Nephroprotective Activity Research Articles

EFFECT OF 2-HYDROXY-N-NAPHTHALENE-1-YL-2-(2-OXO-1,2-DIHYDRO-INDOLE-3-YLYDENE)-ACETAMIDE ON KIDNEY FUNCTION IN EXPERIMENTAL RENAL FAILURE

Heterocyclic compounds are the basis for a significant number of medicinal substances. Among them, there is indole and derivatives of 2-oxoindolin-3-glyoxylic acid. This group of compounds has been found out to have neurotropic effects as well as cardio- and hepatoprotective properties. This preceded the study of their nephroprotective activity in the experimental pathology. The aim of the work is to study the effect of 2-hydroxy-N-naphthalen-1-yl-2(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide on the excretory function of kidneys in the experimental acute renal failure.
 Materials and methods. Experiments were performed on 24 adult male rats. Compound 18 was administered is a dose of 12 mg/kg. Ethyl-methyl-hydroxypyridine succinate in a dose of 100 mg/kg served as a reference preparation. Glycerol-induced acute kidney damage was modelled by intramuscular injection of the 50 % glycerol solution. Under the condition of water load, the excretory kidney function, kidney mass coefficients, creatinine and urea content in the blood plasma were assessed by the standard methods.
 Results. Glycerol-induced kidney damage did not cause the death of test animals. It significantly reduced the rate of glomerular filtration and water resorption; proteinuria developed due to an increase in protein concentration and a decrease in its excretion as compared to the parameters of intact rats. This change in the kidney function was accompanied by an increase in the content of creatinine and urea in the blood plasma. The use of the reference preparation ethyl methyl hydroxypyridine succinate prevented a decrease in the rate of glomerular filtration, increased creatinine excretion, but did not affect the values ​​of other parameters. Compound 18 showed an antiproteinuric effect. The substance under investigation did not change probably or worsen other parameters. In glycerol-induced kidney damage, ethyl methyl hydroxypyridine succinate and compound 18 did not effectively prevent the increase in kidney mass coefficient.
 Conclusion. In glycerol-induced kidney damage, compound 18 in a dose of 12 mg/kg did not cause a pronounced nephroprotective effect.

Review on Medicinal Importance of Butea monosperma Lam. (Taub)

Butea monosperma is a renowned therapeutic plant, a medium size deciduous tree broadly dispersed in India, Bangladesh, Cambodia, Myanmar, China South-Central, Nepal, Laos, Sri Lanka, China Southeast, Pakistan, and Vietnam. Butea monosperma is being used in customary medication preparation from the pre historic period. It is acknowledged as the forest’s flame and is often branded as Dhak or Palash. It is described in Upanishads, Susruta Samhita, Vedas, Ashtanga Sangraha, Astanga Hridaya, and Charka Samhita. It belongs to the family of Fabaceae, which has an extensive range of vigorous principles, and it has phytoconstituents such as glycosides, flavonoids, etc.This revisional analysis is focused on the pharmacological actions, mainly shown by seeds, flowers, fruits, barks,leaves, etc., like anti-diabetic, anthelmintic, hepatoprotective, anti-stress, anti-implantation, anti-convulsant, wound healing, giardiasis, anti-oxidant, anti-dopaminergic, anti-microbial, sunscreen, anti-diarrheal, free radical scavenging, anti-filarial, anti-fungal, nephroprotective, protease inhibitor, osteogenic, hemagglutinating, anti-ulcer, giardiasis, anti-asthmatic, anti-inflammatory, anti-fertility and anti-cancer activity. GC-MS analysis of Butea monospermashows the attendance of important compounds which is volatile and HPLC analysis for non-volatile, which supplies light to its medicinal properties. These therapeutic chattels may provide impending active principles with advanced usefulness and the leastafter-effects as equated to accessible artificial drugs.

In vitro antioxidant, anti-inflammatory and ex vivo nephroprotective activities of Chenopodium ambrosioides

Chenopodium ambrosioides is a medicinal plant used in Togo to treat nephropathy and other diseases. The present study was undertaken to evaluate the in vitro antioxidant and anti-inflammatory capacity and the ex vivo nephroprotective capacity of Chenopodium ambrosioides extract. Antioxidant potential was determined in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging, total antioxidant capacity and reducing power tests. Egg albumin denaturation and membrane stabilization tests were carried out to assess its anti-inflammatory effect. The ex vivo nephroprotective activity of the extract was performed in vitro using Fe2Cl2 to induce high levels of malonic dialdehyde (MDA) in kidney homogenate. Results showed that the extract significantly reduced MDA (P < 0.001) and protein levels in the kidney. In vitro, the extract demonstrated its ability to scavenge DPPH (IC50 = 401.57±0.39), reduce ferric iron, and have a total antioxidant capacity of 49.49 ± 0.37 mg EAA/g. The extract also inhibited ovalbumin denaturation and prevented hemolysis, with IC50 values of 61.83 ± 0.69 µg/mL and 637.78 ± 0.26µg/mL respectively. Phytochemical screening revealed the presence of polyphenols, flavonoids, alkaloids, tannins, and saponosides in the extract. This study concludes that Chenopodium ambrosioides extract has anti-inflammatory and antioxidant properties, and can be used in the treatment of nephropathy.

Helicanthes elasticus (Desr.) Danser: Its Pharmacological Potentials and New Prospects

Helicanthes elasticus (Desr.) Danser is a member of family Loranthaceae which is found widely growing on mango trees in southern India. Alkaloids, carbohydrate, steroids, tannins, saponins, phenols, flavonoids and triterpenoids are mainly believed to be responsible for its wide therapeutic actions. It is known to possess medicinal activities such as antimicrobial activity, immunomodulatory hepatoprotective, antioxidant, anti diabetic, diuretic and natriuretic activity, cytotoxicity (anti-tumour activity), anti-asthmatic and anti-anaphylactic, anti-arthritic, anti-ulcer, anti-inflammatory, anti urolithiatic and nephroprotective activity. In this work information concerning pharmacological activities possessed by different parts of Helicanthes elasticus has been keenly observed and summarized.

Morphological changes in the kidney tissue of rats with experimental diabetes mellitus and during correction with metformin and modulators of hydrogen sulfide metabolism

Annotation. Metformin is widely used for pharmacocorrection of diabetic nephropathy in type 2 diabetes mellitus. However, the mechanisms of the protective effect of metformin on the kidneys remain unclear, in particular, the contribution of the hydrogen sulfide system to metformin’s nephroprotective effect is unknown. Therefore, the aim of our study was to assess the role of metformin and its combination with modulators of hydrogen sulfide metabolism in the correction of histological changes in the kidneys of streptozotocin-induced diabetic rats. The studies were performed on 30 white non-linear male rats, which were divided into five groups: 1 group - control; group 2 – animals with experimental diabetes, which was initiated by a single intraperitoneal injection of streptozotocin (40 mg/kg of weight) in 0.1 M citrate buffer (pH 4.5); Group 3 - animals with experimental diabetes, which were treated with metformin (500 mg/kg/day, intragastrically) from the 3rd to the 28th day; Group 4 - animals with diabetes mellitus, which, along with metformin, were administered NaHS (56 μmol/kg/day, intragastrically); Group 5 - animals with diabetes mellitus, which, along with metformin, were administered propargylglycine (442 μmol/kg/day, intragastrically). Histological examinations were performed according to generally accepted methods using an Olympus BX-41 light microscope (Olympus Europe GmbH, Japan). It was found that animals with experimental diabetes develop nephrosclerosis and glomerular hypertrophy, damage to the endothelium of kidney vessels, interstitial inflammation, and edema, and dystrophic and necrobiotic changes in the glomeruli. The administration of metformin to diabetic animals reduced the severity of nephrosclerosis, glomerular hypertrophy, destruction of vascular endotheliocytes, inflammation, and damage to the glomerular apparatus. The use of the hydrogen sulfide donor NaHS increased the nephroprotective activity of metformin, while the introduction of the hydrogen sulfide synthesis inhibitor- propargylglycine, significantly reduced the protective effect of metformin on the kidneys. The obtained results of the histological examination justify the feasibility of implementation of a hydrogen sulfide donor in order to potentiate the renoprotective effect of metformin.

In vitro and in vivo antiplasmodial activities of leaf extracts from Sonchus arvensis L.

BackgroundMalaria continues to be a global problem due to the limited efficacy of current drugs and the natural products are a potential source for discovering new antimalarial agents. Therefore, the aims of this study were to investigate phytochemical properties, cytotoxic effect, antioxidant, and antiplasmodial activities of Sonchus arvensis L. leaf extracts both in vitro and in vivo.MethodsThe extracts from S. arvensis L. leaf were prepared by successive maceration with n-hexane, ethyl acetate, and ethanol, and then subjected to quantitative phytochemical analysis using standard methods. The antimalarial activities of crude extracts were tested in vitro against Plasmodium falciparum 3D7 strain while the Peter's 4-day suppressive test model with P. berghei-infected mice was used to evaluate the in vivo antiplasmodial, hepatoprotective, nephroprotective, and immunomodulatory activities. The cytotoxic tests were also carried out using human hepatic cell lines in [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay.ResultThe n-hexane, ethyl acetate, and ethanolic extracts of S. arvensis L. leaf exhibited good in vitro antiplasmodial activity with IC50 values 5.119 ± 3.27, 2.916 ± 2.34, and 8.026 ± 1.23 μg/mL, respectively. Each of the extracts also exhibited high antioxidant with low cytotoxic effects. Furthermore, the ethyl acetate extract showed in vivo antiplasmodial activity with ED50 = 46.31 ± 9.36 mg/kg body weight, as well as hepatoprotective, nephroprotective, and immunomodulatory activities in mice infected with P. berghei.ConclusionThis study highlights the antiplasmodial activities of S. arvensis L. leaf ethyl acetate extract against P. falciparum and P. berghei as well as the antioxidant, nephroprotective, hepatoprotective, and immunomodulatory activities with low toxicity. These results indicate the potential of Sonchus arvensis L. to be developed into a new antimalarial drug candidate. However, the compounds and transmission-blocking strategies for malaria control of S. arvensis L. extracts are essential for further study.

Nephroprotective effects of Datura stramonium leaves against methotrexate nephrotoxicity via attenuation of oxidative stress-mediated inflammation and apoptosis in rats.

Methotrexate (MTX) is a frontline antimetabolite anticancer drug which is used in different cancer treatments but its nephrotoxicity is a notable drawback that limits its clinical use. The present study was undertaken to examine whether Datura stramonium leaf extract (DSLE) could block MTX nephrotoxic side effect in rats. Animals were divided randomly into Control, Ethanol extract, MTX, and Extract + MTX groups. DSLE (200 mg/kg bw) was orally administered for 21 days, while MTX was injected intraperitoneally (ip) on the 18th day. Serum levels of urea, creatinine and uric acid were determined. Kidney samples were used to determine glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, and renal levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and caspase-3. Injection of MTX resulted in considerable increases (p<0.05) in creatinine, urea, and uric acid levels as well as renal MDA, NO, IL-6, TNF-α and caspase-3 compared to the controls. SOD and GPx increased significantly, while GSH was significantly depleted. Interestingly, DSLE markedly reduced (p<0.05) levels of creatinine, urea, uric acid, TNF-α, NO, MDA and caspase-3, whereas renal GSH increased markedly compared to the MTX group. DSLE has nephroprotective activity against MTX toxicity. However, further mechanistic studies are needed.

Antidiabetic Properties of Nymphaea Species (Water Lilies): A Review

Abstract: Diabetes mellitus is a highly prevalent metabolic disease specified by increased blood glucose and impaired insulin function. Various antidiabetic drugs are currently being used, but plant sources of antidiabetic agents are of recent scientific interest as they possess multitarget effects and the most negligible side effects. Nymphaea species (water lilies) have long been traditionally taken as food and antidiabetic agents. Growing research evidence suggests that different Nymphaea species exhibit antidiabetic activity. Therefore, we took an endeavor to summarize the available scientific literature on the antidiabetic activity of the genus Nymphaea. We extensively searched in three search engines and selected 27 in vivo, 9 in vitro, and 4 in silico studies regarding antidiabetic properties of 7 Nymphaea species named Nymphaea stellata, Nymphaea pubescens, Nymphaea lotus, Nymphaea alba, Nymphaea nouchali, Nymphaea rubra, and Nymphaea odorata. All these studies coincided with the conclusion that the Nymphaea species have effective antidiabetic properties and safety. Therefore, Nymphaea species are potential candidates for evidence-based complementary and alternative medicine and integrative medicine. The species have been found to show antidiabetic properties by antihyperglycemic, antihyperlipidemic, pancreatic β-cell-regenerating, insulin secretion and sensitivity promoting, glucose uptake and metabolizing protein-expressing, intestinal glucose metabolizing enzyme inhibiting, hepatoprotective, cardiovascular protective, nephroprotective, antioxidant, and anti-inflammatory activity. A variety of antidiabetic compounds have been identified in the 7 Nymphaea species, which can be responsible for the antidiabetic activity exerted by diverse mechanisms. Future studies should be conducted on other Nymphaea species and different plant parts and diabetic parameters to investigate their antidiabetic activity and responsible phytochemical contents.

Nephroprotective effect of Physalis peruviana L. calyx extract and its butanolic fraction against cadmium chloride toxicity in rats and molecular docking of isolated compounds

BackgroundCadmium is an environmentally toxic metal that has deleterious effects on both animals and humans due to its accumulation in different body tissues. Physalis peruviana L. fruit and calyx contain many active constituents which are used traditionally for their different biological activities. Based on the traditional uses of P. peruviana L. calyx, we aimed to evaluate the nephroprotective effect of their 80% aqueous methanol extract (AME) and n-butanol fraction (Bu.F.) against cadmium chloride-induced nephrotoxicity in rats and to correlate this activity with phytoconstituents isolated using molecular docking studies.MethodsThe n-butanol fraction of P. peruviana L. calyx was fractionated using various chromatographic techniques and the isolated compounds were identified based on their chemical and spectroscopic data. The nephroprotective activity was assessed using cadmium chloride-induced nephrotoxicity in the rat model, by measuring some important parameters such as body weight, kidney weight, serum urea, and creatinine levels, oxidative stress markers, inflammatory markers, and histopathological examinations of kidney tissue. Molecular docking studies of the isolated compounds were performed.ResultsThree withanolides named 4 β-hydroxywithanolide E (1), Physalin B (2) and 3α, 14β-dihydroxywithaphysalin N (3) were isolated and identified from the n-butanol fraction of P. peruviana L calyx extract. The extract and its butanol fraction significantly improved the serum kidney function markers and tissue oxidative status including malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT). Additionally, the extracts significantly decreased the levels of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappaB (NF-κβ). Moreover, the histological changes were ameliorated by the extracts. The molecular docking study showed that the isolated compounds displayed a remarkable inhibitory activity against IκB kinase.ConclusionThe AME and its butanol fraction of P. peruviana L calyx showed potential nephroprotective activity against cadmium chloride-induced nephrotoxicity which is correlated at least in part to its considerable withanolides content.

Phytochemical analysis and nephroprotective potential of Ajwa date in doxorubicin-induced nephrotoxicity rats: Biochemical and molecular docking approaches.

The purpose of this study is to evaluate the likely defensive impact of Ajwa date aqueous extract (AJDAE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. Sixty male Wister albino rats were randomly and equally separated into six groups (n= 10), and they were treated as follows: untreated control group, extract groups administered with 0.75 and 1.5mg kg bw of AJDAE, toxicant control group administered with DOX, and prophylactic groups were treated with 0.75 and 1.5 mg/kg of AJDAE and 15 mg/kg DOX. Biochemical parameters, antioxidant enzymes, renal functions, DNA integrity, and histopathology were studied to evaluate the nephroprotective activity of AJDAE. Furthermore, bioactive compounds were utilized for in silico molecular docking. AJDAE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, calcium, phosphorous, and uric acid), antioxidative markers, and MDA. Noticeable histopathological improvements supported this result. Results of in silico studies revealed that d-Mannitol, 6TMS derivative, palmitic acid, and TMS derivative had a higher docking score with human soluble epoxide hydrolase (-10.9kcal/mol) and NF-κB-DNA (-7kcal/mol). The present findings indicated that AJDAE could decrease ROS generation and lipid peroxidation (LPO) and repair the DOX injection-related DNA damage.

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1β, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.

A Review on Antioxidant Properties of Extracts Obtained from the Leaf, Stem, Bark and Flower of Calotropis Species

Traditional medicine can be a valuable source in primary health care due to its enriching acceptability and enhanced compatibility with the human body with minimal side effects. Karanjwa Caesalpinia bonducella Linn is an important medicinal plant used in the Unani system of medicine for a long time due to its multiple therapeutic properties. The present review aimed to explore the existing data of the drug about its conventional uses based on its phytochemical constituents and pharmacological actions. Karanjwa review was undertaken by exploring the bibliographic database viz. Science Direct Pub Med Scopus and Google Scholar. The search was carried out using the terms lsquoKaranjwarsquo lsquoCaesalpinia bonducella lsquoFever nutrsquo lsquoGajgarsquo. Moreover books published in Urdu and English were also used to gather information as representative literature. The plant is known for its use in the treatment of different systemic ailments due to the presence of steroidal saponins fatty acids hydrocarbons phytosterols isoflavones amino acids and phenolics alkaloids present bonducin a homoisoflavone. In the Unani system of medicine the pharmacological actions of Karanjwa include antipyretic anti-inflammatory antimicrobial tonic desiccatives antispasmodic immuno-modulators antioxidant anxiolytic antidepressant hypoglycaemic antiallergic and antihistaminic anti asthmatic hepatoprotective anticancer and nephroprotective activities. The present study explored the pharmacological phytochemical and therapeutic properties of Caesalpinia bonducella Linn. Many pharmacological activities mentioned in Unani medicine have been validated and several activities need further exploration owing to its immense therapeutic scope.

Phytomedicinal properties of Hygrophila schulli (Neeramulliya).

Hygrophila schulli which is known as "Neermulli'' in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of H. schulli whole plant or its parts for the treatment of different communicable and non-communicable diseases including diabetes mellitus and tuberculosis. Active constituents and secondary metabolites including alkaloids, tannins, steroids, proteins, flavonoids, and glycosides are identified to possess antimicrobial, antitumor, antioxidant, hepatoprotective, anthelmintic, nephroprotective, antidiabetic, anticataract, anti-inflammatory, anti-nociceptive, hematopoietic, diuretic, antiurolithiatic, antipyretic, neuroprotection, and anti-endotoxin activities. In this review, we reviewed clinical studies, patents, and analytical studies from the earliest found examples from 1886 to the end of 2021. We critically analyzed and attempt to summarize the information based on bioactivities and chemical composition of H. schulli plant extracts which will be of future use for researchers in this field.

Jamun (Syzygium cumini (L.) Skeels): The conventional underutilized multifunctional plant-an exotic gleam into its food and functional significance

Jamun is a valuable therapeutic plant in India and is also referred to as “Black Jamun ” while, all the plant parts, i.e., leaves, bark, fruit, roots, and seeds, have therapeutic applications. The fruits are perishable seasonal berries containing the pulp and are processed into several value-added products like health drinks, juices, squashes, jellies, and wine leaving behind kernels as a significant waste. The kernels are not only rich in carbohydrates, protein, minerals, and crude fibers but also contain a substantial variety of biogenic phytochemicals with versatile applications in both the food and nonfood industries. The enormous functional properties of these bioactive compounds get well-reported while the plant parts are used to produce a variety of traditional medicines with antioxidants, anti-diabetic, anti-pyretic, nephroprotective, and anti-diarrheal activities. Amongst all, the anti-diabetic properties are the most promising and explored as the seeds contain jambosin, alkaloid, and anti-mellin or jambolin glycosides, which impede the diastatic starch to sugar conversion. The plant has a long history of therapeutic applications with limited documented evidence to support its use. Health-conscious people often seek healthy diets loaded with natural substances with the highest functional properties, which has resulted in increased consumption of Jamun fruits in the recent past. Thus, there is a need to evolve, establish and document the traditional medicinal use of the Jamun with strong scientific rationales to outspread its consumption further. Therefore, the present era demands scientific intervention to explore this plant for its utilization in the food and pharmacy industry. • Syzygium cumini, contains phytochemicals with enormous functional and therapeutic applications. • Fruits are processed into variety of traditional medicines and functional foods. • Limited clinical evidences to support role of Syzygium cumini in the therapeutic health management. • Systematic studies required to increase the utilization of Syzygium cumini in both food and pharmaceutical industry.

Liraglutide ameliorates gentamicin-induced acute kidney injury in rats via PGC-1α- mediated mitochondrial biogenesis: Involvement of PKA/CREB and Notch/Hes-1 signaling pathways.

Acute kidney injury (AKI) is a challenging side effect which may clinically impede the use of gentamicin (GM). The present study explored the impact of liraglutide (Lir) on GM-induced kidney injury in rats. Lir (0.2 and 0.4mg/kg, s.c) was given for 10days (a dose/day) starting 3days before giving GM (100mg/kg, i.p) once daily for 7days. Interestingly, Lir notably ameliorated GM-induced elevated levels of renal injury markers; urea and creatinine. Moreover, Lir remarkably mitigated malondialdehyde (MDA) level and elevated glutathione (GSH) level as well as superoxide dismutase (SOD) activity. Also, Lir pre-treatment notably diminished inflammatory markers levels; interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule (VCAM), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (INF-γ). In addition, Lir significantly replenished expression of Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α), Protein kinase A (PKA), cAMP response element-binding protein (CREB), nuclear Nuclear factor erythroid 2-related factor 2 (Nrf2), heme Oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2), and remarkably attenuated expression of Notch homolog 1 (Notch1), Hairy and enhancer of split-1 (Hes-1), Bcl-2-associatedX(Bax), cleaved caspase 3 and nuclear Nuclear factor Kappa B (NF-κB (p65)). The nephroprotective activity of Lir was further confirmed by histopathological examination as well as transmission electron microscopy (TEM). In conclusion Lir achieved its nephroprotective effects through the amelioration of oxidative stress, inflammatory and apoptotic manifestations. It is worth-mentioning that the current study is the first to focus on the involvement of mitochondrial biogenesis and its upstream regulators, PKA/CREB and Notch/Hes-1 signaling pathways in the nephroprotective potentials of Lir. The attenuation of the aforementioned injurious aspects is partially attributed to the improvement of the mitochondrial status as demonstrated by elevated PGC-1α expression via acceleration of PKA/CREB and abatement of Notch/Hes-1 signaling pathways.

The Nephroprotective Effects of Hibiscus sabdariffa Leaf and Ellagic Acid in Vitro and in Vivo Models of Hyperuricemic Nephropathy

Hyperuricemic nephropathy (HN) is caused by urate crystals that get deposited in the kidney and contribute to renal fibrosis. Uric acid (UA) has been proven to directly cause renal mesangial cell oxidative stress and fibrosis in the pathogenesis of HN. Some antioxidants can be used as chemopreventive agents of HN. Hibiscus sabdariffa leaf extracts (HLE), rich in polyphenol, have been shown to possess hypoglycemic, antioxidant, hypolipidemic, antiatherosclerotic, and anticancer effects. The aim of the study is to examine the inhibitory effect of HLE and its main component ellagic acid (EA) on renal fibrosis. In vitro, mouse renal glomerular mesangial SV40MES13 cells pretreated with UA were demonstrated to trigger obvious morphological changes and viability loss, as well as affect matrix metalloproteinases (MMPs) activities. Noncytotoxic doses of HLE and EA abolished the UA-induced cell injury and MMP-2/9 secretion. In addition, HLE and EA exhibited antioxidant and anti-inflammatory effects on the UA-treated cells with a reduction in transforming growth factor-beta (TGF-β) production. Next, the UA-activated pro-fibrotic factors, extracellular matrix (ECM) deposition, and epithelial-mesenchymal-transition (EMT) were inhibited by HLE or EA. Mechanistic assays indicated that antifibrotic effects of HLE might be mediated via TGF-β/Smad signaling, as confirmed by the transfection of Smad7 siRNA. In vivo, HLE and EA supplementations significantly alleviated HN development, which may result from inhibiting adenine-induced TGF-β production accompanying oxidative stress and inflammation, as well as fibrogenesis. Our data imply that EA-enriched HLE regulates the TGF-β/Smad signaling, which in turn led to reduced renal mesangial cell injury and fibrosis in HN and provided a new mechanism for its nephroprotective activity.

Production, Function, and Applications of the Sesquiterpenes Valencene and Nootkatone: a Comprehensive Review

Valencene and nootkatone, two sesquiterpenes, extracted from natural sources, have great market potential with diverse applications. This paper aims to comprehensively review the recent advances in valencene and nootkatone, including source, production, physicochemical and biological properties, safety and pharmacokinetics evaluation, potential uses, and their industrial applications as well as future research directions. Microbial biosynthesis offers a promising alternative approach for sustainable production of valencene and nootkatone. Both compounds exert various beneficial activities, including antimicrobial, insecticidal, antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, hepatoprotective, and nephroprotective and other activities. However, most of the studies are performed in animals and in vitro, making it difficult to give a conclusive description about their health benefits and extend their application. Hence, more attention should be paid to in vivo and long-term clinical studies in the future. Moreover, valencene and nootkatone are considered safe for consumption and show great promise in the applications of food, cosmetic, pharmaceutical, chemical, and agricultural industries.

Investigation of the nephroprotective activity of Moringa peregrina leaves aqueous extract in mice

Traditional remedies for Moringa peregrina leaves have a variety of uses with confirmed biological and therapeutic effects, as per published reports. The current study aims to evaluate the ability of the leaves aqueous extract to protect from nephrotoxicity in gentamicin-treated mice. Phytochemical analysis for the aqueous extract was performed using DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay for antioxidants, Folin-Ciocalteu, AlCl3 and HPLC- MS/MS analysis, focusing on phenol and flavonoid content. The nephroprotective activity of the prepared extract was evaluated by means of variable biochemical parameters including Creatinine (Cr), Uric Acid (UA), and Urea (Ur). In addition, histological examination of renal tissues was performed in all mice groups (control, gentamicin-induced (150 mg/Kg i.p) and aqueous extract-orally treated groups (500 and 1000 mg/Kg)). Findings reveal that the prepared extract has total phenols (555.57±0.92mg/g, equivalent to gallic acid), flavonoids (40.08±1.56 mg/g, equivalent to quercetin), and DPPH IC50 (3.10 µg/ml). HPLC-MS/MS analysis revealed the presence of 10 phenols and flavonoids compounds. In vivo studies showed a significant (P &amp;lt; 0.05) reducing effect for the high-dose treatment, on serum and urine concentrations for UA, Cr, and U, among the nephrotoxicity induced mice. Low-dose treated group showed significant reduction on serum concentration of UA, Cr and U, but only for Cr concentration in urine. The histological examination showed an improvement in the image of the renal tissue among the induced-nephrotoxicity mice, which was treated with high-dose extract. In conclusion, leaves aqueous extract of M. peregrina have shown potential protective effect to counteract some of the gentamicin consequences on kidney functions.

Nephroprotective Activity of Papaloquelite (Porophyllum ruderale) in Thioacetamide-Induced Injury Model.

Acute kidney injury and impaired kidney function is associated with reduced survival and increased morbidity. Porophyllum ruderale is an edible plant endemic to Mexico used in Mexican traditional medicine. The aim of this study was to evaluate the nephroprotective effect of a hydroalcoholic extract (MeOH:water 70:30, v/v) from the aerial parts of P. ruderale (HEPr). Firstly, in vitro the antioxidant and anti-inflammatory activity of HEPr was determined; after the in vivo nephroprotective activity of HEPr was evaluated using a thioacetamide-induced injury model in rats. HEPr showed a slight effect on LPS-NO production in macrophages (15% INO at 40 µg/mL) and high antioxidant activity in the ferric reducing antioxidant power (FRAP) test, followed by the activity on DPPH and ABTS radicals test (69.04, 63.06 and 32.96% of inhibition, respectively). In addition, values of kidney injury biomarkers in urine (urobilinogen, hemoglobin, bilirubin, ketones, glucose, protein, pH, nitrites, leukocytes, specific gravity, and the microalbumin/creatinine) and serum (creatinine, urea, and urea nitrogen) of rats treated with HEPr were maintained in normal ranges. Finally, 5-O-caffeoylquinic, 4-O-caffeoylquinic and ferulic acids; as well as 3-O-quercetin glucoside and 3-O-kaempferol glucoside were identified by HPLC as major components of HEPr. In conclusion, Porophyllum ruderale constitutes a source of compounds for the treatment of acute kidney injury.

Nephroprotective Activity of an Aqueous Extract of Alchornea Cordifolia Stapf. (Euphorbiaceae) on Acute Kidney Injury Induced by Paracetamol in Rat

Nephroprotective Activity of an Aqueous Extract of Alchornea Cordifolia Stapf. (Euphorbiaceae) on Acute Kidney Injury Induced by Paracetamol in Rat