Hura crepitans stem bark extract: A potential remedy to sub-acute liver damage.

ETHNOPHARMACOLOGICAL SIGNIFICANCE AND AIM: Hura crepitans is commonly used to treat liver diseases in Nigeria and Ghana. Previous studies have supported its ethnomedicinal use in protecting the liver. The present study aimed at assessing the effect of H. crepitans stem bark on the subacute carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The protective activities of ethanolic extract of H. crepitans stem bark was evaluated in CCl4-induced subacute liver damage in rats (1:1 v/v in olive oil, intraperitoneally (i.p.), twice weekly for 8 weeks). Blood samples were obtained from the rats and used for some biochemical analysis such as liver function test (Aspartate transaminase, AST; Alanine aminotransferase, ALT; and Alkaline phosphatase, ALP), liver fibrotic indices (Aspartate platelet ratio index, APRI; AST/ALT and AST/PLT ratios) and oxidative stress markers (Malondialdehyde, MDA; Reduced glutathione, GSH; Glutathione S-transferase, GST; Glutathione peroxidase, GPx; and superoxide dismutase, SOD). Histopathological analyses were carried out to determine the expression of pro-inflammatory (NF-κB, COX-2, IL-17 and IL-23) using immunohistochemical techniques. RESULTS: Oral administration of H. crepitans to CCl4-induced hepatic injured rats significantly decreased oxidative stress, increased the levels of SOD, GSH, GST and GPx with reduced MDA levels. The plant also mitigated liver injury as evidenced in the significantly reduced levels of AST, ALT and ALP, while it inhibited the inflammatory process via the inhibition of NF-κB, and consequently down-regulateed the pro-inflammatory cytokines COX-2, IL-17 and IL-23, respectively. Biochemical observations were supported by improvement in liver microarchitecture. CONCLUSION: The Hura crepitans demonstrated antioxidant, antiinflammatory and antifibrotic effect in hepatic injured rats. The study in a way justifies the traditional use of the plant for the treatment of subacute liver diseases in Nigerian Traditional medicine.

Modulation of Oxidative Stress and Inflammatory Cytokines as Therapeutic Mechanisms of Ocimum americanum L Extract in Carbon Tetrachloride and Acetaminophen-Induced Toxicity in Rats.

Liver diseases have now become a global canker due to increasing drug abuse and several viral infections. The current medicines on the market are woefully inadequate and limited in the application against these diseases. Fortunately, medicinal plants continue to serve as a potential source of drug discovery that could be explored to improve the situation. The present study, therefore, evaluated the hepatoprotective activities of the aqueous extract of various parts (leaves, flower and stem) of Ocimum americanum L on carbon tetrachloride (CCl4)- and acetaminophen-induced toxicity in rats. The protective effect of the plant was assessed using biochemical parameters, histology, levels of liver antioxidants, and expression of some pro-inflammatory cytokines (NF-κß and IL-1) in the liver. The leaves and stem extracts, orally administered for 7 days at 250 mg/kg, effectively prevented CCl4-induced elevation of serum biochemical parameters, prooxidants, as well as the expression of NFk-B and IL-1, which were comparable to Silymarin (standard drug). A comparative histopathological analyses of the liver exhibited virtually normal architecture compared with CCl4-treated group. The findings showed that the hepatoprotective effect of Ocimum americanum was probably due to the inhibition of oxidative stress and downregulation of proinflammatory cytokines by the effective parts of the medicinal plant.

Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs.

Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig's pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 µg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic.

Polyphenol-Rich Fraction of Parquetina nigrescens Mitigates Dichlorvos-Induced Cardiorenal Dysfunction Through Reduction in Cardiac Nitrotyrosine and Renal p38 Expressions in Wistar Rats.

Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.

Antioxidant Potential of the Methanol Extract of Parquetina nigrescens Mediates Protection Against Intestinal Ischemia-Reperfusion Injury in Rats.

Parquetina nigrescens is a medicinal herb with recognized antioxidant properties and potential to alleviate conditions associated with oxidative stress, including gastric ulcers. We investigated the protective potential of methanol extract of Parquetina nigrescens (MEPN) against ischemia-reperfusion injury in the intestine of rats. Thirty (30) male Wistar albino rats were randomly assigned into five groups with Group I made up of control rats and Group II consisting of rats experimentally subjected to ischemia and reperfusion (IR) by clamping of the superior mesenteric artery (SMA) for 30 minutes and 45 minutes, respectively. Groups III and IV rats also had IR, but were initially pre-treated with MEPN at 500 mg/kg and 1000 mg/kg respectively, for seven days. Rats in Group V were also pre-treated with Vitamin C, for seven days, before induction of IR. The results showed marked reduction in intestinal epithelial lesions in groups treated with MEPN, compared to the IR group which had severe villi erosion, inflammatory cell infiltration and hemorrhages. There were significant increases in Malondialdehyde (MDA) and significant reductions in reduced glutathione (GSH) and Glutathione S-transferase (GST) activity with IR injury, while pre-treatment with either MEPN or Vitamin C prevented these effects. Increases in Glutathione peroxidase (GPX), Catalase (CAT) and Superoxide dismutase (SOD) with IR provided evidence for adaptive responses to oxidative injury during IR and preservation of enzyme activity by MEPN and Vitamin C. Taken together, Parquetina nigrescens provided considerable alleviation of intestinal injury produced by IR, at values much as effective as that offered by Vitamin C.

Modulatory effects of cod liver oil on the antioxidant status and oxidative stress induced by acute exposure to carbon tetrachloride (CCL4) in experimental animal models.

BACKGROUND: This work was designed to investigate the modulatory effects of cod liver oil on the acute exposure to carbon tetrachloride (CCL4) in experimental animal models. METHODS: Markers of oxidative stress, enzymic and non-enzymic antioxidants were assessed in the liver and kidney. RESULTS: The results showed significant (p<0.05) increase in the total protein of the kidney of rats pretreated with cod liver oil compared to the control and CCL4-treated groups. Acute exposure to CCL4 also significantly (p<0.05) increased thiobarbituric acid reactive substances in the liver of rats treated with cod liver oil compared to the CCL4-treated rats. The reduced glutathione (GSH) content in the liver of the rats administered with CCL4 decreased significantly compared to that in all other treatment groups, whereas rats pretreated and co-administered with cod liver oil and CCl4 showed significant (p<0.05) improvement in the liver GSH content. The catalase (CAT) activity in the liver of rats exposed to CCL4 decreased (p<0.05) significantly, whereas the activity increased (p<0.05) significantly in the rats that were treated with cod liver oil compared to the CCl4 only-treated group. The percentage inhibition of superoxide dismutase (SOD) increased (p<0.05) significantly in the liver of rats administered cod liver oil compared to the CCL4-treated rats and the control. CONCLUSIONS: Taken together, cod liver oil attenuates CCL4-induced toxicity and oxidative stress in the liver but not in the kidney of rats acutely exposed to CCL4.

Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage.

INTRODUCTION: This study was designed to evaluate the ameliorative and hypocholesterolemic effects of dietary supplementation of Cnidoscolus aconitifolius leaf meal (CALM) on hepatic injury and kidney injury associated with protein energy malnutrition (PEM). MATERIALS AND METHODS: In this study, PEM was induced in weaning male Wistar albino rats by feeding them with low protein diet for 2 weeks. The effects of several recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed were assessed in PEM rats. Plasma biochemical parameters were assessed as well. RESULTS: After the induction of PEM, results obtained showed significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (T.P), total bilirubin (T.Bil), triglycerides, total cholesterol, low density lipoproteins (LDL), blood urea nitrogen (BUN), and creatinine with significant reduction in plasma high density lipoproteins (HDL), albumin, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)), bicarbonate (HC03(-)), and phosphate (P04(2-)) in PEM rats. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks caused significant (P < 0.05) reduction in plasma values of ALP, ALT, AST, T.bil, T.P., LDL, total cholesterol, triglycerides, BUN, creatinine, and significant increase in HDL and complete restoration of plasma electrolytes. CONCLUSIONS: C. aconitifolius in protein deficient diets has a protective role against hepatic injury and renal damage associated with PEM.

Toxicological evaluations of methanolic extract of Moringa oleifera leaves in liver and kidney of male Wistar rats.

BACKGROUND: This study was conducted to investigate toxicological effects associated with prolonged consumption of Moringa oleifera leaves as a beverage. METHODS: Thirty rats were used in this study. They were grouped into five groups of six rats. Rats in group I received 2 mL/kg body weight (b.w.) of corn oil (vehicle). Animals in groups II, III, IV and V received 50, 100, 200 and 400 mg/kg b.w. of methanolic extract of M. oleifera (MEMO) for 8 weeks. Serum collected was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, blood urea nitrogen (BUN) and creatinine. RESULTS: There was a significant (p<0.05) increase in serum total protein and globulin in a dose-dependent manner. Rats that received MEMO at 200 and 400 mg/kg b.w. showed a significant (p<0.05) increase in serum ALT, AST, BUN and creatinine which pointed to hepatic and kidney damage. All experimental animals that received MEMO had a significant (p<0.05) increase in body weight in a dose-dependent manner. CONCLUSIONS: This study therefore confirms for the first time that chronic administration of M. oleifera leaves might predispose to hepatic and kidney damage.

Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora.

BACKGROUND: This study was designed to investigate the hepatoprotective and in vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria breviflora (LB) in experimental animals. METHODS: Forty nine Wistar albino rats were divided into seven groups of seven. Group I served as the control group; rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone; Groups III-VI received different concentrations of plant extract (100, 250 and 500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a reference hepatoprotective agent. RESULTS: There was a significant (p<0.05) increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level decreased significantly. Pretreatment with LB extract led to a significant (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and H2O2generation. The activities of marker enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II). CONCLUSIONS: The present study suggested that treatment with LB extract enhances the recovery from CCL4 induced hepatic damage and oxidative stress via its antioxidant and hepatoprotective properties.

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract.

OBJECTIVE: To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). METHODS: Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. RESULTS: Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. CONCLUSIONS: The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug.

Cnidoscolus aconitifolius leaf extract protects against hepatic damage induced by chronic ethanol administration in Wistar rats.

AIMS: This study focused on the possible protective effect of Cnidoscolus aconitifolius leaf extract (CA) against hepatic damage induced by chronic ethanol administration in rats. METHODS: Male Wistar rats were distributed into seven groups of six rats each. The first group was the control, second group received 20% ethanol-only (7.9 g/kg), third and fourth groups were pre-treated with CA (100 and 200 mg/kg, respectively) before treatment with ethanol. The fifth and sixth groups received CA and kolaviron (KV; 200 mg/kg), respectively, while the seventh group received KV and ethanol. KV served as the reference antioxidant. RESULTS: Ethanol-treated rats had significantly (P < 0.05) elevated serum and liver post-mitochondrial malondialdehyde, an index of lipid peroxidation. Ethanol toxicity lowered the antioxidant defense indices, such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Specifically, the activities of hepatic SOD and CAT decreased by 48 and 51%, respectively, while the level of GSH decreased by 56%. In addition, serum total cholesterol, triglycerides and low-density lipoproteins-cholesterol levels were significantly (P < 0.05) elevated in ethanol-treated rats. Also, significant (P < 0.05) elevation in serum alanine and aspartate aminotransferases, and γ-glutamyl transferase activities were observed in ethanol-treated rats. Supplementation with CA significantly (P < 0.05) decreased the activities of liver marker enzymes, stabilized the lipid profiles and restored the antioxidants status of ethanol-treated rats. The activities of CA were comparable with KV in the ethanol-treated rats. This observation was supported by histopathological examination of liver slides. CONCLUSION: These findings suggest the hepatoprotective and antioxidant effects of CA leaf extract, which offered protection against ethanol-induced toxicity.

Phytochemical investigation and proximate analysis on the leaves of Cnidoscolus aconitifolius.

The study was designed to carry out the phytochemical screening and the proximate analysis of Cnidoscolus aconitifolius leaves. The results obtained showed the presence of tannins, saponin, alkaloids, and flavonoids with the absence of glycosides. The proximate analysis and mineral composition of C. aconitifolius leaves showed high levels of crude protein, ash, and fiber, in that order, and low fat content with concomitant presence of minerals such as sodium, manganese, magnesium, potassium, calcium, iron, phosphate, and zinc. The leaves of C. aconitifolius have high nutrient potentials and could be used as nutraceuticals in complementary foods, especially in sub-Saharan Africa.

Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice.

BACKGROUND: Ethanolic leaf extract of Cnidoscolus aconitifolius was evaluated for analgesic and anti-inflammatory activities. METHODS: The analgesic activity of the extract was assayed by the formalin-induced paw licking test, acetic acid-induced abdominal writhing and hot plate test, whereas its anti-inflammatory activity was determined by its effects on carrageenan-induced paw edema. RESULTS: The extract of C. aconitifolius prolonged the reaction time of mice to pain in a dose-dependent manner. The optimal analgesic effect of the extract was obtained when the extract was administered 90 min before pain stimulation in the hot plate test. The extract of C. aconitifolius (100 or 200 mg/kg b.w.) inhibited acetic acid-induced irritation of paws of rats comparably with that of indomethacin (10 mg/kg b.w.) and had significantly lower mean number of lickings of paws than the control rats (p<0.05). Carrageenan-induced edema was markedly inhibited (p<0.05) by the extracts (100 and 200 mg/kg b.w.) when compared with control rats. Inhibition of writhing movement in rats administered with the extract was lower (p<0.05) than rats administered with indomethacin but its effect was dose-dependent. CONCLUSIONS: Our investigations show that C. aconitifolius possesses significant anti-inflammatory and analgesic activities that should be explored.

Molecular targets of [6]-gingerol: Its potential roles in cancer chemoprevention.

A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic activities. [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti-inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha) expression through suppression of I-kappaB alpha (IkappaBalpha) phosphorylation, nuclear factor kappa B (NF-kappaB) nuclear translocation. Other antiproliferative mechanisms of [6]-gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]-gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic.

Curcumin: from food spice to cancer prevention.

Curcumin [1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6 heptadiene-3, 5-dione] is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. It is known to have a variety of biologic and pharmacologic activities, including anti-inflammatory, anti-oxidant, and anticarcinogenic potential. It is a potent inhibitor of cytochrome P450 with capacity to simultaneously induce detoxifying enzymes such as glutathione S-transferase and as such may find application as a chemopreventive agent. Curcumin is a potent inhibitor of cyclooxygenase-2, lipooxygenase, ornithine decarboxylase (ODC), nuclear factor-kappaB, c-Jun N-terminal kinase and protein kinase C and has also been demonstrated to play a vital role against pathological conditions such as cancer, atherosclerosis, and neurodegenerative diseases.