Role of Herbal Drugs in Nephrotoxicity and Neurological Disorder: Connecting a Bridge between Kidney and Brain
Deepika Dutta*, S.L Harikumar, Amarjot Kaur Grewal.
Rayat and Bahra Institute of Pharmacy, Sahauran, Mohali, Punjab.
*Corresponding Author E-mail: tanu.dutta3@gmail.com.
ABSTRACT:
Nephrotoxicity is a poisonous effect of some substances both chemical and medication on kidneys. It is the ninth leading cause of death in United States. Dementia is the loss of memory and cognitive improvement. It is estimated that nearly 13-16 million people will suffer from dementia by 2050. The nature provides a new opportunity to regain all the losses caused by medication or by ageing. Cognitive impairment and chronic kidney disease are becoming increasingly prevalent in the aging US population. A number of herbs traditionally employed in various disease conditions have yielded positive responses. Kidney and brain are the vital organs of the body. Moderate renal impairment, reflected by a higher Serum Creatinine, is associated with an excess risk of incident dementia among individuals in good excellent health. Various herbal drugs such as curcumin, asthwagandha and garlic etc. have been evaluated in both nephrotoxicity and dementia. Various studies revealed that kidney disease exacerbate various cognitive impairments, so the drugs which are beneficial in the kidney disorder can treat various kinds of neuronal disorders. Oxidative stress and inflammation act as the key mediators in kidney and brain disorders, so the drugs with antioxidant potential can be used as a potent target. In this review we will summarize the role of herbs in nephrotoxicity and dementia connecting the link between kidney and brain.
KEYWORDS: Dementia, Nephrotoxicity and Herbs.
INTRODUCTION:
Kidneys are organs that have various vital roles in the body. Their primary role is to maintain the homeostatic balance and excreting the nitrogenous waste in the form of urine. Nephrotoxicity is an inherent adverse effect of certain antibiotics, anticancer drugs and other synthetic molecules. Studies have examined the risks for dementia and cognitive impairment among people with chronic kidney disease. An elevated serum creatinine concentration was associated with a 37% increased risk for incident dementia1. Chronic kidney disease is associated with a number of other factors that have been proposed as mediators of cognitive impairment, including anemia, increased levels of inflammatory cytokines, oxidative stress, and alterations in lipid and homocysteine metabolism2, 3. Recent studies of end-stage renal disease patients treated with dialysis have found exceedingly high rates of clinical dementia and cognitive dysfunction compared with the general population. Neurological and nephrological sign persist when there is imbalance in the oxidative defense mechanism.
Plants with antioxidant activity are more effective in decreasing the oxidative stress in kidneys as well as brain. Treatment of patients with antioxidant or anti-inflammatory drugs can prevent the prevalence of the diseases. Recently, impaired kidney function was reported to be associated with dementia and cognitive impairment4,5. Dementia and cognitive decline impair the quality of life and are associated with a profound disease burden, morbidity, and mortality, not only in patients but also in caregivers. Impaired kidney function is associated with a more rapidly decline in cognitive, especially in semantic memory, episodic memory, and working memory. The relationship between both the diseases can open new stage to treat both the diseases with same medication.
Role of herbs in nephrotoxicity and dementia:
1. Curcuma longa:
Curcuma longa in nephrotoxicity:
Generation of free radicals in the renal cortex plays an important role in the pathogenesis of gentamicin-induced nephrotoxicity. Curcumin, which is isolated from turmeric, has been confirmed to have a strong antioxidant and free radical scavenging actions. Curcumin suppressed renal toxicity by blocking oxidative injury and restore the antioxidant enzymatic profile 6. In other studies Curcumin had a protective effect against the development of adriamycin renal injury. It suppressed renal toxicity by blocking oxidative injury in the kidney because it prevented adriamycin -induced rise in lipid peroxides. Curcumin treatment also increased the glutathione content and glutathione peroxidase activity of kidney tissues in adriamycin rats.
Curcuma longa in dementia:
While in brain curcumin modulates the inflammatory response by down-regulating the activity of cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase (iNOS) enzymes; inhibits the production of the inflammatory cytokines tumor necrosis factor-alpha (TNF-a), interleukin (IL) -1, -2, -6, -8, and -127,8. Curcuminoids as a mixture is pharmacologically different form of purified curcumin. Curcuminoids mixture is known to inhibit lipid peroxidation in rat brain homogenates, scavenge nitric oxide radicals, protect cells from Aβ(1–42) insults, inhibit Aβ induced inflammatory cytokines expression, enhance memory and inhibit in-vitro beta amyloid fibril formation in addition to its strong AChE inhibitory activity.
2. Ashwagandha (Withania somnifera):
Ashwagandha (Withania somnifera) in Nephrotoxicity:
Withania somnifera root extract in the regulation of lead toxicity with has been investigated in liver and kidney tissues. It significantly decreased Lipid peroxide levels and increased the activities of antioxidant enzymes, viz., superoxide dismutase (SOD) and catalase (CAT), thus retaining normal peroxidative status of the tissues9.
Ashwagandha (Withania somnifera) in dementia:
Its role in brain was also examined; oral administration of a semipurified extract of the root of Withania somnifera consisting of active constituents such as withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer’s disease transgenic mice10.
3. Coriandrum sativum:
Coriander sativum in nephrotoxicity:
Coriandrum sativum Linn. (Umbelliferae, C. sativum) is cultivated throughout the world for its use as spice and as a folk medicine. Aqueous and ethanolic extracts of Coriandrum sativum can prevent or slow down the oxidative damage induced by lead in mice. The effect of lead on LPO level, GSH concentration, antioxidant enzyme activity and some biochemical variables were reversed by treatment with plant extracts. Lead intoxication yields to a partial failure in the ion pump transport of tubules cells which in turn produces tubular swelling and causes necrosis and vacuolization of the tubules. Kidney of mice ingested to lead plus Coriandrum sativum extracts shows the tubules appear more or less normal. Thus coriander extract produced protective effects in renal tissue against lead toxicity11.
Coriander sativum in dementia:
The results from various studies showed that administration of C. sativum aqueous extract improved memory deficits induced by scopolamine injection and exhibited higher inhibition of lipid peroxidation when compared with ascorbic acid in both rat liver and brain homogenates. Stress and free radicals have been implicated in loss of memory and cognitive deficits. The mechanism by which C. sativum extract acts in attenuating the memory deficits induced by scopolamine could be due to its free radical scavenging activity12.
4. Bacopa monnieri:
Bacopa monnieri in nephrotoxicity:
Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. Gentamicin induced nephrotoxicity is characterized by increased levels of urea, creatinine and decreased levels of albumin and uric acid, the oxidative stress markers such as SOD, GR, GST, CAT, TBARS, GSH in renal tissues were found to be altered. The nephroprotective effect of Bacopa monnieri is by enhancing antioxidant activity with natural antioxidants and scavenging the free radicals13. Effect of Bacopa monniera on liver and kidney toxicity in chronic use of opioids was evaluated Pretreatment with extract has shown to possess a significant protective effect against morphine-induced liver and kidney functions they decrease serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenases and gamma-glutamyl transferase activities and urea, creatinine and uric acid level significantly.
5. Hemidescus indicus:
Hemidescus indicus in nephrotoxicity:
The treatment with H. indicus helped in the management of renal impairment, which was induced by gentamicin in rats. This is evident from the results obtained for various kidney function tests for gentamicin, along with the results from the plant treated group, and is in comparison with the results found for the gentamicin recovery group. The plant shows promise as an adjunct therapy alongside aminoglycosides as it reduces nephrotoxicity caused by aminoglycosides15.
Hemidescus indicus in dementia:
Ayurveda emphasizes use of herbs, nutraceuticals or lifestyle changes for controlling age related neurodegenerative disorders. Dementia is one of the age-related mental problems, and a characteristic symptom of Alzheimer’s disease. Ethanolic extract Hemidescus indicus of was found to be significant in conditioned avoidance response as well as radial arm maze task performance. It is reported to possess antioxidant activity, which might protect the susceptible brain cells from oxidative stress resulting in reduced brain damage and improved neuronal function16.
6. Andrographis paniculata:
Andrographis paniculata in nephrotoxicity:
Andrographis paniculata is the plant used in Ayurveda for several remedies. The plant is claimed to possess immunological, antibacterial, anti-inflammatory, antithrombotic, and hepatoprotective properties. Andrographolide, one of the major chemical constituents of the plant A. paniculata, has been reported to possess antioxidant activity Aqueous extract of A. paniculata was able to produce considerable alleviation from the nephrotoxic action of gentamicin and hence exhibits marked renoprotective activity and can be deemed to be a good bioagent for the treatment of acute renal injury induced by nephrotoxins17.
Andrographis paniculata in dementia:
Andrographolide exhibited neuroprotective effects, with accompanying suppression of nuclearfactor kappa B (NF-κB) and microglial activation, reduction in the production of cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-1 and pro- inflammatory factors such as prostaglandinE2 (PGE2)18.
7. Silymarin:
Silymarin in nephrotoxicity:
Nephrotoxicity is a major and dose- limiting side effect of cisplatin, with an incidence reported as 6-13%. Nephrotoxicity is a major and dose- limiting side effect of cisplatin, with an incidence reported as 6-13% (1). Renal side effects of cisplatin include distal renal tubular acidosis, hypomagnesaemia, hypocalcaemia, hyperuricemia, erythropoietin deficiency, thrombotic microangiopathy and chronic renal failure. Cisplatin caused a decrease in creatinine clearance and an increase in proteinuria, urinary activity of the proximal tubular enzymes and fractional excretion of magnesium. Pre-treatment of rats with silymarin completely prevented the decline in creatinine clearance and proteinuria and partially ameliorated proximal tubular impairment such as enzymuria and magnesuria19.
Silymarin in dementia:
Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti-inflammatory, cytoprotective and anticarcinogenic effects. Inflammatory mediators activate inflammation in the neurons and hence leading to neuroinflammation and further generation of dementia. Silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-α and nitric oxide (NO), and reduced the damage to dopaminergic neurons20.
8. Portulaca Oleracea:
Portulaca Oleracea in nephrotoxicity:
Gentamicin elicited deleterious nephrotoxic effects by causing severe damage to renal mitochondria by suppressing antioxidant defense mechanism, Co-administration of aqueous Portulaca Oleracea extract and fish oil was found to improve the adverse changes in the kidney functions with an increase in antioxidants activities and reduction of peroxidation. aqueous Portulaca Oleracea extract supplementation may provide a cushion for a prolonged therapeutic option against GM nephropathy without harmful side effects21.
Portulaca Oleracea in dementia:
Betacyanins from Portulaca oleracea markedly reversed the D-gal-induced learning and memory impairments, as measured by behavioral tests. The activities of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in D-gal-treated mice were enhanced while the content of the lipid peroxidation product malondialdehyde (MDA) was decreased by betacyanin administration. These results suggest that the neuroprotective effect of betacyanins against D-gal-induced neurotoxicity might be caused, at least in part, by an increase in the activities of antioxidant enzymes with a reduction in lipid peroxidation22.
9. Spirulina:
Spirulina in nephrotoxicity:
Spirulina is rich in protein, free amino acids, sugars, fatty acids, vitamins and trace elements, is an important economic value of healthy food.Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of reactive oxygen metabolites and lipid peroxidation in kidney, caused by the decreased levels of antioxidants and antioxidant enzymes. Pretreatment with Spirulina protected the rats from Cisplatin-induced nephrotoxicity. The rise in plasma urea, creatinine, urinary beta-NAG, plasma and kidney tissue MDA and histomorphological changes were significantly attenuated by Spirulina23.
Spirulina in dementia:
Spirulina in mice with D-galactose induced aging has improved learning and memory function24. It also decreased levels of antioxidants and antioxidant enzymes.
10. Garlic ( Allium sativum ):
Garlic ( Allium sativum ) in nephrotoxicity:
Garlic ( Allium sativum ) is a biennial herb of the family Liliaceae .Pharmacological research on garlic has shown the thiosulfinates free radical scavenging and inhibition of lipid peroxidation. The bulb of the plant has been used in many parts of the world as stimulant, carminative, antiseptic, anthelmintic (ascaris and oxyuris), expectorant and diuretic, diaphoretic, antiasthmatic, whooping cough, tuberculosis, bronchoectasis and gangrene. The ameliorative effects of vitamin C and garlic (Allium sativum) on nephrotoxicity and biochemical alterations induced in lead-exposed rats were investigated. Garlic and vitamin C significantly ameliorated elevations in the plasma levels of lead, uric acid, creatinine25.
Garlic in dementia:
The high fructose diet may contribute to spatial memory deficits. Iranian shallot or garlic extracts appear to improve learning and memory impairments in fructose-fed rats. Studies revealed that only one dosage level, high doses and longer duration may be needed to assess the long-term benefit of Iranian shallot and garlic extracts on memory impairment and lipid metabolism in high fructose feeding animals26.
CONCLUSION:
Renal impairment is associated with an increased risk of stroke and cognitive dysfunction and dementia. Kidney disease is associated with oxidative stress and increased number of inflammatory mediators while elevated levels of inflammatory cytokines have been demonstrated in neuropathology specimens from patients with dementia. .Serum lipid levels have also been linked with cognitive impairment. The relatively recent introduction of renal diseases has led to a shift in emphasis in the type of neurological problem. A cerebro-renal connection exists clinically. Chronic kidney disease markers may be helpful to evaluate the future risk of neuronal disease. Protection of the damaged organ will shift to protection of multiple hidden damaged organs. Brain-kidney connection may contribute to prevention of impaired quality of life from multiple organ dysfunctions. The use of herbal supplements in the US has increased dramatically in recent years. . Role of various herbs with antioxidant activity and anti-inflammatory activity was evaluated in both the disease conditions. Plants have not only been the source of drug molecules but as well as the source of feedstock molecules that can be transformed in drugs. A number of extracts of natural products and dietary antioxidants have been reported to show protective effects against nephrotoxicity and neurological disorders. In this review we have summarized the role of herbal drugs in nephrotoxicity and neuronal disorders connecting a bridge between kidney and brain associated disorders.
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Received on 22.07.2013 Modified on 29.07.2013
Accepted on 02.08.2013 © RJPT All right reserved
Research J. Pharm. and Tech. 6(10): October 2013; Page 1165-1168