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Tunisian Nephroprotective Plants: A Review

  • Wissem Aidi Wannes*  and
  • Moufida Saidani Tounsi
Journal of Exploratory Research in Pharmacology   2023;8(1):74-91

doi: 10.14218/JERP.2022.00031

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Citation: Wannes WA, Tounsi MS. Tunisian Nephroprotective Plants: A Review. J Explor Res Pharmacol. 2023;8(1):74-91. doi: 10.14218/JERP.2022.00031.

Abstract

In Tunisian folk medicine, several herbs are prescribed for reducing renal damage and to avoid kidney related complications. These can be of immense value in combating renal damage. In this review, we provide a description of the current literature on the use of indigenous herbs as alternative medicine for treating renal damage. The aim of this review was to collect information on promising active phytoconstituents such as organosulfur compounds, polyphenols, terpenes, alkaloids phenylpropanoids, and polysaccharides from Tunisian plants that have been scientifically examined for their nephroprotective capacities. Twenty-nine Tunisian medicinal plants have been reported for their significant nephroprotective activities against renal toxicities in animal models. Lamiaceae was the most commonly used Tunisian plant family used for renal protection. The leaves were maximally used for nephroprotection compared to the other plant parts. Nephrotoxicity is commonly the result of several nephrotoxins. Many studies have focussed on drug-caused renal failure which is one of the major problems in medical practice. Other studies focused on other important nephrotoxicity factors, including drugs and industrial chemicals. This literature review highlights the use of some medicinal plants as nephroprotective agents. To defend against this nephrotoxicity, some medicinal plants, known as nephroprotective agents, have been highlighted in this review.

Keywords

Nephroprotective effect, Kidney, Renal failure, Toxicity, Medicinal plants, Tunisia

Introduction

The kidneys are vital organs that have several physiological functions. Their principle role is to maintain homeostasis of body fluids by filtering and secreting metabolites and minerals from the blood and excreting the nitrogenous waste along with water, as urine. The kidneys also help to regulate blood pressure, glucose metabolism, and erythropoiesis.1

The kidneys filter about 180 liters of blood daily, about four times the quantity traversing any other organ. Consequently, the kidneys are highly exposed to toxins in the blood and are susceptible to tissue damage.2 Kidney disease is the ninth leading cause of death,3 and patients with kidney disease have significant morbidity and mortality.4

The number of patients presenting with kidney disorders is increasing at an alarming rate.5 Currently, there are approximately over one million people worldwide who require dialysis or a functioning graft. Kidney replacement has been the only therapy for end stage of renal failure, and dialysis has remained the only alternative when a kidney transplant is not possible.3

Nephrotoxicity is one of the most common kidney problems induced by drugs or toxins.6 A number of potent therapeutic drugs, including aminoglycoside antibiotics, chemotherapeutic agents and chemical reagents (ethylene glycol, carbon tetrachloride, and sodium oxalate), and heavy metals (lead, mercury, cadmium, and arsenic), can adversely affect the kidney resulting in acute renal failure.3 In addition to drugs, other factors can lead to acute renal failure, such as age, diabetes, hypertension, liver disease, and oliguria.5 Nephroprotective agents, such as those found in medicinal plants, have protective and curative capacities against nephrotoxicity (Fig. 1). Co-administration of various medicinal plants possessing nephroprotective activity along with different nephrotoxic agents may attenuate toxicity.7 Previously, Tunisian medicinal plants have been used to treat diabetes,8 ulcer,9 cancer10, liver,11 and coronavirus12 illnesses. In this review, we highlighted the current literature focused on Tunisian nephroprotective plants.

Tunisian medicinal plants play nephroprotective roles by inhibiting oxidative stress, apoptosis and kidney injury.
Fig. 1  Tunisian medicinal plants play nephroprotective roles by inhibiting oxidative stress, apoptosis and kidney injury.

We searched the PubMed, Scientific Information Database, Scopus, Web of Science, Science Direct, Google and Google Scholar databases for primary literature using the keywords nephroprotective effect, kidneys, nephrotoxicity, renal failure, medicinal plants, and Tunisia. A total of 175 researches were included in this work. The different experimental nephroprotectve researches allowed describing 29 Tunisian medicinal plants for their significant nephroprotective activities against renal toxicities in animal models (Table 1).13–50 These toxicities were made by several toxins belonging to drugs, industrial additives and pesticides (Table 2).14,17,20–22,24,25,28,29,31,37–43,45,47,49,51

Table 1

Tunisian medicinal plants with nephroprotective activity

Scientific plant namePart used*ExtractBioactive compoundsNephrotoxin usedReferences
Allium sativum		ClovesMethanolOrganosulfur compound (allicin)Deltamethrin13
Artemisia arborescens		LeavesAqueous ethanolPhenolic compounds (vanillic acid, coumarin, rutin, luteolin, naringenin and quercetin)Estradiol + progesterone14
Artemisia campestris		Aerial partsEssential oilTerpenes (β-pinene, p-cymene and α-pinene)Deltamethrin15
Chlorpyrifos16
Capparis spinosa		LeavesMethanolPhenolic compounds (rutin, resveratrol, coumarin, luteolin and epicatechin)Cisplatin17
Ceratonia siliqua		LeavesEthyl acetatePhenolic compounds (syringic acid, myricetin glycosides and gallic acid derivatives)CCl418
Citrus limon		LeavesEssential oilTerpene (limonene)Aspirin19
Eryngium maritimum		SeedsMethanolPhenolic compounds (caffeic acid, protocatechuic acid gallic acid, luteolin and kaempferol)Cisplatin20
Eucalyptus globulus		LeavesAqueousPhenolic compounds (rutin, ellagic acid, chlorogenic acid, and quercetin 3-glucuronide)Acetaminophen21
Euphorbia bivonae		LeavesPolysaccharidesMonosaccharides (saccharose, arabinose, inositol, glucose, pyranose, trehalose and fructose)Hydrogen peroxide22
Globularia alypum		LeavesMethanolPhenolic compound (globularin)Deltamethrin23
Hammada scoparia		LeavesMethanolAlkaloids (carnegine and N-methylisosalsoline) and flavonoids (isorhamnetin triglycerides)Ethanol24
Hyparrhenia hirta		Aerial partsMethanolFlavonoid compounds (apigenin, quercetin and luteolin)Sodium nitrate25
Lavandula stoechas		Aerial partsEssential oilTerpenes (tricyclene, cymene, Δ-Cadinene and Selina-3,7(11)-diene)Malathion26
Lycium europaeum		LeavesMethanolPhenolic compounds (cisplatin, caffeic acid, gallic acid, naringenin, epicatechin, vanillic acid, rutin and p-coumaric acid) PolysaccharideCCl427
PolysaccharideCisplatin28
Malva sylvestris		Flowers LeavesAqueousPhenolic compounds (gallic acid, p-coumaric acid, vanillic acid, rutin, kaempferol, quercetin and luteolin)Vanadium29
MethanolLithium carbonate30
Mentha piperita		LeavesEssential oilTerpenes (menthol and iso-menthone)CCl431
Morus alba		LeavesAqueous acetonePhenolic compounds (chlorogenic acid and its derivatives)Glyphosate32
Nitraria retusa		FruitsAqueousPhenolic compounds (chlorogenic acid, p-coumaric acid, caffeic acid, gallic acid and kaempferol)Penconazole33
Olea europea		FruitsOilPhenolic compounds (oleuropein and hydroxytyrosol)Acrylamide34
LeavesAqueousDeltamethrin35
FruitsEthanolBisphenol A36
Diclofenac37
Opuntia ficus-indica		CladodesAqueousPhenolic compounds quercetin, vanillic acid, gallic acid, rutin, kaempferol, catechin, epicatechin, coumarin, isorhamnetin and caffeic acid)Lithium carbonate38
Sodium dichromate39
Periploca angustifolia		LeavesPolysaccharidesMonosaccharides (saccharose, trehalose, L-inositol and M-inositol)Cadmium40
Phoenix dactylifera		FruitsAqueousPhenolic acids (ferulic, caffeic and p-coumaric acids)Dichloroacetic acid41
Pinus halepensis		NeedlesEssential oilTerpenes (Z-β-caryophyllene, β-myrcene and α-pinene)Aspirin42
Rhus tripartitum		FruitsMethanolPhenolic acid (betulinic acid)Cisplatin43
Rosmarinus officinalis		LeavesAqueousPhenolic compounds (carnosic and rosmarinic acids)CCl444
Salvia officinalis		Aerial partsEssential oilTerpenes (β-caryophyllene, limonene and carvacrol)Vanadium45
Teucrium polium		Aerial partsAqueousphenylpropanoid glycosides (verbascoside and poliumoside), flavones (apigenin and its derivatives) and two methoxyflavonesCCl446
Trigonella foenum-graecum		SeedsPowderFlavonoid glycosides (vicenin-2, isoschaftoside and isoorientin)Aluminum chloride47
CCl448
Vitis vinifera		Seeds/SkinEthanolPhenolic compounds (2,5-dihydroxybenzoïc acid gallic acid, and vanillin)Doxorubicin49
FruitsPowderOxidative stress50

*Sientific plant names were followed by references. CCl4, carbon tetrachloride.

Table 2

Effect of Tunisian medicinal plants on different nephrotoxins

Nephrotoxicity factorsModel nephrotoxin usedScientific plant name*
PesticidesDeltamethrinAllium sativum13; Artemisia campestris15; Globularia alypum23; Olea europea35
ChlorpyrifosArtemisia campestris16
MalathionLavandula stoechas26
GlyphosateMorus alba32
PenconazoleNitraria retusa33
AcrylamideOlea europea34
CCl4Ceratonia siliqua18; Lycium europaeum27; Mentha peperita31; Rosmarinus officinalis44; Teucrium polium46; Trigonella foenum-graecum48
Industrial additivesBisphenol AOlea europea36
Hydrogen peroxydeEuphorbia bivonae22
Cadmium SodiumPeriploca angustifolia40
dichromateOpuntia ficus-indica39
Sodium nitrateHyparrhenia hirta25
VanadiumMalva sylvestris29; Salvia officinalis45
DrugsDichloroacetic acidPhoenix dactylifera41
DoxorubicinVitis vinifera49
AcetomophenEucalyptus globules21
Aluminum chlorideTrigonella foenum-graecum47
AspirinCitrus limon51; Pinus halepensis42
CisplatinCapparis spinosa17; Eryngium maritimum20; Lycium europaeum28; Rhus tripartitum43
DiclofenacOlea europea37
EstradiolArtemisia arborescens14
EthanolHammada scoparia24
Lithium carbonateOpuntia ficus-indica38; Malva sylvestris31
ProgesteroneArtemisia arborescens14

CCl4, carbon tetrachloride.

Allium sativum

Allium sativum belongs to the family of Alliaceae, popularly known as garlic. It has reported anti-atherosclerotic, cardioprotective, neuroprotective, antihyperlipidemic, antidiabetic, antihypertension, antistress, anticancer, antiviral, antibacterial, antifungal, anti-oxidant, and dermatologic properties.52 Ncir et al.13 determined that the nephroprotective potential of the methanol extract from A. sativum cloves (20 mg/kg body weight (BW) against deltamethrin (7.2 mg/kg BW) caused oxidative damage in rat kidneys. Deltamethrin treatment increased kidney conjugated dienes and lipid peroxidase (LPO) levels. However, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were decreased. Garlic administration regulated these changes provoked by deltamethrin. Allicin is one of the major bioactive components of garlic constituted from the stable precursor allicin by the enzyme action alliinase when garlic cloves are crushed or macerated. García Trejo et al.53 determined that allicin had beneficial effects in chronic kidney disease compared to Losartan.

Artemisia arborescens

Artemisia arborescens is a perennial evergreen woody shrub belonging to the family of Asteraceae.54A. arborescens is a widely used traditional medicine that possesses ethnomedical and biological benefits.55 The beneficial effects of the aqueous ethanol extract from A. arborscens leaves (200 mg/kg BW) were studied against oestroprogestative-induced (35 mg/kg of estradiol and 125 mg/kg of progesterone, BW) kidney damage in rats. A. arborescens extract was found to optimize many parameters of oestroprogestative toxicity.14 The protective effect of A. arborescens was mainly attributed to the presence of phenolic acids and flavonoids. A. arborescens is rich in catechic acid, caffeic acid, epicatechic acid, vanillic acid, naringenin, coumarin, cinamic acid, quercetin, rutin, luteolin, kaempferol, and isorhamnetin. Among these phenolics, the potent nephroprotective effect of vanillic acid,56 coumarin,57 rutin,58 and luteolin59 was determined against cisplatin-induced nephrotoxicity in rats. Additionally, the renal protective potential of naringeninn60 and quercetin61 was studied in cadmium-induced oxidative renal dysfunction in rats.

Artemisia campestris

Artemisia campestris is a perennial herb belonging to the family of Asteraceae. A. campestris has many medicinal actions including anthelmintic, antidiabetic, anticancer, antimicrobial, antifungal, antihypertensive, emmenagogue, and antivenom. It has been also used to treat cutaneous, genital, digestive, and respiratory disorders.62 Saoudi et al.15 investigated the protective effects of A. campestris essential oil against deltamethrin nephrotoxicity in rats. Deltamethrin toxicity caused a significant increase in creatinine, urea, and uric acid levels, and a decrease in LPO, SOD, CAT and GPx. However, A. campestris essential oil reduced the deltamethrin-induced alterations in serum levels, lipid peroxidation, and oxidative stress. The protective effect of A. campestris essential oil could be attributed to its anti-oxidant potential. Similar results were obtained by Saoudi et al.16 who determined the protective effect of A. campestris essential oil against chlorpyrifos-induced kidney injury in rats. Akrout et al.63 found that A. campestris essential oil was dominated by β-pinene, p-cymene, and α-pinene. In fact, Başar64 reported that pinenes in volatile oils derived from plants are used widely to treat renal stone disease.

Capparis spinosa

Capparis spinosa is a spontaneous xerophyte plant belonging to Capparaceae family, widely found in the Mediterranean. C. spinosa is popularly used as a condiment65 and medicinal plant.66 It is used in traditional medicine to treat diseases such as gastrointestinal problems, hypertension, anemia,67 rheumatism,68 and diabetes.69 It is also an analgesic, anti-arthritic,70 antihemorrhoidal, anticancer,71 anti-inflammatory,72 depurative, diuretic,73 emmenagogue, and anti-oxidant.74 The nephroprotective action of the methanolic C. spinosa (200 mg/kg in olive oil) was determined against cisplatin-provoked (13 mg/kg in olive oil) kidney injury in rats. Pre-treatment with the methanolic extract of C. spinosa leaves 7 days before cisplatin exposure and daily thereafter significantly reduced plasma levels of creatinine, urea, and uric acid, reduced malondialdehyde (MDA) levels, and reduced anti-oxidant enzyme activity of SOD, CAT, and GPx in the kidney and reversed the kidney damage.17 The leaf of this plant is rich in rutin, resveratrol, coumarin, epicatechin, and luteolin,73 all of which have been shown to demonstrate protection against cisplatin-induced nephrotoxicity in rats, as reported by Radwan and Fattah58 for rutin, Valentovic et al.75 for resveratrol, Sen et al.57 for coumarin, Tanabe et al.76 for epicatechin, and Domitrović et al.59 for luteolin.

Ceratonia siliqua

Ceratonia siliqua is a slow-growth ever-green tree belonging to the Leguminosae family, cultivated for years in the Mediterranean region. C. siliqua fruits, brown pods 10–25 cm in length, have traditionally been used as animal and human food. The seed is mainly used for gum extraction. C. siliqua pods, bark, and leaves have been used in Tunisian folk medicine as a laxative, diuretic, antidiarrheal, and to treat gastroenteritis of lactating babies.77 Animals received the ethyl acetate extract of C. siliqua leaves (250 mg/kg BW) daily by intraperitoneal injection for 8 days followed by a single dose of CCl4 (1 ml/kg in olive oil) using an intragastric tube after 24 hours of the last dose showed increased levels of urea, creatinine, and LPO with a concomitant decrease in SOD, CAT, and GPx in the kidney. Pretreatment with ethyl acetate extract of C. siliqua leaves had a potent nephroprotective effect in accordance with histopathological observations. The leaf extract of this plant mainly contains syringic acid, myricetin glycosides, and gallic acid derivatives.18 Sancak et al.78 noted the potent protective effect of syringic acid on kidney ischemia-reperfusion injury. The beneficial effect of myricetin on renal function was reported by Ozcan et al,79 and Asci et al.80 determined the beneficial impact of gallic acid against methotrexate-induced kidney injury in rats.

Citrus limon

Citrus limon is a medicinal plant of the family Rutaceae found in Tunisia and other Mediterranean countries (Egypt, Italy, Spain and Turkey).81C. limon has been used in folk medicine to treat obesity, diabetes, high lipid, cardiovascular diseases, brain disorders, and some cancer types.51C. limon leaf essential oil (1 ml/kg) was evaluated for its nephroprotective effect against a high dose of aspirin-induced acute kidney damage (600 mg/kg) in rats. C. limon essential oil protected against aspirin, showing a decrease in thiobarbituric acid reactive substances (TBARS) and an increase in SOD, CAT, and GPx.82 Limonene is the main component of C. limon essential oil fruits,82 leaves,83 and peels.84 Rehman et al.85 reported the protective role of limonene against doxorubicin-induced renal damage in the treatment of cancer.

Eryngium maritimum

Eryngium maritimum is a perennial herbaceous halophyte plant belonging to the Apiaceae family, which is widely distributed in dunes and sandy beaches of several Mediterranean countries and the Black Sea, Atlantic, and Baltic coasts. It has been introduced into parts of eastern North America and Australia.86E. maritimum has numerous folk medicinal uses including as a diuretic, kidney stone inhibitor, aphrodisiac, expectorant, anthelmintic, and antitoxin against various infections.87 Increases in serum levels of creatinine, urea, and uric acid caused by cisplatin (13 mg/kg in corn oil) were restored by methanolic E. maritimum seed extract (150 mg/kg in corn oil), accompanied by an increase in CAT, SOD and GPx.20 Mejri et al.20 reported that this seed extract was rich in caffeic acid, gallic acid, protocatechuic acid, kaempferol, and luteolin. Matboli et al.88 explained the curative potential of caffeic acid against diabetic kidney disease, and Nabavi et al.89 showed that gallic acid isolated from Peltiphyllum peltatum had nephroprotective activity against sodium fluoride-induced kidney damage. Protocatechuic acid was found as a protective agent against cadmium-induced toxicity in the kidney and liver.90 Vijayaprakash et al.91 showed that kaempferol had significant nephroprotective potential against mercuric chloride-induced nephrotoxicity in rats. Luteolin was also found to be effective against cisplatin-induced nephrotoxicity in mice .59

Eucalyptus globulus

Eucalyptus globulus is a very common tree throughout the world belonging to the Myrtaceae family. Its leaves, bark, and fruit have been traditionally used as remedies to treat inflammation and promote wound healing.92E. globules treatment has been shown to effectively protect against acetaminophen-provoked nephrotoxicity in mice by restoring SOD, CAT, and GPx levels. The nutraceutical advantage of E. globulus extract is attributed to its flavonoid, flavonol, and phenolic compounds.21 Ferreira et al.93 found that E. globulus leaves were rich in rutin, ellagic acid derivatives, quercetin 3-glucuronide, and chlorogenic acid, which have all been investigated for their nephroprotective effects.58,94–96

Euphorbia bivonae

Euphorbia bivonae is an herbaceous plant belonging to the Euphorbiaceae family and is widespread in the coastal areas of the Mediterranean basin.97E. bivonae has several biological properties, including antiproliferative,98 anti-oxidant, nephroprotective,22 and hepatoprotective99 effects. Athmouni et al.22 evaluated the preventive action of E. bivonae leaf polysaccharides against hydrogen peroxide (H2O2)-induced toxicity in human embryonic kidney (HEK293) cells. Results revealed that H2O2-exposure induced a significant increase in intracellular reactive oxygen species and lipid peroxidation in HEK293 cells. However, E. bivonae polysaccharide pretreated cells (100 µg/mL) significantly enhanced the anti-oxidant status (SOD, CAT, GPx, and GSH) of HEK293 cells that were decreased after H2O2 exposure. Accordingly, the HEK293 cells pretreated with E. bivonae polysaccharide compounds had enhanced cell viability following H2O2 exposure. Polysaccharide analysis showed the richness of E. bivonae in seven monosaccharides: saccharose, arabinose, inositol, glucose, pyranose, trehalose, and fructose.

Globularia alubum

Globularia alubum is a perennial shrub plant belonging to the Globulariaceae family, widely distributed in the Mediterranean area and largely used for its therapeutic virtues.100G. alubum species are known for their medicinal properties.101G. alypum is commonly used as a hypoglycaemic, laxative, cholagogue, stomachic, and purgative agent, as well as in the treatment of renal disease.23 The protective effect of methanol extract from G. alypum leaves (400 mg/kg in corn oil) against the nephrotoxicity induced by a chronic exposure to deltamethrin (4 mg/kg in corn oil) has been studied in rats. Deltamethrin administration provoked kidney damage, and treatment with G. alypum leaf extract restored plasma creatinine, urea, and uric acid levels and reduced the elevated MDA and PC levels. G. alypum leaf extract has been shown to restore renal activity in accordance with histopathological observations owing to its bioactive compounds.102G. alypum leaf extract is rich mainly in globularin (60.31%). Merghache et al.103 isolated this phenolic compound and determined its antidiabetic and antilipidemic capacities in normal and streptozotocin-induced diabetic rats.

Hammada scoparia

Hammada scoparia is a small highly-branched halophytic shrub belonging to the Chenopodiaceae family. It is widely used in North African traditional medicine to prevent several diseases such cancer, hepatitis, inflammation, and obesity. The methanol extract of H. scoparia leaves (200 mg/kg/day) was evaluated for its renoprotective effect against ethanol-induced (4 g/kg) renal dysfunction in rats. H. scoparia extract attenuated the increase of TBARS in kidneys, and enhanced the anti-oxidant status of rats by increasing the levels of SOD, CAT, and GPx. The overexpression of glycogen synthase kinase–3β and proline–rich tyrosine kinase 2 in kidneys of ethanol–treated rats was normalized after H. scoparia extract treatment.24H. scoparia leaf extract is rich in alkaloids (carnegine and N-methylisosalsoline) and flavonoids (isorhamnetin triglycerides), as reported by Bourogaa et al.104 and Ben Salah et al.105 Qiu et al.106 determined the potential renoprotective effects of isorhamnetin in a type 2 diabetic rat model.

Hyparrhenia hirta

Hyparrhenia hirta is a perennial grass belonging to the Poaceae family. It is native to the southern Africa and Mediterranean regions.107H. hirta is used in traditional medicine for its diuretic properties.108 Bouaziz et al.25 studied the nephroprotective effect of methanolic extract from H. hirta aerial parts (200 mg/kg in corn oil) against sodium nitrate-induced kidney (400 mg/kg in corn oil) dysfunction. Sodium nitrate-mediated oxidative stress in kidneys is characterized by enhanced lipid peroxidation and reduced CAT, SOD, and GPx activity. Renal damage was histologically characterized by degeneration of renal tubule cells and mononuclear cell infiltration. A reversal of anti-oxidant enzymes and peroxidative damage in kidneys by H. hirta extract has been attributed to its anti-oxidant and antiperoxidative properties and its role as a scavenger of free radicals, which could be due to its flavonoid content, namely apigenin, quercetin, and luteolin derivatives.109 The potent nephroprotective effect of apigenin,110 quercetin,111 and luteolin59 was determined against cisplatin-induced nephrotoxicity in rats.

Lavandula stoechas

Lavandula stoechas is a medicinal plant belonging to the Lamiaceae family.112 Selmi et al.26 investigated the nephroprotective activity of L. stoechas aerial part essential oil (10, 30, and 50 mg/kg) against malathion-induced (200 mg/kg) oxidative stress in mice. Malathion treatment decreased body weight and perturbated metabolic parameters. However, L. stoechas essential oil abolished all malathion-induced body gain loss and kidney relative weight increase, hemodynamic, and metabolic disorders, as well as renal oxidative stress.26 The chemical composition of L. stoechas essential oil is characterized by the presence of d-fenchone, α-pinene, camphor, camphene, Eucapur, limonene, linalool, and endobornyl acetate. The essential oils also contain smaller percentages of tricyclene, cymene, Δ-cadinene, and selina-3,7(11)-diene.113 These molecules are the prime anti-oxidant source of this plant, and underlie its ability to scavenge free radicals, which are the major cause of lipid peroxidation.114

Lycium europaeum

L. europaeum is a spiny shrub belonging to the Solonaceae Family and is dispersed throughout all countries in the Mediterranean basin.115 It has been used in numerous traditional remedies for skin burning, rheumatic pain, constipation, hypertension, infectious ailments, and kidney and liver disorders.116 Cisplatin treatment has been shown to significantly augment serum levels of urea, creatinine, uric acid, and blood urea nitrogen in mice. L. europaeum leaf polysaccharide has been shown to reduce these renal biochemical parameters. Similar results were observed for the methanol extract from L. europaeum leaves on kidney injury induced by cisplatin27 and by CCl4.28L. europaeum leaf extract is rich in caffeic acid, gallic acid, naringenin, epicatechin, vanillic acid, rutin, and coumaric acid. Its nephroprotective activity against cisplatin has been attributed to caffeic acid phenethyl ester,117 gallic acid,118 naringenin,60 epicatechin,76 vanillic acid,56 rutin,58 and p-coumaric acid.119

Malva sylvestris

Malva sylvestris is a common mallow belonging to the Malvaceae family. This plant is native to Europe, Asia, and North Africa, and its medicinal applications include its use as a diuretic, laxative, spasmolytic, lenitive, and choleretic. Malva sylvestris is also used as bronchodilator, expectorant, antitussive, and antidiarrheal, and has been highly recommended for acne and skin care, and as an antiseptic, emollient, and demulcent.120 The decoction of M. sylvestris leaves and flowers was investigated for its nephroprotective action against vanadium-induced kidney damage in rats.29 For 90 days, rats were given 0.2 g dw/kg BW of M. sylvestris decoction and 0.24 mmol/kg BW of vanadium in drinking water. Results showed that vanadium poisoning resulted in a significant increase in the formation of free radicals and anti-oxidant enzymes (SOD, CAT, and GPX) in the kidney. However, treatment with M. sylvestris decoction restored lipid peroxidation levels, anti-oxidant enzyme activities, and histological features, which appeared normal compared to control rats. The beneficial effects of M. sylvestris leaf extract (0.2 g/kg) were also observed against lithium carbonate-induced (25 mg/kg) renal damage in rats.30 As reported by Ben Saad et al.30 the protective properties of M. sylvestris extract could be related to its rich make-up of phenolic acids (epicatechic acid, gallic acid, coumaric acid, vanillic acid, and catechic acid) and flavonoids (rutin, kaempferol, quercetin, and luteolin). In fact, potent nephroprotective effects of gallic acid,118p-coumaric acid,119 vanillic acid,56 rutin,58 kaempferol,91 quercetin,61 and luteolin59 were found against several kidney toxicities in rats.

Mentha peperita

Mentha peperita is a native genus of the Mediterranean region belonging to the Lamiaceae family. It is widely used in food and in traditional medicine.121 Bellassoued et al.31 investigated M. peperita leaf essential oil for its nephroprotective action against CCl4-induced renal failure in rats. M. peperita leaf essential oil was orally administrated for 7 consecutive days (5, 15, 40 mg/kg BW) to rats prior to CCl4 (1 ml/kg BW) intraperitoneal treatment. Results showed that pretreatment with M. peperita leaf essential oil at 15 and 40 mg/kg prior to CCl4 significantly reduced stress parameters (urea and creatinine). A significant reduction in kidney lipid peroxidation (TBARS) and an increase in anti-oxidant enzymes (SOD, CAT, and GPx) were also observed after treatment with M. peperita leaf essential oil (40 mg/kg) compared to CCl4-treated rats. Furthermore, pretreatment with M. peperita leaf essential oil at 40 mg/kg markedly ameliorated the histopathological hepatic and kidney lesions induced by CCl4. M. peperita leaf essential oil contains active ingredients including menthol and iso-menthone. These two compounds exhibit a potent anti-inflammatory activity,121 indicating that M. peperita leaf essential oil could be a promising natural product against CCl4-induced oxidative damage in the kidney, consistent with that reported by Bellassoued et al.31

Morus alba

The leaves of M. alba of the Moraceae family, commonly known as mulberry, are mainly used as food for silk worms and are sometimes used as cattle fodder in different parts of the world.122 The infusion and decoction of leaves have been used to prevent or treat urinary disorders.123 The aqueous acetonic extract of M. alba leaves (100 mg/kg) was studied against glyphosate-induced (100 mg/kg) kidney injury in mice.32 Renal oxidative stress induced by glyphosate was evidenced by an increase in MDA and protein carbonyl levels and a decline in SOD activity. M. alba leaf extract appeared to modulate these altered biochemical parametres by maintaining free iron and Ca2+ homeostasis, as well as regulating endogenous anti-oxidant enzymes. The aqueous acetonic fraction of M. alba leaves is rich in chlorogenic acid and its isomers,32 which can protect kidneys from glyphosate-induced nephrotoxicity.96

Nitraria retusa

Nitraria retusa belongs to the Nitrariaceae family and is used for its anti-inflammatory properties124 and to facilitate healing.125 In this study, the nephroprotective effect of aqueous extract from N. retusa fruit (300 mg/kg BW) against penconazole (67 mg/kg BW) caused kidney injury.33N. retusa treatment provoked a significant decrease in the levels of MDA, H2O2, protein carbonyl and advanced oxidation protein products, as well as improved alkaline phosphatase (ALP) and gamma glutamyltranspeptidase activities. Polyphenol constituents of N. retusa fruit aqueous extract could enhance their anti-oxidant activities in nephroprotection. N. retusa fruit extract mainly contains hydroxycaffeic acid, epicatechin derivatives, p-coumaric acid, cyanidin derivative, 3-O-methylgallic acid, taxifoline, chlorogenic acid, and kaempferol derivative. Among these phenolics, chlorogenic acid,96p-coumaric acid,119 caffeic acid,88 gallic acid,118 and kaempferol91 are known for their potent nephroprotection.

Olea europea

Olea europea is a known olive tree belonging to the Oleaceae family. It represents a great economic and social importance owing mainly to the great value of olive oil. This olive oil is the primary source of fat in the Mediterranean diet, which has been associated with low mortality related to cardiovascular disease.126 Ghorbel et al.34 found that extra vierge olive oil abrogated acrylamide-induced nephrotoxicity. Ethanolic extract from O. europea fruit (200 mg/kg BW) and its phenolic compound, oleuropein (50 mg/kg BW), has been shown to protect against nephrotoxicity caused by deltamethrin (15 mg/kg bw) in rats.35 Deltamethrin administration can increase MDA levels and reduce SOD and CAT activities. O. europea fruit and oleuropein have been used as treatments for inflammation and apoptosis. Oleuropein, verbascoside, luteolin-7-glucoside, apigenin-7-glucoside, and hydroxytyrosol are the main components of the ethanolic extract from O. europea fruit.35 The nephroprotective effect of oleuropein and hydroxytyrosol extracted from Tunisian olive leaf extract have been investigated in rats treated with bisphenol A.36 In a recent study, Soussi et al.37 found that the aqueous extract of Tunisian O. europaea leaves protected against kidney damage induced by diclofenac in mice.

Opuntia ficus-indica

Opuntia ficus-indica is a plant popularly known as prickly pear belonging to the Cactaceae family. It is widely distributed in the Mediterranean area, Mexico, and South Africa, and is widely known because of its nutritional and medicinal usage.127 Administration of lithium carbonate (25 mg/kg BW) has been shown to cause a significant increase in serum creatinine, uric acid, and urea levels. Additionally, a significant decrease in SOD, CAT, and GPx activities was associated with a significant increase in MDA levels. However, treatment with O. ficus indica extract (100 mg/kg BW) prevented these alterations and maintained the anti-oxidant status in rats. Histopathological observations support this biochemical evidence of nephroprotection.38 Similar results were obtained for the aqueous extract from O. ficus-indica cladodes on kidney injury induced by sodium dichromate.39 As reported by Saad et al.,38 the aqueous extract from O. ficus-indica cladodes was characterized by the presence of quercetin, vanillic acid, gallic acid, rutin, kampferol, catechin, epicatechin, coumarin, isorhamnetin, and caffeic acid. All of these phenolic compounds have been well studied for their potent nephroprotection, particularly quercetin,61 vanillic acid,56 gallic acid,118 rutin,58 kaempferol,91 catechin,128 epicatechin,65 coumarin,57 isorhamnetin,106 and caffeic acid.88

Periploca angustifolia

Periploca angustifolia evergreen shrub is a member of the Apocynaceae family. It is found wild in North Africa (from Morocco to Egypt), southern Spain, Sicily, Malta, Crete, Lebanon, and Syria. P. angustifolia is used in traditional medicine for diabetes, rheumatism, hemorrhoids, and gastric ulcer.129 The preventitive action of polysaccharides isolated from P. angustifolia leaves against cadmium-caused oxidative stress in kidneys of rats has been tested. Results indicated that cadmium treatment increased the levels of urea and creatinine in the serum. The increased levels of protein oxidation and lipid peroxidation along with decreased activities of SOD, CAT and GPx were ameliorated by P. angustifolia polysaccharides pre-treatment. Histopathological studies also supported the prevention action of P. angustifolia polysaccharides. Saccharose is the major monosaccharide component of P. angustifolia leaves, followed by trehalose, L-inositol, and M-inositol, as reported by Athmouni et al.40

Phoenix dactylifera

Phoenix dactylifera is a tree commonly known as date palm belonging to the Arecaceae family. P. dactylifera is mostly cultivated for the consumption of its fruit, which has been utilized since ancient times as an important staple food and in ethnomedicine in different parts of the world.130 The fruit of P. dactylifera is used as a detersive and astringent for intestinal ailments, treatment for sore throat, colds, bronchial asthma, to relieve fever, cystisis, gonorrhea, edema, liver and abdominal ailments, and to counteract alcohol intoxication.131 Dichloroacetic acid administration (2 g/l) caused augmentation of renal MDA levels and significant diminution of GSH levels. Moreover, dichloroacetic acid altered the anti-oxidant enzyme activities and deteriorated renal function, as assessed by increased plasma urea, uric acid, and creatinine levels. Treatment with P. dactylifera extract (4 ml/kg) significantly normalized the plasma levels of creatinine, urea, and uric acid, reduced the MDA levels, significantly normalized anti-oxidant enzyme activities and GSH levels, and restored the kidney histology in rats.41 Therefore, it has been speculated that P. dactylifera extract protects rats from kidney damage through its anti-oxidant capacity attributed to make-up of phenolic acids, mainly ferulic, caffeic, and p-coumaric acids.41 In fact, ferulic,132 caffeic,88 and p-coumaric119 acids are known for their efficient nephroprotective action.

Pinus halepensis

Pinus halepensis is a tree belonging to the Pinaceae family found around the Mediterranean basin. The resin and decoction of all Pinus species have antiseptic, diuretic, rubefacient, vermifuge, antidiabetic, and cicatrisant properties.133 Bouzenna et al.42 studied the protective effect of essential oil from P. halepensis needles on aspirin-induced acute kidney damage in rats. Rats were orally treated with P. halepensis essential oil (1 ml/kg) for 56 days and then given aspirin (600 mg/kg) orally thrice a day at an interval of 4 h for 4 successive days. Results showed that aspirin induced an increase in serum biochemical parameters as well as oxidative stress in kidney. There was an increase in TBARS and a decrease in SOD, CAT, and GPx in kidney. Administration of P. halepensis essential oil corrected these parameters. Hamrouni et al.134 found that the essential oil of Tunisian P. halepensis needles was characterized by the predominance of monoterpene hydrocarbons, mainly β-caryophyllene, β-myrcene and α-pinene. These volatile compounds could interact to protect against aspirin-induced nephrotoxicity.

Rhus tripartitum

Rhus tripartitum is a dioecious shrub belonging to the Anacardiaceae family.135R. tripartitum is widely used to treat many diseases such as diarrhea and dysentery, colitis, gastointestinal diseases, inflammatory diseases, diabetes, haemoptysis, conjunctivitis, animal bites and poisons, hemorrhoids, sexual disease, fever, pain, and various cancers. Tlili et al.43 investigated the protective action of methanolic extract from R. tripartitum fruit (200 mg/kg in olive oil) against cisplatin-induced (13 mg/kg) nephrotoxicty in rats. The increased levels of biochemical parameters (creatinine, urea, and uric acid) were attenuated by pretreatment with R. tripartitum fruit extract. Histopathologic observation showed that pretreatment with R. tripartitum fruit extract restored the pathology. These results could be due to the richness of R. tripartitum fruit extract in phenolics, especially betulinic acid. In fact, the efficient renoprotective effects of betulinic acid isolated from Cornus walteri in cisplatin-provoked renal toxicity were determined by Lee et al.136

Rosmarinus officinalis

Rosmarinus officinalis, commonly known as rosemary is a perennial, aromatic medicinal plant belonging to the Lamiaceae family. It is shrub-shaped with branches full of leaves, exuding a characteristic fragrance.137 One study evaluates the effects of aqueous extract from R. officinalis leaves against kidney toxicity induced by CCl4 in mice. Results showed that the renal damage induced by CCl4 was associated with a rise in oxidative stress, an increase of TBARS, and changes the nephropathology parameters including creatinine, blood urea nitrogen, and urea. However, a decrease in GSH levels and anti-oxidant enzymes (SOD, CAT, and GPx) was observed. These findings were substantiated by histological analysis. Pretreatment with R. officinalis leaf extract attenuated CCl4-related toxic effects.44 The polyphenolic profile of Tunisian R. officinalis leaf extract is characterized by its richness in carnosic and rosmarinic acids.138 The potent nephroprotective effects of carnosic139 and rosmarinic140 acids were observed in cisplatin-induced nephrotoxicity in rats.

Salvia officinalis

Salvia officinalis, popularly known as sage, is a member of the Lamiaceae family. It is an aromatic plant widely distributed in the world. Since ancient times, S. officinalis has been an ingredient in perfumes, a flavoring in a variety of food preparations,141 and a medicinal plant used to fight fever, rheumatism, perspiration, sexual malfunction, chronic bronchitis, and various mental diseases.142 Koubaa et al.45 evaluated the impact of the essential oil from S. officinalis aerial parts (15 mg/kgBW) on renal nephrotoxicity induced by vanadium (5 mg/kg BW) in rats. A marked increase in LPO and PCO levels with a significant decrease in SOD, CAT, and GPx. However, the administration of S. officinalis essential oil significantly restored these biochemical markers and pathological lesions. This protective effect seems to be due to the richness of S. officinalis essential oil in β-caryophyllene, limonene, carvacrol, caryophyllene, borneol, α-pinene, and α-thujene, as reported by Koubaa et al.45 Horváth et al.143 found that β-caryophyllene ameliorated cisplatin-induced nephrotoxicity. Rehman et al.85 reported the protective role of limonene against renal damage induced by the anticancer drug doxorubicin. The protective effect of carvacrol on renal function in gentamicin-induced nephrotoxicity in rats was determined by Ahmadvand et al.144

Teucrium polium

Teucrium polium is defined as golden germander belonging to the Lamiaceae family. It has been used to treat abdominal pain, indigestion, and diabetes. The aqueous extract of T. polium aerial parts (5 g/l) was investigated against CCl4-induced (0.5 ml/kg) nephrotoxicity in rats. CCl4 treatment increase serum renal markers (urea and creatinine) and lipid peroxidation and decreased anti-oxidant enzymes (SOD, CAT and GPx). However, pretreatment with T. polium extract protected against oxidative damage and biochemical changes induced by CCl4, which were validated by histopathological observations.46 According to Goulas et al.,145T. polium aerial part extract is characterized by the presence of phenylpropanoid glycosides (verbascoside and poliumoside), flavones (apigenin and its derivatives), and two methoxyflavones, with poliumoside being the most abundant and active component of T. polium extract.

Trigonella foenum-graecum

Trigonella foenum-graecum is an annual herb popularly known as fenugreek that belongs to the Leguminosae family. It is native to an area extending from Iran to northern India and widely cultivated in China, India, Egypt, Ethiopia, Morocco, Ukraine, Greece, and Turkey.146 It is an ancient traditional medicinal plant147 due to its olfactory, antifever, anti-inflammatory, antimicrobial, anticancer, antidiabetic, antihyperglycemic, laxative, galactogogue, and digestive effects. Belaïd-Nouira et al.47 evaluated fenugreek seeds (5% in the diet) for their effects on rat nephrotoxicity caused by aluminum chloride (500 mg/kg BW for one month then 1,600 ppm via drinking water). Aluminum chloride inhibited ALP, decreased total antioxidant status, and an induced LPO in the blood and brain. Treatment with fenugreek seed powder helped to restore normal plasma values of urea, creatinine, ALP, and glucose, as well as increased the total antioxidant status, inhibited LPO, and alleviated histopathological changes in the injured kidney. Belguith-Hadrich et al.148 also determined the potent renoprotective action of fenugreek seeds on renal oxidative stress and nephropathy caused by a high cholesterol diet in rats. Mbarki et al.48 noted that fenugreek seed supplementation protected the kidney from CCl4-induced oxidative stress and toxicity in rats. According to Belaïd-Nouira et al,47 Belguith-Hadrich et al,148 and Mbarki et al,48 the anti-oxidant activity of fenugreek seeds could be attributed to polyphenols, particularly flavonoids. Three flavonoid glycosides were detected in methanol extract from the fenugreek seed extract: vicenin-2, isoschaftoside, and isoorientin.149

Vitis vinifera

Vitis vinifera is a perennial, woody climbing grapevine belonging to the Vitaceae family. It is indigenous to southern Europe and western Asia and is cultivated today in all temperature regions of the world.150 Grape seeds contain 6–20% oil, used for edible purposes, soaps, and as a linseed substitute. A malagma made from the seed is a folk remedy for condylomata of the joints. Leaves astringent has been used in diarrhoea. The juice of unripe fruit astringent has been used to treat throat affections. Dried fruit as demulcent, cooling, sweet, laxative, stomachic, has been used in thirst, body heat, coughs, hoarseness, consumption, and wasting diseases. The fruit, prepared in various manners, is said to be a remedy for mola, uterine tumors, and hardness of the liver, tumors, and cancer.151 Mokni et al.49 evaluated the protective effect of the ethanol extract from V. vinifera seeds and skin against doxorubicin-induced renal toxicity in rats. Animals were treated with the ethanol extract from V. vinifera seeds and skin for 8 days and administered doxorubicin (20 mg/kg) 4 days later. Results showed that doxorubicin induced renal toxicity by affecting the renal architecture and plasma creatinine. Doxorubicin also induced oxidative stress characterized by an increase in MDA, calcium, and H2O2 and a decrease in CAT and SOD. Unexpectedly, doxorubicin increased peroxidase and decreased carbonyl protein and plasma urea. Treatment with V. vinifera extract counteracted almost all adverse effects induced by doxorubicin. Turki et al.50 conducted an investigation of supplementation with grape seed extract capsules (2 g GSE/day) or placebo on chronic kidney disease patients for 6 months. Grape seed ameliorated inflammation by decreasing C-reactive protein and triglyceridemia and counteracted anemia and thrombocytopenia. Grape seed extract is a polyphenolic mixture exhibiting anti-oxidant and anti-inflammatory properties as reported by Turki et al.50 According to Mokni et al.,49 the main compound of grape seed and skin extracts are 2,5-dihydroxybenzoïc acid, gallic acid, and vanillin. Among these phenolic compounds, gallic acid118 and vanillin152 have been well studied for their potent nephroprotection.

Future directions

Research on Tunisian nephroprotective plants has been mainly done in a laboratory setting with a limited number of animals. Thus, additional studies must be done with a greater number of experiments, different animal models, and human subjects. It should be mentioned that this is the first review that summarizes several reports on Tunisian nephroprotective plants. The literature demonstrates that these plants contain bioactive compounds that could be used to treat kidney disease. This review may be valuable to health professionals, scientists, and scholars working in the field of pharmacology and therapeutics to produce new safety drug formulations to treat kidney diseases.

Conclusions

In this review, 29 Tunisian medicinal plants were summarized for their significant nephroprotective activities against renal toxicities in animal models. Lamiaceae family was the most commonly used nephroprotective Tunisian plant. Leaves were maximally used for nephroprotection compared to the other plant parts. In the case of Indian nephroprotective plants, Asif153 also reported that the leaves were most frequently used in the treatment of nephrotoxicity, with the most dominant family being Euphorbiaceae. In this review, most studies focused on drug-induced renal failure, which is a major challenge in medical practice. Other studies focused on other important nephrotoxicity factors, including industrial chemicals, particularly CCl4-induce nephrotoxicity. In general, CCl4 enhanced levels of renal markers (urea and creatinine) in the serum of experimental animals. It also increased oxidative stress markers resulting in increased LPO with a concomitant decrease in SOD, CAT, and GPx in the kidney. To protect against this nephrotoxicity, some medicinal plants, have curative properties attributed to various complex chemical substances as organosulfur compounds, polyphenols, polysaccharides, phenylpropanoids, terpenes, and alkaloids.

Abbreviations

ALP: 

alkaline phosphatase

CAT: 

catalase

CCl4: 

carbon tetrachloride

GPx: 

glutathione peroxidase

GSH: 

reduced glutathione

H2O2: 

hydrogen peroxide

LPO: 

lipid peroxidase

MDA: 

malondialdehyde

PCO: 

protein carbonyl

ROS: 

reactive oxygen species

SOD: 

superoxide dismutase

Declarations

Acknowledgement

None.

Funding

None.

Conflict of interest

The authors declare no conflicts of interest.

Authors’ contributions

Conceptualization (WAW); writing (WAW); methodology (WAW); investigation (WAW); formal analysis (WAW); data curation (WAW); resources (WAW); supervision (MST); writing, review, and editing (WAW). All authors have read and agreed to the published version of the manuscript.

References

  1. Javaid R, Aslam M, Nizami Q, Javaid R. Role of antioxidant herbal drugs in renal disorders: An overview. Free Rad Antiox 2012;2(1):1-5 View Article PubMed/NCBI
  2. Janakiraman M, Jeyaprakash K. Nephroprotective potential of medicinal plants: A Review. Biochem 2015;4(9):543-547 View Article PubMed/NCBI
  3. Sundararajan R, Bharampuram A, Ravindranadh Koduru R. A review on phytoconstituents for nephroprotective activity. Pharmacoph 2014;5(1):160-182 View Article PubMed/NCBI
  4. Satlin LM, Bockenhauer D. Physiology of the developing kidney: potassium homeostasis and its disorder. Pediatr Nephrol 2016;17:219-246 View Article PubMed/NCBI
  5. Ali Noorani A, Gupta K, Bhadada K, Kale MK. Protective effect of methanolic leaf extract of Caesalpinia bonduc (L) on gentamicin-induced hepatotoxicity and nephrotoxicity in rats. Iranian J Pharmacol and Ther 2011;10(1):21-25 View Article PubMed/NCBI
  6. Porter GA, Bennett WM. Nephrotoxic acute renal failure due to common drugs. Am J Physiol 1981;241(1):F1-F8 View Article PubMed/NCBI
  7. Gaikwad K, Dagle P, Choughule P, Joshi YM, Kadam V. A review on some nephroprotective medicinal plants. Int J Pharm Sci Res 2012;3(8):2451-2454 View Article PubMed/NCBI
  8. Aidi Wannes W, Marzouk B. Research progress of Tunisian medicinal plants used for acute diabetes. J Acute Dis 2016;5(5):357-363 View Article PubMed/NCBI
  9. Aidi Wannes W, Saidani Tounsi M, Marzouk B. A review of Tunisian medicinal plants with anticancer activity. J Complement Integr Med 2017;15(1):20170052 View Article PubMed/NCBI
  10. Aidi Wannes W, Saidani Tounsi M. Research advances in ulcer treatment using Tunisian medicinal plants. Biointerface Res Appl Chem 2017;7(3):2035-2039 View Article PubMed/NCBI
  11. Aidi Wannes W, Saidani Tounsi M, Marzouk B. Tunisian hepatoprotective plants. Chem Res J 2018;3(3):148-167 View Article PubMed/NCBI
  12. Aidi Wannes W, Saidani Tounsi M. Can medicinal plants contribute to the cure of Tunisian COVID-19 patients?. J Med Plants Stud 2020;8(5):218-226 View Article PubMed/NCBI
  13. Ncir M, Saoudi M, Sellami H, Rahmouni F, Lahyani A, Makni Ayadi F, et al. In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney. Arch Physiol Biochem 2018;124(3):207-217 View Article PubMed/NCBI
  14. Dhibi S, Bouzenna H, Samout N, Tlili Z, Elfeki A, Hfaiedh N. Nephroprotective and antioxidant properties of Artemisia arborescens hydroalcoholic extract against oestroprogestative-induced kidney damages in rats. Biomed Pharmacother 2016;82:520-527 View Article PubMed/NCBI
  15. Saoudi M, Badraoui R, Bouhajja H, Ncir M, Rahmouni F, Grati M, et al. Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Biomed Pharmacother 2017;94:955-963 View Article PubMed/NCBI
  16. Saoudi M, Badraoui R, Rahmouni F, Jamoussi K, El Feki A. Antioxidant and protective effects of Artemisia campestris essential oil against chlorpyrifos-induced kidney and liver injuries in rats. Front Physiol 2021;12:618582 View Article PubMed/NCBI
  17. Tlili N, Feriani A, Saadoui E, Nasri N, Khaldi A. Capparis spinosa leaves extract: Source of bioantioxidants with nephroprotective and hepatoprotective effects. Biomed Pharmacother 2017;87:171-179 View Article PubMed/NCBI
  18. Hsouna AB, Saoudi M, Trigui M, Jamoussi K, Boudawara T, Jaoua S, et al. Characterization of bioactive compounds and ameliorative effects of Ceratonia siliqua leaf extract against CCl4 induced hepatic oxidative damage and renal failure in rats. Food Chem Toxicol 2011;49(12):3183-3191 View Article PubMed/NCBI
  19. Bouzenna H, Dhibi S, Samout N, Rjeibi I, Talarmin H, Elfeki A, et al. The protective effect of Citrus limon essential oil on hepatotoxicity and nephrotoxicity induced by aspirin in rats. Biomed Pharmacother 2016;83:1327-1334 View Article PubMed/NCBI
  20. Mejri H, Tir M, Feriani A, Ghazouani L, Allagui MS, Saidani-Tounsi M. Does Eryngium maritimum seeds extract protect against CCl4 and cisplatin induced toxicity in rats: Preliminary phytochemical screening and assessment of its in vitro and in vivo antioxidant activity and antifibrotic effect. J Funct Food 2017;37:363-372 View Article PubMed/NCBI
  21. Dhibi S, Mbarki S, Elfeki A, Hfaiedh N. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat. Bosn J Basic Med Sci 2014;14(2):99-104 View Article PubMed/NCBI
  22. Athmouni K, Belhaj D, El Feki A, Ayadi H. Optimization, antioxidant potential, modulatory effect and anti-apoptotic action in of Euphorbia bivonae polysaccharides on hydrogen peroxide-induced toxicity in human embryonic kidney cells HEK293. Int J Biol Macromol 2018;116:482-491 View Article PubMed/NCBI
  23. Bellakhdar J, Claisse R, Fleurentin J, Younos C. Repertory of standard herbal drugs in the Moroccan pharmacopoeia. J Ethnopharmacol 1991;35(2):123-143 View Article PubMed/NCBI
  24. Bourogaa E, Jarraya R, Jarraya, Damak M, El Feki A. Therapeutic efficacy of Hammada scoparia extract against ethanol induced renal dysfunction in Wistar rats. J Food Biochem 2017;41(2):e12307 View Article PubMed/NCBI
  25. Bouaziz H, Rafrafi M, Ben Salah G, Marrekchi R, Kammoun H, Jamoussi K, et al. Nitrate provoked kidney toxicity and DNA impairment in adult rats: Alleviation by Hyparrhenia hirta. Pak Vet J 2015;35(4):397-402 View Article PubMed/NCBI
  26. Selmi S, Jallouli M, Gharbi N, Marzouki L. Hepatoprotective and renoprotective effects of Lavender (Lavandula stoechas L.) essential oils against malathion-induced oxidative stress in young male mice. J Med Food 2015;18(10):1103-1111 View Article PubMed/NCBI
  27. Rjeibi I, Feriani A, Ben Saad A, Ncib S, Sdayria J, Hfaiedh N, et al. Lycium europaeum Linn as a source of polysaccharide with in vitro antioxidant activities and in vivo anti-inflammatory and hepato-nephroprotective potentials. Journal of Ethnopharmacol 2018;225:116-127 View Article PubMed/NCBI
  28. Rjeibi I, Feriani A, Ben Saad A, Ncib S, Sdayria J, Saidi I, et al. Phytochemical characterization and bioactivity of Lycium europaeum: A focus on antioxidant, antinociceptive, hepatoprotective and nephroprotective effects. Biomed Pharmacother 2017;95:1441-1450 View Article PubMed/NCBI
  29. Marouane W, Soussi A, Murat JC, Bezzine S, El Feki A. The protective effect of Malva sylvestris on rat kidney damaged by vanadium. Lipids Health Dis 2011;10:65 View Article PubMed/NCBI
  30. Ben Saad A, Rjeibi I, Brahmi D, Smida A, Ncib S, Zouari N, et al. Malva sylvestris extract protects upon lithium carbonate-induced kidney damages in male rat. Biomed Pharmacother 2016;84:1099-1107 View Article PubMed/NCBI
  31. Bellassoued K, Ben Hsouna A, Athmouni K, Pelt JV, Makni Ayadi F, Rebai T, et al. Protective effects of Mentha piperita L. leaf essential oil against CCl4 induced hepatic oxidative damage and renal failure in rats. Lipids Heal dis 2018;17:1-14 View Article PubMed/NCBI
  32. Rebai O, Fattouch S, Amri M. Nephroprotective effect of aqueous acetonic extract of Morus alba and its underlying mechanisms against glyphosate-induced toxicity - in vivo model. Pestic Phytomed 2021;36(1):45-59 View Article PubMed/NCBI
  33. Chaâbane M, Koubaa M, Soudani N, Elwej A, Grati M, Jamoussi K, et al. Nitraria retusa fruit prevents penconazole-induced kidney injury in adult rats through modulation of oxidative stress and histopathological changes. Pharm Biol 2017;55(1):1061-1073 View Article PubMed/NCBI
  34. Ghorbel I, Elwej A, Fendri N, Mnif H, Jamoussi K, Boudawara T, et al. Olive oil abrogates acrylamide induced nephrotoxicity by modulating biochemical and histological changes in rats. Ren Fail 2017;39(1):236-245 View Article PubMed/NCBI
  35. Maalej A, Mahmoudi A, Bouallagui Z, Fki I, Marrekchi R, Sayadi S. Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis. Food Chem Toxicol 2017;106(Pt A):455-465 View Article PubMed/NCBI
  36. Mahmoudi A, Ghorbel H, Bouallegui Z, Marrekchi R, Isoda H, Sayadi S. Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups’. Exp Toxicol Pathol 2015;67(7-8):413-425 View Article PubMed/NCBI
  37. Soussi R, Hfaiedh N, Saklya M, Ben Rhouma K. The aqueous extract of Olea europaea leaves protects from haematotoxicity and kidney damage induced by diclofenac in Swiss albino mice. Royal Soci Chem 2019;9(40):23352-23361 View Article PubMed/NCBI
  38. Saad AB, Rjeibi I, Ncib S, Zouari N, Zourgui L. Ameliorative effect of cactus (Opuntia ficus indica) extract on lithium-induced nephrocardiotoxicity: a biochemical and histopathological study. Biomed Res Int 2017;2017:8215392 View Article PubMed/NCBI
  39. Hfaiedh M, Brahmi D, Zourgui MN, Zourgui L. Phytochemical analysis and nephroprotective effect of cactus (Opuntia ficus-indica) cladodes on sodium dichromate-induced kidney injury in rats. Appl Physiol Nutr Metab 2019;44(3):239-247 View Article PubMed/NCBI
  40. Athmouni K, Belhaj D, El Feki A, Ayadi H. Optimization, antioxidant properties and GC-MS analysis of Periploca angustifolia polysaccharides and chelation therapy on cadmium-induced toxicity in human HepG2 cells line and rat liver. Int J Biol Macromol 2018;108:853-862 View Article PubMed/NCBI
  41. El Arem A, Thouri A, Zekri M, Saafi EB, Ghrairi F, Zakhama A, et al. Nephroprotective effect of date fruit extract against dichloroacetic acid exposure in adult rats. Food Chem Toxicol 2014;65:177-184 View Article PubMed/NCBI
  42. Bouzenna H, Samout N, Amani E, Mbarki S, Tlili Z, Rjeibi I, et al. Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats. J Oleo Sci 2016;65(8):701-712 View Article PubMed/NCBI
  43. Tlili N, Feriani A, Allagui MS, Saadoui E, Khaldi A, Nasri N. Effects of Rhus tripartitum fruit extract on CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 2016;94(8):801-807 View Article PubMed/NCBI
  44. Hamed H, Boulila S, Ghrab F, Kallel R, Boudawara T, El Feki A. The preventive effect of aqueous extract of Rosemary (Rosmarinus officinalis) leaves against the nephrotoxicity of carbon tetrachloride in mice. Arch Physiol Biochem 2020;126(3):201-208 View Article PubMed/NCBI
  45. Koubaa FG, Abdennabi R, Salah ASB, El Feki A. Microwave extraction of Salvia officinalis essential oil and assessment of its GC-MS identification and protective effects versus vanadium-induced nephrotoxicity in Wistar rats models. Arch Physiol Biochem 2019;125(5):404-413 View Article PubMed/NCBI
  46. Rahmouni F, Badraoui R, Amri N, Elleuch A, El-Feki A, Rebai T, et al. Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C. Toxicol Mech Methods 2019;29(5):313-321 View Article PubMed/NCBI
  47. Belaïd-Nouira Y, Bakhta H, Haouas Z, Flehi-Slim I, Ben Cheikh H. Fenugreek seeds reduce aluminum toxicity associated with renal failure in rats. Nutr Res Pract 2013;7(6):466-474 View Article PubMed/NCBI
  48. Mbarki S, Alimi H, Bouzenna H, Elfeki A, Hfaiedh N. Phytochemical study and protective effect of Trigonella foenum graecum (Fenugreek seeds) against carbon tetrachloride-induced toxicity in liver and kidney of male rat. Biomed Pharmacother 2017;88:19-26 View Article PubMed/NCBI
  49. Mokni M, Hamlaoui S, Kadri S, Limam F, Amri M, Marzouki L, et al. Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury. Pak J Pharm Sci 2016;29(3):961-968 View Article PubMed/NCBI
  50. Turki K, Charradi K, Boukhalfa H, Belhaj M, Limam F, Aouani E. Grape seed powder improves renal failure of chronic kidney disease patients. EXCLI J 2016;15:424-433 View Article PubMed/NCBI
  51. Campêlo LM, de Almeida AA, de Freitas RL, Cerqueira GS, de Sousa GF, Saldanha GB, et al. Antioxidant and antinociceptive effects of Citrus limon essential oil in mice. J Biomed Biotechnol 2011;2011:678673 View Article PubMed/NCBI
  52. Bongiorno PB, Fratellone PM, LoGiudice P. Potential health benefits of garlic (Allium sativum): A narrative review. J Complement Integr Med 2008;5(1):1-24 View Article PubMed/NCBI
  53. García Trejo EMÁ, Arellano Buendía AS, Sánchez Reyes O, García Arroyo FE, Arguello García R, Loredo Mendoza ML, et al. The beneficial effects of allicin in chronic kidney disease are comparable to losartan. Int J Mol Sci 2017;18(9):E1980 View Article PubMed/NCBI
  54. Gonzalez J, Cruz Freire JM, Domınguez H, Parajo JC. Production of antioxidants from Artemisia arborescens wood by solvent extraction of hemicellulose hydrolysates. Food Chem 2004;84:243-251 View Article PubMed/NCBI
  55. Mulyaningsih S, Sporer F, Zimmermann S, Reichling J, Wink M. Synergistic properties of the terpenoids aromadendrene and 1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens. Phytomedicine 2010;17(13):1061-1066 View Article PubMed/NCBI
  56. Sindhu G, Nishanthi E, Sharmila R. Nephroprotective effect of vanillic acid against cisplatin induced nephrotoxicity in wistar rats: a biochemical and molecular study. Environ Toxicol Pharmacol 2015;39(1):392-404 View Article PubMed/NCBI
  57. Sen Z, Jie M, Jingzhi Y, Dongjie W, Dongming Z, Xiaoguang C. Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis. Evid Based Complement Alternat Med 2017;2017:5350161 View Article PubMed/NCBI
  58. Radwan RR, Abdel Fattah SM. Mechanisms involved in the possible nephroprotective effect of rutin and low dose γ irradiation against cisplatin-induced nephropathy in rats. J Photochem Photobiol B 2017;169:56-62 View Article PubMed/NCBI
  59. Domitrović R, Cvijanović O, Pugel EP, Zagorac GB, Mahmutefendić H, Škoda M. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology 2013;310:115-123 View Article PubMed/NCBI
  60. Renugadevi J, Prabu SM. Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology 2009;256(1-2):128-134 View Article PubMed/NCBI
  61. Wang J, Pan Y, Hong Y, Zhang QY, Wang XN, Kong LD. Quercetin protects against cadmium-induced renal uric acid transport system alteration and lipid metabolism disorder in rats. Evid Based Complement Alternat Med 2012;2012:548430 View Article PubMed/NCBI
  62. Dib I, Angenot L, Mihamou A, Ziyyat A, Tits M. Artemisia campestris L. Ethnomedicinal, phytochemical and pharmacological review. J Herb Med 2017;7:1-10 View Article PubMed/NCBI
  63. Akrout A, Chemli R, Chreïf I, Hammami M. Analysis of the essential oil of Artemisia campestris L. Flav Fragr J 2001;16(5):337-339 View Article PubMed/NCBI
  64. Başar A. The dissolving effect of α- and β pinenes in pine resin to kidney stone. Acad J Med Pl 2014;2(6):85-87 View Article PubMed/NCBI
  65. Rivera D, Inocencio C, Obon C, Alcaraz F. Review of food and medicinal uses of Capparis L. subgenus Capparis (Capparidaceae). J Econ Bot 2003;57:515-534 View Article PubMed/NCBI
  66. Jiang HE, Li X, Ferguson DK, Wang YF, Liu CJ, Li CS. The discovery of Capparis spinosa L. (Capparidaceae) in the Yanghai Tombs (2800 years b.p.), NW China, and its medicinal implications. J Ethnopharmacol 2007;113(3):409-420 View Article PubMed/NCBI
  67. Eddouks M, Lemhadri A, Michel JB. Hypolipidemic activity of aqueous extract of Capparis spinosa L. in normal and diabetic rats. J Ethnopharmacol 2005;98(3):345-350 View Article PubMed/NCBI
  68. El-Hilaly J, Hmammouchi M, Lyoussi B. Ethnobotanical studies andeconomic evaluation of medicinal plants in Taounate Province (Northern Morocco). J Ethnopharmacol 2003;86:149-158 View Article PubMed/NCBI
  69. Lemhadri A, Mohamed E, Thierry S, Remy B. Antihyperglycaemic andanti-obesity effects of Capparis spinosa and Chamaemelum nobile aqueous extracts in HFD mice. Am J Pharmacol Toxicol 2007;2(3):106-110 View Article PubMed/NCBI
  70. Feng X, Lu J, Xin H, Zhang L, Wang Y, Tang K. Anti-arthritic active fraction of Capparis spinosa L. fruits and its chemical constituents. Yakugaku Zasshi 2011;131(3):423-429 View Article PubMed/NCBI
  71. Matsuyama K, Villareal MO, El Omri A, Han J, Kchouk ME, Isoda H. Effect of Tunisian Capparis spinosa L. extract on melanogenesis in B16 murine melanoma cells. J Nat Med 2009;63(4):468-472 View Article PubMed/NCBI
  72. Rajesh P, Selvamani P, Latha S, Saraswathy A, Rajesh Kannan V. A review on chemical and medicobiological applications of capparidaceae family. Pharmacogn Rev 2009;3(6):378-387 View Article PubMed/NCBI
  73. Sher H, Al-Yemeni MN, Sher H. Forest Resource utilization assessment for economic development of rural community, Northern parts of Pakistan. J Med Plants Res 2010;4(12):1197-1208 View Article PubMed/NCBI
  74. Allaith AAA. Assessment of the antioxidant properties of the caper fruit (Capparis spinosa L.) from Bahrain. J Assoc Arab Univ Basic Appl Sci 2014 2016;19:1-7 View Article PubMed/NCBI
  75. Valentovic MA, Ball JG, Brown JM, Terneus MV, McQuade E, Van Meter S, et al. Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress. Toxicol In Vitro 2014;28(2):248-257 View Article PubMed/NCBI
  76. Tanabe K, Tamura Y, Lanaspa MA, Miyazaki M, Suzuki N, Sato W, et al. Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy. Am J Physiol Renal Physiol 2012;303(9):F1264-F1274 View Article PubMed/NCBI
  77. Kivçak B, Mert T, Ozturk HT. Antimicrobial and cytotoxic activity of Ceratonia siliqua L. Extracts. Turk J Biol 2002;26:197-200 View Article PubMed/NCBI
  78. Sancak EB, Akbas A, Silan C, Cakir DU, Turkon H, Ozkanli SS. Protective effect of syringic acid on kidney ischemia-reperfusion injury. Ren Fail 2016;38(4):629-635 View Article PubMed/NCBI
  79. Ozcan F, Ozmen A, Akkaya B, Aliciguzel Y, Aslan M. Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. Clin Exp Med 2012;12(4):265-272 View Article PubMed/NCBI
  80. Asci H, Ozmen O, Ellidag HY, Aydin B, Bas E, Yilmaz N. The impact of gallic acid on the methotrexate-induced kidney damage in rats. J Food Drug Anal 2017;25(4):890-897 View Article PubMed/NCBI
  81. Di Vaio C, Grazianib G, Gasparib A, Scaglione G, Nocerino S, Ritieni A. Essential oils content and antioxidant properties of peel ethanol extract in 18 lemon cultivars. Sci Hortic 2010;126:50-55 View Article PubMed/NCBI
  82. AL-Jabri NN, Hossain MA. Comparative chemical composition and antimicrobial activity study of essential oils from two imported lemon fruits samples against pathogenic bacteria. Beni-Suef Univ J Basic Appl Sci 2014;3(4):247-253 View Article PubMed/NCBI
  83. Kirbaslar G, Kirbaslar I. Composition of Turkish bitter orange and lemon leaf oils. J Essent Oil Res 2004;16(2):105-108 View Article PubMed/NCBI
  84. Lota ML, de Rocca Serra D, Tomi F, Jacquemond C, Casanova J. Volatile components of peel and leaf oils of lemon and lime species. J Agric Food Chem 2002;50(4):796-805 View Article PubMed/NCBI
  85. Rehman MU, Tahir M, Khan AQ, Khan R, Oday-O-Hamiza, Lateef A, et al. D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats. Exp Biol Med (Maywood) 2014;239(4):465-476 View Article PubMed/NCBI
  86. Isermann M, Rooney P. Biological Flora of the British Isles: Eryngium maritimum. J Ecol 2014;102(3):789-821 View Article PubMed/NCBI
  87. Erdem SA, Nabavi SF, Orhan IE, Daglia M, Izadi M, Nabavi SM. Blessings in disguise: a review of phytochemical composition and antimicrobial activity of plants belonging to the genus Eryngium. Daru 2015;23:53 View Article PubMed/NCBI
  88. Matboli M, Eissa S, Ibrahim D, Hegazy MGA, Imam SS, Habib EK. Caffeic Acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin- induced diabetic rat. Sci Rep 2017;7(1):2263 View Article PubMed/NCBI
  89. Nabavi SM, Habtemariam S, Nabavi SF, Sureda A, Daglia M, Moghaddam AH, et al. Protective effect of gallic acid isolated from Peltiphyllum peltatum against sodium fluoride-induced oxidative stress in rat’s kidney. Mol Cell Biochem 2013;372(1-2):233-239 View Article PubMed/NCBI
  90. Adefegha SA, Omojokun OS, Oboh G. Modulatory effect of protocatechuic acid on cadmium induced nephrotoxicity and hepatoxicity in rats in vivo. Springerplus 2015;4:619 View Article PubMed/NCBI
  91. Vijayaprakash S, Langeswaran K, Kumar SG, Revathy R, Balasubramanian MP. Nephro-protective significance of kaempferol on mercuric chloride induced toxicity in Wistar albino rats. Biomed Aging Pathol 2013;3:119-124 View Article PubMed/NCBI
  92. Sugimoto K, Nakagawa K, Hayashi S, Amakura Y, Yoshimura M, Yoshida T, et al. Hydrolyzable tannins as antioxidants in the leaf extract of Eucalyptus globulus possessing tyrosinase and hyaluronidase inhibitory activities. Food Sci Technol Res 2009;15:331-336 View Article PubMed/NCBI
  93. Santos Ferreira C, Pereyra A, Patriarca A, Mazzobre MF, Polak T, Abram V, et al. Phenolic compounds in extracts from Eucalyptus globulus leaves and Calendula officinalis flowers. J Nat Res Prod 2016;2(1):53-57 View Article PubMed/NCBI
  94. Ayhanci A, Cengiz M, Mehtap Kutlu H, Vejselova D. Protective effects of ellagic acid in D-galactosamine-induced kidney damage in rats. Cytotechnology 2016;68(5):1763-1770 View Article PubMed/NCBI
  95. Wong CC, Botting NP, Orfila C, Al-Maharik N, Williamson G. Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6). Biochem Pharmacol 2011;81(7):942-949 View Article PubMed/NCBI
  96. Domitrović R, Cvijanović O, Šušnić V, Katalinić N. Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury. Toxicology 2014;324:98-107 View Article PubMed/NCBI
  97. Frederick C. Guide illustré de la flore Zingaro, Palerme. L’Epos Publishing Company; 1999, 100 View Article PubMed/NCBI
  98. Di Stefano V, Pitonzo R, Schillaci D. Chemica constituents and anti-proliferative activity of Euphorbia bivonae. Chem Nat Comp 2011;47(4):630-663 View Article PubMed/NCBI
  99. Athmouni K, El Feki A, Ayadi H. Hepatotoxic effects of Euphol-rich fractions from Euphorbia bivonae-Relevance to cytotoxic and anti-tumor activities. Pathophysiology 2019;26(1):69-76 View Article PubMed/NCBI
  100. Jrah Harzallah H, Neffati A, Skandrani I, Maaloul E, Chekir Ghedira L, Mahjoub T. Antioxidant and antigenotoxic activities of Globularia alypum leaves extracts. J Med P Res 2010;4(19):2048-2053 View Article PubMed/NCBI
  101. Le Floch E. Boulos Loufty. —Medicinal Plants of North Africa Reference Publication, Inc. 218 St. Clair River Drive, Box 344. Algonac, Michigan 48001, 1983. Journ d’Agric Trad et de Bota Appl 1984;XXXI:127 View Article PubMed/NCBI
  102. Feriani A, Del Mar Contreras M, Talhaoui N, Gómez-Caravaca AM, Taamalli A, Segura-Carretero A, et al. Protective effect of Globularia alypum leaves against deltamethrin induced nephrotoxicity in rats and determination of its bioactive compounds using high-performance liquid chromatography coupled with electrospray ionization tandem quadrupole–time-of-flight mass spectrometry. J Funct Food 2017;32:139-148 View Article PubMed/NCBI
  103. Merghache S, Zerriouh M, Merghache D, Tabti B, Djaziri R, Ghalem S. Evaluation of hypoglycaemic and hypolipidemic activities of Globularin isolated from Globularia alypum L. in normal and streptozotocin-induced diabetic rats. J Appl Pharmaceut Sci 2013;3(4):1-7 View Article PubMed/NCBI
  104. Bourogaa E, Nciri R, Mezghani-Jarraya R, Racaud-Sultan C, Damak M, El Feki A. Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats. J Physiol Biochem 2013;69(2):227-237 View Article PubMed/NCBI
  105. Ben Salah H, Jarraya R, Martin MT, Veitch NC, Grayer RJ, Simmonds MS, et al. Flavonol triglycosides from the leaves of Hammada scoparia (POMEL) ILJIN. Chem Pharm Bull (Tokyo) 2002;50(9):1268-1270 View Article PubMed/NCBI
  106. Qiu S, Sun G, Zhang Y, Li X, Wang R. Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model. Biomed Rep 2016;4(5):628-634 View Article PubMed/NCBI
  107. Clayton WD. A revision of the genus Hyparrhenia. Kew Bulletin, Addit. Ser. 2. London: HMSO 1969;2:1-96 View Article PubMed/NCBI
  108. Boukef MK. Medecine traditionnelle et pharmacopee: Les Plantes dans la médecine traditionnelle tunisienne. Paris: Agence De Cooperation Culturelle Et Technique; 1986, 350 View Article PubMed/NCBI
  109. Bouaziz-Ketata H, Ben Salah G, Ben Salah H, Marrekchi R, Jamoussi K, Boudawara T, et al. Nitrate-induced biochemical and histopathological changes in the liver of rats: Ameliorative effect of Hyparrhenia hirta. Biomed Environ Sci 2014;27(9):695-706 View Article PubMed/NCBI
  110. Hassan SM, Khalaf MM, Sadek SA, Abo-Youssef AM. Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Pharm Biol 2017;55(1):766-774 View Article PubMed/NCBI
  111. Chaudhary S, Ganjoo P, Raiusddin S, Parvez S. Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. Protoplasma 2015;252(1):209-217 View Article PubMed/NCBI
  112. Benabdelkader T, Zitouni A, Guitton Y, Jullien F, Maitre D, Casabianca H, et al. Essential oils from wild populations of Algerian Lavandula stoechas L.: composition, chemical variability, and in vitro biological properties. Chem Biodivers 2011;8(5):937-953 View Article PubMed/NCBI
  113. Sebai H, Selmi S, Rtibi K, Souli A, Gharbi N, Sakly M. Lavender (Lavandula stoechas L.) essential oils attenuate hyperglycemia and protect against oxidative stress in alloxan-induced diabetic rats. Lipids Health Dis 2013;12:189 View Article PubMed/NCBI
  114. Kogiannou DA, Kalogeropoulos N, Kefalas P, Polissiou MG, Kaliora AC. Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells. Food Chem Toxicol 2013;61:152-159 View Article PubMed/NCBI
  115. Polunin O, Smythies BE. Flowers of south-west Europe a field guide. Oxford: Oxford University Press; 1973, 544 View Article PubMed/NCBI
  116. Said O, Khalil K, Fulder S, Azaizeh H. Ethnopharmacological survey of medicinal herbs in Israel, the Gollan Heights and the West Bank region. J Ethnopharmacol 2002;83(3):251-265 View Article PubMed/NCBI
  117. Ozen S, Akyol O, Iraz M, Söğüt S, Ozuğurlu F, Ozyurt H, et al. Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats. J Appl Toxicol 2004;24(1):27-35 View Article PubMed/NCBI
  118. Akomolafe SF, Akinyemi AJ, Anadozie SO. Phenolic acids (gallic and tannic acids) modulate antioxidant status and cisplatin induced nephrotoxicity in rats. Int Sch Res Notices 2014;2014:984709 View Article PubMed/NCBI
  119. Ekinci Akdemir FN, Albayrak M, Çalik M, Bayir Y, Gülçin İ. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines 2017;5(2):E18 View Article PubMed/NCBI
  120. Leporatti ML, Ghedira K. Comparative analysis of medicinal plants used in traditional medicine in Italy and Tunisia. J Ethnobiol Ethnomed 2009;5:31 View Article PubMed/NCBI
  121. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999;12(4):564-582 View Article PubMed/NCBI
  122. Singh R, Bagachi A, Semwal A, Kaur S, Bharadwaj A. Traditional uses, phytochemistry and pharmacology of Morus alba Linn.: A review. J Med Plant Res 2013;7(9):461-469 View Article PubMed/NCBI
  123. Yang Y, Gong T, Liu C, Chen RY. Four new 2-arylbenzofuran derivatives from leaves of Morus alba L. Chem Pharm Bull (Tokyo) 2010;58(2):257-260 View Article PubMed/NCBI
  124. Iida A, Usui T, Zar Kalai F, Han J, Isoda H, Nagumo Y. Protective effects of Nitraria retusa extract and its constituent isorhamnetin against amyloid β-induced cytotoxicity and amyloid β aggregation. Biosci Biotechnol Biochem 2015;79(9):1548-1551 View Article PubMed/NCBI
  125. Shaltout KH, Sheded MG, El-Kady HF, Al-Sodany YM. Phytosociology and size structure of Nitraria retusa along the Egyptian Red Sea coast. J Arid Environ 2003;53:331-345 View Article PubMed/NCBI
  126. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013;368(14):1279-1290 View Article PubMed/NCBI
  127. Alimi H, Hfaiedh N, Bouoni Z, Hfaiedh M, Sakly M, Zourgui L, et al. Antioxidant and antiulcerogenic activities of Opuntia ficus indica f. inermis root extract in rats. Phytomedicine 2010;17(14):1120-1126 View Article PubMed/NCBI
  128. Sardana A, Kalra S, Khanna D, Balakumar P. Nephroprotective effect of catechin on gentamicin-induced experimental nephrotoxicity. Clin Exp Nephrol 2015;19(2):178-184 View Article PubMed/NCBI
  129. Ghrabi Z. A guide to medicinal plants in North Africa. Gland: IUCN Centre for Mediterranean Cooperation; 2005 View Article PubMed/NCBI
  130. Abu-Reidah IM, Gil-Izquierdo Á, Medina S, Ferreres F. Phenolic composition profiling of different edible parts and by-products of date palm (Phoenix dactylifera L.) by using HPLC-DAD-ESI/MSn. Food Res Int 2017;100(Pt 3):494-500 View Article PubMed/NCBI
  131. Barh D, Mazumdar BC. Comparative nutritive values of palm saps before and after their partial fermentation and effective use of wild date (Phoenix sylvestris Roxb.) sap in treatment of anemia. Res J Med Med Sci 2008;3(2):173-176 View Article PubMed/NCBI
  132. Bunel V, Antoine MH, Nortier J, Duez P, Stévigny C. Nephroprotective effects of ferulic acid, Z-ligustilide and E-ligustilide isolated from Angelica sinensis against cisplatin toxicity in vitro. Toxicol In Vitro 2015;29(3):458-467 View Article PubMed/NCBI
  133. Uncini Manganelli RE, Camangi F, Tomei PE. Curing animals with plants: traditional usage in Tuscany (Italy). J Ethnopharmacol 2001;78(2-3):171-191 View Article PubMed/NCBI
  134. Hamrouni L, Hanana M, Amri I, Romane AE, Gargouri S, Jamoussi B. Allelopathic effects of essential oils of Pinus halepensis Miller: chemical composition and study of their antifungal and herbicidal activities. Arch Phytopathol Plant Protect 2015;48:145-158 View Article PubMed/NCBI
  135. Mahjoub MA, Ammar S, Mighri Z. A new biflavonoid and an isobiflavonoid from Rhus tripartitum. Nat Prod Res 2005;19(8):723-729 View Article PubMed/NCBI
  136. Lee S, Jung K, Lee D, Lee SR, Lee KR, Kang KS, et al. Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity. Bioorg Med Chem Lett 2015;25(23):5613-5618 View Article PubMed/NCBI
  137. De Oliveira JR, Camargo SEA, De Oliveir LD. Rosmarinus officinalis L. (rosemary) as therapeutic and prophylactic agent. J Biomed Sci 2019;26:1-22 View Article PubMed/NCBI
  138. Bahri S, Ben Ali R, Gasmi K, Mlika M, Fazaa S, Ksouri R, et al. Prophylactic and curative effect of rosemary leaves extract in a bleomycin model of pulmonary fibrosis. Pharm Biol 2017;55(1):462-471 View Article PubMed/NCBI
  139. Sahu BD, Rentam KK, Putcha UK, Kuncha M, Vegi GM, Sistla R. Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity. Food Chem Toxicol 2011;49(12):3090-3097 View Article PubMed/NCBI
  140. Domitrović R, Potočnjak I, Crnčević-Orlić Z, Škoda M. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food Chem Toxicol 2014;66:321-328 View Article PubMed/NCBI
  141. Kozłowska M, Laudy AE, Przybył J, Ziarno M, Majewska E. Chemical composition and antibacterial activity of some medicinal plants from Lamiaceae family. Acta Pol Pharm 2015;72(4):757-767 View Article PubMed/NCBI
  142. Alinezhad H, Baharfar R, Zare M, Azimi R, Nabavi SF, Nabavi SM. Biochemical activities of acetone extracts of Hyssopus angustifolius. Acta Pol Pharm 2012;69(4):617-622 View Article PubMed/NCBI
  143. Horváth B, Mukhopadhyay P, Kechrid M, Patel V, Tanchian G, Wink DA, et al. β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radic Biol Med 2012;52(8):1325-1333 View Article PubMed/NCBI
  144. Ahmadvand H, Tavafi M, Asadollahi V, Jafaripour L, Hadipour-Moradi F, Mohammadrezaei-Khoramabadi R, et al. Protective effect of carvacrol on renal functional and histopathological changes in gentamicin-induced-nephrotoxicity in rats. Zahedan Res Med Sci 2016;18(4):e6446 View Article PubMed/NCBI
  145. Goulas V, Gomez-Caravaca AM, Exarchou V, Gerothanassis I. P, Segura-Carretero A, Gutiérrez AF. Exploring the antioxidant potential of Teucrium polium extracts by HPLC–SPE–NMR and on-line radical-scavenging activity detection. LWT - Food Sci Technol 2012;46(1):104-109 View Article PubMed/NCBI
  146. Petropoulos GA. Fenugreek-the genus Trigonella. 1st ed. London: CRC Press; 2002, 120-127 View Article PubMed/NCBI
  147. Basu A, Basu SK, Ashwani K, Sharma M, Chalghoumi R, Hedi A, et al. Fenugreek (Trigonella foenum-graecum L.), a potential new crop for Latin America. Am J Soc Issues Humanit 2014;4:145-162 View Article PubMed/NCBI
  148. Belguith-Hadriche O, Bouaziz M, Jamoussi K, El Feki A, Makni-Ayedi F. Renoprotective effects of fenugreek seeds against oxidative stress in hypercholesterolemic fed rats. Herald J Agric Food Sci Res 2014;3(1):7-13 View Article PubMed/NCBI
  149. Keskes H, Belhadj S, Jlail L, El Feki A, Sayadi S, Allouche N. LC-MS-MS and GC-MS analyses of biologically active extracts of Tunisian Fenugreek (Trigonella foenum-graecum L.) Seeds. J Food Meas Charact 2018;12(1):209-220 View Article PubMed/NCBI
  150. Nassiri-Asl M, Hosseinzadeh H. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds. Phytother Res 2009;23(9):1197-1204 View Article PubMed/NCBI
  151. Valli Kanagarla NSSA, Kuppast IJ, Veerashekar T, Laxman Reddy C. A review on benefits and uses of Vitis vinifera (Grape). Res Rev BioSci 2013;7(5):175-180 View Article PubMed/NCBI
  152. Zabad IEM, Amin MN, El-Shishtawy MM. Protective effect of vanillin on diabetic nephropathy by decreasing advanced glycation end products in rats. Life Sci 2019;239:117088 View Article PubMed/NCBI
  153. Asif M. A review on various medicinal plants with for nephroptotective activity. Int J Recent Adv Biotech Nanotech 2017;1(1):1-29 View Article PubMed/NCBI

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