Nella terza installazione digestiva ho deciso di scardinare l’ordine cronologico della discussione saltando ad una serie di minimonografie di piante con un certo bagaglio di letteratura sperimentale e clinica, e che, più o meno tirate per i tricomi, possono dirsi piante anche alimentari. Ci sarà tempo per ritornare a discorsi di ordine più teorico.

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Cynara cardunculus subsp. cardunculus Hayek — Asteraceae

Native to the Mediterranean area; the basal leaves were used as medicine as far back as ancient Roman times. It was used, as was characteristic of bitter remedies, primarily as a digestive and liver aid, to help stimulate the appetite, provide relief from nausea, stomach ache, flatulence, and a sense of fullness. More recently it has been described as liver protective, a choleretic, and a cholagogue. As with many members of the Asteraceae, it contains bitter-tasting sesquiterpene lactones, although the most characteristic and active compounds are caffeoylquinic acids (e.g. chlorogenic acid; 1,5-dicaffeoylquinic acid, neochlorogenic acid, criptochlorogenic acid, plus cinarine – 1,3-dicaffeoylquinic acid – only in hot acqueous extracts) and flavonoids.

Various experimental studies have shown promising choleretic and digestive activities of the dry extract of artichoke leaves. Total extract, fenolic acids and caffeoylquinic acids all show choleretic effects both in vitro¹ and in vivo² and they increases gastrointestinal peristalsis.³

These experimental studies are partly supported by clinical investigations that have shown that artichoke preparations may relieve digestive complaints (sensation of fullness, loss of appetite, nausea and abdominal pain) through an increase in the formation and flow of bile, probably mainly due to the presence of flavonoids and caffeoylquinic acids, but also via the bitter-tasting sesquiterpene lactones.⁴ In fact, the German Commission E approves the use of fresh or dried artichoke leaf for dyspeptic problems due to its choleretic action,⁵ and the ESCOP monograph reports as indications digestive disorders such as stomachache, nausea, emesis, sensation of fullness, flatulence.⁶

A post-marketing surveillance study reported by Held⁷ included 417 patients with hepatic and biliary tract disease treated for four weeks with artichoke leaf extract (1% caffeoylquinic acids, 1500 mg/day). In 65-77 % of patients, abdominal pain, bloating, meteorism, constipation, lack of appetite, and nausea were eliminated after one week, and in 52-82% of patients, after four weeks.

A mode of action study (a crossover, randomized, double blind clinical study, vs. placebo, with one-day treatment periods separated by an eight-day washout period) using an aqueous dry extract (4.5-5:1) on 20 subjects with acute or chronic metabolic disorders, showed that administration of six capsules (total weight 1.92 g) intraduodenally caused a peak increase (100 to 150 % compared to baseline) in bile one hour later, which lasted for three hours. The study inferred, but did not demonstrate, therapeutic benefit for dyspepsia. It suffered from many shortcomings: the study was too short, the sample size was small, it wasn’t conducted on subjects with dyspepsia, and the product was not delivered orally.⁸

A second post-marketing surveillance study included 553 subjects with dyspepsia, who were administered an average of 1.5 g of dry extract (3.8-5.5:1) for an average of 43.5 days. There was a clinically relevant reduction in dyspeptic symptoms for 71% of the subjects in 6 weeks of treatment (66% flatulence, 76% abdominal pain, 82% nausea and 88% emesis).⁹

Walker, Middleton, and Petrowicz reported an analysis of a patient subset from the initial survey by Fintelmann and Menssen with key symptoms of irritable bowel syndrome (n=279). These patients experienced significant reductions in symptoms (emesis 95%, nausea 85%, abdominal pain 75%).¹⁰

In a similar open study that lasted six months on 203 subjects suffering from dyspepsia, there was an average reduction (after 21 days) of 66% of the same range of symptoms. The global efficacy was evaluated by the physicians as being good or excellent in 85.7% of the cases.¹¹

In a more recent double-blind, randomized controlled trial vs. placebo on 244 patients with

functional dyspepsia, the verum treatment (1920 mg dry extract/die) improved/reduced? symptoms and improved quality-of-life measures after six weeks.¹²

In an open, dose-ranging postal study, 454 healthy patients with self-reported dyspepsia were treated with a dry extract, at 320 or 640 mg daily. Both dosages reduced all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score.¹³ A subset analysis of the study, identifying post hoc 208 subjects suffering with IBS, showed a significant fall in disease incidence of 26.4% after 2 months.¹⁴

Thirty subjects with functional dyspepsia consumed an iced dessert with or without artichoke extract. The results show that ingestion of the dessert induces a reduction of symptom severity and range even without the extract, but that the presence of the extract intensifies the effects.¹⁵

A prospective cohort study on 311 patients with functional dyspepsia analyzed the efficacy of a commercial mixture of dry extracts of artichoke leaf (15% of chlorogenic acid – 150 mg per capsule), dandelion radix (Taraxacum officinalis – 2% of inulin), turmeric rhizome (Curcuma longa – 95% of curcumin) and rosemary (Rosmarinus officinalis) microencapsulated essential oil. After 60 days of treatment, a statistically significant gradual reduction in symptom severity was noted, and a global clinical response, defined as a 50% reduction in the total scores of all symptoms, was recorded in 38% of patients at 30 days.¹⁶

Taraxacum officinale G.H. Weber ex F. H. Wigg — Asteraceae

A perennial weed widely distributed in the warmer temperate zones of the Northern Hemisphere. Its roots and rhizomes have been used extensively since ancient times in Europe as a bitter tonic and for the treatment of various disorders such as dyspepsia, heartburn, spleen and liver complaints, hepatitis and anorexia.¹⁷

The intensely bitter-tasting compounds are sesquiterpene lactones of the eudesmanolide, guaianolide and germacranolide types¹⁸ (previously known as taraxacin) and are unique to Taraxacum. The drug contains also triterpene alcohols (taraxastane-type), phytosterols , lupane-type triterpene and hydroxycinnamic acids.¹⁹

In Germany, Commission E supports using Taraxacum officinale folia to treat loss of appetite, dyspepsia, bloating and flatulence, while radix with folia is recommended to treat disturbed bile flow, loss of appetite and dyspepsia.²⁰

ESCOP recommends T. officinale radix for restoring hepatic and biliary function, dyspepsia and loss of appetite.²¹

Intragastric administration of an aqueous or 95% ethanol extract of the whole plant (dose non specified) to rats increased bile secretion by 40% in over 2 hours.²²

Dandelion decoction administered by injection to dogs doubled the volume of bile secreted.²³ A similar effect was observed following intraduodenal administration to rats.²⁴

An herbal combination containing Calendula officinalis, Taraxacum officinale, Hypericum perforatum, Melissa officinale and Foeniculum vulgare reduced intestinal pain in 96% of 24 patients by the 15th day in an uncontrolled trial involving patients with chronic colitis. Defecation was normalized in patients with diarrhea syndrome.²⁵

A prospective cohort study on 311 patients with functional dyspepsia analyzed the efficacy of a mixture of dry extracts of artichoke leaf, dandelion radix, turmeric rhizome and rosemary essential oil. After 60 days of treatment, a statistically significant gradual reduction in symptom severity was noted; and a global clinical response – defined as a 50% reduction in the total scores of all symptoms – was recorded in 38% of patients at 30 days.²⁶

Silybum marianum (L.) Gaertn. — Asteraceae

Plant indigenous to North Africa, Asia Minor and southern Europe, have been used since ancient times for the treatment of gastrointestinal and hepatic complaints like anorexia,²⁷ colic and abdominal cramps,²⁸ and nausea.²⁹

It is nowadays mainly known for its important hepatoprotective and hepartoregenerative activity but, being a bitter remedy, it shows classic digestive activity, although the clinical evidence is lacking (Commission E recognizes this by suggesting its use as a treatment of dyspeptic complaints). The seeds contain a complex mixture of flavolignans termed silymarin, which seems to be the main active principle ingredient?.³⁰ Other important compounds are the flavonoids quercetin, dehydroksampferol and (+)-taxifolin, saponins, poliacetylenes and essential oils.

An experimental study has shown that intragastric administration of an acetone extract of fruit containing silybin increased the volume and dry mass of excreted bile in rats.³¹

Although there are no direct clinical data, Silybum marianum has been tested in a fixed preparation combining Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, Silybum marianum and Chelidonium majus. This preparation has shown a general activity on dyspepsia,³² in particular: a reduced acid output, increased mucin secretion, prostaglandin E(2) release and a decrease in leukotriene levels.³³ A second study showed protection against the development of gastric acidity rebound/reflux? and inhibited the serum gastrin level in rats.³⁴

Citrus limon (L.) Burmann fil. — Rutaceae

The rind has been used both in the West and in the East as a tonic digestive, strongly aromatic and slightly bitter, used in decoction and alcoholic extracts. In Traditional Chinese Medicine it is used to resolve gastrointestinal disorders such as abdominal and epigastric bloating, belching, nausea and emesis, inappetence and diarrhea, and in the West for colicky indigestions, abdominal bloating, slow digestion, and nervous dyspepsia. The juice has traditionally been used as a digestive, astringent, stomachic, antispasmodic and carminative, used for the treatment of inappetence, gastralgy, nausea, and gastric acid reflux.³⁵

The epicarp is very rich in an essential oil dominated by monoterpenes (60-95%) in particular R(+)-limonene (up to 70%), and linear aldheides (citrals), but also characterized by photoactive furocoumarins (more than 5%).³⁶ Also present are phenolic compounds, flavonoids, pectin and various organic acids from the juice.³⁷

Lemon juice and extracts exert both indirect and direct actions on gastrointestinal activity. Particularly interesting are the indirect (cognitive and sensory mediated) ones.

It is well known that both lemon aroma and flavor are sialagogues, that is, that they influence the cephalic phase of digestion (salivation). In an interesting study comparing the effects of different visual stimuli, Christensen and Navazech show that there is a stronger response (a higher salivary volume) to visual stimuli of acidic (lemon juice) and pungent foods (pizza with hot peppers).³⁸ Lemon odor and the introduction of lemon juice into the oral cavity both cause an increase in the volume of saliva, statistically higher than that caused by a non-stimulus (pure air or pure water).³⁹ Moreover, according to Davenport, the lemon juice seems to be able to influence not only the quantity but also the quality (in terms of compositions) of the saliva, which becomes richer in proteins.⁴⁰ This suggests that prior knowledge of the food items can modify the cephalic phase of digestion, and reinforces the thesis of a relationship between secondary metabolites and gastrointestinal physiology: the presence or the supposed presence of possibly hazardous substances (irritant, bitter, astringents, etc.) not only alters the salivary volume but increases the percentage of compounds like praline, which offer a certain degree of protection from irritant compounds such as tannins.

The study by Bauslaugh showed a relationship between salivation and gastrointestinal motility during olfactory stimulation,⁴¹ and it is well known that pepsinogen, gastrin and HCl secretions are influenced by cephalic stimulations,⁴² hence possibly by the organoleptic stimulation by lemon juice.

The palatability and the absence of gastrointestional adverse symptoms have already been tested in a commercial product containing lemon juice and various herb extracts.⁴³

Apart from sensory, indirect activities, lemon juice can directly affect gastrointestinal secretions. 100 ml. of orange and lemon juice have shown very potent stimulant action on pancreatic secretion (higher output, higher bicarbonate content, higher enzymatic content), compared to other stimuli, and the peak response was observed earlier (60 minutes for the juice, 90 minutes for the other stimuli). In general the juice had a response quantitatively and qualitatively comparable to secretin.⁴⁴

The fruit juice and some of its components (caffeic acid, ferulic acid, hesperidine, p-coumaric acid) show choleretic/cholagogue and antispasmodic action.⁴⁵

The essential oil and many of its components are rubefacient⁴⁶ and stimulant carminative;⁴⁷ limonene is myorelaxant and antispasmodic at high doses, as are many of the other essential oil components: a-pinene, a-terpinene, bergapten, b-pinene, cariophillen, geraniol, mircene, nerale, terpinen-4-olo.⁴⁸ Hence, they may? could play a role in the antispasmodic and carminative activity of lemon rind extract and lemon juice.

Pectin shows stomachic action and gastrointestinal protective activity.⁴⁹

Foeniculum vulgare Mill. — Apiaceae

Commonly employed as a culinary herb and as a remedy to improve digestion in traditional systems of medicine; they have been used since ancient Roman and Egyptian times as a valuable warming carminative and aromatic digestive. Fennel has? also had a persistent/consistent reputation as an ingredient in “gripe water” and other remedies for infant colic.

Given in the form of a homemade tea or infusion, fennel is a useful standby for dyspepsia, bloating and flatulence, and poor appetite.⁵⁰

It contains an essential oil mainly composed of trans-anethole (30-90%), (+)-fenchone (6-30%) and estragole (methylchavicol – ca. 5% ); and also contains flavonoids and coumarines.

Only a handful of modern clinical trials are reported in the literature, demonstrating – together with its widespread traditional use – a reduction in colic in babies, and a reduction in the symptoms of chronic colitis.

A randomized placebo-controlled trial tested a fennel seed oil emulsion, compared with placebo, on 125 infants, 2 to 12 weeks of age, diagnosed with colic. The emulsion eliminated colic in 65% of infants in the treatment group, compared to 23.7% of infants in the control group with an Absolute Risk Reduction (ARR) = 41%.⁵¹

A mixture containing chamomile (Matricaria recutita), fennel (Foeniculum vulgare) and lemon balm (Melissa officinalis) was found to have significant benefits in the treatment of infantile colic in a double-blind, placebo-controlled study on 93 breastfed infants, treated twice a day for 1 week. Crying time reduction was observed in 85.4% of subjects.⁵²

However, two subsequent experimental studies in mice, while confirming the reduction of intestinal motility at dosages similar to those used in human trials, showed that the major contribution to the antispasmodic activity is due to Matricaria recutita and Melissa officinalis.⁵³

In an uncontrolled clinical study twenty-four patients with chronic non-specific colitis were treated with a herb combination of Taraxacum officinale, Hipericum perforatum, Melissa officinaliss, Calendula officinalis and Foeniculum vulgare. As a result of the treatment, the spontaneous and palpable pains along the large intestine disappeared in 95.83 per cent of the patients by the 15th day of their admission to the clinic.⁵⁴

Backed by weaker clinical evidence, but supported by very widespread and validated traditional use, are the indications for digestive complaints: dyspepsia with bloating and flatulence, poor appetite and indigestion.⁵⁵

In animal studies, fennel has been shown to be antispasmodic, prokinetic and secretagogue.

Isolated trans-anethole reduced contractions of a rat diaphragm preparation;⁵⁶ the essential oil seems able to reduce smooth muscle spasms in various in vitro models,⁵⁷ but this activity seems concentration -dependent, with spasmogenic effect at lower doses, and spasmolytic at higher ones.⁵⁸

The ethanol extract⁵⁹ and the aqueous infusion show⁶⁰ spasmolytic effects.

Intragastric administration of 24.0 mg/kg bw of the fruits increased spontaneous gastric motility in unanaesthetized rabbits.⁶¹

An aqueous extract of the fruits (10% p/v), administered to anaesthetized rats via gastric perfusion at 0.15 ml/minutes, significantly increased gastric acid secretions.⁶²

The admixture of 0.5% fennel fruits to the diet of rats for 6 weeks reduced the food transit time by 12%,⁶³ while the admixture of fennel fruits (0.5%) and mint (1%) for 8 weeks stimulated a higher rate of secretion of bile acids in rats, and a significant enhancement of secreted intestinal enzymes, particularly lipase and amylase.⁶⁴

Melissa officinalis L. — Lamiaceae

A very popular traditional herb used in infusion for restlessness and dyspepsia, especially among children. It contains very low amounts of essential oil (0.02-0.37%), organoleptically characterized by the aldheydes geranial and neral, and 6% of rosmarinic acid.

There is a dearth of clinical research on the digestive activity of Lemon balm, and the only two existing clinical studies are based on formulas and not on the single herb extract.

A randomized, double-blind, placebo-controlled trial showed significant improvement of colic in babies given a chamomile, fennel and lemon balm preparation compared with babies given a placebo.⁶⁵

A fixed commercial combination of extracts of Melissa officinalis, Mentha spicata and Coriandrum sativum was tested on 32 irritable bowel syndrome patients and compared to placebo for 8 weeks in a clinical study. The study shows that the combination reduces the severity and frequency of abdominal pain and of bloating better than placebo.⁶⁶

There is little doubt that the ethanol fraction of the plant, and in particular the volatile oil component, is responsible for the antispasmodic activity of the herb. The ethanol extracts and the essential oil have shown inhibition of artificially-induced contraction of smooth muscles,⁶⁷ but there are also contrasting data.⁶⁸ The essential oil was more effective than its isolated components, but it has been observed that neral and geranial were more active than citronellal and β-cariophillen.⁶⁹

Mentha xpiperita L. — Lamiaceae

Without doubt one of the most world-renowned aromatic plants, and the most important one in terms of annual production, both of the dried herb and essential oil. It has always been used in traditional learned and folk medicine as a carminative, antispasmodic, antiemetic and digestive, both in the West and in the East.

It contains a large amount of essential oil characterized by the presence of a monoterpene alcohol, menthol, which is responsible for many of the activities of the herb and for its characteristic aroma. It also contains flavonoid compounds and hydroxycinnamic compounds.⁷⁰

Peppermint has also been the focus of a fair amount of good quality research, both experimental and clinical, that supports many of the traditional claims. In particular it has shown antispasmodic, carminative and choleretic activities.

The essential oil reduces intracolonic pressure.⁷¹ In an open study of 20 patients, peppermint essential oil used alongside a colonoscope relieved colonic spasms,⁷² and it had the same effect when administered with barium enemas.⁷³

The essential oil is also able to reduce tension in hypertonic intestinal smooth muscles? in cases? of IBS.⁷⁴

In healthy volunteers, intragastric administration of a dose equivalent to 180 mg peppermint oil, reduced intraesophageal pressure within 1-7 minutes of infusion.⁷⁵

Oral administration of the essential oil delayed the gastric emptying time in healthy volunteers and in patients with dyspepsia,⁷⁶ and it slowed small intestinal transit time in 12 healthy volunteers.⁷⁷

A combination of essential oils (90 mg of peppermint and 50 mg of caraway in an enteric-coated capsule) was tested in various studies.

The combination produced smooth muscle relaxation of stomach and duodenum;⁷⁸ in a double-blind, placebo-controlled multicentre trial with 45 patients it improved symptoms of dyspepsia, reducing pain in 89.5% of patients and improving Clinical Global Impression scores in 94.5% of patients.⁷⁹

The same combination tested on 223 dyspeptic patients in a prospective, randomized, reference and double-blind controlled multicentre trial, significantly reduced pain,⁸⁰ and tested on 96 outpatients with dyspepsia, significantly reduced pain by 40% and reduced sensations of pressure, heaviness and fullness.⁸¹

The formula was shown to be as effective as Cisapride in reducing both the magnitude and frequency of pain,⁸² and it had a relaxing effect on the gall bladder.⁸³

In a systematic review of herbal medicines for functional dyspepsia, the authors found 17 randomized clinical trials, nine of which involved peppermint and caraway combination preparations. Symptoms were reduced by all treatments; 60- 95% of patients reported improvements in symptoms.⁸⁴

The essential oil and fractions of it have been shown to have gastrointestinal smooth muscle relaxant activity and to inhibit spontaneous smooth muscle contractions both in vitro and in vivo.⁸⁵ Some data are also available on the antispasmodic effects of the ethanol extract, as well as flavonoids isolated from the leaf.⁸⁶

The carminative activity of peppermint is, in fact, probably due to a relaxing action on the gastrointestinal sphincters,⁸⁷ and to a reduction of the volume of intestinal gas by the antimicrobial, anti-fermentative and antifoaming effects of the essential oil.⁸⁸

Choleretic activity (increased bile secretion and increased synthesis of bile acids) has been demonstrated in animal models for the herb, various flavonoid fractions, flavomentin, the essential oil and menthol.⁸⁹ The effect probably derives from the spasmolytic activity of menthol and other terpenes on the Oddi’s sphincter.⁹⁰

The essential oil seems to be acting by interacting with smooth muscle Ca channels probably by inhibiting the influx of extracellular Ca ions without effects on their intracellular mobilization, and menthol has been isolated as the most important compound.⁹¹

The antiemetic and prokinetic effects of peppermint oil and of (-)-menthol are due at least partly to their binding to the 5-HT(3) receptor ion-channel complex, in a manner similar to that of ginger.⁹²

Matricaria chamomilla L. — Asteraceae

It has been a highly popular family herb since antiquity, generally used for nervous excitability and digestive disorders, stomach cramping, dyspepsia and flatulence. This tradition of use notwithstanding, much of the research data concentrate on antinflammatory and vulnerary activity.

However, its antispasmodic and relaxant effects provide a theoretical basis for its use in gastrointestinal conditions, and the German Commission E approves chamomile for gastrointestinal spasms and inflammatory diseases of the gastrointestinal tract.

It contains an essential oil, flavonoids (in particular apigenin and its related flavonoid glycosides), and proazulenes (sesquiterpene lactones) including matricin, matricarin and desacetlymatricarin.⁹³

Although a well-known and widely used herb, almost no substantial clinical research exists into the remedy’s use for digestive disorders, and only a few well designed clinical studies are available There are however some experimental studies pointing to antispasmodic activity of the plant and its constituents on smooth muscle.

In an open, multicentre study, 104 patients with gastrointestinal complaints (gastritis, flatulence and mild intestinal spasms) were treated for 6 weeks with an oral chamomile extract (standardized for 0.05% alpha-bisabolol and 0.15% apigenin-7-glucoside), with 44.2% of subjects self-reporting symptom free.⁹⁴

In a double-blind study, a herbal decoction (150 mL/day containing Matricaria chamomilla, Verbena officinalis, Glycyrrhiza glabra, Foeniculum vulgare and Melissa officinalis) was tested for seven days on 68 healthy infants with colic. 57% of the infants experienced relief compared to 26% in the placebo group.⁹⁵

In another trial – prospective, double-blind and randomized – a preparation containing chamomile extract and pectin was tested on children aged 6 months to 5.5 years with uncomplicated diarrhea. The preparation reduced duration and severity of diarrhea significantly faster than the placebo.⁹⁶

Whole extracts and isolated components demonstrate a dose-dependent antispasmodic effect in vitro.⁹⁷ The major activity was related to (-)-α-bisabolol, the cis-spiroethers,⁹⁸ and the flavonoids (in particular apigenin).⁹⁹ Bisabolol oxides A and B, the essential oil, other flavonoids and the small amount of coumarins were less active in vitro.¹⁰⁰

The mechanisms for chamomile antispasmodic activity are still unclear. However, at least one mechanism has been proposed: the inhibition of cAMP- and cGMP-phosphodiesterases by flavonoids.¹⁰¹

Chamomile also increases production of bile by the liver.¹⁰²

Cymbopogon citratus (DC.) Stapf. — Poaceae

An aromatic tropical grass, whose essential oil is characterized by the presence of citrals (up to 90%) and monoterpenes. It also contains triterpenoids and flavonoids. It has been traditionally deemed a carminative, a light sedative, an analgesic, an antiemetic and an antispasmodic.¹⁰³

It is most frequently used as a remedy for gastrointestinal disorders, in particular stomachache, acids indigestion, abdominal cramps, diarrhea, and dyspepsia.¹⁰⁴

There are, however, no clinical data available, and only a few experimental data showing that di essential oil is strongly antispasmodic and carminative.¹⁰⁵

Aloysia citrodora Palau — Verbenaceae

Used in Latin America, USA and Europe as an aromatic ingredient in fruit salads, jams, cold drinks or as an infusion.¹⁰⁶ The plant is rich in an essential oil dominated by citrals. It also contains flavonoids, phenolic acids and tannins.¹⁰⁷

Various authors report its digestive,¹⁰⁸ spasmolytic,¹⁰⁹ stomachic,¹¹⁰ and carminative activity,¹¹¹ and it has been used for gastrointestinal and spasmodic disorders, e.g. flatulence, dyspepsia, colic, nausea, etc.¹¹²

There are, however, no clinical data in support of these claims, but there are some experimental data.

The essential oil and many of its components are aperitive, analgesic/antinociceptive, and antispasmodic.¹¹³ . Cineole and borneol are choleretics and secretagogues.¹¹⁴

Chlorogenic acids could act synergistically with the essential oil as digestives, and vitexin shows an antispasmodic activity.¹¹⁵

Caceres reports of a clinical study (impossible to track down) which allegedly shows a positive effect of the plant on inappetence, slow digestion, gastralgy and emesis.¹¹⁶

Illicium verum, Hook. f. — Illiciaceae and Pimpinella anisum L. — Apiaceae

Both popular aromatic remedies: the first in China, where it is a component of the very famous five spice powder, together with cinnamon/cassia, cloves, fennel and Sichuan pepper; and the second in Europe and North America. Both are used quite often in food recipes (Star Anise in garam masala spice blends and the rice dish biriyani, and Aniseed in many flavored drinks)

These two fruits are deemed carminative and stomachic and they are taken internally in the treatment of abdominal pain and digestive disturbances. They are often included in remedies for indigestion, and they are believed to be effective for children’s digestive upsets, including colic pain.¹¹⁷ Some people chew the fruits after meals for better digestion. The essential oils are used as a stimulant, stomachic, carminative.

Star Anise is characterized by its essential oil content, particularly rich in prenylated C6-C3 compounds (phenylpropanoids: anethole and its analogues, estragole, eugenol), but contains also neolignans and sesquiterpenes in addition to several common flavonoids, diterpenoids and triterpenoids.¹¹⁸

Aniseed contains an essential oil whose major component is trans-anethole.

Their traditional use notwithstanding, there is no clinical evidence supporting it, but there are limited experimental data. The essential oil of Aniseed and trans-anethole both seem to act as antispasmodics in vitro and in vivo on animal models. They antagonize artificially-induced spasms and decrease the rate and extent of contractions of smooth muscle preparations,¹¹⁹ possibly via Ca-channel blockage and the NO-cGMP pathway.¹²⁰ Many authors point to antispasmodic,¹²¹ carminative¹²² and digestive activities,¹²³ suggesting use for abdominal colic, inappetence, dyspepsia, flatulence.

Zingiber officinale Roscoe — Zingiberaceae

Probably one of the oldest domesticated spices in human history. It has a prominent role in Asian systems of medicine where it is used for the treatment of dyspepsia, flatulence, colic, vomiting, diarrhea, spasms and to stimulate the appetite, but over the centuries has become part of western cuisine and pharmacopoea as well.¹²⁴

The ginger rhizome contains an essential oil (1-4%) and a resin, known collectively as oleoresin. The chief constituents of the essential oil are the sesquiterpenes a-, and b-zingiberene, which are responsible for the characteristic aroma. The resin contains pungent phenolic compounds called gingerols, gingerdioles and gingerdiones, and their corresponding dehydration products known as shogaols.¹²⁵

According to the studies, ginger exerts several effects in the gastrointestinal tract: secretagogue (saliva, bile, pancreatic juices, gastric juices), antiemetic, intestinal antispasmodic and gastric prokinetic.

It stimulates the flow of saliva, bile and gastric secretions.¹²⁶ An extract containing the oleoresin and administered intraduodenally to rats produced an increase in the bile secretion, while the aqueous extract was not active. These results point towards the oleoresin as the active principle, and in fact it was shown that [6]- gingerol and [10]-gingerol were mainly responsible for the cholagogic effect.¹²⁷ An oral dose of ginger enhanced rat pancreatic lipase, sucrase and maltase activity, and stimulated trypsin and chymotrypsin.¹²⁸

The essential oil,¹²⁹ a 95% ethanol extract,¹³⁰ a hot water extract¹³¹ and of a formula containing ginger, Pinellia ternata, Citrus aurantium, Pachyma hoelen, and Glycyrrhiza glabra,¹³² were all shown to possess antispasmodic activity on intestinal smooth muscles.

The rhizome extract, shogaols and gingerols all increased gastric motility in animal models and in humans.

In a clinical study ginger, assumed before meals, increased number and frequency of contractions in the corpus and in the antrum, and frequency of contractions in the duodenum. Assumed after meals, it contributed to motility to a lesser degree.¹³³

Ginger and a Japanese formula (Dai-Kenchu-To) containing ginger, Zanthoxylum fruit and ginseng root, both induced phasic contractions in the gastric antrum..¹³⁴

Previous clinical data had shown that ginger did not affect the gastric emptying rate.¹³⁵ There were suggestions, however, that this lack of activity was due to low dosage of ginger rhizome.

The prokinetic activity was confirmed in other in vitro and in vivo tests, that showed that ginger extract enhances the intestinal transit of charcoal meal and that it acts through a spasmogenic, dose-dependant cholinergic agonistic effect on the post-synaptic muscarinic M3 receptors in the stomach fundus. It also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors. At the same time it shows spasmolytic activity at the intestinal level (also possessed by 6-shogaol, 6-gingerol, 8-gingerol and 10-gingerol), probably through a Ca2 + antagonist effect.¹³⁶

Various constituents found in Ginger, 6-, 8- and 10-gingerol, 6-shogaol, and galanolactone, act as serotonin receptor antagonists, which could explains the antispasmodic effects on visceral smooth muscle.¹³⁷ They could exert their effect by binding to receptors in the signal cascade behind the 5-HT(3) receptor ion-channel complex, perhaps substance P receptors or muscarinic receptors.¹³⁸

At the same time two compounds (10-shogaol and 1-dehydro-6-gingerdione), and particularly the whole lipophilic extract, have shown to partially activate the 5-HT(1A) receptor (20-60% of maximal activation).¹³⁹

The serotonin receptor antagonist activity may partly explain the antiemetic effect of ginger, since these receptors do mediate peristalsis and emesis,¹⁴⁰ and the constituents active on these receptors were also active as anticholinergic antiemetics, in the following descending order of potency: 6-shogaol> or= 8-gingerol>10-gingerol> or = 6-gingerol.¹⁴¹

Many clinical studies have shown the positive antiemetic effects (prevention and treatment of nausea) of Ginger and many of its constituents (shogaols, gingerols, zingerones) under different circumstances.¹⁴²

A systematic review of six controlled studies found that Ginger was more effective than placebo in some studies of postoperative nausea and vomiting. Of the three studies conducted in postoperative nausea and vomiting, two suggested that Ginger was superior to placebo and equally as effective as metoclopramide, whereas one found no benefit.¹⁴³

A recent Cochrane review on 20 trials concluded that Ginger might be of benefit in cases of nausea and emesis, but that the evidence to date was weak.¹⁴⁴

Capsicum annuum L. — Solanaceae

A native American plant that has been exported all over the world and has conquered both the cuisine and the medicine of Europe, Africa and Asia, in a very interesting reverse spice journey.

Capsicum’s main active chemical group is that of the capsaicinoids, a group of pungent alkaloids whose prototype is capsaicin (8-methyl-N-vanillyl-6-nonenamide), which has been tested for its analgesic effect.¹⁴⁵

The scientific evidence about capsicum and capsaicinoids and their effects on the gastrointestinal tract is rather contrasting. It is well known that capsaicin can interact with the vanilloid receptor VR1 and that this interaction can lead to direct and indirect effects. The interaction causes a selective impairment of the activity of nociceptive C-type fibers carrying pain sensations to the central nervous system, causing, on chronic dosage, analgesic and anti-inflammatory effects.¹⁴⁶ These have been evaluated in patients suffering from heartburn¹⁴⁷ and functional dyspepsia, with encouraging results.¹⁴⁸

The data on gastric secretions and motility are less clear: some studies found a stimulation of gastric emptying¹⁴⁹ and of secretions,¹⁵⁰ others found no difference,¹⁵¹ and others even found a reduction in activity.¹⁵²

The intake of red pepper has caused a reduced energy intake, suppression of hunger and increased satiety,¹⁵³ an activity in line with a possible effect on the secretion of CCK.

Carica papaya L. — Caricaceae

A tropical plant original to the dry flatlands of Mesoamerica (South Mexico and Guatemala). The fruit is one of the most important fruits in the tropics and worldwide, and its fermented products are well known in the field of FF for its antioxidant properties.¹⁵⁴ Its juice and jams made out of the fruit pulp are used also for digestive complaints (constipation, diarrhea, dyspepsia, enteritis), and it is supposed to possess carminative, cholagogue and digestive activities.¹⁵⁵ It contains various proteolytic enzymes like papaine and chymopapaine; carotenoids, monoterpenoids; and organic acids.¹⁵⁶

Papaine is a proteasis (similar to bromelin) with wide-range specificity, it hydrolyses polypeptides, amides and esters, particularly when used in an alkaline environment, and is used in digestive disorders; chymopapaine is very similar but less active. Although the mature fruit is less rich in papaine than the unripe one, the quantity is still sufficient to give a biological bases to the traditional digestive claims for the fruit and its derivatives.

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Note

1 ESCOP Monographs on the medicinal uses of plant drugs. Devon, European Scientific Cooperative on Phytotherapy, 2003

2 Preziosi P, Loscalzo B “L’azione sulla coleresi, sul colesterolo ematico e sulla lipoidosi colesterolica del principio attivo del carciofo e di sostanze ad esso correlate”. Fitoterapia. 1956; 27:666-72; Bombardelli E, Gabetta B, Martinelli EM, “Gas-liquid chromatographic and mass-spectometric investigation of Cynara scolymus extracts”. Fitoterapia. 1977; 48:143-152.

3 Lietti A. “Choleretic and cholesterol lowering properties of two artichoke extracts”. Fitoterapia. 1977; 48:153-58

4 Kraft K “Artichoke leaf extract–Recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts”. Phytomedicine. 1997; 4 (4): 369-378; Wegener T, Fintelmann V. “Pharmacological properties and therapeutic profile of artichoke (Cynara scolymus L.)”. Wien Med Wochenschr. 1999;149(8-10):241-7.

5 Blumenthal M, Busse W, Hall T, Goldberg A, Gruenwald J, Riggins C, Rister S, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S Klein. Austin, TX: American Botanical Council, 1998

6 ESCOP 2003 Op. Cit.

7 Held C “Artischoke bei Gallenwegsdyskinesien: Workshop “Neue Aspekte zur Therapie mit Choleretika.” Kluvensiek. 1991; 2: 9. Cited in Kraft 1997 Op. Cit.

8 Kirchhoff R, Beckers CH, Kirchhoff GM, Trinczek-Gartner H, Petrowicz O, Reimann HJ “Increase in choleresis by means of artichoke extract”. Phytomedicine. 1994; 1: 107-115

9 Fintelmann V. “Antidyspeptische und lipidsenkende Wirkungen von Artischockenextrakt: Ergenbnisse klinischer Untersuchungen zur Wirksamkeit und VertraNglichkeit von Hepar-SL forte an 553 Patienten”. Zeitschrift fur Allgemeinmedizin. 1997; 72 (Suppl. 2): 3-19. Cited in Kraft 1997 Op. Cit.; Fintelmann V, Menssen HG. “Aktuelle Erkenntnisse zur Wirkung von ArtischockenblaNtterextrakt als Lipidsenker und Antidyspeptikum”. Deutsche Apotheker-Zeitung. 1996; 136: 1405. Cited in Kraft 1997 Op. Cit.;

10 Walker AF, Middleton RW, Petrowicz O “Artichoke leaf extract reducessymptoms of irritable bowel syndrome in a post-marketing surveillance study”. Phytotherapy Research. 2001; 15 (1): 58-61

11 Fintelmann V, Petrowicz O Naturamed. 1998; 13:17-26

12 Holtmann G, Adam B, Haag S, Collet W, Grunewald E, Windeck T. “Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial”. Aliment Pharmacol Ther. 2003 Dec;18(11-12):1099-105

13 Marakis G, Walker AF, Middleton RW, Booth JC, Wright J, Pike DJ. “Artichoke leaf extract reduces mild dyspepsia in an open study”. Phytomedicine. 2002 Dec;9(8):694-9.

14 Bundy R, Walker AF, Middleton RW, Marakis G, Booth JC. “Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis” J Altern Complement Med. 2004; Aug;10(4):667-9)

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16 Sannia A. “Phytotherapy with a mixture of dry extracts with hepato-protective effects containing artichoke leaves in the management of functional dyspepsia symptoms”. Minerva Gastroenterol Dietol. 2010 Jun;56(2):93-9

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18 Hansel R, Kartarahardja M, Huang JT, Bohlmann F. “Sesquiterpenlacton-beta- D-glucopyranoside sowie ein neues Eudesmanolid aus Taraxacum officinale“. Phytochemistry. 1980; 19:857-861; Zielinska, K. and W. Kisiel. “Sesquiterpenoids from roots of Taraxacum laevigatum and Taraxacum disseminatum“. Phytochemistry. 2000; 54: 791-794

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20 Blumenthal et al 1998 Op. Cit.

21 ESCOP 2003 Op. Cit.

22 Bohm K “Studies on the choleretic action of some medicinal plants” Arzneimittelforschang. 1959; 9:376-378

23 ESCOP 2003 Op. Cit.

24 ESCOP 2003 Op. Cit.

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26 Sannia A. 2010 Op. Cit.

27 Fleming, T. et al. PDR for Herbal Medicine, 1st ed., Medical Economics Co., Montvale, NJ, 1998

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