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Nephroprotective and curative effects of Ficus religiosa latex extract against cisplatin-induced acute renal failure
Pharmaceutical Biology
Abstract
Context:
Ficus religiosa L. (Moraceae) is widely planted in the tropics. Its chemical constituents include tannin, saponin gluanol acetate, β-sitosterol, leucoanthocyanidin and leucoanthocyanin which are used for the treatment of pain, inflammation, impotence, menstrual disturbances, uterine tonic and urine related problems.
Objective:
To determine the possible nephroprotective and curative effects of F. religiosa latex methanol extract against cisplatin induced acute renal failure.
Materials and methods:
Methanol extract was obtained by maceration process. Rats were divided in five groups. Group 1 was administered acacia (2% w/v) of 5 ml/kg throughout the experiment; group 2 was treated with single dose of cisplatin (5 mg/kg i.p.) on the 1st day; group 3 (200 mg/kg p.o.) of extract control for the 1st to 10th day, group 4 (200 mg/kg p.o.) of extract from the 1st to 10th day and a single dose of cisplatin (5 mg/kg, i.p.) on 11th day while group 5 received the same dose of cisplatin on day 1 and extract (200 mg/kg p.o.) from the 7th to 16th day.
Results:
Phytochemical screening of the extract revealed the presence of glycoside, alkaloids, tannins (phenolic compounds), flavonoids and amino acids. The half maximal inhibitory concentration (IC50) values of the extract were 31.75 ± 0.12 and 18.35 ± 0.48 µg/ml, respectively. The cisplatin-treated group 2 showed significant changes; renal functions, biochemical parameters and histopathology were significantly (**p < 0.01) recovered by 200 mg/kg curative and protective groups.
Discussion and conclusion:
These findings demonstrated that F. religiosa latex and constituents have excellent nephroprotective and curative activities and thus have great potential as a source for natural health products.
... All 25 articles included in the study has been listed as per the outcomes and findings were mentioned in Table 1. Among those selected studies, Most of the studies found experimental animal models (Ghosh et al., 2016;Cagno, et al., 2015;Ahuja et al., 2011;Patil et al., 2011;Singh & Goel, 2009;Kapoor et al., 2011;Singh, Singh, & Goel, 2011;Yadav & Srivastava, 2013;Raisagar et al., 2019;Choudhari, Suryavanshi, & Kaul-Ghanekar, 2013;Sankar et al., 2014;Pandit et al., 2010;Gulecha and Sivakumar., 2011;Aqil and Ahmad.,2013;Hemaiswarya et al., 2009;Khan et al., 2011;Charde et al., 2010;Uma et al., 2009) One study on Experimental food products and for study based on Review (Singh et al., 2016;Sahoo, 2012;Akhtar et al., 2000;Murugesu et al., 2021). ...
... Articles found on genital ulcers and sores (Ghosh et al., 2016;Khan et al., 2011), anti-amnesic , antiviral (Cagno, et al., 2015), bronchoconstriction (Ahuja et al., 2011), anticonvulsant (Patil et al., 2011;Singh & Goel, 2009;Singh, Singh, & Goel, 2011), anti-asthma (Kapoor et al., 2011), nephroprotective (Yadav & Srivastava, 2013), Wound healing and antiinflammatory (Raisagar et al., 2019;Charde et al., 2010), cervical and anti-cancer (Choudhari, Suryavanshi, & Kaul-Ghanekar, 2013;Sankar et al., 2014;Gulecha and Sivakumar., 2011), antidiabetic (Pandit et al., 2010), Respiratory activity (Mousa et al., 1994), anti-bacterial andantifungal (Aqil andAhmad.,2013;Hemaiswarya et al., 2009;Uma et al., 2009). ...
... Three studies used bark (Ghosh et al., 2016;Cagno, et al., 2015;Raisagar et al., 2019;Choudhari et al., 2013;Pandit et al., 2010;Khan et al., 2011;Uma et al., 2009), leaves (Kapoor et al., 2011;Singh, Singh, & Goel, 2011;Sankar et al., 2014;Gulecha and Sivakumar., 2011;Aqil and Ahmad.,2013;Hemaiswarya et al., 2009;Charde et al., 2010), Fig (Kaur et al., 2010Ahuja et al., 2011;Singh & Goel, 2009;, root (Patil et al., 2011) and latex (Yadav & Srivastava, 2013). ...
Objective: The aim of the study was to conduct a systematic literature review to investigate Ficus religiosa a traditional medicine used in the Management of several diseases. Methods: On November 9, 2022, an electronic search of the literature was conducted in the databases PubMed database and Google Scholar, looking up all publications published in English. The review was not constrained by any factors (such as study design, geographic location, or time period). Results: The starting data set search chose a sum of 1680 articles, 103 in PubMed, 1454 in Google Researcher, and 123 records from different sources. A sum of 1410 (complete copies viewed as 270) was tracked down in the wake of eliminating the copied articles, and subsequent to perusing the title and edited compositions the screen records 289 were additionally diminished to 38 articles with complete text. These 38 examinations selected the full-text investigation, which brought about the rejection of 13 investigations and produced a final 25 articles included for foundational investigation. Conclusion: This study showed that Ficus religiosa has beneficial effects on health in several diseases due to its high phytochemical content. Therefore, Ficus religiosa has the potential to be used as a pharmaceutical product for health.
... Methanolic fruit extract demonstrated notable effects in guinea pigs generated by histamine and acetylcholine [19]. Nephroprotective Activity An investigation in which the extract was given to rats revealed that Ficus religiosa latex extract demonstrates nephroprotective efficacy against cisplatin-induced acute renal failure, suggesting potential advantages in reducing renal damage and enhancing kidney function [20]. Anti-fertility Activity Methanolic extract of Ficus religiosa fruits was shown to have anti-fertility effects on goat uteruses in an animal investigation. ...
Ficus religiosa (F. religiosa), commonly known as the "Peepal" tree, is a sacred fig
variety native to India with immense medicinal and cultural importance. The tree,
belonging to the Moraceae family, is widely distributed across South and Southeast
Asia. Phytochemical screening reveals the presence of various bioactive compounds
including tannins, saponins, flavonoids, steroids, terpenoids, and cardiac glycosides.
Traditional medicinal systems, especially Ayurveda, have used various parts of the tree
for treating different diseases, including asthma, diabetes, diarrhea, and sexual
disorders. Modern pharmacological studies have confirmed many of the traditional uses
through scientific investigation. The study has shown remarkable antibacterial,
anthelmintic, anti-asthmatic, analgesic, anti-inflammatory, anti-diabetic,
anticonvulsant, nephroprotective, anti-fertility, anti-Parkinson, and hepatoprotective
activities. Its rich phytochemical composition, which includes compounds such as
bergapten, β-sitosterol, stigmasterol, and several amino acids, is attributed to its
therapeutic potential. The latex, bark, leaves, and fruits of the plant have shown distinct
medicinal properties, supporting its role in traditional healthcare systems. This review
aims to provide a comprehensive analysis of Ficus religiosa, the botanical features,
phytochemical composition, traditional applications, and pharmacological activities of
religiosa may be established as its therapeutic potential in modern medicine
... Alkaloids, glycosides, amino acids, flavonoids and tannins show nephroprotective activities. Methanolic extracts of latex 200 mg/kg dose show this effect in Wistar rat models by decreasing levels of urea and creatinine (Yadav and Srivastava, 2013). ...
Herbal drugs are one of the world’s oldest and most precious gifts. Medicinal herbs and plants have a prominent place in the healthcare system, with Ficus religiosa, being one of the most important. It is commonly knowns as fig, which is widely used in traditional medicinal systems as antiulcer, anticonvulsant, wound healing, antinephropathic, antiviral, analgesic, anti-inflammatory, antimicrobial, immunostimulant, antihyperlipidemic, antioxidant, antiasthmatic, parasympathetic modulatory, anti-acetylcholinesterase, anticancer and cognitive enhancing agents. Secondary metabolites isolated from the plant such as stigmasterol, methyl oleanolate, lanosterol, caffeic acid, bergenin, amides, lupin 3-one, β-sitosterol, n-octacosanol, and flavonoids are considered to be the principal bioactive compounds of F. religiosa. The purpose of this review was to outline the phytochemistry, pharmacology and toxicity profile of F. religiosa. Aside from plant morphology and phytochemistry, the application of the plant in the most recent discoveries and nanotechnology was also explored. Furthermore, the review addresses recent therapeutic breakthroughs and identifies areas for further research that should be addressed in future studies. Bangladesh Pharmaceutical Journal 27(2): 223-238, 2024 (July)
... These factors might contribute to free radical scavenging and antagonism nephrotoxicity which were produced by cisplatin in renal failure. 14 ...
... Literature review showed that ROS plays an important role in inflammation by activating T cells that damage other cells & stimulate inflammation 5 . Previous studies showed that various pathological factors produce ROS due to an imbalance between oxidant and antioxidant defense system 6,7 . ...
Background: According to international society of nephrology about 2 million people die with AKI every year. Aim: To evaluate the effect of GR ligands on renal functions of mice induced by nephrotoxic poison Concanavalin-A. Study design: Experimental study. Methodology: The study was conducted at Agriculture University of Faisalabad-Pakistan following approval from ethical committee. Mice having age around 10 weeks, weighing 25 to 30 grams, kept under observation at animal house facility at University of Agriculture for 9 days. Subject animals (n=12) were equally divided into 3 groups, 1st was control group, 2nd was treated group and 3rd was untreated group. Renal markers, creatinine, urea and BUN were estimated from blood sample by using serum analyzer. The collected data was analyzed by using SPSS version 20. ANOVA ware applied with P-value< 0.05 as significant. Results: Analysis of kidney function test showed significance increase in creatinine, urea and BUN level in Con-A induced toxic group. They were normalized in pretreated groups receiving GR ligand (Dexa). Conclusion: It was concluded that glucocorticoids ameliorated the Con-A induced nephrotoxicity by significantly reducing the elevated kidney biomarker levels including creatinine, urea and BUN in mice serum. Keywords: Glucocorticoids, Serum Urea, BUN and Concanavalin-A.
... The anti-inflammatory potential of another Ficus spp. was investigated using its latex on cisplatin-induced liver injury. An in vivo study carried out by Yadav and Srivastava [67] has demonstrated the hepato-curative and nephroprotective effects of F. religiosa latex (defatted) methanolic extract. The latex-treated group with cisplatin-induced liver injury has shown protective and curative symptoms upon treatment with 200 and 300 mg/kg, with an observable reduction in the hyaline droplets, tubular dilation, and recovery. ...
Ficus is one of the largest genera in the plant kingdom that belongs to the Moraceae family. This review aimed to summarize the medicinal uses, phytochemistry, and pharmacological actions of two major species from this genus, namely Ficus benghalensis and Ficus religiosa. These species can be found abundantly in most Asian countries, including Malaysia. The chemical analysis report has shown that Ficus species contained a wide range of phytoconstituents, including phenols, flavonoids, alkaloids, tannins, saponins, terpenoids, glycosides, sugar, protein, essential and volatile oils, and steroids. Existing studies on the pharmacological functions have revealed that the observed Ficus species possessed a broad range of biological properties, including antioxidants, antidiabetic, anti-inflammatory, anticancer, antitumor and antiproliferative, antimutagenic, antimicrobial, anti-helminthic, hepatoprotective, wound healing, anticoagulant, immunomodulatory activities, antistress, toxicity studies, and mosquitocidal effects. Apart from the plant parts and their extracts, the endophytes residing in these host plants were discussed as well. This study also includes the recent applications of the Ficus species and their plant parts, mainly in the nanotechnology field. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PMC, Research Gate, and Scopus. Overall, the review discusses the therapeutic potentials discovered in recent times and highlights the research gaps for prospective research work.
... Tetramethylpyrazine inhibits HMGB1/ TLR4/NF-κB and activates the NRF2 and PPAR-γ signaling pathways to achieve nephroprotective effects [110]. Ficus religiosa latex extract has glycoside, alkaloid, and amino acid constituents and shows excellent nephroprotective and curative effects in rats [111]. A study indicated that berberine exerted a nephroprotective effect via the inhibition of oxidative stress, inflammation, autophagy, and apoptosis in cisplatin-induced AKI [112]. ...
Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%–35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.
... It improves renal damage by increasing the levels of GSH, SOD, CAT, and decreasing lipid peroxidation. The central nephroprotective mechanism is elicited by flavonoids(antioxidants), amino acids present in the plant (Yadav and Srivastava, 2013). ...
The kidney is essential for the physiological functions of the body. When exposed to high concentrations of toxins, these may induce the toxicity of the kidney (kidney injury), leading to renal failure and precipitating a condition called nephrotoxicity. The toxicity may result from hemodynamic changes and directly harm the cells and tissue, and causes obstruction of renal excretion. Nephrotoxicity can also be induced by renal impairment leads to kidney-specific detoxification and diminished kidney function by ischemia and toxicants/drugs. Considering the possible damage to kidneys by drugs, patients are using the naturally derived substance, including herbal drugs or nutraceuticals. However, the safety concerns of herbal drugs and formulation in inducing kidney injury are an area of research. The present review is a concerted effort to assemble information mainly focusing on the kidney injury, its comprehensive categorization, i.e., mechanism of interaction of various enzyme systems of kidneys with drugs of herbal and synthetic origin and their outcomes. Moreover, the review also put forth the details of herbal drug that precipitate kidney injury and ameliorate it. The review is being put forward with an incentive to provide researchers with a comprehensive and updated literature on kidney injury by drugs of natural and synthetic origin and their molecular targets in the kidney.
... In another study, the renal protection of flavonoids was evaluated and they found a reduction of the inflammatory factors in the pathophysiological process of ischemia-reperfusion (Zhao et al., 2016). The literature findings also demonstrate that extracts containing tannins exert a protective effect on the kidneys, as demonstrated by Yadav and Srivastava (2013), who showed that Ficus extract, rich in tannins, has a protective action against renal damage caused by cisplatin. In addition, carotenoids, also found in E. uniflora extract, have a protective effect on renal function during ischemia-reperfusion, through reduction of lipid peroxidation and free radical production (Augusti et al., 2008). ...
Acute kidney injury (AKI) is characterized by a rapid and potentially reversible decline in renal function. We hypothesized that Eugenia uniflora (pitanga) may present a protective effect in AKI due to its antioxidant properties. Extract from pitanga leaves (200 mg/kg, gavage) or vehicle was administered to Wistar rats (28 days) prior to AKI induction by 45-minute bilateral renal ischemia. Renal hemodynamic was quantified after 24 h of reperfusion to determine the glomerular filtration rate (GFR), renal blood flow (RBF) and renal vascular resistance (RVR). Renal production of reactive oxygen species and apoptosis, SOD and catalase expression and activity were determined. Treatment with pitanga prevented AKI-induced decrease in GFR and RBF, as well as the rise in RVR. Pitanga also prevented the increased oxidative stress and apoptosis, probably due to a rise in antioxidant enzymes activity and expression. These results demonstrate a protective effect of pitanga extract on AKI development.
... There are many previous studies have been well documented that cisplatin induces toxicity in liver [22] kidney [23,24], due their free radical oxidative stress by interacting with DNA [25]. ...
Objective:
To investigate effect of cisplatin on biochemical parameter and histology of pancreas and testis in Wistar rats.
Material and methods:
Single dose cisplatin (10 mg/kg) was injected by intraperitoneal route in Wistar rats. Blood was withdrawn on 7th day from cisplatin treated rats by retro-orbital sinus for biochemical estimation. Further rats were scarified and dissected out their pancreases and testes for estimation of antioxidant enzymes and histopathological study.
Results:
The cisplatin-treated group showed a significantly (P < 0.01) increased blood glucose level, Glycosylated hemoglobin in blood on the 7th day as compared to the control group. Whereas cisplatin-treated group showed significantly (p < 0.001) increased lipid peroxidation and decreased reduced glutathione, superoxide dismutase, catalase in pancreatic and testicular tissue as compared to the control group. Histopathological sections of the pancreatic tissue showed marked vasoconstriction and micro infiltration were observed however testicular tissue showed degeneration in some somniferous tubules and also greatly depleted of germ cells in cisplatin treated group.
Conclusion:
These findings demonstrated that the cisplatin could be induced diabetes and testicular toxicity due to their free radical mediated oxidative stress.
... F. religiosa latex and constituents have excellent nephroprotective and curative activities and thus have great potential as a source for natural health products. The possible nephroprotective and curative effects of F. religiosa latex methanol extract against cisplatin-induced acute renal failure was determined by Yadav and Srivastava (2013). The anti-ulcer activity and acute toxicity of F. religiosa leaf ethanolic extract in animal models were evaluated by Gregory and co-workers (2013). ...
In the present study, we highlight the antioxidant potential of aqueous extract of Ficus religiosa L. leaves in equine plasma and erythrocyte suspension. In this study, we have focused on the antioxidant effect of leaf extract obtained from F. religiosa on oxidative stress biomarkers [2-thiobarbituric acid reactive substances (TBARS), carbonyl derivatives content of protein oxidative modification (OMP), total antioxidant capacity (TAC)] using the equine erythrocytes model. Freshly collected leaves were washed, weighted, crushed, and homogenized in 0.1M phosphate buffer (pH 7.4) (in proportion 1:19, w/w). The equine erythrocyte aliquots and plasma were used in the study. A volume of 0.1 ml of the F. religiosa extract was added to 1.9 ml of clean equine erythrocytes or 1.9 ml of plasma. For positive control (blank), phosphate buffer was used. Treatment by extract reduced the erythrocytes TBARS level by 25.3 % (p=0.009), while plasma TBARS level was increased by 75.6 % (p=0.000), as compared to untreated erythrocytes. When plasma was incubated with extract, the ketonic derivatives level was significantly increased by 22.8 % (p=0.000), while non-significantly decrease both aldehydic and ketonic derivatives of OMP was observed. Treatment by F. religiosa extract caused the increase of TAC in plasma and erythrocyte suspension when compared to untreated erythrocytes. However, these changes were statistically non-significant. All these data suggest that F. religiosa could be explored for its antioxidant potential in equine erythrocyte suspension.
... Animal studies with bioactive compounds have been given in Table 5. Anti-diabetic property of bark of F. religiosa has been reported in streptozotocin induced type 2 diabetic rats with the usage of aqueous extracts of bark (Alsnafi, 2017) [2] and (Kaur et al., 2011) [33] . [5] Anti-ulcer activity Ethanolic extract of leaves (2000 mg/kg of body weight) showed anti-ulcer property in albino mice Ulcer area prevented and gastric secretion was reduced (Gregory et al., 2013) [14] Anti-asthmatic activity [50] Hepatoprotective effect Methanolic extracts of latex (300 mg/kg of body weight) showed hepatoprotective effect in cisplatin induced liver injury in wistar rats Inflammatory infiltrate was degenerated (Yadav, 2015) [51] Other uses of Ficus religiosa F. religiosa is being used to cure various infections and food poisonings. The bark is used to cure skin diseases, mouth ulcers, diabetes and bone fracture. ...
Medicinal plants play a vital role in improving health of people. Hundreds of medicinal plants have been used to cure various diseases since ancient times. Ficus religiosa (Peepal) has an important place among herbal plants. Almost every part of this tree i.e. leaves, bark, seeds and fruits are used in the preparation of herbal medicines. Therapeutic properties of this tree in curing a wide range of diseases can be attributed to its richness in bioactive compounds namely flavonoids, alkaloids, tannins, saponins, phenols etc. Its antimicrobial, anti-diabetic, anticonvulsant, wound healing, anti-inflammatory and analgesic properties have made it a popular herbal tree and its parts are placed as important ingredient in modern pharmacological industry. The documentation of traditional and modern usage of F. religiosa under one heading can help researchers to design and develop new functional foods from F. religiosa.
... Some species of the Moraceae have been shown to possess significant nephroprotective activity. They include F. religiosa latex on cisplatin [7], F. dalhousiae leaf methanolic extracts on gentamicin and acetaminophen [8], F. carica leaf extract on gentamicin [9], F. racemosa aqueous bark extract on gentamicin [10] and F. benghalensis latex on cisplatin [11]. Ficus pumila Linn. is a creeping vine-like fig plant which also belongs to the family Moraceae. ...
... Group IV: CP + AHE (Post-treated); administered AHE (400 mg/kg b.w/day, p.o.) for 1 week after CP injection [44]. ...
Abstract
Background
Cisplatin (CP) drug is platinum compounds used for the treatment of various human malignancies. However, adverse outcomes related to CP restrict its usage. Acacia hydaspica is a natural shrub with various pharmacological properties. The current investigation aimed to assess the protective potential of A. hydaspica polyphenol rich ethyl acetate extract (AHE) against cisplatin (CP) induced pulmonary toxicity.
Methods
Rats were divided into six groups. Group 1 served as control (saline); Group 2 (drug control) recieved single dose of CP (7.5 mg/kg i.p.) on 1st day; Group 3 (extract control) (400 mg/kg bw, p.o.) received AHE for one week; Group 4 (Post-treated) and Group 5 (pretreated) received AHE (400 mg/kg bw/day, p.o) for 7 days after and before CP (7.5 mg/kg b.w., i.p.) respectively; Group 6 (Standard control) received silymarin (100 mg/kg b.w/7 days) before CP. At the end of dosing rats were sacrificed and pulmonary tissue samples were processed for the evaluation of antioxidant enzymes, oxidative stress markers, genotoxicity and histopathological alterations.
Results
CP caused body weights loss and increase pulmonary tissue weight. The CP significantly increases oxidative stress markers and decreases tissue antioxidant enzyme levels. Furthermore, CP induced deleterious changes in the microanatomy of pulmonary tissue by rupturing the alveolar septa, thickening of alveolar walls, and injuring the cells with subsequent collapse of blood vessels. AHE pretreatment returned MDA, NO, H2O2 production and improved tissue antioxidant enzyme levels to near normalcy. The histological observations evidenced that AHE effectively rescues the lungs from CP-mediated oxidative damage. CP induction in rats also caused DNA fragmentation which was restored by AHE treatment. Our results suggest that pretreatment more significantly improve CP induced deleterious effects compared with post treatment indicating protective effect. Potency of AHE pretreatment is similar to silymarin.
Conclusion
These findings demonstrated that A. hydaspica AHE extract might serve as potential adjuvant that prevents CP persuaded pulmonary toxicity due to its intrinsic antioxidant potential and polyphenolic constituents.
... At present, with the introduction of evidence-based medicine, we can predict the effect of the use of a number of nephroprotective drugs in complex therapy of the disease. Their choice for today is great, but interest in nephroprotective drugs of plant origin does not decrease [3][4][5][6][7][8][9] . The highest requirements for the production of phytopreparations at all stages and the rational approach to phytotherapy, modern scientific and technical achievements of the pharmaceutical industry have become part of the concept of phyto-engineering (phytoneering)the priority direction of the work of a number of companies, including Bionorica (Germany). ...
Chronic kidney disease (CKD) is a global problem all over the world. Special attention is paid to the action of natural compounds. This research was aimed to investigate the effect of complex phytochemical preparation (Herba centaurii, Radix levistici and Folia rosmarini) on dynamics of morphological changes in kidney tissue in animals with glomerulonephritis. We found a positive dynamics in the structure of the nephron, which allows us to conclude that its nephroprotective effect is expressed.
... The test samples, ranging from 1 to 20 µg.mL -1 (2 mL), were put into test tubes containing 2 mL of 1 mM DPPH solution, covered with parafilm, and incubated in the dark for 1 h. Absorbance was noted at 515 nm and IC 50 was determined (6,5,9,44). ...
The nephroprotective activity of hydro-alcoholic (HAEAM) and ethyl acetate (EAEAM) extracts of Aegle marmelos leaves were evaluated against nephrotoxicity induced by cisplatin (CP), a widely used chemotherapeutic agent in cancer therapy. Wistar rats were treated with CP (6 mg.kg–¹; i.p.). Treatment groups received the same dose of CP, along with HAEAM and EAEAM (200 and 400 mg.kg–1) orally for 5 d. Blood urea nitrogen (BUN), serum creatinine, and antioxidant enzymes were estimated in renal tissues. EAEAM exhibited minimum IC50 values 6.13 ± 1.05, 67.34 ± 1.7, 59.7 ± 3.9, and 49.17 ± 2.19 μg.mL–¹. EAEAM (400 mg.kg–¹) decreased the creatinine levels from 2.29 ± 0.387 to 0.96 ± 0.095 mg.dL–¹ and BUN from 92.06 ± 7.949 to 38.18 ± 5.686 mg.dL–¹ and restored the activities of renal antioxidant enzymes, decreased the lipid peroxidasde (LPO) levels from 158.70 ± 3.542 to 106.91 ± 5.876 nM.g–¹, and increased superoxide dismutase (SOD) levels from 12.59 ± 0.463 to 29.95 ± 5.222 U.g–¹, glutathione (GSH) from 0.24 ± 0.029 to 0.57 ± 0.048 μM.g–¹, and catalase (CAT) from 1.14 ± 0.067 to 3.27 ± 0.296 U.mg–¹).
... 6 Free radicals are involved in the development of degenerative diseases. They have been implicated in the pathogenesis of liver damage, 7,8 diabetes, 9,10 nephrotoxicity, 11,12 cancer, 13 cardiovascular disorders, neurological disorders, inflammation 14 and in the process of aging. 15 It is well known that a significant increase in steatosis and fibrosis leads to lethal cirrhosis of the liver in humans. ...
Self microemulsifying formulation is an approach used for enhancing the bioavailability of poorly soluble molecules due to their lipidic nature and small particle size. The objective of the present study was to evaluate the hepatoprotective activity of poorly soluble hydroxy- and polyhydroxy-organic phytomolecules rich Lagerstroemia speciosa leaves extract in modern formulation i.e. “Self microemulsifying System”.
Different doses of SME (Self microemulsifying) formulation of L. speciosa leaves extract were evaluated for the hepatoprotective activity against carbon tetrachloride induced liver toxicity in rats. The parameters evaluated were (a) biochemical parameters like serum enzymes: aspartate aminotransferase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (ALP) and total bilirubin (b) liver antioxidant parameters as estimation of Lipid peroxidation (LPO), catalase (CAT), Superoxide dismutase (SOD) activity and concentration of reduced glutathione (GSH). Oral administration of SME formulation provided the significant protection in marker enzyme of treated group at 100 mg/kg, p.o. as AST (P < 0.001), ALT (P < 0.001), ALP (P < 0.001) and total bilirubin (P < 0.001) comparable to the group treated with silymarin. Treatment with SME formulation at the doses of 100 mg/kg, p.o. significantly prevented the rise in levels of LPO significantly (P < 0.001). The GSH, SOD and CAT contents had significantly (P < 0.001) increased in SME formulation treated groups whereas carbon tetrachloride intoxicated group had shown significant decrease in these parameters compared to control group. Formulation at the dose 100 mg/kg, p.o. has shown maximum protection which was almost comparable to those of the normal control and standard. The histological observations further uphold the results for hepatoprotective activity.
... Scheuer and his colleague 41) reported that oxidative stress is a pathogenetic factor in lipid-induced nephropathy. Nephrons are the basic unit of renal tissue and used for filtering the ultra-filtrate especially for excretion of renal markers viz., urea, uric acid and creatinine 42) . During HCD condition, more amount of ROS are generated, which in turn damage nephron (depletion in nephron count) that leads to decreased filtration rate and thereby increasing the levels of renal markers functional parameters such as urea, uric acid and creatinine in serum and hence the level of marker enzymes were notably elevated in HCD fed rats. ...
Objective: The present study was designed to assess the beneficial effects of alcoholic (ethanol) extract of fruit of Avocado (AEFA) on biochemical, histological, and gene expression study in hypercholesterolemic diet fed nephropathy induced albino rats. Experimental design: Avocado fruit pulp was extracted with 90% ethanol, finally filtered and dried. Group-I rats as control, Group-II fed with hypercholesterolemic diet (HCD) for 45 days [4% cholesterol and 1% cholic acid], Group-III fed with HCD for 45 days + AEFA (300 mg/kg body weight/day orally) for last 30 days and Group-IV fed with AEFA alone. Collection of blood and excision of kidney were done for various biochemical and histological analysis. Result: The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal markers (serum urea, creatinine and uric acid) and renal lipid peroxidation (LPO) products were markedly mitigated in AEFA treated hypercholesterolemic rats. FRSA factors were significantly increased, on supplementation with AEFA. Administration with AEFA, the mRNA levels of eNOS and iNOS genes was expressively up-regulated and down-regulated. Histomorphological observations shown that, AEFA admirably protects the renal tissues from hypercholesterolemia-mediated oxido-lipidemic damage. Discussion and conclusion: From this study it was conjectured that AEFA can act as nephroprotective agent by attenuating the serum lipid profile, renal oxidative stress, besides regulating the mRNA expression of NOS in renal artery.
... Nephroprotective and curative effects of F. religiosa latex extract can work against cisplatin-induced acute renal failure (Yadav and Srivastava, 2013). ...
Ficus religiosa L., Moraceae, is widely planted in the tropics. The chemical constituents of F. religiosa include tannin, saponin gluanol acetate, β-sitosterol, leucoanthocyanidin, and leucoanthocyanin. These are used for the treatment of pain, inflammation, impotence, menstrual disturbances, and urine related problems, and as uterine tonic. The present study aimed to evaluate hepatoprotective effects of F. religiosa latex on cisplatin induced liver injury in Wistar rats. In experimental protocol contained five groups of rats (n = 6). In which, group I (control) was administered acacia (2%, w/v) of 5 ml/kg throughout the experiment for 16 days. The group II (cisplatin treated) was administered single dose of cisplatin (7.5 mg/kg i.p.) on 1st day. Group III (extract control) was administered 300 mg/kg p.o. of extract for 1st to 10th day. Group IV (Protective) was administered extract (300 mg/kg p.o.) of F. religiosa latex for 1st to 10th day and administered single dose of cisplatin (7.5 mg/kg i.p.) on 11th day and group V (Curative) received single dose of cisplatin (7.5 mg/kg i.p.) on day 1st, and administered extract (300 mg/kg p.o.) from 7th to 16th days. On the 6th day in cisplatin treated, 10th day in extract control and 16th day in control, protective and curative, blood withdrawn from retro-orbital sinus of rats for biochemical estimation for serum and dissected out the livers for estimation of antioxidant enzymes and histopathological works. The cisplatin-treated group 2 showed a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatocytes cells degeneration inflammatory infiltrate and necrosis it's were significantly (**p < 0.01) alleviates by protective groups.
... Scheuer and his colleague (2000) reported that oxidative stress is a pathogenetic factor in lipidinduced nephropathy. Nephrons are the basic unit of renal tissue and used for filtering blood especially for excretion of urea, uric acid, and creatinine (Yadav & Srivastava, 2013). During the HCD condition a greater amount of ROS is generated which in turn damage nephrons (depletion in nephron count) which leads to a decreased filtration rate and thereby increasing the levels of renal functional parameters (markers) such as urea, uric acid, and creatinine in serum and hence the level of marker enzymes was notably elevated in HCD-fed rats. ...
Context:
Bacopa monniera L. (Scrophulariaceae) is used as a traditional medicine in India for various ailments such as epilepsy, mental disorders, and also as a cardio-tonic. However, its nephroprotective role is still unknown.
Objective:
The present study assesses the modulatory impact of the alcoholic (ethanol) extract of Bacopa monniera (AEBM) on renal oxido-lipidemic stress in hypercholesterolemic rats.
Materials and methods:
B. monniera (1 kg) was extracted with 90% ethanol, filtered, and dried (52 g). Group-I rats as control, Group-II rats fed with a hypercholesterolemic diet (HCD) for 45 d [4% cholesterol and 1% cholic acid], Group-III rats fed with HCD for 45 d + AEBM (40 mg/kg, body weight) for last 30 d, and Group-IV AEBM alone rats. Blood and kidney were removed to analyze lipid, antioxidant status, and histological analysis.
Result:
The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters (urea, creatinine, and uric acid), and lipid peroxidation (LPO) products were significantly attenuated (p < 0.01) in AEBM-treated hypercholesterolemic rats. Activities of both enzymic (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR)) and non-enzymic antioxidant (GSH, Vit-C, and Vit-E) were significantly increased (p < 0.01), on supplementation with AEBM. Administration with AEBM the mRNA levels of eNOS and iNOS genes was significantly up-regulated and down-regulated (p < 0.01). Histomorphological observations also evidenced that AEBM effectively protects the kidney from hypercholesterolemia-mediated oxido-lipidemic damage.
Discussion and conclusion:
From this study, we hypothesized that AEBM can act as renoprotective agent by attenuating the renal oxido-lipidemic stress via regulating NOS level and thereby protects the nephron in hypercholesterolemic rats.
Ficus (Moraceae) is an exceptionally large pantropical genus with over 800 species worldwide. Of the 36 Ficus species native to Nepal, 21 are indigenously used as food, fodder, fuel wood, vegetable, medicine, etc. and F. religiosa, F. benghalensis, F. benjamina, especially have a high religious value for both Hindus and Buddhists and are deemed sacred. They have wide range of distribution, habitats, and life forms. F. religiosa used in traditional medicine for about 50 types of disorders and F. benghalensis is medicinally most important species and used to treat 22 ailments. Extracts of different parts of the plant are rich in bioactive compounds. The fruits, leaves, barks, roots (almost all parts of the plant) extracts exhibit different pharmacological activities like antioxidant, antidiabetic, antihyperlipidaemic, anti-inflammatory, antiarthritic, gastroprotective and anticancer. Almost all parts of plant of Ficus species possess a variety of pharmacological properties, which are proven to be beneficial for mitigation and treatment of different diseases. Ficus species (to be precise F. carica) have high demand in markets.
Ethnopharmacological relevance
Kidney disease (KD) is one of the serious health issues, which causes worrisome morbidity and economic burden. Therapeutic strategies are available however majority of them are associated with severe adverse effects and poor patient compliance and adherence. This explorative article was undertaken to provide a holistic review of known nephroprotective (NP) phytoconstituents along with their research-based evidences on mechanism, sources, and clinical trials that may play essential role in prevention and cure of KD.
Aim of the study
The present systematic review aimed to provide in-depth and better evidences of the global burden of KD, phytoconstituents as NP with emphasis on mechanism of action both in vitro and in vivo, their wide biological sources as well as their clinical efficacy in management of kidney disease and its related disorders.
Material and methods
Comprehensive information was searched systematically from electronic databases, namely, PubMed, Sciencedirect, Wiley, Scopus, Google scholar and Springer until February, 2021 to find relevant data for publication on phytoconstituents with nephroprotective potential.
Results
In total, 24,327 articles were screened in first search for “phytoconstituents and medicinal plants for nephroprotection and kidney disorder”. On the basis of exclusion and inclusion criteria, 24,091 were excluded. Only 236 papers were spotted to have superlative quality data, which is appropriate under titles and sub-titles of the present review. The phytoconstituents having multiple research evidence along with wide number of medicinal plants sources and mechanism reported for nephroprotection have been selected and reviewed.
Conclusion
This review, based on pre-clinical and clinical data of NP phytoconstituents, provides scientific-basis for the rational discovery, development and utilization of these upcoming treatment practices. Further,-more clinical studies are warranted to improve the pharmacodynamic and pharmacokinetic understanding of phytoconstituents. Also, more specific evaluation for natural sources is needed.
Abstract Cisplatin (CisPT) is a chemotherapeutic drug that outcomes in adverse effects. In this study, we examined the effect of A. hydaspica ethyl acetate extract (AHE) in an animal model of cisplatin-induced acute kidney injury (AKI). 36 male Sprague Dawley rats were used in the AKI rat model, and CisPT (7.5 mg/kg BW, i.p) single dose was given. In the pretreatment module, AHE (400 mg/kgBW/day, p.o) was given for 7 days before and after CisPT injection. While in the post-treatment group AHE was administered for 7 days after a single CisPT shot. The standard group received silymarin (100 mg/kg BW, p.o) for 7 days before and after CisPT injection. In HCT 116 tumor xenografts (n = 32) two groups of mice were pretreated with 400 mg/kg AHE orally for 7 days and two groups were treated with distilled water. On day 7 of pretreatment one distilled water and one AHE pretreated group were injected i.p with 15 mg/kg bw dose followed by another dose of CisPT 2 wk later. AHE groups were additionally treated with 400 mg/kg AHE for 3 days/week for 2 weeks. CisPT significantly deteriorated renal function parameters, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin and blood urea nitrogen. CisPT treatment increased oxidative stress markers, while lower renal antioxidant enzymes. AHE pretreatment ameliorates significantly (p
Acute renal failure (ARF) is a life-threating disease with high mortality percentage. Two important mechanisms of ARF are inflammation and oxidative stress. Plants are rich source of antioxidant compounds and have a strong anti-inflammatory activity, so they may be useful for the treatment of ARF. Some herbal medicines are effective against different models of experimentally induced ARF such as cisplatin, gentamicin, glycerol, and ischemia–reperfusion injury. Some of these plants such as ginseng, black seed, ginger, garlic, grape, pomegranate, saffron, and green tea are so famous and are effective against various models of ARF. However, we found several articles examining the effectiveness of different plants for treating ARF. In the current article, we discussed plants and natural products that are effective in the treatment of ARF.
Objective:
To assess the modulatory impact of alcoholic extract of fruit of Mengkudu (AEFM, Morinda citrifolia L., Rubiaceae) on renal oxido-lipidemic stress in hypercholesterolemic albino rats.
Methods:
Twenty-four male albino rats were randomly divided into four groups with six rats in each group: group I as control, group II fed with hypercholesterolemic diet (HCD) for 45 days (4% cholesterol and 1% cholic acid), Group III rats fed with HCD for 45 days + AEFM (300 mg/kg body weight/day orally) for last 30 days and group IV normal rats fed AEFM alone. The blood was collected using ethylenediamine tetraacetic acid (EDTA) as an anticoagulant for various biochemical analysis, and excision of kidney was done for histological analysis.
Results:
The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters and lipid peroxidation products were markedly mitigated in AEFM treated hypercholesterolemic rats (group III) compared to group I (P<0.01). Activities of both enzymic and non-enzymic free radical scavenging factors were significantly increased in group III compared to group I (P<0.01). In group III the mRNA levels of interstitial endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) genes were obviously up-regulated (P<0.01) and down-regulated in (P<0.05) compared with group I. Histomorphological observations also exhibited similar as in group III AEFM commendably protects the renal tissues compared with group I (P<0.01).
Conclusion:
AEFM can act as nephroprotective agent by attenuating the renal oxidative stress, lipid levels as well as regulating NOS level and by this means protects the kidney in hypercholesterolemic induced nephropathy experimental rats.
The rate of autoxidation of epinephrine and the sensitivity of this autoxidation to inhibition by superoxide dismutase were both augmented, as the pH was raised from 7.8 → 10.2. O2⁻, generated by the xanthine oxidase reaction, caused the oxidation of epinephrine to adrenochrome and the yield of adrenochrome produced per O2⁻ introduced, increased with increasing pH in the range 7.8 → 10.2 and also increased with increasing concentration of epinephrine. These results, in conjunction with complexities in the kinetics of adrenochrome accumulation, lead to the proposal that the autoxidation of epinephrine proceeds by at least two distinct pathways, only one of which is a free radical chain reaction involving O2⁻ and hence inhibitable by superoxide dismutase. This chain reaction accounted for a progressively greater fraction of the total oxidation as the pH was raised. The ability of superoxide dismutase to inhibit the autoxidation of epinephrine at pH 10.2 has been used as the basis of a convenient and sensitive assay for this enzyme.
The medicinal plants are used in traditional treatments to cure variety of diseases for thousands of year. The aim of this study was to identify such plants with antimicrobial and antioxidant efficacy for controlling some food borne pathogens. The locally available plants viz., Ficus religiosa, Leucas aspera, Holarrhena antidysenterica and Psidium guajavai were selected for the study. Various methods were tried to standardize the extraction of antimicrobial agents. Methanol extraction of P. guajava showed high antimicrobial activity against the food borne pathogens like S. typi, Pseudomonas spp and B. Subtilis. Whereas in case of antifungal H. antidysenterica showed more activity with maximum of 23mm inhibition zone against Aspergillus spp. The high antioxidant activity of 36ìg/100mg was observed in Psidium guajava. The GC-MS study also revealed the various phytic components for H. antidysenterica, which assured that it has high antimicrobial, anticancer activity against the food borne pathogens. It was concluded that plant extract can be used as a preservatives against the food borne pathogens.
Methanol extracts of some commonly used plant materials of ethnoveterinary importance in Pakistan were screened for their in vitro anthelmintic activity. Results revealed that Zingiber officinale killed all the test worms (Haemonchus contortus) within two hours post exposure being 100% effective. Allium sativum and Cucurbita mexicana extracts were equally effective at 2 and 4 h post exposure; by 6 h post exposure, however, the earlier was 100% effective; whereas, C. mexicana could not kill all the worms and was 83.4% effective. Ficus religiosa was 100% effective by 4 h post exposure, and was as good as A. sativum and Z. officinale by 6 h post exposure. Majority of the worms exposed to control (normal saline) remained alive till 4 h post exposure, and thereafter, 50% of them died by 6 h post exposure. It was concluded that all the studied plants had some anthelmintic activity, therefore, in vivo trials may be conducted for further evidence for their use in animals on scientific basis.
A spectrophotometric method has been developed for the quantitative determination of antioxidant capacity. The assay is based on the reduction of Mo(VI) to Mo(V) by the sample analyte and the subsequent formation of a green phosphate/Mo(V) complex at acidic pH. The method has been optimized and characterized with respect to linearity interval, repetitivity and reproducibility, and molar absorption coefficients for the quantitation of several antioxidants, including vitamin E. The phosphomolybdenum method, in combination with hexane monophasic extraction, has also been adapted for the specific determination of vitamin E in seeds. The results obtained with the proposed method were validated by comparison with a standard HPLC method. The phosphomolybdenum method is routinely applied in our laboratory to evaluate the total antioxidant capacity of plant extracts and to determine vitamin E in a variety of grains and seeds, including corn and soybean.
Cis -diamminedichloroplatinum(II) (CP), an important antineoplasic drug, shows remarkable toxicity to the kidney. Methods to reduce CP nephrotoxicity include the use of sodium selenite. The aim of the present study was to investigate the interaction between orally administered selenium and CP in the rat. After observing the effects of CP on body growth rate, urinary volume, serum creatinine, serum selenium levels, creatinine clearance, renal malondialdehyde, and glutathione levels, as well as on renal light microscopically visible lesions, the effects of the sodium selenite administration by gavage of 2 mg per kg of body wt. 24 h and 1 h prior to a single CP intraperitoneal injection of 5 mg per kg of body wt. followed by its daily administration for the 7 subsequent days on these parameters, were examined. CP increased renal malondialdehyde, renal glutathione, and serum creatinine and decreased creatinine clearance. Lipid peroxidation is one of the mechanisms by which CP induces renal damage. Selenium treatment decreased the effect of CP on serum creatinine, and renal malondialdehyde levels, but did not affect the other parameters with the exception of kidney necrosis which was also diminished by this treatment.
Objectives: To assess the protective effect of quercetin, a plant bioflavonoid, on cisplatin (CisDDP) induced nephrotoxicity in rats. Methods: Effect of the simultaneous treatment of quercetin (20 mg/kg, i.p., once a week x5) on cisplatin (3mg/kg, i.p., once a week x 5) induced renal epitheleal damage and lipid peroxidation was studied in the kidney of rats. Levels of markers indicative of nephrotoxicity such as urea, uric acid and creatinine were assessed in the serum. Changes in body weight were noted every week. The total protein content, levels of lipid peroxides and the activities of Na+ K+ATPase, Ca2+ ATPase and Mg2+ ATPase were also assayed in the kidney. The glutathione content and the activities of antioxidant enzymes such as super oxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-s-transferase were estimated in the kidney. Results: Cisplatin administration caused a significant increase in the levels of all serum biochemical indices. The levels of lipid peroxides (in terms of TBA reactants) were increased significantly in serum and kidney. The activities of Na+ K+ATPase, Ca2+ ATPase and Mg2+ ATPase were decreased significantly in the kidney. The glutathione content and activities of antioxidant enzymes were decreased considerably in the kidney of cisplatin treated rats when compared to normal control. Quercetin administration per se did not cause any change compared to the controls. However concominant treatment of quercetin with cisplatin showed considerable decrease in levels of markers for nephrotoxicity and lipid peroxides and increased ATPase activities compared to CisDDP treated group. Glutathione content and antioxidant enzyme activities were significantly increased. Conclusion: Quercetin has significantly cytoprotective effect in cisplatin-induced renal tubular damage in vivo in rats.
METHODS for measuring antioxidants and appraising antioxidant activity appear to be of two general types. If the chemical nature of the antioxidant is known, one may strive for a test specific for the compound or group of interest; for example, the nitroprusside test for sulphydryl groups. Alternatively one may observe the inhibition of some natural oxidative process such as the β-oxidation of fats, as a function of the added antioxidant.
The changes in renal epithelial morphology that accompany acute kidney injury are often subtle. At least four cellular fates can be identified in acute kidney injury: cells may be necrotic; cells may become apoptotic; they may replicate and divide; or they may appear indifferent to the stress (Figure 1). Frank necrosis, as is often seen experimentally, is not prominent in the vast majority of human cases. Necrosis is usually patchy, involving small clusters of cells, sometimes resulting in small areas of denuded basement membrane. Less obvious injury is more often noted, including loss of brush borders, flattening of the epithelium, intratubular cast formation, and dilatation of the lumen. While proximal tubules show many of theses changes, injury to the distal nephron can also be demonstrated when human biopsy material is closely examined. The distal nephron is also the site of obstruction by desquamated cells and cellular debris.
Necrosis is a catastrophic breakdown of regulated cellular homeostasis and is accompanied by massive tissue damage leading to rapid collapse of internal homeostasis of the cell [1]. It is characterized by cell swelling with early loss of plasma-membrane integrity, major alterations of the organelles, and swelling of the nucleus with flocculation of the chromatin. Affected cells rupture and the cellular components spill into the surrounding tissue space evoking an inflammatory response. Apoptosis is also a feature of nephrotoxic injury and a distinction can be made between necrosis and apoptosis based on morphological criteria (Table 1).
Ficus religiosa L. (Moraceae) has been extensively used in traditional medicine for a wide range of ailments of the central nervous system, endocrine system, gastrointestinal tract, reproductive system, respiratory system and infectious disorders.
To comprehend the fragmented information available on the botany, traditional uses, phytochemistry, pharmacology and toxicology of F. religiosa to explore its therapeutic potential and future research opportunities.
All the available information on F. religiosa was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar, Agricola and Web of Science) and a library search.
Ethnomedical uses of F. religiosa are recorded throughout South Asia, where it has been used for about 50 types of disorders. Phytochemical research had led to the isolation of phytosterols, amino acids, furanocoumarins, phenolic components, hydrocarbons, aliphatic alcohols, volatile components and few other classes of secondary metabolites from F. religiosa. Fresh plant materials, crude extracts and isolated components of F. religiosa showed a wide spectrum of in vitro and in vivo pharmacological activities like, antidiabetic, cognitive enhancer, wound healing, anticonvulsant, anti-inflammatory, analgesic, antimicrobial, antiviral, hypolipidemic, antioxidant, immunomodulatory, antiasthmatic, parasympathetic modulatory, esterogenic, antitumor, antiulcer, antianxiety, antihelmintic, endotheilin receptor antagonistic, apoptosis inducer and hypotensive.
F. religiosa emerged as a good source of traditional medicine for the treatment of asthma, diabetes, diarrhea, epilepsy, gastric problems, inflammatory disorders, infectious disorders and sexual disorders. Although many of the experimental studies validated its traditional medicinal uses, but employed uncharacterized crude extracts. Thus, it is difficult to reproduce the results and pinpoint the bioactive metabolite. Hence, there is a need of phytochemical standardization and bioactivity-guided identification of bioactive metabolites. The results of few pharmacological studies and bioactive metabolites already reported in F. religiosa warrant detailed investigation for its potential against cancer, cardiovascular disorders, neuroinflammatory disorders, neuropsychiatric disorders, oxidative stress related disorders and parasitic infections. The outcome of these studies will further expand the existing therapeutic potential of F. religiosa and provide a convincing support to its future clinical use in modern medicine.
One of the major etiologies in pathogenesis of type 2 diabetes especially complications is oxidative stress. Aqueous extract of Ficus religiosa at a dose of 100 and 200 mg/kg orally decreased the fasting blood glucose in streptozotocin induced type 2 diabetic rats. The drug had enzyme induction effect with respect to catalase (CAT) and glutathione peroxidase (GSH-Px) activity, however decreased the exaggerated activity of superoxide dismutase (SOD) in type 2 diabetic rats. F. religiosa modulated the enzymes of antioxidant defence system to combat oxidative stress. As a result, glutathione (GSH-reduced form) was restored and inhibited the formation of malondialdehyde. Drug at higher dose (200 mg/kg) had more pronounced effect. F. religiosa, a rasayana group of plant drug having anti-diabetic activity along with antioxidant potential was beneficial in treatment of type 2 diabetes.
A thiobarbituric acid (TBA) test procedure with reasonable reproducibility applicable to the assay of lipoperoxides in various animal tissue homogenates is described. It was concluded that the deproteinization of homogenate prior to coloration is not needed, but double wavelength measurement is necessary to avoid interference and the reaction should be performed with phosphoric acid at a definite pH near 2.0. The most reproducible procedure is as follows: To 0.5 ml of 10% homogenate of the tissue sample, add 3 ml of 1% H3PO4 and 1 ml of 0.6% TBA aqueous solution; stir and heat the mixture on a boiling water bath for 45 min. After cooling, add 4 ml of n-butanol, shake, and separate the butanol layer by centrifugation; determine the optical density of the butanol layer at 535 and 520 nm; and calculate the difference of optical density between the two determinations to be taken as the TBA value.
A simple colorimetric assay for catalase activity has been described using K2Cr2O7/acetic acid reagent. Kat. f values of different enzyme sources were determined by the colorimetric method and compared with the values obtained by titrimetric methods.
Plasma membranes have been prepared from rat normal liver cells, regenerating liver cells and Yoshida ascites hepatoma 66 cells after intact cells were first bound to polylysine-coated polyacrylamide beads, and the membrane-associated Mg2+ -ATPase activity was assayed directly on beads with membrane attached. With plasma membranes from normal liver cells, Km for ATP and V were found to be higher than those in regenerating liver cells and hepatoma cells. Vanadate caused a different sensitivity of the activity, without an effect in normal liver cells and with an inhibition in regenerating liver cells and hepatoma cells. The activity in normal and regenerating liver cells decreased with increasing temperature above 24-30 degrees C, while the activity in hepatoma cells continued to increase linearly to 37 degrees C. Unlike the enzyme in normal and regenerating liver cells, the hepatoma enzyme was shown to have a higher phase transition temperature and lower activation energies. In all three kinds of cells the activity was increased by the dephosphorylation of plasma membranes and unaffected by the phosphorylation. By means of histochemical Mg2+ -ATPase staining applied on polyacrylamide gels, at least three major bands which show the enzymic activity were visible in normal and regenerating liver and a single band was detected in hepatoma cells.
A low-affinity Ca2+-ATPase from erythrocyte membranes has been purified by agarose suspension electrophoresis and polyacrylamide gel electrophoresis in the absence of detergents. For maximal activity a calcium concentration above 10 mM is required. The activity is independent of magnesium. The Km value for ATP is about 60 microM. The enzyme appears in two forms (A and B) with similar amino acid composition. The specific activity of A is higher than that of B. Gel electrophoresis in SDS of A gives a pattern consisting of two bands. B gives the same pattern; the only difference between the patterns is the ratio of the amounts of protein in the bands. The apparent molecular weight of the proteins in the two SDS bands has been estimated at 23000 and 21000, respectively. The results obtained can be explained by assuming that the two proteins corresponding to the two bands obtained in SDS electrophoresis have a similar structure and can associate to complexes A and B. We have also shown that electrophoretic and chromatographic supporting media can induce aggregation of (membrane) proteins. Artificial complexes can thus be formed and cause misinterpretation of the data obtained. This may be the reason why some authors have speculated that Ca2+-ATPase is active only in complex with other proteins such as spectrin and actin.
When cisplatin is administered in the form of a cisplatin-methionine substitution complex, high doses of cisplatin can be tolerated with no obvious signs of renal toxicity. We have demonstrated that male Wistar rats receiving a single i.p. dose of cisplatin-methionine at a 1:5 ratio (by weight) did not exhibit cisplatin-induced nephrotoxicity, while cisplatin administered alone at an identical concentration (6 mg/kg) resulted in marked renal toxicity in all animals treated. Using renal cortical slices prepared from untreated rats, we demonstrated that cisplatin, but not cisplatin-methionine, inhibited the accumulation of 14C-tetraethylammonium (TEA). This observation suggests that cisplatin, unlike cisplatin-methionine, is a substrate for the organic base transport system. In addition, cisplatin alone was more cytotoxic to C6 glioma cells in vitro than the cisplatin-methionine complex. Exposure of C6 glioma cells to cisplatin-methionine, however, resulted in a 50%-60% reduction in 3H-thymidine incorporation at cisplatin:methionine ratios up to 1:10. These results indicate that cisplatin-methionine is significantly cytotoxic yet lacks cisplatin-associated renal toxicity and may, therefore, have a role in the treatment of human malignancies.
The ethanol extract of the roots of Cassia auriculata was studied for its nephroprotective activity in cisplatin- and gentamicin-induced renal injury in male albino rats. In the cisplatin model, the extract at doses of 300 and 600 mg/kg body wt. reduced elevated blood urea and serum creatinine and normalized the histopathological changes in the curative regimen. In the gentamicin model, the ethanol extract at a dose of 600 mg/kg body wt. reduced blood urea and serum creatinine effectively in both the curative and the preventive regimen. The extract had a marked nitric oxide free-radical-scavenging effect. The findings suggest that the probable mechanism of nephroprotection by C. auriculata against cisplatin- and gentamicin-induced renal injury could be due to its antioxidant and free-radical-scavenging property.
Dictionary of Indian Medicinal Plants Aqueous extract of Ficus religiosa Linn reduce oxidative stress in experimentally induced type 2 diabetic rats
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- Popli
- Sp
Husain A, Virmani OP, Popli SP, et al. (1992). Dictionary of Indian Medicinal Plants. Lucknow, India: CIMAP, 546. Kirana H, Agarwal SS, Srinivasan BP. (2009). Aqueous extract of Ficus religiosa Linn reduce oxidative stress in experimentally induced type 2 diabetic rats. IJEB 47:822–6.
Cellular mechanism of nephrotoxicity
- D Portilla
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Methods to achieve controlled drug delivery: The biochemical engineering approach
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Presence of enzyme system of mammalian tissue
- S L Bontin
Bontin SL. (1970). Presence of enzyme system of mammalian tissue. Wiley Inter Sci 197:257–363.
Dictionary of Indian Medicinal Plants
- A Husain
- O P Virmani
- S P Popli
The role superoxide anion in the auto-oxidation of epinephrine and a simple assay of SOD
- H P Mishra
- I Fridovich
Comparative study of plasma membrane magnesium ion ATPase activities in normal regenerating and malignant cell
- T Ohinishi
- Y Suzuki
- K Ozawa
Effect of dietary oral selenium on cisplatin induced nephrotoxicity in rats
- Hdc Francescato
- R S Costa
- Smr Camargo
Purification and characterization of two forms of the low affinity calcium ion ATPase from erythrocyte membrane
- S Hjerken
- H Pan
In vitro anthelmintic activity of Allium sativum, Zingiber officinale, Curcurbita mexicana and Ficus religiosa
- Zafar Iqbal
- Khalid Qazi
- Nadeem
- M N Khan