Liver immunology and herbal treatment

Table 1 Features of CD4+ cell subsets

	Th1	Th2	T17	Treg	Tfh
Produced Cytokines	IFN-gama, TNF-alpha, IL-2	IL-4, IL-5, IL-9, IL-10, IL-13	IL-17A, IL-17F, IL-21, IL-22, IL-26	TGF-beta, IL-10	CXCR5, IL-21
Immune response mediated aginst	Intracellular pathogens	Extracellular parasites, allergy, humoral response	Extracellular bacteria and fungi, autoimmunity	IgA secretion, self-tolerance	Differentiation of B cells
Master transcription factors for differentiation	T-bet	GATA-3	RORct	Foxp3	Bcl6
Effected cells	Macrophages, cytotoxic cells activated	Eosinophils, mast cells activated	Neutrophils activated	B cells activated Th1, Th2, Th17 supressed	B cells activated

IFN: Interferons; IL: Interleukin; TGF: transforming growth factor; TNF: Tumor necrosis factor.

Table 2 Plants are effective on liver disorders and immune system

Common name	Scientıfic name	Effectıve part	Phytochemıcal content	Preparatıon on lıver dısorders1	Ref.
Chaff-flower	Achyranthes aspera L.	Whole plant	Ecdysterone, achyranthine, betaine, pentatriaontane, 6-pentatriacontanone, hexatriacontane and tritriacontane	Natrossil natiris	[28-30]
Fennel	Foeniculum vulgare Mill.	Root	Coumarins (bergapten, ısopimpinellin, anthotoxin), flavonoids (quercetin, rutin)	Presselin dyspeptikum presselin, bupleurum compound phytomedicine, epagest lampugnani	[18,25,31]
Korean Ginseng, Chinese Red Ginseng	Panax ginseng Mey.	Root	Polysaccharides, saponins, ginsenoside	Tripid teguhsindo	[32-34]
Yarrow	Achillea sp.	Flower	Volatile oils, flavonoids, terpenoids, alkaloids, saponins, sesquiterpenlactones	Liv-52 drops, cheiranthol klein	[35-38]
Carqueja	Baccharis trimera (Less) DC	Epigeous part	Flavonoids, diterpenoids	Boldina Plata	[39-41]
Chicory	Cichorium intybus L.	Aerial part, root, leaf	Saccharides, methoxycoumarin cichorine, flavonoids, essential oils, anthocyanins	Natusor hepavesical soria natural, Liv-52 drops	[42-46]
Globe artichoke	Cynara cardunculus var. scolymus L.	Leaf	Sesquiterpenes lactones (cynaropicrin), flavonoids (cynaropicrin), phenolic acids (mainly caffeic acid derivatives)	Livstim mediherb, livton complex mediherb, lorbihepatic bioquimico, olocynan makros, rapacholin C herbapol wroclaw, farmasa, sylicynar herbapol poznan, alcafelol luper, bagohepat bago, armstrong, benevolus schwabe, boldina plata, cinarepa cristalfarma, colachofra EMS, cynarex roux-ocefa, herbapol wroclaw, cynarzym N altana, digestron loprofar, epagest lampugnani, figatil catarinense, salus, hecrosine B12 ortoquimica, hepatofalk falk, jurubileno ıbefar	[47,48]
Pale purple coneflower	Echinacea pallida (Nutt.) Nutt. Echinacea angustifolia (DC.) Hell. Echinacea purpurea (L.) Moench	Whole plant	Alkamides, polysaccharides, glycoproteins, cichoric acid (a derivate of caffeic acid)	Andrographis complex mediherb, kalbe, hepatin lapi, ımudator pyridam, herbal cleanse vitaplex	[49-52]
Faise daisy	Eclipta alba (syn E. prostrata L.)	Aerial part	Tannins, flavonoids, coumestans, saponins, alkaloids	Dipana promed	[53,54]
Chamomile	Matricaria chamomilla L.	Flower	Coumarin (herniarin and umbelliferone), phenylpropanoids (chlorogenic acid and caffeic acid), flavonoids (apigenin, apigenin-7-o-glucoside, luteolin, luteolin-7-o-glucoside, quercetin, rutin, naringenin), blue essential oils	Presselin dyspeptikum presselin, cholesol herbapol wroclaw, gotas digestivas bunker	[42,55-57]
Milk thisle	Silybum marianum (L.) Gaertn.	Seed	Polyphenolic flavonoids(silymarin, isosilyins, silibinins, silydianin silychristin)	Liverine cardinal, livermin korean ginseng, liverton sıffra, livosil-b centaur, livstim mediherb, livton complex mediherb, lomacholan lomapharm, phytohepar steigerwald, poikicholan lomapharm, prol procare, samarin berlin pharm, schwohepan S schworer, silegon teva, silibene merckle, silicur hexal, silimalon nikkho, silimarin benedetti, silimarit bionorica, silimax filofarm, silirex lampugnani, siliver farmasa, silliver abbott, silmar hennig, silvaysan sanum-kehlbeck, silybon micro, silygal ıvax, silyhexal hexal, sily-sabona sabona, mepha, sivylar ranbaxy, sylicaps herbapol lublin, sylicynar herbapol poznan, sylimarol herbapol pruszkow	[18,19,58,59]
				Syliverin aflofarm, sylivit herbapol poznan, solas, vionin nf tempo scan pacific, alepa duopharm, apihepar madaus, vıa tris, aptivium liver support cynergen, ardeyhepan emonta, ardeypharm, bibol leloup hexa, bilisan duo repha
				Bioglan liver-vite bioglan, bupleurum complex mediherb, bupleurum compound phytomedicine, carsil sopharma, cefasliymarin cefak, cheiranthol klein, soho capsule/syrup, depatox progen, durasilymarin merck dura, eleparon sankyo, epagest lampugnani, flavobion zentiva, hegrimarin strathmann, strathmann, hepabene ratiopharm, merckle, ratiopharm, hepabesch strathmann, hepadigenor baliarda, hepaduran v otw, loges
				Capsule, hepamax dankos, hepa-merz sil merz, hepar-pasc pascoe, heparsyx n syxyl, heparviton bode, tempo scan pacific, hepatin lapi, kalbe, falk, darya-varia, hepatos, Yung shin, heplant spitzner, herbal liver formula faulding, worwag, legalon-madaus, laragon roemmers, ıfet, leveron vesco, limarin serum ınstitute, herbal cleanse vitaplex
Dandelion	Taraxacum officinale G.	Root	Sesquiterpenes, saponins, phenolic compounds, flavonoids, sugars	Naturica DFM ıkapharmindo, livstim mediherb, livton complex mediherb, berberis complex blackmores, cholesol herbapol wroclaw, cinarepa cristalfarma, hepatofalk falk, herbal cleanse vitaplex	[60-63]
Radish	Raphanus sativus L.	Leaf, root	Flavanoids, terpenoids, alkaloids, saponins, sterols	Rapacholin AC herbapol wroclaw, rapacholin c herbapol wroclaw	[64-67]
Caper	Capparis spinosa L.	Root bark	Sugars (glucose, arabinose, mannose, galactose), lipid, volatile oils	Liv-52 drops	[68-71]
Kinkéliba	Combretum micranthum G. Don	Leaf	catechins, glycosylflavones, flavans, galloylated c-glycosylflavone derivatives, flavan-piperidine alkaloid	Tisane mediflor N°5 hepatique	[72-74]
Arjuna	Terminalia arjuna (Roxb.) Wight and Arn.	Bark	Arjunolic acid, tomentosic acid, arjunin, β-sitosterol, ellagic acid, leucodelphinidin, tannins	Liv-52 drops	[75-77]
Coffee senna	Cassia occidentalis L.(Senna occidentalis)	Leaf	Anthraquinones, saponins, sterols, triterpenes, quinines, tannins, flavonoids	Tisane mediflor N°5 hepatıque, Liv-52 drops	[78-80]
Liquorice, Licorice	Glycyrrhiza glabra L.	Root	Triterpene saponins, flavonoids, isoflavonoids and chalcones, glycyrrhizic acid	Tisane mediflor N°5 hepatıque, neo-minophagen C dexa, torii, curliv soho, soho capsule/syrup	[18,26,81]
Holy basil	Ocimum sanctum Linn.	Leaf	Volatile oils (eugenol, euginal, urosolic acid, carvacrol, linalool, limatrol, caryophyllene, methyl carvicol), anthocyans, alkaloids, flavonoids, tannins, carbohydrates,xylose, polysaccharides	Andrographis complex mediherb	[22,82-85]
Rosemary	Rosmarinus officinalis L.	Leaf	Diterpenoids, triterpenoids, phenolic acids, and flavonoids, carnosic acid, carnosol, rosmarinic acid	Tisane mediflor N°5 hepatıque, natusor hepavesical soria natural, cinarepa cristalfarma	[86-88]
Red sage, Danshen	Salvia miltiorrhiza Bunge.	Root	Tanshinones (tanshinone ı, tanshinoneıı, cryptotanshinone) miltirone and salvianolic acid a, b	Bupleurum complex mediherb	[18,89,90]
Common mallow	Malva sylvestris L.	Leaf	Amino acids/protein derivatives, flavonoids, mucilages, terpenoids, phenol derivatives, coumarin	Tisane mediflor N°5 hepatıque	[91-93]
Tinospora, Guduchi, Giloya	Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi)	Root, stem	Flavonoids, alkaloids, sesquiterpenes, diterpenes arabinogalactan, syringine, cordiol, cordioside, cordifoliosides (a and b), berberine, tinosporine, giloin, giloinin	Dipana promed	[22,33,94-96]
Boldo, Boldu, Boldus	Peumus boldus Molina	Leaf	Alkaloids (isoquinoline-boldine, isoboldine, 6a,7-dehydroboldine, isocorydine, isocorydine-n-oxide, norisocorydine, laurolitsine, laurotetanine, n-methyllaurotetanine, reticuline, (-)-pronuciferine, sinoacutine), flavonoids, volatile oil, coumarin, resin, tannin)	Tisane mediflor N°5 hepatıque, natrossil natiris, natusor hepavesical soria natural, prinachol zurita, farmasa, alcafelol luper, berberis complex blackmores, boldina plata, boldopeptan neo quimica, colachofra ems, cynarzym N altana, eparema nycomed, figatil catarinense, gotas digestivas bunker, jurubileno ıbefar	[97-99]
Greater celandine	Chelidonium majus L.	Aerial parts	Isoquinoline alkaloids, such as sanguinarine, chelidonine, chelerythrine, berberine and coptisine, (-)-turkiyenine)	Livstim mediherb, livton complex mediherb, natusor hepavesical soria natural, schwohepan S schworer, berberis complex blackmores, chelicur hasco-lek, cynarzym N altana, hepatofalk falk, falk, darya-varia	[100-105]
Gale of the wind	Phyllanthus niruri L.	Whole plant	Flavonoids, alkaloids, terpenoids, lignans, polyphenols, tannins, coumarins and saponins	Natrossil natiris, meprofarm, dipana promed, gramuno graha, hepimun landson, ımudator pyridam	[106-108]
Kutki	Picrorhiza kurroa Royle ex Benth.	Rhizome, root	Iridoid glycoside (picrovil)	Dipana promed	[109,110]
Rhubarb	Rheum emodi	Rhizome	Anthraquinone (rhein, chrysophanol, aloe-emodin, emodin, physcion, and their glycosides) and stilbene (picetannol, resveratrol and their glycosides), flavonoids, glycosides, tannins, volatile oils, saponins	Natrossil natiris, boldopeptan neo quimica, eparema nycomed, SIT, hepatofalk falk	[111]
Magnolia-vine, Schisandra	Schisandra chinensis (Turcz.) Baill.	Fruit	Dibenzocyclooctadiene derivative lignans (or schisandra lignans), organic acids (citric, malic, fumaric and tartaric acid), sugars, vitamic C, vitamin E, phenolic acids, tannins, phytosterols, essential oil	Curliv soho, soho capsule/syrup, hepacell medikon, hepamax dankos	[31,112,113]
European black nightshade	Solanum nigrum L.	Whole plant	Glycoalkaloids, glycoproteins, polysaccharides, polyphenolic compounds (gallic acid, catechin, protocatechuic acid (pca), caffeic acid, epicatechin, rutin, naringenin)	Liv-52 drops, dipana promed	[114-117]
French tamaris	Tamarix gallica L.	Aerial parts	Tannin, tamarixin, tamauxetin, troupin, 4-methylcoumarin and 3,3’-di-o-methylellagic acid, tannic acid, 4-methylcoumarin and 3,3’-di-o-methylellagic acid	Liv-52 drops	[118,119]
Turmeric	Curcuma longa L.	Rhizome	Curcuminoid	Meprofarm, tripid teguhsindo, turmerik knop, aptivium liver support cynergen, chelicur hasco-lek, galena, ıvax, cinarepa cristalfarma, depatox progen, heparviton bode, tempo scan pacific, kalbe, hepatin lapi, falk	[22,31,120]
Ginger	Zingiber officinale Roscoe	Rhizome	Volatile oils, pungent phenol compounds [sesquiterpenoids,beta-sitosterol palmitate, isovanillin, glycol monopalmitate, hexacosanoic acid 2,3-dihydroxypropyl ester, maleimide-5-oxime, p-hydroxybenzaldehyde adenine, 6-gingerol, 6-shogaol, 1-(omega-ferulyloxyceratyl) glycerols]	Presselin dyspeptikum presselin, dipana promed, herbal cleanse vitaplex	[121-127]

¹Martindale W, Sweetman SC. Martindale: The complete drug reference. Pharmaceutical press, 2007.

Table 3 Commonly used plants on liver disorders and their effect mechanisms

Scientific name	Effect/mechanism on liver	Effect/mechanısm on immun system	Ref.
Curcuma longa L.	Acute liver damage by chemicals, e.g., ethanol, CCl4, Dimethylnitrosamines	Immunostimulant, immunomodulatory	[18,22-24]
		The extract of the rhizome C. longa increased both Th1 (IL-2 and IFN gamma) and Th2 (IL-10) cytokines indicating its dual immune functions. NR-INF-02 significantly increased the IL-2 and IFN gamma levels in Con A stimulated splenic lymphocytes. The above results indicated that NR-INF-02 showed a specific immunity response by stimulating both Th1 and Th2 cells
		Polysaccharide fraction of the rhizome showed potent immunostimulatory activity towards proliferation of splenocytes cell number and IL-10 secretion. Polysaccharides might be contributing to this proliferative and cytokine release property in murine splenocytes
		Hot water extracts of the rhizome showed that the high polarity fraction exhibited stimulatory effects on PBMC. The cytokine productions (TGF-beta, TNF-alpha, GM-CSF, IL-1alpha, IL-5, IL-6, IL-8, IL-10, IL-13, etc.) have been modulated by a polysaccharide-enriched fraction.The proportion of CD14 positive stained PBMC was increased by the fraction
		Anti-HIV-1 and HIV-2
Foeniculum vulgare Mill.	Oxidative stress of the liver bacterial and viral infections anti-inflammatory, acute hepatotoxicity	Immunomodulatory	[18,25]
		Antimicrobial, antifungal
Glycyrrhiza glabra L.	Cirrhosis fibrosis chronic viral hepatitis B and C	Immunomodulatory	[18,26,27]
		Leukocyte count and phagocytic index (carbon clearance) was increased significantly with the treatment of water extract of G. glabra root. Zinc (45 mg/kg) in combination with ALE (0.75 g/kg) showed highly significant increase of leukocyte count and phagocytic index
Silybum marianum (L.) Gaertn.	Oxidative stress inflammation and fibrosis alcohol-induced cirrhosis mushroom poisoning viral hepatitis	Immunomodulatory	[18,19]
		Flavonoids from S. marianum normalize immunoregulatory defects via restoration of the cellular thiol status. T-cell activation (CD69), along with a significant decrease in TNF

IFN: Interferons; TNF: Tumor necrosis factor; IL: Interleukin; TGF: transforming growth factor; HIV: Human immunodeficiency virus; PBMC: Peripheral blood mononuclear cells; GM-CSF: Granulocyte-macrophage colony-stimulating factor; ALE: Aqueous liquorice extract.