Biosci. Biotech. Res. Comm. 8(2):
An update on the role of medicinal plants in amelioration of aluminium toxicity
Gajendra Mahor and Sharique A Ali*
Rajeev Gandhi National Fellow UGC New Delhi
Department of Biotechnology, Sai•a Science College, Bhopal- 462001, India
Aluminium (Al) is the third most common element as well as the natural component (8%) of
KEY WORDS: ALUMINIUM, ALZHEIMER’S, PARKINSON’S DISEASE, HEAVY METALS, MEDICINAL PLANTS, PHYSIOLOGICAL PARAMETERS.
Heavy Metals like copper, silver, zinc, cadmium, gold, mercury, lead, chromium, iron, nickel, tin, arsenic, sele- nium, molybdenum, cobalt, manganese, and aluminium are natural components of Earth’s crust, which cannot
*Corresponding Author: firstname.lastname@example.org Received 20th July, 2015
Accepted after revision 30th November, 2015 BBRC Print ISSN:
©A Society of Science and Nature Publication, 2015. All rights reserved.
Online Contents Available at: http//www.bbrc.in/
be degraded, therefore plants and animals have been exposed by them since the beginning of life on earth. Heavy metals are among the contaminants in the envi- ronment which are mainly librated by various human activities and have potential contribution to produce heavy metal toxicity. The history of heavy metal poison-
Gajendra Mahor and Sharique A. Ali
ing has been reviewed many times in the books, research papers and reviews, whom all are stated that residual metals in the environment is a serious threat to animal, human health and aquatic ecosystem, (Ganrot et al., 1986; Cha et al., 1987; Baker et al., 1991; Jarup et al., 2003; Krewski et al., 2007; Yokel et al., 2008; Ezejiofor, et al., 2013; Miraj et al., 2014; Benouadah et al., 2015).
In all the heavy metals aluminium is most commonly used metal, abundantly distributed in our environ- ment and is most toxic to the various animals including humans. It was !rst produced experimentally in 1825 by the Danish chemist Hans Christian Oersted and later the German, French, and Austrian chemists Friedrich Woh- ler, Henri Sainte Claire Deville, and Carl Joseph Bayer upgraded isolation ef!ciencies and puri!cation tech- nologies. Due to its reactivity, aluminium is found only in combination with other elements like oxygen, silicon or "uorine that are commonly found in soil, minerals and rocks. (Lukiw et al., 2001; Verstraeten et al., 2008; Proudfoot et al., 2009; Kawahara et al., 2010, Negishi 2011; Hussein et al., 2013; Jefferson et al., 2014; Exley et al., 2015).
Human beings and animals they are naturally exposed to relatively large amounts of aluminium from food, water and air. Other Source of expose to aluminium in salt, deodorants, antacids, cookware, baking powder, processed cheeses, (Guilbert et al., 1986; Kosier et al., 1990; Yokel et al., 2001; Solfrizzi et al., 2003; Frank et al., 2009; Tchounwou et al., 2011; Darbre et al., 2013; Najar et al., 2014; Laghlimi et al., 2015).
Recently, however, aluminum toxicity has increased precipitously. Today, nearly 80% of those tested for metal toxicity reveal excessively high hair aluminium levels. It is linked with a number of disorders in man including Alzheimer’s disease, Parkinson’s, dementia and osteomalacia, neurological degenerative, muscu- lar dystrophy, multiple sclerosis and cancer, (Pignatti and Mariani, 2002; Kawahara et al., 2005; Verstraeten et al., 2008; Kumar and Gill, 2009; Turner et al., 2014; McGreevy et al., 2015).
Aluminium level in drinking water varies due to presence of aluminium coagulants 100 μg/L or greater, (Wettstein et al., 1991). Higher doses of aluminium con- sumed exceeds the body’s capacity to excrete it, the excess is then deposited in various tissues, including nerves, brain, muscle, bone, heart, liver, kidneys, spleen, testis, (Harrington et al., 1994; Stacchiotti et al., 2006).
It is completely useless or toxic for the human and other living organism or essential micronutrients but toxic when overdosed aluminium toxicity has been reported to impair the formation and release of par- athyroid hormone. The parathyroid glands concentrate aluminium above levels in surrounding tissues. Treat- ment of aluminium toxicity in renal failure patients
often reactivates hyperparathyroidism, which to a cer- tain extent is helpful for bone remodelling and healing, (Arieff et al., 1979, 1980; Leehey et al., 1985; Hendrick et al., 1992; Arieff, 1993; Kanwar et al., 1996; Pande 2006; Flora et al., 2008 Rebecca et al., 2014; Hegazy et al., 2015).
These metals have been found to be lethally hazard- ous to both animals and human above certain levels. it’s have been inevitably exposed to metals due to their ubiquity in nature, contaminated air, water, soil and food, wide use in industry and
The pollution of the aquatic environment with metals has become a serious health concern because of their toxicity and accumulation by organisms, (Mendil et al., 2010; Shah et al., 2010). The greatest concern for alu- minium toxicity in North America occurs in areas that are affected by wet and dry acid deposition, such as eastern Canada and the
In solution, the metal can combine with several dif- ferent agents to affect toxicity. aluminium is extremely common throughout the world and is innocuous under circumneutral or alkaline conditions. However, in acidic environments, it can be a major limiting factor to direct (toxic) and indirect (e.g. food chain) effects on wildlife vertebrates like !sh, amphibians, reptiles, birds and mam- mals, (Lewin et al., 1920; Sparling & Lowe., 1996; Anane and Creppy, 2001; Damien et al., 2004; Newairy et al., 2009; Akhigbe et al., 2011; Gibbons 2015).
The toxicity of aluminium has been studied exten- sively in !sh, less so in invertebrates, amphibians, and birds, and not at all in reptiles and
et al., 2011; Maharajan & Parurukmani 2012; Slaninova et al., 2014; Abadi et al., 2015).
Aluminium sulphate is used as a mordant in dyeing, in the leather industry, paper industry,
In amphibians, embryos and young larvae are typi- cally more sensitive than older larvae.
Elevation in the liver enzymes (AST, ALT and ALP) was noticed in aluminium toxicity due to liver dys- function and disturbance in the biosynthesis of these enzymes which all are indicative of liver damage and thus impaired liver function, (Ajith et al., 2007). Transaminases are intracellular enzymes and the most sensitive biomarkers, released into the circulation after damage and necrosis of hepatocytes like AST and ALT can be used in the assessment of liver function. Alumin- ium caused a signi!cant elevation in the activity of ALP.
Increase in the activity of ALP can attributed to severe damage to cell membranes or increased permea- bility of plasma membrane. However, they reported that the increase in the activity of ALP in blood might be due to the necrosis of liver, kidney and lung. The aluminium treated group, (Klein et al., 1989; Chinoy et al., 2001;
Gajendra Mahor and Sharique A. Ali
Demerdash et al., 2004; Saied et al., 2014; Kalaiselvi et al., 2015).
Aluminium causes toxic effect on biochemical param- eters i.e. Plasma glucose, Urea, Creatinine, Cholesterol, Trigycerides, Total Protein showed an increasing trend because prolonged metallic stress in the experimental animals makes adaptation dif!cult and creates weak- ness, anemia. These parameters have been effectively used as potential biomarkers of aluminium toxicity to animals and human in the !eld of environmental bio- monitoring. The other toxic effects of these contami- nants are also known decrease to the antioxidant enzy- matic activity due to presence of ROS and vitamin C that are the indication of lipid peoxidation in certain animal and human beings, (Lagerwerft et al., 1974; Flora et al., 1986; Zaman et al., 1993; Kowalczyk et al., 2004; Vino- dhini and Narayanan, 2008; Newairy et al., 2009; Ashor et al., 2015).
Different doses of aluminium to rats signi!cantly decreased level of red blood cell count and white blood cell count, total haemoglobin due to cause of found ane- mia and results showing that erythrocyte life span and inhibition of haemoglobin synthesis. Microcytic anemia was due to iron de!ciency. High Al levels also leads to microcytic anemia as Fe is unable to reverse the Al asso- ciated anemia, it was deduced that Al interferes with the metabolism of Fe, (Kaiser et al., 1984).
High concentration of Al decreases the average osmotic fragility of red cells in animals with renal fail- ure, (Drueke et al., 1986b). In High Al levels in plasma and red cells also leads to severe anemia but it can be reversed by terminating the Al concentration, (Cannata et al., 1983; Basha et al., 2012; Ibrahim et al., 2012, Mahdy et al., 2012, Hore et al., 2014; Pfadenhauer et al., 2014 Kisnieriene et al., 2015).
Increased lipid peroxidation was reported in the rats consuming diets with AlCl3. Hematological parameters blood used for the determination of erythrocyte count, hemoglobin content and Hct, mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) values were studied according to Feldman et al., (2000). Total and differential leukocytic count Total leukocyte count was performed by using improved neubauer hemocy- tometer. Chronic exposure and inhalation of aluminium "ake powder leads to dilation and hypertrophy of the right side of the heart in male factory workers who eventually died (McLaughlin et al., 1962; Mitchell et al., 1961; Ghorbel et al., 2015).
The cardiac effects may have been secondary to pul- monary !brosis and poor pulmonary function, (Singh RB, et al., (1989). Patients of peripheral circulatory fail- ure induced due to aluminium phosphide poisoning were reported. Chief symptoms were vomiting and epigastric
Gajendra Mahor and Sharique A. Ali
pain. Sensorium was normal in most of the patients. This might be because of direct toxic action of phosphine on myocardium and later when phosphine gets excreted either through lungs or kidney leads to improvement in LV systolic function, (Gupta et al., 1995; Pandey et al., 2013; Elabbassi et al., 2014; Solgi et al., 2015).
Aluminium and Enzyme activities due to its high reactivity, Al3+ is able to interfere with several biologi- cal functions, including enzymatic activities in key met- abolic pathways, (Akeson et al., 1989). Salts of Al may bind to DNA and RNA, inhibit such enzymes as hexoki- nase, acid and alkaline phosphatases, phosphodiesterase and phosphooxydase Al intoxication through the inhi- bition of kinase enzyme has been reported. Hexokinase is a
Aluminium toxicity may result in a drastic reduction or a complete failure of spermatogenesis and steroido- genesis by following ways. First Aluminium may block voltage sensitive calcium channels in hypothalamus cells and decreased the GnRH secretion which further responsible for the decrease in FSH and LH in pituitary as GnRH synthesis and secretion also depends on Ca2+, (Platt et al., 1994; Shahraki et al., 2004). Decreased level of FSH and LH disrupts the process of spermatogenesis and secretion of testosterone by Leydig cells.
Secondly, FSH and LH exert their actions on ster- oidogenesis by mainly regulating intracellular Ca2+ con- centration through
IMPORTANT ROLE OF PLANT EXTRACTS IN DETOXIFICATION OR AMELIORATING THE EFFECTS OF ALUMINIUM TOXICITY
Nevertheless the fact that the phytochemicals contain plenty of "avonoids and polyphenols like antioxidants, they may also help ameliorate the heavy metals medi- ated toxicity in human and other animals.
Coriandrum sativum belongs to the family Umbellif- erae, known for its carminative and cooling properties. Its coriander extracts have phenolic compounds and "a- vonoides, these compounds contribute to the antioxida- tive activity, (Wangensteen et al., 2004). Phenolic sub- stances such as "avonoids, cumarins, cinnamic acid and caffeicacids are believed to have antioxidant properties, which plays an important role against degeneration, (Wiseman et al., 2000).
Coriander seed’s aqueous extract showed protection and an improvement in therapeutic action on pyramidal cell of cerebral cortex against neurodegenerative disor- ders and Alzheimer’ disease induced by aluminium chlo- ride treatment, (Enas et al., 2011). Antioxidant activity of coriander seed aqueous extract, was due to antioxidant enzymes which promoted oxygen to the brain, which could prevent oxidative damage caused by interaction between aluminium cation and unstable oxygen from abnormal mitochondria and protect pyramidal cells in cerebral cortex against damage induced by aluminium chloride overload, (Walton et al., 2007; Lu et al., 2013; Aslani et al., 2014; Benso et al., 2015).
Wattakaka volubilis which belongs to Asclepiadaceae family it is a tall wood climber which is densely densely lenticulate branches, quite bene!cial for amelioration of metal toxicity, (Yogita et al., 2013). occurring through- out the warmer regions of India and Nicobar Islands. W.volubilis (Linn) is used as a phytomedicine compound for liver diseases, (Rani et al., 2014). It has been also demonstrated that W. volubilis methanolic extract of powder form was very effective against the aluminium toxicity in rats, (Bais et al., 2015).
Clinical observation this study showed that enzy- matic analysis and histological, biochemical, organ weight, body weight examination were carried out. The extract of Wattakaka volubilis (Linn) was found to pos- sess hepatoprotective activity in a dose dependent man- ner and the effect was comparable with silymarin, a standard drug.
The extract signi!cantly reduce the toxicity of Alu- minium sulphate caused in liver due to the presence of phytoconstituents such as alkaloids, sterols, tannins, triterpenoids and "avonoids which are also known hepatoprotectant. Wattakaka volubilis leaf extract showed the highest hepatoprotective activity in against Aluminium Sulphate induced hepatotoxicity. The pos- sible action may be due to its hepatoprotective constitu- ents and antioxidant compounds present in the extract, (Rani et al., (2014).
Bacopa monniera (B. monniera), A small creep- ing herb locally known as ‘Brahmi’ in India, belongs to the family of Scrophulariaceae, and is mostly found throughout India, B. monniera have been recommended by ancient Ayurvedic for the treatment of neurological
disorders associated with free radical induced damages, (Stough et al., 2001). it has been demonstrated that in the Journal of Alzheimer’s Disease examines the evi- dence for the
Jasonia candicans & Jasonia montana which belong to Asteraceae are well known detoxi!cation agents. Their extracts have displayed the potent effects against Al toxicity due to their
Polyphenols are abundant in Jasonia montana and are used as antioxidants. Ethanolic extract of Jasonia candicans and Jasonia montana were used in regres- sion of the neurodegeneration characteristics of Alzhe- imer’s disease, (Hussein et al., 2011). High content of terpenes, sesquiterpenes and "avonoids in the ethanolic extract of the selected plants was responsible for the anticholinesterase activity,
Amelioration by Jasonia montana against lipid per- oxidation in liver and kidney of
Garlic (Allium sativum L.) is one of the oldest Indian medicinal plant Garlic its has been valued for centuries
Gajendra Mahor and Sharique A. Ali
for its medicinal properties. Garlic (Allium sativum L.) is one of the earliest known medicinal plant (Metwally et al., 2009) possesses many healthful properties that are related to its bioactive compounds, vitamins and min- erals and trace elements (Selenium and Germanium). a wide range of medicinal properties,immunomodulatory hepatoprotective, antimutagenic and anticarcinogenic effects.
Reviews have shown that garlic can protect us from various pollutants and heavy metals like arsenic and lead Depending on personal requirements or prefer- ences, garlic supplements are available in a wide range of potencies, (Gupta et al., 2015).
The plant extract of Triphala and Garlic per se and in combination were used to treat aluminium poised mice. concurrent use of garlic and Triphala dry powder reduced aluminum concentration indicating the poten- tial activity in combination against alunimium toxic- ity in albino mice, (Cha et al., 1987; Sinha et al., 2011; Eteng et al., 2012; Ranjbar et al., 2013; Ting et al., 2014; Niino et al., 2015).
Turmeric (Curcuma longa) which belongs to Zingib- eraceae family is a rhizomatous herbaceous perennial plant. The active constituents are turmerone oil and water soluble curcuminoids, including curcumin, (Kim et al., 2001; Sandur et al., 2007). Curcumin is the princi- pal curcuminoid and is responsible for the yellow color of the turmeric root, (Shishodia et al., 2005; Yang et al., 2005). Turmeric is
The metabolites of Turmeric such as glucoronides appear to lack any pharmacological activity. The sys- temic elimination of Turmeric is another contributing factor for low bioavailability. Protective effects dem- onstrated (Ghoneim et al., 2002) by curcumin against ischaemia/reperfusion insult in rat forebrain. The initial review reports demonstrated by Wahlstorm and Blennow result showed that after giving the oral administration of 1g/kg curcumin to rats, more than 75% of curcumin was excreted in feces and negligible amount was detected in urine of animal model, (Wahlstrom and Blennow, 1978). Turmeric Showed that Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and !setin in a
Gajendra Mahor and Sharique A. Ali
ease), (Olanow et al., 1999; Zbarsky et al., 2005; Lang et al., 2006; Kumar et al., 2014; Lin et al., 2015).
Ashwagandha (Withania somnifera) which belongs to Solanaceae has been used extensively in Ayurveda as a nervine tonic, aphrodisiac, and ‘adaptogen’ and helps the body adapt to stress, (Mishra LC, et al., 2000). It has rejuvenative (rasayana), antioxidant activity, free radical scavenging activity. Alkaloid extract of Ashwagandha root exhibited a calming effect on the central nervous system (CNS). Ashwagandha contains varities of ster- oidal compounds, amino acids (including tryptophan), and high amounts of iron, (Russo et al., 2001; Kelley et al., 2008; Wollen et al., 2010). One of the components, Withanamides has been shown to scavenge free radi- cals generated during the initiation and progression of AD. Neuronal cell death triggered by amyloid plaques was also blocked by with anamides, (Dhuley et al., 1998; Parihar et al., 2003).
Ashwagandha has been reported to increase memory and learning, (Tohda et al., 2005). Aqueous extracts of this herb have been found to increase cholinergic activ- ity, including increases in the acetylcholine content and cholineacetyl transferase activity in rats, (Schliebs et al., 1997; Tohda et al., 2000; Kuboyama et al., 2002). Treat- ment with the methanol extract of Ashwagandha caused neurite outgrowth in a dose- and
Ginger which belongs to Zingiberaceae family (Zin- giber of•cinale Roscoe) is one of the most commonly used herbal tea ginger is rich in a large number of bioac- tive substances, including gingerols and shogaols, phe- nolic ketone derivatives. Ginger is used medicinally for its hepatoprotective and antioxidant, antidiabetic and hypolipidemic and
Allium cepa has been associated with reduced lipid peroxidation index (malondialdehyde (MDA) and increased superoxide dismutase (SOD).
the female reproductive systems can include such things as menstrual problems, altered sexual behavior, infertil- ity, altered puberty onset, altered length of pregnancy, lactation problems, altered menopause onset and preg- nancy outcome, (Qin et al., 2013: Vahdani and Khaki 2014; Rajeshwari et al., 2015).
Oral Al exposure during pregnancy can cause a syn- drome including growth retardation, delayed ossi!ca- tion, and malformation at Al doses that also reduced maternal weight gain. At the perinatal age, aluminum is highly neurotoxic and inhibits prenatal and postnatal brain development. In addition, maternal dietary expo- sure to excess aluminum during gestation and lacta- tion which did not produce maternal toxicity would be capable of causing permanent neurobehavioral de!cits in weanling mice and rats, (Golub et al., 1986; Hussein et al., 2013; Muhammed et al., 2014; Berihu et al., 2015).
Rosmarinus of•cinalis commonly known as Rose- mary which belongs to lamiaceae. Their extract contains a high amount of total phenolics, is able to donate elec- trons, and therefore should be able to donate electrons to reactive radicals, converting them into more stable and unreactive species, (Dorman et al., 2003). The protec- tive action by rosemary extract in brain tissue through decreases in NOS activity, and subsequently, NO pro- duction. Therefore, they suggest that rosemary extract has an antioxidant effect as a free radical scavenger in this organ rosemary contains essential oils, terpenoids, "avonoids and alkaloids. Some of its constituents such as rosmarinic acid (RA) have been reported as powerful antioxidant protecting against free radicals damage and to reduce hepatotoxicity other researchers revealed the potential of RA for prevention of neurodegenerative dis- eases such as stroke, AD and PD, usually caused by an excess of free radicals. Unlike many drugs and natural antioxidants, RA was found to be able to cross blood brain so called pathologically
CONCULSION AND FUTURE PERSPECTIVES
Previous reviews and this recent update on aluminium toxicity demonstrate that use of aluminium is on a sig- ni!cant rise and it is not safe but the accumulation of aluminium in the body has yet to become the subject of serious investigation and consideration in medicine. Considering this state of affairs, the present review has tried to provide compiled reports and summarised state- ments to evaluate the protective effects of medicinal plant extracts like Coriandrum sativum , Wattakaka vol- ubilis, Bacopa monniera, Jasonia candicans and Jaso- nia Montana, Terminalia chebula, Terminalia bellerica,
Emblica of•cinalis, Curcuma longa, Withania somnifera Zingiber of•cinale, Roscoe, Allium cepa and Rosmari- nus of•cinalis extracts against the toxic effects of the highly hubiquitous metal aluminium which is increas- ing in animals and human beings leading to serious health problems. To combat with this malady, medicinal plants can be potent drugs which, have the potential of antitoxic, antioxidant, detoxi!cation with amelioration effects against heavy metals.
Medicinal plant extracts have a considerable role to play in the amelioration of Al toxicity in animals and human caused by higher Aluminium accumula- tion in body organ Use of Al was increasing day by day and it become a recent hazard, by it excessive use. Even though, till quite recently, at the molecular level, our understanding of how aluminium exert these toxic effects is still rudimentary. There is a general consen- sus that proteins are key targets of aluminium. Metals interfere with the biological activity of native, folded proteins through diverse modes of interaction; they may bind to free thiols or other functional groups in proteins displace essential metal ions in metalloproteins; or cata- lyze oxidation of amino acid side chains. In this situ- ation, the need of the hour is to develop safe and non toxic natural detoxi!cation agents which can be used for amelioration of ever increasing metal exposure and toxicity These earlier and recent studies reviewed here, make us strongly believe that natural supplementation perspective, though observed in animal model, will have sustainable curative value among the already af"icted populations, neutralizing impact on freshly emerging metal toxicity scenario and possible proactive protec- tion to those potentially susceptible to aluminium expo- sure. Indian herbs have high potential in overcoming Al toxicity in animal models. It hold extreme promise for future treatment of Al toxicity in animals and human.
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