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IntroductionThe influence of urban green spaces on public health is receiving unprecedented attention. Managing urban greenspaces sustainably requires an understanding of the mechanisms behind the positive effects of urban biodiversity on the wellbeing of residents. Urban parks could improve mental restoration of park users. The restoration potential may be influenced by the biophysical characteristics of the park.MethodsThis study aimed to understand two aspects of urban parks in Multan, Pakistan: (a) How does the perception of biodiversity and the quality of urban parks relate to mental restorativeness of park visitors? (b) What are the determinants of respondents' willingness to pay for the conservation and management of park biodiversity and quality in urban parks? Data were collected from October 2021 to December 2021 through a cross-sectional survey in which 550 park visitors were interviewed from six randomly selected urban parks in Multan. Multiple linear regression analysis, a binary logistic model, and a chi-square test were applied to analyze the data.Results and discussionThe study empirically highlights the positive contribution of park visits to mental restorativeness. Biodiversity and quality were positively correlated with the mental restorativeness of park visitors. Sixty-two percent (62%) of the visitors were reluctant to pay, whereas 38% were ready to pay between Rs. 850/3.7$ and Rs. 1,700/7.4$ each year. Education, occupation, and monthly income significantly positively affected the respondent's WTP attitudes. The study highlights the importance of using urban parks as tools to promote mental restorativeness, combat social stress, and increase urban vegetation cover.

Abstract This study aimed at investigating the chemical composition and the hepatoprotective activities of Plumbago indica L. and P. auriculata Lam. LC–MS/MS analyses for the hydroalcoholic extracts of the aerial parts of the two Plumbago species allowed the tentative identification of thirty and twenty-five compounds from P. indica and P. auriculata, respectively. The biochemical and histopathological alterations associated with thioacetamide (TAA)-induced liver fibrosis in rats were evaluated in vivo where rats received the two extracts at three different dose levels (100, 200 and 400 mg/kg p.o, daily) for 15 consecutive days with induction of hepatotoxicity by TAA (200 mg/kg/day, i.p.) at 14th and 15th days. Results of the present study showed a significant restoration in liver function biomarkers viz. alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transferase and total bilirubin. The liver homogenates exhibited increased levels of antioxidant biomarkers: reduced glutathione (GSH) and catalase (CAT), accompanied with decline in malondialdehyde (MDA). Furthermore, treated groups exhibited a significant suppression in liver inflammatory cytokines: tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6), and fibrotic biomarker: alpha smooth muscle relaxant. Histopathological examination of the liver showed normality of hepatocytes. Noteworthy, P. indica extract showed better hepatoprotective activity than P. auriculata, particularly at 200 mg/kg. To sum up, all these results indicated the hepatoprotective properties of both extracts, as well as their antifibrotic effect was evidenced by reduction in hepatic collagen deposition. However, additional experiments are required to isolate their individual secondary metabolites, assess the toxicity of the extracts and explore the involved mechanism of action.

Background: Tumor microenvironment, specifically tumor-associated macrophages, plays an important role in tumor initiation and progression. CD163 has been recognized as a valuable specific macrophage marker. Cyclooxygenase-2 (Cox2) plays a role in tumor progression. CD31 is reliable for estimation of the density of microvesseles (MVD), which has prognostic importance in several malignant tumors. Thus, the current study was conducted to test the association between CD163, Cox2, and CD31 expression with the prognosis of classical Hodgkin lymphoma (cHL) patients and their potential correlation with clinicopathological variables. Method: CD163, Cox2, and CD31 expressions were examined in newly diagnosed patients with cHL through immunohistochemistry on tissue biopsy and the results were correlated with the patients’ outcome after the median follow-up, which was about 35 months. Results: 104 patients were included in this study. High CD163 was found in 32.7% of the patients. Cox2 was positive in 42.3% of them. CD 31 with high MVD (≥10%) was found in 51% of the subjects. A significant association was detected between CD163 and Cox2 with tumor stage (P = 0.001, and P = 0.001) and IPS score. Regarding CD31, we could not find any significant associations with disease parameters, except with histological subtype (P = 0.001). A significant relationship was observed between Cox2 and CD163 expression and the relapse rate (P = 0.001, P = 0.01, respectively). Regarding survival, only Cox2 showed a significant association with disease-free survival (P = 0.0379). Conclusion: These findings suggested that Cox2 and CD163 expression can be used as predicator for early relapse and as new therapeutic targets in cHL.

Introduction: Recently, the recovery of waste products from plants as a source of biologically active compounds has increased interest. Therefore, the current research aims to evaluate the anti-inflammatory, immunomodulatory and antimicrobial activities of the fixed oil of Cucumis melo L seeds, as well as to investigate its physicochemical parameters and chemical composition. Methods: Anti-inflammatory activity was examined using carrageenan-induced rat paw edema assay. The antimicrobial activity was assayed against Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans by well diffusion method. The chemical composition of the oil was determined by gas chromatography/mass spectrometry (GC/MS), α-tocopherol was estimated by high-performance liquid chromatography (HPLC). Results: Cucumis melo oil had no toxicity and possessed a promising anti-inflammatory activity. Moreover, the oil exhibited a reasonable decrease in the pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and a significant increase in the anti-inflammatory cytokine (IL-10). The oil exhibited a reasonable antimicrobial activity against all tested organisms. The major identified compound in the unsaponifiable matter was (1-methyldodecyl) benzene (8.76%), while the major fatty acid was methyl linoleate (14.10%). The results of physicochemical characterization revealed the better quality of Cucumis melo oil. The amount of α-tocopherol in the oil was 23.5 μg/mL, which is considered a reasonable amount. Conclusion: These findings indicate that the fixed oil of Cucumis melo L seeds might be used as a safe natural anti-inflammatory, immunomodulatory and antimicrobial agent.

Purpose: Aging is associated with hepatic morphological and physiological deterioration due to the accumulation of endogenous and exogenous free radicals and the resultant oxidative stress. The present study aims to investigate the effect of Haematococcus pluvialis microalgae on hepatic changes associated with D-galactose (D-Gal)-induced aging in rats. Methods: Aging was induced in rats by daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis biomass, its carotenoid and polar fractions for two weeks. Twenty four hours after the last dose, blood samples were collected and the liver tissues were isolated for further biochemical and histopathological examinations. Results: D-Gal induced aging was associated with an elevation in serum liver function parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich H. pluvialis restored the serum liver function parameters as well as hepatic CAT, GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and IL-6. Histopathological examination emphasized all the previous results. Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93 kcal/mol estimated free energy of binding as well as moderate affinities towards IL-6 and NF-KB through a docking study. Conclusion: ATX-rich H. pluvialis showed beneficial effects by ameliorating the hepatic changes associated with D-Gal induced aging in rats due to its modulatory role of the Nrf2/Keap pathway.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by using an alcoholic extract of the flowering aerial parts of Plumbago auriculata Lam. Dynamic Light Scattering (DLS) revealed that the average size of synthesized ZnO NPs was 10.58 ± 3.350 nm and the zeta potential was −19.6 mV. Transmission electron microscopy (TEM) revealed that the particle size was in the range from 5.08 to 6.56 nm. X-ray diffraction (XRD) analysis verified the existence of pure hexagonal shaped crystals of ZnO nanoparticles with an average size of 35.34 nm in the sample, which is similar to the particle size analysis acquired by scanning electron microscopy (SEM) (38.29 ± 6.88 nm). HPLC analysis of the phenolic ingredients present in the plant extract showed that gallic acid, chlorogenic acid, and catechin were found as major compounds at concentrations of 1720.26, 1600.42, and 840.20 µg/g, respectively. Furthermore, the inhibitory effects of ZnO NPs and the plant extract against avian metapneumovirus (aMPV) subtype B were also investigated. This assessment revealed that the uncalcinated form of Nano-ZnO mediated by P. auriculata Lam. extract possessed a significant antiviral activity with 50% cytotoxic concentration (CC50) and 50% inhibition concentration (IC50) of 52.48 ± 1.57 and 42.67 ± 4.08 µg/mL, respectively, while the inhibition percentage (IP) was 99% and the selectivity index (SI) was 1.23.

Retinoids are essential during early cardiovascular morphogenesis. However, recent studies showed their important role in cardiac remodeling in rats with hypertension and following myocardial infarction. The present study aimed to investigate the effect of zeaxanthin heneicosylate (ZH); a carotenoid ester isolated from Dunaliella salina microalgae, on cardiac dysfunction ensuing d-galactose injection in rats. Rats injected with d-GAL (200 mg/kg; I.P) for 8 weeks were orally treated with ZH (250 μg/kg) for 28 consecutive days. Results showed that d-GAL injection caused dramatic electrocardiographic changes as well as marked elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase. A reduction in the cardiac contents of glucose transporter-4 and superoxide dismutase along with the elevation of inducible nitric oxide synthetase and interleukin-6 was also noticed. Oral administration of ZH significantly improved the above mentioned cardiac aging manifestations; this was further emphasized through histopathological examinations. The effect of ZH is mediated through the interaction with retinoid receptor alpha (RAR-α) as evidenced through a significant elevation of RAR-α expression in cardiac tissue following the lead of an in silico molecular docking study. In conclusion, zeaxanthin heneicosylate isolated from D. salina ameliorated age-associated cardiac dysfunction in rats through the activation of retinoid receptors.

Objective(s): Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study aimed to examine the efficacy of Ginkgo biloba extract EGb 761 (GBE) in the treatment of L-arginine-induced AP and its associated lung injury. Materials and Methods: Forty rats were randomly assigned into four groups. The normal group received only saline intraperitoneally while the other groups received two intraperitoneal L-arginine injections (250 mg/100 g b.wt) separated by a 1-hour interval to provoke AP. GBE (200 and 400 mg/kg/day, PO) was administered for 2 weeks post-induction of pancreatitis. Sera and pancreatic tissues were isolated. Results: The outcome of the present study revealed that GBE ameliorated the elevated levels of serum amylase, lipase, and pancreatic inflammatory mediators viz., tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase P38 (MAPK-P38), c-Jun N-terminal kinase 1 (JNK1), and nuclear factor-kappa B (NF-κB). Moreover, GBE restored the pancreatic gene expression of Toll-like receptor 4 (TLR4) and prostatic acid phosphatase-2 (PAP-2). Pancreatic and lung histopathological examinations confirmed the aforementioned parameters. Conclusion: GBE interfered with the mechanistic pathway of L-arginine-induced acute pancreatic and its associated lung injury. Due to its anti-inflammatory properties, GBE can be used as a novel therapeutic candidate for the treatment of AP through down-regulating TLR-4/MAPK-p38/JNK and MAPK-p38/NF-κB signaling cascades. [ABSTRACT FROM AUTHOR]

Objective: This study examines the impact of volumetric alterations and PTV shifting on the quality of adaptive intensity-modulated radiation (IMRT) plans and their effectiveness in treating head and neck cancer. Methods: The research was carried out at the Sohag Cancer Centre in Egypt, including a sample of 36 individuals diagnosed with head and neck squamous cell carcinoma (HNSCC). Patients were chosen based on the following criteria: locally progressed and node-positive malignancy, oropharyngeal cancer, oral cavity cancer, and unknown primary. The research used dynamic intensity-modulated radiation therapy (D-IMRT) to establish treatment plans and SIEMENS SOMATOM DEFINITION CT scanners to acquire 3D anatomical images. The median dosage per fraction was observed at 1.64 to 2.12 Gy. Using the conformance index (CI) and the homogeneity index (HI), the quality of the plan was assessed. The threshold for statistical significance was set at 0.05. Results: The study analyzed patients with unilateral and bilateral HNSCC tumors, with most having bilateral tumors. The findings demonstrated that the tumor PTV was significantly reduced as a consequence of the suggested adaptive radiation techniques. The homogeneity and conformity indexes were used to evaluate the plan's quality (HI). The maximal homogeneity index (HI) was reached at fractions 14 and 7, respectively. The correlation between the reduction of PTV and CI was initially positive after fraction 7 but became negative after fractions 14 and 21. It was also shown that HI is positively correlated with PTV changes after fractions 7 and 14, while it was negative after 21 fractions. Conclusion: The use of adaptive radiotherapy in intensity-modulated radiation therapy (IMRT) treatment planning improves plan quality and decreases error rates due to tumor margin movement. Following radiation fractions, PTV shifting affects the homogeneity index (HI). [ABSTRACT FROM AUTHOR]

Introduction: The influence of urban green spaces on public health is receiving unprecedented attention. Managing urban greenspaces sustainably requires an understanding of the mechanisms behind the positive effects of urban biodiversity on the wellbeing of residents. Urban parks could improve mental restoration of park users. The restoration potential may be influenced by the biophysical characteristics of the park. Methods: This study aimed to understand two aspects of urban parks in Multan, Pakistan: (a) How does the perception of biodiversity and the quality of urban parks relate to mental restorativeness of park visitors? (b) What are the determinants of respondents' willingness to pay for the conservation and management of park biodiversity and quality in urban parks? Data were collected from October 2021 to December 2021 through a cross-sectional survey in which 550 park visitors were interviewed from six randomly selected urban parks in Multan. Multiple linear regression analysis, a binary logistic model, and a chi-square test were applied to analyze the data. Results and discussion: The study empirically highlights the positive contribution of park visits to mental restorativeness. Biodiversity and quality were positively correlated with the mental restorativeness of park visitors. Sixty-two percent (62%) of the visitors were reluctant to pay, whereas 38% were ready to pay between Rs. 850/3.7$ and Rs. 1,700/7.4$ each year. Education, occupation, and monthly income significantly positively affected the respondent's WTP attitudes. The study highlights the importance of using urban parks as tools to promote mental restorativeness, combat social stress, and increase urban vegetation cover. [ABSTRACT FROM AUTHOR]

Purpose: Aging is associated with hepatic morphological and physiological deterioration due to the accumulation of endogenous and exogenous free radicals and the resultant oxidative stress. The present study aims to investigate the effect of Haematococcus pluvialis microalgae on hepatic changes associated with D-galactose (D-Gal)-induced aging in rats. Methods: Aging was induced in rats by daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis biomass, its carotenoid and polar fractions for two weeks. Twenty four hours after the last dose, blood samples were collected and the liver tissues were isolated for further biochemical and histopathological examinations. Results: D-Gal induced aging was associated with an elevation in serum liver function parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich H. pluvialis restored the serum liver function parameters as well as hepatic CAT, GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and IL-6. Histopathological examination emphasized all the previous results. Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93 kcal/mol estimated free energy of binding as well as moderate affinities towards IL-6 and NF-KB through a docking study. Conclusion: ATX-rich H. pluvialis showed beneficial effects by ameliorating the hepatic changes associated with D-Gal induced aging in rats due to its modulatory role of the Nrf2/Keap pathway. [ABSTRACT FROM AUTHOR]

Context:Gleditsia triacanthosL. (Leguminosae) pods are used in folk medicine for pain relief as anodyne and narcotic. Objective: The objective of this study is to evaluate analgesic activity ofGleditsia triacanthosmethanolic fruit extract (MEGT) and its saponin-containing fraction (SFGT). Materials and methods: Peripheral analgesic activity was assessed using the acetic acid-induced writhing model in mice at doses of 140, 280, and 560 mg/kg and formalin test in rats at 100, 200, and 400 mg/kg doses. Central analgesic activity was evaluated using the hotplate method in rats (100, 200, and 400 mg/kg). Results: In the writhing test, six mice groups treated with MEGT and SFGT found ED50values 268.2 and 161.2 mg/kg, respectively, displayed a significant decrease in writhing count compared with the group treated with standard drug indomethacin (14 mg/kg). SFGT (280 and 560 mg/kg) showed 64.94 and 70.78% protection, respectively, which are more than double % protection caused by indomethacin (31.82%). In the formalin test, MEGT and SFGT (ED50values 287.6 and 283.4 mg/kg for phase I as well as 295.1 and 290.4 mg/kg for phase II, respectively) at 400 mg/kg showed significant % inhibition in both phase I (18.86 and 52.57%) and phase II (39.36 and 44.29%) with reference to 10 mg/kg indomethacin (56.0 and 32.29%). MEGT and SFGT caused significant delay in responses in hotplate model (ED50values 155.4 and 200.6 mg/kg, respectively) compared with that of 10 mg/kg indomethacin at 30, 60, and 120 min. Discussion and conclusion: Central and peripheral analgesic activities induced byGleditsia triacanthosfruits might account for its uses in folk medicine. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO NPs) were synthesized by using an alcoholic extract of the flowering aerial parts of Plumbago auriculata Lam. Dynamic Light Scattering (DLS) revealed that the average size of synthesized ZnO NPs was 10.58 ± 3.350 nm and the zeta potential was −19.6 mV. Transmission electron microscopy (TEM) revealed that the particle size was in the range from 5.08 to 6.56 nm. X-ray diffraction (XRD) analysis verified the existence of pure hexagonal shaped crystals of ZnO nanoparticles with an average size of 35.34 nm in the sample, which is similar to the particle size analysis acquired by scanning electron microscopy (SEM) (38.29 ± 6.88 nm). HPLC analysis of the phenolic ingredients present in the plant extract showed that gallic acid, chlorogenic acid, and catechin were found as major compounds at concentrations of 1720.26, 1600.42, and 840.20 µg/g, respectively. Furthermore, the inhibitory effects of ZnO NPs and the plant extract against avian metapneumovirus (aMPV) subtype B were also investigated. This assessment revealed that the uncalcinated form of Nano-ZnO mediated by P. auriculata Lam. extract possessed a significant antiviral activity with 50% cytotoxic concentration (CC50) and 50% inhibition concentration (IC50) of 52.48 ± 1.57 and 42.67 ± 4.08 µg/mL, respectively, while the inhibition percentage (IP) was 99% and the selectivity index (SI) was 1.23. [ABSTRACT FROM AUTHOR]

Olmesartan (OLM), an angiotensin receptor blocker, was tested against diabetes/insulin resistance (IR) models associated with renal/cardiovascular complications. Methods: we tested its potential role against diabetes-induced hepatic hitches using an IR/type2 diabetic (IR/D) model induced by high fat/high fructose diet for 7 weeks ​+ ​a single sub-diabetogenic dose of streptozotocin (35mg/kg; i.p). IR/D rats were orally treated with OLM (10 ​mg/kg), pioglitazone (PIO; 5 or 10 ​mg/kg) or their combinations for 4 consecutive weeks. OLM alone opposed the detrimental effects of IR/D; it significantly improved metabolic parameters, liver function, and abated hepatic oxidative stress, and inflammatory cytokine interleukin-6 (IL-6) and its upstream mediator nuclear factor kappa B. Consequently, OLM turned off the downstream cue p -Jak2/STAT3/SOCS3. Moreover, it suppressed the elevated AGE/RAGE /p- JNK pathway and increased the PPARγ/adiponectin cue to signify its anti-inflammatory and anti-oxidant capacity (GSH, MDA). Nevertheless, co-administration of OLM to PIO showed a synergistic improvement in all the aforementioned parameters in a dose dependent manner. Additionally, OLM with PIO 10 provoked a surge in hepatic PPARγ and adiponectin (5 and 6 folds) with a sharp decrease of about 85% in the NF-κB/IL-6/ p -STAT3/SCOS3 pathway. These effects were confirmed by the histopathological study. In conclusion, OLM and its combination with PIO enhanced insulin sensitivity and guarded against hepatic complications associated with type 2 diabetes probably via modulating various inter-related pathways; namely, metabolic alteration, renin-angiotensin system, inflammatory trajectories, as well as oxidative stress. This study manifests the potential synergistic effects of OLM as an adjuvant therapy to the conventional antidiabetic therapies. Image 1 [ABSTRACT FROM AUTHOR]

Retinoids are essential during early cardiovascular morphogenesis. However, recent studies showed their important role in cardiac remodeling in rats with hypertension and following myocardial infarction. The present study aimed to investigate the effect of zeaxanthin heneicosylate (ZH); a carotenoid ester isolated from Dunaliella salina microalgae, on cardiac dysfunction ensuing d-galactose injection in rats. Rats injected with d-GAL (200 mg/kg; I.P) for 8 weeks were orally treated with ZH (250 μg/kg) for 28 consecutive days. Results showed that d-GAL injection caused dramatic electrocardiographic changes as well as marked elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase. A reduction in the cardiac contents of glucose transporter-4 and superoxide dismutase along with the elevation of inducible nitric oxide synthetase and interleukin-6 was also noticed. Oral administration of ZH significantly improved the above mentioned cardiac aging manifestations; this was further emphasized through histopathological examinations. The effect of ZH is mediated through the interaction with retinoid receptor alpha (RAR-α) as evidenced through a significant elevation of RAR-α expression in cardiac tissue following the lead of an in silico molecular docking study. In conclusion, zeaxanthin heneicosylate isolated from D. salina ameliorated age-associated cardiac dysfunction in rats through the activation of retinoid receptors. [ABSTRACT FROM AUTHOR]

1,4-Dihydropyridine (DHP) is an important class of calcium antagonist. It inhibits the influx of extracellular Ca(2+) through L-type voltage-dependent calcium channels. Two series of nifedipine analogues were synthesized and evaluated as calcium antagonists. The ortho-nitrophenyl ring of nifedipine was replaced with an ortho- or a meta-chlorophenyl substituent. The IC50 values revealed that some of the compounds are similar to or more active than nifedipine. Substitution with groups of suitable bulkiness, such as ethyl ester, at the 3- and 5-positions of the DHP ring gave 3h, which is approximately three-fold more active than nifedipine as a calcium antagonist. A docking study with the DHP receptor model was performed to interpret the differences in calcium antagonist activities. The molecular docking study demonstrated that the lipophilicity of the substituted phenyl group at the 4-position of the DHP ring is an important factor that could increase the activity of the calcium antagonist taking the steric factor into consideration. Bulky groups interfere with ring-to-ring hydrophobic interaction with Tyr(1460) and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5-positions of the DHP ring as an approach to increase activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring may ensure strong binding to the receptor and hence stabilization of the closed-channel conformation.

The benzofuran-morpholinomethyl-pyrazoline hybrids 4a-e, 5a-e and 6a-j were synthesized via reaction of α,β-unsaturated carbonyl compounds 3a-e with hydrazine hydrate, semicarbazide or thiosemicarbazide. Applying the Mannich reaction to 5-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-methoxybenzofuran-6-ols 7a-e with morpholine hydrochloride and paraformaldehyde afforded positional isomeric 7-morpholinomethyl derivatives 4a-e and N-morpholinomethyl derivatives 8a-e. All the synthesized compounds showed significant vasodilatation properties in isolated thoracic aortic rings of rats precontracted using the standard norepinephrine hydrochloride technique. Compounds 3d, 3e, 5a-c, 6b, 6c, 6f, 6h and 6i exhibited activity (IC50 0.3185-0.4577 mM) superior to that of prazocin (IC50 0.487 mM), while 5d, 6j and 8c showed comparable activity (IC50 0.4789-0.4951 mM). The quantitative structure-activity relationship study revealed a correlation between the observed vasorelaxant activities of the newly synthesized compounds and their different physicochemical parameters, especially solubility, in addition to structure connectivity and energetic quantities calculated from stored three dimensional (3D) conformations. Absorption, distribution, metabolism and elimination (ADME) evaluation showed good agreement with the biological results obtained.