GI Tract Herbal Remedies

1. GI Tract Herbal Remedies

2. Natural Standard Database • An international research collaboration with the following mission: “provide objective, reliable information that aids clinicians, patients, and healthcare institutions to make more informed and safer therapeutic decisions”. • Founded by clinicians and researchers to provide high-quality evidence-based information about complementary & alternative therapies.

3. Natural Standard Database • They have developed a validated rating scale (A-F) which evaluates the qualityof available data. • All monographs undergo a blinded editorial & peer review process. • Monographs are written by MD, PharmD, PhD, ND, nurses from top universities worldwide. • Access directly when on campus and go through library remote access off campus (just use your SU login username & password). www.naturalstandard.com

4. National Center for Complementary and Alternative Medicine (NCCAM) • Established by Congress in 1992 as the NIH branch “Office of Alternative Medicine” (OAM) but its name was changed to NCCAM in 1999. • Access http://nccam.nih.gov and select “Clinical Trials” in upper menu. Then select “All NCCAM Clinical Trials” and choose particular ongoing trials based upon disease state. Select “Completed Trials” to see list of completed trials & associated publications.

5. Available funding to NCCAM • National Center for Complementary and Alternative Medicine • FY 2008: $121.6 million • FY 2007: $121.4 million • FY 2006: $122.7 million • FY 2005: $123.1 million • FY 2004: $117.7 million • FY 2003: $114.1 million • FY 2002: $104.6 million • FY 2001: $89.2 million • FY 2000: $68.7 million • FY 1999: $50.0 million • Office of Alternative Medicine • FY 1998: $19.5 million • FY 1997: $12.0 million • FY 1996: $7.7 million • FY 1995: $5.4 million • FY 1994: $3.4 million • FY 1993: $2.0 million • FY 1992: $2.0 million

6. Office of Dietary Supplements (ODS) • NIH office mandated by DSHEA in 1994 to serve as a “clearing house for information on dietary supplements”. http://dietary-supplements.info.nih.gov • Select “Health Information” from upper menu and click on “IBIDS (International Bibliographic Information on Dietary Supplements” under the NIH Database & Research Resources section. • Also select “Research” in upper menu and click on “NIH Botanical Research CentersProgram”. Connect to the 6 university based research centers funded by NCCAM and ODS.

7. Herbs used to treat GI disorders • Licorice (Glycyrrhiza glabra) • Ginger (Zingiber officinalis) • Peppermint (Mentha piperta) • Chamomile (Matricaria recutita) • Milk Thistle (Silybum marianum) • Kutkin (Picrorrhiza kurroa) • Turmeric (Curcuma longa) • Boswellia (Boswellia serrata)

8. Licorice (Glycyrrhiza glabra)

9. Herbaceous perennial legume (related to beans & peas) native to southern Europe & Asia. Flowers vary from purple to pale whitish blue. Seed pods are 1 inch long & contain several seeds. Grown as a root crop in southern Europe Glycyrrhiza glabra leaves & flowers

10. Native to most of North America. Not seen in southeast US. Used as food & medicine by American Indians. Commonly used to flavor tobacco products. American licorice (Glycyrrhiza lepidota)

11. Licorice roots

12. Licorice (Glycyrrhiza glabra) • Glycyrrhiza derived from Greek meaning “sweet root” (50x sweeter than cane sugar). • The roots contain the medicinally active constituents. • Most of “licorice” flavoring in the US is from anise seeds (contains anethole). • Licorice has been used in Egypt, Greece, and China for thousands of years • DGL (Deglycyrrhizinated licorice) also effective clinically in ulcer treatment. • Carbenoxolone (BIGASTRONE); semisynthetic derivative of glycyrrhetinic acid.

13. Anise seeds and flower (source of licorice tasting compound anethole)

14. Glycyrrhizin Anethole Steroid like structure of glycyrrhizin compared to anethole

15. Shrub native to West Africa The fruit contains miraculin which changes perception of acidic sour foods to sweet. Miraculin itself is not sweet. Miraculin is a glycoprotein consisting of 191 amino acids. Used as a food additive in Japan Synsepalum dulcificum

16. Native to tropical forests of southern & central India Used in Ayurvedic medicine for treatment of diabetes. Leaves contain the glycoside gymnemic acid which is an anti-sweet compound. Suppresses sweet taste of most all sweeteners …takes ~ 10 min for tongue to recover sweet taste. Gymnema sylvestre

17. Licorice (Glycyrrhiza glabra) • Principle Constituents : (rhizomes and roots) • * triterpenoid glycosides (glycyrrhizin & glycyrrhetinic acid). • * isoflavone antioxidants (hispaglabrin, glabrin)…see complete chemical composition in Phytochemical andEthnobotanical Databasewww.ars-grin.gov/duke/ • 1o Clinical Use : • * treatment & prevention of stomach ulcers • (many supportive studies in animals & humans) • Other Potential Uses : • * antimicrobial * antitumor *anti-inflammatory ( blocks the enzyme which degrades cortisol in tissues) • * inhibits platelet aggregation * LDL oxidation

18. Licorice and treatment of peptic ulcers • Gastric & intestinal mucosal damage by ethanol and NSAIDs markedly reduced by licorice in several rat studies. • Licorice shown to  PGE2 in gastric mucosa • Licorice root extracts  release of secretin resulting in  gastric acid secretion in rats • Human studies in Japan have shown up to 70% healing rate for gastric ulcers • Edema, hypokalemia, & hypertension commonly seen in ~ 30% of patients

19. Licorice (cont) • MOA : • *antiulcer effect - inhibition of enzymes which • break down protective prostaglandins in gastric • mucosa (thus see  in PGs) • * stimulates T-cell production of interferon as • well as having direct antiviral effects • Toxicity and Precautions : • * high doses stimulate aldosterone receptor • resulting in  H2O & sodium retention (BP) • * can lead to hypokalemia

20. Antiviral activity of licorice • Several studies show antiviral effects against HIV both in vitro and in vivo • Several clinical studies mainly in Japan since 1992 have demonstrated the efficacy of licorice in treatment of viral hepatitis A, B, and C. • Glycyrrhizin suppressed the secretion of hepatitis B surface antigen in vitro via interfering with intracellular transport and sialylation of the protein.

21. Ginger (Zingiber officinale)

22. Ginger (Zingiber officinale)

23. Beehive Ginger in Costa Rica

24. Wild ginger (Asarum caudatum) used by American Indians for various digestive disorders

25. Ginger (Zingiber officinale) • Native to southern Asia but now cultivated in tropical & subtropical countries esp. China, India, & Jamaica • Used as medicine since ancient times by Greek, Roman, and Arabic physicians • Dried ginger has been used to treat stomachache, diarrhea, and nausea for thousands of years • Std. Ginger extract (Zintona  from Israel) is approved as OTC for prevention of motion sickness in Germany,Switzerland, Austria, and Finland • In the US ginger is sold as a dietary supplement as a digestive aid, for nausea, and in cold and flu remedies

26. Active constituents in Ginger root • Ginger rhizomes contain an oleoresin (4 -7.5%) made up of the following: • Volatile oil containing 30-70% sesquiterpenes mainly zingeberene & -bisabolene • Non-volatile pungent compounds (gingerols, shogaols, and zingerone • Rhizomes also contain a potent proteolytic enzyme called zingibain

27. Pharmacological activity in Ginger • Antiemetic (via GI tract not CNS): relieves nausea & vomiting in motion sickness, following surgery, and during pregnancy • Anti-oxidant (Zingerone  liver microsomal lipid peroxidation) • Anti-inflammatory ( prostaglandin, thromboxane, and leukotriene biosynthesis) •  muscle tone and peristalsis in intestines in humans • Anti-spasmodic activity in rats

28. Pharmacological activity (Ginger) • Promotes salivary, gastric acid, and bile secretion • Inhibits platelet aggregation ( only at high doses ~10 grams) • Gingerol activates Ca 2+ - ATP ase in heart and shows a positive inotropic effect • Protection against ulcer formation in animal studies • may promote peripheral circulation

29. Clinical trial evidence for antiemetic effects • British study showed that powdered Ginger (~1gm) was more effective than dimenhydrinate in reducing nausea when subjects were blind-folded in a tilted rotating chair. • Recent US study failed to confirm this study • 2 studies in 80 naval cadets showed ↓ seasickness • Post operative nausea ↓ in two trials • Several studies showed that 1 gm ginger reduced nausea during pregnancy

30. Ginger in motion sickness • Summary: 6 clinical trials done since 1982 in 1,979 subjects. results: Only 2 of the 6 studies showed positive effects. • First study Mowrey 1982 in Britain; 36 subjects were blind-folded in a tilted rotating chair & given 1 g powdered ginger or 100 mg dimenhydrinate …results: ginger was more effective than the drug in reducing nausea. • U.S. study in 1991 failed to reproduce this positive effect of ginger • Conclusion: insufficient evidence to support its effectiveness in motion sickness

31. Ginger in Hyperemesis Gravidarum (Nausea/Vomiting of Pregnancy) • Summary: 5 clinical trials (using 0.5-1.5 g of ginger) have been carried out since 1990 in just over 500 women…. results: 3 of these studies showed statistically significant benefits • Willett’s et al 2003, J Obstet Gynecol; 120 women <20 wks pregnant given equivalent to 1.5 g dried ginger or placebo 4x daily for 4 days….results: nausea improved but no change in frequency of vomiting. Follow up of all pregnancies showed no adverse effects in infants.

32. Ginger and Chemotherapy-induced nausea and vomiting • 2 previous (1987,1995) small human studies showed promise. • Current NCCAM study (completed in 2007)… “Phase II Trial Of Encapsulated Ginger As A Treatment For Chemotherapy Induced Nausea And Vomiting”. 180 patients participated in the study. Ginger given 2x daily for 3 days following chemo

33. Other clinical evidence for efficacy • Clinical and animal studies have shown that ginger ↓ pain and swelling in arthritis • Animal studies document an effect of ginger to  GI motility and protects against ulcer formation

34. Side Effects and Toxicity • Has been used safely for thousands of years in many cultures • Some question as to the safety in pregnancy…one early report of interactions with testosterone receptors in fetus ?????

35. Effective Dosage and Administration • 2-4 gm /day of cut rhizome or dried extract • Powdered rhizome 0.25-1.0 gm 3x day • Infusion (tea): 0.25-1.0 gm in 150 ml of boiling water 3x day

36. Peppermint (Mentha piperita)

37. Spearmint Leaf Peppermint Leaf Peppermint vs Spearmint ???

38. Many Products are flavored with Peppermint EO

39. Peppermint (Mentha piperita) • Perrenial herb which is a natural sterile hybrid of Mentha aquatica (water mint) & Mentha spicata (spearmint)…arose in a patch of spearmint growing in England in 1696 and has been cultivated ever since. • Name is from Greek Mintha (a mythical character who has turned into this plant) and Latin piper meaning pepper • Many varieties or chemotypes are now cultivated • US is the leading producer of peppermint oil

40. Electron micrographic image of peppermint leaf…note oil glands

41. Peppermint History • Popular in ancient Greek, Roman, and Egyptian cultures • The oil is official in many pharmacopoeias (leaf and oil are in US National Formulary) • Especially popular in Germany ** common uses in US • Carminative in antacids • Treatment of nonulcer dyspepsia & IBS • Counterirritant in topical analgesics • Decongestant in inhalants & lozenges • Antiseptic and flavoring agent in mouthwashes, gums, and toothpastes

42. Other popular uses of peppermint • Opening of sinuses when inhaled • Aching muscles (analgesic effect) • Mental alertness (CNS stimulant) • Insect repellent • Headache relief (from tension)

43. Clinical trial supported uses • Treatment of non-ulcerous dyspepsia • Spastic colon syndrome • Irritable bowel syndrome (IBS)…use enteric coated capsules. • Prevention of postoperative abdominal distention • Relief of tension headaches ( = to1000 mg acetaminophen) MOA: Peppermint oil  GI motility viainhibition of smooth muscle contraction via blocking calcium influx into muscle

44. Effects of peppermint on GI spasms Colonic spasms: • 2001 Japanese study in 409 patients. PO reduced colonic spasms during colonoscopy by 88.5%. Gastric spasms: • 2003 Japanese study in 100 patients used PO to directly relax stomach smooth muscle during endoscopy. Esophageal spasms: • 2001 study at Cedar-Sinai Medical Center in California found that PO blocked spasms completely as assessed by perfusion manometry measurements.

45. Peppermint and Irritable Bowel Syndrome (IBS) • J.Gastroenterol. 1997 Study in Taiwan in 110 patients with IBS (52 patients took an enteric coated peppermint oil formulation called Colpermin 3-4x daily 15-30 min before meals for 1 month). Results: 79 and 73% of these PO treated patients showed  abdominal pain and stool frequency. • J. Pediatrics 2001 U. Missouri study in 42 children (8-10 yr) with IBS. Enteric coated PO for 2 weeks resulted in  severity of GI pain in 75% of the children

46. Peppermint and IBS.. continued Systematic Review published in Phytomedicine 2005: • Identified 16 clinical trials looking at PO and IBS. Nine of 16 were randomized double-blind cross-over studies. • Twelve of the 16 studies were placebo controlled with several comparing the effects of conventional anticholinergic drugs. • Eight of the 12 placebo controlled trials showed a statistically significant beneficial effect of PO on IBS symptoms.

47. Pharmacology of Peppermint’s sensory nerve & analgesic effects • Peppermint oil (PO) has a direct antinociceptive effect by desensitizing the tongue to capsaicin form hot peppers. • When applied topically PO stimulates the cold receptors in the dermis via blockade of voltage gated channels causing depolarization • Inhalation of PO causes enhancement of the nasal sensation of airflow via effects on nasal sensory nerve endings

48. Pharmacopeial grade peppermint leaf • Composed of dried whole or cut leaf with <5% stem fragments > 1mm diameter & <10% leaves with brown spots Composition requirement: • 30-50% menthol (free alcohol) • 14-32% menthone (ketone) • 2.8-10% methylacetate (ester) • 1.5-10% isomenthone • 1.0-9.0% menthofuran • 1.0-5.0% limonene • 3.5-14% cineole • <4% pulegone ; <1% carvone

49. Menthol

50. Peppermint dosage & administration Internal use: • Average single dose is 0.2 ml of the essential oil • For IBS use 0.6 ml of essential oil in enteric coated capsules • As an inhalant: 3-4 drops of essential oil in hot water: deeply inhale the steam vapor External use: 5-20% essential oil in liniment or ointment