization of harvesting season for this industrially valuable medicinal plant will lead to sustainable sources of good quality raw material to herbal drug industry.

The genus Berberis has high significance in Indian and other traditional systems of medicine due to the presence of iso -quinoline alkaloids. This study was conducted to record the metabolic variation in eight Berberis spp. collected from the Western Himalayan region. The RP-HPLC-PDA chromatogram separates the markers jatrorrhizine, palmatine and berberine at specific retention time, 11.45, 16.41 and 18.15 min respectively. The method was validated on linearity, precision and recovery indices as per International Conference on Harmonisation (ICH) guidelines. The maximum content of berberine, palmatine and jatrorrhizine was found in Berberis asiatica (1.74% ± 0.032, 1.63% ± 0.028 and 0.264% ± 0.012, respectively) on % dry weight basis. This study will help in phyto-marker-based identification and differentiation of various Berberis species, which can be used as an alternative to the official drug Daruharidra i.e. Berberis aristata .

Malnutrition and hunger is a serious global issue, however, wild fruits possess the potential of combatting it being rich in nutrients. Stereospermum chelonoides (L.f.) DC., commonly known as "Patala" in Ayurvedic text, is a large wild tree bearing edible, yet, underutilized fruits consumed by the locals in Western parts of India and neighboring countries. The present study focuses on the nutritional profile of S. chelonoides fruit along with quantification of bioactive constituents using RP-HPLC-PDA and evaluation of in-vitro anti-oxidant and, anti-microbial activity. The fruit was found rich in nutritional composition having protein (2.41 % ± 0.007), fibre (3.46 % ± 0.02) and carbohydrate (90.19 % ± 1.73) with energy value of 368.2 ± 3.94 Kcal/100g. The elemental analysis of fruit resulted in macronutrients Ca, Mg and Na and micronutrients Fe, Mn, Zn, and Cu in amounts comparable to common marketed fruits. The RP-HPLC-PDA analysis revealed the presence of six phenolic compounds in all 3 extracts made from the fruit in which highest amount are present in hydro-alcoholic extract. All the extracts exhibited potent antioxidant activity evaluated through DPPH assay and oxygen radical absorbing capacity (ORAC), with highest activity in hydro-alcoholic extract. All the analyzed extracts also exhibited potent inhibition, against four human pathogens namely Pseudomonas aeruginosa , Vibrio cholerae , Escherichia coli, and Shigella flexneri . Therefore, it is evident from the study that the fruit of S. chelonoides has immense potential as a nutraceutical supplement and may help in the management of nutrient deficiency and malnutrition among rural and tribal communities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Coscinium fenestratum (Goetgh.) Colebr. is widely used for urinary disorders and kidney stones by ethnic communities in southern India. The species is documented in various ancient Indian Ayurvedic literatures having therapeutic use in 'Ashmari' i.e., urolithiasis. The present study aims at validation of in-vitro anti-urolithiatic potential of various extracts of C. fenestratum stem along with identification and quantification of major bioactive alkaloids, i.e., berberine and palmatine through HPTLC and LC-MS/MS. Water extract showed maximum anti-urolithiatic activity which on further kinetic analysis, showed concentration dependent inhibitory delay in nucleation and aggregation of calcium oxalate crystals. Berberine and palmatine were quantified with maximum content in methanolic extract (0.478 ± 0.003 and 0.0358 ± 0.001) followed by chloroform and petroleum ether extracts. The study validates ethnobotanical use of C. fenestratum as anti-urolithiatic agent. Further, species can also be explored as a substitute for Berberis spp. for the alkaloid metabolites i.e., berberine and palmatine.

Background: Extended spectrum β-lactamases (ESBLs) are a group of beta-lactamase enzymes that confer resistance to the oxyimino-cephalosporins and monobactams. The emergence of ESBL - producing genes possesses a serious threat for treating infections since it is associated with multi-drug resistance. This study was focused to identify the ESBLs producing genes from Escherichia coli isolates from clinical samples from a referral-level tertiary care hospital in Lalitpur., Methods: This was a cross-sectional study conducted from September 2018 to April 2020 at the Microbiology Laboratory of Nepal Mediciti Hospital. Clinical samples were processed, and culture isolates were identified and characterized following standard microbiological techniques. An antibiotic susceptibility test was performed by a modified Kirby-Bauer disc diffusion method as recommended by Clinical and Laboratory Standard Institute guidelines.Extended -spectrum beta-lactamases were phenotypically confirmed by the combined disc method. The ESBL-producing genes bla TEM , bla CTX-M and bla SHV were confirmed by PCR., Results: Of the 1449 total E. coli isolates, 22.29% (323/1449) isolates were multi-drug resistant (MDR). Among the total MDR E. coli isolates, 66.56% (215/323) were ESBL producers. The maximum number of ESBL E. coli was isolated from urine 90.23% (194) followed by sputum 5.58% (12), swab 2.32% (5), pus 0.93% (2), and blood 0.93% (2). The antibiotic susceptibility pattern of ESBL E. coli producers showed the highest sensitivity toward tigecycline (100%) followed by polymyxin b, colistin and meropenem. Out of 215 phenotypically confirmed ESBL E. coli, only 86.51% (186) isolates were found to be positive by PCR for either bla TEM or bla CTX-M genes. Among the ESBL genotypes, the most common were bla TEM 63.4% (118) followed by bla CTX-M 36.6% (68)., Conclusion: The emergence of MDR and ESBL - producing E. coli isolates with high antibiotic - resistant rates to commonly used antibiotics and increased predominance of major gene types bla TEM is a serious concern to the clinicians and microbiologists. Periodic monitoring of antibiotic susceptibility and associated genes would help guide the rationale use of antibiotics for treating the predominant pathogen E. coli in the hospitals and healthcare facilities of the communities., (© 2023. The Author(s).)

Ethno Pharmacological Relevance: Eulophia nuda, locally known as "Amarkand" is an edible orchid, traditionally used as food and ethnomedicine in arthritis, as a blood purifier, vermifuge, in bronchitis, scrofulous glands etc. AIM: The present study focuses on the proximate-nutrient analysis, metabolic profiling of bioactive phenolic acids (PA's) and validation of anti-arthritic activity in E. nuda., Materials: The proximate, nutrition and element (macro-micro) content were evaluated as per standard protocols. The anti-arthritic activity was evaluated via different Invitro models and bioactive phenolics were quantified through calibrated HPLC-UV (PDA) method, as per ICH guidelines., Results: The species contains a considerable amount of proximate i.e. ash, fiber, crude alkaloid, total phenolics, and flavonoid. It is a rich source of macro-micro nutrients, carbohydrates and energy, at par with conventional cereals and super-foods like finger millet, foxtail millet etc. It also contains seven PA's viz. gallic acid, protocatechuic acid, caffeic acid, syringic acid, vanillin acid, ferulic acid and quercetin. The PA's content varies from 4.00 to 83.50 μg/ml. The anti-arthritic potential of the plant extract based on several in-vitro-models showed a promising inhibitory effect on inflammation and uric acid synthesis., Conclusion: The study scientifically validates the traditional claims of this traditional orchid as food and ethnomedicine. The species can be commercially explored as a supplement to combat nutritional deficiency among rural communities., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gloriosine, the predominant metabolite of Gloriosa superba L., shares chemical properties with colchicine. We analyze the microtubule-binding affinity of gloriosine at the colchicine binding site (CBS) using an in silico-in vivo approach. The In silico docking of gloriosine showed a binding score of (-) 7.5 kcal/Mol towards β-tubulin at CBS and was validated by overlapping the coupling pose of the docked ligand with co-crystallized colchicine. 2D plots (Ligplot +) showed > 85% overlap between gloriosine and colchicine. The ADMET profile of gloriosine was in accordance with Lipinski's rule of five. Gloriosine belongs to class II toxicity with anLD 50 value of 6 mg/kg. In vivo and transmission electron microscopy studies revealed that gloriosine induces abnormalities in cell division such as condensed chromosomes in C-metaphase and enlarged nucleus with increased nuclear material. Gloriosine treated cells exhibited mitotic index of about 14% compared to control of 24% and high anti-proliferative activity i.e. 63.94% cell viability at a low concentration (0.0004 mg/ml). We conclude that gloriosine has a strong affinity for β-tubulin at CBS and thus can be used as a colchicine alternative in cytology and other clinical conditions., (© 2023. The Author(s).)

Background: Gloriosa superba is a valuable Ayurvedic medicinal plant and is in high demand in the world market for its colchicine content, which is used to treat gout., Objective: The study aims (1) to record the metabolic variations in major bioactive metabolites, colchicine and gloriosine, in the natural populations of G. superba from Western Ghats and adjoining areas in India and (2) to develop HPTLC protocol for the identification of elite chemotypes of species and regulation of quality raw material, extract, and finished material., Method: Simultaneous quantification of colchicine and gloriosine in 22 natural populations through validated HPTLC as per ICH guidelines., Results: Colchicine and gloriosine were identified at Rf 0.51 ± 0.03 and 0.41 ± 0.05 and the content varied from 0.021 to 0.86% and 0.003 to 0.198%. The method was found linear at a concentration range of 0.1-0.7 µg/spot, and LOD (3.3 σ/S) and LOQ (10 σ/S) was 0.71 and 2.16 µg/spot. The method was precise in the concentration range of 100-300 ng/spot, with 98.29% and 101.12% recovery (% RSD) for colchicine and gloriosine. Subsequently, four elite chemotypes were identified based on cluster analysis of metabolite content., Conclusion: The developed HPTLC method is linear, accurate, precise, and robust for simultaneous quantification of colchicine and gloriosine metabolite(s). Intraspecific metabolic variation was significant among the collected population, leading to the identification of four elite chemotypes., Highlights: Colchicine is an industrially viable metabolite and is therefore quintessential to the development of an economical and analytical method to regulate the quality of raw material, extract, and finished products., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study aims to investigate the structural and vibrational features of cefradine (the first-generation cephalosporin antibiotic) based on spectroscopic experiments and theoretical quantum chemical approach. The fundamental structural aspects of cefradine have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, intramolecular hydrogen bonding, and molecular docking analysis. The most stable minimum energy conformer of the title molecule was identified by performing a one-dimensional potential energy surface scan along the rotational bonds at B3LYP/6-311++G (d,p) level of theory. The vibrational features of the molecule and information about the coupled modes were predicted. The chemical reactivity and stability of all the possible conformers of cefradine were estimated based on the HOMO-LUMO energy gap and NBO approach. The overall picture of accumulation of charges on individual atoms of the molecule was predicted by molecular electrostatic potential (MEP) surface map which in turn identifies the nucleophilic and electrophilic region or sites. The quantitative analysis of electrophilicity and nucleophilicity indices was done by Hirshfeld charge analysis and it was found that N8 atom is the most prominent site for nucleophilic attack while C14 atom is feasible for electrophilic attack. QTAIM study has also been performed to investigate the nature and strength of hydrogen bonding interactions. Besides, molecular docking studies were performed to examine the active binding residues of the target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Context: Obtaining intravenous (IV) access is one of the very frequent invasive procedures performed in hospital care settings. This has several complications some of which are serious in nature. However, the incidence and seriousness of these complications as well as the burden of this complication on patient management are often underestimated. Identification of susceptible patients and the risk factors are important to ensure better outcomes., Aims: The aim of this study was to document the various local complications of intravenous access and to identify the risk factors associated with it., Settings and Design: Prospective observational study with three hundred and one surgical patients. Study duration of 1 year., Methods and Material: Indication of IV access, site, size of IV cannula used, category of personnel involved as well as local complications at access site were documented. Dressing at cannula site were changed every 72 h or earlier. Cannula and site of access were changed in case of any complication., Statistical Analysis Used: Results analysed using SPSS software (IBM Inc). Frequency calculated as average and percentage. Chi-square test used for statistical significance. Relative risk calculated., Results: Females, overweight, diabetics and smokers were found at more risk. Requirement of major surgery, IV access by paramedical personnel, IV access over joints and when kept beyond 3 days were found to have more complications. 5.7% of patients had serious complications requiring surgical intervention., Conclusions: Our study shows that local complications at IV access site are very common with occurrence in more than fifty percent patients. Several risk factors are identified. Not all demographic and clinical risk factors are readily modifiable. However many of the complications can easily be minimized by following basic precautions., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Background: Increased oxidative stress is a major cause of aging and age-related diseases. Erythrocytes serve as good model for aging studies. Dihydrotachysterol is known to induce premature aging feature in rats mimicking Hutchinson-Gilford progeria syndrome., Aim: In the present study, attempts have been made to explore the differential response of young and senescent erythrocytes separated by density gradient centrifugation from accelerated senescence model of rats mimicking Hutchinson-Gilford progeria syndrome and naturally aged rats., Methods: The erythrocytes of naturally aged and progeroid rats were separated into distinct, young and old cells on the basis of their differential densities. The parameters of oxidative stress and membrane transport systems were studied., Discussion and Conclusion: Our study provides evidence that organismal aging negatively affects oxidative stress markers and membrane transport systems in both young and old erythrocytes. This study further substantiates that the changes in progeria model of rats resemble natural aging in terms of erythrocyte senescence.

Although several etiological factors contribute to the complexity of the aging process, the ultimate component of macromolecular damage and consequent cell death involves the altered redox balance inclined towards increased ROS production and/or decreased antioxidant protection. Given that, the chronic dihydrotachysterol (DHT) intoxication in rats induce Hutchinson Gilford progeria like syndrome, the present study provides the evidence for altered redox balance as evidenced by alteration in parameters of oxidative stress in blood plasma and erythrocytes including MDA, GSH, FRAP AOPP PMRS, AGEs, AChE and osmotic fragility which substantiate the suitability of the model for aging studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

250 patients with evidence of pulmonary tuberculosis and 50 nontubercular patients as a control group were subjected to Tuberculin test, Chest X-Ray, sputum microscopy, screening for HIV by ELISA and confirmation by Western blot if ELISA test was found positive. In the study group, 11 tested positive for HIV-1 and 239 tested seronegative, however, in the control group all patients were HIV seronegative. HIV infection was most prevalent in young males in the 21-40 year age group, with a history of tuberculosis, either residing, or working in an urban area away from their family. All our cases were of the HIV-1 serotype.

The Dautrey procedure was used to treat 12 patients with chronic recurrent dislocation of the temporomandibular joint. There was no recurrent dislocation in 11 patients during a follow-up period of up to 5 years and 2 months, and joint function appeared to be undisturbed. The surgical procedure and evaluation of the results are presented.