Protective effects of goldenseal (Hydrastis canadensis L.) on acetaminophen-induced hepatotoxicity through inhibition of CYP2E1 in rats

Katsunori Yamaura, Maki Shimada, Noriyuki Nakayama, Koichi Ueno

Pharmacognosy Research 2011 3(4):250-255

Background: Goldenseal (Hydrastis canadensis L.) inhibits various cytochrome P450 (CYP) isoforms such as CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A in vitro. High doses of acetaminophen (APAP) generate the highly reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), catalyzed mainly by CYP2E1. The aim of this study was to investigate the hepatoprotective effects of orally administrated goldenseal against APAP-induced acute liver failure (ALF) via inhibition of CYP2E1. Materials and Methods: Male Wistar rats were treated orally with goldenseal (300 and 1000 mg/kg) 2, 18, and 26 h before and 6 h after oral APAP (400 mg/kg) administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as serum APAP concentration were evaluated. Results: Goldenseal extract inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A activity, and the inhibitory effect on CYP2E1 was the strongest (IC 50 4.32 μg/mL). Treatment with goldenseal (300 mg/kg) significantly attenuated the APAP-induced increase in serum AST and ALT, and the hepatoprotective effect of goldenseal was stronger than that of silymarin (200 mg/kg). Moreover, serum APAP concentration was increased by goldenseal treatment, presumably as a result of the inhibitory effect of goldenseal on the metabolism of APAP to NAPQI. Conclusion: These results suggest that goldenseal ameliorates APAP-induced ALF and that this protection can likely be attributed to the inhibition of CYP2E1 activity, which generates the highly reactive intermediate of APAP.

Effects of the oral administration of nonpolar extract from Ardisia squamulosa Presl (Myrsinaceae) leaves on spermatogenesis in rats

Dennis D Raga, Glorina N Pocsidio, Annabelle A Herrera

Pharmacognosy Research 2011 3(4):260-265

Background: Several Ardisia species have been found to possess numerous bioactivities but their reproductive toxicity has been poorly explored. In the present study, the effects of the leaf hexane extract of Philippine indigenous Ardisia squamulosa on epididymal sperm count, %viability and %aberration of sperms and weights of seminal vesicle, cauda epididymis, and testes in addition to the weights of liver, kidney, and body were evaluated. Methods: The extracts at daily dose levels of 1, 10, and 100 mg/Kg BW in 10% polysorbate-80 in corn oil were administered by gavage for 8 successive days to 8-10 weeks old male SD rats and sacrificed after 9 days. Daily body weights and final organ weights were measured. Sperm from the cauda epididymis was extracted and measured according standard sperm parameters (sperm count, morphology, viability and membrane integrity). Results: Significant findings were the decline of left epididymal sperm count to testis weight ratio and increase in %sperm morphological aberration from both cauda epididymis obtained with the 10 mg/Kg BW dose. Conclusion: The hexane extract from Ardisia squamulosa had significant effect on sperm count but with negligible effect on sperm morphology and viability.

Acetylcholine and memory-enhancing activity of Ficus racemosa bark

Faiyaz Ahmed, JN Narendra Sharath Chandra, S Manjunath

Pharmacognosy Research 2011 3(4):246-249

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and enhancement of acetylcholine (Ach) levels in brain using acetylcholinesterase inhibitors is one of the most important approaches for the treatment of AD. Methods: In this study, aqueous extract of Ficus racemosa Linn. (Moraceae) bark having anti-infl ammatory, antioxidant, and anticholinesterase activity was evaluated for its ability to enhance Ach levels, and to ascertain its antidementia activity in rats. This work was carried out under the assumption that the F. racemosa extract may show combination of actions which could be beneficial in the treatment of AD, such as neuroprotection, attributed to antioxidant and anti-infl ammatory property and may elevate levels of Ach like Ficus hispida extract reported earlier. Results: Administration of the extract at two levels viz., 250 and 500 mg/kg signifi cantly raised (P ≤ 0.05) Ach levels in hippocampi of rats compared to control. The percentage enhancement in Ach levels was found to be 22% and 38%, respectively. Further, the extract at both dosage levels elicited signifi cant reduction (P ≤ 0.05) in transfer latency on elevated plus-maze, which was used as an exteroceptive behavioral model to evaluate memory in rats. Conclusion: It is inferred that it would be worthwhile to explore the potential of F. racemosa in the management of Alzheimer disease.

Assessment of antioxidant potentials of free and bound phenolics of Hemidesmus indicus (L) R.Br against oxidative damage

Smitha Jayaram, Shylaja M Dharmesh

Pharmacognosy Research 2011 3(4):225-231

Background: Hemidesmus indicus R.Br. is a twining shrub commonly found in India, which was known to have wide pharmacological actions. 2-hydroxy-4-methoxy-benzoic acid (HMBA) and a number of pregnane glycosides were believed to be responsible for its various bioactivities. Until now, there are no reports regarding the antioxidant properties of phenolics from H. indicus. Objective: To establish the role of phenolics in the properties of H.indicus. Materials and Methods: Hemidesmus free phenolic fraction (HDFP) and Hemidesmus bound phenolic fraction (HDBP) have been isolated from H. indicus, and the antioxidant activity was evaluated for inhibition of lipid peroxidation, DNA protection, free radical scavenging (FRS), reducing power and cytoprotective activities. Results: HDFP and HDBP exhibited potent inhibition of lipid peroxidation (IC 50 – 19.5 ±0.5 and 21.7 ±0.5 μg gallic acid equivalent – GAE/mL), FRS (IC 50 – 7 ± 0.2 and 8.6 ± 0.2 μgGAE/mL), reducing power (110.3 ± 2 and 33.5 ± 1 U/g) and red blood cell protection (14.8 ± 0.4 and 14.5 ± 0.5 mg GAE/mL). HDFP is constituted by gallic (18%), caffeic (17%), ferulic acids (16%) and HDBP by syringic acid (35%) as major phenolic acids. Besides, both HDFP and HDBP contained significant levels of HMBA; in HDFP (10%) and HDBP (57%), respectively. Results indicated a 34-and 27-folds better contribution to the antioxidant activity by HDFP and HDBP, respectively, than that of HMBA. Conclusion: Potent antioxidant activities of phenolics may be one of the mechanisms by which H.indicus is effective against several health disorders as encountered in traditional medicines.

Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

Snehal S Patel, Ramesh K Goyal

Pharmacognosy Research 2011 3(4):239-245

Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o.) for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Results: Injection of STZ produced significant loss of body weight (BW), polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUC glucose level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. Conclusion: The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes.

Screening of radical scavenging activity and polyphenol content of Bulgarian plant species

Milena Nikolova

Pharmacognosy Research 2011 3(4):256-259

Background: Discovery of new plant species with antioxidant properties is a priority of many research teams. Most of the species included in this study are unstudied for antioxidant properties, but they are taxonomically related to reference plants with well-documented antioxidant activity. Materials and Methods: Free radical scavenging activity of plant extracts was evaluated using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. An aluminum chloride colorimetric method was used for flavonoid determination. The amount of phenolic compounds in the extracts was estimated by using the Folin-Ciocalteu reagent. Results: As a result of screening, it was found that the significant antioxidant properties possess several unstudied until now plant species (Veronica bellidioides L., V. kellereri Deg. et Urm, V. vindobonensis (M. Fisher) M. Fisher,
V. beccabunga L., V. rhodopaea L., V. austriaca (Velen.) Degen., Clinopodium vulgare L., Stachys recta L., Clematis vitalba L., and Xeranthemum annum L.). The antioxidant potential of the new species is comparable to that of reference medicinal plants. Conclusions: The existing data presented here provide new information for antioxidant potential of plant species that have not been traditionally used as medicinal plants.

Indigenous anti-ulcer activity of Musa sapientum on peptic ulcer

P Prabha, Thirunethiran Karpagam, B Varalakshmi, A Sohna Chandra Packiavathy

Pharmacognosy Research 2011 3(4):232-238

Background: Peptic ulcer disease (PUD), encompassing gastric and duodenal ulcers is the most prevalent gastrointestinal disorder. The pathophysiology of PUD involves an imbalance between offensive factors like acid, pepsin and defensive factors like nitric oxide and growth factors. The clinical evaluation of antiulcer drugs showed tolerance, incidence of relapses and side-effects that make their efficacy arguable. An indigenous drug like Musa sapientum possessing fewer side-effects is the major thrust area of present day research, aiming at a better and safer approach for the management of PUD. Material and Methods: The unripe plantain bananas (Musa sapientum) were shade-dried, powdered and used for phytochemical analysis and as antiulcer drug. In our present study Group I rats served as control and were treated with saline, Group II was indomethacin-induced ulcerated rats, Group III received aqueous extract of Musa sapientum along with indomethacin and Group IV received esomeprazole along with indomethacin for 21 days. The anti-ulcerogenic activity was investigated by performing hematological, mucosal, antioxidant profile in comparison with the standard drug esomeprazole. Results: Our findings from High – Performance Thin Layer Chromatography (HPTLC) analysis showed that Musa sapientum has an active compound a monomeric flavonoid (leucocyanidin) with anti-ulcerogenic activity. Results were expressed as mean ± SD. All our results are in congruous with the results of standard drug esomeprazole. Conclusion: It could be clearly concluded that administration of the aqueous extract of Musa sapientum at the dose used in this study tends to ameliorate ulcers. Its use in indigenous medicine should be scientifically scrutinized with further research.

Antioxidant and antibacterial properties of green, black, and herbal teas of Camellia sinensis

Eric W.C Chan, Eu Ying Soh, Pei Pei Tie, Yon Peng Law

Pharmacognosy Research 2011 3(4):266-272

Background: The role of non-polymeric phenolic (NP) and polymeric tannin (PT) constituents in the antioxidant and antibacterial properties of six brands of green, black, and herbal teas of Camellia sinensis were investigated. Materials and Methods: Total phenolic content (TPC) and ascorbic acid equivalent antioxidant capacity (AEAC) were assessed using the Folin-Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, respectively. Minimum inhibitory dose (MID) against Gram-positive Micrococcus luteus, Staphylococcus aureus, and Bacillus cereus, and Gram-negative. Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa was assessed using the disc-diffusion method. Teas were extracted with hot water successively three times for one hour each time. The extracts were fractionated using Sephadex LH-20 column chromatography to obtain the NP and PT constituents. Results: Extraction yields ranged from 12 to 23%. Yields of NP fractions (70−81%) were much higher than those of PT fractions (1−11%), suggesting that the former are the major tea components. Ranking of antioxidant properties of extracts was green tea>black tea>herbal tea. For all six teas, antioxidant properties of PT fractions were significantly higher than extracts and NP fractions. Extracts and fractions of all six teas showed no activity against the three Gram-negative bacteria. Green teas inhibited all three Gram-positive bacteria with S. aureus being the least susceptible. Black and herbal teas inhibited the growth of M. luteus and B. cereus, but not S. aureus. The most potent were the PT fractions of Boh Cameron Highlands and Ho Yan Hor with MID of 0.01 and 0.03 mg/disc against M. luteus. Conclusion: Results suggested that NP constituents are major contributors to the antioxidant and antibacterial properties of teas of C. sinensis. Although PT constituents have stronger antioxidant and antibacterial properties, they constitute only a minor component of the teas.

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