In Silico Modeling and Structural Analysis of Soluble Epoxide Hydrolase Inhibitors for Enhanced Therapeutic Design.

Human soluble epoxide hydrolase (sEH), a dual-functioning homodimeric enzyme with hydrolase and phosphatase activities, is known for its pivotal role in the hydrolysis of epoxyeicosatrienoic acids. Inhibitors targeting sEH have shown promising potential in the treatment of various life-threatening diseases. In this study, we employed a range of in silico modeling approaches to investigate a diverse dataset of structurally distinct sEH inhibitors. Our primary aim was to develop predictive and validated models while gaining insights into the structural requirements necessary for achieving higher inhibitory potential. To accomplish this, we initially calculated molecular descriptors using nine different descriptor-calculating tools, coupled with stochastic and non-stochastic feature selection strategies, to identify the most statistically significant linear 2D-QSAR model. The resulting model highlighted the critical roles played by topological characteristics, 2D pharmacophore features, and specific physicochemical properties in enhancing inhibitory potential. In addition to conventional 2D-QSAR modeling, we implemented the Transformer-CNN methodology to develop QSAR models, enabling us to obtain structural interpretations based on the Layer-wise Relevance Propagation (LRP) algorithm. Moreover, a comprehensive 3D-QSAR analysis provided additional insights into the structural requirements of these compounds as potent sEH inhibitors. To validate the findings from the QSAR modeling studies, we performed molecular dynamics (MD) simulations using selected compounds from the dataset. The simulation results offered crucial insights into receptor-ligand interactions, supporting the predictions obtained from the QSAR models. Collectively, our work serves as an essential guideline for the rational design of novel sEH inhibitors with enhanced therapeutic potential. Importantly, all the in silico studies were performed using open-access tools to ensure reproducibility and accessibility.

Oxidative Stress and Male Infertility: Role of Herbal Drugs.

Infertility is a universal health problem affecting 15% of couples, out of which 20-30% cases are due to male infertility. The leading causes of male infertility include hormonal defects, physical reasons, sexual problems, hazardous environment, stressful lifestyle, genetic factors, epigenetic factors, and oxidative stress. Various physiological functions involve reactive oxygen species (ROS) and nitrogen species at appropriate levels for proper smooth functioning. ROS control critical reproductive processes such as capacitation, acrosomal reaction, hyperactivation, egg penetration, and sperm head decondensation. The excessive free radicals or imbalance between ROS and endogenous antioxidant enzymes damages sperm membrane by inducing lipid peroxidation causing mitochondrial dysfunction and DNA damage that eventually lead to male infertility. Numerous synthetic products are available in the market to treat infertility problems, largely ending in side effects and repressing symptoms. Ayurveda contains a particular group of Rasayana herbs, called vajikarana, that deals with nourishment and stimulation of sexual tissues, improves male reproductive vitality, and deals with oxidative stress via antioxidant mechanism. The present study aims to describe oxidative stress and the role of herbal drugs in treating male infertility.

Heat Shock Factors in Protein Quality Control and Spermatogenesis.

Proper regulation of cellular protein quality control is crucial for cellular health. It appears that the protein quality control machinery is subjected to distinct regulation in different cellular contexts such as in somatic cells and in germ cells. Heat shock factors (HSFs) play critical role in the control of quality of cellular proteins through controlling expression of many genes encoding different proteins including those for inducible protein chaperones. Mammalian cells exert distinct mechanism of cellular functions through maintenance of tissue-specific HSFs. Here, we have discussed different HSFs and their functions including those during spermatogenesis. We have also discussed the different heat shock proteins induced by the HSFs and their activities in those contexts. We have also identified several small molecule activators and inhibitors of HSFs from different sources reported so far.

Attenuation of nociceptive pain and inflammatory disorders by total steroid and terpenoid fraction of Euphorbia tirucalli Linn root in experimental in vitro and in vivo model.

The plant Euphorbia tirucalli Linn has been successfully used as a tribal folk medicine in India and Africa for the management of acute inflammatory, arthritic, nociceptive pain and asthmatic symptoms. The present study was conducted to assess the anti-inflammatory, analgesic, anti-asthmatic and anti-arthritic role of the total steroid and terpenoid rich fractions of the hydro-alcoholic extract of E. tirucalli root (STF-HAETR). STF-HAETR fraction demonstrated 71.25 ± 2.5 and 74.25 ± 5.1% protection against acetic acid-induced pain and central neuropathic pain at 75 and 100 mg/kg doses, respectively. It showed 96.97% protection against acute inflammation at 100 mg/kg with 1.6-fold better activity than the standard drug. The fraction exhibited such efficacy via inhibition of proinflammatory cytokines TNF-α, IFN-γ, by 61.12 and 65.18%, respectively, at 100 µg/mL. Inhibition of cyclooxygenase and Nitric oxide synthase in a dose-dependent manner affirms its analgesic and anti-inflammatory activity. The spectrophotometric analysis reveals that STF-HAETR induces ameliorative effect against heat-induced denaturation of Bovine serum albumin (BSA) and exhibits significant anti-proteinase activity. The plant fraction also demonstrated anti-asthmatic activity by displaying 62.45% protection against histamine induced bronchoconstriction or dyspnoea. Our findings suggest that STF-HAETR could be an effective safe therapeutic agent to treat nociceptive pain, acute inflammation, asthma, and arthritis which may authenticate its traditional use.

Potential of the plant Thespesia populnea in the treatment of ulcerative colitis.

CONTEXT: Thespesia populnea Sol. ex Correa (Malvaceae), an indigenous tree species in India, is of interest to researchers because traditionally its heartwood is used in the treatment of ulcer and colic pain. OBJECTIVE: To validate its folk use in the treatment of ulcerative colitis (UC). MATERIALS AND METHODS: Mice were administered intrarectal DNBS and then treated with different plant extracts (100 and 200 mg/kg), 30 min before and 24 and 48 h after DNBS infusion. Colonic mucosal injury was assessed by macroscopic and histological examination. Furthermore, malondialdehyde (MDA), myeloperoxidase (MPO), protease, and hemoglobin (Hb) contents were measured in tissue and blood samples. RESULTS: Administration of various extracts ameliorated macroscopic and microscopic scores which were altered due to DNBS treatment in mice. Hb concentration in blood was restored significantly by the aqueous extract to 17.20 ± 0.5, which was reduced to 13.80 ± 0.5 after treatment with DNBS. MDA level was increased to 10.82 nm/mg and 10.25 nm/ml in tissue and blood, respectively, due to DNBS treatment which was reduced to 2.69 nm/mg and 3.59 nm/ml in tissue and blood, respectively, by aqueous extract treatment. Similarly, MPO level was increased to 412 U/mg and 404 U/ml in tissue and blood, respectively, which was significantly reduced to 205 U/mg and 219 U/ml in tissue and blood, respectively, by aqueous extract treatment. Aqueous extract significantly reduced protease activity which was markedly increased in DNBS-treated animals. DISCUSSION AND CONCLUSION: Aqueous extract of heartwood of T. populnea is effective in the treatment of UC.

A brief understanding of process optimisation in microwave-assisted extraction of botanical materials: options and opportunities with chemometric tools.

INTRODUCTION: Extraction forms the very basic step in research on natural products for drug discovery. A poorly optimised and planned extraction methodology can jeopardise the entire mission. OBJECTIVE: To provide a vivid picture of different chemometric tools and planning for process optimisation and method development in extraction of botanical material, with emphasis on microwave-assisted extraction (MAE) of botanical material. METHODS: A review of studies involving the application of chemometric tools in combination with MAE of botanical materials was undertaken in order to discover what the significant extraction factors were. Optimising a response by fine-tuning those factors, experimental design or statistical design of experiment (DoE), which is a core area of study in chemometrics, was then used for statistical analysis and interpretations. RESULTS: In this review a brief explanation of the different aspects and methodologies related to MAE of botanical materials that were subjected to experimental design, along with some general chemometric tools and the steps involved in the practice of MAE, are presented. A detailed study on various factors and responses involved in the optimisation is also presented. CONCLUSION: This article will assist in obtaining a better insight into the chemometric strategies of process optimisation and method development, which will in turn improve the decision-making process in selecting influential extraction parameters.

Co-infectious Uveitis With Syphilis and Lyme Disease: A Case Report.

Uveitis is the inflammation of the uveal tract (i.e., iris, ciliary body, and choroid). Uveitis is categorized into the following three types based on the anatomical location of inflammation: anterior, intermediate, and posterior uveitis. Severe cases may lead to panuveitis, where all three layers may become inflamed potentially resulting in permanent vision loss. Uveitis can arise from different underlying disorders, including infectious causes or autoimmune disorders. Syphilis and Lyme disease are uncommon causes of uveitis. Eye involvement can occur at any stage in Lyme disease, characterized by diverse manifestations such as conjunctivitis, episcleritis, keratitis, uveitis, neuroretinitis, and retinal vasculitis. Patients may present with symptoms of blurred vision, eye pain or discomfort, visual floaters, headache, or intolerance to light. Patients can risk vision loss if not diagnosed and treated promptly.

Azadiradione up-regulates the expression of parvalbumin and BDNF via Ube3a.

Azadiradione is a small bioactive limonoid found in the seed of Azadirachta Indica, an Indian medicinal plant commonly known as Neem. Recently, it has been shown to ameliorate the disease pathology in fly and mouse model of Huntington's disease by restoring impaired proteostasis. Here we report that the azadiradione could be involved in modulating the synaptic function through increased expression of Ube3a, a dual function protein having ubiquitin ligase and co-activator functions and associated with Angelman syndrome and autism. Treatment of azadiradione to HT22 hippocampal cell line and in adult mice induced the expression of Ube3a as well as two important synaptic function and plasticity regulating proteins, parvalbumin and brain-derived neurotropic factor (BDNF). Interestingly, another synaptic plasticity modulating protein Arc (activity-regulated cytoskeletal associated protein) was down-regulated by azadiradione. Partial knockdown of Ube3a in HT22 cell abrogated azadiradione induced expression of parvalbumin and BDNF. Ube3a-maternal deficient mice also exhibited significantly decreased expression of parvalbumin and BDNF in their brain and treatment of azadiradione in these animals did not rescue the altered expression of either parvalbumin or BDNF. These results indicate that azadiradione-induced expression of parvalbumin and BDNF in the brain is mediated through Ube3a and suggest that azadiradione could be implicated in restoring synaptic dysfunction in many neuropsychiatric/neurodegenerative disorders.

Finding structural requirements of structurally diverse α-glucosidase and α-amylase inhibitors through validated and predictive 2D-QSAR and 3D-QSAR analyses.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemic state. The α-glucosidase and α-amylase are considered two major targets for the management of Type 2 DM due to their ability of metabolizing carbohydrates into simpler sugars. In the current study, cheminformatics analyses were performed to develop validated and predictive models with a dataset of 187 α-glucosidase and α-amylase dual inhibitors. Separate linear, interpretable and statistically robust 2D-QSAR models were constructed with datasets containing the activities of α-glucosidase and α-amylase inhibitors with an aim to explain the crucial structural and physicochemical attributes responsible for higher activity towards these targets. Consequently, some descriptors of the models pointed out the importance of specific structural moieties responsible for the higher activities for these targets and on the other hand, properties such as ionization potential and mass of the compounds as well as number of hydrogen bond donors in molecules were found to be crucial in determining the binding potentials of the dataset compounds. Statistically significant 3D-QSAR models were developed with both α-glucosidase and α-amylase inhibition datapoints to estimate the importance of 3D electrostatic and steric fields for improved potentials towards these two targets. Molecular docking performed with selected compounds with homology model of α-glucosidase and X-ray crystal structure of α-amylase largely supported the interpretations obtained from the cheminformatic analyses. The current investigation should serve as important guidelines for the design of future α-glucosidase and α-amylase inhibitors. Besides, the current investigation is entirely performed by using non-commercial open-access tools to ensure easy accessibility and reproducibility of the investigation which may help researchers throughout the world to work more on drug design and discovery.

Possible fasciocidal activity of methanol extract of Dregea volubilis leaves.

In eastern and southern part of India Dregea volubilis (Family Asclepediaceae) is widely used as anthelmintic in traditional system of medicine. The present study was conducted to evaluate the fasciocidal activity of the methanol extract of D. volubilis leaves (MEDV) and to observe the drug's effect on organisms through scanning electron microscopic (SEM) study. Live parasites (Trematode: Fasciola gigantica) were collected in 0.9% phosphate-buffered saline from the bile ducts of buffalo. Those were incubated in the said media at 37 ± 1 °C either as control, or with MEDV at 5, 10, 25, 50 and 100 mg/ml as test groups or with albendazole at 10mg/ml as standard group. The efficacy of the extract was determined on the basis of paralysis (temporary loss of spontaneous movement of the organisms) and/or death of the liver flukes. Death was confirmed when the organisms lost their motility permanently and their motility could not be revived even when vigorously shaken or dipped in warm water. MEDV at all concentration effectively paralyzed first and then killed the liver flukes (p < 0.001). Maximum fasciocidal activity was found with concentration of 100 mg/ml at 38.83 ± 3.41 min. Through SEM study, severe damages were observed in both the suckers as well as on the tegumental surfaces of the treated liver flukes. The study confirmed the fasciocidal activity of the MEDV.

Design of experiment approach for the process optimisation of microwave assisted extraction of lupeol from Ficus racemosa leaves using response surface methodology.

INTRODUCTION: Triterpenoids are a group of important phytocomponents from Ficus racemosa (syn. Ficus glomerata Roxb.) that are known to possess diverse pharmacological activities and which have prompted the development of various extraction techniques and strategies for its better utilisation. OBJECTIVE: To develop an effective, rapid and ecofriendly microwave-assisted extraction (MAE) strategy to optimise the extraction of a potent bioactive triterpenoid compound, lupeol, from young leaves of Ficus racemosa using response surface methodology (RSM) for industrial scale-up. MATERIAL AND METHOD: Initially a Plackett-Burman design matrix was applied to identify the most significant extraction variables amongst microwave power, irradiation time, particle size, solvent:sample ratio loading, varying solvent strength and pre-leaching time on lupeol extraction. Among the six variables tested, microwave power, irradiation time and solvent-sample/loading ratio were found to have a significant effect (P < 0.05) on lupeol extraction and were fitted to a Box-Behnken-design-generated quadratic polynomial equation to predict optimal extraction conditions as well as to locate operability regions with maximum yield. RESULTS: The optimal conditions were microwave power of 65.67% of 700 W, extraction time of 4.27 min and solvent-sample ratio loading of 21.33 mL/g. Confirmation trials under the optimal conditions gave an experimental yield (18.52 µg/g of dry leaves) close to the RSM predicted value of 18.71 µg/g. CONCLUSION: Under the optimal conditions the mathematical model was found to be well fitted with the experimental data. The MAE was found to be a more rapid, convenient and appropriate extraction method, with a higher yield and lower solvent consumption when compared with conventional extraction techniques.

Effect of methanol extract of Bombax malabaricum leaves on nitric oxide production during inflammation.

In different parts of India, Bombax malabaricum DC. (Family: Bombacaceae), a lofty deciduous tree with large leaves, is traditionally used in inflammation. The aim of the present study was to confirm its antiinflammatory activity and to search for the possible mechanism of action for methanol extract of Bombax malabaricum leaves (MEBM). The anti-inflammatory activity of MEBM was evaluated in a carrageenan-induced model of acute inflammation. As inflammation usually involves increased nitric oxide (NO) production, effect of MEBM on lipopolysaccharide-induced NO production in mouse peritoneal macrophages was studied to evaluate its possible mechanism of action. It was found that MEBM was non-toxic up to a dose of 2 g/kg for mice and rats, orally. MEBM (100, 200, and 400 mg/kg) significantly reduced carrageenan-induced rat paw edema (p < 0.05, p < 0.01, p < 0.001, respectively). In mice peritoneal macrophages, the IC50 for MEBM was 258.33 +/- 6.96 microg/mL and it was non-toxic up to 125 microg/mL. MEBM (0-100 microg/mL) reduced lipopolysaccharide-induced NO production in macrophages in a dose-dependent fashion (p < 0.001). Hence, MEBM possesses antiinflammatory activity, mediated through inhibition of NO production.

In Silico Mining and Characterization of High-Quality SNP/Indels in Some Agro-Economically Important Species Belonging to the Family Euphorbiaceae.

(1) Background: To assess the genetic makeup among the agro-economically important members of Euphorbiaceae, the present study was conducted to identify and characterize high-quality single-nucleotide polymorphism (SNP) markers and their comparative distribution in exonic and intronic regions from the publicly available expressed sequence tags (ESTs). (2) Methods: Quality sequences obtained after pre-processing by an EG assembler were assembled into contigs using the CAP3 program at 95% identity; the mining of SNP was performed by QualitySNP; GENSCAN (standalone) was used for detecting the distribution of SNPs in the exonic and intronic regions. (3) Results: A total of 25,432 potential SNPs (pSNP) and 14,351 high-quality SNPs (qSNP), including 2276 indels, were detected from 260,479 EST sequences. The ratio of quality SNP to potential SNP ranged from 0.22 to 0.75. A higher frequency of transitions and transversions was observed more in the exonic than the intronic region, while indels were present more in the intronic region. C↔T (transition) was the most dominant nucleotide substitution, while in transversion, A↔T was the dominant nucleotide substitution, and in indel, A/- was dominant. (4) Conclusions: Detected SNP markers may be useful for linkage mapping; marker-assisted breeding; studying genetic diversity; mapping important phenotypic traits, such as adaptation or oil production; or disease resistance by targeting and screening mutations in important genes.

Multi-model in silico characterization of 3-benzamidobenzoic acid derivatives as partial agonists of Farnesoid X receptor in the management of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a pathological condition which is strongly correlated with fat accumulation in the liver that has become a major health hazard globally. So far, limited treatment options are available for the management of NAFLD and partial agonism of Farnesoid X receptor (FXR) has proven to be one of the most promising strategies for treatment of NAFLD. In present work, a range of validated predictive cheminformatics and molecular modeling studies were performed with a series of 3-benzamidobenzoic acid derivatives in order to recognize their structural requirements for possessing higher potency towards FXR. 2D-QSAR models were able to extract the most significant structural attributes determining the higher activity towards the receptor. Ligand-based pharmacophore model was created with a novel and less-explored open access tool named QPhAR to acquire information regarding important 3D-pharmacophoric features that lead to higher agonistic potential towards the FXR. The alignment of the dataset compounds based on pharmacophore mapping led to 3D-QSAR models that pointed out the most crucial steric and electrostatic influence. Molecular dynamics (MD) simulation performed with the most potent and the least potent derivatives of the current dataset helped us to understand how to link the structural interpretations obtained from 2D-QSAR, 3D-QSAR and pharmacophore models with the involvement of specific amino acid residues in the FXR protein. The current study revealed that hydrogen bond interactions with carboxylate group of the ligands play an important role in the ligand receptor binding but higher stabilization of different helices close to the binding site of FXR (e.g., H5, H6 and H8) through aromatic scaffolds of the ligands should lead to higher activity for these ligands. The present work affords important guidelines towards designing novel FXR partial agonists for new therapeutic options in the management of NAFLD. Moreover, we relied mainly on open-access tools to develop the in-silico models in order to ensure their reproducibility as well as utilization.

Bioengineered dual fluorescent carbon nano dots from Indian long pepper leaves for multifaceted environmental and health utilities.

In this article, we present the synthesis of Piper longum leaves-derived ethanolic carbon dots (PLECDs) using the most simplistic environmentally friendly solvothermal carbonization method. The PLECDs fluoresced pink color with maximum emission at 670 nm at 397 nm excitation. Additionally, the dried PLECDs dissolved in water showed green fluorescence with higher emission at 452 nm at 370 nm excitation. The UV spectra showed peaks in the UV region (271.25 nm and 320.79 nm) and a noticeable tail in the visible region, signifying the efficient synthesis of nano-sized carbon particles and the Mie scattering effect. Various functional groups (-OH, -N-H, -C-H, -C = C, -C-N, and -C-O) were identified using Fourier transform infrared spectroscopy (FTIR). Its nanocrystalline property was revealed by the sharp peaks in the X-ray diffraction (XRD). High-resolution transmission electron microscopy (HRTEM) photomicrograph displayed a roughly spherical structure with a mean size of 2.835 nm. The energy dispersive X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) revealed the elemental abundance of C, O, and N. The high-performance thin-layer chromatography (HPTLC) fingerprint of PLECDs showed an altered pattern than its precursor (Piper longum leaves ethanolic extract or PLLEE). The PLECDs sensed Cu2+ selectively with a limit of detection (LOD) and limit of quantification (LOQ) of 0.063 µM and 0.193 µM, respectively. It showed excellent cytotoxicity toward MDA-MB-231 (human breast cancer), SiHa (human cervical carcinoma), and B16F10 (murine melanoma) cell lines with excellent in vitro bioimaging outcomes. It also has free radical scavenging activity. The PLECDs also showed outstanding bacterial biocompatibility, pH-dependent fluorescence stability, photostability, physicochemical stability, and thermal stability.

Modulatory effect of polyphenolic extracts of Ichnocarpus frutescens on oxidative stress in rats with experimentally induced diabetes.

BACKGROUND & OBJECTIVES: The role of oxidative stress in the development of diabetes mellitus and its vascular complications are extensively studied. Hyperglycaemia causes oxidative damage by generation of reactive oxygen species and results in the development of complications. The present study was undertaken with the objective of exploring the anti-hyperglycaemic potential of polyphenolic enriched extract of Ichnocarpus frutescens in streptozotocin induced (n-STZ) neonatal diabetic rats (pups) for six weeks and to study oxidative stress and antioxidant status. METHODS: Two days old pups were rendered diabetic by single injection of streptozotocin (90 mg/kg body wt, ip). At the end of the treatment period, the level of blood glucose, serum biochemical markers, serum lipid levels and liver malondialdehyde, tissue antioxidant levels were measured. RESULTS: A marked rise was observed in the levels of fasting blood glucose (230.33 mg/dl), lipid profiles, lipid peroxidative products and a significant decrease in tissue antioxidants (superoxide dismuatase, catalase and reduced glutathione) and serum high density lipoprotein cholesterol levels in STZ treated rats. Oral administration of polyphenolic extract (150 and 300 mg/kg body wt, po) decreased fasting blood glucose levels (187.66 and 170.50 mg/dl, respectively) of STZ-treated diabetic rats significantly (P<0.01), when compared with control rats. In addition, the polyphenolic extract showed favourable effect (P<0.01) on the reduced tissues antioxidants level, liver glycogen level, high density lipoprotein level, with significant (P<0.01) reduction of elevated lipid peroxidation products. Histopathological study of the pancreas showed the protective role of polyphenolic extract. INTERPRETATION & CONCLUSIONS: Our study showed the antioxidant of effect polyphenolic extract of I. frutescens in STZ induced experimental diabetes. The results also suggested that this polyphenolic rich extract could be potentially useful for hyperglycaemia treatment to correct the diabetic state.

Anthelmintic effect of a methanol extract of Bombax malabaricum leaves on Paramphistomum explanatum.

Bombax malabaricum (family Bombacaceae) is used as anthelmintic in traditional system of medicine in Southern Punjab of Pakistan. The objective of this study was to evaluate the anthelmintic activity of the methanol extract of B. malabaricum leaves (MEBM). Live parasites (trematode: Paramphistomum explanatum) were collected from buffalo in 0.9% phosphate-buffered saline. It was incubated in Petri dishes at 37 ± 1°C in media containing either no extract (control) or MEBM, the test drug at 10, 25, 50, and 100 mg/ml dose level or albendazole, the standard drug at 10 mg/ml. The efficacy of the extract or albendazole was measured on the basis of the loss of spontaneous movement and/or death of the trematodes. Paralysis was considered when there is no movement unless shaken vigorously. Death was confirmed when the trematodes completely lost their motility, even when vigorously shaken or dipped in warm water (50°C), followed by fading away of their body color. The trematodes, both drug treated and others, were further processed for SEM study using the standard method. All trematodes died with all the above-mentioned doses of MEBM within a short period of time (less than 45 min) which was statistically highly significant (p < 0.001). MEBM at 100 mg/ml showed maximum efficacy. It paralyzed and killed trematodes in 18.50 ± 0.62 and 22.17 ± 0.48 min, respectively. SEM study showed that MEBM-treated trematodes were stretched. The study established the anthelmintic activity of MEBM.

Anthelmintic effect of a methanol extract of leaves of Dregea volubilis on Paramphistomum explanatum.

Dregea volubilis (family Asclepediaceae) is widely used as anthelmintic in traditional system of medicine in eastern and southern part of India. The aim of this study was to evaluate the anthelmintic activity of the methanol extract of D. volubilis leaves (MEDV) and to observe its effect through SEM study. Live parasites (trematode Paramphistomum explanatum) were collected from buffalo in 0.9% phosphate-buffered saline (PBS). It was incubated at 37 ± 1°C in media containing either no extract (control), the test drug, MEDV at four dose levels (10, 25, 50, and 100 mg/ml) or the standard drug, albendazole, at a dose of 10 mg/ml. The effectiveness of the extract was judged on the basis of the loss of spontaneous movement and/or complete destruction or death of the trematodes. After being removed from the experimental medium, trematodes were dipped in PBS at 37 ± 1°C and on gentle stimulation, the paralyzed parasite showed immobility. Death was confirmed when it completely lost its motility even when vigorously shaken or dipped in warm water (50°C). The trematodes, both drug treated and others, were further processed for SEM study using standard method. The anthelmintic activity was found with all the doses through paralysis and death of the organisms (p < 0.001). Maximum anthelmintic activity was found with a dose of 100 mg/ml. Minor damage was observed with both suckers, but severe distortion was found with tegumental surface of the treated trematodes. The present SEM-based study established the anthelmintic activity of MEDV.

Analgesic and anti-inflammatory activity of ß-sitosterol isolated from Nyctanthes arbortristis leaves.

Nyctanthes arbortristis Linn. (Oleaceae) is one of the well-known Indian medicinal plant. Various extracts of leaves of the plant were screened for analgesic activity by hot plate test and acetic acid-induced writhings and anti-inflammatory activity by carrageenan-induced hind paw edema method at the dose of 50 mg/kg, i.p. Petroleum ether extract was found to be most active and hence subjected to activity-guided fractionation. Results showed that ß-sitosterol (5, 10 and 20 mg/kg, i.p.) was responsible for the significant and dose-dependent activity comparable with the standard extract. ß-Sitosterol from N. arbortristis leaves might be responsible for analgesic and anti-inflammatory activity.

In vitro and in vivo antitumor activity of a methanol extract of Dregea volubilis leaves with its antioxidant effect.

CONTEXT: In India, Dregea volubilis (L.f.) Benth. ex Hook.f. (Asclepediaceae), a large twining shrub with a woody vine, is used to treat tumors traditionally. OBJECTIVE: This study evaluated the in vitro and in vivo antitumor activity of the methanol extract of Dregea volubilis leaves (MEDV) and elucidated its possible mechanism of action. MATERIALS AND METHODS: In vitro antitumor activity of MEDV was evaluated against Ehrlich ascites carcinoma (EAC) cell-line. In vivo antitumor and antioxidant activity of MEDV at three dose levels (50, 100, and 200 mg/kg) were determined against EAC tumor-bearing mice. After 24 h of EAC inoculation, the extract was administered for 9 consecutive days. After the administration of the last dose on the 9th day followed by 18 h fasting, mice from all groups were sacrificed to determine antitumor activity and hematological profiles along with liver related biochemical parameters like lipid peroxidation, antioxidant enzymatic activity, etc. RESULTS: For in vitro antitumor activity, IC(50) value of MEDV for EAC tumor cells was 85.51 ± 4.07 µg/ml. The MEDV showed a decrease in tumor volume, packed cell volume and viable cell count and an increase in the non-viable cell count of the EAC tumor-bearing mice (p < 0.001). Hematological profile reverted near to normal level in extract treated mice. MEDV decreased the hepatic lipid peroxidation level and enhanced superoxide dismutase and catalase level in tumor-bearing mice (p < 0.001). DISCUSSION AND CONCLUSION: MEDV exhibited in vitro and in vivo antitumor activity in EAC tumor-bearing mice mediated through augmenting antioxidant defense system.