Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats.

CONTEXT: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. OBJECTIVE: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th-32nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done. RESULTS: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 µmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 µg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations. CONCLUSION: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.

Vanillic Acid Ameliorates Cationic Bovine Serum Albumin Induced Immune Complex Glomerulonephritis in BALB/c Mice.

Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016. © 2016 Wiley Periodicals, Inc.

Improved anti-diabetic activity of glibenclamide using oral self nano emulsifying powder.

The objective of the present study was to improve solubility, dissolution rate and therapeutic efficacy of a BCS Class II drug, glibenclamide by using oral self nano emulsifying powder. The powder was prepared by adsorbing the mixture of oil, surfactant and co-surfactant onto a carrier with large surface area; Aerosil 200. The ratios of oil and Smix (surfactant/co-surfactant mixture) required to produce an emulsion was optimized based on percentage transmittance studies and particle size determinations. The optimized formulation was subjected to in vitro dissolution study and in vivo therapeutic efficacy in rabbits by monitoring blood glucose levels. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction studies revealed that the drug was present in amorphous form in the final formulation. The in vivo study in rabbits indicated the improved therapeutic efficacy of glibenclamide in self-nanoemulsifying powder compared to plain drug.

Antioxidant activity and functional properties of enzymatic protein hydrolysates from common carp (Cyprinus carpio) roe (egg).

Previously, we have reported the composition, molecular mass distribution and in vivo immunomodulatory effects of common carp roe protein hydrolysates. In the current study, antioxidative activity and functional properties of common carp (Cyprinus carpio) roe (egg) protein hydrolysates, prepared by pepsin, trypsin and Alcalase, were evaluated. The three hydrolysates showed excellent antioxidant activities in a dose dependent manner in various in vitro models such as 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6)-sulfonic acid (ABTS(+)) radical scavenging activity, ferric reducing antioxidant power (FRAP) and ferrous ion (Fe(2+)) chelating ability. Enzymatic hydrolysis significantly increased protein solubility of the hydrolysates to above 62 % over a wide pH range (2-12). Carp roe hydrolysates exhibited good foaming and emulsification properties. The results suggest that bioactive carp roe protein hydrolysates (CRPHs) with good functional properties could be useful in health food/nutraceutical/pharmaceutical industry for various applications.

Antiproliferative, ACE-inhibitory and functional properties of protein hydrolysates from rohu (Labeo rohita) roe (egg) prepared by gastrointestinal proteases.

Previously, we have reported the chemical composition, molecular mass distribution and antioxidant activity of rohu roe protein hydrolysates. In the current study, antiproliferative, angiotensin-converting enzyme (ACE)-inhibitory activities and functional properties of protein hydrolysates from rohu (Labeo rohita) roe proteins, prepared by gastrointestinal proteases (pepsin and trypsin), were investigated. Antiproliferative activity was evaluated against human colon cancer cell line Caco-2. The results showed that the pepsin hydrolysate possessed dose dependent inhibitory effect on Caco-2 cell line. Pepsin and trypsin hydrolysates displayed ACE-inhibitory activity in vitro. The ACE-inhibitory activity of the hydrolysate generated by pepsin (47 ± 1.7 %, at 1 mg/ml) is higher than that obtained by trypsin (36 ± 3.2 %). Additionally, the undigested rohu roe proteins and its hydrolysates exhibited functional properties. Solubilities of the hydrolysates were above 81 ± 9.2 % at all pH values tested. Pepsin and trypsin hydrolysates showed good foaming capacity (45-211 %) and emulsification activity (4-29 m(2)/g). The foaming abilities and emulsifying activity index (EAI) were affected by pH. The results suggest that protein hydrolysates from rohu roe could be useful in food industry for various applications.

Increased brain uptake of docetaxel and ketoconazole loaded folate-grafted solid lipid nanoparticles.

Docetaxel is used in the treatment of many types of cancer, but its entry into the brain is restricted by p-glycoprotein (p-gp) efflux. A potential drug-drug interaction exists between docetaxel and ketoconazole because both agents are metabolized hepatically by the cytochrome P-450 system, and ketoconazole can inhibit p-gp efflux of docetaxel at blood brain barrier. Hence, these two drugs were loaded in solid lipid nanoparticles (SLNPs) and surface of these NPs were modified with folic acid for brain targeting. These NPs were characterized for particle size, zeta potential, entrapment efficiency, in vitro drug release, cytotoxicity, and cell uptake in brain endothelial cell lines. Plasma and brain pharmacokinetics have shown increased brain uptake of docetaxel with surface-modified dual drug-loaded SLNPs. Brain permeation coefficient (K(in)) of folate-grafted docetaxel and ketoconazole loaded SLNPs was 44 times higher than that of Taxotere. Hence, these NPs were suitable for the delivery of lipophilic anticancer drugs to the brain. FROM THE CLINICAL EDITOR: In this paper, successful delivery of docetaxel and ketoconazole is reported using solid lipid nanoparticles surface modified with folic acid for brain targeting, which may pave the way to optimized clinical applications of lipophilic anticancer drugs to the brain.

ß-Hydroxybutyric acid grafted solid lipid nanoparticles: a novel strategy to improve drug delivery to brain.

Delivery of drugs to brain is an elusive task in the therapy of many serious neurological diseases. With the aim to create a novel formulation to enhance the drug uptake to brain, betreliesoxybutyric acid (HBA) grafted docetaxel loaded solid lipid nanoparticles (HD-SLNs) were explored. Transportation of HD-SLNs relies on the transport of novel ligand, HBA, by monocarboxylic acid transporter (MCT1). Expression of MCT1 transporter on brain endothelial cells (bEnd cells) was studied using immunocytochemistry. Stearylamine-HBA conjugate was used to modify the surface of SLNs and it was confirmed using XPS (X-Ray Photon Spectroscopy) analysis. In vitro release studies revealed the controlled release of drug from HD-SLNs. Cytotoxicity and cell uptake studies revealed the increased uptake of docetaxel with HD-SLNs. Mechanism involved in the uptake of HD-SLNs was studied in bEnd cells by saturating MCT1 with excess HBA. Pharmacokinetic and brain distribution demonstrated increased docetaxel concentrations in brain compared with Taxotere®. FROM THE CLINICAL EDITOR: The authors of this study demonstrate enhanced drug delivery to the brain using a novel formulation of beta-hydroxybutyric acid grafted docetaxel loaded solid lipid nanoparticles. The results show increased uptake of docetaxel compared with Taxotere.

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design.

CONTEXT: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. OBJECTIVE: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. METHODS: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. RESULTS: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. CONCLUSION: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

Correction to: Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.

[This corrects the article DOI: 10.1007/s40200-022-01074-4.].

Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.

Objectives: Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer's disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)-induced rats. Methods: Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (Na+K+-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab. Results: Metformin treatment significantly (p < 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO (p < 0.01 and p < 0.05). The lipid profile was significantly (p < 0.001) controlled with cardiometabolic functions. Conclusions: Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline.

SGLT inhibitors as antidiabetic agents: a comprehensive review.

Diabetes is one of the most common disorders that substantially contributes to an increase in global health burden. As a metabolic disorder, diabetes is associated with various medical conditions and diseases such as obesity, hypertension, cardiovascular diseases, and atherosclerosis. In this review, we cover the scientific studies on sodium/glucose cotransporter (SGLT) inhibitors published during the last decade. Our focus on providing an exhaustive overview of SGLT inhibitors enabled us to present their chemical classification for the first time.

Unexpected in vivo anti-inflammatory activity observed for simple, surface functionalized poly(amidoamine) dendrimers.

We report unexpected anti-inflammatory properties for naked, unmodified poly(amidoamine) (PAMAM) dendrimers bearing simple surface functionality (e.g., -NH(2), -OH, etc.). This property was discovered serendipitously while studying the drug delivery features of PAMAM dendrimer-indomethacin complexes. Activity was quantitated by using three independently recognized in vivo anti-inflammatory assay methods, namely, (1) the carrageenan-induced paw edema model (acute activity), (2) the cotton pellet test, and (3) the adjuvant-induced arthritis assay in rats (chronic activities). Those dendrimers bearing amine or hydroxyl surface groups exhibited significant anti-inflammatory activity in the carrageenan-induced paw edema model. For example, [core: 1,2-diaminoethane]; (G = 4.0); {dendri-poly(amidoamine)-(NH(2))(64)} (i.e., G4-NH(2)) exhibited a mean percent inhibition of 35.50 +/- 1.6% 3 h after administration and [core: 1,2-diaminoethane] (G = 4.0); {dendri-poly(amidoamine)-(OH)(64)} (i.e., G4-OH) gave a mean percent inhibition of 31.22 +/- 1.58% 3 h after administration. On the other hand, [core: 1,2-diaminoethane] (G = 4.5); {dendri-poly(amidoamine)-(CO(2)H)(128)} (i.e., G4.5-CO(2)H) exhibited mild anti-inflammatory activity with a mean percent inhibition of 14.00 +/- 2.5% 3 h after administration. Unexpectedly, G4-NH(2) showed significantly higher activity compared to naked indomethacin (i.e., 50 +/- 3.1% vs 22 +/- 1.2%) using the cotton pellet granuloma model. Similarly, in the adjuvant-induced arthritis model, G4-NH(2) compared to naked indomethacin gave a mean percent inhibition of 30 +/- 1.9% versus 11 +/- 0.9% 14 days after administration.

Bioactivity-guided isolation of cytotoxic constituents from stem-bark of Premna tomentosa.

A bioassay-guided fractionation and chemical investigation of the stem bark of Premna tomentosa resulted in the isolation and characterization of four new icetexane diterpenes (1-4), along with the known compounds coniferaldehyde (5), syringaldehyde (6), lupeol (7), betulin (8), and 2-(4-methoxyphenyl)-2-butanone (9). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. The new compounds exhibited diverse functionalities on a common icetexane diterpene skeleton. In addition, cytotoxic activities of the icetexanes (1-3) were evaluated by determining their inhibitory effects on the human cancer cell lines (MCF-7, HT-29, Hep-G2, A-431, and A-549). Compounds 1 and 3 showed selective inhibitory activity against MCF-7 (15.96microg/mL and 15.84microg/mL) and HT-29 cell lines (16.21microg/mL and 14.57microg/mL), respectively.

First stereoselective total synthesis and anticancer activity of new amide alkaloids of roots of pepper.

The first stereoselective total synthesis of new natural amide alkaloids 1-3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a trans regioselective opening of 2,3-epoxy alcohol, Horner-Wadsworth-Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids 1-3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time.

Effect of Resveratrol on biofilm formation and virulence factor gene expression of Porphyromonas gingivalis in periodontal disease.

Periodontal disease is an oral inflammatory disease that destroys the tooth supporting periodontal tissues resulting in tooth loss. Porphyromonas gingivalis is a keystone pathogen that plays a significant role in periodontitis. In previous studies, resveratrol has shown significant results by targeting inflammatory and adhesive markers. Virulence factors of P. gingivalis play an important role in the bacterial adhesion and colonization. In this study, we aimed to demonstrate the anti-biofilm and anti-bacterial activity of resveratrol and also study the effect of resveratrol on the expression of virulence factor genes of P. gingivalis using reverse transcriptase polymerase chain reaction (RT-PCR). The anti-microbial and anti-biofilm activity of resveratrol on P. gingivalis was carried out by broth microdilution assay and biofilm adhesion reduction-crystal violet assay, respectively. We carried out the gene expression analysis by RT-PCR with the P. gingivalis treated compound to analyze the change in the expression of virulence factors: fimbriae and gingipain. Minimal inhibitory concentrations (MIC) of resveratrol against P. gingivalis and other clinical strains are in the range of 78.12-156.25 µg/mL. Resveratrol dose-dependently prevented the biofilm formation and also attenuated the virulence of P. gingivalis by reducing the expression of virulence factor genes such as fimbriae (type II and IV) and proteinases (kgp and rgpA). Resveratrol demonstrated superior anti-bacterial and anti-biofilm activity against P. gingivalis. There was significant reduction in the expression of fimbriae and gingipain with the resveratrol-treated compound. The results suggest that resveratrol, due to its multiple actions, may become a simple and inexpensive therapeutic strategy for treating periodontal disease.

Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies.

Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs 15a-b, with a potential for selective therapy of solid tumors by PMT and ADEPT have been designed, synthesized and evaluated for selective cytotoxicity in the presence of the enzyme beta-glucuronidase. The prodrugs have been found to possess reduced cytotoxicity compared to the parent moieties, and are excellent substrates for the enzyme, exhibiting cytotoxicity selectively in the presence of the enzyme. Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs.

Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier.

Mucoadhesive nanoparticles (NPs) could be an exciting prospect for trans-nasal insulin delivery as they have higher surface area to cover highly vascularised nasal absorptive area providing a greater concentration gradient; hence the present study makes an attempt in this regard. Starch NPs were prepared by different crosslinkers using various methodologies and were loaded with insulin. Emulsion crosslinked particles were smaller in size compared to gel method (351 vs 997 nm), and size is further reduced when epichlorohydrin is used as crosslinking agent compared to POCl3 (194 vs 810 nm). NPs of epichlorohydrin emulsion were further optimized with variable crosslinking to evaluate the effect of degree of crosslinking on in vivo performance. In vitro, a size dependent first order diffusion controlled insulin release with an initial burst effect was found, which is higher with NPs of small size and least crosslinking. Formulation of EE-NPs with Na glycocholate showed a superior hypoglycemic action compared to other NPs formulations containing the former and lysophosphatidylcholine as permeation enhancers. The hypoglycemic effects were more pronounced with medium crosslinked NPs (EE-L2-NPs), which showed a nadir of 70% reduction of plasma glucose and significant effects until 6h. The peak plasma insulin level (Cmax) of medium crosslinked EE-L2-NPs (258 muIU/ml at 1h) vindicates the pharmacodynamic effect, which was found to be superior compared to all other formulations. The release rate and higher associated surface area might work in tandem, and could be greatly amplified when combined with permeation enhancers to make starch NPs an efficient trans-nasal mucoadhesive carrier of insulin.

Potential in vitro antioxidant and protective effects of Soymida febrifuga on ethanol induced oxidative damage in HepG2 cells.

There is increasing evidence that oxidative stress is implicated in pathogenesis of various diseases, including alcoholic liver injury. In the present study, we investigated the comparative protective effects of leaf, bark, root and root bark extracts of Soymida febrifuga (Roxb.) A. Juss. (Meliaceae) against ethanol induced oxidative damage in HepG2 cells. Comparatively, methanolic and aqueous extracts of bark and leaf significantly attenuated the cytotoxicity of the ethanol, as determined by cytotoxicity, lipid peroxidation, lactate dehydrogenase, alanine aminotransferases and asparatate aminotransferases, than the root and root bark extracts. Ethanol induces liver toxicity through free radical generation so initially in vitro antioxidant activity of the extracts was evaluated. Methanolic and aqueous extracts of bark and leaf have shown higher total phenolic content, reducing power, metal chelating, superoxide, hydroxyl radical, hydrogen peroxide and nitric oxide (murine macrophage cells) scavenging activity than the root and root bark extracts.

Evaluation of antimicrobial, antioxidant and wound-healing potentials of Holoptelea integrifolia.

The methanolic extracts of Holoptelea integrifolia (Roxb.) (Urticaceae) leaves (MLE) and stem bark (MSBE) were studied for the wound-healing potential. Since wound healing is severely hampered by microbial infection and reactive oxygen species (ROS), this study was undertaken to evaluate antimicrobial and antioxidant activity apart from wound-healing activity. The antimicrobial property of the Holoptelea was studied against the six bacterial and five fungal strains using the agar well diffusion method and minimum microbicidal concentration and minimum inhibitory concentration were determined for each strain, in which methanolic extract of stem bark (MSBE) has shown bigger zone of inhibition (11.3-20.4 mm) than methanolic extract of leaves (MLE) (9.6-14.9 mm). The anti-oxidant activity was evaluated by DPPH free radical scavenging activity using HPLC method. The IC(50) values obtained for MSBE (TPC: 78.53+/-1.26 mg/g) and MLE (TPC: 57.71+/-1.45 mg/g) were 37.66+/-0.48 and 50.36+/-0.59 microg/well, respectively. In excision wound model, more than 90% wound healing was recorded in treated groups by 14 days of post surgery, where as only 62.99% was observed in the control group. In incision model, higher breaking strengths and higher hydroxyproline content in treated groups suggested higher collagen re-deposition than the control group. Finally, histopathology studies conformed wound-healing activity of Holoptelea integrifolia.