Herbal remedies for GI disorders

Dr. Hajhashemi

Dept. of Pharmacology

Isfahan University of Medical Sciences

Some Examples

Hepatica leaves have 3 lobes,just like the liver

Snakeroot

Walnut: looks sort of likea brain!

Tomatoes are red and havefour chambers, just like the heart.

lungwort

Active Principles

• A big idea from the early 1800’s: The reason that certain plants are effective against particular diseases is because they contain specific chemical compounds (the active principles) , with the rest of the plant material irrelevant.

– If you isolate (or synthesize) the active principle, you can control the dosage people are given and avoid giving them other plant compounds that might have bad side effects.

– In contrast, the amount a plant contains can vary with environmental conditions, age of the plant, the plant’s genetics, and many other factors.

– Also, it is possible to determine whether a given plant is actually effective, or which parts of mixtures are important.

• This concept led to people trying to extract the active principles from plants. For instance: which works better, soaking the plant material in cold water, hot water, alcohol, etc.? Which part of the plant produces the most active principle?

– Lots of help from alchemy, the precursor to modern chemistry.

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Digoxin

• The active chemical compounds in foxglove were isolated in the early 1900’s. They are several steroid glycosides, with the most active one being digoxin. It is still used in treating congestive heart failure.

• Digoxin increases the pumping force of the heart muscles. Too much can lead to a heart attack.

• Heart disease is the leading cause of death in the US. Dropsy was very common 200 years ago, but it is easily treated today.

Coumarin and Blood Clotting• Coumarin is a chemical compound that produces the smell of

freshly mown grass. It is used in the perfume industry, as a substitute for vanilla, and as a flavoring agent for tobacco.

• Coumarin can be converted into a powerful anti-coagulant by enzymes found in fungi.– The blood doesn’t clot, causing the victim to bleed to death.

• Origin: In the 1920’s, cows at Wisconsin dairy farms started bleeding to death after de-horning or castration, and some just spontaneously. A little observation showed that it occurred after that had eaten hay that had been made from sweet clover and was moldy. Non-moldy hay had no effect.

• Chemists at the University of Wisconsin developed an assay for blood clotting using rabbits, and after several years of effort, they isolated the active compound.

More Coumarin• Clover makes good silage: cows like the

way it tastes. Care must be taken to prevent fungal infection, which converts the sweet-smelling coumarin to the anti-coagulant dicoumarol.

• It proved to be useful for preventing blood clots, which can kill by blocking blood circulation in the heart or brain.

• Once dicoumarol was isolated, various chemical modifications were tried, and soon a much stronger one, warfarin, was created.

– Named for the Wisconsin Alumni research Foundation (WARF).

• Warfarin interferes with vitamin K, which is needed for blood clotting. The antidote to warfarin is large doses of vitamin K.

Ephedrine• Ephedrine is a stimulant and nasal decongestant. It is

chemically similar to amphetamines. It is an alkaloid derived from plants in the genus Ephedra, which (unlike almost all other plants we are examining) is a gymnosperm.

• It has long been used in traditional Chinese medicine to treat asthma and bronchitis.

• In sports, ephedrine is considered a performance-enhancing drug and is banned.

• The illegal dugs methamphetamine and MDMA (Ecstasy) can be made relatively easily from ephedrine and its close mimic pseudoephedrine (also found in plants). For this reason, most states regulate the amount you can buy.

– In Illinois you are required to show identification, give them your address, and you can only but 1 package a day.

Reserpine and Schizophrenia

• Snakeroot is the common name of several unrelated plants with long coiled roots. It fits the Doctrine of Signatures quite well, and so it has been used to treat snakebite in several different cultures.

• We are concerned here with Rauwolfia serpentina, the snakeroot that grows in India. It is also used in traditional Chinese medicine, and was discovered by the semi-legendary emperor Shen Nung. It was used as a general poison antidote, and as a tranquilizer and cure for insanity.

• In the 1950’s, the alkaloid reserpine was isolated from snakeroot. It acts as a sedative, and was used as a treatment for schizophrenia. It also lowered blood pressure

• Today, resperine is mostly used to combat high blood pressure. It causes the blood vessels to relax. However, other drugs have taken its place. Hypertension is a major medical issue, so much scientific effort goes into finding drugs to control it effectively. The sedative effects of reserpine are a strongly negative side effect for this use.

Drugs from plant originPhysostigmine Pilocarpine

Atropine Hyoscine

Ephedrine Digoxine

Quinidine Morphine

Vincristine Vinblastine

Paclitaxel Colchicine

Extracts vs. Active principles

Colic

• The mother of a newborn infant asks you about natural remedies for her baby’s colic. The baby is crying 4 hours a day. They’ve tried car rides, bouncy seats, etc.

• The grandmother has recommended Gripe Water, star anise, and fennel tea

• What are these things and are they safe?

Gripe Water

• Traditionally – dill extract ± bicarbonate (Woodard’s™), ± alcohol;

• Dill, fennel and caraway are spasmolytics

• Some include ginger, fennel (Baby’s Bliss™), chamomile, cinnamon and other herbs (Wellements™)

• Some contain homeopathic remedies and activated charcoal (eg. Colic Calm™)

• GRAS; allergies possible; small RCTs suggest benefits

Supermint

Flatulence

Sugar Malabsorption in Functional Abdominal

Bloating• 36 pts with functional abdominal bloating

• 72% had sugar malabsorption (6 lactose, 12 fructose plus sorbitol, and 8 both)

• 65% pts with malabsorption had symptoms of sugar intolerance during the breath test

Probiotics- possible mechanism

• Changes in the relative production of anti-inflammatory to proinflammatory cytokines

• Colonic bacteria metabolize nutrient substrates with the formation of gas and production of flatulence

• Flatulence induce propulsive contractions and accelerate transit, or enhance fluid and sodium absorption in the Colon

Pharmacological Therapies• Gas-Reducing Substances: silicone

derivates, charcoal or simethicone- questionable efficacy

• Enzymatic preparations = popular (data???)

• Tegaserod (5-HT4 receptor partial agonist) effective in IBS w bloating

• Peppermint oil - has a spasmolytic effect (menthol= CCB)

Nausea and Vomiting

Antidopaminergics

5-HT3 antagonists

Antihistaminic

Ginger for Nausea

• Numerous RCTs suggest benefits of ginger in preventing and treating nausea

Zingiber officinale (Ginger)

Parts Used: RootNausea & vomiting, travel sickness, digestive symptoms – colic & wind

To treat vertigo Arthritis

Decreases cardiovascular riskProphylaxis for migraines (with feverfew)Topical – ginger compress for mastitis

Cautions: low dose in children, low dose 1 week before surgery.

Ginger has been reported to be effective as a prophylactic against seasickness. Ingestion of powdered ginger root 1 g was found to significantly reduce the tendency to vomit and experience cold

sweating in 40 naval cadets, compared with 39 cadets who received placebo. Powdered ginger root 1.88 g has been reported to be superior to dimenhydrinate 100 mg in preventing the gastrointestinal symptoms of motion sickness induced by a rotating chair.

A systematic review of six randomised controlled trials of ginger preparations included three trials involving patients with post-operative nausea and vomiting, and three further trials in patients with seasickness (motion sickness), morning sickness (emesis of pregnancy) and cancer chemotherapy-induced nausea (one trial in each condition). Two of the three studies assessing the effects of ginger in post-operative nausea and vomiting found that ginger was more effective than placebo and as effective as metoclopramide in reducing nausea.

A randomised, double-blind, crossover trial involving women with nausea of pregnancy assessed the effects of capsules of powdered ginger root 250 mg, or placebo, administered orally four

times daily for four days. It was reported that symptom relief was significantly greater during treatment with ginger than with placebo, and that significantly more women stated a preference.

Dyspepsia

• Iberogast™, German remedy containing 8 herbs: Iberis amara, Chelidonii, Cardui, Melissae folium, Carvi, Liquiritiae radix, Angelicae, Matricariae, Menthae piperitae, Mentha spicata

• Meta-analysis of studies in 595 adults shows positive effects on dyspepsia in adults (Melzer J, 2004)

Peptic ulcer

Glycyrrhiza glabra

Licorice: Glycyrrhiza glabra

• Contains: glycyrrhizin, glycyrrhizic acid, polyphenols, and polysaccharides

• Inhibits 11 beta-hydroxysteroid dehydrogenase + other enzymes involved in the metabolism of corticosteroids. → increased cortisol levels

• Anti-inflammatory and mineralocorticoid effects (BP, edema)

Aloe vera

Aloe veraIs useful for GERD

Reduces acid and pepsin secretions

Has cytoprotective effect

Has shown good activity in IBS and ulcerative colitis

Affects immune system

Helps healing burns and wounds

Herbs effective against H. pylori

 

GingerThe gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since H. pylori is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the anti-H. pylori effects of ginger and its constituents were tested in vitro.

GingerThe methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a MIC range of 6.25 to 50 μg/mL. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all H. pylori strains with an MIC range of 0.78 to 12.5 μg/mL and with significant activity against the CagA-positive strains.

Turmeric  Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa L.), has been shown to prevent gastric and colon cancers in rodents. H. pylori is a group 1 carcinogen and is associated with the development of gastric and colon cancer. A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H. pylori, including 5 CagA-positive strains. Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 6.25 -50 μg/mL.

ThymeA popular herbal remedy in ancient Egypt, Greece and Rome, thyme was mainly used for headaches, digestive problems, respiratory illness, and as a mood-enhancer. Thyme was very effective at inhibiting the bacteria. Thyme extract was compared with several antibacterials; it had a significant inhibitory effect on H. pylori.

Licorice 

In a recent study at the Institute of Medical Microbiology and Virology, Germany, researchers found that licorice extract produced a potent effect against strains of H. pylori that are resistant against clarithromycin.

Berberine

  Berberine is a plant alkaloid isolated from the roots and bark of several plants including Berberis vulgaris. Berberine is known to have antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. More recently, berberine had been demonstrated to be effective against H. pylori.

Constipation

• Mineral oil, bisacodyle, lactulose, MOM

• Senna, Cascara, Castor oil, Psyllium

Fiber for constipation

• It depends (dried fruit anyone?)• Fiber is safe if taken with sufficient

water; no intestinal obstruction; no allergies– Bran– Psyllium (Plantago. ovata and P.

psyllium)– Flax seeds also contain lignans and

omega three fatty acids

• Side effects: flatulence, abdominal pain, diarrhea, dyspepsia, nausea

Psyllium

psyllium seeds are bulk laxatives. They absorb water in the gastrointestinal tract to form a mucilaginous mass which increases the volume of faeces and hence promotes peristalsis.

Uses and Administration

They are used in the treatment of constipation, especially in diverticular disease and irritable bowel syndrome , and when excessive straining at stool must be avoided, for example after anorectal surgery or in the management of haemorrhoids.

Dose The usual dose is about 3.5 g one to three times daily by mouth, although higher doses have been given. It should be taken immediately after mixing in at least 150 mL water or fruit juice. The full effect may not be achieved for up to 3 days.

ADR Preexisting complaints such as flatulence and bloating may worsen during the first few days of treatment, but subside during the further course of treatment.

Stimulant laxative herbs

• Cascara sagrada (Rhamni purshiana) and Senna (Senna folum); castor oil

• FDA approved for patients 2 years and older

• Use sparingly and briefly• Chronic use can lead to dependence• Side effects: cramping, diarrhea,

severe diaper rash

Cassia angustifolia

Senagol syrup

Senagraph

Senaline

Senamed

C-lax

Golghand majun

1-2 teaspoonful tid, 0.5h after meals

Satureja hortensis

Fig. 1. Effect of SHEO and dicyclomine on tension development to 80 mM KCl in isolated ileum of rats. Sigmoidal curve fitted through the points in presence of dicyclomine (square; n=6). The line through the circles shows the response to SHEO (n=6). Ordinate scale, response expressed as percent of the control response to KCl (80 mM) prior to addition of drugs; abscissa scale, log10 concentration of drugs. The points are mean and the vertical bars show the S.E.M.

Lomex oral dropLomex soft capsule

Standardized :

carvacrol (17.5-22.5 mg in each capsule)

IBD

Immune system

Greater expression of cytokines such as interleukin (IL)-1-β, IL-6, IL-12, tumor necrosis factor α (TNF-α) and interferon (IFN)-γ were demonstrated in patients with IBD. Recent meta-analyses confirmed the efficacy of anti-TNF-α drugs for induction of remission in UC but not CD.

Oxidative stress

Recent studies have shown decreased total antioxidant capacity and increased reactive oxygen molecules in patients with IBD

Microbes

Total microbial count is higher in CD. However, current meta-analyses have only confirmed the efficacy of antibiotics for CD but not probiotics

Nuclear factor-κB

These proteins are a family of structurally related eukaryotic transcription factors that promote the expression of over 150 genes, many of which play important roles in the regulation of inflammation and apoptosis. Excess or inappropriate activation of nuclear factor (NF)-κB has been observed in human IBD. Thus, inhibitors of NF-κB can be used as a treatment strategy for the management of IBD

Other factors

Nitric oxide

Cyclooxygenase-2

Leukotriene B4

Plants for IBD

Pistacia lentiscus

Commiphora mukul

Foeniculum vulgare

Terminalia chebula

Plantago ovata and P. Psyllium

Boswellia carterii

Pistacia lentiscusOleogum resin inhibited the production of pro-inflammatory substances such as NO and prostaglandin E2.

It has shown potent hydroxyl radical scavenging activity

Treating CD patients with oleogum resin from P. lentiscus resulted in the reduction of TNF-α secretion (P = 0.028). Macrophage migration inhibitory factor (MIF) release was significantly increased (P = 0.026) .

IBS and medicinal herbs

Peppermint – Mentha piperita

Parts Used: LeafAntispasmodic

Relives irritable bowel syndromeSpasmodic gut complaints

Cooling, antibacterialImproves bile production and secretion

Gall bladderReduces catarrh of respiratory tract

Oil – antimicrobial, relieves headaches

• Peppermint oil is a smooth muscle relaxant and may be used for symptoms of IBS. A systematic review evaluating peppermint for this syndrome found evidence that peppermint oil improved symptoms over placebo. A subsequently published short-term (two to four weeks) RCT also found benefit from peppermint oil over placebo in adults. Because of the smooth muscle relaxant characteristics of peppermint oil, it may exacerbate gastroesophageal reflux symptoms.

IBS - Peppermint• Peppermint (Mentha piperita);

primary ingredient, 29% - 48% menthol

• Uses: many digestive complaints, including colic, flatulence, diarrhea, dyspepsia, indigestion, nausea and vomiting

• Relaxes smooth muscle and slows GI transit

• Approved by German Commission E

Peppermint oil– Action: When used in enteric-coated capsule form, the menthol in peppermint oil is released

into the colon. It blocks calcium channels of the nifedipine type in the smooth muscle, thereby

exerting a spasmolytic effect on the colon.

Pharmacokinetic Peppermint oil is relatively rapidly absorbed after oral administration and eliminated mainly via the bile. The major biliary metabolite is menthol glucuronide, which undergoes enterohepatic circulation. The urinary metabolites result from hydroxylation at the C-7 methyl group at C-8 and C-9 of the isopropyl moiety, forming a series of mono- and dihydroxymenthols and carboxylic acids, some of which are excreted in part as glucuronic acid conjugates.

The menthol does not enter into the circulation owing to a high first-pass effect.

–A recent metaanalysis of available clinical trials showed some efficacy over 4 to 6 weeks.

• Pharmacology

– Pharmacological properties: Peppermint oil has antimicrobial, choleretic, and carminative effects. It induces smooth-muscle spasmolysis and produces a cooling sensation when applied to the skin.

Important constituents:

–Menthol (35–45 %), menthone (15–20 %), menthyl acetate (3–5 %), neomenthol (2.5–3.5%), isomenthone (2–3 %), menthofuran (2–7 %), and 1,8-cineole (6–8 %).

Contraindications

• – Internal use: Individuals with biliary tract obstruction, inflammation of the gallbladder or severe liver damage should not use peppermint oil.

• Owing to its cholagogic action, the herb can induce acute abdominal pain in patients with gallstones.

• GERD

Contraindications

• – External use: Peppermint oil preparations should not be applied to the face, especially the nose or the eyes, of infants and small children due to the risk of respiratory side effects such as respiratory arrest.

Adverse effects:• Peppermint oil can upset the stomach of

sensitive individuals.

• Persons who tend to develop GERD should avoid peppermint oil.

• Menthol-containing essential oils can increase the spasms of bronchial asthma.

Dose

Usual doses in adults and adolescents from the age of 15 years are 0.2 mL three times daily by mouth, (increased to 0.4 mL three times daily if necessary) for up to 2 to 3 months. The capsules should be taken half to one hour before food and swallowed whole, not chewed.

Zataria multiflora

Active constituents:thymol, carvacrol

Standardized : 5.5-6.5 mg thymol in each soft gel capsule

Carminative

Antispasmodic

Antinociceptive

Thyme – Thymus vulgaris

Parts Used: LeafAntibiotic

Use to relieve colds and fluRelieves coughing, expectorant

For coughs, colds, bronchitis, upper respiratory tract infections

Effective against H.pylori in combinationCan be used as a gargle with Sage for sore throats

Antihemorrhoid medicinal herbs

GRADE SYMPTOMS AND SIGNS MANAGEMENT

First degree Bleeding; no prolapse Dietary modifications

Second degree Prolapse with spontaneous reduction Rubber band ligation

  Bleeding, seepage Coagulation

    Dietary modifications

Third degree Prolapse requiring digital reduction Surgical hemorrhoidectomy

  Bleeding, seepage Rubber band ligation

    Dietary modifications

Fourth degree Prolapsed, cannot be reduced Surgical hemorrhoidectomy

  Strangulated Urgent hemorrhoidectomy

    Dietary modifications

Myrtus communis

Medicinal usesMyrtle occupies a prominent place in the writings of Hippocrates, Pliny, Dioscorides, Galen, and the Arabian writers. In addition a recent systematic review of herbal medicines, have proven a positive effect for myrtle compounds in the treatment of rhinosinusitis . In several countries (particularly in Europe and China) there have been a tradition for prescribing this substance for sinus infections. The active substance is known as Myrtol. An ointment containing the essential oil myrtle was effective against Herpessimplex virus (HSV) infection. An extract of the berries of myrtus had significant ulcer-protective effects when administered to rats.

Myrtus communis

1- Astringent

2- Hemostatic

3- Antibacterial, antifungal

4- Antinociceptive

Compared with antihemorrhoid ointment and suppository

Lidocaine

Hydrocortisone

Al subacetate

Zinc oxide

Results of a DB study

Compared with anti-hemorrohid ointment

MG ointment caused significant reduction of pain, itching, bleeding, tenesmus

Useful for 1st and 2nd degrees

Ref: Farahvash et al. 2001

Conclusions • Researchers have focused on herbal drugs

• Herbal drugs can treat many disease.

• Herbal drugs can cause severe herb-drug interaction

• Herbal drugs are not useful for emergency situations

• Herbal drugs must not be substituted for drugs such as insulin.

• Adultration (sibutramine, cortons, …)

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