Effective Treatment of Solitary Rectal Ulcer Syndrome by Using Photobiomodulation Therapy: A Case Report.

Objective: To investigate the efficacy of Photobiomodulation therapy (PBMT) for the treatment of solitary rectal ulcer syndrome (SRUS). Background: SRUS is a benign disease, diagnosed by symptoms, clinical, and histological findings. PBMT has been reported for the treatment of various inflammation-based diseases including aphthous ulcer, but still no such study on the treatment of SRUS is published. Materials and methods: A 29-year Asian women, diagnosed for SRUS of 0.57 cm diameter, was treated by a laser at 635 nm through seven sessions. Laser fluence of 85 J/cm2 was delivered to ulcer lesion during each session for 10 min. Clinical results were valued by physician with sigmoid probe throughout PBMT sessions and no medicines were prescribed to the patient. Results: After seven sessions, the lesion was completely healed with 100% clinical response. In follow-up, patient did not respond to any additional/recurring abnormality, and no side effects were observed. Conclusions: In conclusion, PBMT by using laser at 635 nm is an effective treatment for SRUS without any side effects and patient remained comfortable throughout treatment sessions. Patient registration No. H-744/23.

Prediction of cell migration potential on human breast cancer cells treated with Albizia lebbeck ethanolic extract using extreme machine learning.

Cancer is one of the major causes of death in the modern world, and the incidence varies considerably based on race, ethnicity, and region. Novel cancer treatments, such as surgery and immunotherapy, are ineffective and expensive. In this situation, ion channels responsible for cell migration have appeared to be the most promising targets for cancer treatment. This research presents findings on the organic compounds present in Albizia lebbeck ethanolic extracts (ALEE), as well as their impact on the anti-migratory, anti-proliferative and cytotoxic potentials on MDA-MB 231 and MCF-7 human breast cancer cell lines. In addition, artificial intelligence (AI) based models, multilayer perceptron (MLP), extreme gradient boosting (XGB), and extreme learning machine (ELM) were performed to predict in vitro cancer cell migration on both cell lines, based on our experimental data. The organic compounds composition of the ALEE was studied using gas chromatography-mass spectrometry (GC-MS) analysis. Cytotoxicity, anti-proliferations, and anti-migratory activity of the extract using Tryphan Blue, MTT, and Wound Heal assay, respectively. Among the various concentrations (2.5-200 µg/mL) of the ALEE that were used in our study, 2.5-10 µg/mL revealed anti-migratory potential with increased concentrations, and they did not show any effect on the proliferation of the cells (P < 0.05; n ≥ 3). Furthermore, the three data-driven models, Multi-layer perceptron (MLP), Extreme gradient boosting (XGB), and Extreme learning machine (ELM), predict the potential migration ability of the extract on the treated cells based on our experimental data. Overall, the concentrations of the plant extract that do not affect the proliferation of the type cells used demonstrated promising effects in reducing cell migration. XGB outperformed the MLP and ELM models and increased their performance efficiency by up to 3% and 1% for MCF and 1% and 2% for MDA-MB231, respectively, in the testing phase.

Prediction of Cell Migration in MDA-MB 231 and MCF-7 Human Breast Cancer Cells Treated with Albizia Lebbeck Methanolic Extract Using Multilinear Regression and Artificial Intelligence-Based Models.

Breast cancer is a common cancer affecting women worldwide, and it progresses from breast tissue to other parts of the body through a process called metastasis. Albizia lebbeck is a valuable plant with medicinal properties due to some active biological macromolecules, and it's cultivated in subtropical and tropical regions of the world. This study reports the phytochemical compositions, the cytotoxic, anti-proliferative and anti-migratory potential of A. lebbeck methanolic (ALM) extract on strongly and weakly metastatic MDA-MB 231 and MCF-7 human breast cancer cells, respectively. Furthermore, we employed and compared an artificial neural network (ANN), an adaptive neuro-fuzzy inference system (ANFIS), and multilinear regression analysis (MLR) to predict cell migration on the treated cancer cells with various concentrations of the extract using our experimental data. Lower concentrations of the ALM extract (10, 5 & 2.5 µg/mL) showed no significant effect. Higher concentrations (25, 50, 100 & 200 µg/mL) revealed a significant effect on the cytotoxicity and proliferation of the cells when compared with the untreated group (p < 0.05; n ≥ 3). Furthermore, the extract revealed a significant decrease in the motility index of the cells with increased extract concentrations (p < 0.05; n ≥ 3). The comparative study of the models observed that both the classical linear MLR and AI-based models could predict metastasis in MDA-MB 231 and MCF-7 cells. Overall, various ALM extract concentrations showed promising an-metastatic potential in both cells, with increased concentration and incubation period. The outcomes of MLR and AI-based models on our data revealed the best performance. They will provide future development in assessing the anti-migratory efficacies of medicinal plants in breast cancer metastasis.

Phytoconstituents of Datura metel extract improved motor coordination in haloperidol-induced cataleptic mice: Dual-target molecular docking and behavioural studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a prominent health challenge characterized by complex aetiology and limited therapeutic breakthroughs. Datura metel (DM) is a medicinal plant containing active phytoconstituents with neuropharmacological potentials. In traditional medicine, it exerts anticholinergic, anti-inflammatory and antioxidant effects, and protection from organophosphate poisoning inclusively involved in the pharmacotherapy of PD. Its other PD-related medicinal potency includes treatment of motor sickness and bradycardia. However, the exact mechanisms of anti-PD effects of its phytoconstituents remain underexplored. MATERIALS AND METHODS: In this study, methanolic extract of DM was evaluated for anti-PD behavioural effects in vivo haloperidol-induced cataleptic mice. The GC-MS-identified phytochemicals were studied for one-drug-multi-target inhibitory mechanisms against some key targets for PD treatment, alpha-synuclein (ASN) and dopa decarboxylase (DDC) using molecular docking. RESULTS: and discussion: Chronic administration of 50, 100 and 200 mg/kg of DM extract improved the 14-s latency time induced by haloperidol to 54, 54 and 57 s respectively, whereas levodopa (30 mg/kg) produced 47 s in rotarod tests. Similarly, the descending times for haloperidol-induced cataleptic mice were significantly reduced from 110 s to 17.7, 17.7 and 12.5 s by the respective chronic doses of DM extract, whereas levodopa-administered mice spent 17.5 s descending the same 30 cm pole. The interesting motor coordination enhancements are suggestively due to synergistic inhibition of ASN and DCC by the phytoconstituents of DM, especially, atropine and scopolamine. From the docking analysis, the two phytochemicals interacted more potently with the active therapeutic sites of the dual targets than levodopa and carbidopa. CONCLUSION: Methanolic extract of DM contains active phytochemicals for multi-target-directed antiparkinsonian mechanisms amenable for further studies.

LC-MS and GC-MS Profiling of Different Fractions of Ficus platyphylla Stem Bark Ethanolic Extract.

The exploration of medicinal plants in traditional medicine for the treatment of diseases has been practiced for long, globally, because of its cultural acceptability, availability, and affordability. This study investigated the qualitative and quantitative estimation of phytochemicals present in Ficus platyphylla stem bark as well as determined the reducing power and antioxidant property of each fraction against DPPH and NO radicals. The study further elucidated the presence of possible compounds in different fractions (methanol, ethyl acetate, petroleum ether, and chloroform) of Ficus platyphylla stem bark (FPSB) extract using GC-MS, LC-MS, and FTIR techniques. Qualitative phytochemical analysis reveals the presence of phytochemicals: saponin, flavonoids, tannins, phenols, steroids, alkaloids, and glycoside in the ethanolic extract. The LC-MS study of methanol and ethyl acetate fractions reveals the presence of thirteen and three compounds, respectively. GC-MS analysis shows the presence of trans-13-octadecenoic acid as the main compound 38.07% and cis-vaccenic acid as the least compound (0.10%) in the petroleum ether fraction. The main compound in the chloroform fraction is 12-oleanen-3-yl acetate, (3. alpha.) with a peak area percentage of 49.25% and oleic acid been the least compound with 0.07% peak area. The FTIR analysis reveals that the fractions contain compounds with hydroxyl, aromatic, methyl, methylene, methyne, long aliphatic chain, ethers, ether-oxy, peroxides, etc. The analyzed fractions reveal compounds with potential pharmacological activity in the management of pathological conditions.

Oligochaeta ramosa (Roxb.) Extract Regulates Lipid Metabolism and Exerts Hepatoprotective Effects in Cadmium-Induced Hepatic Injury in Rats.

Environmental pollutants present a potential source of toxicity when exposed to humans. The study was aimed at investigating the potential of Oligochaeta ramosa (Roxb.) as a hepatoprotective agent in cadmium-induced hepatotoxicity causing lipid profile disturbance. The aqueous methanolic (30 : 70 v/v) extract of O. ramosa Roxb. (AME.Or) was subjected to preliminary phytochemical analysis, whereas the antioxidant activity of its constituents was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The hepatoprotective and antihyperlipidemic effects of AME.Or was investigated by dividing animals into five groups (A-E). Animals were either treated with normal saline or CdCl2 (6.5 mg/kg, intraperitoneally) followed by treatment with silymarin (100 mg/kg), or AME.Or (200 mg/kg) and AME.Or (400 mg/kg) for consecutive three weeks. Blood samples were collected, and the serum lipid profile was assessed on the 11th and 21st day of treatment. Histopathological analysis was performed after euthanization. In vitro analysis of AME.Or revealed 64% inhibition as free radicals scavenging potential during DPPH, total phenolic content (TPC) (79.92 mgGAE/g), and total flavonoids content (TFC) (38.75 mgRE/g). The group intoxicated with CdCl2 showed significantly high (p ≤ 0.05) levels of the liver function indicators and lipid profile than in the control group. The higher dose of AME.Or (400 mg/kg) significantly decreased the aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin (p ≤ 0.001), decreased total cholesterol and triglycerides (p ≤ 0.01) while significantly increased high density lipoprotein (HDL; p ≤ 0.01) as compared to the intoxicated group. The histopathological analysis of the liver revealed signs of necrosis in the intoxicated group, while AME.Or treated groups showed marked improvement. The findings accentuate the therapeutic importance of O. ramosa (Roxb.) as a hepatoprotective remedy.

Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.

Arsenic (As) is a toxic metalloid and human carcinogen that may cause hepatotoxicity. Fisetin (3, 3', 4', 7-tetrahydroxyflavone) is a phytoflavonoid, which shows diverse therapeutic activities. This study aimed to examine the remedial potential of fisetin against As-instigated hepatotoxicity in adult male rats. To accomplish this aim, albino rats (N = 48) were evenly classified into 4 groups: control group, As (10 mg/kg) group, fisetin (2.5 mg/kg) + As (10 mg/kg) group, and fisetin (2.5 mg/kg) group. After one month of treatment, biochemical assay, total protein content (TPC), hepatic serum enzymes, inflammatory as well as pro- or anti-apoptotic markers, and histopathological profile of hepatic tissues were estimated. As administration disordered the biochemical profile by decreasing activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS), and thiobarbituric acid reactive substances (TBARS). TPC was also considerably reduced after exposure to As. Furthermore, As markedly raised the levels of liver serum enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) as well as the levels of inflammatory markers, i.e., nuclear factor- κB (NF-κB), tumor necrosis- α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclo-oxygenase-2 (COX-2) activity. Besides, it lowered the level of antiapoptotic markers (Bcl-2) and upregulated the levels of proapoptotic markers (Bax, Caspase-3, and Caspase-9). Additionally, As exposure led to histopathological damage in hepatic tissues. However, fisetin administration remarkably alleviated all the depicted hepatic damages. For further verification, the screening of several dock complexes was performed by using the GOLD 5.3.0 version. Based on docking fitness and GOLD score, the ranking order of receptor proteins with fisetin compound is superoxide dismutase, interleukin, aspartate aminotransferase, alkaline phosphatase, TNF-alpha, alanine transaminase, cyclo-oxygenase 2, antiapoptotic, and glutathione reductase. Out of these three receptor proteins superoxide dismutase, interleukin, and aspartate aminotransferase showed the best interaction with the fisetin compound. In vivo and in silico outcomes of the current study demonstrated that fisetin could potentially ameliorate As-instigated hepatotoxicity.

Recent advances on therapeutic potentials of gold and silver nanobiomaterials for human viral diseases.

Viral diseases are prominent among the widely spread infections threatening human well-being. Real-life clinical successes of the few available therapeutics are challenged by pathogenic resistance and suboptimal delivery to target sites. Nanotechnology has aided the design of functionalised and non-functionalised Au and Ag nanobiomaterials through physical, chemical and biological (green synthesis) methods with improved antiviral efficacy and delivery. In this review, innovative designs as well as interesting antiviral activities of the nanotechnology-inclined biomaterials of Au and Ag, reported in the last 5 years were critically overviewed against several viral diseases affecting man. These include influenza, respiratory syncytial, adenovirus, severe acute respiratory syndromes (SARS), rotavirus, norovirus, measles, chikungunya, HIV, herpes simplex virus, dengue, polio, enterovirus and rift valley fever virus. Notably identified among the nanotechnologically designed promising antiviral agents include AuNP-M2e peptide vaccine, AgNP of cinnamon bark extract and AgNP of oseltamivir for influenza, PVP coated AgNP for RSV, PVP-AgNPs for SARS-CoV-2, AuNRs of a peptide pregnancy-induce d hypertension and AuNP nanocarriers of antigen for MERS-CoV and SARS-CoV respectively. Others are AgNPs of collagen and Bacillus subtilis for rotavirus, AgNPs labelled Ag30-SiO 2 for murine norovirus in water, AuNPs of Allium sativum and AgNPs of ribavirin for measles, AgNPs of Citrus limetta and Andrographis Paniculata for Chikungunya, AuNPs of efavirenz and stavudine, and AgNPs-curcumin for HIV, NPAuG3-S8 for HSV, AgNPs of Moringa oleifera and Bruguiera cylindrica for dengue while AgNPs of polyethyleneimine and siRNA analogues displayed potency against enterovirus. The highlighted candidates are recommended for further translational studies towards antiviral therapeutic designs.

Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.

Synthetic ß-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD.

Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a ß hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-ß plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC50 value of 67 µg/ml against AChE and 96 µg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC50 value observed as 171 µg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.

Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach.

Plants belongs to Asteraceae family are reported to be rich in major phytochemical including flavonoids and are documented to acquire antidiabetic response. Antidiabetic effects of salvigenin, eupatilin and cirsilineol were screened on in-vitro enzyme inhibition and in-vivo streptozotocin animal models. Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) produced antidiabteic responses in streptozotocin model for diabetes. All natural flavonoids reduces the blood glucose level to a significant level (*P<0.05, **P<0.01, ***P<0.001, n=8) but promising results were observed in eupatilin at dose of 7.5mk/kg (364.12±4.3 to 128.41±4.2mg/dL, n=8) and at dose of 7.5mk/kg 363.65±4.8 to 126.14±5.1mg/dL, n=8). Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) for 28 days showed a substantial fall (*P<0.05, **P<0.01, ***P<0.001, n=8) in total cholesterol, LDL and triglcerides (TGs) in comparison to diabetic model. The isolated flavonoids reduced considerably the serum ALP, SGPT and SGOT in rats intoxicated with streptozotocin. The results indicate that the flavonoids may be useful in the development of new antidiabetic drugs.

Development of tri-component antibacterial hybrid fibres for potential use in wound care.

OBJECTIVE: Tri-component antibacterial psyllium-alginate-chitosan fibres were developed and their properties were studied with reference to their application in health-care. METHOD: Psyllium was co-extruded with sodium alginate as a carrier into a coagulation bath containing calcium chloride and hydrolysed chitosan. Different concentrations of the hydrolysed chitosan were used and an in vitro assessment of antibacterial activity of the produced fibres was carried out against the known pathogens of Staphylococcus aureus and Escherichia coli. The effect of hydrolysed chitosan bath composition on physical and mechanical properties of produced fibres was also examined. RESULTS: Chitosan-containing fibres demonstrated a 70-130% thicker dry diameter than the control fibre (F1). The linear density of the fibre increased from 6.8 to 10 tex as the chitosan concentration increased from 10g/l to 30g/l (fibre type F1 to F4). With the addition of hydrolysed chitosan, distilled water absorption was increased while the saline and solution-A (0.83% w/v NaCl and 0.03% w/v CaCl2) absorption decreased. The percentage strain of hybrid fibres was lower than the control fibre due to the inclusion of hydrolysed chitosan. At lower viscosities of the hydrolysed chitosan bath, the fibres were much stiffer due to better penetration of the hydrolysed chitosan. Similarly, at lower viscosities, the tenacities of the hybrid fibres were higher than the control fibre. The hydrolysed chitosan-treated fibres were more effective against Staphylococcus aureus than the Escherichia coli, and the antibacterial activity increased with the decrease in viscosity of the hydrolysed chitosan bath. CONCLUSION: We developed novel PAC fibres. Antibacterial testing showed that hydrolysed chitosan was more effective against Gram-positive bacteria than Gram-negative bacteria.

Evaluation of in vitro and in vivo anti-inflammatory effects of (-)-pseudosemiglabrin, a major phytoconstituent isolated from Tephrosia apollinea (Delile) DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Tephrosia apollinea (Delile) DC (Leguminosae) has been used in folk medicine in Arabian countries to treat inflammatory disorders. The plant has been described to treat swelling, bone fracture, bronchitis, cough, earache and wounds. AIM OF THE STUDY: the current study aims to evaluate the anti-inflammatory properties of the major active phytoconstituent of T. apollinea and elucidate the mechanisms by which it inhibits inflammation in vitro and in vivo. MATERIAL AND METHODS: The compound, (-)-pseudosemiglabrin (SSG) was isolated as a major component from the aerial parts of T. apollinea using column chromatography techniques. Sub-chronic in vivo anti-inflammatory effect of SSG was assessed using cotton pellet granuloma assay in SD rats and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) were measured, whereas, tail flick assay was performed to assess the analgesic effect of SSG. Furthermore, the anti-inflammatory effects of SSG were confirmed by measuring the levels of IL-1, TNF-α, and NO in vitro using human macrophage cell lines (U937). In addition COX inhibition assay was also conducted in cells-free system. In silico study was performed to dock SSG in cyclooxygenase enzymes and opioid receptor to predict its structure-activity and molecular mechanism. RESULTS: SSG displayed potential inhibition of granuloma tissue in rats and significantly (P<0.05) lowered the production of cytokines (TNF- α and IL-1) in vivo as well as human macrophages. Further investigation revealed that, SSG selectively inhibited COX-2 by 60% with negligible effect on COX-1. The selectivity of SSG towards COX-2 was confirmed in silico wherein, SSG demonstrated significant binding affinity with binding energy (-9.42kcal/mol). The binding found to be through covalent energy with Ser-530 amino acid residue of the active pocket of COX-2. SSG was found to prolong the flick tail time in mice by two folds. Further computational studies reveal that SSG binds to opioid receptor (µ-OR) through Ile-144 and Thr-218 with affinity two folds compared to the reference compounds, codeine and aspirin. CONCLUSION: In the present study the major phytoconstituent (-)-pseudosemiglabrin (SSG) from the aerial parts of T. apollinea demonstrated potent anti-inflammatory effect by inhibiting of granuloma tissue in rats and prolonging the tail flick time in mice. Investigation of levels of pro-inflammatory cytokines in SSG-treated rats and human macrophages demonstrated that SSG significantly inhibited TNF-α and IL-1. Also SSG showed selective inhibitory effect towards COX-2. In silico study exhibited pronounced binding affinity between SSG and µ-opioid receptor better than that of codeine and aspirin. The obtained results justify the use of aerial parts of T. apollinea to treat various inflammatory diseases and indicate that (-)-pseudosemiglabrin has a great potential to be further developed as a promising anti-inflammatory drug.

Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats.

BACKGROUND: This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA. METHODS: The chloroform fraction of VA (200 mg/kg and 400 mg/kg body weight) was administered to SDRs for 7 and 14 days. Thereafter, the expression (transcription) of key carbohydrate regulatory genes was evaluated in selected tissues - adipose, muscle and liver. Also, the body weight and blood glucose changes were monitored. RESULTS: A 14-day administration of 200 mg and 400 mg of the extract and metformin (500 mg/kg) showed a striking decrease (P <0.05) in the expression of the gluconeogenic enzymes - fructose 1,6-bisphosphatase, phosphoenol pyruvate carboxykinase and glucose 6-phosphatase in the liver and muscle compared to the diabetic control. These genes were highly expressed in tissues of untreated diabetic rats (P <0.05) indicating severe gluconeogenesis. Furthermore, the extract as well as metformin significantly increased glucose oxidation via the pentose phosphate pathway (PPP) i.e. increased expression of the glucose 6-phosphate dehydrogenase (G6PDH) gene (P <0.05) in the liver. Conversely, the expression of the G6PDH in the muscle and adipose tissues significantly decreased (P <0.05), suggesting enhanced utilization of NADPH and ribose in the clearance of reactive oxygen species and for expression of other relevant genes respectively. Also, transcription of the cell proliferation regulatory enzyme, phosphatidylinositol 3-kinase increased in the liver, but decreased in the muscle and adipose tissues (P <0.05) upon treatment with the extract or metformin, implying that the liver responded to the VA and metformin treatments more than other organs. The extract administration also caused a decrease in the expression of key enzymes of glycolysis namely hexokinase and phosphofructokinase, suggestive of a glucose sparing for ribose and NADPH production in PPP. CONCLUSION: Overall, data obtained in this study suggest that VA exerts little or no effect on glycolysis; rather, it may achieve its anti-diabetic action by a simultaneous suppression of gluconeogenesis and potentiation of glucose oxidation via PPP pathway, almost exclusively in the liver.

Anti-inflammatory and antioxidant activities of the methanol extract of Gynura segetum leaf.

Gynura segetum, family Compositae, is a cultivated species and can be found growing in the tropical regions of Indonesia and Malaysia. The plant is known for its use for the treatment of cancer, inflammation, diabetes, hypertension and skin afflictions. In the current study, in vivo anti-inflammatory effect of the methanol extract G. segetum leaf and its antioxidant effect in vitro have been investigated for the first time. The in vitro antioxidant activities of the methanol extract were measured using common methods including total phenolic content; total flavonoid content; scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ß-carotene bleaching assays. The in vivo anti-inflammatory activities were tested using the cotton pellet implanted animal model. The measurement of pro-inflammatory cytokine (TNF-α and IL-1) levels in the blood samples of the rats was carried out by using ELISA kits. The inhibitory activity on cyclooxygenase (COX) enzyme of methanol extract was also evaluated. The methanol extract exhibited good antioxidant activity which is associated with their total phenolic and flavonoid contents. Methanol extract strongly inhibited the granuloma tissue formation in rats and the anti-inflammatory potential was mediated through the inhibition of pro-inflammatory cytokines and COX-2 enzyme activities. Taken together, the present study suggests that G. segetum's leaf is a natural source of antioxidants and has potential therapeutic benefits against chronic inflammation.

Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract.

CONTEXT: Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures. OBJECTIVE: To fractionate A. indica leaf extracts using bioactivity guided manner for identification of the active anti-inflammatory principles. MATERIALS AND METHODS: Polarity-gradient sequential extracts (petroleum ether, chloroform, methanol, and water) of A. indica leaves were screened for their anti-inflammatory potential using the carrageenan-induced rat paw edema model (1 g/kg). The chloroform extract was sequentially fractionated to obtain n-hexane (F-1), n-hexane-chloroform (F-2), and chloroform (F-3) fractions and their inhibitory effect on rat paw edema was evaluated (500 mg/kg). Inhibitory effect of F-2 on granuloma formation, plasma interleukin (IL-1), and tumor necrosis factor (TNF-α) was assessed at the doses of 100, 200, and 400 mg/kg using the cotton pellet assay in rats. Three sub-fractions (SF-1, SF-2, and SF-3) were obtained upon chromatography of F-2, and their inhibitory effect on cyclooxygenase was assessed at 200 µg/mL concentration. The sub-fractions were subjected to gas chromatography-mass spectrometry (GC-MS). RESULTS: All the extracts showed significant anti-inflammatory effect; however, chloroform extract was the most effective against paw edema (53.25% inhibition). The three fractions of chloroform extract showed significant effect, while F-2 being the most potent (51.02%). F-2 demonstrated dose-dependent inhibition of granuloma and cytokines. Interestingly, all the sub-fractions of F-2 inhibited COX-1 and COX-2 with almost equal potential. GC-MS revealed that chemically the sub-fractions were totally different from each other. DISCUSSION AND CONCLUSION: Anti-inflammatory effect of A. indica is a result of cumulative and synergistic effects of diversified constituents with varying polarities that collectively exert the effect via suppression of cyclo-oxygenases and cytokines (IL-1 and TNF-α).

Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells.

OBJECTIVES: Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells. METHODS: (2-Hydroxypropyl)-ß-cyclodextrin inclusion complex and solid dispersions (carboxymethyl cellulose, polyvinylpyrrolidone and sodium lauryl sulphate) of KA were prepared. In addition, a salt of KA, potassium koetjapate was synthesized. KEY FINDINGS: Potassium koetjapate demonstrated higher solubility than the other tested formulations with enhanced cytotoxicity against HCT 116 cells. The enhanced efficacy of potassium koetjapate is attributed to apoptotic induction of nuclear condensation and disruption of mitochondrial membrane potential in the cells. Interestingly, potassium koetjapate was found to be safe in rats after oral administration (LD50 > 2000 mg/kg). CONCLUSIONS: The salt formulation of KA appears to modulate the capability of the parent compound by enhancing its solubility and improves its bioefficacy against colon cancer cells, suggesting attractive roles for its applications in medicine.

Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions.

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent for the treatment of inflammatory and angiogenesis-related diseases.

Ethyl-p-methoxycinnamate isolated from kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...

Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts.

Phaleria macrocarpa, commonly known as Mahkota dewa is a medicinal plant that is indigenous to Indonesia and Malaysia. Extracts of P. macrocarpa have been used since years in traditional medicine that are evaluated scientifically as well. The extracts are reported for a number of valuable medicinal properties such as anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant and vasorelaxant effect. The constituents isolated from different parts of P. macrocarpa include Phalerin, gallic acid, Icaricide C, magniferin, mahkoside A, dodecanoic acid, palmitic acid, des-acetylflavicordin-A, flavicordin-A, flavicordin-D, flavicordin-A glucoside, ethyl stearate, lignans, alkaloids andsaponins. The present review is an up-to-date summary of occurrence, botanical description, ethnopharmacology, bioactivity and toxicological studies related to P. macrocarpa.