Alpha-pine self-emulsifying nano formulation attenuates rotenone and trichloroethylene-induced dopaminergic loss.

AIM: The current investigation's goals are to pharmacologically evaluate the neurotherapeutic role of the bioactive compound Alpha Pinene (ALP)-loaded Self-emulsifying nano-formulation (SENF) in neurotoxin (Rotenone and the Industrial Solvent Trichloroethylene)- induced dopaminergic loss. It is believed that these models simulate important aspects of the molecular pathogenesis of Parkinson's disease. MATERIAL AND METHODS: The ALP-nano-formulation's anti-Parkinson's activity was compared to ALP suspension in Wistar rats after rotenone and trichloro ethylene-induced dopaminergic loss. Neurobehavioral and motor performances were measured on the 14th, 21st, and 28th day in the rotenone model. However, in the trichloroethylene model, it was measured from the 4th to the 8th week. RESULTS: Significant neurobehavioral improvement has been found in ALP-SENF treated animals then untreated and animals treated with plain ALP suspension. Furthermore, biochemical tests reveal marked expression of catalase, glutathione, and superoxide dismutase, which significantly combat the (Oxidative stress) OS-induced neurodegeneration. CONCLUSION: The antioxidant effect of ALP-SENF likely includes free radicals neutralization and the activation of enzymes associated with antioxidant activity, leading to the enhancement of neurobehavioral abnormalities caused by rotenone and trichloroethylene.

Neuroprotective effect of α-pinene self-emulsifying nanoformulation against 6-OHDA induced neurotoxicity on human SH-SY5Y cells and its in vivo validation for anti-Parkinson's effect.

Oxidative stress (OS) is involved in the multifaceted pathogenic paradigm of neurodegenerative diseases like Parkinson's disease (PD). Monoterpenes like α-pinene (ALP) is considered to be a therapeutically potent antioxidant agent able to attenuate and scavenge various reactive oxygen species and reactive nitrogen species. The present study aimed to evaluate the in vitro and in vivo neuroprotective effect of α-pinene self-emulsifying nanoformulation (ALP-SENF) for PD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was done to evaluate the neurotoxic dose of the ALP-SENF; however, the neuroprotective effect was assessed by 6-hydroxydopamine (6-OHDA) induced neurotoxicity model on SH-SY5Y taking NAC (N-acetyl-l-cysteine) as standard. The in vivo anti-Parkinson's activity of the ALP-SENF was compared with that of the plain ALP suspension by using reserpine antagonism and haloperidol-induced Parkinsonism model in rats. Various behavioral tests and biochemical antioxidant enzymes were estimated. The in vitro results revealed that treatment with ALP-SENF at a concentration of 100 and 200 µM was found to show significant neuronal SH-SY5Y cell viability against 50 µM 6-OHDA. ALP-SENF treated animals have seen significant neurobehavioral improvement. Furthermore, the levels of antioxidative enzymes in biochemical test reveals a marked enhancement in the expression of antioxidant enzymes that significantly attenuated the OS induced neurodegeneration. Due to the mechanisms of their antioxidant action, it was probably due to the scavenging of free radicals and the expression of antioxidant enzymes. It also improved neurobehavioral changes induced by reserpine and haloperidol.

Evaluating Motor Dysfunction and Oxidative Stress Induced by Trichloroethylene in Wistar Rats.

Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene (TCE) contributes to the development of Parkinson's disease (PD). TCE induced LRRK2 kinase activity in the rat brain and produced a significant dopaminergic lesion in the nigrostriatal tract with elevated oxidative stress. Here we have utilized TCE-induced PD model for the assessment of test drug. Oral gavage administration of TCE at a dose of 1000 mg/kg/day for 6 weeks was utilized to induced PD. Muscle grip strength was estimated by rotarod and grid performance test. Motor activity by actophotometer and locomotor stability were assessed by forelimb locomotor scale (FLS) and forelimb step alternation test (FSAT). However, the postural stability was assessed by postural stability test (PST). Biochemical estimation consists of determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), GSH level (reduced glutathione), and nitrite concentration.

Role of Apoptotic-targeted Phytoconstitutent-loaded Antipsoriatic Nanobiocomposites.

Psoriasis is an inflammatory and proliferative autoimmune dermatological disorder. It is a skin ailment that is defined by particular, drab-red or peach-pink stiff areas with silvery scales patches. Other typical characteristics include the proliferation of epidermal layer, aberrant keratinization, hyperkeratosis, increased micro capillary vascularization, and infiltration of inflammatory mediator loaded cells. Conventional pharmacotherapies currently available can only provide minor advantages. Nanomedicines based on nanotechnology can potentially improve the efficacy and safety of psoriasis medications. Apoptosis plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest, in particular, regarding psoriasis. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. We reviewed the available studies on the efficacy of antiapoptotic therapies in psoriasis. We'll look at phytochemicals in this review, which are natural components found in plants with antiapoptotic activity that are frequently used to treat psoriasis. For improved topical treatment, we also take into consideration the advantages of loading phytoconstituents as medicines into lipid based nanocarriers. The utilization of herbal nanomedicines in psoriasis, as well as nano delivery carrier system for phytoconstituents with improved therapeutic profiles and decreased toxicity, are the subjects of this review. The study's purpose is to find more effective herbal nanomedicines for treating psoriasis. In the treatment of psoriasis, phytoconstituents that have shown antipsoriatic potential in recent years, as well as phytoconstituents loaded based nanomedicines, have a lot of promising roles to be explored. Furthermore, very few patents have been found in the field of nanotechnology utilizing lipid-based nanocarrier system for the treatment of psoriasis. Therefore, this review greatly compels the researcher to validate the process development of lipid-based drug delivery system for the patentability of the product. This should be in a view of shifting in the applicability of the drug delivery system for general public health as a potential treatment option in psoriasis.

Unveiling the Molecular Mechanism of Diosmetin and its Impact on Multifaceted Cellular Signaling Pathways.

BACKGROUND: Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities. OBJECTIVE: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases. METHODS: A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023. RESULTS: The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis. CONCLUSION: The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Neuroprotective validation of pectin in T2DM-induced allodynia and hyperalgesia in diabetic peripheral neuropathic pain.

AIM: To validate neuroprotective effect of pectin against neuropathic pain in diabetic rodents. MATERIAL AND METHOD: Pectin was isolated and characterised from different sources to validate its neuroprotective effect against T2DM associated neuropathic pain. The antioxidant activity of pectins was done by the DPPH method. Type-2 diabetes mellitus (T2DM) was induced in Wistar albino rats by high-fat diet and high-fat emulsion feeding for 2 weeks followed by a single i.p. of Sterptozotocin in 3rd week. The animals were grouped as positive control and Citrus sinensis (L.) Osbeck peel pectin (CSL-OP) as test group and treated for the next 4 weeks. Body weight and blood glucose were measured up to 8 weeks; however, behavioural assessment was done at the end of 5th to 8th week. RESULT: CSL-OP restored the reduced body weight and elevated blood glucose with increased pain threshold and improved walking performance. CONCLUSION: CSL-OP prevented progression of early diabetic neuropathy with anti-oxidant activity.

Insight to Combat Post COVID-19 Mortality: Complications and their Biomarkers.

BACKGROUND: COVID-19 is a severe acute respiratory syndrome that has become a prominent source of morbidity and mortality around the world. With millions infected globally by the COVID-19 epidemic, long-term care for COVID-19 survivors has become a global concern. As a result, research into the long-term pulmonary and extrapulmonary consequences and complications of COVID is absolutely necessary. OBJECTIVES: In an attempt to better understand and mitigate post recovery mortality, early detection of the post recovery complication might prevent the severity of the complication and can be recovered. As per cases reported, post covid extrapulmonary complications were more than pulmonary complications. However, the post covid pulmonary complications were found to be more lethal and nonrecoverable in most of the cases than extrapulmonary complications. METHODS: The present review is an attempt to reveal the role and importance of biomarkers associated with critical post covid pulmonary complications. COVID-19 is associated with post-covid pulmonary fibrosis, pulmonary endothelial dysfunction, pulmonary aspergillosis, pulmonary mucormycosis, biomarkers and WHO, as keywords were used to retrieve updated information. PubMed, and Google Scholar were used as search engines for this. RESULTS: There must be a better knowledge of the post-COVID-19 pulmonary problems in terms of systemic pathophysiological results to create multidisciplinary clinics to address both long-term symptoms and potential long-term consequences. This can be achieved by revealing the molecular pathogenesis that can be validated by certain biomarkers and various diagnostic techniques. Accordingly, the clinical program can be designed to treat and effectively manage the post covid pulmonary complications in early-stage to prevent mortality. CONCLUSION: In order to deal with the specific logistical problems given by pandemic circumstances, effective interdisciplinary collaboration models draw on experiences learned during the early phases of the pandemic.

Exploration of Antibiofilm and In Vivo Wound Healing Activity of p-Cymene-Loaded Gellan/PVA Nanofibers.

Wound dressings with outstanding biocompatibility, antimicrobial, and tissue regeneration activities are essential to manage emerging recalcitrant antifungal infections to speed up healing. In this study, we have engineered p-cymene-loaded gellan/PVA nanofibers using electrospinning. Morphological and physicochemical properties of the nanofibers were characterized using a multitude of techniques to validate the successful integration of p-cymene (p-cym). The fabricated nanomaterials exhibited strong antibiofilm activity against Candida albicans and Candida glabrata compared to pure p-cymene. In vitro biocompatibility assay demonstrated that nanofibers did not possess any cytotoxicity to the NIH3T3 cell lines. In vivo, full-thickness excision wound healing study showed that the nanofibers were able to heal skin lesions faster than the conventional clotrimazole gel in 24 days without forming any scar. These findings unraveled p-cymene-loaded gellan gum (GA)/poly(vinyl alcohol) (PVA) nanofibers as an effective biomaterial for cutaneous tissue regeneration.

Formulation and Evaluation of Isradipine Nanosuspension and Exploring its Role as a Potential Anticancer Drug by Computational Approach.

BACKGROUND: T-type calcium channels are aberrantly expressed in different human cancers and regulate cell cycle progression, proliferation, migration, and survival. FAK-1 can promote tumor protein degradation (p53) through ubiquitination, leading to cancer cell growth and proliferation. Similar findings are obtained regarding protease inhibitors' effect on cytokine-induced neutrophil activation that suppresses Granulocyte-macrophage colony-stimulatingfactor (GM-CSF) TNF-α-induced O2 release and adherence in human neutrophils without affecting phosphorylation of Extracellular signal-regulated kinase (ERK) and p38. Nanosuspensions are carrier-free, submicron colloidal dispersions, which consist of pure drugs and stabilizers. Incorporating drug loaded in nanosuspensions offer a great advantages of passive drug targeting with improved solubility, stability, and bioavailability, as well as lower systemic toxicity. OBJECTIVE: The present investigation objective was to establish a molecular association of Protease and Focal Adhesion Kinase 1 as cancer targets for isradipine, a calcium channel blocker (CCB). Furthermore, the study also aimed to formulate its optimized nanosuspension and how the physical, morphological, and dissolution properties of isradipine impact nanosuspension stability. METHODS: Five different molecular targets, namely Cysteine Proteases (Cathepsin B), Serine Proteases (Matriptase), Aspartate Proteases, Matrix Metalloproteases (MMP), and FAK-1 were obtained from RCSB-PDB, which has some potential associations with inhibition in cancer pathogenesis. Molecular interactions of these targets with CCB isradipine were identified and established by molecular simulation docking studies. Isradipine-loaded nanosuspension was prepared by precipitation technique by employing a 23 factorial design. PVP K-30, poloxamer 188, and sodium lauryl sulfate (SLS) were used as polymer, co-polymer, and surfactant, respectively. The nanosuspension particles were assessed for particle size, zeta potential, viscosity, polydispersity index (PDI), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), In-vitro drug release kinetics, and short-term stability study. RESULTS: Considerable interactions were found with Cysteine, Serine, Aspartate, Threonine, and Matrix metalloproteases with binding energies of -3.91, -6.7, -3.48, -8.42, respectively. Furthermore, the interaction of isradipine with FAK-1 was compared with 7 native ligands and was found to show significant interaction with binding energies of - 8.62, -7.27, -7.69, -5.67, -5.41, -7.44, -8.21, respectively. The optimized nanosuspension was evaluated and exhibited a particle size of 754.9 nm, zeta potential of 32.5 mV, viscosity of 1.287 cp, and PDI of 1.000. The In-vitro dissolution of the optimized formulation (F8) was found to be higher (96.57%) as compared to other formulations. CONCLUSION: Isradipine could act as a potential inhibitor of different proteases and FAK-1 associated with tumor growth initiation, progression, and metastasis. Furthermore, isradipine-loaded nanosuspension with optimized release could be utilized to deliver the anticancer drug in a more targeted way as emerging cancer nanotechnology.

Formulation and Evaluation of α-Pinene Loaded Self-emulsifying Nanoformulation for In-Vivo Anti-Parkinson's Activity.

AIM: The present study was aimed to developed and optimize the self-nano emulsifying drug delivery system of α-pinene (ALP-SNEDDS) and evaluate its in-vivo anti-Parkinson's activity. BACKGROUND: Different lipid-based drug delivery technologies have been researched to upgrade drug bioavailability and expand their clinical adequacy upon oral administration. Self-emulsifying drug delivery systems (SEDDS) have pulled in developing the interest specifically for self nano emulsifying drug delivery systems (SNEDDS). OBJECTIVE: The present work was attempted to improve the bioavailability of the ALP by defining the role of self-nano emulsifying formulations for its neuroprotective effect. METHODS: Miscibility of the ALP was estimated in various excipient components to select the optimized combination. Self-nano emulsification, thermodynamic stability, the effect of dilution on robustness, optical clarity, viscosity, and conductivity tests were performed. The in-vivo anti-Parkinson's activity of the ALP-SNEDDS formulations were done using Pilocarpine antagonism induced Parkinsonism in rodents. Behavioral tests like tremulous jaw movements, body temperature, salivation, and lacrimation are performed. RESULTS: Two optimized formulations, composed of Anise oil, Tween 80, and Transcutol-HP of Oil: Smix ratio (4:6 and 3:7) were selected. The Smix ratio for both the formulation was 2:1. The particle size was found to consistent with the increase in dilution. The mean negative zeta potential of the formulations was found to be increased with an increase in dilution. The TEM images of the formulations revealed spherical shape of the droplet. The in-vitro drug release profile was found to be significant as compared to plain ALP suspension. CONCLUSION: The results of in-vivo studies indicate that nanosizing and enhanced solubilization of oral ALP-SNEDDS formulations significantly improved the behavioral activities compared to plain ALP suspension.

GLP-1 Targeted Novel 3-phenyl-7-hydroxy Substituted Coumarins Mitigate STZ-induced Pancreatic Damage and Improve Glucose Homeostasis in OGTT Method.

BACKGROUND: Worldwide, type 2 diabetes mellitus accounts for a considerable burden of disease, with an estimated global cost of >800 billion USD annually. For this reason, the search for more effective and efficient therapeutic anti-diabetic agents is continuing. Recent studies support the search for coumarins or related compounds with potential blood glucose-lowering properties. AIM: The study aims to design, synthesize and evaluate the hypoglycemic activity of a new class of 7-hydroxy coumarin derivatives. OBJECTIVE: To explore and establish the in-silico-driven pharmacological role of a new class of 7- hydroxy coumarin derivatives as the therapeutic strategies against type 2 diabetes mellitus. METHODS: A new class of 7-hydroxy coumarin derivatives was designed by assessment of their physicochemical properties and molecular docking against the Glucagon-like peptide-1 (GLP-1) receptor. Two novel series of 30 compounds were synthesized. The chemical structures of all the synthesized analogues have been elucidated by spectral studies of IR, 1H-NMR, and mass spectroscopy. After considering the molecular docking score and their physicochemical properties, the compounds were screened out for the evaluation of their hypoglycemic potential. The compounds were investigated for their hypoglycemic activity using a streptozotocin (STZ) induced diabetic model and an oral glucose tolerance test (OGTT) method at different dose levels. RESULTS: The molecular docking studies of synthesized derivatives reveal significant molecular interaction with the various amino acid residues of the GLP-1 receptor. IR spectral analysis revealed a strong band of -NH stretching in the range of 3406.7-3201.61 cm-1 and one strong band for the lactone carbonyl group of the coumarin ring in the range of 1722.0-1703.5 cm-1, confirming the chemical structure of all produced compounds. The synthesized coumarin analogues with the best docking score exhibited remarkable hypoglycemic potential as assessed by the STZ model and the OGTT method. CONCLUSION: Coumarin derivatives explored a good structure-activity relationship (SAR) and produced significant hypoglycemic potential.

Ameliorative Effect of Acetyl L-carnitine in Alzheimer's Disease via Downregulating of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive Deficit in Mouse Model.

AIMS: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model. BACKGROUND: Alzheimer's disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD. OBJECTIVE: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer's disease (AD) in the mouse model. MATERIALS AND METHODS: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+ SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α. RESULTS: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice. CONCLUSION: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC's potential to be used as a supplementation in the pharmacotherapy of AD.

Bioactive Loaded Lipid-based Nanostructures: A Novel Insight for Age-related Neurodegeneration.

Substantial affirmation suggested that oxidative stress remains an impelling target, contributing to initiate and exacerbate the multiple neurological complications in age-related neurodegeneration (ARN). Factors including gene and environmental toxins are now becoming the most threatening cause of oxidative stress, which leads to mitochondrial dysfunction of the neurons that ultimately causes permanent loss of their functionality. Clinical trials on antioxidants are still in the pipeline to access them as a potential therapeutic class. But this raised the generosity for not only to investigate the module of the antioxidant mechanism but also to justify the drug delivery and dose regimen. Biological barriers, predominantly, Blood-brain barrier (BBB) and rapid firstpass metabolism, are some of the potential obstacles for the effective targeting of the therapeutic agent. Bioactive drugs with antioxidant capacity, loaded with lipid-based Nano career system have revealed to be a novel therapeutic intervention for ARN. The review will deal with the comprehensive state-of-art methodology for the delivery of bioactive loaded lipid Nanocarriers to treat neurodegeneration. A systematic analysis of published reports will help the researchers to understand the role of natural compound loaded Nanoengineered system in the field of ARN as a potential Nano therapeutic intervention.

Antimicrobial, anti-inflammatory and wound healing activity of polyherbal formulation.

According to Ayurveda, individual herbs are insufficient to achieve a desired therapeutic effect. When it is optimized as multiple herbs composition in a particular ratio it will give a therapeutic effect in a better way with reduced toxicity. In order to develop such an intervention, the present study was intended to develop a polyherbal drug from methanolic extracts of Plumbago zeylanica Linn, Datura stramonium Linn and Argemone mexicana Linn. The study also aimed to evaluate the impact of polyherbalism on antimicrobial and antioxidant effect, thereafter the ratio of individual plant extracts was optimized accordingly to treat the wound. The poyherbal drug was put on preclinical trial to access the anti-inflammatory and wound healing activity as 2% and 5% polyherbal carbopol-940 gels. The antimicrobial activity was assessed by agar well diffusion and broth dilution method while wound healing activity was evaluated by excision and incision wound models. Topical anti-inflammatory activity was assessed by carrageenan induced paw oedema. The findings of the study revealed the synergistic antimicrobial potential of Polyherbal drug against gram-positive and negative strains. Polyherbal carbopol- 940 gels (2% and 5%w/w) promoted the wound healing and anti-inflammatory effect. The high rate of wound contraction (<0.0001), early epithelialization period (<0.0001) and increased wound breaking strength (<0.0001) were observed in 2% and 5% polyherbal gel treated group when compared to the normal control and negative control group. The antimicrobial and anti-inflammatory effect of Polyherbal drug provoked and promoted the wound healing process through accelerated remodelling of damaged tissue.

Hydroxyproline: A Potential Biochemical Marker and Its Role in the Pathogenesis of Different Diseases.

Hydroxyproline is a non-essential amino acid found in collagen and few other extracellular animal proteins. It's two isomeric forms trans-4-hydroxy-L-proline and trans-3-hydroxy-L-proline play a crucial role in collagen synthesis and thermodynamic stability of the triple-helical conformation of collagen and associated tissues. Various abnormalities in hydroxyproline metabolism have been shown to play key roles in the pathophysiology and pathogenesis of different diseases. The elevated level of hydroxyproline is observed in several disorders, e.g., graft versus host disease, keloids, and vitiligo while its decreased level is a marker of poor wound-healing. This review explores the potential of using hydroxyproline as a biochemical marker to understand the pathogenesis, molecular pathophysiology and treatment of these diseases. The review concludes with an outlook on the scope and challenges in the clinical implementation of hydroxyproline as a biomarker.

Evaluation of antitussive and anti-asthmatic activity of Tabernaemontana divaricata(L.) R. Br. Ex Roem. and Schult.

BACKGROUND: The study was aimed to investigate the antitussive and anti-asthmatic activities of ethanolic extract of Tabernaemontana divaricata (TDEE) leaves by in vivo and in vitro models. Recently, indole alkaloids (monoterpenoid indole alkaloids) have been approved as investigational new drug for clinical trial in respiratory diseases, and T. divaricata has already proven its potential for the presence of indole alkaloids. MATERIALS AND METHODS: Acute toxicity studies of TDEE were performed in accordance with the Organization for Economic Cooperation and Development guidelines no. 425. The sensitized guinea pigs were screened out and divided into control, standard, and TDEE-treated groups. Anti-asthmatic activity of TDEE was assessed by in vitro guinea pig tracheal chain method and in vivo bronchoprotective test method using aminophylline as a standard drug. Taken codeine as standard, antitussive activity was evaluated by in vivo citric acid-induced tussive response. RESULTS: TDEE was found to be safe up to 2000 mg/kg, body weight. TDEE exhibits maximum bronchi relaxation of 91.66% and 92.83% against acetylcholine and histamine-induced contraction, respectively. TDEE exhibited maximum and significant (P < 0.001) bronchoprotection of 42.28% at the dose level of 200 mg/kg, body weight. TDEE at aerosolic dose of 6% (w/v) exhibited decreased average cough frequency (4.83 ± 0.30) which is quite significant (P < 0.001) and effective as compared to standard drug codeine. Based on the histopathological evidences, TDEE-treated groups showed reduced inflammatory cell infiltration and had restored epithelial damage. CONCLUSION: The results of the study revealed the potent antitussive and anti-asthmatic activities of T. divaricata, which support its further implication for the treatment of cough-associated complications such as cough variant asthma.

Evaluation of potent phytomedicine for treatment of psoriasis using UV radiation induced psoriasis in rats.

The aim of present study was to determine the effect of newly formulated gels and suspensions of extractive Phytoconstituents of Woodfordia fructicosa flowers and Gardenia gummifera leaves by using UV Radiation induced psoriasis in rats. Both plants are traditionally claimed to be useful in treatment of number of skin diseases. However, there are no established scientific reports for their potential in psoriasis. Formulated Gels and Suspensions of ethanolic extract of both plants were tested for acute dermal and oral toxicity study respectively. The results of acute dermal toxicity at concentration 1% w/w and oral toxicity at dose 1000mg/kg showed that the gels and suspensions were safe. Psoriasis was induced in Wistar rats by espousing 10% area of total body by UV radiations. Anti-psoriatic activity was performed by applying 0.1% gel and orally at a dose 100mg/kg body weight in rats. Severity Index, histological study and biochemical estimation were analyzed. The results of our studies showed that the test formulations (Gels and Suspensions) of both plant extracts exhibited potential effect in anti-psoriatic activity.

Pharmacological Investigation of the Wound Healing Activity of Cestrum nocturnum (L.) Ointment in Wistar Albino Rats.

Objectives. The present study was aimed at investigating the wound healing effect of ethanolic extract of Cestrum nocturnum (L.) leaves (EECN) using excision and incision wound model. Methods. Wistar albino rats were divided into five groups each consisting of six animals; group I (left untreated) considered as control, group II (ointment base treated) considered as negative control, group III treated with 5% (w/w) povidone iodine ointment (Intadine USP), which served as standard, group IV treated with EECN 2% (w/w) ointment, and group V treated with EECN 5% (w/w) ointment were considered as test groups. All the treatments were given once daily. The wound healing effect was assessed by percentage wound contraction, epithelialization period, and histoarchitecture studies in excision wound model while breaking strength and hydroxyproline content in the incision wound model. Result. Different concentration of EECN (2% and 5% w/w) ointment promoted the wound healing activity significantly in both the models studied. The high rate of wound contraction (P < 0.001), decrease in the period for epithelialization (P < 0.01), high skin breaking strength (P < 0.001), and elevated hydroxyproline content were observed in animal treated with EECN ointments when compared to the control and negative control group of animals. Histopathological studies of the EECN ointments treated groups also revealed the effectiveness in improved wound healing. Conclusions. Ethanolic extract of Cestrum nocturnum (EECN) leaves possesses a concentration dependent wound healing effect.