The gut-liver axis: emerging mechanisms and therapeutic approaches for nonalcoholic fatty liver disease and type 2 diabetes mellitus.

Nonalcoholic fatty liver disease (NAFLD), more appropriately known as metabolic (dysfunction) associated fatty liver disease (MAFLD), a prevalent condition in type 2 diabetes mellitus (T2DM) patients, is a complex condition involving hepatic lipid accumulation, inflammation, and liver fibrosis. The gut-liver axis is closely linked to metabolic dysfunction, insulin resistance, inflammation, and oxidative stress that are leading to the cooccurrence of MAFLD and T2DM cardiovascular diseases (CVDs). The purpose of this review is to raise awareness about the role of the gut-liver axis in the progression of MAFLD, T2DM and CVDs with a critical analysis of available treatment options for T2DM and MAFLD and their impact on cardiovascular health. This study analysed over 100 articles on this topic, using online searches and predefined keywords, to understand and summarise published research. Numerous studies have shown a strong correlation between gut dysfunction, particularly the gut microbiota and its metabolites, and the occurrence and progression of MAFLD and type 2 diabetes mellitus (T2DM). Herein, this article also examines the impact of the gut-liver axis on MAFLD, T2DM, and related complications, focusing on the role of gut microbiota dysbiosis in insulin resistance, T2DM and obesity-related cardiovascular complications. The study suggests potential treatment targets for MAFLD linked to T2DM, focusing on cardiovascular outcomes and the molecular mechanism of the gut-liver axis, as gut microbiota dysbiosis contributes to obesity-related metabolic abnormalities.

Comparative study on phytochemical screening of polyphenol rich extracts of Euphorbia tithymaloidesL. with special emphasis on antiglycation and anti-diabetic potential.

The present study evaluated a range of biological activities of Euphorbia tithymaloides L. (Family: Euphorbiaceae) in relation to diabetes and associated complications. This plant has antioxidant and anti-inflammatory properties, but its potential for the management of hyperglycaemia and subsequently, the inhibition and reversal of advanced glycation end products has not yet been pinpointed. The objectives of this work centred around comparative iv-vitro phytochemical screening of different plant parts, followed by antidiabetic, antiglycation and glycation-reversing activities of Euphorbia tithymaloides. Rutin and luteolin, two main bioactive compounds with significant antiglycation potentials, were also quantified using a recently developed and validated HPLC-PDA method. Leaf extract showed significantly higher potency than root and stem extracts in terms of antioxidant, anti-inflammatory, antidiabetic and antiglycation activity. A combination of enzymatic inhibition and HPLC phytochemical screening provided additional evidence to consider this plant a promising source for deepening the investigation on antidiabetic plant agents.

Madhuca longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high fat diet.

BACKGROUND: Metabolic disorder is characterized as chronic low-grade inflammation which elevates the systemic inflammatory markers. The proposed hypothesis behind this includes occurrence of hypoxia due to intake of high fat diet leading to oxidative stress and mitochondrial dysfunction. AIM: In the present work our aim was to elucidate the possible mechanism of action of hydroethanolic fraction of M. longifolia leaves against the metabolic disorder. METHOD AND RESULTS: In the present investigation, effect of Madhuca longifolia hydroethanolic fraction (MLHEF) on HFD induced obesity and diabetes through mitochondrial action and selective GLUT expression has been studied. In present work, it was observed that HFD (50% of diet) on chronic administration aggravates the metabolic problems by causing reduced imbalanced oxidative stress, ATP production, and altered selective GLUT protein expression. Long term HFD administration reduced (p < 0.001) the SOD, CAT level significantly along with elevated liver function marker AST and ALT. MLHEF administration diminishes this oxidative stress. HFD administration also causes decreased ATP/ADP ratio owing to suppressed mitochondrial function and elevating LDH level. This oxidative imbalance further leads to dysregulated GLUT expression in hepatocytes, skeletal muscles and white adipose tissue. HFD leads to significant (p < 0.001) upregulation in GLUT 1 and 3 expression while significant (p < 0.001) downregulation in GLUT 2 and 4 expressions in WAT, liver and skeletal muscles. Administration of MLHEF significantly (p < 0.001) reduced the LDH level and also reduces the mitochondrial dysfunction. CONCLUSION: Imbalances in GLUT levels were significantly reversed in order to maintain GLUT expression in tissues on the administration of MLHEF.

Expanded porous-starch matrix as an alternative to porous starch granule: Present status, challenges, and future prospects.

Exposing the hydrated-soft-starch matrix of intact grain or reconstituted flour dough to a high-temperature-short-time (HTST) leads to rapid vapor generation that facilitates high-pressure build-up in its elastic matrix linked to large deformation and expansion. The expanded starch matrix at high temperatures dries up quickly by flash vaporization of water, which causes loss of its structural flexibility and imparts a porous and rigid structure of the expanded porous starch matrix (EPSM). EPSM, with abundant pores in its construction, offers adsorptive effectiveness, solubility, swelling ability, mechanical strength, and thermal stability. It can be a sustainable and easy-to-construct alternative to porous starch (PS) in food and pharmaceutical applications. This review is a comparative study of PS and EPSM on their preparation methods, structure, and physicochemical properties, finding compatibility and addressing challenges in recommending EPSM as an alternative to PS in adsorbing, dispersing, stabilizing, and delivering active ingredients in a controlled and efficient way.

Current advancement in the preclinical models used for the assessment of diabetic neuropathy.

Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition.

Vitamin K2 protects against aluminium chloride-mediated neurodegeneration.

Recent studies have shown that, coupled with other environmental factors, aluminium exposure may lead to neurodegeneration resulting in cognitive impairment resembling Alzheimer's disease. Menaquinone, a form of vitamin K2, aids in maintaining healthy bones and avoids coronary calcification. It also has anti-inflammatory and antioxidant properties. Here, we study the neuroprotective effects of vitamin K2 (MK-7) using the animal model of Alzheimer's disease (AD). Aluminium chloride (AlCl3; 100 mg/kg for 3 weeks orally) was administered to Swiss albino mice to induce neurodegeneration and Vitamin K2 (100 g/kg for 3 weeks orally) was applied as treatment. This was followed by behavioural studies to determine memory changes. The behavioural observations correlated with proinflammatory, oxidative, and brain histopathological changes in AlCl3-treated animals with or without vitamin K2 treatment. AlCl3 administration led to memory decline which was partially restored in Vitamin K2 treated animals. Myeloperoxidase levels in the brain increased due to AlCl3-mediated inflammation, which Vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers induced by AlCl3 were reversed by Vitamin K2. Also, Vitamin K2 helps to restore hippocampal BDNF levels and reduced the amyloid ß accumulation in AlCl3-administered animals. Additionally, Vitamin K2 protected the hippocampal neurons against AlCl3-mediated damage as observed in histopathological studies. We conclude that Vitamin K2 could partially reverse AlCl3-mediated cognitive decline. It increases acetylcholine and BDNF levels while reducing oxidative stress, neuroinflammation, and ß-amyloid deposition, thus protecting the hippocampal neurons from AlCl3-mediated damage.

Neuroprotective effect of Vitamin K2 against gut dysbiosis associated cognitive decline.

Vitamin K2/ Menaquinones produced predominantly by the gut microbiome improve bone health and prevent coronary calcification. The central nervous system has been linked with gut microbiota via the gut-brain axis and is strongly associated with psychiatric conditions. In the present study, we show the role of Vitamin K2 (MK-7) in gut dysbiosis-associated cognitive decline. Gut dysbiosis was induced in mice by administering Ampicillin (250 mg/kg twice a day orally) for 14 days and Vitamin K2 (0.05 mg/kg) for 21 days with or without antibiotic treatment and altered gene expression profile of intestinal microbes determined. This was followed by behavioural studies to determine cognitive changes. The behavioural observations are then correlated with proinflammatory, oxidative, and brain and intestinal histopathological changes in antibiotic-treated animals with or without vitamin K2 administration. With the use of antibiotics, Lactobacillus, Bifidobacterium, Firmicutes, and Clostridium's relative abundance reduced. When vitamin K2 was added to the medication, their levels were restored. Cognitive impairment was observed in behavioural trials in the antibiotic group, but this drop was restored in mice given both an antibiotic and vitamin K. Myeloperoxidase levels in the colon and brain increased due to gut dysbiosis, which vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers brought on by antibiotics were also decreased by vitamin K2. Additionally, vitamin K2 guarded against alterations in intestine ultrastructure brought on by antibiotic use and preserved hippocampus neurons. So, it can be concluded that vitamin K2 improved cognitive skills, avoided hippocampus neuronal damage from antibiotics, and lowered intestine and brain inflammation and oxidative stress.

Oligosaccharide and Flavanoid Mediated Prebiotic Interventions to Treat Gut Dysbiosis Associated Cognitive Decline.

Oligosaccharides are potential prebiotic which maintains gut microbiota and improves gut health. The association of gut and brain is named as gut-brain-axis. Gut dysbiosis disrupts gut-brain-axis and effectively contributes to psychiatric disorders. In the present study, Xylo-oligosaccharide (XOS) and Quercetin were used as therapeutic interventions against gut dysbiosis mediated cognitive decline. Gut dysbiosis was established in mice through administration of Ampicillin Sodium, orally for 14 days. XOS and quercetin were administered separately or in combination along with antibiotic. Gene expression studies using mice faecal samples showed both XOS and quercetin could revive Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were reduced due to antibiotic treatment. FITC-dextran concentration in serum revealed XOS and quercetin protected intestinal barrier integrity against antibiotic associated damage. This was verified by histopathological studies showing restored intestinal architecture. Moreover, intestinal inflammation which increased after antibiotic treated animals was reduced upon XOS and quercetin treatment. Behavioural studies demonstrated that gut dysbiosis reduced fear conditioning, spatial and recognition memory which were reversed upon XOS and quercetin treatment. XOS and quercetin also reduced inflammation and acetylcholine esterase which were heightened in antibiotic treated animal brain. They also reduced oxidative stress, pro-inflammatory cytokines and chemokines and protected hippocampal neurons. In conclusion, XOS and quercetin effectively reduced antibiotic associated gut dysbiosis and prevented gut dysbiosis associated cognitive decline in mice.

Neuroprotective Efficacy of Apple Cider Vinegar on Zinc-High Fat Diet-Induced Mono Amine Oxidase Alteration in Murine Model of AD.

OBJECTIVE: Monoamine Oxidase (MAO), which catalyzes the oxidative deamination of amines present in the brain and peripheral tissues, is involved in the metabolism of monoamines and is vital for cognition. This study was designed to examine the protective effect of Apple Cider Vinegar (ACV) on MAO and amine neurotransmitters such as dopamine (DA), serotonin (5-HT), non-adrenaline (NA) levels. METHOD: In this experiment, out of five groups, three groups of animals were pretreated with one of the test drugs each i.e., Chrysin (10 mg/kg), ACV (0.7% v/v) and Rivastigmine (2.5 mg/kg) along with Zn with high fat diet (HFD) for 3 months and the rest two groups were that of control and disease induced. After the treatment period, mice were examined for MAO-A & B, DA, 5-HT and NA level estimation. RESULTS: The results showed that Zn with HFD had induced a significant increase (p < 0.01, p < 0.001) in MAO-A & B levels and a significant decrease (p < 0.001) in the levels of 5-HT, DA, and NA. Pretreatment of test drugs with Zn with HFD caused a restoration activity and a significant decrease (p < 0.01, p < 0.05) in MAO-A & B levels and a significant increase (p < 0.05, p < 0.01, p < 0.001) in the level of DA, 5HT and NA as compared to the Zn treated group. Amongst all three test drugs mentioned above, the ACV-treated group showed the most improvement during pretreatment. CONCLUSIONS: The findings suggest that ACV, might prove to be a beneficial nutraceutical & provide a protective effect against Alzheimer's disease (AD)-like neurological diseases.

Heart rate variability time domain features in automated prediction of diabetes in rat.

Diabetes is a very common occurring disease, diagnosed by hyperglycemia. The established mode of diagnosis is the analysis of blood glucose level with the help of a hand-held glucometer. Nowadays, it is also known for affecting multi-organ functions, particularly the microvasculature of the cardiovascular system. In this work, an alternative diagnostic system based on the heart rate variability (HRV) analysis and artificial neural network (ANN) and support vector machine (SVM) have been proposed. The experiment and data recording has been performed on male Wister rats of 10-12 week of age and 200 ± 20 gm of weight. The digital lead-I electrocardiogram (ECG) data are recorded from control (n = 5) and Streptozotocin-induced diabetic rats (n = 5). Nine time-domain linear HRV parameters are computed from 60 s of ECG data epochs and used for the training and testing of backpropagation ANN and SVM. Total 526 (334 Control and 192 diabetics) such datasets are computed for the testing of ANN for the identification of the diabetic conditions. The ANN has been optimized for architecture 9:5:1 (Input: hidden: output neurons, respectively) with the optimized learning rate parameter at 0.02. With this network, a very good classification accuracy of 96.2% is achieved. While similar accuracy of 95.2% is attained using SVM. Owing to the successful implementation of HRV parameters based automated classifiers for diabetic conditions, a non-invasive, ECG based online prognostic system can be developed for accurate and non-invasive prediction of the diabetic condition.

Evaluation of the mechanism of anticancer activity of deltamethrin in Jurkat-J6 cell line.

Deltamethrin (DLM) is an α-cyano type-II synthetic pyrethroid compound which is extensively used in different agricultural and home pest control. The advantages of pyrethroids over other insecticides are that they are relatively non-toxic to birds and mammals and show high efficacy at relatively lower concentrations. DLM may have dual characteristics i.e. at low molar-concentration, it is nontoxic to normal healthy cells but can induce apoptotic cell death in cancerous cells. There is no reported work based on such hypothesis. Thus, this study has been designed to explore the anticancer property of DLM and the mechanism behind the apoptotic cell death by DLM in cancer cell line (Jurkat J6). Molecular docking study indicates that DLM has the greater binding affinity towards MCL-1 receptor. MTT assay has revealed some significant loss in the viability of cancerous cells by DLM. Further estimation of ROS and GSH have shown the significant oxidative stress induced by DLM in concentration-time dependent manner. DLM has also increased the caspase-3 activity and the apoptotic cells significantly while a decrease in interleukin-2 level has also been observed. The pre-treatment with thiol antioxidant and caspase inhibitor has confirmed the role of oxidative stress and the possibility of other pathways. These observations reveal that DLM may act as anticancer agent at lower concentrations (0.1-1 µM), though the further detailed investigation is warranted.

Influence of Musa sapientum L. on pharmacokinetic of metformin in diabetic gastroparesis.

OBJECTIVE: To investigate the effect of Musa sapientum L. (MS) bark juice in diabetic gastroparesis and its effect on pharmacokinetic of metformin (MET). METHODS: Diabetes was induced in rats by administering alloxan (120 mg/kg) saline solution and maintained for 8 week. All the 18 Sprague-Dawley rats were divided into three groups (n =6 in each group): normal control, diabetic control and MS bark juice. Assessment of diabetes was done by glucose oxidase-peroxidase method on the 3rd day of alloxan administration. The effects of MS bark juice (100 mL/kg) on gastric emptying time, intestinal transit time, contractility of fundus and pylorus as well as gastric acid secretion in chronic diabetic rats were observed after 8 weeks of alloxan administration. The effect of MS bark juice on the pharmacokinetic of orally administered single dose of MET (350 mg/kg) was evaluated on the 57th day of protocol. Any drugs that may reduce the blood glucose level or influence the fibrinolytic system were not used in this study. RESULTS: The MS bark juice significantly reduced the blood glucose level in the diabetic rats (P<0.01). There was significant decrease in the pylorus motility and increase in the gastric emptying time, intestinal transit time, contractility of fundus, gastric acid secretion in the MS bark juice treated group (P<0.01). There was significant decrease in the time at which drug at a maximum concentration, half life of drug and increase in the maximum concentration of drug in the plasma of MET in MS bark juice treated group as compared to diabetic control group (P<0.01). CONCLUSION: MS bark juice effectively manages diabetic gastroparesis and thereby improves the bioavailabilty of MET when administered with MS bark juice.

Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in STZ-induced diabetic rats.

BACKGROUND: The present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals. METHODS: Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL. RESULT: There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals. CONCLUSIONS: The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.

Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies.

The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies.

Antidiabetic activity of Pterospermum acerifolium flowers and glucose uptake potential of bioactive fraction in L6 muscle cell lines with its HPLC fingerprint.

The present study was designed to estimate the detailed antidiabetic activity of Pterospermum acerifolium (L.) Willd flowers. In vitro alpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE) and its various fractions. The active ethyl acetate fraction (PAFEF) was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3) and subjected to acute toxicity studies followed by antidiabetic screening in vivo by streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg) reduced the levels of fasting blood glucose, significantly (P<0.001) compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes in ß-cells. PAFE2 showed 32.6±1.93% glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to 13.7±2.51%. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis.

Evaluation of in silico, in vitro α-amylase inhibition potential and antidiabetic activity of Pterospermum acerifolium bark.

CONTEXT: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use. OBJECTIVE: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark. MATERIALS AND METHODS: In silico studies were performed between human pancreatic α-amylase (HPA) and ß-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30 mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats. RESULTS: In silico studies showed the potent inhibition of ß-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (Ki) of 269.35 nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30 mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p < 0.01) and increased the levels of HDL-C, catalase, GSH, SOD significantly (p < 0.01) as compared to that of diabetic control animals. Histological studies on PABE3 treated group showed remarkable positive changes in ß-cells. CONCLUSION: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.

Eleutherine indica L. accelerates in vivo cutaneous wound healing by stimulating Smad-mediated collagen production.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherine indica L. has been used for healing of wound, painful and irregular menstruation, dysentery and lesions, and topically used as antiseptic and antimicrobial agent in folk medicine. In the present study, methanolic extracts of Eleutherine indica was subjected to scientific investigation for in-vivo cutaneous wound healing in wistar rat. MATERIALS AND METHODS: In-vivo wound healing activity of Eleutherine indica was evaluated by using circular excision experimental models, followed by histopathological and western blot analysis. The healing potential was comparatively assessed with a reference gentamicin sulfate hydrogel (0.01% w/w). Wound contraction measurement, hydroxyproline estimation and western blot for COL3A1, bFGF, Smad-2, -3, -4, and -7 were performed. RESULTS: The methanolic extract of Eleutherine indica showed accelerated wound healing activity as evidenced by fast wound contraction rate and higher hydroxyproline content of granulation tissue. Western blot revealed the Smad-mediated collagen production promoting property of Eleutherine indica methanolic extract. Histopathological examinations also supported the experimental findings. CONCLUSION: The study revealed that Eleutherine indica promotes wound healing by augmenting Smad-mediated collagen production in wound granulation tissue.

Evaluation of wound healing and antimicrobial potentials of Ixora coccinea root extract.

OBJECTIVE: To evaluate the wound healing and antimicrobial activity of root extracts of Ixora coccinea (I. coccinea). METHODS: To investigate the wound healing efficacy of root extract of I. coccinea Linn, five groups of animals were divided each containing six animals. Two wound models including incision and excision wound models were used in this study. The parameters studied were tensile strength on incision wound model and in terms of wound contraction for excision wound model were compared with standard Nitrofurazone (NFZ) ointment (0.2% w/w). Six extracts (ethanol, aqueous, petroleum ether, benzene, chloroform and ethyl acetate) of I. coccinea were screened for in vitro growth inhibiting activity against different bacterial strains viz, Staphylococcus aureus, Bacillus pumilius, Enterococcus faecalis, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa and fungi Candida albicans and Aspergillus niger were compared with the standard drugs ciprofloxacin and chloramphenicol for antibacterial and griseofulvin for antifungal screening. The serial dilution and cup (or) well plate methods were used for the antimicrobial study and MIC was determined. RESULTS: The ethanolic extract showed significant (P<0.001) wound healing activity when compared to standard drug NFZ with respect to normal control group. Amongst all, ethanolic extract showed highly significant antibacterial activity against all bacterial strains used in this study when compared to standard. The aqueous extract showed moderate significant inhibition against all bacterial strains when compared to standard. All the extracts were shown negligible activity against the fungal strains used in this study. CONCLUSIONS: The ethanolic root extract of I. coccinea showed pronounced wound healing and antibacterial activity. The probable reason to heal the wound was that the external application of the extract prevented the microbes to invade through the wound thus the protection of wound occurs against the infection of the various organisms.

Synthesis, antispasmodic and antidiarrheal activities of some 1-substituted imidazole derivatives.

A series of 1-substituted imidazoles 1a-d and 2a-d were synthesized and screened for antispasmodic and antidiarrheal activities. Antispasmodic activity was tested at various concentrations on isolated tissue preparations; concentration-response curves were plotted and compared with atropine. All compounds were found to inhibit contraction of the guinea pig ileum. Castor oil-induced diarrhea model in rats was used for evaluation of antidiarrheal activity. Parameters such as intestinal transit and volume of intestinal fluid were measured for antidiarrheal activity at 40 mg kg-1 dose and compared with the standard drug loperamide at 6 mg kg-1 dose. Defecation frequency in the test group was found to be significantly lower (p < 0.01) compared to the control group and comparable with that of the standard. The present study reveals that the compounds exert antidiarrheal activity through possible inhibition of intestinal movement and reduction of capillary permeability in the abdominal cavity.

The antihyperglycemic effect of aerial parts of Salvia splendens (scarlet sage) in streptozotocin-induced diabetic-rats.

Salvia splendens (Labiatae) is widely used in Indian traditional medicine for the control of diabetes mellitus. In this study, the hypoglycemic effects produced by the acute and subacute administration of various extracts of S. splendens were investigated. Both the aqueous extract (SSAE) and the methanolic extract (SSME) from the aerial parts resulted in significant reductions of glycemia in streptozotocin (STZ)-induced diabetic rats after oral administration at a dose of 100 and 200 mg/kg, respectively. On oral administration, aqueous and methanolic extracts showed statistically significant (P < 0.001) effect by reducing the effect of glycemia in STZ-induced diabetic rats. These findings suggest the significant antihyperglycemic potential of the S. splendens extracts in ameliorating the diabetic conditions in diabetic rats. No significant effects were found in the normal rats.