INTRODUCTION:

Urolithiasis is one of the extensive disorders which are more existence on the urinary tract. Formation of stone is one of the throbbing urological illnesses which are occurring roughly 12% of the global population and its re-occurrence rate in males’ is 70-81% and 47-60% in female¹. The rate of contingency is 3 times more in men than women, because of elevating capacity of testosterone and inhibiting capacity of estrogen in stone formation.⁽²⁾Formation of stone is also caused due to the polarity between the protagonist and inhibitors.^(3,4,45)

Calcium-containing calculi are predominant in males and females. However, UL remains a disease with a clear predominance in males for all stone compositions except for infection stones.⁽⁵⁾Currently, uric acid composition seems to be the second most common stone in both genders. The process of forming stones in the kidney, bladder, and urethra (urinary tract) is called as Urolithiasis.⁽⁶⁾ Stones form twice as often in men as women.

The nature of stones that clog the ureter or renal pelvis, is an piercing discontinuous pain that diverges from the flank to the groin or the genital area and through the inner thigh.⁽¹⁾ The nature and the type of stones are named based on their composition of mineral deposits. The most regular type of stones are struvite (magnesium ammonium phosphate), calcium oxalate, urate, cystine and silica^(1,7) The most frequent type of kidney stones occurring worldwide is the Calcium stones. Preventative measures depend on the type of stones. The formation of stone in the urinary system, i.e. in the kidney, ureter, and urinary bladder or in the urethra is called urolithiasis. ‘Urolithiasis’ = uro (urine) and lithos(stone).⁽⁸⁾

EPIDEMIOLOGY:

The prevalence of urolithiasis is increasing globally and is observed across sex, age, and race. Although the prevalence is between 5 and 10% in Europe, it is as high as 20% in some wealthy countries such as Saudi Arabia, U.S, Germany, Italy, Greece etc.,^(9,47) Natural plants have been used throughout the human history for various purposes as much of the tale where the herbal is used as the medicine. On an average 25% of the drug prescribed throughout the world are derived from plants.^(10,53)

In India, the Ayurvedic arrangement of pharmaceutical, ‘Pashanabheda ’aggregate plants, asserted to be valuable in the treatment of urinary stones. ‘Pashanabheda' is a Sanskrit expression utilized for the gathering of plants with the diuretic and anti-urolithiasis exercise (Pashana= stone; Bheda=break).

Table 1: Different region with high prevalence of kidney stones.⁽⁹⁾

Country	Year	Population	Prevalance
United States	1964–1972 1976–1980 1982 1988–1994	All All All All	2.62% 3.8% 5.4% 5.2%
Italy	1983 1993–1994	All All	1.17% 1.72%
Scotland	1977 1987	All All	3.83% 3.5%
Spain	1977 1979 1984 1987 1991	All All All All All	0.1% 3% 4.16% 2% 10%
Iceland	1991	All	3.9%
Thebece, Greece	2005	Age >_{_} 14 years	15.2%
U756u75

Thus a survey has been made to specify the investigations did on these plants, which has enriched phytoconstituents to dissolve those stones. The old Sanskrit literature in India, the Vedas, the Puranas and the Samhita defined the first time about renal calculi and their treatments.⁽¹¹⁾ The Charka samhita had defined anatomy, physiology and pathology of renal calculi in Mutravahaashmari with analysis and its treatment. The Sushrutasamhita had also focused about surgical operation with detailed explanation and sort of renal calculi, traits of renal calculi, etiology and signs and symptoms in AshmariNidana with clinical description and explained renal calculi remedy in Ashmari Chikitistia Sthanam.⁽¹²⁾

Fig 1: Location of stones in different parts of kidney and urinary bladder.⁽⁶⁾

Pathophysiology of uric acid stone:

Stone growth starts with the formation of crystals in supersaturated urine which then adhere to the urothelium, thus creating the nidus for subsequent stone growth⁽^46,49-52). The biological processes that anchor crystals to the urothelium are incompletely understood. Many, but not all, calcium oxalate stones develop on Randall's plaques which are composed of calcium phosphate (= hydroxyapatite) crystals.⁽¹³⁾ These grow to erode the urothelium, forming a nucleus for calcium oxalate deposition. More recent theories focus on the role of cell surface molecules which favor or inhibit crystal adhesion. Urothelial injury and repair after a stone episode may increase surface expression of these molecules to prefer further crystal adhesion. Thus ‘stones beget stones’ because there may be a residual nucleus on which new stones may form and up-regulation of molecules favoring crystal adhesion. Stone prevention focuses on identifying and enhancing the risk factors for crystal formation.

Fig 2: Pathophysiology of stone formation in kidney.

PASHANBHEDAPLANTS:

Pashanbheda is a lithotropic and diuretic drug that is commercially available and is used for treating renal problems. In Sanskrit, (Pasha=stone, Bheda= To Break). There are some plants known by the name Pashanbheda mainly because of their lithotrophic and diuretic activities.⁽¹⁴⁾ However, one plant that is widely accepted for these activities is the Bergenialingulata. This is a medicinal plant which is used for treating different types of ailments. It is found in the Himalayas and also in the Khasi Hills of Assam. Pashanbhed is also recommended for curing the abdominal tumor, breaking up calculi and painful micturition.^(15,16)

Restorative Uses of Pashanbhed:

Pashanbheda is utilized as a part of Unani and Ayurveda drug framework for the treatment of different sicknesses and particularly urinary stones. The foundation of the plant has purgative, cooling, abortifacient, Spanish fly and cooling properties. The foundations of this plant are utilized for treating urinary releases, vesicular calculi, bladder illnesses, over the top uterine drain, menorrhagia, heart infections, splenic extension and loose bowels.⁽¹⁷⁾ Other restorative employments of Pashanbhed include

Ÿ Roots of the plant can be rubbed and given with nectar for kids who are getting teeth.

Ÿ Wounds, bubbles, consume and cuts can be recuperated by utilizing the dried root glue of Pashanbhed remotely.

Ÿ Pashanbhed squeeze or root glue can be taken orally to get freed of intestinal parasites and roundworms.

Ÿ The juice extracted from Pashanbhed leaves can be utilised as a part of the type of ear drop for restoring ear infection.

Ÿ The decoction of the new foundations of Pashanbheda can be utilized for treating urinary clutters, urogenital disarranges and stomach issue.

Ÿ Paste made out of the foundation of this plant can help in relieving a blockage.

Ÿ Root powder of Pashanbheda is successful in treating fever.

Diet mediated:

Presence of pretty concentrated calcium, oxalate and phosphorus-containing materials in urine can motive formation of kidney stones. Waste products of the food within the bloodstream are carried to the kidneys and excreted in urine. Diet and fluid consumption are critical factors out of numerous different elements that may promote or inhibit kidney stone formation. Diets high in dehydrating foods and compounds, such as sugar, salt, and alcohol, can contribute to the development of kidney stones. Certain foods, though otherwise nutritious, are also naturally rich in oxalate. In susceptible folks, specific ingredients can sell stone formation but commonly now not associated with those who aren't vulnerable. Step one in the prevention of kidney stones is to apprehend the causes and sorts of stone formed. Laboratory evaluation of stones because it passes in urine or retrieved surgically or with a scope inserted through the urethra into the bladder or ureter gives the direct indication of a kind of stone. Blood and urine are to be examined for different tiers of chemicals, inclusive of calcium, oxalate and sodium to decide the type of kidney stone.^(18,48) The facts associated with kind of stone facilitates the fitness care issuer to indicate weight-reduction plan modifications that can prevent future kidney stone increase.

Avoid:

Almonds, Rhubarb, Okra, beets, Potato chips, fries, Nut butters, Bran flakes, Brinjal, spinach and foods which are high in oxalate.

Phytoconstituents :

The active constituents in the plants have greater impact to show the desired activity, thus the resistivity and strength to the plants has been seen through the presence of flavonoids, which also provides various pharmacological activities^(19,54). The total content of phenol and flavonoids rich portions shows the antioxidant property and can be used to treat from oxidative stress damage.^(20,54,55), and saponin is also one of the major constituent present in seed and leaves of the plant, which has polycyclic aglycone, referred to as sapogenin and saraponins^(21,56).

Table 3: Plants with Phytoconstituents to treat kidney stones:

HERBAL PLANTS	FAMILY	THERAPEUTIC USES	PHYTOCONSTITUENT	MOA
Moringa Oleifera Lam⁽²²⁾	Moringaceae	Anti enemic, Antihypertensive, Diarrhoea, Diabetes, HIV, HSV-1	Saponin glycosides	Decrease oxalate by acting on endogenous Oxalate synthesis’ Increase urine output
Solanum xanthocarpum⁽²³⁾	Solanaceae	Flatulence, Constipation, Antiviral, ringworm, cancer, antifertility, hypoglycemia.	Steroidal Saponinglycoalkaloid, flavonoid, sterol, phenolic tannins.	It increases the level of glycosaminoglycan and thus inhibits CaOX Crystal and reduce its urinary concentration.
Trigonellafoenumgraceum (Fenugreek)^{(24, , 57)}	Leguminosae	Flatulence, diarrohea, constipation, menstruration, PCOD, obesity, anemia.	Sapogenins, diosgenin, saponin, Beta Carotene, polyphenol	It maintains CaOX in the dispersed state and eliminates stones in the smaller size, by increasing dieresis, antioxidation and lower lipid peroxidation in the liver.
Aerevalanata⁽²⁵⁾	Amaranthaceae	Anti-microbial, cough, asthma, Gonorrohea, hepatitis, strangury, Alzhiemer’s, anemia.	Alpha-amyrin, beta- sitosterol, flavonoids, comsterol, tannins, quercetin, butelin.	The plant has two main active constituents quercetin, butelin, which reduce oxalate synthesis
Nigellia sativa L seed (Black cumin)⁽²⁶⁾	Ranunculaceae	Anti-inflammatory, Anti-hypertensive, Anti-diabetic, anti-cancer.	Thymoquinone, saponin, alpha-hederine, isoquinolone, thymohydroquinone	Thymoquinone is the main active ingredient which reduce the stone deposit and reduce the concentration of calcium oxalate in urine.
Urticadioica (stinging nettle)⁽²⁷⁾	Urticaceae	Diuretic, laxative, diarrhoea, benign prostatic hyperplasia, oedema, arthritis and gout	Flavonoids, Anthocyanins, and Saponins, protocatechuic acid, salicylic acid, luteolin, gossypetin, rutin, kaempferol‑3‑O‑rutinoside, kaempferol‑3‑O‑glucoside and chlorogenic acid.	The methanolic extract cause the inhibition of the calcium and oxalate deposition and the growth of a crystal, it leads to decreased urinary creatinine level and reduction of supersaturation of lithogenic enhancing agents
Punicagranatum (Pomegranate)^{(28, 29, 58)}	Punicaceae	A sore throat coughs, urinary infections, arthritis, expel worms, cancer prevention, prostate cancer, Alzheimer’s disease, Blood pressure, anti-viral.	Polyphenols. Alkaloid, Anthocyanins	The constituents are capable of scavenging free radicals. Themethanolic extract reduced the level of ROS (reactive oxygen species), iNOS (inducible Nitric Oxide Synthase), nuclear factor-kB and p38-mitogen protein-activated kinase, by inhibitingoxidative stress damage and anti-lipid peroxidation.
Camellia sinensis ( Green tea )^{(30, 31, 32))}	Theaceae	Lowers risk of cancer, Alzheimer’s, Parkinson's, Diabetes, Cardiovascular disease, obesity, anti-atherosclerotic.	Polyphenols, Catechin(Epigallocatechingallate (EGCG), epigallocatechin (GGC), epicatechingallate (ECG), and epicatechin (EC), ) L-theanine	It inhibited the growth of crystals in the kidney Of rats, diminished the excretion of oxalate, and exerted inhibitory effects on the activities of -glutamyltranspeptidase and N-acetyl-_-D-glucosaminidase as well as it decreased the supersaturation of brushite down-regulated the osteopontin (OPN) protein expression, increased superoxide dismutase (SOD), elevated Bcl-2 expression and lowered the apoptotic index in the rat model of kidney stones
Dolichosbiflorus L( Horsegram)^{(33, 34)}	Fabaceae	Ozonea, fever, digestive problem, weight loss, diabetes, asthma, astringent, bronchitis, menstrual cramp, constipation, leucorrhea.	Phenolic Compounds ( quercetin), alkaloids, phytosterols (_Beta-sitosterol), saponins, glucosides (such as Beta-galactosidases and alpha-mannosides)	Aqueous extract of the plant showed the highest dissolution of stones compared to other extracts, the hydro-alcoholic extract of seeds showed inhibitory Activity on nucleation and aggregation of calcium oxalate monohydrate crystals.
Ammivisnaga L (Khella)⁽³⁵⁾	Apiaceae,	Bronchial Asthma, Hypertriglyceridemia, angina pectoris, urologic.	khellin and visnagin, Visnadine	The aqueous extract of this fruit accelerated the dissolution of cystine stones and the incidence of calcium oxalate crystal deposition, increasing urinary excretion of citrate along witha decrease of oxalate excretion.
Phyllanthusniruri Linn⁽³⁶⁾	Euphorbiaceae	Anti-hepatoxicity, HIV, anti-hypertensive, anti-hyperuricemic, anti-plasmodic.	Flavonoid, alkaloid, terpenoid, tannin, coumarin, saponin , polyphenols.	Decreases the accumulation of callus formation in the kidney.
^.Rubusidaeus (Rasberry)⁽³⁷⁾	Rosaceae	Diarrohea, menstrual bleeding, vaginal discharge, menstrual cramp, varicose vein , .	Tannins, flavone glycoside, organic acid, vitamin c, irons, minerals, anthocyanin.	The extract decrease the urinary excretion of element that act as calculus promoters as well as decrease the level of calcium and oxalate which shows that it interfere with tubular transport.
Herniariahirsute⁽³⁸⁾	Caryophyllaceae	UTI, Lung problem, gout, arthiritis, blood purifier, muscle and joint pain.	Triterpene, saponin, quercetin, flavonoid.	The extract lead to increase in Mg²⁺ content, which is a potent calculi inhibitor leading in decrease in the size of the stone and increasing it output and also promotion of nucleation.

Few Other Medicinal plants to dissolve kidney stones:

Rosa Canina L:⁽³⁹⁾

It is a deciduous shrub belonging to the family Rosaceous; it is commonly known as Dog rose. It has been used for cold, flu, diuretic mild laxative, astringent, anti-viral etc.,. The RC is an excellent anti-oxidant for the kidney as it can prevent it from any oxidative stress damage, as they are susceptible to oxalate- induced free radical damage. The RC has higher urinary citrate concentration, and thus hypercitraturia activity might also be responsible for the reduction of stones as urinary citrate can inhibit CaOXsupersaturation through the formation of complexes with calcium and direct inhibition of crystal growth through aggregation.⁽⁴³⁾

Lygodiumjaponicum:⁽⁴⁰⁾

It is a dried spore belonging to Schizaeceae family; it has been commonly used to treat bloating, as the diuretic, as the expectorant, gonorrhea, eczema, jaundice, UTI etc., The ethanolic extract cause improvement in urinary calcium and Oxalate in renal content to decrease significantly with only a few renal stones. Whereas CaOX crystal and high level of oxalate cause membrane injury mediated by lipid peroxidation by generating oxygen free radical, which promotes for the formation of calcium oxalate crystal which adheres on the renal tubule.

Hypericumperforatum:⁽⁴¹⁾

It is commonly known as St John wort, and it belongs to the family of Hypericaciae. It has been widely used for treating anxiety, depression, malaria, sciatica, rheumatic, anti-inflammatory, antiviral, HIV, SAD (Severe Anxiety Disorder). The extract decreases the renal oxidative stress which protects the renal tubule; it also decreases the number and size of the calcium oxalate deposits in urine.

Bergeniaciliata:⁽⁴²⁾

It is a plant belonging to the family Saxifragaceae and is also known as Pakhanbhed. The constituents present are Bergenin, gallic acid, gallic, Beta-sitosterol, catechin-7-O-glucoside. It has been widely used for treating fever, diarrhoea, pulmonary infections, anti-cancer, anti-diabetic etc., The phenolic compound extracted and separated from the ethyl acetate fraction of the leaves showed more dissolution of the stones. This extract was more effective in dissolving calcium phosphate (67.74%) stones than oxalate (36.95%) stones.

BryophyllumpinnatumLeaf:⁽⁴³⁾

It is a plant belonging to the family Crassulaceae and is a perennial herb, which is commonly known as pattharcatta. It has been widely used for the treatment of diabetes, asthma, hypertension, constipation, earaches, haemorrhoids; jaundiceetc., The polyphenols found in the extract has shown to dissolve stone by inhibiting crystal formation or increasing crystal dissolution. The antioxidant effect of the extract has shown the ability to suppress Calcium Oxalate Monohydrate crystals binding in the epithelial cells.

Rubiacordifoliaroot:⁽⁴⁴⁾

It is a flowering plant belonging to the family Rubiaceae; it is commonly known as Indian madder. In medicine, it has been widely used as immune-modulatory, anti-inflammatory, blood purifier, arthritis etc., The hydro-alcoholic extract of the root prevented the change in urinary calcium, oxalate, phosphates excretion based on the given dose, the increased level of calcium oxalate crystal deposits in the renal tubule were reversed by the extract and also prevented the renal impairment functions. This is due to the anti-oxidative property present inside the extract which can eliminate the oxidative stress damage caused by the free scavenging radicals and the oxalate.

CONCLUSION:

In this the herbal medicine is taken as a pretext from various studies showed that the use of phytochemicals is being a promising constituents to reduce or dissolve kidney stones. In recent, the allopathic and surgical interventions of kidney stones via various aspects are not much prevalent to reduce kidney stones than those with the herbal constituents. Evidence of herbal medicines shown reported with minimal side effects. In these studiesit has shown a major reduction with Alkaloids such as quercetin, triterpene, saponin, polyphenolsand flavonoids plays an extensive role in the treatment of Nephrolithiasis.

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Received on 31.10.2018 Modified on 19.12.2018

Research J. Pharm. and Tech 2019; 12(9):4539-4544.

DOI: 10.5958/0974-360X.2019.00781.9

Type	Frequency	Sex	Crystal	Radiography
Calcium oxalate / mix	75	M	Envelope	Round, radiodense, sharply outlined.
Calcium phosphate (brushite)	5	F> M	Amorphous; Alkaline urine	Small, radiodense, sharply outlined.
Uric acid	5-15	M=F	Diamond ; Acid urine	Round staghorn, radiolucent, filling defect.
Struvite (Mgand NH⁴⁺ PO₄)	10-20	F	Coffin lid	Staghorn, laminated radiodense.
Cystine	1	M=F	Hexagon	Staghorn, radiodense.