A Critical Review on Antiurolithiatic Activity of Bioactive Phytoconstituents

 

Dheepa Anand¹*, Chandrasekar R², Sivagami B³

²Department of Pharmacology, Cherans College of Pharmacy, Coimbatore, Tamilnadu, India.

¹Associate Professor, Department of Pharmacognosy, Seven Hills College of Pharmacy, Tirupati, Chitoor, Andhrapradesh, India.

³Associate Professor, Department of Pharmaceutical Analysis, Seven Hills College of Pharmacy, Tirupati.

 

ABSTRACT:

New drugs are introduced in the market every year and new diseases are emerging every year and there is no cure for existing diseases. Though new drugs   are being   approved   by   the FDA   every   year, controlling emerging    infections is a global concern. Due to increased side effects and toxicity the modern world is turning towards herbal medicine. Due to few reasons like global warming, food habits and modern life style disease like Urolithiasis places a significant economic burden on the healthcare system, especially in developed and developing countries where, owing to changes in food habits and lifestyle, the prevalence of stone disease has significantly increased over the last few decades; unfortunately, it will probably continue to increase for a number of reasons. Despite considerable improvements in the development of new herbal therapies for the management of urinary stones, the incidence of urolithiasis is increasing worldwide. However, it is evident that crystal retention, cell apoptosis, renal cell injury, and associated stone promoters or inhibitors play important roles for kidney stone formation. In addition, the identification of novel phytoconstituents on the basis of molecular and cellular alterations in relation to stone formation will help develop better herbal remedies. Moreover, better understanding of the mechanisms of urolithiasis associated with stone inhibitors or promoters will be critical for stone-removing medications. This review encompasses different medicinal plants, polyherbal formulations and phytoconstituents used in the treatment of Kidney stones. More interdisciplinary research is needed to develop new plant-derived high-quality natural products to treat and prevent the formation of kidney stones.

 

 

INTRODUCTION:

Kidney stones are one of the most painful urologic disorders. Renal stone affects 5 to 15% of adults. Epidemiological studies revealed that nephrolithiasis is more common in men (12%) than in women (6%) and is more prevalent between the ages of 20 to 40 in both sexes¹. Urinary stones affect 10–12% of the population in industrialized countries². The incidence of urinary stones has been increasing over the last years while the age of onset is decreasing³. With a prevalence of > 10% and an expected recurrence rate of ~ 50%, the stone disease has an important effect on the healthcare system⁴. The aetiology of this disorder is multifactorial and is strongly related to dietary lifestyle habits or practices. Most calculi in the urinary system arising from a common component of urine, e.g. calcium oxalate representing up to 80% of analyzed stones. In India, 12% of the population is expected to have urinary stones, out of which 50% may end up with the loss of kidneys or renal damage. Also, nearly 15% of the population of northern India suffers from kidney stones⁵. Urinary calculi is the third prevalent disorder in the urinary system. Urolithiasis is a common disease with an increasing incidence and prevalence worldwide that appears even more pronounced in industrialized countries⁶. Once recurrent, the subsequent relapse risk is raised and the interval between recurrences is shortened⁷. Features associated with recurrence include a young age of onset, positive family history, infection stones and underlying medical conditions⁸. Urolithiasis or nephrolithiasis represents the clinical condition of kidney stone disease. Stone formation in the urinary tract has been recognized for thousands of years, but during the last few decades, the pattern and incidence of the disease have changed markedly.

 

Figure 1 Phytoconstituents

 

Urolithiasis refers to the solid nonmetallic minerals in the urinary tract. Among the several types of kidney stones, the most common are calcium oxalate. The formation of these stones involves several physico-chemical events, beginning with crystal nucleation, aggregation, and ending with retention within the urinary tract⁹. Ethylene glycol (EG) is rapidly absorbed and metabolized in the liver via alcohol dehydrogenase/ aldehyde dehydrogenase to glycolic acid. Glycolic acid is oxidized to glyoxylic acid, which, in turn, is further oxidized to oxalic acid by glycolate oxidase. High doses of EG (>2,500 mg/kg body wt), particularly when given as an oral bolus, cause the saturation dependent accumulation of glycolic acid in the plasma. So, glycolate oxidase (GO) is one of the rate-limiting enzymes in the metabolism of EG¹⁰.

The mechanism of stone formation is a complex process which results from several physicochemical properties including supersaturation, crystal nucleation, precipitation, crystal growth, aggregation of crystals and retention of urinary stone constituents within tubular cells. There are various types of kidney stones which include cystine stones, calcium oxalate stones, calcium phosphate stones, struvite stones and uric acid stones. However, it is evident that crystal retention, cell apoptosis, renal cell injury, and associated stone promoters or inhibitors play important roles for kidney stone formation. ¹¹

 

Figure 2 Mechanism of Stone Formation

 

Systematic research needs to be undertaken, in an attempt to explore botanicals as alternative and/or complementary medicines for the treatment of urolithiasis. Furthermore, understanding the underlying pathophysiology, pathogenesis, and genetic basis of kidney stone formation will hopefully lead to discover novel drugs and strategies to manage urolithiasis in the near future. The herbal preparations for the treatment of kidney stone have been known since long for its safety. Further, the herbal preparations remove the kidney stones fast and more effectively without damaging the kidneys. These preparations are cost effective and having lesser side effects than allopathic medicines. The application of newer technologies needs to be improved upon the earlier known herbal composition to achieve enhanced efficacy with more synergistic effect and better patient compliance and which is cost effective for the treatment of kidney stone and other urinary disorders like inflammation and urinary stent related problems.^{12, 13}

 

Table No 1 This table specifies medicinal plants and phytoconstituents used in the treatment of Urolithiasis

Name	Phytoconstituents and Standards	Extract	Animal model	Reference
Asparagus racemosus		Ethanolic extract	Ethylene glycol (EG) and ammonium chloride (AC	14
Lantana camara	Oleanolic acid	Ethanolic extract	Zinc  disc implantation induced urolithiatic model	15
Cucumismelo seeds		Methanolic extract	In vitro antiurolithiatic activity	16
A. lanata	Quercetin and betulin	Crude extract	Ethylene glycol induced urolithiasis model	17
Herniaria hirsuta, Opuntia ficus-indica, Zea mays and Ammi visnaga	Polyhydroxylated molecules	Crude extracts	In vitro antiurolithiatic activity	18
Trigonella foenum-graecum	Polyphenols or flavonoids	Aqueous extract	In vitro litholytic activity Cystine  uric acid and pure carbapatite	19
Mimusops elengi		Petroleum ether, chloroform, and alcohol extracts	Ethylene glycol induced urolithiasis in rats	20
Bergenia ligulata	Pashanbhed hexane, toluene, dichloromethane (DCM), n-butanol, and water fractions	Aqueous extract	Ethylene Glycol Induced Renal Calculi in Rat	21
Viburnum opulus L.,	Chlorogenic acid		Sodium Oxalate-Induced Urolithiasis Rat Model	22
Gossypium herbaceum	Neeri	Ethanolic and Aqueous extracts	In vitro Antiurolithiatic Activity Calcium oxalate crystals	23
Melia azedarach	Allopurinol	Aqueous and alcoholic extracts	Ethylene glycol-induced calcium oxalate urolithiasis	24
Musa sp.,	Cystone	Methanolic extracts	In vitro nucleation and aggregation assay calcium oxalate crystallization	25
Biophytum sensitivum		Methanolic extract	Zinc disc-implanted Urolithiasis model	26
Pedalium murex		Ethyl acetate extract	Anti-urolithiatic of Struvite crystal	27
Costus spiralis Roscoe	Bethanecol atropine	Water extract	Antiurolithiatic activity of Implants of calcium oxalate crystals or zinc disc	28
Ipomoea eriocarpa		Ethanol leaf extract	Ethylene glycol-induced urolithiasis in rats	29
Chloris barbata	Neeri	Ethanolic and Aqueous extracts	In vitro antiurolithiatic activity	30
Momordica charantia		Aqueous Extract Alcoholic Extract	Ethylene glycol induced urolithiasis in rats	31
Pergularia daemia	Cystone	Alcoholic extract	Ethylene glycol	32
Ipomoea eriocarpa	cystone	ethanol leaf extract	Ethylene glycol-induced urolithiasis in rats	33
Daucus carota	Saponins tannins, flavonoids and polyphenolic content	Root extract	In vitro calcium oxalate (CaOx) urolithiasis	34
Boldoa purpurascens Cav.	Cystone	Aqueous extract from leaves	In vitro and in vivo calcium oxalate (CaOx)	35
Macrotyloma uniflorum Linn.		Aqueous extract	Ethylene glycol induced urolithiasis in rats	36
Alphonsea sclerocarpa Thwaites	Saponins and flavonoids	Ethanolic leaf extract	Ethylene glycol induced urolithiasis in rats	37
Phaseolus vulgaris	Cystone	Ethanolic extract	Calcium oxalate urolithiasis ethylene glycol (EG) and ammonium chloride	38
Holarrhena antidysenterica	Cystone	Aqueous methanolic extract	Ethylene glycol induced urolithiasis in rats	39
Tribulus terrestris	Cystone	Aqueous extract	In vivo urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats	40
Annona squamosa Linn.		Ethanolic leaf extract	Ethylene glycol-induced urolithiasis model	41
Tragia involucrata	Silver nanoparticles phenol, flavonoid, terpenoid and sterol	Aqueous extract	In vitro struvite growth inhibitory activity	42
Brassica oleracea Gongylodes and Desmostachya bipinnata		Aqueous extract	Ethylene glycol with ammonium chloride	43
Quercus gilva Blume	Polyphenolic Compounds	Crude extract	Ethylene glycol-induced urolithiasis model	44
Origanum vulgare		Crude extract	Ethylene glycol-induced urolithiasis model	45
Boerhaavia diffusa and Tribulus terrestris	Cystone		Ethylene glycol-induced urolithiasis model	46
Launaea procumbens		methanolic extract	Ethylene glycol-induced urolithiasis model	47
Lemon juice			Ethylene glycol-induced urolithiasis model	48
Brown seaweeds	Fucoxanthin		Ethylene glycol-induced renal calculus	49
Hordeum vulgare seeds		Ethanolic extract	Ethylene glycol-induced urolithiasis	50
Macrotyloma uniflorum		Aqueous extract	Ethylene glycol induced urolithiasis in rats	51
Triclisia gilletii Staner	Phenols, steroids, saponins, and flavonoids		Ethane-1,2-diol-induced urolithiasis	52
Piper longum Linn	Piperine		In Vitro – In Vivo Evaluation of Antiurolithiatic activity	53
Solanum nigrum		Hydroalcoholic extract	Ethylene glycol induced urolithiasis in rats	54
Vigna radiata	Neeri	Aqueous extract	In vitro antiurolithiatic activity	55
Aerva lanata, Sphaeranthus indicus, Merremia emarginata	Cystone	Methanolic extracts	In vitro Antilithiatic activity	56
Costus igneus	Cystone	Methanolic extract	In-Vitro Anti-Urolithic Activity	57
Stzygium cumini	Cystone	Ethanolic extract	In vitro anti-urolithiatic activity	58
Terminalia arjuna	Cystone	Ethanolic extract	Ethylene glycol-induced urolithiasis model	59

 

Table No 2 Antiurolithiatic activity of Polyherbal Formulations

Name	Phytoconstituents and Standards	Extract	Animal model	Reference
Lithocare	Polyherbal formulation		Ethylene glycol (EG) induced urolithiasis in Wistar rats	60
Pashanabhedadi Ghrita	Ammonium oxalate		Gentamicin injection induced renal calculi in albino rats	61
Gokhsuradi churna			Calcium oxalate crystallization was induced by the addition of 0.01M sodium oxalate solutions in synthetic urine and nucleation method	62
Polyherbal Formulation	Saponins		Antiurolithiatic Activity	63
Polyherbal formulation			Ethylene glycol-induced urolithiasis model	64
Gokshuradi Yog		Gokshuradi polyherbal aqueous extracts	Ethylene glycol-induced urolithiasis model	65
Sirupeelai Samoola Kudineer	Cystone		Ethylene glycol-induced Renal Calculus in Experimental Rats	66
Amlodipine			Ethylene glycol-induced urolithiasis model	67
Polyherbal Formulation	Lithout tablets		In-vitro inhibition of Calcium Oxalate Crystallization Turbidimetric model	68

 

CONCLUSION:

Isolation of metabolites containing bioactive compounds like flavonoids, phenolic compounds, alkaloids, can be obtained by different extraction techniques and the isolated compound can be characterized by various spectroscopic methods to determine the structure elucidation and activity. The therapeutic activity of the isolated bioactive compound can be therapeutically determined by in vitro, in vivo studies and clinical studies. This review can be a reference for young researchers and scientists for future studies to develop potent formulations containing phytoconstituents with enhanced efficacy, fewer toxicity and side effects and cost effective methods of extraction isolation and characterization of natural compounds. The therapeutic activity can be determined by different in-vitro, in-vivo animal models and clinical trials. Hence a novel cost effective herbal formulation can be prepared and evaluated for its efficacy and safety with less side effects and toxicity and reach the people in an affordable price for the treatment of kidney disorders. More interdisciplinary research is needed to develop new plant-derived high-quality natural products to treat and prevent the formation of kidney stones.

 

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Received on 13.01.2021         Modified on 23.02.2021

Accepted on 16.03.2021  ©AandV Publications All right reserved