Choleretic and cholagogic effects of anticholelithiatic plants

Choleretic and cholagogic effects of anticholelithiatic plants: History

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Subjects: Gastroenterology & Hepatology

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A large number of people suffer from gall stone worldwide and this problem is now being increased significantly due to the malnutrition, changes in living style, lack of exercise and conditions i.e. industrialization. Medicinal plants are used from centuries due to their cultural acceptability, efficacy, safety and fewer side effects as compared to modern synthetic medicines

Gall stone
anticholelithiatic
choleretic
cholagogue
ethnomedicine

1. Introduction

Gallstone is a worldwide problem. Its pervasiveness gives off an impression of being higher in Western world (>10%) than in Asian countries (3–10%). Female sex, older age, hyperlipidemia, higher body mass index (BMI), diabetes mellitus and alcohol consumption have been accounted for as danger factors for gallstone problem. Cholelithiasis (gallstone formation) is generally found in adults as compared to children. The frequency of gall stones among children is 1.9%. About 10 - 20% adult population of Western countries suffers from gall stones ^[1].

The gallbladder is a sac situated under the liver. It stores and concentrates the bile, produced in the liver. Bile acids play an important role in the assimilation of fats and is delivered from the gallbladder into the upper small digestive tract (duodenum) in response to food, especially fats. Development of stones inside the gall bladder is known as cholelithiasis. In this condition, hard stones of cholesterol or bile pigments are formed in the gallbladder. If these stones are found in the common bile duct, the condition is known as choledocholithiasis. Most of the stones are composed of cholesterol ^[2].

Bile is composed of bile salts, cholesterol and lecithin. It is present in a solution form by a delicate harmony. The proportion between bile salts and cholesterol is very important. In bile, cholesterol is in equilibrium with bile salts and with phosphatidylcholine. When the cholesterol becomes too concentrated in the bile then it saturates the bile acids and start to form crystals. As a result, a sludge is formed which contains cholesterol, calcium salts, mucin, and bilirubin and ultimately stones are developed ^[3].

2. Choleretic and cholagogic effects of anticholelithiatic plants

It is reported that the gallbladder smooth muscle (GBSM) bundles and their associated contractions are responsible to form gallbladder tone. The gallbladder performed a motor function, with 20-30% emptying at 1-2 hrs. intervals during the fasting state while 70–80% emptying after stimulation by cholecystokinin (CCK) when a diet is taken. The gallbladder contraction and relaxation is very important in driving the flow of bile salts in enterohepatic circulation and facilitate the absorption of lipids and fat-soluble vitamins. It is observed that changes occur in gallbladder smooth muscles in the gallbladder harboring lithogenic bile prior to inflammation and stone formation. Many factors are responsible in the pathogenesis of gallstone disease in which, gallbladder hypomotility and the resultant prolonged stasis of lithogenic bile are the most important. This malfunction is a very early event in the development of Gallstone disease, which occurs only in a few days after the onset of the lithogenic diet and becomes worse as the ailment progresses from microlithiasis to gallstones. Muscle contractility is diminished in gallbladders from patients with cholesterol stones. Impaired emptying of gallbladder may results in prolonged stasis of lithogenic bile in the gallbladder, which allows more time and a permissive environment for cholesterol crystallization and aggregation of that cholesterol into macroscopic gallstones.

A longer stay of bile in the gallbladder may lead to its hyperconcentration by gallbladder epithelial cells (GBECs). Increase in secretion of pro-nucleating mucins by GBECs is considered as an important factor responsible for gallstone formation. The gel-forming mucins made favorable environment for gallstone formation as it accelerate the nucleation of cholesterol monohydrate crystals from supersaturated bile ^[4]. There are three important factors responsible for cholesterol gallstone formation, bile composition (in particular cholesterol supersaturation and hydrophobic bile salts), factors promoting cholesterol crystallization (e.g. certain biliary proteins) and impaired gall bladder motility. In cholesterol gallstone disease, elevated biliary concentrations of cholesterol and hydrophobic bile salts are associated with biliary stasis. The main features of gallstone problems are biliary cholesterol elevation, cholesterol stones, decreased gallbladder contractility and cholecystitis ^[5]. Improving gallbladder motility with a prokinetic agent leads to a significant reduction in cholesterol crystallization. Gallbladder motility is promoted or increase or stimulated by CCK (Cholecystokinin) release, CCK receptor stimulation and decrease inflammation ^[6]. Medicinal plants having hepatobiliary effect are important therapeutic agents for cholestasis. These are called as choleretics (increasing bile production) and cholagogues (promoting the flow of bile from the liver and gall bladder into the intestines) ^[7].

Table 1: Anticholelithiatic plants with choleretic effects

Medicinal plants	Part/Mode of preparation
Acorus calamus L.	Rhizomes ^[8]
Achillea millefolium L.	Aerial parts ^{[9, 10]}
Agrimonia eupatoria L.	Leaves infusion and decoction ^[11]
Ajuga iva (L.) Schreb.	Leaves infusion ^[12]
Allium cepa L.	Bulb extract ^[13]
Alpinia officinarum Hance.	Roots ^[14]
Amomum compactum Sol. ex Maton.	Roots and rhizome ^[14]
Andrographis paniculata (Burm.f.) Nees.	Whole plant [9, 15]
Apium graveolens L.	Fruits and seeds ^[14]
Armoracia rusticana P.Gaertn., B.Mey. & Scherb.	Leaves ^[14]
Artemesia absinthium L.	Leaves ^[16]
Artemesia capillaris Thunberg.	Aerial parts ^[17-19]
Artemisia abrotanum L.	Aerial parts ^[17]
Artemisia absinthium L.	Whole plant ^[8], Leaves decoction ^[12]
Artemisia arborescens (Vaill.) L.	Leaves decoction ^[12]
Artemisia scoparia Waldst. & Kitam.	Aerial parts [17, 20-22]
Artemisia vulgaris L.	Leaves [9, 16]
Azadirachta indica A. Juss.	Leaves ^[23]
Boerhaavia diffusa L.	Whole plant ^[24]
Buplureum rotundifolium Griffithii.	Aerial parts ^[17]
Camellia sinensis Kuntze.	Leaves ^[18]
Canscora decussata (Roxb.) Roem. & Schult.	Roots and rhizomes ^[17]
Cercis siliquastrum L.	Seeds ^[17]
Cichorium endivia L.	Flowers ^[25]
Cinnamomum verum J. Presl.	Bark ^[14]
Cirsium arvense (L.) Scop.	Leaves and roots decoction ^[26]
Cnicus benedictus L.	Whole plant ^[27]
Coptis chinensis Franchet.	Rhizome ^[18]
Crocus sativus L.	Flower petal ^[14]
Curcuma longa L.	Roots [14, 28]
Cynara scolymus L.	Leaves and roots ^[29]
Dioscorea villosa L.	Roots ^[30]
Dipteryx odorata (Aubl.) Willd.	Seeds ^[14]
Eclipta alba (L.) Hassk.	Whole plant ^[31]
Elaeocarpus ganitrus Roxb. ex G.Don.	Leaves ^[9]
Euonymus europaeus L.	Root bark ^[16]
Euphorbia palustris L.	Aerial parts ^[17]
Euphorbia stepposa Zoz ex Prokh.	Aerial parts ^[17]
Fumaria capreolata L.	Whole plant infusion ^[12]
Fumaria officinalis L.	Whole plant infusion ^[12]
Galium aparine L.	Aerial parts ^[9]
Gardenia jasminoides J.Ellis. & Gardenia fructus	Fruits ^[32]
Gentiana lutea L.	Roots ^[33]
Gentiana manshurica Kitag.	Roots and rhizome ^[34]
Gentiana scabra Bunge.	Roots ^[18]
Gnaphalium uliginosum L.	Whole plant ^[8]
Hibiscus sabdariffa L.	Flowers ^[9]
Hypericum perforatum L.	Aerial parts ^[28]
Inula helenium L.	Roots decoction ^[26]
Kaempferia galanga L.	Rhizome ^[14]
Lapsana communis L.	Whole plant extract ^[26]
Lindera benzoin (L.) Blume	Leaves ^[14]
Linum usitatissimum L.	Seed decoction ^[35]
Lippia integrifolia (Griseb.) HIERON	Aerial parts ^[36]
Mentha × piperita L.	Leaves decoction ^{[37, 38]}
Mentha piperita L.	Leaves ^[8]
Mentha pulegium L.	Whole plant ^[18]
Menyanthes trifoliata L.	Leaves ^[8]
Momordica subangulata Blume	Leaves ^[39]
Moringa oleifera Lam.	Seeds ^[14]
Naregamia alata Wight & Arn.	Whole plant ^[39]
Nasturtium officinale R.Br.	Fresh plant as salad ^[27]
Nigella sativa L.	Seeds ^[14]
Persea americana Mill.	Fruits, Leaves ^[14]
Phellodendron amurense Rupr.	Bark ^[18]
Phyllanthus rheedei Wight.	Whole plant ^[40]
Pinellia ternata (Thunb.) Makino.	Rhizomes ^[41]
Plantago major L. / Plantago asiatica L.	Seeds ^[17]
Polygonum bistorta (L.) Samp.	Whole plant ^[42]
Prunus dulcis (Mill.) D.A.Webb.	Seeds oil ^[14]
Raphanus sativus var. niger (Mill.) J.Kern.	Root juice ^[43]
Reseda luteola L.	Flowers ^[17]
Rheum palmatum L.	Roots ^[27]
Rheum paltatum L.	Roots [18, 21]
Rhus coriaria L.	Leaves ^[14]
Rubia peregrina L.	Roots infusion ^[12]
Saussurea amara (L.) Candolle.	Aerial parts ^[44]
Schisandra chinensis (Turcz.) Baill.	Berries ^[45]
Scutellaria baicalensis Georgi.	Roots [18, 19, 21]
Silybum marianum (L.) Gaertn.	Leaves ^[16]
Solanum melongena L.	Fruits ^[46]
Sophora flavescens Aiton.	Roots ^[18]
Syringa oblata Lindley, Gard. Chron.-	Leaves ^[17]
Tanacetum vulgare L.	Flowers ^[8]
Taraxacum mongolicum Handel-Mazetti.	Whole plant ^[18]
Taraxacum officinale (L.) Weber ex F.H.Wigg.	Leaves ^[8]
Tecomella undulata (Sm.) Seem.	Bark ^[9]
Theobroma cacao L.	Beans ^[14]
Tilia platyphyllos Scop.	Bark ^[17]
Trigonella foenum-graecum L.	Seeds ^[14]
Uncaria gambir (W.Hunter) Roxb.	Leaves ^[17]
Viburnum opulus L.	Berries ^[8]
Zea mays L.	Cobs and corn silk ^[8]
Zygophyllum coccineum L.	Leaves ^[17]
Zygophyllum gaetulum Emb. & Maire	Leaves decoction ^[12]

Table 2: Anticholelithiatic plants with cholagogic effects

Meyna laxiflora Robyns	Fruits decoction ^[9]
Moringa oleifera Lam.	Leaves, seeds and roots ^[53], Flowers ^[54]
Moringa pterygosperma Gaertn.	Flowers ^[9]
Naregamia alata Wight & Arn.	Roots ^[9]
Nyctanthes arbor-tristis L.	Leaves ^[9]
Ononis arvensis L.	Aerial parts ^[17]
Patrinia villosa (Thunb.) Juss.	Roots ^[55]
Persea americana Mill.	Fruits ^[14]
Phyllanthus amarus Schumach. & Thonn. / Phyllanthus niruri L.	Leaves ^[56]
Pimpinella saxifraga L.	Leaves, roots ^[9]
Piper longum L.	Fruits ^[57]
Piper nigrum L.	Fruits ^[14]
Platycodon grandiflorum (Jacq.) A.DC.	Roots ^[58]
Polypodium vulgare L.	Rhizome ^[9]
Pongamia pinnata (L.) Pierre.	Seed oil ^[59]
Ricinus communis L.	Leaves ^[60]
Rubia tinctorium L.	Roots ^[61]
Rumex crispus L.	Roots ^[18]
Salvia officinalis L.	Leaves and flowers ^[9]
Sanguinaria canadensis L.	Roots ^[62]
Saponaria officinalis L.	Roots ^[9]
Silybum marianum (L.) Gaertn.	Fruits ^[63]
Solanum melongena L.	Whole plant ^[17]
Syzygium aromaticum (L.) Merr. & L.M. Perry.	Flowering buds ^{[9, 17]}
Terminalia belerica Roxb.	Fruits ^[17]
Terminalia tomentosa Wight & Arn.	Leaves ^[9]
Vangueria spinosa (Roxb. ex Link) Roxb.	Fruits ^[9]
Veronicastrum virginicum (L.) Farw.	Bark ^[18]
Yucca gloriosa L.	Fruits ^[9]
Zea mays L.	Cobs and corn silk ^[37]
Zingiber officinale Roscoe.	Rhizome ^[14]

This entry is adapted from the peer-reviewed paper 10.22271/phyto.2021.v10.i2a.13664

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