Nephroprotective Potential of Linagliptin and Glimepiride: a Comprehensive Review

Hepatotoxicity and renal failure are two of the major complications of diabetes mellitus, among its numerous other complications. The primary cause of liver and kidney problems is the oxidative stress that is brought on by persistently high blood sugar levels. The current study aimed to assess the possible hepatic and nephron protective roles of a novel anti-diabetic poly herbal preparation containing dried leaves of Tinospora cordifolia, dried bark of Cinnamomum zeylanicum, dried seeds of Trigonella foenum, and dried seeds of Nigella sativa in streptozotocin (STZ) induced diabetic rats. Experimentally diabetes in Albino rats was induced by using streptozotocin. By examining several biochemical indicators to gauge their impact on the liver and kidney, diabetic rats were tested against an in-house prepared novel poly herbal formulation. Hepatic glycogen (HG), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total proteins (TP), total bilirubin (TB), direct (DB) and indirect bilirubin (IB), albumin, and globulin were used to measure the hepatoprotective efficacy. Blood urea nitrogen (BUN), urea, uric acid, and creatinine were used as kidney function markers to assess the nephroprotective potential. Six rats were placed in each of the thirteen groups, ethanolic extract polyherbal preparation was chosen for further testing of its hepatoprotective and nephroprotective potentials since it significantly reduced blood glucose levels in our prior trials. In streptozotocin-induced diabetic albino rats, the impaired liver and kidney functions significantly improved. The presence of active phytochemical ingredients may be the cause of the reversal of hepatic renal biochemical changes. Accordingly, the study came to the conclusion that the poly herbal combination (EHPH) efficiently heals diabetes-related liver and renal issues as well as prevents subsequent difficulties.

Many high-altitude plants, such as Hedyotis aspera, need to be explored for their possible medicinal value. The current study explored the protective effect of Hedyotis aspera methanolic extract whole plant (HAME) against gentamicin-induced nephrotoxicity in rats. It profiled their phytocontents using HPLC-QTOF-MS/MS analytic methods. The LC-MS analysis of HAME revealed 27 compounds. Eight compounds followed Lipinski’s rule of five and were found to be potential TNF-α inhibitors with binding affinities of −6.9, −6.3, −6.3, and −6.3 Kcal/mol, such as 14,19-Dihydroaspidospermatine, coumeroic acid, lycocernuine and muzanzagenin. All potential compounds were found to be safe according to the ADMET analysis. The in vitro 2,2-diphenyl-1-picrlhydrazyl (DPPH) assay assessed the antioxidant activity. The nephroprotective activity was assessed in rats using a gentamicin-induced nephrotoxicity model. The in vivo analysis involved histological examination, tissue biochemical evaluation, including a kidney function test, catalase activity (CAT), reduced glutathione (GSH) levels, superoxide dismutase (SOD), and the inflammatory mediator TNF-α. Based on DPPH activity, HAME showed a scavenging activity IC50 of 264.8 ± 1.2 µg/mL, while results were compared with a standard vitamin C IC50 of 45 ± 0.45 µg/mL. Nephrotoxicity was successfully induced, as shown by elevated creatinine and uric acid levels, decreased kidney antioxidant levels, and increased TNF-α in gentamicin-treated rats. The HAME treatment significantly reduced serum creatinine and uric acid levels, increased GSH (p < 0.01 **), CAT (p < 0.01 **), and SOD (p < 0.001 ***), and decreased TNF-α (p < 0.001 ***) in nephrotoxic rats. The histopathological examination of the groups treated with HAME revealed a notable enhancement in the structural integrity of the kidneys as compared to the group exposed to gentamicin. Biochemical, histopathological, and phytochemical screening of HAME suggests that it has nephroprotective potential, owing to the presence of 14,19-Dihydroaspidospermatine, coumeroic acid, lycopene, and muzanzagenin.

12 - Nephrotoxicity and Nephroprotective Potential of African Medicinal Plants

Background/Objectives: Chronic kidney disease (CKD) is a progressive pathology, with high global prevalence, associated with inflammation and oxidative stress. Given the limited capacity of conventional treatments to reverse renal damage, complementary alternatives have emerged such as supplementation with anthocyanins from maqui (Aristotelia chilensis), known for their antioxidant and anti-inflammatory properties. This review analyzes the evidence for their impact on CKD progression. Methods: A narrative review of the experimental literature regarding maqui anthocyanins, their bioavailability, and their effects on oxidative stress, inflammation, and CKD to January 2025 was conducted. Articles without peer review or without a focus on Aristotelia chilensis were excluded, guaranteeing an updated compilation on its nephroprotective potential. Results: Anthocyanins have shown benefits in reducing oxidative stress, inflammation, and glycemia regulation. Preclinical studies suggest improvements in renal function as well as less fibrosis. Human trials indicate positive effects on metabolism, although evidence in CKD patients is limited. Bioavailability remains a challenge to optimizing efficacy. Conclusions: Maqui is a promising source of anthocyanins, with nephroprotective potential. However, robust clinical studies are required to determine its safety, optimal dose, and long-term impact in CKD. Its incorporation into evidence-based therapeutic strategies could offer an innovative approach in the management of this disease. More clinical studies are needed to validate the preclinical findings and optimize the therapeutic use of maqui in CKD.

Background: The Unani medical system uses single medications or formulations, which are combinations of multiple drugs, to manage a variety of ailments. The Unani physician used these formulations in their clinics. A Polyherbal Unani Formulation (PUF) was selected to explore its Anti-thrombocytopenic activity. This formulation is used in fever, and based on its ingredients, the Anti-thrombocytopenic activity was explored. Aim: The research aimed to examine the anti-thrombocytopenic and hemostatic effect of a compound Unani herbal formulation in the busulfan-induced male Sprague Dawley (SD) rats. Methods: Busulfan-induced thrombocytopenia method was used in this study. Preventive and curative regimens were tested, and platelet counts, bleeding time, clotting time, Haematological and biochemical blood tests were carried out. The histopathology was also done at the end of the experiments. The decoction of the PUF was used in the male SD rats for this study. Results: The PUF did not show anti-thrombocytopenic activity in the preventive regimen, but in the curative regimen, it exhibited increased platelet count, much better in animals than busulfan control animals and showed mild anti-thrombocytopenic activity. It has also shown hepatoprotective and nephroprotective potential in the preventive and curative regimen. Conclusion: PUF exhibited mild anti-thrombocytopenic activity in the curative study and hepatoprotective and nephroprotective potential in this study. Major Findings: Present study demonstrated the mild anti-thrombocytopenic activity in curative regimen, and hepatoprotective as well as nephroprotective potential of a traditional Unani formulation in preventive and curative regimen.

Plants have been an incredible reservoir of remedy for multitudinous of times. It has been recognized by researchers as an ancient form of medicine to cure common population. About four billion population of the world, i.e., 80% of the total world population presently use the traditional system of medicine or herbal drugs for primary health care. In India, > 65% of the total population use herbal medicinal products for the treatment of diseases. Over the eras, many plant species have been investigated for possible medical applications. It has been trusted in all cultures and communities throughout the world due to their lesser side effects, higher safety and efficacy against health illness. Aerva plants are known widely for their exceptional medicinal uses. They have been employed conventionally for their medicinal properties by the common folk in several regions of the world. This indicates the efficacy of these remarkable herbs. They are also known for their multiple biological activities such as anti-oxidant, anti-bacterial, anti-lithiatic, Hepato protective, anti-diabetic, anti-cancer, anti-hyper lipidemic and nephro protective potential. These pharmacological actions are associated with the presence of valuable nutrients and biochemical compounds such as sterols/terpenes, flavonoids, alkaloids, phenolics and sugars. This review article includes the detailed exploration of the morphology, phyto chemistry and pharmacological aspects of Aerva lanata in an attempt to provide a direction for further research.

BackgroundCisplatin is an outstanding anticancer drug, but its use has been decreased remarkably due to sever nephrotoxicity. R. vesicarius L. is a leafy vegetable that is evident with anti-angeogenic, anti-inflammatory, anti-proliferative, hepatoprotective, and nephroprotective potential. Therefore, this study was designed to inspect its methanol extract (RVE) for possible nephroprotective effect.MethodsPrimarily, in vitro antioxidant activity of RVE was confirmed based on 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging aptitude. Thereafter, Swiss Albino male mice were treated with cisplatin (2.5 mg/kg) for 5 successive days to induce nephrotoxicity. Recovery from nephrotoxicity was scrutinized by treating the animals with RVE (25, 50, and 100 mg/kg) intraperitoneally (i.p.) for the next 5 consecutive days. After completion of treatment, mice were sacrificed and kidneys were collected. Part of it was homogenized in sodium phosphate buffer for evaluating malondialdehyde (MDA) level, another part was used to evaluate gene (NQO1, p53, and Bcl-2) expression. Moreover, the hydrogen peroxide (H2O2) neutralizing capacity of RVE was evaluated in HK-2 cells in vitro. Finally, bioactive phytochemicals in RVE were determined using gas chromatography–mass spectrometry (GC-MS).ResultsRVE showed in vitro antioxidant activity in a dose-dependent fashion with 37.39 ± 1.89 μg/mL IC50 value. Treatment with RVE remarkably (p < 0.05) decreased MDA content in kidney tissue. Besides, the expression of NQO, p53, and Bcl-2 genes was significantly (p < 0.05) mitigated in a dose-dependent manner due to the administration of RVE. RVE significantly (p < 0.05) reversed the H2O2 level in HK-2 cells to almost normal. From GC-MS, ten compounds including three known antioxidants “4H-Pyran-4-one, 2, 3-dihydro-3,5-dihydroxy-6-methyl-”, “Hexadecanoic acid”, and “Squalene” were detected. The extract was rich with an alkaloid “13-Docosenamide”.ConclusionOverall, RVE possesses a protective effect against cisplatin-induced kidney damage.

The phytochemical constituents in the aqueous methanolic leaf extract of Triclisia gilletii responsible for its nephroprotective potentials against ethane-1,2-diol induced nephrolithiasis as previously investigated in our laboratory were elucidated. The extract was prepared using 80% aqueous methanol in 72 h, Phytochemical contents of aqueous methanolic extract of Triclisia gilletii (TGME) was identified using both a Thermo Scientific DSQII single quadrupole gas chromatography (GC) and a Thermo Scientific liquid chromatography (LCQ Fleet system) tandem mass spectroscopy. The chromatogram acquisition, detection of mass spectral peaks and their waveform processing were performed using Xcalibur MS Software (Thermo Scientific Inc.). GC-MS analysis revealed the presence of phenols, fatty acids, vitamins and steroids. Likewise, for LC-MS analysis kaempferol and dihydrovomifoliol-O-glucoside were detected. The identified constituents have possible contributively effect on the acclaimed pharmacological potential of Triclisia gilletii against ethane-1,2-diol induced nephrolithiasis.

The mechanical extraction of various phytochemicals from Phlomis stewartii (P. stewartii) was modeled using response surface methodology (RSM). The Box-Behnken design (BBD) was used to optimize the three independent variables comprising of 17 experimental runs, with the experiments randomly arranged to minimize the effects of unexpected variation in the observed dependent variables {extraction yield, total phenolic content (TPC), and total flavonoid content (TFC)} due to systematic errors. The speed (X1, 100, 150 and 200rpm), solvent volume (X2, 100 and 150 and 200 mL), and extraction time (X3, 2, 5 and 100h) at 3-levels (high and low coded levels) were used to evaluate BBD of RSM. Results showed that the maximum value of yield, TPC and TFC in leaves ethanol extracts (LEE); flower ethanol extract (FEE), and whole plant ethanol extracts (WPEE) were observed at the following extraction conditions: A X1 of 150rpm, X2 of 200 mL and X3 at 8h. The minimum values were observed at an X1 of 150rpm, X2 of 100 mL and X3 of 2h. Analysis of variance (ANOVA) and the interaction effects of independent factors showed that X2 and X3 significantly positively influenced the response variables. These values closely matched the predicted yield, TPC and TFC. High-performance liquid chromatography (HPLC) analysis reveals that hydroxybenzoic acid, p-coumaric acid, gallic acid, chlorogenic acid, and salicylic acid, are the major secondary metabolites in the extracts. Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of different compounds such as thiazole, 2-ethylacridine, silicic acid, arsenous acid, 3,5-ethanoquinolin-10-one, and hexahydropyridine. All these identified compounds exhibit a wide range of various biological potential, including anti-viral, anti-inflammatory, anti-diabetic and anti-bacterial activities. The highest α-amylase inhibitory potential IC50 (53.33 ± 0.21µg/mL), and α-glucosidase inhibitory potential IC50 (51.07 ± 0.17µg/mL) were shown by LEE extracts. The study concludes that LEE extracts may have anti-inflammatory, immunomodulatory, antioxidant, hepatoprotective, and nephroprotective potential, suggesting potential for further investigation in diabetes management.

This research aims to investigate the in vitro and in vivo nephroprotective activity of Michelia champaca leaves extracts in gentamicin-induced nephrotoxicity rats. The flavonoid and phenols-rich fractions of Michelia champaca leaves extract were subjected to in silico methods based on in vitro investigations, using renal target proteins. The results of the in vitro antioxidant study of extracts were tested for cytoprotective MTT assay and anti-inflammatory efficacy by protein denaturation assay using human embryonic kidney cells (HEK293). The in vivo nephroprotective potential of the extract was evaluated at a lower dose of 250 mg/kg and a higher dose of 500 mg/kg body weight in gentamicin-induced nephrotoxicity in rats with histopathological investigations. The Michelia champaca hydroalcoholic extract (MCHAE) shows remarkable binding affinity with bonding interactions of flavonoids and phenolics-based ligands observed with the target proteins that provided early information. The in vitro cell lines study revealed no cytotoxicity and better anti-inflammatory effect on HEK293 cells with cytoprotective and nephroprotective efficacy of MCHAE. The in vivo nephroprotective activity improved at a dose of 500mg/kg of MCHAE than Michelia champaca ethanolic extract (MCEE). Histopathological investigations revealed the improvement in gentamicin-induced renal toxicity by the MCHAE orally treated group compared to other groups. These results of MCHAE are more effective than MCEE and have a marked in vitro antioxidant, and cytoprotective effect in HEK293 cell lines, with good interaction scores of ligands in molecular docking studies with nephroprotective potential benefits in gentamicin-induced nephrotoxicity in rats.

Objective: The aim of the current study was to investigate the hepatoprotective, nephroprotective, and cholesterol-lowering activity of aqueous extract of Murraya koenigii (MK) leaves against AlCl3-induced oxidative stress in rats.&#x0D; Methods: Wistar albino rats were distributed into six groups (6 each). Group I (control), and Group II administered with distilled water, and aluminum chloride (AlCl3), (40 mg/kg body weight [b.w], oral), respectively. Group III rats were treated with standard Vitamin E (100 mg/kg b.w, p.o) and AlCl3 (40 mg/kg b.w, oral). Group IV, V, and VI received aqueous extract of leaves of Murraya koenigii (AEMK) (100 mg/kg b.w, peroral [p.o], 200 mg/kg b.w, p.o, and 400 mg/kg b.w, p.o), respectively, for a period of 35 days.&#x0D; Results: Histopathological examination was observed deformities in hepatic and renal tissues due to aluminum exposure which augment the aforementioned results. Coadministration of AEMK along with Al significantly restored the serum biomarkers to their near-normal levels and has the ability to overcome Al-induced oxidative stress, manifested by a significant reduction in hepatic and renal malondialdehyde level. It increased cellular antioxidant defense, particularly by increasing GPx, glutathione, GR, and catalase levels, preserved normal hepatic and renal histological architecture.&#x0D; Conclusion: It could be concluded that AEMK has significant radical scavenging activity and can mop up Al-induced toxicity, suggesting hepatoprotective and nephroprotective potential.

ObjectiveSafranal is a natural product from saffron (Crocus sativus L.) with anti-inflammatory and nephroprotective potential. This study aimed to explore the role of safranal in a cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis (MGN).MethodsAfter model establishment, Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage. A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters. Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG, C3, and Sirt1. Western blotting was performed to measure the protein levels of podocin, nephrin, Sirt1, and factors involved in the NF-κB/p65 pathway. Inflammatory cytokine levels in renal homogenates were determined by ELISA.ResultsSafranal at 100 or 200 mg/kg reduced kidney weight (2.07 ± 0.15 g and 2.05 ± 0.15 g) and the kidney somatic index (0.83 ± 0.08% and 0.81 ± 0.08%) in MGN rats compared with those in the model group without drug administration (2.62 ± 0.17 g and 1.05 ± 0.1%). C-BSA increased the urine protein level to 117.68 ± 10.52 mg/day (compared with the sham group, 5.03 ± 0.45 mg/day), caused dysregulation of renal function indicators, and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples. All the biochemical and histological changes were improved by safranal administration. Safranal at two doses also increased the fluorescence intensities of IgG (0.1 ± 0.009 and 0.088 ± 0.008) and C3 (0.065 ± 0.006 and 0.048 ± 0.004) compared with those in the MGN group (0.15 ± 0.013 and 0.086 ± 0.008). Additionally, safranal reversed the downregulation of podocin, nephrin, and Wilms tumor protein-1 (WT1) levels and reversed the high inflammatory cytokine levels in MGN rats. Mechanistically, safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.ConclusionsSafranal ameliorates renal damage, inflammation, and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.

Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity

A triherbal formulation prepared from a mixture of the leaves of Gongronema latifolium Benth., Ocimum gratissimum L. and Vernonia amygdalina Delile (GOV) was evaluated for hepato-nephro protective and antioxidant properties against D-galactosamine-induced hepatic and renal toxicity in Wistar albino rats. Normal Wistar albino rats were divided into seven groups of seven animals each. Two control experiments were setup which included normal rats treated with D-galactosamine and normal rats that received only distilled water. Three groups were treated with different doses of GOV extract (2000, 4000 and 8000mg kg-1 b. wt) and some standard hepatoprotective drugs such as Liv 52 and silymarin for 13 days prior to intoxication with D-galactosamine. The activities of serum liver enzymes, concentrations of some biochemical analytes, effect on heamatologic parameters and antioxidant status were monitored. The results showed that rats treated with GOV dose dependently exhibited significant (p<0.05) decrease in levels of ALP, ALT, AST, GGT, LDH, cholesterol, creatinine, triglycerides, urea and MDA and subsequently significantly (p<0.05) increased the albumin, total protein, catalase, GPx, GSH, GST and SOD levels when compared to the toxin control rats. The data from this study suggest that the triherbal formulation possess hepato- and nephro-protective potential against D-galactosamine induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases.

Background: Nephrotoxicity induced by drugs is a common cause of renal failure, particularly with agents like cyclophosphamide used in cancer treatment. Natural antioxidants found in plants offer diverse therapeutic benefits. Tinospora cordifolia, a medicinal plant known for its hepatoprotective, diuretic, carminative, digestive, and anti-helminthic properties, was investigated for its potential to counter cyclophosphamide-induced kidney damage in rats. Materials and Methods: Extracts were prepared from dried Tinospora powder, rich in flavonoids, polyphenolics, and alkaloids. Rats were divided into control and treatment groups, with varying doses of the Tinospora extract alongside cyclophosphamide. The blood sample was evaluated for creatinine, urea and BUN. Results: Treatment with the extract, particularly at 400 mg/kg, significantly reduced creatinine levels, as well as serum urea and blood urea nitrogen (p&lt;0.01). These results highlight Tinospora cordifolia's nephroprotective potential, attributed to its flavonoid and polyphenol content. Conclusion: This study underscores the promise of plant-derived compounds in mitigating drug-induced kidney damage, suggesting Tinospora cordifolia as a potential adjunct therapy to preserve renal function during chemotherapy. Further research is needed to elucidate mechanisms and validate these findings for clinical application.