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Herbal remedies for GI disorders. Dr. Hajhashemi Dept. of Pharmacology Isfahan University of Medical Sciences. Some Examples. lungwort. Hepatica leaves have 3 lobes, just like the liver. Walnut: looks sort of like a brain!. Tomatoes are red and have four chambers, just like
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Herbal remedies for GI disorders Dr. Hajhashemi Dept. of Pharmacology Isfahan University of Medical Sciences
Some Examples lungwort Hepatica leaves have 3 lobes, just like the liver Walnut: looks sort of like a brain! Tomatoes are red and have four chambers, just like the heart. Snakeroot
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.
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 origin Physostigmine Pilocarpine Atropine Hyoscine Ephedrine Digoxine Quinidine Morphine Vincristine Vinblastine Paclitaxel Colchicine
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
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: Root Nausea & vomiting, travel sickness, digestive symptoms – colic & wind To treat vertigo Arthritis Decreases cardiovascular risk Prophylaxis 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)
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 Is 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
Ginger The 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.
Ginger The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitrowith 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.
Thyme A 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 bloatingmay 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
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.
