Protective role of nutraceuticals against myocarditis.

Myocarditis is an inflammatory disease of the myocardium that mostly affects young adults. The disease is commonly caused by viral infection, medications, autoimmune disorders, and inflammatory conditions. Nearly 50% of the cases of myocarditis are due to post-viral immune response in a setting of an identifiable or non-identifiable infection. The clinical manifestation is nonspecific ranging from asymptomatic courses to sudden death in infants and young patients. This review describes the properties of phytochemicals as plant-derived active ingredients which can be used in the prevention and treatment of myocarditis and its associated risk factors. Meanwhile, it has illustrated epidemiological analyses, mechanism of action, and the metabolism of phytochemicals in animal and human clinical trials. We also mentioned the precise mechanism of action by which phytochemicals elicit their anti-viral, anti-inflammatory, antioxidant, and immunomodulatory effects and how they regulate signal transduction pathways. Nevertheless, comprehensive clinical trials are required to study the properties of phytochemicals in vivo, in vitro, and in silico for a proper management of myocarditis. Our findings indicate that phytochemicals function as potent adjunctive therapeutic drugs in myocarditis and its related complications.

Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies.

BACKGROUND: Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents. SUMMARY: Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.

Prevention and management of idiosyncratic drug-induced liver injury: Systematic review and meta-analysis of randomised clinical trials.

Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and findings of RCTs in the prevention and management of idiosyncratic DILI. A systematic literature search up to January 31st, 2020 was performed. Recognised scales were used to assess methodological bias and quality of the studies. Quantitative and qualitative analyses were performed. Heterogeneity was assessed with I2 statistic. Overall, 22 RCTs were included: 12 on prevention (n = 2,471 patients) and 10 in management (n = 797) of DILI/non-acetaminophen DILI-related acute liver failure (ALF). Silymarin (eight studies), bicyclol (four), magnesium isoglycyrrhizinate (three), N-acetylcysteine (three), tiopronin (one), L-carnitine (one), and traditional Chinese medicines (two) were tested in the intervention arm, while control arm mostly received standard supportive care or placebo. Main efficacy criteria in the prevention RCTs was DILI incidence or peak of liver enzymes value. In management RCTs, the efficacy parameter was usually 50 % decrease or normalisation of liver enzymes, or survival rate in DILI-related ALF patients. Overall, 15 trials described the randomisation method, eight were double-blind (n = 672) and nine had sample size estimation (n = 880). Four RCTs involving 377 patients used an intention-to-treat analysis. Based on the scarce number of trials available, tested agents showed limited efficacy in DILI prevention and management and a favourable safety profile. In conclusion, heterogeneity among studies in DILI case qualification and methodologic quality was evident, and the RCTs performed demonstrated limited efficacy of specific interventions. International research networks are needed to establish a framework on RCTs design and therapeutic endpoints.

Bioactive Molecules from the Alpinia Genus: A Comprehensive Review.

BACKGROUND: Floral has diversity and unique nature due to the complex structure and component. Alpinia is an important genus of the Zingiberaceae family having complex taxonomical diversity. The presence of many unique bioactive molecules makes this genus, a pharmaceutically important genus. They provide a wide range of medicinal properties, including traditional remedies to modern therapeutic applications. METHODS: Extracts of Alpinia mostly contain bioactive molecules and secondary metabolites such as polyphenolics, tannins, flavonoids and other therapeutically important compounds. These bioactive molecules are biologically active, treating against inflammation, cancer, arterial hypertension, and other deadly diseases. RESULTS: These bioactive molecules can act as natural enzyme inhibitors for some of the deadly diseases and can block the pathway for metabolic activities. In addition, these genera have played a major role in multidisciplinary studies of phytochemistry, ethnobotany, and pharmacological aspects in day-to-day life. CONCLUSION: Therefore, this review highlights the fewer known facts of the genus Alpinia in terms of bioactive molecules and its significant therapeutic applications to help in combating major diseases of humans.

Novel Therapeutic Approaches Against Acetaminophen-induced Liver Injury and Acute Liver Failure.

Liver injury and acute liver failure caused by acetaminophen (APAP, N-acetyl-p-aminophenol, paracetamol) overdose is a significant clinical problem in most western countries. The only clinically approved antidote is N-acetylcysteine (NAC), which promotes the recovery of hepatic GSH. If administered during the metabolism phase, GSH scavenges the reactive metabolite N-acetyl-p-benzoquinone imine. More recently, it was shown that NAC can also reconstitute mitochondrial GSH levels and scavenge reactive oxygen/peroxynitrite and can support mitochondrial bioenergetics. However, NAC has side effects and may not be efficacious after high overdoses. Repurposing of additional drugs based on their alternate mechanisms of action could be a promising approach. 4-Methylpyrazole (4MP) was shown to be highly effective against APAP toxicity by inhibiting cytochrome P450 enzymes in mice and humans. In addition, 4MP is a potent c-Jun N-terminal kinase inhibitor expanding its therapeutic window. Calmangafodipir (CMFP) is a SOD mimetic, which is well tolerated in patients and has the potential to be effective after severe overdoses. Other drugs approved for humans such as metformin and methylene blue were shown to be protective in mice at high doses or at human therapeutic doses, respectively. Additional protective strategies such as enhancing antioxidant activities, Nrf2-dependent gene induction and autophagy activation by herbal medicine components are being evaluated. However, at this point, their mechanistic insight is limited, and the doses used are high. More rigorous mechanistic studies are needed to advance these herbal compounds. Nevertheless, based on recent studies, 4-methylpyrazole and calmangafodipir have realistic prospects to become complimentary or even alternative antidotes to NAC for APAP overdose.

Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution.

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses.

Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.

Protective effects of methanol extract of Plukenetia conophora seeds and 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl on the reproductive function of male Wistar rats treated with cadmium chloride.

OBJECTIVES: Male infertility caused by exposure to heavy metals is a current global issue. Exposure to cadmium chloride (CdCl2) negatively affects the male reproductive system. Many infertile people, especially in developing countries, resort to folkloric treatment. Plukenetia conophora is used in Nigerian folk medicine to promote fertility. This study investigated the effects of Plukenetia conophora (PC) and 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl (DDMP) on Wistar rats with cadmium chloride-induced testicular damage. METHODS: Forty-two male Wistar rats (150-190g) were divided into seven groups (n=6) and treated daily for 54 days as follows: Controls (normal saline); CdCl2 (2mg/kg single IP dose); CdCl2 + 200 mg/kg vitamin E; CdCl2 + 100 or 200 mg/kg PC; and CdCl2 + 25 or 50 mg/kg DDMP. The rats were sacrificed 55 days after the start of the study; Samples were collected for analysis. Biochemical parameters malondialdehyde, nitric oxide, antioxidant enzymes, and proton pumps were measured by spectrophotometry. Reproductive hormones were measured using ELISA. Data were analysed using ANOVA and differences in mean values were considered significant at p<0.05. RESULTS: Significant increases in sperm count, motility, and viability were observed in the groups given CdCl2+Vitamin E, CdCl2+PC or CdCl2+DDMP as compared with the CdCl2 group. Malondialdehyde and nitric oxide levels in the groups treated with CdCl2+PC or CdCl2+DDMP decreased significantly when compared with the group given CdCl2. Significant increases were observed in antioxidant enzymes, proton pump, and testosterone in the groups treated with CdCl2+PC or CdCl2+DDMP, respectively. CONCLUSION: Plukenetia conophora alleviated male reproductive toxicity induced by cadmium chloride in Wistar rats. 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl present in Plukenetia conophora may be responsible for the ameliorative effects.

Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model.

SCOPE: Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). MATERIALS AND RESULTS: Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS). On day 21 of the experiment, pigs were administrated with LPS or saline. At 2 h and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA, and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity, and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adapter molecule, receptor-interacting protein kinase 2 (RIPK2). CONCLUSION: These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways.

Escalation of liver malfunctioning: A step toward Herbal Awareness.

ETHNOPHARMACOLOGICAL RELEVANCE: About 2-5% of the world's population is suffering from liver toxicity including Pakistan with the second highest rate of hepatitis prevalence. Liver is a vital body organ which not only performs metabolic activities but also aids in detoxification, storage and digestion of food. Now a day's malnutrition, alcohol consumption and drug addiction are major causes of liver diseases throughout the world. In fact, there is no possible outcome to compensate liver malfunction for long term, and transplantation of liver is the only option left after the irretrievable injury of hepatic function. Subsequently, natural based therapeutic approaches are in the process of scrupulous testing as strong hepatoprotective mediator. In this regard plants are well thought hepatoprotective agents having multiple active components. In this review, based on species' pharmacology and safety we have compiled some plants which show strong hepatoprotective activity, main phytoconstituents with biological activities and few commercially used herbal formulations. MATERIALS AND METHODS: Ethnopharmacological information was gathered by an extensive literature survey like WHO monographs on selected herbal medicinal plants (Vol 1-Vol 4); Principles and Practice of Phytotherapy, Mills S and Bone K, Churchill Livingstone, London, UK; Herbal Drugs and Phytopharmaceuticals, Wichtl M Medpharm Press, Stuttgart 3rd edn; Pharmacology and Applications of Chinese Materia Medica Vols 1 and 2, Chang H-M and But P P-H World Scientific, Singapore; British Herbal Compendium Vol. 2, Bradley P British Herbal Medicine Association, Bournemouth, UK; ESCOP Monographs 2nd edn. Thieme, Stuttgart, Germany; as well as by using electronic databases such as Pubchem, Chemspider, http://www.herbal-ahp.org; http://www.ahpa.org; http://whqlibdoc.who.int/publications/2003/9241546271.pdf; http://www.escop.com, Pubmed, HubMed and Scopus. RESULTS: Data for more about 29 plants have been accomplished for their bioactive constituent(s), biological activities and medicinal uses. Some of the plants have been identified as strong hepato-modulator. Such knowledge about traditional medicinal plants can be globally applied for safe and evidence based use in pharmacological applications. CONCLUSION: With the rise in liver risks a meek struggle has been made to draw attention toward herbal therapy. Hepatoprotective constituents of said plants are expressed with chemical structures. However, for certain plants active constituents are not still isolated/purified but overall plant extract was found effective in providing protection against hepatic injury. As a future perspective, there is need to purify plant active constituents for ethnomedical rationale.

Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage.

Doxorubicin (DXR) is one of the most important chemotherapeutic agent. However, nephrotoxicity reduces its clinical utility in humans. The aim of the study was to investigate protective effects of curcumin (CMN) against DXR-induced nephrotoxicity. Rats were subjected to oral treatment of CMN (100 and 200 mg/kg body weight) for 7 days. Nephrotoxicity was induced by single intra peritoneal injection of DXR (40 mg/kg body weight) on the fifth day and then the experiment was terminated on the eighth day. Nephroprotective effects of CMN were associated with decrease in serum toxicity markers and increase in antioxidant enzyme activities. CMN was able to reduced the levels of inflammatory markers such as TNF-α, NF-κB, IL-1ß, iNOS and COX-2 in the rats. It also reduced the expressions of apoptotic marker including caspase-3, and oxidative DNA damage marker including 8-OHdG. Collectively, these findings indicated that CMN protect against DXR-induced nephrotoxicity.

Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats.

In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol + lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol + lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.

The inhibitory effects of Dracocephalum moldavica L. (DML) on rat cerebral ischemia reperfusion injury.

Ischemia reperfusion injury (IRI) is closely associated with oxidative stress and inflammatory responses. Dracocephalum moldavica L. (DML), a Chinese herbal medicine is known to exert protective effects on myocardial ischemia reperfusion injury in rats by inhibiting oxidation damage and inflammatory reactions. However, the effectiveness of DML in cerebral ischemia reperfusion injury (CIRI) as a protective substance and the underlying mechanisms remain to be determined. The aim of this study was thus to examine the influence of DML on CIRI using a rat model induced by 2-h transient middle cerebral artery occlusion (MCAO) produced by intraluminal suture blockade followed by 22 h reperfusion. The parameters determined include neurological behavior, histochemical assessment of cerebral infarct volume, and determination of various metabolic biomarkers. Data showed that DML markedly improved neurobehavioral scores and reduced cerebral edema and infarction. In addition, DML significantly reduced malondialdehyde (MDA) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), in addition, marked decrease in levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Data suggest that the protective effects of DML on CIRI may be related to processes involving antioxidation and anti-inflammation.

Cardioprotective effect of Platycodon grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy: study protocol for a randomized controlled trial.

BACKGROUND: Anthracyclines, alone or in combination with other drugs, are among the most effective chemotherapeutic agents to treat breast cancer both in the adjuvant and neoadjuvant setting. Unfortunately, anthracycline-associated dose-dependent cardiotoxicity is a limiting factor in clinical use. Extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity. However, most cardioprotective agents have shown little effect in clinical trials. Herbal medicines are pure, natural substances that have been used for centuries in many countries, including China. This trial aims to evaluate the cardioprotective effects and safety of Platycodon grandiflorum granules compared to placebo granules in patients with early breast cancer receiving anthracycline-based chemotherapy. METHOD/DESIGN: This study is a single-center, double-blinded, randomized, placebo-controlled, parallel-group trial. A total of 120 patients will be randomly allocated in a 1:1 ratio to receive either P. grandiflorum granules or placebo granules twice daily for 12 weeks. The primary outcome is heart failure (either clinical or subclinical). The secondary outcomes include all-cause mortality, cardiac death, electrocardiogram (ECG) findings, left ventricular diastolic function, longitudinal systolic strain and velocities measured by tissue Doppler imaging, cardiac biomarkers, such as troponin I (TnI), brain natriuretic peptide (BNP), and creatine kinase isoenzymes (CK-MB). Assessments will be performed at baseline (before randomization) and 3, 6, 9, 12, 16, and 20 weeks after randomization. DISCUSSION: This will be the first clinical trial to evaluate the cardioprotective effects and safety of P. grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. TRAIL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16009256 . Registered on 23 September 2016.

Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.

Cadmium (Cd) is a toxic environmental and occupational pollutant with reported toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano-zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release a great amount of Zn2+ in their environment. This research was carried out to investigate the more potent properties of the metal zinc among sub-acute cadmium intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg bw) for 28 days. The experimental animals were decapitated, and the biochemical biomarkers (enzymatic and non-enzymatic) were determined in their serum after oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with a one-way ANOVA and t test. P < 0.05 was considered as statistically significant. The haematocrit (HCT) significantly increased and blood coagulation time significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride, total cholesterol, LDL, and free fatty acids increased significantly in the cadmium- and nano-zinc-treated rats compared with the controls. However, albumin, total protein, and HDLc significantly decreased in the cadmium- and nano-zinc-treated rats compared with the controls (P < 0.05). It seems that in the oral administration of nano-zinc, the smaller sizes with low doses and the larger sizes with high doses are more toxic than metallic zinc. In a few cases, an inverse dose-dependent relationship was seen as well. This research showed that in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not suitable for protection against cadmium intoxication.

Ameliorated Effects of (-)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats.

The aim of the study was to assess the protective effect of (-)-epigallocatechin gallate (EGCG), a flavonoid abundant in green tea, against ammonium metavanadate (AMV)-induced oxidative stress in male Wistar rats. Four groups of animals have been used, a control group and three test groups. In the first test group, AMV was intra-peritoneally (i.p) injected daily (5 mg/kg body weight for five consecutive days). The second test group of animals was also injected daily with EGCG (5 mg/kg body weight) during the same period. However, the third test group was i.p. injected with both AMV and EGCG (5 mg/kg body weight for five consecutive days). When given alone, AMV induced an oxidative stress evidenced by an increase of lipid peroxidation levels (expressed as TBARS concentration) in kidney. In these animals, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were significantly decreased, suggesting significant reduction of the antioxidant defense system at the cell level. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In AMV-treated animals receiving EGCG, the oxidative stress was much less pronounced and activities of antioxidant enzymes were kept close to control values. Histopathological changes were less prominent. Our results confirm that green tea and other sources of flavonoids might confer a strong protection against ammonium metavanadate-induced oxidative stress.

Genotoxic and chemopreventive assessment of Cynara scolymus L. aqueous extract in a human-derived liver cell line.

Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.

The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats.

The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3ß- and 17ß-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.

Keto-supplemented Low Protein Diet: A Valid Therapeutic Approach for Patients with Steroid-resistant Proteinuria during Early-stage Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Low protein diets supplemented with keto acid (sLPD) are recommended for patients with stage 3-5 chronic kidney disease (CKD). This study assessed whether sLPD is beneficial for patients with steroid-resistant proteinuria during early-stage CKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A 1-year randomized controlled trial was conducted from 2010 to 2012. In this study, 108 proteinuric patients who were steroid-resistant were assigned to a sLPD group (0.6 g/kg/d with 0.09 g/kg/d keto acids) or a normal protein diet group (NPD, 1.0 g/kg/d). Estimated dietary protein intake, urinary protein excretion, remission rate, renal function, nutritional status, and blood pressure were measured. RESULTS: Baseline characteristics were comparable between the sLPD group (47 patients) and the NPD group (49 patients). Urinary protein excretion significantly decreased in sLPD compared to NPD in months 6, 9, and 12 (P<0.05). Proteinuria reduction was higher in sLPD than in NPD (P<0.001) at the end of the study. Complete remission and partial remission rates were higher in sLPD than in NPD. Serum albumin and pre-albumin levels were higher in sLPD than in NPD in months 9 and 12 (P<0.05). Serum total cholesterol and triglyceride levels declined more significantly in sLPD than in NPD (P<0.01) at the end of the study. There were no differences in nutritional status, renal function, hemoglobin, or blood pressure between the two groups. CONCLUSIONS: sLPD is both nutritionally safe and beneficial, providing nephroprotective effects for early-stage CKD patients with steroid-resistant proteinuria.

A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives.

Hepatoprotective effects of natural compounds have been frequently attributed to their antioxidant properties and the ability to mobilize endogenous antioxidant defense system. Because of involvement of oxidative stress in virtually all mechanisms of liver injury, it is a reasonable presumption that antioxidant properties of these compounds may play a key role in the mechanism of their hepatoprotective activity. Nevertheless, growing evidence suggests that other pharmacological activities of natural compounds distinct from antioxidant are responsible for their therapeutic effects. In this review, we discussed currently known molecular mechanisms of the hepatoprotective activity of 27 most intensively studied phytochemicals. These compounds have been shown to possess anti-inflammatory, antisteatotic, antiapoptotic, cell survival and antiviral activity through interference with multiple molecular targets and signaling pathways. Additionally, antifibrotic properties of phytochemicals have been closely associated with apoptosis of hepatic stellate cells and stimulation of extracellular matrix degradation. However, although these compounds exhibit a pronounced hepatoprotective effects in animal and cell culture models, the lack of clinical studies remains a bottleneck for their official acceptance by medical experts and physicians. Therefore, controlled clinical trials have an imperative in confirmation of the therapeutic activity of potentially hepatoprotective compounds. Understanding the principles of the hepatoprotective activity of phytochemicals could guide future drug development and help prevention of clinical trial failure. Also, the use of new delivery systems that enhances bioavailability of poorly water soluble compounds may improve the results already obtained. Most importantly, available data suggest that phytochemicals possess a various degree of modulation of specific signaling pathways, pointing out a need for usage of combinations of several hepatoprotective compounds in both experimental studies and clinical trials.