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.

*Corresponding Author E-mail: chandrumnrcop@gmail.com

 

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.

 

KEYWORDS: Urolithiasis, Medicinal Plants, Phytoconstituents, Kidney Stones, Renal Calculi.

 

 


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

Res. J. Pharmacognosy and Phytochem. 2021; 13(2):95-100.

DOI: 10.52711/0975-4385.2021.00015