Granular support vector machine to identify unknown structural classes of protein.

To date, classification of structural class using local protein structure rather than the whole structure has been gaining widespread attention. It is noted that the structural class lies in local composition or arrangement of secondary structure, while the threshold-based classification method has restricted rules in determining these structural classes. As a consequence, some of the structures are unknown. In order to determine these unknown structural classes, we propose a fusion algorithm, abbreviated as GSVM-SigLpsSCPred (Granular Support Vector Machine--with Significant Local protein structure for Structural Class Prediction), which consists of two major components, which are: optimal local protein structure to represent the feature vector and granular support vector machine to predict the unknown structural classes. The results highlight the performance of GSVM-SigLpsSCPred as an alternative computational method for low-identity sequences.

In vivo antitrypanosomal activity of Garcinia hombroniana aqueous extract.

The anti-Trypanosoma evansi activity of Garcinia hombroniana (seashore mangosteen) leaves aqueous extract was tested on experimentally infected Sprague-Dawley rats. Treatment of infected rats with G. hombroniana extract resulted in a significantly extended post-infection longevity (p < 0.05), compared to the untreated control group. The possible mode of antitrypanosomal effect of the plant extract was also investigated on cultured T. evansi in HMI-9 medium with the addition of 25 µg/ml G. hombroniana aqueous extract. It was observed that the addition of G. hombroniana extract resulted in the inhibition of trypanosomal kinetoplast division, with no significant inhibitory effect on nuclear division. It is concluded from the current study that the aqueous extract of G. hombroniana has a potential antitrypanosomal activity through the inhibition of kinetoplast division, as one of the possible mechanisms of its antitrypanosomal effect. This plant could serve as a possible source of new antitrypanosomal compounds.

Antitrypanosomal screening and cytotoxic effects of selected medicinal plants.

Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 µg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 µg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.

Hepatoprotective activity of dried- and fermented-processed virgin coconut oil.

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.

Bixa orellana leaves extract inhibits bradykinin-induced inflammation through suppression of nitric oxide production.

OBJECTIVE: The present study was conducted to assess the anti-inflammatory effect of a crude aqueous extract of Bixa orellana leaves (AEBO) and to examine the possible involvement of nitric oxide (NO) in its anti-inflammatory mechanism. MATERIALS AND METHODS: The air-dried, powdered leaves were soaked in distilled water (1:20 w/v) at 50°C for 24 h and the supernatant obtained was freeze-dried (yield 8.5% w/w). The dosage was recorded as the mass of extract per kg b.w. of rats in all inflammatory assays (bradykinin-induced paw edema, peritoneal vascular permeability and NO assay). RESULTS: Pretreatment with AEBO for 4 consecutive days exhibited significant inhibitory activity against inflammatory models, the bradykinin-induced hind paw edema model and bradykinin-induced increased peritoneal vascular permeability at both doses in dose-dependent manner. In addition, AEBO was also found to significantly suppress the production of NO at doses of 50 and 150 mg/kg. CONCLUSION: This study provides scientific data to support the traditional use of B. orellana leaves in treating inflammation. Results from this study suggest that AEBO exerts anti-inflammatory effects. Part of this anti-inflammatory effect may be associated with its antibradykinin activity and may be related to a reduction of the NO production.

Utilizing shared interacting domain patterns and Gene Ontology information to improve protein-protein interaction prediction.

Protein-protein interactions (PPIs) play a significant role in many crucial cellular operations such as metabolism, signaling and regulations. The computational methods for predicting PPIs have shown tremendous growth in recent years, but problem such as huge false positive rates has contributed to the lack of solid PPI information. We aimed at enhancing the overlap between computational predictions and experimental results in an effort to partially remove PPIs falsely predicted. The use of protein function predictor named PFP() that are based on shared interacting domain patterns is introduced in this study with the purpose of aiding the Gene Ontology Annotations (GOA). We used GOA and PFP() as agents in a filtering process to reduce false positive pairs in the computationally predicted PPI datasets. The functions predicted by PFP() were extracted from cross-species PPI data in order to assign novel functional annotations for the uncharacterized proteins and also as additional functions for those that are already characterized by the GO (Gene Ontology). The implementation of PFP() managed to increase the chances of finding matching function annotation for the first rule in the filtration process as much as 20%. To assess the capability of the proposed framework in filtering false PPIs, we applied it on the available S. cerevisiae PPIs and measured the performance in two aspects, the improvement made indicated as Signal-to-Noise Ratio (SNR) and the strength of improvement, respectively. The proposed filtering framework significantly achieved better performance than without it in both metrics.

Screening of microfilaricidal effects of plant extracts against Dirofilaria immitis.

Canine dirofilariasis is a common tropical parasitic disease of companion animals, caused by infestation of Dirofilaria immitis filarids within the pulmonary arteries and extending into the right heart. Increased reports of adverse reactions elicited by current microfilaricidal agents against D. immitis such as neurological disorders, circulatory collapse and potential resistance against these agents, warrant the search for new agents in forms of plant extracts. The use of plant extracts in therapeutic medicine is commonly met with scepticism by the veterinary community, thus the lack of focus on its medical potential. This study evaluated the presence of microfilaricidal activities of the aqueous extracts of Zingiber officinale, Andrographis paniculata and Tinospora crispa Miers on D. immitisin vitro at different concentrations; 10mg/ml, 1mg/ml, 100 microg/ml, 10 microg/ml and 1 microg/ml within 24h, by evaluation of relative microfilarial motility as a measure of microfilaricidal activity. All extracts showed microfilaricidal activity with Z. officinale exhibiting the strongest activity overall, followed by A. paniculata and T. crispa Miers. It is speculated that the microfilaricidal mechanism exhibited by these extracts is via spastic paralysis based upon direct observation of the microfilarial motility.

SPlitSSI-SVM: an algorithm to reduce the misleading and increase the strength of domain signal.

Protein domains contain information about the prediction of protein structure, function, evolution and design since the protein sequence may contain several domains with different or the same copies of the protein domain. In this study, we proposed an algorithm named SplitSSI-SVM that works with the following steps. First, the training and testing datasets are generated to test the SplitSSI-SVM. Second, the protein sequence is split into subsequence based on order and disorder regions. The protein sequence that is more than 600 residues is split into subsequences to investigate the effectiveness of the protein domain prediction based on subsequence. Third, multiple sequence alignment is performed to predict the secondary structure using bidirectional recurrent neural networks (BRNN) where BRNN considers the interaction between amino acids. The information of about protein secondary structure is used to increase the protein domain boundaries signal. Lastly, support vector machines (SVM) are used to classify the protein domain into single-domain, two-domain and multiple-domain. The SplitSSI-SVM is developed to reduce misleading signal, lower protein domain signal caused by primary structure of protein sequence and to provide accurate classification of the protein domain. The performance of SplitSSI-SVM is evaluated using sensitivity and specificity on single-domain, two-domain and multiple-domain. The evaluation shows that the SplitSSI-SVM achieved better results compared with other protein domain predictors such as DOMpro, GlobPlot, Dompred-DPS, Mateo, Biozon, Armadillo, KemaDom, SBASE, HMMPfam and HMMSMART especially in two-domain and multiple-domain.

Diuretic properties of Orthosiphon stamineus Benth.

ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus has been used in traditional medicine for centuries especially to treat diseases of the urinary system. AIM OF THE STUDY: To investigate the diuretic activity, to elucidate its possible mechanism and to evaluate the renal effects of Orthosiphon stamineus extract. MATERIALS AND METHODS: Water extracts were administered orally at doses of 5 and 10 mg/kg to Sprague-Dawley rats and the control groups were given commercial diuretic drugs either furosemide or hydrochlorthiazide at 10 mg/kg. Urine volume, urine pH, urine density and urine electrolytes were determined every hour for 4h. Blood was assayed for glucose, albumin, blood urea nitrogen (BUN) and creatinine. RESULTS: O. stamineus extract exhibited dose-dependent diuretic activity. However, excretion of Na+ and Cl(-) was not markedly elevated, but urinary excretion of K+ was significantly increased. O. stamineus extracts slightly increased the serum BUN, creatinine and blood glucose level. Although these levels were statistically significant when compared to control, these levels were still within normal range. CONCLUSIONS: O. stamineus exhibited diuretic activity, but was less potent than furosemide and hydrochlorothiazide. Care should be taken when consuming this herb as slight increase of kidney function enzymes was recorded.

Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats.

Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.

Liver injury induced by the non-steroidal anti-inflammatory drug mefenamic acid.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat musculoskeletal disorders, inflammation and to control pain. Virtually all NSAIDs are capable of producing liver injury ranging from mild reversible elevation of liver enzymes to severe hepatic necrosis. METHODS: Mice were dosed intraperitoneally with mefenamic acid either one day at 100mg/kg and 200mg/kg, or 14 days dosing at 50mg/kg/day and 100mg/kg/day. Plasma was taken for alanine aminotransferase activity. Mice were sacrificed at the end of the study. Livers were removed and weighed. Liver samples were taken for histology. results: One-day doses of mefenamic acid revealed dose-dependent hepatocyte degeneration in the liver parenchyma. There were no significant changes in plasma alanine aminotransferase activity. Interestingly, 14-day daily doses induced hepatocellular necrosis, massive degeneration and inflammation. This was accompanied by a significant increase in plasma alanine aminotransferase activity and significant increase in the liver weight in the 100mg/kg/day mefenamic acid-dosed mice. CONCLUSION: Results from this study suggest that mefenamic acid is capable of producing hepatotoxicity and care should be taken when prescribing or using this drug.

Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study.

Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.