High-Throughput Bioprinting Method for Modeling Vascular Permeability in Standard Six-well Plates with Size and Pattern Flexibility.

Vascular permeability is a key factor in developing therapies for disorders associated with compromised endothelium, such as endothelial dysfunction in coronary arteries and impaired function of the blood-brain barrier. Existing fabrication techniques do not adequately replicate the geometrical variation in vascular networks in the human body, which substantially influences disease progression; moreover, these techniques often involve multi-step fabrication procedures that hinder the high-throughput production necessary for pharmacological testing. This paper presents a bioprinting protocol for creating multiple vascular tissues with desired patterns and sizes directly on standard six-well plates, overcoming existing resolution and productivity challenges in bioprinting technology. A simplified fabrication approach was established to construct six hollow, perfusable channels within a hydrogel, which were subsequently lined with human umbilical vein endothelial cells to form a functional and mature endothelium. The computer-controlled nature of 3D bioprinting ensures high reproducibility and requires fewer manual fabrication steps than traditional methods. This highlights VOP's potential as an efficient high-throughput platform for modeling vascular permeability and advancing drug discovery.

Coaxial bioprinting of a stentable and endothelialized human coronary artery-sized in vitro model.

Atherosclerosis accounts for two-thirds of deaths attributed to cardiovascular diseases, which continue to be the leading cause of mortality. Current clinical management strategies for atherosclerosis, such as angioplasty with stenting, face numerous challenges, including restenosis and late thrombosis. Smart stents, integrated with sensors that can monitor cardiovascular health in real-time, are being developed to overcome these limitations. This development necessitates rigorous preclinical trials on either animal models or in vitro models. Despite efforts being made, a suitable human-scale in vitro model compatible with a cardiovascular stent has remained elusive. To address this need, this study utilizes an in-bath bioprinting method to create a human-scale, freestanding in vitro model compatible with cardiovascular stents. Using a coaxial nozzle, a tubular structure of human coronary artery (HCA) size is bioprinted with a collagen-based bioink, ensuring good biocompatibility and suitable rheological properties for printing. We precisely replicated the dimensions of the HCA, including its internal diameter and wall thickness, and simulated the vascular barrier functionality. To simplify post-processing, a pumpless perfusion bioreactor is fabricated to culture a HCA-sized model, eliminating the need for a peristaltic pump and enabling scalability for high-throughput production. This model is expected to accelerate stent development in the future.

The effects of lumbar stabilization exercises with and without jaw movements in non-specific low back pain (A randomized controlled trial).

Objective: This study aimed to investigate the added effect of jaw clenching on the efficacy of lumbar stabilization exercises to manage chronic non-specific low back pain. Methods: This randomized controlled trial was conducted at the Sindh Institute of Physical Medicine and Rehabilitation (SIPM&R) Karachi from April 2021 to April 2023. Eighty patients with chronic non-specific low back pain participated in this study. Forty patients each were randomly allocated to the lumbar stability exercise (LSE) group' and the lumbar stability exercise with teeth clenching (LSETC) group. Patients in both groups performed respective exercises twice weekly for 12 weeks. The Numeric Pain Rating Scale (NPRS), Roland Morris Disability Questionnaire (RMDQ), and Pressure Biofeedback Unit (PBU) were used to assess pain, disability, and muscle endurance respectively. Data were collected at the baseline, after six weeks and 12 weeks of intervention. A p-value of <0.05 was considered statistically significant. Results: Both groups showed statistically significant improvements in pain, disability, and muscle endurance. Upon further stratification, participants aged 20-30 years in the LSETC group showed significantly higher scores than the LSE group for NPRS, RMDQ, and PBU after 12 weeks. Overall, the LSETC group showed relatively higher improvement in mean scores for NPRS, RMDQ, and PBU than the LSE group. Conclusion: Lumbar stabilization exercises with and without jaw movement are effective for the treatment of chronic non-specific low back pain. The addition of teeth clenching enhanced the effectiveness of lumbar stability exercises, especially in young adults. Trial Registration: Clinicaltrials.gov (NCT04801212), Prospectively registered on March 16, 2021.

Bioinks for bioprinting using plant-derived biomaterials.

Three-dimensional (3D) bioprinting has revolutionized tissue engineering by enabling the fabrication of complex and functional human tissues and organs. An essential component of successful 3D bioprinting is the selection of an appropriate bioink capable of supporting cell proliferation and viability. Plant-derived biomaterials, because of their abundance, biocompatibility, and tunable properties, hold promise as bioink sources, thus offering advantages over animal-derived biomaterials, which carry immunogenic concerns. This comprehensive review explores and analyzes the potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues. Modification and optimization of these materials to enhance printability and biological functionality are discussed. Furthermore, cancer research and drug testing applications of the use of plant-based biomaterials in bioprinting various human tissues such as bone, cartilage, skin, and vascular tissues are described. Challenges and limitations, including mechanical integrity, cell viability, resolution, and regulatory concerns, along with potential strategies to overcome them, are discussed. Additionally, this review provides insights into the potential use of plant-based decellularized ECM (dECM) as bioinks, future prospects, and emerging trends in the use of plant-derived biomaterials for 3D bioprinting applications. The potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues is highlighted herein. However, further research is necessary to optimize their processing, standardize their properties, and evaluate their long-termin vivoperformance. Continued advancements in plant-derived biomaterials have the potential to revolutionize tissue engineering and facilitate the development of functional and regenerative therapies for diverse clinical applications.

Biological effects of culture medium on Tetraselmis chuii and Dunaliella tertiolecta: Implications for emerging pollutants degradation.

In this study, laboratory-scale cultivation of T. chuii and D. tertiolecta was conducted using Conway, F/2, and TMRL media to evaluate their biochemical composition and economic costs. The highest cell density (30.36 × 106 cells/mL) and dry weight (0.65 g/L) for T. chuii were achieved with Conway medium. This medium also produced biomass with maximum lipid content (25.65%), proteins (27.84%), and total carbohydrates (8.45%) compared with F/2 and TMRL media. D. tertiolecta reached a maximum cell density of 17.50 × 106 cells/mL in F/2 medium, which was notably lower than that of T. chuii. Furthermore, the media cost varied from US$0.23 to US$0.74 for each 1 L of media, primarily due to the addition of Na3PO4, KNO3, and cyanocobalamin. Thus, biomass production rates varied between US$38.81 and US$128.80 per kg on a dry weight basis. These findings comprehensively compare laboratory conditions and the costs associated with biomass production in different media. Additionally, this study explored the potential of T. chuii and D. tertiolecta strains, as well as their consortia with bacteria, for the degradation of various emerging pollutants (EPs), including caffeine, salicylic acid, DEET, imidacloprid, MBT, cimetidine, venlafaxine, methylparaben, thiabendazole, and paracetamol. Both microalgal strains demonstrated effective degradation of EPs, with enhanced degradation observed in microalgae-bacterial consortia. These results suggest that the symbiotic relationship between microalgae and bacteria can be harnessed for the bioremediation of EPs, thereby offering valuable insights into the environmental applications of microalgal cultivation.

Mechanical release of homogenous proteins from supramolecular gels.

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.

Spatial distribution of physicochemical parameters and drinking and irrigation water quality indices in the Jhelum River, Pakistan.

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.

The role of reduced graphene oxide on mitigation of lead phytotoxicity in Triticum aestivum L.plants at morphological and physiological levels.

Rapid global industrialization and an increase in population have enhanced the risk of heavy metals accumulation in plant bodies to disrupt the morphological, biochemical, and physiological processes of plants. To cope with this situation, reduced graphene oxide (rGO) NPs were used first time to mitigate abiotic stresses caused in plant. In this study, rGO NPs were synthesized and reduced with Tecoma stans plant leave extract through modified Hummer's methods. The well prepared rGO NPs were characterized by ultra-violet visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Zeta potential, and scanning electron microscopy (SEM). However, pot experiment was conducted with four different concentrations (15, 30, 60, 120 mg/L) of rGO NPs and three different concentrations (300, 500,700 mg/L) of lead (Pb) stress were applied. To observe the mitigative effects of rGO NPs, 30 mg/L of rGO NPs and 700 mg/L of Pb were used in combination. Changes in morphological and biochemical characteristics of wheat plants were observed for both Pb stress and rGO NPs treatments. Pb was found to inhibit the morphological and biochemical characteristics of plants. rGO NPs alone as well as in combination with Pb was found to increase the chlorophyll content of wheat plants. Under Pb stress conditions and rGO NPs treatments, antioxidant enzyme activities like ascorbate peroxidases (APX), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were observed. Current findings revealed that greenly reduced graphene oxide NPs can effectively promote growth in wheat plants under Pb stress by elevating chlorophyll content of leaves, reducing the Pb uptake, and suppressing ROS produced due to Pb toxicity.

Non-invasive imaging techniques for early diagnosis of bilateral cardiac dysfunction in pulmonary hypertension: current crests, future peaks.

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease that eventually leads to heart failure (HF) and subsequent fatality if left untreated. Right ventricular (RV) function has proven prognostic values in patients with a variety of heart diseases including PAH. PAH is predominantly a right heart disease; however, given the nature of the continuous circulatory system and the presence of shared septum and pericardial constraints, the interdependence of the right and left ventricles is a factor that requires consideration. Accurate and timely assessment of ventricular function is very important in the management of patients with PAH for disease outcomes and prognosis. Non-invasive modalities such as cardiac magnetic resonance (CMR) and echocardiography (two-dimensional and three-dimensional), and nuclear medicine, positron emission tomography (PET) play a crucial role in the assessment of ventricular function and disease prognosis. Each modality has its own strengths and limitations, hence this review article sheds light on (i) ventricular dysfunction in patients with PAH and RV-LV interdependence in such patients, (ii) the strengths and limitations of all available modalities and parameters for the early assessment of ventricular function, as well as their prognostic value, and (iii) lastly, the challenges faced and the potential future advancement in these modalities for accurate and early diagnosis of ventricular function in PAH.

Exploring the Potential of Nitrogen-Doped Graphene in ZnSe-TiO2 Composite Materials for Supercapacitor Electrode.

The current study explores the prospective of a nitrogen-doped graphene (NG) incorporated into ZnSe-TiO2 composites via hydrothermal method for supercapacitor electrodes. Structural, morphological, and electronic characterizations are conducted using XRD, SEM, Raman, and UV analyses. The electrochemical study is performed and galvanostatic charge-discharge (GCD) and cyclic voltammetry (CV) are evaluated for the supercapacitor electrode material. Results demonstrate improved performance in the ZnSe-NG-TiO2 composite, indicating its potential for advanced supercapacitors with enhanced efficiency, stability, and power density. Specific capacity calculations and galvanic charge-discharge experiments confirmed the promising electrochemical activity of ZnSe-NG-TiO2, which has a specific capacity of 222 C/g. The negative link among specific capacity and current density demonstrated the composite's potential for high energy density and high-power density electrochemical devices. Overall, the study shows that composite materials derived from multiple families can synergistically improve electrode characteristics for advanced energy storage applications.

Insights into measles virus: Serological surveillance and molecular characterization.

BACKGROUND: Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to challenge existing control measures. This study aimed to estimate the prevalence and investigate the molecular epidemiology of the measles virus (MeV) in KPK and explore the vaccination status among the suspected individuals. METHODS: A cross-sectional study was conducted between February and October 2021. A total of 336 suspected measles cases from the study population were analyzed for IgM antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Throat swabs were randomly collected from a subset of positive cases for molecular analysis. Phylogenetic analysis of MeV isolates was performed using the neighbor-joining method. The vaccination status of individuals was also recorded. RESULTS: Among the suspected participants, 61.0% (205/336) were ELISA positive for IgM antibodies, with a higher prevalence in males (64.17%) compared to females (57.04%). The majority of cases (36.0%) were observed in infants and toddlers, consistent with previous reports. The majority of IgM-positive cases (71.7%) had not received any dose of measles vaccine, highlighting gaps in vaccine coverage and the need for improved immunization programs. Genetic analysis revealed that all MeV isolates belonged to the B3 genotype, with minor genetic variations from previously reported variants in the region. CONCLUSION: This study provides valuable insights into the genetic epidemiology of the MeV in KPK, Pakistan. The high incidence of measles infection among unvaccinated individuals highlights the urgency of raising awareness about vaccine importance and strengthening routine immunization programs.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

Design, optimization, and comparative analysis of wide-band polarization conversion along with dual coding sequences for RCS reduction.

In this paper, a wideband polarization conversion metasurface is designed. Additionally, coding and chessboard metasurfaces are specifically tailored for radar cross-section reduction (RCS). Initially, a compact unit cell demonstrating exceptional polarization conversion performance is introduced, achieving a polarization conversion ratio (PCR) exceeding 90 % across frequencies ranging from 7.9 to 22.7 GHz. The PCR remains effective even when oblique incidence angles of up to 30 ∘ are utilized across this frequency band. Roger RT5880, with a thickness of 0.254 mm, serves as the substrate. An airgap is introduced between the substrate and the ground plane to enhance the polarization conversion bandwidth. This unit cell serves as the fundamental building block for subsequent metasurface configurations. To assess the scalability and effectiveness, a 36 × 36 unit array is assembled, confirming efficient polarization conversion capabilities extending to larger structures. Moreover, a 1-bit coding unit "0" and "1" are formed by the Pancharatnam-Berry phase based on the same-sized meta-atom with 90 ∘ orientations. The robustness and practicality of the design are demonstrated by creating 12 × 12 lattices and evaluating their RCS reduction potential under two distinct scenarios: a chessboard pattern and a coding-based scheme. Notably, its results indicate substantial RCS reduction across a broad frequency spectrum (7.9 to 22.7 GHz) for both configurations. This study demonstrates the wide-ranging applicability of metasurface design, making it a valuable contribution to the fields of microwave engineering, polarization control, and radar stealth technology. Owing to its simplicity, bandwidth, and versatility, this approach offers innovative solutions for diverse real-world applications.

A continuous cuffless blood pressure measurement from optimal PPG characteristic features using machine learning algorithms.

Background and objective: Hypertension is a potentially dangerous health condition that can be detected by measuring blood pressure (BP). Blood pressure monitoring and measurement are essential for preventing and treating cardiovascular diseases. Cuff-based devices, on the other hand, are uncomfortable and prevent continuous BP measurement. Methods: In this study, a new non-invasive and cuff-less method for estimating Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP), and Diastolic Blood Pressure (DBP) has been proposed using characteristic features of photoplethysmogram (PPG) signals and nonlinear regression algorithms. PPG signals were collected from 219 participants, which were then subjected to preprocessing and feature extraction steps. Analyzing PPG and its derivative signals, a total of 46 time, frequency, and time-frequency domain features were extracted. In addition, the age and gender of each subject were also included as features. Further, correlation-based feature selection (CFS) and Relief F feature selection (ReliefF) techniques were used to select the relevant features and reduce the possibility of over-fitting the models. Finally, support vector regression (SVR), K-nearest neighbour regression (KNR), decision tree regression (DTR), and random forest regression (RFR) were established to develop the BP estimation model. Regression models were trained and evaluated on all features as well as selected features. The best regression models for SBP, MAP, and DBP estimations were selected separately. Results: The SVR model, along with the ReliefF-based feature selection algorithm, outperforms other algorithms in estimating the SBP, MAP, and DBP with the mean absolute error of 2.49, 1.62 and 1.43 mmHg, respectively. The proposed method meets the Advancement of Medical Instrumentation standard for BP estimations. Based on the British Hypertension Society standard, the results also fall within Grade A for SBP, MAP, and DBP. Conclusion: The findings show that the method can be used to estimate blood pressure non-invasively, without using a cuff or calibration, and only by utilizing the PPG signal characteristic features.

Formulation and Preparation of Losartan-Potassium-Loaded Controlled-Release Matrices Using Ethocel Grade 10 to Establish a Correlation between In Vitro and In Vivo Results.

In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 µg/mL), AUCo (5931.10 ± 1.232 µg·h/mL), AUCo-inf (7348.46 ± 0.234 µg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes.

Dual-band 5G MIMO antenna with enhanced coupling reduction using metamaterials.

This article introduces a miniaturized dual-band multiple input multiple output (MIMO) antenna with wide bandwidth and high isolation. The design incorporates ground plane modifications and utilizes metamaterials to achieve dual-band operation in the millimeter wave spectrum for 5G applications, specifically operating at the 28/38 GHz frequency bands. The proposed antenna maintains its dual-band functionality despite its compact size of 3.8 [Formula: see text] 3.7 [Formula: see text] 0.787 [Formula: see text] (without the feed line). The antenna is fabricated on a Rogers RT5880 substrate with a thickness of 0.787 mm and with relative permittivity [Formula: see text] = 2.2. The MIMO system comprises two symmetric radiating elements positioned in close proximity, resulting in mutual coupling levels of [Formula: see text] 20 dB and [Formula: see text] 12 dB at 25 GHz and 37 GHz, respectively. Modifications are made to the ground length to enhance the isolation at the higher frequency band while embedding metamaterials effectively reduces the coupling at the lower frequency band. The incorporation of metamaterials leads to an enhanced bandwidth from 3.8 to 4.8 GHz in the desired lower band (24-28.8 GHz) and from 3.8 to 4.2 GHz in the higher band (36.6-40.8 GHz). The proposed system can operate across the 28/38 GHz bands using a compact design, thus offering reasonable isolation, an envelope correlation coefficient below 0.0001, and a significant diversity gain (> 9.99 dB). These attributes emphasize the system's suitability for 5G millimeter-wave cellular communications.

Translation, cross-cultural adaptation and psychometric properties of the Urdu version of the back pain functional scale in low back pain patients.

BACKGROUND: Translation and validation of important scales in other languages reduce bias in reporting the functional status of the patient. OBJECTIVE: To translate the Back Pain Functional Scale into Urdu (BPFSu), adapt it for use in other cultures, and evaluate its psychometric properties. METHOD: According to Beaton guidelines, translation and cultural adaption was carried out. On 100 Urdu-literate men and women aged 18-60 years with lower back pain, the final BPFSu was assessed for psychometric qualities. First at baseline and again after 7 days, participants completed the BPFSu, the Functional Rating Index (FRI), and the Numeric Pain Rating Scale (NPRS). RESULTS: Internal consistency of the BPFSu was excellent (Cronbach's alpha: 0.937). No floor and ceiling effects were found Excellent test-retest reliability (ICC = 0.882, CI 95%; 0.830-0.919) was achieved. Spearman correlation coefficient showed criterion validity with the NPRS (rho =â⁢⁢0.701, p⩽ 0.001) and Pearson correlation coefficient showed construct validity with the FRI (r=â⁢⁢0.740, p⩽ 0.001). The minimum detectable changes were 9.96, while the standard error of measurement was 3.6. CONCLUSION: The BPFSu is a valid and reliable instrument for assessing physical function in individuals experiencing low back discomfort.

Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne.

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.