Open Access Opinion Article

Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview

A.S. V. Prasad

International Journal of Biochemistry Research & Review, Page 1-12
DOI: 10.9734/ijbcrr/2019/v26i230094

Fibrates are a class of medication that mainly lowers the blood triglyceride levels. They reduce the LDL and increase the levels of HDL C, in the blood. Clofibrate, the first member to be discovered  in 1962 , and introduced in USA in 1967, is withdrawn in 2002, due to unexplained hepatomegaly, hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early 1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome,  macrovascular and microvascular diabetic complications  like stroke, myocardial infarction, peripheral vascular disease  and  diabetic  retinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) ,  FIELD trail.  (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,   ACCORD -Lipid trial  (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and  BIP (Bezafibrate Infarction Prevention Study)  trial and angiography trials, like LOCAT (Lopid Coronary Angiography Trial)  and BECLAIT (Bezafibrate Coronary Atherosclerosis Intervention Trial) demonstrated the  beneficial effects of gemfibrozil and fenofibrate. 
Their mechanism of action remained obscure for three decades, ie till 1990s, when their mode of action was found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)
 modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involving  the various  enzymes like LCAT (Lecithin-cholesterol acyl transferase)  and CYP7A1 etc.  (cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) ) ,  transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP, OATP (Na+-dependent taurocholate transporter / organic anion transporters) . These are the.) and nuclear factors like LXR, PPAR alfa etc. (liver orphan receptor α , and peroxisome proliferative nuclear factor) , in relation to the mechanisms  of action of fibrates are discussed . Areas of current interests in literature are briefed.

Open Access Original Research Article

Evaluation of the Toxicity of the Ethanol Extract 70% of the Bark of Terminalia macroptera (Combretaceae) on Whistar Rats

Traore Youssouf, Koné Monon, Ouattara Abou, Bahi Calix, Nathalie Kouadio Guessennd, Coulibaly Adama, Dosso Mireille

International Journal of Biochemistry Research & Review, Page 1-17
DOI: 10.9734/ijbcrr/2019/v26i230090

Nowadays, many medicinal plants have proved effective in combating the phenomenon of bacterial multi-resistance against conventional antibiotics. However, the use of these plants, traditionally is done without precise doses. And this inaccuracy of dose is a real problem of traditional medicine. Thus prospecting for empirically administered plant extract requires dosage monitoring to avoid the risk of a fatal therapeutic accident. It is in this context that the study of the toxicity of Terminalia macroptera which presents itself as an anti-infectious agent, capable of overcoming certain strains of antibiotic-resistant bacteria has been initiated. The objective of this study is to evaluate the toxicity of 70% ethanol extract of T.macroptera in rats and to deduce its safety. With regard to the evaluation of the toxicity, rats were used whose mass varies between 100 and 170 grams. Then, using OECD Guideline 425, (2006), acute toxicity was achieved. Then the 100, 300 and 500 mg / kg bm doses were used in sub-acute toxicity to evaluate biochemical and hematological parameters. The results show an LD50> 5000 mg / kg bm. Therefore, according to the OECD classification, the hydroethanolic extract belongs to category 5, non-toxic substances. Also, the biochemical and hematological results revealed that the extract did not change at any time at P <0.05, biochemical marker levels (UREE, ASAT, ALAT, CK and LDH), reflecting vital organs of the body. So the extract would have no effect on the heart, liver and kidneys. 70% ethanol extract of T. macroptera would be safe for use as a drug and therefore could contribute to the production of Traditionally Enhanced Medicines (MTAs).

Open Access Original Research Article

Effects of Black Seed (Nigella sativa) and Uziza Leaf (Piper guineense) on Electrolytes, Urea and Creatinine of Wistar Albino Rats

Okoye Ngozi Franca, Igwilo, Elvis Ikenna

International Journal of Biochemistry Research & Review, Page 1-10
DOI: 10.9734/ijbcrr/2019/v26i230092

Aim: For centuries, plant and plant products have played a pivotal role in medication. This study evaluated the effect of aqueous extract of black seed (Nigella sativa) and uziza leaf (Piper guineense) on electrolytes, urea and creatinine of Wistar rats.

Materials and Methods: Twenty-five Wistar rats were used for the study; the rats were arranged into five groups with five rats each. Sucrose and margarine were used to induce hyperglycemia and hyperlipidemia respectively on the rats with the exception of the rats in the positive control group.  The rats in the negative control were induced using the sucrose and margarine but were not treated using the aqueous extracts. The rats in the uziza group were treated with 2 ml of uziza aqueous leaf extract, while the rats in the black seed group were treated with 2 ml of black seed aqueous extract. The rats in the black seed & uziza leaf group were treated with 2ml of the combined aqueous extract.

Results: The results showed that the extracts had a decreasing effect which was time dependent on the electrolytes. The highest decrease was obtained on the third week of feeding compared to the control (P=.05). The sodium levels (mmol/L) showed for the negative control (198.23 ± 1.96), positive control (108.15 ± 1.60), uziza leaf (98.28 ± 4.17), black seed (101.67 ± 4.24), black seed & uziza (90.83 ± 2.14).  The decrease for potassium levels (mEq/L) showed for the negative control (0.90 ± 0.06), positive control (0.05 ± 0.10), uziza leaf (0.07 ± 0.18), black seed (0.06 ± 0.19), black seed & Uziza (0.05 ± 0.10). Furthermore, the extracts also had a reducing effect on urea and creatinine levels with the highest reduction obtained on the third week (p=0.05).  The urea levels (mmol/L) showed for the negative control (26.84 ± 0.05), positive control (15.15 ± 1.20), uziza leaf (12.83 ± 0.98), black seed (12.16 ± 2.01), black seed & uziza (11.48 ± 1.78). The extracts also decreased creatinine levels (mmol/L) with the negative control (284.58 ± 0.33), positive control (182.73 ± 3.67), uziza leaf (194.16 ± 18.30), black seed (167.34 ± 14.66), black seed & uziza (174.46 ± 10.66). 

Conclusion: The extracts significantly decreased the elevated electrolytes levels and therefore uziza leaf and black seed can be used to restore kidney function.

Open Access Original Research Article

Ameliorative Activity of Pumpkin (Cucurbita maxima) Fruit and Seeds Powders on Diabetic, Oxidative and Pancreatic Status in Rats

Alyae, M. S. Gabal

International Journal of Biochemistry Research & Review, Page 1-9
DOI: 10.9734/ijbcrr/2019/v26i230093

Background: Diabetes mellitus is the one of the most common endocrine diseases that is characterized by hyperglycemia, altered metabolism with an increased risk of much complications. Besides drugs classically used for the treatment of diabetes several species of plants have been described as having a hypoglycemic activity with decreased side effects.

Aim of the Work: This work aimed to investigate the possible anti-diabetic effect of oral administration of pumpkin (Cucurbita maxima) fruit flesh and seeds powders on Streptozotocin induced diabetic rats via studying blood glucose levels, oxidative biomarkers as well as islets of Langerhans structure changes.

Materials and Methods: 60 adult albino rats of Sprague-Dawely strains (200±5 gm) were classified into five groups of ten animals each except diabetic control group was composed of twenty rats as follow Group I: healthy control; Group II: diabetic control ,Group III, IV and V: diabetic rats received 2 g pumpkin fruit, seeds, fruit and seeds mixture powders respectively /kg body weight daily by oral intubation.

Results: The results of present study showed that pumpkin powders caused significant improvements (P≤0.05) in blood glucose, insulin levels and glycated hemoglobin percent compared to diabetic control group. Also pumpkin powders improved antioxidants activities and healed Langerhans islets by increasing their number and size in comparison with diabetic control group. Conclusion: The present study showed that pumpkin powders may normalize the various biochemical and pancreatic tissues abnormalities resulted due to diabetes metabolic disorders and it is a source of potent anti-diabetic agent. The diabetic rats that were administered with the pumpkin fruit powder, exhibited the highest improvements.

Open Access Original Research Article

Antibacterial Activity of Locally Prepared Herbal Cough Extracts against Klebsiella pneumoniae and Streptococcus pneumoniae

Atuheirwe Maxine, Jacob Stanley Iramiot

International Journal of Biochemistry Research & Review, Page 1-9
DOI: 10.9734/ijbcrr/2019/v26i230095

Aim: Cough due to Klebsiella pneumoniae and Streptococcus pneumoniae is currently managed by conventional antibiotics and herbal extracts in Uganda. However, much as these herbal extracts are extensively used, their antibacterial activity is not known. This study aimed at determining the antibacterial activity of the selected locally prepared herbal cough extracts against two bacterial strains i.e. Klebsiella pneumoniae (ATCC 700603), and Streptococcus pneumoniae (ATCC 49619).

Methods: The herbal cough extracts were screened for antibacterial activity using Agar-well diffusion method for determining zone of inhibition, macro broth dilution method for Minimum Inhibitory Concentration (MIC) determination and Streak plate method for Minimum Bactericidal Concentration (MBC).

Results: In vitro evaluation of antibacterial activity of the 5 brands of herbal cough extracts against K. pneumoniae and S. pneumoniae   revealed that all extracts possessed significant antimicrobial effects against all microorganisms tested (p < 0.05). However, MM04 (35.6±0.0) mm and MM03 (33.6±1.5) mm had maximum zones of inhibition as compared to other herbal extracts against K. pneumoniae and S. pneumoniae respectively. Average MIC results for extracts against K. pneumoniae   indicated that MM01 had the highest MIC (2.5000 mg/ml) while MM03 had the least MIC (0.0625 mg/ml). Average MIC results for extracts against S. pneumoniae showed MM01 had the highest MIC (2.0000 mg/ml) while MM03 3 had the least MIC (0.0438 mg/ml). Average MBC results for extracts against K. pneumoniae indicated that MM01 had the highest MBC (4.000 mg/ml) while MM03 had the least MBC (0.030 mg/ml). Average MBC results for extracts against S. pneumoniae showed MM01 had the highest MBC (4.000 mg/ml) while MM03 had the least MBC (0.033 mg/ml).

Conclusion: The results obtained in present study were revealed that locally prepared herbal extracts had significant antibacterial activity. Hence they can be used as promising alternatives of antibiotics used against Respiratory Tract Infections due to K. pneumoniae and S. pneumoniae.