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1. A new herbal combination, Etana, for enhancing erectile function: an efficacy and safety study in animals.

Qinna N, Taha H, Matalka KZ, Badwan AA.

[1] Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan [2] Central Research Lab, The Jordanian Pharmaceutical Manufacturing Co. PLC (JPM), Naor, Jordan.

We present herein a new herbal combination called Etana that is composed of five herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia (Tongkat Ali), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola) and flower pollen extracts. Most of the above-mentioned extracts have a long historical and traditional use for erectile dysfunction (ED). On the basis of the mechanism of action of each of the above, a combination is introduced to overcome several physiological or induced factors of ED. This study was conducted to show an enhancement of erectile function in male rats. The animals were observed for 3 h after each administration for penile erection, genital grooming and copulation mounting, and the penile erection index (PEI) was calculated. The maximum response was observed at the concentration of 7.5 mg kg(-1) of Etana. At a 7.5 mg kg(-1) single dose, the percentage of responding rats was 53+/-7 with a PEI of 337+/-72 compared with 17+/-6 with a PEI of 30+/-10 for control animals. This PEI was significantly (P<0.001) higher than each single component and than the sum of any two herbal components of Etana. When compared with sildenafil citrate, Etana induced more pronounced PEI than 0.36 mg kg(-1), but similar to 0.71 mg kg(-1) of sildenafil. Furthermore, full acute and sub-acute toxicity studies showed no toxic effects of Etana. In conclusion, this study describes a new and safe combination of herbal components that enhance erectile function in male rats. Clinical studies are warranted for evaluating Etana's significance in ED.International Journal of Impotence Research advance online publication, 4 June 2009; doi:10.1038/ijir.2009.18.

PMID: 19494825 [PubMed - as supplied by publisher]


2. Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia.

Krishnamurthy RG, Senut MC, Zemke D, Min J, Frenkel MB, Greenberg EJ, Yu SW, Ahn N, Goudreau J, Kassab M, Panickar KS, Majid A.

Division of Cerebrovascular Diseases and Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan.

Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate- or beta-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia. (c) 2009 Wiley-Liss, Inc.

PMID: 19382233 [PubMed - as supplied by publisher]


3. An improved HPLC-UV method for the simultaneous quantification of triterpenic glycosides and aglycones in leaves of Centella asiatica (L.) Urb (APIACEAE).

Rafamantanana MH, Rozet E, Raoelison GE, Cheuk K, Ratsimamanga SU, Hubert P, Quetin-Leclercq J.

IMRA (Institut Malgache de Recherches Appliquées), BP 3833, 101 Antananarivo, Madagascar; Laboratoire de Pharmacognosie, Unité CHAM, LDRI (Louvain Drug Research Institute), UCL (Université catholique de Louvain), Av. E. Mounier 72, 1200 Bruxelles, Belgium.

The simultaneous quantification of madecassoside, asiaticoside, madecassic acid and asiatic acid in Centella asiatica by HPLC-UV is proposed. Asiaticoside was used as reference for the quantification of heterosides and asiatic acid for aglycones. The evaluation of the extraction efficiency of the four molecules led to use Soxhlet extraction for 8h. The method was validated and was found to be accurate in the concentration range of 1.0-3.0mg/ml for asiaticoside and 0.5-2.0mg/ml for asiatic acid with CV <3% for all investigated compounds. LOD and LOQ were, respectively, 0.0113 and 1.0mg/ml for asiaticoside and 0.0023 and 0.5mg/ml for asiatic acid. This method was shown to be convenient for routine analysis of samples of C. asiatica.

PMID: 19349219 [PubMed - as supplied by publisher]


4. Modulation of lipid metabolism by Centella asiatica in oxidative stress rats.

Hussin M, Hamid AA, Mohamad S, Saari N, Bakar F, Dek SP.

Dept of Food Science, Faculty of Food Science and Biotechnology, Univ Putra Malaysia, Serdang, Selangor, Malaysia.

A study was carried out to investigate the effects of Centella asiatica leaf on lipid metabolism of oxidative stress rats. The rats were fed 0.1% hydrogen peroxide (H(2)O(2)) with either 0.3% (w/w) C. asiatica extract, 5%C. asiatica powder (w/w), or 0.3% (w/w) alpha-tocopherol for 25 wk. Results of the study showed that C. asiatica powder significantly (P < 0.05) lowered serum low-density lipoprotein compared to that of control rats (rats fed H(2)O(2) only). At the end of the study C. asiatica-fed rats were also found to have significantly (P < 0.05) higher high-density lipoprotein and lower triglyceride level compared to rats fed only normal diet. However, cholesterol level of rats fed both C. asiatica extract and powder was found to be significantly (P < 0.05) higher compared to that of control rats. It was interesting to note that consumption of C. asiatica significantly decreased body and liver weights of the rats. Histological examinations revealed no obvious changes in all rats studied. Quantitative analysis of C. asiatica leaf revealed high concentration of total phenolic compounds, in particular, catechin, quercetin, and rutin.

PMID: 19323754 [PubMed - in process]


5. In Vitro and In Vivo Modulation of Cartilage Degradation by a Standardized Centella asiatica Fraction.

Hartog A, Smit HF, van der Kraan PM, Hoijer MA, Garssen J.

Danone Research, P.O. Box 7005, 6700 CA Wageningen, The Netherlands. anita.hartog@danone.com.

Osteoarthritis (OA) is a degenerative joint disease in which focal cartilage destruction is one of the primary features. The present study aims to evaluate the effect of a Centella asiatica fraction on in vitro and in vivo cartilage degradation. Bovine cartilage explants and bovine chondrocytes cultured in alginate were stimulated with IL-1beta in the presence or absence of different concentrations (2, 5 and 10 mug/ml) of a standardized Centella asiatica triterpenes (CAT) fraction. The CAT fraction inhibited the IL-1beta-induced proteoglycan (PG) release and nitric oxide (NO) production by cartilage explants in a dose-dependent manner. The IL-1beta-induced reduction in PG synthesis and proliferation of chondrocytes cultured in alginate were counteracted by the CAT fraction at a concentration of 10 mug/ml. In a zymosan-induced acute arthritis model, the CAT fraction inhibited PG depletion without modulating joint swelling and inflammatory cell infiltration. In conclusion, the present study demonstrated for the first time that the tested Centella asiatica fraction was able to inhibit the zymosan-induced cartilage degradation in vivo without affecting the zymosan-induced inflammatory cell infiltration and joint swelling. The in vitro data indicate that the cartilage protective activity might at least partially be induced by the inhibition of NO production. The overall results indicate a possible disease modifying osteoarthritic activity of the Centella asiatica fraction.

PMID: 19307458 [PubMed - in process]


6. Determination of asiatic acid in beagle dog plasma after oral administration of Centella asiatica extract by precolumn derivatization RP-HPLC.

Zheng XC, Wang SH.

Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.

A novel precolumn derivatization reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV-vis detection for the quantitative determination of total concentration of asiatic acid (AA) in beagle dog plasma is described. AA was extracted with n-hexane-dichloromethane-2-propanol (20:10:1, v/v/v) from plasma, which had been hydrolyzed by acid and derivatized with p-Toluidine. Chromatographic separation was achieved on a C(18) column using gradient elution in a water-methanol system. Detection was set at UV wavelength of 248nm. A calibration curve ranging from 0.01 to 1.5microg/mL was shown to be linear, and the lower limit of quantification (LLOQ) was 0.01microg/mL. The intra- and inter-day precisions which were determined by three different concentrations (0.05, 0.2 and 0.8microg/mL) ranged from 4.4% to 13.1% and 4.6% to 14.2%, respectively. Mean extraction recoveries were no less than 65% for AA and ursolic acid (IS). Plasma samples containing asiatic acid were stable for 30 days at -20 degrees C. The method was successfully applied to a pharmacokinetic study in beagle dogs after oral administration of Centella asiatica extract, and the main pharmacokinetic parameters obtained were: T(1/2), 4.29h; T(max), 2.70h; C(max), 0.74microg/mL; AUC(0-t) and AUC(0-infinity), 3.74 and 3.82microgh/mL, respectively.

PMID: 19167274 [PubMed - indexed for MEDLINE]


7. Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice.

Li H, Gong X, Zhang L, Zhang Z, Luo F, Zhou Q, Chen J, Wan J.

Department of Pharmacology, Chongqing Medical University, Chongqing 400016, People's Republic of China.

Madecassoside (MA), a triterpenoid product isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study was undertaken to determine whether madecassoside (MA) is efficacious against collagen-induced arthritis (CIA) in mice and its possible mechanisms. DBA/1J mice were immunized with bovine type II collagen and treated with MA (3, 10 and 30 mg/kg d, i.g.) from days 21 to 42 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. In vitro proliferation of spleen cells was examined using 3-[4,5-dimethylthylthiazol-2-yl]-2, 5-diphenyltetrazoliumbromide (MTT) assay. Plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) and the expression of prostaglandin E(2) (PGE(2)), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in synovial tissues were also determined. The results showed that comparing with untreated CIA mice, treated with MA dose-dependently suppressed the clinical arthritis score and joints tissues pathological damage, reduced the proliferation of spleen cells, plasma levels of TNF-alpha and IL-6, synovial tissues PGE(2) production and COX-2 protein expression, however, the expression of COX-1 in synovial tissues did not change and the plasma levels of IL-10 were increased. These results suggest that MA can effectively alleviate inflammatory response on CIA, and anti-inflammatory effects of MA can be attributed, at least partially, to the inhibition of pro-inflammatory mediators, including COX-2 expression, PGE(2) production, TNF-alpha and IL-6 levels and the up-regulation anti-inflammatory molecule IL-10.

PMID: 19135346 [PubMed - in process]


8. Comparison of the effects of collagenase and extract of Centella asiatica in an experimental model of wound healing: an immunohistochemical and histopathological study.

Ermertcan AT, Inan S, Ozturkcan S, Bilac C, Cilaker S.

Department of Dermatology, Celal Bayar University, Faculty of Medicine, Manisa, Turkey. draylinturel@hotmail.com

In this study, we compared the effects of collagenase and Centella asiatica in the rat model. Twenty-seven female rats were divided into three groups, and two full-thickness wounds were made for each animal. Collagenase ointment was applied topically to Group I and C. asiatica ointment to Group II rats. In Group III, no treatment was applied. On the third day of treatment, wounds on the left side of three animals of each group were excised. On the fifth and eighth day of the treatments, the same procedure was performed for the remaining animals. Indirect immunohistochemical examination was performed to detect transforming growth factor beta (TGF)-beta, endothelial and inducible nitric oxide synthase (eNOS and iNOS), vascular endothelial growth factor, TGF-alpha, laminin, fibronectin, collagen I, and interleukin-1beta. According to the measurements of the wound areas and wound healing periodo, collagenase was superior to the control group. Immunohistochemical examinations showed strong (+++) iNOS and TGF-beta immunoreactivities in C. asiatica group. eNOS immunoreactivity was moderate (++) in this group. For the collagenase group, iNOS, eNOS, and TGF-beta immunoreactivities were moderate (++). In the collagenase group, while TGF-beta and iNOS immunoreactivities were weaker, laminin and fibronectin reactivities were stronger than in C. asiatica and control groups. Collagenase was superior to C. asiatica according to the immunohistochemical findings. Collagenase ointment significantly improves the quality of wound healing and scar formation and is a more appropriate treatment choice than extract of C. asiatica in the early stages of the wound healing process.

PMID: 19128262 [PubMed - indexed for MEDLINE]


9. Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model.

Dhanasekaran M, Holcomb LA, Hitt AR, Tharakan B, Porter JW, Young KA, Manyam BV.

Department of Neurology, Scott and White Clinic, Texas A & M University System HSC College of Medicine, Texas, USA.

PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid beta plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid beta 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright 2008 John Wiley & Sons, Ltd.

PMID: 19048607 [PubMed - indexed for MEDLINE]


10Protective antioxidant effect of Centella asiatica bioflavonoids on lead acetate induced neurotoxicity.

Ponnusamy K, Mohan M, Nagaraja HS.

Department of Human Biology, International Medical University, Kuala Lumpur, Malaysia.

Lead (Pb) is a neurotoxic heavy metal and children in the developmental stage are particularly susceptible to toxic effects of lead exposure. The brain is the key organ involved in interpreting and responding to potential stressors. Epidemiological investigations have established the relationship between chronic lead exposure and cognitive impairments in young children. Excessive production of radical species plays an important role in neuronal pathology resulting from excitotoxic insults, therefore one plausible neuroprotective mechanism of bioflavonoids is partly relevant to their metal chelating and antioxidant properties. Centella asiatica (CA) is a tropical medicinal plant enriched with bioflavonoids and triterpenes and selenium, reported to rejuvenate the cells and promote physical and mental health. Bioflavonoids are claimed to be exert antimutagenic, neurotrophic and xenobiotics ameliorating and membrane molecular stabilizing effects. The objective of the present work is to study the protective antioxidant effect of pretreatment of CA extract (CAE) on lead acetate induced changes in oxidative biomarkers in the central nervous system (CNS) of mice.

PMID: 19025005 [PubMed - indexed for MEDLINE]


11. Studies on Indian green leafy vegetables for their antioxidant activity.

Gupta S, Prakash J.

Department of Studies in Food Science & Nutrition, University of Mysore, Manasagangotri, Mysore, 570 006, India. sheetalgupta.75@gmail.com

To identify the potential of green leafy vegetables (GLV) as antioxidants, methanolic extracts of Amaranthus sp., Centella asiatica, Murraya koenigii and Trigonella foenum graecum were studied for their antioxidant activity in different systems at multiple concentrations. Total antioxidant activity assessed by phosphomolybdenum method, free radical scavenging activity by 1,1-diphenly-2-picryl hydrazyl (DPPH), reducing power and ferrous ion chelating activity were determined. The GLV were analyzed for ascorbic acid, total and beta-carotene and total polyphenol contents. The ascorbic acid, total carotene, beta-carotene and total phenolic content (tannic acid equivalents) of the GLV ranged between 15.18-101.36, 34.78-64.51, 4.23-8.84 and 150.0-387.50 mg/100 g GLV, respectively. The extracts were found to have significantly different levels of antioxidant activities in the systems tested. The total antioxidant activity was highest in Murraya koenigii (2,691.78 micromol of ascorbic acid/g sample) and least in Centella asiatica (623.78 micromol of ascorbic acid/g sample). The extract concentration causing 50% inhibition of DPPH (IC50) was determined (M. koenigii<C.asiatica<Amaranthus sp.<T. graecum). The maximum DPPH scavenging activity and reducing power was exhibited by Murraya koenigii. Multiple regression analysis showed that the relationship of total antioxidant activity, free radical scavenging activity, and reducing power with polyphenol and total and beta-carotene was highly significant.

PMID: 18985454 [PubMed - indexed for MEDLINE]


12. [Molecular characters of Centella asiatica found with RAPD technology]

Ruan Y, Mo RH, Li M, Huang LQ, Luo Y, Li XY, Zhou J, Wu YS.

Gung Medical University, Nanning 530021, China.

OBJECTIVE: To analyze the DNA molecular characters of Centella asiatica with RAPD technology. METHODS: With the genomic DNA as templates extracted from various source of Centella asiatica samples, optimized RAPD PCR reaction systems had been used. The random promers had been screened to amplify the specific molecular fragments of Centella asiatica. RESULTS: The specific genetic bands of Centella asiatica species from various habitats were established which were highly stable and repeatable and obviously different from those of other families, genuses of plants such as Gynostemma pentaphylum, Tobacco, Cayratia japonica. CONCLUSION: The developed method of RAPD analysis for the genetic character bands of Centella asiatica could be applied to identify real Centella asiatica from its spurious breed plants. The genetic character bands of Centella asiatica amplified with the RAPD method show high homogeneous in several samples from different habitats.

PMID: 18973007 [PubMed - in process]


13. Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica (Linn) During Growth Spurt Period in Rats.

Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S.

Melaka Manipal Medical College, Manipal 576 104, India. mohandaskg@gmail.com or mohandas.rao@manipal.edu.

Centella asiatica (CeA) is a creeping herb, growing in moist places in India and other Asian Countries. Ayurvedic system of medicine, an alternate system of medicine in India, uses leaves of CeA for memory enhancement. Here, we have investigated the role of CeA fresh leaf juice treatment during growth spurt period of rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. The present study was conducted on neonatal rat pups. The rat pups (7-days-old) were fed with 2, 4 and 6 ml/kg body of fresh leaf juice of CeA for 2, 4 and 6 weeks. After the treatment period, the rats were killed, brains removed and amygdaloid neurons impregnated with Silver nitrate (Golgi staining). Amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure dendritic length) quantified. These data were compared with those of age-matched control rats. The results showed a significant increase in dendritic length (intersections) and dendritic branching points along the length of dendrites of the amygdaloid neurons of rats treated with 4 and 6 ml/kg body weight/day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that constituents/active principles present in CeA fresh leaf juice has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.

PMID: 18955230 [PubMed - in process] PMCID: PMC2686623


14. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging.

Singh RH, Narsimhamurthy K, Singh G.

Department of Kayachikitsa, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India. rh_singh2001@yahoo.com

Ayurveda is the oldest system of Medicine in the world, its antiquity going back to the Vedas. It adapts a unique holistic approach to the entire science of life, health and cure. The areas of special consideration in Ayurveda are geriatrics, rejuvenation, nutrition, immunology, genetics and higher consciousness. The Ayurvedic texts describe a set of rejuvenative measures to impart biological sustenance to the bodily tissues. These remedies are called Rasayana which are claimed to act as micronutrients. Some of these Rasayanas are organ and tissue specific. Those specific to brain tissue are called Medhya Rasayana. Such Rasayanas retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and memory enhancing effect. In addition to the long tradition of textual and experience-based evidence for their efficacy, certain recent studies conducted on these traditional remedies on scientific parameters have shown promising results which have been reviewed in this paper for providing lead for further studies. The popular Medhya Rasayanas are Ashwagandha (Withania somnifera Dunal), Brahmi (Bacopa monnieri Linn), Mandukaparni (Centella asiatica Linn) and Sankhapuspi (Convolvulus pluricaulis Chois).

PMID: 18931935 [PubMed - indexed for MEDLINE]


15. Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice.

Shinomol GK, Muralidhara.

Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI, a CSIR Laboratory), Mysore 570020, India.

Despite the increasing popularity of Centella asiatica (a well known plant in ayurvedic medicine) globally, evidence demonstrating its protective efficacy against neurotoxicants in animal models is limited. 3-Nitropropionic acid (3-NPA), a fungal toxin is a well known neurotoxicant which induces selective striatal pathology similar to that seen in Huntington's disease. The present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of C. asiatica (CA) against 3-NPA-induced early oxidative stress and mitochondrial dysfunctions in striatum and other brain regions. We determined the extent of oxidative stress in cytosol and mitochondria of brain regions of male mice (4wk old) given CA prophylaxis (5mg/kgbw) for 10 days followed by 3-NPA administration (i.p., 75mg/kgbw/d) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the untreated mice as evidenced by elevated levels of malondialdehyde, ROS levels and hydroperoxides in the striatum (cytosol and mitochondria), while CA prophylaxis completely attenuated the 3-NPA-induced oxidative stress. 3-NPA also caused significant oxidative stress and protein oxidation in cytosol/mitochondria of other brain regions as well which were predominantly abolished by CA prophylaxis. Significant depletion of GSH levels, total thiols and perturbations in antioxidant enzymic defences in striatum and other brain regions discernible among 3-NPA administered mice were also protected with CA prophylaxis. Interestingly, CA prophylaxis offered varying degree of protection against 3-NPA-induced mitochondrial dysfunctions viz., reduction in the activity of succinic dehydrogenase, ETC enzymes and decreased mitochondrial viability. Collectively these findings clearly suggest that short-term oral intake of a standardized aqueous extract of CA confers marked resistance against the 3-NPA-induced oxidative stress and mitochondrial dysfunctions in brain. Although the precise mechanism/s underlying the prophylactic efficacy of CA merit further investigation, based on these findings, it is hypothesized that it may be wholly or in part related to the enhancement of GSH, thiols and antioxidant machinery in the brain regions of prepubertal mice.

PMID: 18930762 [PubMed - indexed for MEDLINE]


16. An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects.

Wojcikowski K, Wohlmuth H, Johnson DW, Rolfe M, Gobe G.

University of Queensland, Brisbane, Australia. kwojciko@scu.edu.au

AIM: Renal fibrosis is central to progression of most chronic renal pathologies. Antioxidants that protect the tubular epithelium and anti-fibrotics that induce apoptosis of pro-fibrotic myofibroblasts without adversely affecting tubular epithelium may slow progression of renal fibrosis, while toxic substances may exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular epithelial cells (NRK52E) to determine their potential value as therapeutic agents in renal fibrosis involving oxidative stress. METHODS: Herbs were chosen because of their traditional use in kidney or urinary system disorders, or because of recent published interest in their therapeutic or toxic potential in kidney disease. Extracts of herbs were made using a sequential multi-solvent extraction process. Each extract was analysed separately. Extraction solvents were ethyl acetate, methanol and 50% aqueous methanol. Cells were treated with extracts with/without oxidative stress (1.0 mM hydrogen peroxide). Cellular changes (apoptosis, necrosis, mitosis, transdifferentiation) were identified and quantified using defined criteria. RESULTS: All extracts of Dioscorea villosa showed significant toxicity to both cell lines. At low concentrations (5-50 microg/mL) they induced epithelial to mesenchymal transdifferentiation, as demonstrated by increased immunohistochemistry staining for alpha-smooth muscle actin and transforming growth factor-beta1 in treated versus control cells. Angelica sinensis, Centella asiatica, Glycyrrhiza glabra, Scutellaria lateriflora, and Olea europaea demonstrated strong antioxidant effects in epithelial cells and/or apoptotic effects on fibroblasts. CONCLUSION: This investigation has revealed renotoxicity of D. villosa and anti-fibrotic, oxidant potential of several herbal extracts, all of which require further study.

PMID: 18808387 [PubMed - in process]


17. Larvicidal and adulticidal activities of some medicinal plants against the malarial vector, Anopheles stephensi (Liston).

Senthilkumar N, Varma P, Gurusubramanian G.

Department of Biotechnology, Mizoram University, Aizawl, 796 009 Mizoram, India. kumarsysu@hotmail.com

The present study was undertaken to test the efficacy of 11 commonly available medicinal plants and compare its efficacy in relation to larvicidal and mosquitocidal activities against larvae and adults of Anopheles stephensi (Liston). All the medicinal plants and the mixture were effective against larvae of A. stephensi as evidenced by low lethal concentration and lethal time. The lethality varied in adults and plant extracts of mixture; Eucalyptus globulus, Cymbopogan citratus, Artemisia annua, Justicia gendarussa, Myristica fragrans, Annona squamosa, and Centella asiatica were found to be most effective. Larval mortality between 80% and 100% was observed in mixture treatment, C. asiatica and E. globulus. The adults that emerged from all the treatments were malformed. Further, the treated larvae showed significant decrement in the levels of protein, carbohydrate, and lipids and affect negatively the presence of certain amino acids. The present findings have important implications in the practical control of mosquito larvae and adults in the aquatic ecosystem as the medicinal plants studied are commonly available in large quantities. These plant extracts are easy to prepare, inexpensive, and safe for mosquito control which might be used directly as larvicidal and mosquitocidal agents in small volume aquatic habitats or breeding sites of around human dwellings.

PMID: 18787842 [PubMed - indexed for MEDLINE]


18. [Preparation of asiaticoside and madecassoside from the extract of Centella asiatica (L.) Urb using preparative high performance liquid chromatography]


Gao M, Yuan X, Xiao H.

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. gaomz@dicp.ac.cn

A high performance liquid chromatographic (HPLC) method was successfully used to separate asiaticoside and madecassoside from the extract of Centella asiatica (L.) Urb. The raw material containing 20% asiaticoside and 45% madecassoside was dissolved in methanol and used for the preparation of the pure compounds. The flow rate of the mobile phase, injection volume and detection wavelength were optimized. The optimum operation parameters were then selected as follows: a C18 column (50 mm x 200 mm, 5 microm) with methanol-water (60 : 40, v/v) as the mobile phase at a flow rate of 100 mL/min, the detection wavelength of 220 nm, and the injection volume of 1.5 mL at the concentration of 40 mg/mL. Asiaticoside and madecassoside the can be obtained in a 20 min runtime, and the purities of the products were detected by melting point, thin layer chromatography (TLC) and HPLC method. The results showed that the purities of products were above 98%. The effective and rapid method has been successfully applied and to the preparation of asiaticoside and madecassoside from Centella asiatica (L. ) Urb.

PMID: 18724677 [PubMed - in process]


19. Mosquito larvicidal activity of oleic and linoleic acids isolated from Citrullus colocynthis (Linn.) Schrad.

Rahuman AA, Venkatesan P, Gopalakrishnan G.

Unit of Bioactive Natural Products, P.G & Research Department of Zoology, C. Abdul Hakeem College, Melvisharam 632 509 Vellore Dist. Tamil Nadu, India. abdulrahuman6@hotmail.com

In mosquito control programs, botanical origin may have the potential to be used successfully as larvicides. The larvicidal activity of crude acetone, hexane, ethyl acetate, methanol, and petroleum ether extracts of the leaf of Centella asiatica Linn., Datura metal Linn., Mukia scabrella Arn., Toddalia asiatica (Linn.) Lam, extracts of whole plant of Citrullus colocynthis (Linn.) Schrad, and Sphaeranthus indicus Linn. were assayed for their toxicity against the early fourth instar larvae of Culex quinquefasciatus (Diptera: Culicidae). The larval mortality was observed after 24 h exposure. All extracts showed moderate larvicidal effects; however, the highest larval mortality was found in whole plant petroleum ether extract of C. colocynthis. In the present study, bioassay-guided fractionation of petroleum ether extract led to the separation and identification of fatty acids; oleic acid and linoleic acid were isolated and identified as mosquito larvicidal compounds. Oleic and Linoleic acids were quite potent against fourth instar larvae of Aedes aegypti L. (LC50 8.80, 18.20 and LC90 35.39, 96.33 ppm), Anopheles stephensi Liston (LC50 9.79, 11.49 and LC90 37.42, 47.35 ppm), and Culex quinquefasciatus Say (LC50 7.66, 27.24 and LC90 30.71, 70.38 ppm). The structure was elucidated from infrared, ultraviolet, 1H-nuclear magnetic resonance, 13C-NMR, and mass spectral data. This is the first report on the mosquito larvicidal activity of the reported isolated compounds from C. colocynthis.

PMID: 18688644 [PubMed - indexed for MEDLINE]


20. Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice.

Liu M, Dai Y, Yao X, Li Y, Luo Y, Xia Y, Gong Z.

Department of Pharmacology of China Materia Medica, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, China.

Madecassoside is the highest amount of triterpene constituent in Centella asiatica herbs, a frequently prescribed crude drug in southeastern Asian and China for wound healing and scar management. The present study aimed to investigate the therapeutic potential and underlying mechanisms of madecassoside on collagen II (CII)-induced arthritis (CIA) in mice. Madecassoside (10, 20 and 40mg/kg), orally administered from the day of the antigen challenge for twenty consecutive days, dose-dependently alleviated the severity of the disease based on the reduced clinical scores, and elevated the body weights of mice. Histopathological examination indicated that madecassoside alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Moreover, madecassoside reduced the serum level of anti-CII IgG, suppressed the delayed type hypersensitivity against CII in ears, and moderately suppress CII-stimulated proliferation of lymphocytes from popliteal lymph nodes in CIA mice. In vitro, madecassoside was ineffective in the activation of macrophages caused by lipopolysaccharide. It was concluded that madecassoside substantially prevented mouse CIA, and might be the major active constituent of C. asiatica herbs responsible for clinical uses for rheumatoid arthritis. The underlying mechanisms of action may be mainly through regulating the abnormal humoral and cellular immunity as well as protecting joint destruction.

PMID: 18652917 [PubMed - indexed for MEDLINE]


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