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Antihepatotoxic activity of a quantified Desmodium adscendens decoction and D-pinitol against chemically-induced liver damage in rats
... In previous investigations we have reported D-pinitol as the major constituent of the decoction of D. adscendens, being responsible at least in part for the hepatoprotective activity, more specifically the prevention of D-galactosamine-induced liver damage, although the results suggested a synergistic effect by other compounds. [7] In addition, commercially available food supplements are standardized on vitexin. Therefore, this work focused, after a general phytochemical screening, on the isolation and identification of the flavonoids present in D. adscendens, a class of natural products which are generally known to have antioxidative and free radical scavenging properties). ...
... The decoction of D. adscendens was prepared as reported before. [7] Chromatographic methods ...
... This in agreement with literature data, where D-pinitol was found in blood of humans after oral intake of D-pinitol. [7,30] In conclusion, the major flavonoids of a decoction of D. adscendens were characterized as vicenin-2, isoschaftoside, schaftoside, 2″-O-xylosylvitexin, 2″-O-pentosyl-Chexosyl apigenin and a O-hexosyl-C-hexosyl apigenin, tentatively identified as 2″-O-glucosyl-vitexin. It should be noted that passive diffusion through a dialysis membrane of polar compounds may not reflect passive diffusion in the gastrointestinal tract, which requires more lipophilic properties. ...
Objectives
The isolation and identification of the flavonoids present in a decoction of Desmodium adscendens was performed. In view of the oral use of the decoction, this work focused on the stability in gastrointestinal conditions and biotransformation by intestinal microflora in the colon of D‐pinitol, vitexin and the flavonoid fraction of the decoction, as a first step in unravelling its behaviour in the human body.
Methods
The freeze‐dried decoction was first subjected to column chromatography. Subsequently an enriched flavonoid fraction, was separated by repeated semi‐preparative high‐performance liquid chromatography (HPLC) or by HPLC‐SPE. The isolated compounds were elucidated by NMR. Biotransformation experiments were carried in an in vitro gastrointestinal dialysis model.
Key findings
The major flavonoids of a decoction of D. adscendens were characterized as vicenin‐2, isoschaftoside, schaftoside, 2″‐O‐xylosylvitexin, 2″‐O‐pentosyl‐C‐hexosyl apigenin and a O‐hexosyl‐C‐hexosyl apigenin, tentatively identified as 2″‐O‐glucosyl‐vitexin. During their passage in the gastrointestinal dialysis model, vitexin and C‐glycosides thereof were found to be stable. Only the O‐glycosidic bonds of O‐glycosides of vitexin or isovitexin were hydrolysed during the colonic phase.
Conclusions
A D. adscendens decoction was found to be rich in vitexin and isovitexin glycosides from which vitexin and the C‐glycosides thereof were found to be stable in the simulated gastrointestinal tract.
... Unfortunately, a number of reactive species, including free radicals, can damage the liver leading to jaundice, cirrhosis or fatty liver, to name a few. Additionally, viral hepatitis is considered a major health problem throughout the world [109]. Zhou et al. [110] Proves that Dpinitol shows a protective effect against human viral hepatitis caused by D-galactosamine (GalN) in rat model. ...
D-pinitol is a natural compound related to the important family of inositol. It can be found and isolated from many plants, being the active component of ayurvedic remedies from Pinaceae, Asteraceae, Caryophyllaceae, Zygophyllaceous, Cupressaceae, Aristolochiaceae and Sapindaceae. It firstly synthesised and structure characterized from the Sugar pine tree]. D-pinitol is the D-enantiomer of pinitol, it's a 3-O-methyl-D-chiro-inositol. Fortunately, the pharmacological interest in this compound has risen various established multifunctional properties through a variety of signalling pathways: i) anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway; ii) insulinomimetic and metabolic regulator in type 2 diabetes mellitus, via a post-receptor pathway of insulin action; iii) antioxidant; iv) hepatoprotective; v) immuno-modulator, balancing Th1/Th2 cytokines; vi) osteoporosis preventive, through p38/JNK and NF-ⱪB pathways; vii) anti-aging, via reduction of the insulin/IGF-1 signalling (IIS) pathway; viii) improver of creatine retention; ix) preventive and ameliorative of Alzheimer's disease through selective γ-secretase modulation. Thus, the present review compresses the literature reported to date in relation to the Pharmacological effects and metabolic pathways of this naturally occurring compound D-Pinitol ingredient providing an extensive guide for a future utilization of all of its potentialities. The result came out from the compilation of data brings up with the conclusion i.e. the d-pinitol is the immerging phytomolecule which possess various pharmacological activity and therapeutic potency toward various diseases which makes this molecule as a choice of drug in future for the control of various enlisted disease.
... A burr hole was made to open the skull and the dura mater was carefully cut to expose the distal MCA, which was permanently occluded by bipolar electrocautery. [16,19,30], was dissolved in 5% glucose. The drugs or vehicle were administered by tail-vein injection at the onset of reperfusion in the tMCAO model or 20 min after ischemic stroke in the pdMCAO model. ...
The rigorous design of preclinical experimental studies of candidate neuroprotectants for the treatment of acute ischemic stroke is crucial for the success of subsequent randomized clinical trials. The efficacy of Ginkgo biloba extracts (GBEs) in complex mixtures for the treatment of acute ischemic stroke remains unclear. In this preclinical randomized controlled trail (pRCT), the effects of a novel (n)GBE containing pinitol versus traditional (t)GBE without pinitol were evaluated on the mouse models of acute transient and permanent stroke, separately. The sample size, an important aspect of study design, was calculated based on our experimental data. Mice with ischemia that were induced by transient middle cerebral artery occlusion (tMCAO) or permanent distal middle cerebral artery occlusion (pdMCAO), were treated with vehicle, nGBE, tGBE, or pinitol alone by tail-vein injection. Our results showed that nGBE significantly reduced infarct size in mice with tMCAO compared with vehicle-treated control mice. Both nGBE and tGBE significantly reduced infarct size in mice with pdMCAO compared with the vehicle-treated controls. None of the three treatments rescued weight loss or prevented the neurological deficits in either the tMCAO- or pdMCAO-model mice. These findings suggest that nGBE, which includes all of the components of tGBE and pinitol, is neuroprotective in two ischemic stroke models. Additional studies of complex GBE mixtures for stroke treatment compared to single component medications are undergoing evaluation.
... Desmodium adscendens (Fabaceae) is an herbaceous plant found in Africa and South America, where a decoction of leaves and stems is used in traditional medicine for various indications, including the management of asthma and livers related diseases [6]. In the rainforest region, preparations from D. adscendens (DA) are used to treat digestive system disorders or abdominal and back pain [7]. ...
Background: Desmodium adscendens (DA) is an herbaceous plant found in Africa and South America and used in traditional medicine against
liver-related diseases. In the present study, the aqueous decoctions from DA were tested for their antioxidant and hepato-(protective and
curative) properties on CCl4-induced acute injury on primary culture rat hepatocytes. We also investigated its inhibitory effects on hepatitis C
virus (HCV) using genotype 1b subgenomic replicon systems and cell-culture derived HCV particles (HCVcc).
Methods: Five chemical antioxidants assay were used for the evaluation of antioxidant properties of aqueous extract of DA. Hepato-(protective
and curative) activities of DA against CCl4-induced hepatotoxicity in primary rat hepatocytes were assessed by measuring cell viability, alanine
aminotransferase (ALT) activity leakage into the incubation medium and malondialdehyde (MDA) content as markers of lipid membrane
peroxidation. Antiviral activity against hepatitis C virus (HCV) was performed using HCV genotype 1b sub-genomic replicon cell line LucUbiNeoET cells and HCV cell-culture derived particles (HCVcc) by measuring luciferase activity and indirect immunofluorescence respectively.
Antioxidant activity was assessed, and cytotoxicity and oxidative injury were determined by assessing cell viability by the 3-(4, 5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazolium (MTT) and leakage of ALT, a cytosolic enzyme. LucUbiNeo-ET cells were used as HCV genotype 1b replicons
systems and were incubated with various concentrations of plant extract. The antiviral activity was assayed by measuring the luciferase activity
in cell lysates by reporter gene assay.
Results: Average yield of 4.16 ± 0.44 million cells/g of liver and viability of 90 ± 1.29 % were obtained. Hepatocyte viability was not affected by
increasing concentrations of plant extracts. Moreover, treatment of cells with plant extracts at concentrations of 1 -1000 µg/mL before and after
oxidative injury provided a cytoprotective effect to the cells by increasing the percent of cell viability, reducing ALT leakage and decreasing the
formation of malondialdehyde and an antioxidant capacity was noted. A strong activity was observed with D. adscendens harvested before
flowering (DA1) compared to its activity after flowering (DA2). DA1 extract was tolerated by LucUbiNeo-ET cells up to the concentration of 500
µg/mL after 24 h of incubation. DA1 extract at 25 µg/mL produced a significant (p<0.01) decrease in HCV infection compared to the DMSOtreated group.
Conclusions: These findings indicate that Desmodium adsccendens aqueous extracts possess promising hepatoprotective effects against CCl 4-
induced liver injury and HCV infection. These support its traditional use for the management of some liver diseases.
Keywords: Desmodium adscendens, Hepatotoxicity; Primary rat hepatocytes; HCV; Carbon tetrachloride.
... Studi sperimentali in vivo hanno evidenziato la normalizzazione delle transaminasi in affezioni epatiche, anche severe, quali: steatosi, steato-epatiti, epatiti e stati precritici. La pianta non presenta documentata attività tossica e non ha controindicazioni (15). Il Chrysantellum americanum, originario del Sudamerica e dell'Africa, è risultato un coadiuvante nelle funzioni del pancreas e del fegato, la cui detossicazione avverrebbe grazie all'induzione enzimatica del citocromo P450 (16). ...
Metabolic syndrome (MetS) is a complex trait, involving cardiovascular risk factors, abdominal fat deposition, altered plasma lipid levels, elevated blood pressure and insulin resistance, with increased body mass index (BMI) and waist circumference enlargement.
The affected subjects very often fed with an inadequate nutritional diet in the long term develop liver dysfunction on a steato-inflammatory basis with dyspepsia, meteorism, constipation and other gastrointestinal symptoms, leading to a poor life quality. This retrospective observational study evaluates the effects of a balanced diet integrated with Desmodium adscendens and Chrysantellum americanum as agents to restore hepatic detoxification for the improvement of some parameters (body weight, BMI and waist circumference) in subjects with or at risk of developing MetS. Fifty subjects (37 women and 13 men) aged between 21 and 67 went to the Second Opinion clinic to review their dietary intake, most of them being overweight and in 30% of cases affected by MetS and/or hyperlipidaemia. Their major complaint had been the anaesthetic waist circumference enlargement with meteorism and dyspepsia. Then, we propose a slimming diet called "detoxination" followed by a "maintenance" phase supplemented with 6 capsules/day of 200 mg of Desmodium adscendens and 6 capsules/day of 250 mg
of Chrysantellum americanum for 33 days. Each subject measured the waist circumference, as well as the weight and height at the first visit, while subsequent controls occurred after 1 month and 3 months. A body weight reduction of 4 and 6.4% was obtained after 1 month and at the end of the treatment period, respectively. The BMI underwent an overall reduction of 15% at the end of the treatment period (6% after the first month). Finally, the waist circumference decreased by 6.2 and 8.5% after the
the first and third month of treatment, respectively. The integration of a slimming diet aimed at detoxification, supplemented with natural extracts acting on hepatic metabolism, produced significant results on body weight, BMI and waist circumference,
improving these parameters probably through epigenetic mechanism in an effective synergic way leading to full patient satisfaction and life quality improvement.
... For instance, Desmodium adscendens (Desmodium), a plant of African origin with anti-allergic, antioxidant and hepatoprotective properties, has active constituents to preserve liver function, mainly contained in the trunk and leaves, such as triterpenic saponosides, soy saponins, indole alkaloids, fatty acids, flavonoids, tannins, and sterol derivatives. 14 In traditional African medicine, Desmodium extracts are used for the treatment of asthma and liver diseases. 15 Desmodium has also anti-allergic properties that are mediated by the partial inhibition of the biochemical pathway of arachidonic acid synthesis. ...
Background
Neoplasms of the head and neck represent approximately 5% of cancers and they require complex multidisciplinary clinical management. Desmodium adscendens (Desmodium) is a plant that possesses anti-allergic, antioxidant and hepatoprotective properties. Lithothamnium calcareum (Lithothamnium) is a calcified seaweed that possesses remineralization properties and the ability to maintain homeostasis.
Aim
In this single-arm study, we investigated the efficacy of a combination therapy based on Desmovit® which contains Desmodium and Lithothamnium, and chemotherapy in patients with head and neck cancer.
Methods
Twelve patients with histological or cytological diagnosis of stage IV head and neck cancer were enrolled in this study that was approved by the ethics committee of the Unità Operativa Complessa (UOC) di Oncologia Medica Azienda Ospedaliera Ospedali Riuniti Marche Nord and followed the Declaration of Helsinki guidelines. The patients were monitored by investigation of the performance status according to the Glasgow Prognostic Score (GPS), which evaluates the plasma level of C-reactive protein and albumin levels, and the Eastern Cooperative Oncology Group (ECOG) examination. Pain and fatigue were also monitored using the visual analog scale and visual analog fatigue scale, respectively. All the above parameters were assessed biweekly to week 10.
Results
GPS, ECOG, and albumin remained stable throughout the study with a trend towards a decrease in GPS and albumin at week 10 post-treatment. Pain significantly improved at week 8 (P<0.05) while fatigue improved at weeks 8 and 10 (all P<0.01).
Conclusion
We found that chemotherapy, combined with Desmodium and Lithothamnium, improved pain and fatigue in head and neck cancer patients, although we cannot confirm if this was due to Desmodium and Lithothamnium or chemotherapy. The improvement in pain and fatigue was supported by the ECOG performance status remaining stable with the highest score being equal to 2 throughout the study and a trend towards an improvement in GPS performance status and albumin levels.
... Compounds 1-6 ( Fig. 1) were identified by spectral data (UV, IR, MS, HR-ESI-MS, 1 H and 13 C NMR) and comparison with those of literature values as Stigmasterol (1) [18], Bis (2-methylheptyl) phthalate (2) [19,20], Trans-resveratrol (3, 4', 5-trihydroxy -trans stilbene) (3) [21], β-sitosterol-Dglycoside (4) [22,23], Piceatannol (3,4', 5,5'tetrahydroxy-trans stilbene) (5) [21,[24][25][26] and (+) D-pinitol (1D-3-O-methyl-chiro-inositol) (6) [27]. These compounds were isolated for the first time from M. angolense. ...
... Serum ALP level was significantly reduced in Argyrlolobiumroseum aqueous extract treated group as compared to positive control group. This effect may be due to the ability of D. pinitol to modulate cell surface glycoproteins and to protect membrane of both lysosome and mitochondria because of its antioxidant nature 23 . ...
Liver diseases are a matter of serious concern all over the world. They may lead to serious consequences such as cirrhosis and hepatocellular carcinoma. Many efforts are being made to discover new hpatoprotective agents. Herbal medicines are usually considered as safe and effective for various ailments. The therapeutic value of Argyrolobiumroseum has been recognized in traditional medicine. Hepatoprotective effect of aqueous extract Argyrolobiumroseum whole plant against CCl4 induced hepatotoxicity was evaluated. In this study thirty five male rabbits were used. Animals were divided into five groups, containing seven animals in each group. Liver injury was induced by carbon tetra chloride 0.4ml/kg/day (1:1 in olive oil) in twenty eight rabbits. Hepatoprotective effect of aqueous extract of Argyrolobiumroseum with doses of 200mg/kg/day, 400mg/kg/day and 600 mg/kg/day was evaluated. Serum AST, ALP, ALT and total bilirubin were evaluated by using Human CE kits in semiautomatic clinical chemistry analyzer, backman coulter CX5. There was a significant elevation of Alanine transaminase (ALT), alkaline phosphatase (ALP), Aspartate transaminase (AST) and total bilirubin levels indicating development of hepatotoxicity. The level of ALP, ALT, AST and total bilirubin were significantly reduced(pvalue 0.001) in Argyrolobiumroseum (400mg/kg) treated rabbits showing the hepatoprotective effect of Argyrolobiumroseum.
... On a more general level, these species might act on the gall bladder, increasing the flow of bile and its excretion rate. Indeed, for some of these species, a cytoprotective or hepatoprotective effect against chemical or oxidative stress had been confirmed (Hyuncheol et al., 2004;Yanghee et al., 2010;Magielse et al., 2013;Acero et al., 2006). However, such hypothesis will naturally have to be tested on other experimental models in order to better valorize the traditional use of these species. ...
... Unfortunately, a number of reactive species, including free radicals, can damage the liver leading to jaundice, cirrhosis or fatty liver, to name a few. Additionally, viral hepatitis is considered a major health problem throughout the world [107]. ...
D-pinitol is a natural compound related to the important family of inositols. It can be found and isolated from many plants, being the active component of ayurvedic remedies such as Talisa patra (Abies webbiana, A. pindrow) or antidiabetic as Bougainvillea (Bougainvillea spectabilis). Although many synthetic and semi-synthetic methods have been reported for D-pinitol and its derivatives, through chemical and biochemical transformations, Ceratonia siliqua L. (Carob), a Mediterranean tree now in decline, known because of its environmental advantages, is the only raw material from which D-pinitol can be isolated in quantities enough for a viable commercial exploitation. Fortunately, the pharmacological interest in this compound has risen enormously in the last years owing to their established multifunctional properties through a variety of signalling pathways: i) anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway; ii) insulinomimetic and metabolic regulator in type 2 diabetes mellitus, via a post-receptor pathway of insulin action; iii) antioxidant; iv) hepatoprotective; v) immuno-modulator, balancing Th1/Th2 cytokines; vi) osteoporosis preventive, through p38/JNK and NF-ⱪB pathways; vii) anti-aging, via reduction of the insulin/IGF-1 signaling (IIS) pathway; viii) improver of creatine retention; ix) preventive and ameliorative of Alzheimer’s disease through selective g-secretase modulation.
Thus, the present review compress the literature reported to date in relation to the health-promoting effects and metabolic pathways of this naturally occurring super-food ingredient and its derivatives, providing an extensive guide for a future utilization of all of its potentialities, aiming a positive impact in the promotion and recovery of carob crops.
... Desmodium adscendens (Sw) DC is a medicinal plant found in tropical and subtropical parts of the world and its therapeutic importance have been extensively studied over the past few decades. [1][2][3][4][5] The plant has been found to be very useful in the treatment of constipation and other gastrointestinal ailments, bronchial asthma, inflammations, and coughs and colds. 6 Leaf extract of the plant is also applied externally for the treatment of snake bites and wounds in general. ...
Extracts of Desmodium adscendens (Sw) DC are used for the treatment of various diseases but limited toxicological evaluations have been done on the medicinal plant. This study investigates toxicity effects of the leave extract of D adscendens, and the possibility of drug-drug interaction of the plant extract when co-administered with other drugs. Oral administrations of leaf extract of D adscendens to white Wistar rats in an acute toxicity studies allowed the estimation of an LD50 (median lethal dose) value of 1122 mg/kg body weight. In a subchronic toxicity studies, the plant extract caused a decrease in zoxazolamine paralysis time and prevented thiopentone from causing sleep in test animals compared to controls. Overall, the results are consistent with the plant extract being safe at the doses administered in humans. However, the induction of the CYP enzymes is an indication of a possible drug interaction when the plant extract is co-administered with other drugs.
... Many plant extracts are reported to have hepatoprotective effects both in vitro and in vivo, such as milk thistle, licorice roots, Desmodium adscencens and Crepidiastrum denticulatum . Silymarin (flavonolignan), glycyrrhizic acid (triterpene ), D-pinitol and chlorogenic acid (hydroxycinnamate), respectively, were suggested as active components responsible for the hepatoprotective effects of these plants (Kang et al. 2011; Magielse et al. 2013; Lee et al. 2014; Li et al. 2014). AFR and AFP, which contains plentiful amounts of hydrocinnamates and anthocyanins, discovered in this study are valuable candidates because colored potato is a common food crop in contrast to other plants In present study, we discovered that AFR and AFP, antioxidant-enriched fractions from red and purple colored potatoes, protected oxidative stress through antioxidant action in both cultured hepatocytes and mice. ...
Herein, we prepared standardized antioxidant-enriched fractions from red (AFR) and purple (AFP) colored potatoes and evaluated their protective effects against hepatotoxicity induced by oxidative stress. The major compound contained in both AFR and AFP was 5-caffeoylquinic acid. Experiments in vitro showed that AFR and AFP protected against HepG2 cell death induced by tert-butyl hydroperoxide (t-BHP) as determined by cell viability assay. AFR and AFP recovered alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, which increased by t-BHP treatment in HepG2 cells. AFR and AFP also inhibited the cleavage of PARP and caspase-3 in HepG2 cells. Moreover, in vivo experiments in mice showed that AFR and AFP protected against t-BHP-induced hepatotoxicity and recovered serum ALT and AST enzyme activities. AFR and AFP also rescued serum antioxidant enzyme activities, catalase and glutathione peroxidase, which were disturbed by t-BHP treatment. Our data clearly demonstrate that AFR and AFP protect against hepatic damage induced by oxidative stress. Colored potatoes contain plentiful amounts of antioxidant compounds that can be developed into dietary supplements for the improvement of human health. We prepared antioxidant-enriched fractions from red and purple colored potatoes (AFR and AFP, respectively) to be used as hepatoprotective agents. Based on chemical profiling analysis, we found that 5-caffeoylquinic acid can serve as a marker for the standardization of AFR and AFP as functional food materials. AFR and AFP strongly protected against oxidative stress and injury both in cultured hepatocytes and mice. AFR and AFP prevented the cell death of hepatocytes, and they also rescued hepatic damage markers ALT and AST both in cell and animal experiments. Generally, AFP showed higher hepatoprotective activity than AFR. Taken together, AFR and AFP may be promising candidates as functional foods for improving human liver function.
... On aa ussi isolé de la tyramine et de l'hordénine [37]. Plus récemment, a été identifié dans les feuilles et les tiges, un sucre, le d-pinitol [38]. Dest ravaux sur les flavonoïdes ont identifié la présence de vitexine et d'isovitexine (hétérosides de flavones) [33]. ...
... Several plant extracts have been shown to possess hepatoprotective principles. Such plants include Garcinia kola, Bridelia micrantha, Momordica dioica, Mussaenda raiateensis, Moringa oleifera, Glycyrrhiza glabra [2][3][4][5]. ...
Daniella oliveri is a deciduous plant that is commonly found in savanna and open grassland. Various parts of the plant is used by herbalist in the management of different ailments. The present study aims at investigating the hepatoprotective and antioxidant activity of the methanolic extract of D. oliveri leaves.
The hepatoprotective activity was investigated using carbon tetrachloride (CCl4)-induced hepatotoxicity in albino rats. The antioxidant activity was determined using both in vitro (2, 2-diphenyl-1-picrylhydrazine photometric assay) and in vivo (malondialdehyde and catalase level assay) models.
The pretreatment with extract (100, 200, and 400 mg/kg) and silymarin (100 mg/kg) produced a significant (p<0.05) dose-dependent increase in hepatoprotective activity when compared with the negative control group. The extract (25-400 μg/mL concentration) produced a concentration-dependent increase in antioxidant activity in 2, 2-diphenyl-1-picrylhydrazine (DPPH) photometric assay. The IC50 of the extract in DPPH photometric assay was 400 μg/mL concentrations. The extract and silymarin showed a significant (p<0.05) dose-dependent increase in catalase level in treated rats when compared with the negative control group. Also, the extract and silymarin produced a significant (p<0.05) dose-dependent decrease in malondialdehyde level in treated rats when compared with the negative control group.
The results of the study suggest that D. oliveri leaves has a potent hepatoprotective activity that may be linked to its antioxidant activities and validates its use in the traditional management of liver disorders.
... Flavonoids, such as rutin, vitexin and isovitexin, salsoline, soyasaponins, bphenylethylamines, and an indol-3-alkylamine were isolated from D. adscendens (Addy, 1992;N'gouemo et al., 1996). In the course of our investigations, D-pinitol was characterized as a potentially active compound (Magielse et al., 2013). It has hypoglycemic and antiatherogenic activity in vitro and antihyperglycemic, hepatoprotective and anti-inflammatory effects in vivo (Bates et al., 2000;Campbell et al., 2004;Choi et al., 2007;Davis et al., 2000;Do et al., 2008;Kim et al., 2005Kim et al., , 2007Sivakumar and Subramanian, 2009;Yap et al., 2007;Zhou et al., 2008). ...
... Due to the great variety of pharmacological activities, D. adscendens has been a subject of numerous in vitro assays and animal tests, verifying the validity of its use, especially in the treatment of: (i) diseases caused by oxidative stress [7-9], (ii) states of increased activity of the CNS (epilepsy, pain) [10], (iii) liver dysfunction caused by poisoning [11] and (iv) disorders associated with smooth muscle contraction (asthma) [12][13][14][15][16][17]. As mentioned above, one of the well-documented properties of D. adscendens, which certainly contributes to its pharmacological effect, is the antioxidant activity. ...
... Flavonoids, such as rutin, vitexin and isovitexin, salsoline, soyasaponins, bphenylethylamines, and an indol-3-alkylamine were isolated from D. adscendens (Addy, 1992;N'gouemo et al., 1996). In the course of our investigations, D-pinitol was characterized as a potentially active compound (Magielse et al., 2013). It has hypoglycemic and antiatherogenic activity in vitro and antihyperglycemic, hepatoprotective and anti-inflammatory effects in vivo (Bates et al., 2000;Campbell et al., 2004;Choi et al., 2007;Davis et al., 2000;Do et al., 2008;Kim et al., 2005Kim et al., , 2007Sivakumar and Subramanian, 2009;Yap et al., 2007;Zhou et al., 2008). ...
A decoction of the leaves and stems of Desmodium adscendens (Fabaceae), a herb occurring in Africa and South America, is used in traditional medicine. Previous phytochemical research revealed that flavonoids, soyasaponins, β-phenylethylamines, and an indol-3-alkylamine were present. Our investigations have led to the identification of D-pinitol, a carbohydrate with antihyperglycemic, hepatoprotective and anti-inflammatory effects, as a potentially active compound. In order to prepare a quantified extract to be used in in vivo experiments, an analytical method was developed and validated.A gas chromatographic method was developed. Two different derivatization methods, i.e. acetylation and trimethylsilylation, were evaluated. Trimethylsilylation yielded repeatable results and was selected. Five different sugar alcohols were evaluated in order to find a suitable internal standard. Xylitol was chosen since it did not co-elute and its structure closely resembled D-pinitol. Sonication and reflux extraction were investigated in order to obtain a quantitative extraction. This was achieved through reflux extraction during 0.5 h.The method was validated according to the ICH guidelines. The calibration model appeared to be linear, ranging from 5.13 μL/mL to 25.65 μL/mL. The method was precise with an inter-day precision lower than 1.3%. The accuracy ranged from 103.38% to 105.84%. The validated method was used for quantification of D-pinitol in lyophilized decoctions from D. adscendens administered in in vivo experiments. Typically, a D-pinitol level about 5% was measured. Additionally, different food supplements available on the market were screened. The amount D-pinitol found in these supplements ranged from 1.8 mg/capsule to 30 mg/capsule and was 2.0 mg/mL solution.
Desmodium adscendens (Sw.) DC. is a plant of the Fabaceae family especially rich in flavonoids but also in alkaloids, terpenoids, steroids, phenols, phenylpropanoids, glycosides, and volatiles. This herb has been traditionally used in numerous countries all over the world for its pharmacological and biological properties (i.e., it has been used for the treatment of diarrheas, fever, epilepsy, asthma, leishmaniasis, gastroduodenal ulcer, diabetes, hepatic diseases, etc.). Given the wide uses of D. adscendens, this review summarizes all recent data on D. adscendens evaluating its phytochemistry as well as its ethno‐traditional and pharmacological properties. In addition, an association between the phytocompounds of this plant and its potential mechanism of action in cell and animal models has been investigated, focusing with a special emphasis on human experiments. Main biological and pharmacological properties of Desmodium adscendens
Carob is one of the major food trees for peoples of the Mediterranean basin, but it has also been traditionally used for medicinal purposes. Carob contains many nutrients and active natural products, and D-Pinitol is clearly one of the most important of these. D-Pinitol has been reported in dozens of scientific publications and its very diverse medicinal properties are still being studied. Presently, more than thirty medicinal activities of D-Pinitol have been reported. Among these, many publications have reported the strong activities of D-Pinitol as a natural antidiabetic and insulin regulator, but also as an active anti-Alzheimer, anticancer, antioxidant, and anti-inflammatory, and is also immune- and hepato-protective. In this review, we will present a brief introduction of the nutritional and medicinal importance of Carob, both traditionally and as found by modern research. In the introduction, we will present Carob’s major active natural products. The structures of inositols will be presented with a brief literature summary of their medicinal activities, with special attention to those inositols in Carob, as well as D-Pinitol’s chemical structure and its medicinal and other properties. D-Pinitol antidiabetic and insulin regulation activities will be extensively presented, including its proposed mechanism of action. Finally, a discussion followed by the conclusions and future vision will summarize this article.
Synthetic methods of grafting silica with (3-(2,3-epoxypropoxy)-propyl), polyoxyethylated isooctylphenolic, polyethylene glycol octadecyl ether and polyethylene glycol hexadecyl ether groups have been explored. Structure of final materials was investigated by elemental and differential thermal analyses, 13C NMR and FTIR. According to TGA and elemental analysis, data transformation of silanol groups to 2,3-epoxypropoxypropyl groups reaches up 67.61% and 61.02%, respectively. Novel silica-based solid-phase extraction (SPE) cartridges with surface-immobilized of polyoxyethylated isooctylphenolic, polyethylene glycol octadecyl ether and polyethylene glycol hexadecyl ether groups can be prepared with satisfactory densities: 20–30 µmol g⁻¹. Limit of detection of myo-inositol in water-acetonitrile samples (40/60%) is characterized by 1.27 μg per column. Applicability of proposed method using novel SPE cartridges for analysis of myo-inositol in Medicago Sativa L. gives 2.6 g of Myo-In per 1 kg of leaves.
RESUMO A mata atlântica apresenta uma grande biodiversidade de espécies vegetais, algumas ameaçadas. Com usos diversos, muitas sofrem com a pressão humana e pela ausência de manejo de áreas relevantes no bioma. O objetivo do presente estudo foi realizar o levantamento florístico de um campo de altitude sobre corpos de bauxita, identificando espécies com potencial medicinal, no município de Poços de Caldas, Minas Gerais. Fez-se uma revisão de literatura dessas espécies, inferindo sobre sua respectiva importância no uso popular, seus componentes químicos e sua atividade biológica. Identificaram-se 42 espécies com potencial medicinal, distribuídas em 19 famílias, com destaque para Asteraceae (22 espécies). Do total de 42 espécies com potencial medicinal, 39 foram relatadas na literatura quanto ao seu uso popular, 37 têm seus componentes químicos estudados e 27 apresentaram registros de pesquisas com aspectos relacionados à atividade biológica. Percebeu-se a questão de diferença de gênero e de diferença etária em relação ao conhecimento sobre plantas medicinais. Verificou-se que as pesquisas sobre plantas medicinais são fragmentadas e realizadas em menor escala. A elaboração de planos de manejo sustentáveis de produtos não madeireiros com potencial medicinal é uma estratégia para conservar a sociobiodiversidade da mata atlântica. Palavras-chave: ações medicinais; etnobotânica; manejo e conservação; práticas populares.
Cell signaling via inositol phosphates, in particular via the second messenger myo-inositol 1,4,5-trisphosphate, and phosphoinositides comprises a huge field of biology. Of the nine 1,2,3,4,5,6-cyclohexanehexol isomers, myo-inositol is pre-eminent, with "other" inositols (cis-, epi-, allo-, muco-, neo-, L-chiro-, D-chiro-, and scyllo-) and derivatives rarer or thought not to exist in nature. However, neo- and D-chiro-inositol hexakisphosphates were recently revealed in both terrestrial and aquatic ecosystems, thus highlighting the paucity of knowledge of the origins and potential biological functions of such stereoisomers, a prevalent group of environmental organic phosphates, and their parent inositols. Some "other" inositols are medically relevant, for example, scyllo-inositol (neurodegenerative diseases) and D-chiro-inositol (diabetes). It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series.
Zelluläre Signalkaskaden über Inositolphosphate, insbesondere über den sekundären Botenstoff myo-Inositol-1,4,5-trisphosphat und über die Phosphoinositide, umfassen ein riesiges Gebiet der Zellbiologie. Unter den neun 1,2,3,4,5,6-Cyclohexanhexolisomeren ist myo-Inositol vorherrschend, während die “anderen” Inositole (cis-, epi-, allo-, muco-, neo-, L-chiro-, D-chiro- und scyllo-) und ihre Derivate seltener sind oder nicht in der Natur vermutet wurden. Vor kurzem wurden jedoch neo- und D-chiro-Inositolhexakisphosphate in terrestrischen und aquatischen Ökosystemen entdeckt, was zeigt, wie lückenhaft unser Wissen über die Herkunft und möglichen biologischen Funktionen solcher Stereoisomere, einer vorherrschenden Gruppe in der Natur vorkommender organischer Phosphate, und der Inositole als Ausgangsverbindungen ist. Einige “andere” Inositole sind medizinisch bedeutsam, wie scyllo-Inositol (bei neurodegenerativen Erkrankungen) und D-chiro-Inositol (bei Diabetes). Es ist an der Zeit, Funktionen und Anwendungsmöglichkeiten der “anderen” Isomere und ihrer Derivate zu erforschen, vor allem mit Methoden, die für die myo-Inositole inzwischen gut etabliert sind.
Inositol, a hexol widely found in nature with a wide range of physiological and biochemical effects, can promote fat metabolism in liver and other tissues and lower blood cholesterol and thus has been used for the clinical treatment of fatty liver, cirrhosis, atherosclerosis and hyperlipidemia. Some derivatives of inositol have been reported to have different biological activities including hypoglycemic, antitussive, anti-inflammatory and other effects. In recent years, its monomethyl ether derivatives, such as pinitol, quebrachitol, and sequoyiol, have been studied widely. In this paper, the bioactivity, extraction, preparation and applications of these monomethyl ether derivatives of inositol are reviewed. © 2014, Editorial office of Journal of International Pharmaceutical Research. All rights reserved.
The chemical constituents isolated from Desmodium species (Leguminosae) included terpenoids, flavonoids, steroids, alkaloids compounds. Modem pharmacological studies have showed that the Desmodium species have antioxidant, antibacterial, anti-inflammatory, hepatoprotective, diuretic, antipyretic, analgesic and choleretic activity. This article mainly has reviewed the research advances of chemical constituents and biological activities of Desmodium species since 2003.
Alcohol abuse and its medical and social consequences are a major health problem in many areas of the world. The present study was conducted to evaluate the protective effect of methanolic fruit extract of Randia dumetorum (L.) on alcohol-induced liver damage in rats. Rats were divided into five different groups (n=6), group I served as a control, group II received ethanol (3 ml/100 g/day p.o.), group III served as standard group and received silymarin (50 mg/kg p.o.), group IV and V served as extract treatment groups and received 50 & 100 mg/kg methanolic extract of R. dumetorum. All the treatment protocols followed 30 days and after rats were sacrificed blood and liver were used for biochemical and histological studies, respectively. The activities serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), direct bilirubin (DB), total bilirubin (TB) and lipid peroxidation were statistically increased in rats exposed to alcohol while total protein and glutathione decreased compared to control rats. Treatment with R. dumetorum significantly decreased the elevated levels of ALT, AST, TG, DB, TB and lipid peroxidation compared to the group exposed to alcohol only. R. dumetorum significantly resulted in increased levels of total protein and reduced glutathione compared to the group that received alcohol only. Histology of the liver section of the animals treated with R. dumetorum improved the hepatotoxicity caused by alcohol. Hence the study concluded that R. dumetorum has potential hepatoprotective activity.
Individually Andrographis paniculata Nees. (Acanthaceae), Phyllanthus niruri Linn.(Euphorbiaceae) and Phyllanthus emblica Linn. single plant extracts have been reported to have hepatoprotective activity. However, literature survey shows that no sufficient scientific data has been publish on pharmacological evaluation of these plants in combined form.
Hepatoprotective activity of the polyherbal hepatoprotaective formulation (PHF)-containing spray-dried aqueous extracts of Andrographis paniculata Nees. (Acanthaceae), Phyllanthus niruri Linn. (Euphorbiaceae) and Phyllanthus emblica Linn. (Euphorbiaceae), was screened against paracetamol, carbon tetrachloride (CCl(4)), and ethanol-induced hepatic damage in rats. PHF was evaluated by measuring levels of serum marker enzymes like SGOT, SGPT, ALP, direct bilirubin (DB), and lactate dehydrogenase (LDH). The histological studies were also studied support the biochemical parameters. Silymarin was used as standard drug.
Administration of PHF (100 and 200 mg/kg p.o.) significantly inhibited paracetamol, CCl(4) and ethanol-induced elevation levels of SGPT, SGOT, ALP, DB and LDH. A comparative histopathological study of liver exhibited almost normal architecture as compared to toxicant group.
Results suggests that the hepatoprotective effects of PHF might be useful for liver protection due to combined action of all plant extracts along with their phytoconstituents.
Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of
catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pretreatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana, or silymarin reduced the morphological changes that are associated with chronic alcohol
administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.
Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2) with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%).
There were 22 subjects randomized to receive either pinitol 20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded trial.
No toxicity due to the pinitol was observed during the study The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study Final plasma levels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001) greater in the pinitol group compared with placebo.
Four weeks of pinitol treatment did not alter baseline glucose production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.
In this review we discuss the biological significance of D-chiro-inositol, originally discovered as a component of a putative mediator of intracellular insulin action, where as a putative mediator, it accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, rate limiting enzymes of non-oxidative and oxidative glucose disposal.
Early studies demonstrated a linear relationship between its decreased urinary excretion and the degree of insulin resistance present. When tissue contents, including muscle, of type 2 diabetic subjects were assayed, they demonstrated a more general body deficiency. Administration of D-chiro-inositol to diabetic rats, Rhesus monkeys and now to humans accelerated glucose disposal and sensitized insulin action.
A defect in vivo in the epimerization of myoinositol to chiro-inositol in insulin sensitive tissues of the GK type 2 diabetic rat has been elucidated. Thus, administered D-chiro-inositol may act to bypass a defective normal epimerization of myo-inositol to D-chiro-inositol associated with insulin resistance and act to at least partially restore insulin sensitivity and glucose disposal.
Liver diseases are a major problem of worldwide proportions and liver damage is very common since liver has the capacity to detoxicate toxic substances. In this review some of the plants with their extract studied for protective effect in liver diseases were summerised. The varios isolated compounds studied herein are Andrographolide, neo-andrographolide, bacoside-A, colchicine, populnin, naringenin, echinacoside, kolaviron, ternatin, indigtona, rubiadin, bacicalein, baicalin, wogonin, punicalagin, punicalin for their hepatoprotective activity. There are several chemicals have been known to induce heptotoxicity by producing reactive species which cause depletion in tissue thiol, lipid peroxidation, plasma membrane damage like carbontetrachloride, paracetomol, thioacetamide, antituberculer drugs, D galactosamine, liposachharide and arsenic etc.
The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 μl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GalN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity.
The carbon resonances of
1,4-0,O-dimethyl-chiro-inositol are assigned and the β-methylation shifts
ascertained. The relationship between chemical shift and the stereochemistry of
the methoxyl carbons is also examined.
A decoction of the leaves and stems of Desmodium adscendens (Fabaceae), a herb occurring in Africa and South America, is used in traditional medicine. Previous phytochemical research revealed that flavonoids, soyasaponins, β-phenylethylamines, and an indol-3-alkylamine were present. Our investigations have led to the identification of D-pinitol, a carbohydrate with antihyperglycemic, hepatoprotective and anti-inflammatory effects, as a potentially active compound. In order to prepare a quantified extract to be used in in vivo experiments, an analytical method was developed and validated.A gas chromatographic method was developed. Two different derivatization methods, i.e. acetylation and trimethylsilylation, were evaluated. Trimethylsilylation yielded repeatable results and was selected. Five different sugar alcohols were evaluated in order to find a suitable internal standard. Xylitol was chosen since it did not co-elute and its structure closely resembled D-pinitol. Sonication and reflux extraction were investigated in order to obtain a quantitative extraction. This was achieved through reflux extraction during 0.5 h.The method was validated according to the ICH guidelines. The calibration model appeared to be linear, ranging from 5.13 μL/mL to 25.65 μL/mL. The method was precise with an inter-day precision lower than 1.3%. The accuracy ranged from 103.38% to 105.84%. The validated method was used for quantification of D-pinitol in lyophilized decoctions from D. adscendens administered in in vivo experiments. Typically, a D-pinitol level about 5% was measured. Additionally, different food supplements available on the market were screened. The amount D-pinitol found in these supplements ranged from 1.8 mg/capsule to 30 mg/capsule and was 2.0 mg/mL solution.
The flavonoid and triterpenoid soyasaponin content of the aerial parts of Desmodium adscendens from four geographical origins of Africa (Ghana, Nigeria, Sierra Leone, and Togo) has been studied by planar chromatography, because the species is supposed to have hepato-protective activity. Comparative study of these compounds revealed the presence of flavonoids such as vitexine and isovitexine and soyasaponins such as soyasaponin I. The study proves the suitability of TLC analysis of soyasaponins for fingerprinting of this genus.
The hepatoprotective effect of methanolic extract of the leaf of Phyllanthus amarus (P. amarus) against ethanol-induced oxidative damage was investigated in adult male Wistar albino rats. P. amarus (250 and 500 mg/kg/day) and ethanol (5 g/kg/day, 20% w/v) were administered orally to animals for 4 weeks and 3 weeks, respectively. Ethanol treatment markedly decreased the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in the liver, which were significantly enhanced by P. amarus treatment. Glutathione-S transferase (GST), which was increased after chronic ethanol administration, was significantly reduced by P. amarus treatment in the liver. Also, P. amarus significantly increased the activities of hepatic alanine transaminase (ALT) and aspartate transaminase (AST) as well as alkaline phosphatase (ALP), with a concomitant marked reduction in the plasma activity of the transaminases in the ethanol-challenged rats. Lipid peroxidation level, which was increased after chronic ethanol administration, was significantly reduced in the liver by P. amarus co-treatment. Results show that P. amarus leaf extract could protect the liver against ethanol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and increasing the antioxidant defence mechanism in rats.
Silybum marianum or milk thistle (MT) is the most well-researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin-induced liver diseases.
To test whether ethanol feeding could induce Toll-like receptor 4 (TLR4) responses, assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.
Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control, model, low and high dose betaine groups. Except control group, all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 wk. Betaine was administered intragastrically after exposure of ethanol for 4 wk. The changes of liver histology were examined. The expression of TLR4 mRNA and protein was detected by RT-PCR and Western blot, respectively. The serum aminotransferase activity [alanine transarninase (ALT), aspartate aminotransferase (AST)], serum endotoxin, and liver inflammatory factors [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-18 (IL-18)] were also assayed.
Compared with control group, rats of model group developed marked liver injury, accompanied by an increase of ALT (159.41 +/- 7.74 U/L vs 59.47 +/- 2.34 U/L, P < 0.0001), AST (248.25 +/- 1.40 U/L vs 116.89 +/- 3.48 U/L, P < 0.0001), endotoxin (135.37 +/- 30.17 ng/L vs 44.15 +/- 7.54 ng/L, P < 0.0001), TNF-alpha (20.81 +/- 8.58 pg/mL vs 9.34 +/- 2.57 pg/mL, P = 0.0003), IFN-gamma (30.18 +/- 7.60 pg/mL vs 16.86 +/- 9.49 pg/mL, P = 0.0039) and IL-18 (40.99 +/- 8.25 pg/mL vs 19.73 +/- 9.31 pg/mL, P = 0.0001). At the same time, the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption (1.45 +/- 0.07 vs 0.44 +/- 0.04, P < 0.0001; 1.83 +/- 0.13 vs 0.56 +/- 0.08, P < 0.0001). Compared with model group, betaine feeding resulted in significant decreases of ALT (64.93 +/- 6.06 U/L vs 159.41 +/- 7.74 U/L, P < 0.0001), AST (188.73 +/- 1.11 U/L vs 248.25 +/- 1.40 U/L, P < 0.0001), endotoxin (61.80 +/- 12.56 ng/L vs 135.37 +/- 30.17 ng/L, P < 0.0001), TNF-alpha (9.79 +/- 1.32 pg/mL vs 20.81 +/- 8.58 pg/mL, P = 0.0003), IFN-gamma (18.02 +/- 5.96 pg/mL vs 30.18 +/- 7.60 pg/mL, P = 0.0008) and IL-18 (18.23 +/- 7.01 pg/mL vs 40.99 +/- 8.25 pg/mL, P < 0.0001). Betaine also improved liver steatosis. The expression levels of TLR4 mRNA or protein in liver tissues were significantly lowered (0.62 +/- 0.04 vs 1.45 +/- 0.07, P < 0.0001; and 0.65 +/- 0.06 vs 1.83 +/- 0.13, P < 0.0001). There was a statistical difference of TLR4 mRNA and protein expression between high- and low-dose betaine groups (0.62 +/- 0.04 vs 0.73 +/- 0.05, P < 0.0001, and 0.65 +/- 0.06 vs 0.81 +/- 0.09, P < 0.0001).
Betaine can prevent the alcohol-induced liver injury effectively and improve the liver function. The expression of TLR4 increases significantly in ethanol-fed rats and betaine administration can inhibit TLR4 expression.
Liver disorders are one of the common recent problems affects on the human health. These disorders due to many environmental polluted sources. Many herbal, medicinal and pharmaceutical plants and their extracts are widely studied by many researchers. Silybum marianum got a bright reputation in relieve the liver diseases, and that might be for the potent silymarin mixture. Mechanism of action for silymarin conducted mainly to the antiradical and anticarcinogenic roles. Ethyl acetate (100mg/kg bw) and ethanol seed extracts for S. marianum (100mg/kg bw) were tested against the injection (i.p.) by carbon tetrachloride (2 ml/kg bw) the inducer of liver damage. Their activity were compared with standard hepatic drug hepaticum (100mg/kg bw) for 10 days. Ethanolic extract showed the most significantly decrease in the liver enzymes. For the oxidative experiments, ethyl acetate showed the most increase for glutathione level and the risk factor HDL/LDL significantly. Hepaticum was the most powerful group for the significant decreasing for malondialdehyde and fucosidase activity. Some equal improvements were noticed in the histopathological studies for the protective groups.
The aim was to study the effect of naringenin, a biologically active compound, on tissue antioxidant status and lipid peroxidation in ethanol-induced hepatotoxicity in rats.
Rats were divided into four groups: Groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment.
The results showed significantly elevated levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione and vitamins C and E in ethanol-treated rats compared with control rats. Administration of naringenin to rats with ethanol-induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol-treated rats. Histological changes observed in the liver correlated with the biochemical findings.
Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol-induced hepatotoxicity.
Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol which occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. This study was designed to investigate the hepatoprotective and antioxidant properties of carvacrol on D-galactosamine (D-GalN)-induced hepatotoxicity and oxidative damage in male albino Wistar rats. D-GalN hepatotoxic rats exhibited elevation in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and lipidperoxidative markers such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides. Activities of enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and the levels of non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma, erythrocytes, liver, and kidney decreased in the hepatotoxic rats. Oral administration of carvacrol for 21 days brought these parameters towards normal. The biochemical observations were supported by histological studies of rat liver and kidney tissues. These results suggest that carvacrol could afford a significant hepatoprotective and antioxidant effect against D-GalN-induced rats.
The protective effect of Emblica officinalis, a commonly used botanical in many Ayurvedic preparations, was investigated for its effects on liver mitochondria of ethanol-administered rats. Oxidative stress and reactive oxygen species-mediated toxicity are considered two of the key underlying mechanisms responsible for alcohol-induced liver injury and mitochondrial dysfunction. Alcohol-administered rats showed a significant elevation of plasma transaminases (aspartate and alanine aminotransferases), alkaline phosphatase, and gamma-glutamyl transferase compared to control rats. However, activities of hepatic mitochondrial antioxidant enzymes, viz., superoxide dismutase, glutathione peroxidase, and reduced glutathione, were significantly lower. Chronic alcohol feeding also increased lipid peroxide levels, protein carbonyl content, and overproduction of nitric oxide followed by lowered activities of NADH dehydrogenase, succinate dehydrogenase (SDH), and cytochrome c oxidase and content of cytochromes. Administration of E. officinalis fruit extract (EFE) at a dose of 250 mg/kg of body weight/day to alcoholic rats offers protection by simultaneously lowering the carbonyl content and lipid peroxidation and elevating antioxidant enzyme activities, SDH, NADH dehydrogenase, and cytochrome c oxidase activities, and content of cytochromes in hepatic mitochondria. Our data indicate that EFE administration to chronically alcohol-fed rats offers protection against alcohol-induced alterations. The active tannoid principles and nitric oxide scavenging compounds present in EFE may have contributed to the protection observed.
Ononitol monohydrate, structurally similar to glycoside was isolated from Cassia tora L. leaves. Fifty Male rats were divided into five groups. Group I served as normal control. Group II, III and IV rats were induced hepatotoxicity by CCl(4) administering single dose of CCl(4) on 8th day only. Group III was treated with ononitol monohydrate (20mg/kg body weight) and group IV was treated with reference drug silymarin (20mg/kg body weight) both dissolved in corn oil and administering for 8 days. Ononitol monohydrate with corn oil alone was given for 8 days (group V). At the end of the experimental period all the animals were sacrificed and analyzed for biochemical parameters to assess the effect of ononitol monohydrate treatment in CCl(4) induced hepatotoxicity. In in vivo study, ononitol monohydrate decreased the levels of serum transaminase, lipid peroxidation and TNF-alpha but increased the levels of antioxidant and hepatic glutathione enzyme activities. Compared with reference drug silymarin ononitol monohydrate possessed high hepatoprotective activity. Histopathological results also suggested the hepatoprotective activity of ononitol monohydrate with no adverse effect. Hence we conclude that ononitol monohydrate is a potent hepatoprotective agent.
Drug-induced liver injury (DILI) is a major reason drugs fail during development or are withdrawn from the market. The ability to predict, detect, and avoid DILI through appropriate patient selection and effective monitoring has proved to be an elusive goal. Many approved drugs have labeling recommendations for serum enzyme monitoring intended to detect and prevent hepatotoxicity, but such monitoring is often seen as inconvenient, uncomfortable, costly, and inefficient by both patients and doctors, and thus monitoring recommendations are poorly followed, if at all. This review considers whether monitoring works to prevent DILI, whether monitoring recommendations are derived from data or opinions, and whether any better alternatives exist.
The effects of three chemically different groups of compounds, (triterpenoid saponins, beta-phenylethylamines and tetrahydroisoquinolines), known to be present in Desmodium adscendens, on plasma membrane ion channel, cytochrome P450 NADPH-dependent oxygenation of arachidonic acid, and production of prostaglandins by the cyclooxygenase enzyme system, are described. The very high-conductance calcium-activated potassium ion channel, which is responsible for the maintenance of tone in smooth muscles, was activated by the saponins. The cytochrome P450 NADPH-dependent monooxygenase reaction, which produces epoxy- and hydroxylated eicosanoids from arachidonic acid metabolism, was inhibited by an analogue of the tetrahydroisoquinoline present in the plant. This analogue also acted as a reductant in the prostaglandin synthesizing system using microsomes from ram seminal vesicles. The same system was activated by the beta-phenylethylamines found in the plant material, with the formation of more prostaglandins, the type being dependent on the amount of cyclooxygenase enzyme used and the presence or absence of coenzyme.
Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140 intraperitoneal injections of D-galactosamine (500 mg/kg body wt, three times weekly). Controls received injections of saline solution. Cryostat sections of liver tissue obtained on biopsy or autopsy were immunostained with a panel of monoclonal and polyclonal monospecific antibodies reactive with macrophages, T and B lymphocytes, desmin, the extracellular matrix components fibronectin; laminin; collagen types I, III and IV; and the fibronectin receptor alpha 5 beta 1. Total RNA was extracted and Northern-blot analysis was performed with a specific cDNA probe for rat collagen type III. Spotty liver cell necrosis and mild portal and parenchymal inflammation was seen after 10 injections of galactosamine. After 20 to 40 injections, expansion of protal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of cirrhosis at later intervals. These progressive histological changes were paralleled by a gradual increase of desmin-positive cells in developing septa with deposition of fibronectin; collagen types I, III, and IV; and laminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of mRNA for collagen type III. In conclusion, repetitive administration of galactosamine causes progressive liver disease with prominent bile ductule proliferation and development of fibrous septa. These pathological alterations bear some resemblance to the morphological changes in chronic biliary disease in human beings.
Large-conductance calcium-dependent potassium (maxi-K) channels play an important role in regulating the tone of airway smooth muscle and the release of bronchoconstrictive substances from nerves in the lung. Crude extracts of Desmodium adscendens, a medicinal herb used in Ghana as a treatment for asthma, inhibit binding of monoiodotyrosine charybdotoxin (125I-ChTX) to receptor sites in bovine tracheal smooth muscle membranes that have been shown to be associated with maxi-K channels. Using this assay, three active components have been purified and identified by NMR and MS. Comparison with authentic samples revealed the three active components as the known triterpenoid glycosides dehydrosoyasaponin I (DHS-I), soyasaponin I, and soyasaponin III. The most potent of these compounds, DHS-I, is a partial inhibitor of 125I-ChTX binding (Ki = 120 nM, 62% maximum inhibition). Inhibition of 125I-ChTX binding is primarily due to a decrease in the observed maximum number of binding sites, with a smaller decrease in affinity. DHS-I increases the rate of toxin dissociation from its receptor, suggesting that modulation of ChTX binding occurs through an allosteric mechanism. DHS-I reversibly increases the open probability of maxi-K channels from bovine tracheal smooth muscle incorporated into planar lipid bilayers when applied to the intracellular, but not the extracellular, side of the membrane at concentrations as low as 10 nM. In contrast, DHS-I had no effect on several other types of potassium channels or membrane transporters. This natural product is the first example of a high-affinity activator of calcium-dependent potassium channels and is the most potent known potassium channel opener.
The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 microl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GaIN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity.
The hepatoprotective effects of whey protein on two injections of D-galactosamine (300 mg/kg, i.p.) were investigated in rats fed a modified AIN-93M diet formulated with a protein source of casein or whey for 16 d. The whey protein-containing diet clearly suppressed an increase in plasma alanine and aspartate aminotransferase activity, lactate dehydrogenase and bilirubin, which are hepatitis markers, and also hyaluronic acid, a fibrosis marker. In addition, it suppressed histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis. These results suggest that supplementation with whey protein can help prevent the development of hepatitis and portal fibrosis.
The present study was undertaken to investigate the protective effect and possible mechanism of aqueous extract from Phyllanthus amarus Schum. et. Thonn. (PA) on ethanol-induced rat hepatic injury. In the in vitro study, PA (1-4 mg/ml) increased %MTT reduction assay and decreased the release of transaminases (AST and ALT) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic parameters studied in vivo included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), together with histopathological examination. In acute toxicity study, single dose of PA (25, 50 and 75 mg/kg, p.o.) or SL (silymarin, a reference hepatoprotective agent, 5 mg/kg), 24h before ethanol (5 g/kg, p.o.) lowered the ethanol-induced levels of transaminases (AST and/or ALT). The 75 mg/kg PA dose gave the best result similar to SL. Treatment of rats with PA (75 mg/(kg day), p.o.) or SL (5 g/(kg day), p.o.) for 7 days after 21 days with ethanol (4 g/(kg day), p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, HTG and TNF-alpha back to normal. Histopathological observations confirmed the beneficial roles of PA and SL against ethanol-induced liver injury in rats. Possible mechanism may involve their antioxidant activity.
The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (P<0.05), but pinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.
Use of Desmodium in the treatment of hepatitis, and medicaments thereof
- P Tubé Ry
- A M Tubé Ry
Tubé ry, P., Tubé ry, A.M., 1989. Use of Desmodium in the treatment of hepatitis, and medicaments thereof. Patent EP0309342(A1).
Use of pinitol or chiro-inositol for protecting the liver
- Y C Shin
- J Jeon
- J J Kim
Shin, Y.C., Jeon, J., Kim, J.J., 2007. Use of pinitol or chiro-inositol for protecting the liver. Patent US2007098826 (A1).