Phytotherapy for Gastrointestinal System Disorders PDF

Phytotherapy for Gastrointestinal System Disorders Dr. Kamel Mahmoud  Functions of digestive system 1) Intake and digestion of food. 2) Absorption of nutrients from digested food. 3) Elimination of solid waste products. Digestive systems Problems 1- Constipation 2- Diarrhe...

Phytotherapy for Gastrointestinal System Disorders Dr. Kamel Mahmoud  Functions of digestive system 1) Intake and digestion of food. 2) Absorption of nutrients from digested food. 3) Elimination of solid waste products. Digestive systems Problems 1- Constipation 2- Diarrhea 3- Indigestion 4- Peptic ulcer 5- Appetite loss 6- Intestinal worms  I- Constipation A- Bulking In general, constipation is defined as a functional bowel disorder agents characterized by difficult, infrequent, or incomplete defecation. B- Irritating Most studies suggest an increasing constipation prevalence with age. agents A- Bulking Agents 1) Bran  Bran is the hard outer layers of cereal grain (wheat, rice, corn, oats, and barley). It is often produced as a byproduct of milling in the production of refined grains. It is present in cereal grain, including It is rich in dietary fiber, essential fatty acids, proteins, vitamins and minerals. Wheat bran is a proved bulking agent for treatment of constipation in markets for decades. In one clinical study, the administration of wheat bran (20gm/day) was associated with a significant increase in fecal weight (157%), bowel movement frequency (55%), decrease in intestinal transmit time (50%) and increase in percentage fecal moisture (67.4-72.1%).  2) Psyllium Psyllium is a dietary fiber high in mucilage that is not absorbed by small intestine Psyllium products used in market for years by the mechanism of absorbing water and getting bulky stimulating normal bowel elimination &appetite suppressor. Many clinical studies showed that Psyllium increases stool consistency, decreases straining & bloating, & improves the flatulence & quality of life for constipated patients. Due to its high content of fiber, it also decreases serum lipids in mild to moderate hypercholesterolemia as proved by clinical studies in addition to serum glucose control in diabetic patients as approved by FDA in 2014. 3) Dried plums (prunes) Carbohydrates (64%) including dietary fiber, protein (2%), vitamins (K and B) & minerals Prune juice have been traditionally used for the treatment of constipation The European Food Safety Authority concluded in a 2012 review that sorbitol content in Prunes may be responsible for its laxative effect. The report also showed that consumption of 100 grams daily contribute for the maintenance of normal bowel function. A 2011 study on 40 constipated patients concluded that dried plums and psyllium were equally effective in reducing Straining and global constipation symptoms, but dried plums were more effective in increasing the number of complete spontaneous bowel movements per week and improving the stool consistency compared with psyllium. Both were palatable, safe and well tolerated.  Sennosides 2- Irritating agents Anthraquinones, carbohydrates, flavonoids, glycosides Senna (Cassia acutifolia & Cassia angustifolia) (Sennalax®) (Purgaton®) Senna has been used historically for centuries as herbal tea for treatment of constipation. Senna is an FDA-approved over-the-counter (OTC) laxative for adults and children. It is also on the World Health Organization's List of Essential Medicines of the most effective and safe medicines needed in a health system. It is sometimes used for colon cleaning before bowel examination or surgery Mechanism of action: Sennosides irritate the lining of the bowel, promoting colon contractions and bowel movements which cause a laxative effect. Senna also prevents reabsorption of water and electrolytes from the colon, which increases fluids in the intestines and softens stool. Side effects: It may cause abdominal cramps and electrolyte disturbance. Contraindications: It is contraindicated in cases of intestinal obstruction, acute intestinal inflammation, ulcerative colitis, appendicitis, and abdominal pain of unknown origin. Additives: Combination of Senna, Anise and Fennel is used largely in many countries as herbal treatment for chronic constipation. Both anise and fennel have antispasmodic and carminative effects.  Rhubarb (Rheum) Anthraquinones (emodin and rhein) Tannins, catechins, gallic acid and cinnamic acid Rhubarb has been widely used as a traditional Chinese herbal medicine since ancient times as laxative and for the management of GI and renal function disorders, and for the treatment of hyperlipidemia, cancer, & acute ischemic stroke. The laxative mechanism of rhubarb is based on the enhancement of the motility and secretion of water and electrolytes through irritating the movement of colon. Dose: Dried rhubarb extract 20 to 50 mg/kg daily has been used in clinical trials.  Cascara Sagrada Anthraquinone derivatives & their glucosides, (cascarosides). Aloin, Emodin & Chrysophanol The dried bark of cascara has been used for centuries as a laxative. It is available as dietary supplement not OTC laxative drug. Like other irritant laxatives Long term use may cause liver injury, Onset was from few days to 2 months The liver injury ranged from mild to severe, but usually resolved rapidly with discontinuation.  II- Diarrhea Diarrhea is the frequent passage of loose, watery, soft stools. It may be accompanied by abdominal bloating or cramps. Treatment of diarrhea depends on the cause of the loose stool. It is mainly caused by bacterial, viral, fungal infection. This explains the use of antibacterial and antiviral herbs for treatment of diarrhea in traditional medicines. If diarrhea leads to dehydration, it is a sign of potentially serious disease.  Herbal treatments 1) Blackberry leaves, Blueberry leaves, and Red raspberry leaves Blackberry is an astringent herb traditionally used to treat diarrhea. Astringent herbs traditionally used for diarrhea include blackberry leaves, blackberry root bark, blueberry leaves, & red raspberry leaves. All leaves are high in tannins and may relieve acute diarrhea. A close cousin of the blueberry, bilberry, has been used traditionally in Germany for adults and children with diarrhea. Only dried berries or juice should be used—fresh berries may worsen diarrhea. When tannins meet mucous membranes, they interact with those membranes by making them more tight and less permeable; this process is called “astringency”. This feature increases protection to the sub-adjacent layers of mucosa from the microorganisms and irritant chemicals, in addition to slowing intestinal peristalsis.  Carob (Ceratonia siliqua) Condensed tannins (16%–20% of dry weight) Sugar content (sucrose, glucose & fructose) + cellulose & hemicellulose. The carob fruit contains two major parts: the pulp (90%) and the seeds (10%). Many reports described that decoctions of roasted carob powder can be effective for the treatment of acute diarrhea.  Mechanism of action 1) In addition to tannins, the sugars of galactose and mannose act as thickeners for the absorption of water and aid in binding together watery stools. 2) The tannins found in carob have the unusual property of being only partially soluble. The insoluble nature of tannins present in carob extracts have been found to bind bile acids and bacterial toxins, inhibiting in this manner, the growth of bacteria. In a clinical study, Infants aged 3-21 months with acute diarrhea of bacterial and viral origin were treated with oral rehydration fluid with tannin-rich carob pod powder (40% tannins or 21.2% polyphenols and 26.4% dietary fiber), 1.5 g/kg/day. Normalized defecation, body temperature and cessation of vomiting were reached more quickly by the patients who received the carob powder than placebo group.  Anti-rotavirus herbs Black tea Black tea is one of the most consumed beverages in the world. Black tea has been recommended to treat diarrhea in traditional medicine in many cultures. 2003 & 2005 clinical study on >120 Results showed that it can decrease gastrointestinal motility in a dose-dependent way; hence, it can be used to treat gastrointestinal motility disorder such as diarrhea. Tannins and theaflavins: Tannins have astringent effect, while theaflavins can inhibit human and bovine rotavirus, which is one of the common causes of diarrhea among infants and young children. Theaflavins are formed by the oxidation of selected catechins like epicatechin and epigallocatechin-3-gallate (EGCG) in green tea during fermentation. Family of theaflavins includes theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B), theaflavin-3,3′-digallate (TF3) (most active). Theaflavins proved to have anti-inflammation, antibacterial, and anticancer, neuroprotective, antioxidant, cardioprotective, and nephroprotective effects.  III- Indigestion Indigestion can be pain or discomfort in your upper abdomen (dyspepsia) or burning pain behind the breastbone (heartburn). Dyspepsia and heartburn may occur together or individually. Symptoms usually appear soon after eating or drinking. Common associated symptoms include bloating and nausea. In most cases indigestion is related to eating, although it can be triggered by other factors such as smoking, alcohol, pregnancy, stress or taking certain medications. Among various gastrointestinal disorders, functional dyspepsia is one of the most common clinical conditions in general medical practices. The general symptoms of functional dyspepsia include upper abdominal fullness, epigastric pain, belching, bloating, early satiety, nausea, vomiting, heartburn, and loss of appetite.  Types of dyspepsia 1) Ulcer-like dyspepsia in which pain is centered in the upper abdomen and treated by antisecretory agent. 2) Dysmotility-like dyspepsia, in which unpleasant non painful sensation is centered in the upper abdomen, with symptoms like fullness, early satiety, bloating, nausea, and treated with agents increasing gastric emptying rate and digestives. Herbal treatments A- Carminatives B- Bitters (Digestives) C- Demulcents (Soothing agents) A- Carminatives Anise, Fennel, Peppermint, Chamomile, Rosemary, Cumin, Ginger, Cinnamon, Cardamom. All contain essential oils; natural carminative and antispasmodic agents.  Peppermint A 2012 Egyptian clinical study on 221 pregnant women concluded that use of peppermint tea, beside compliance to lifestyle measures are effective on relieving gastroesophageal reflux disease (GERD) Grade 1 (NERD) during pregnancy. The study recommended using peppermint tea in-between meals for relieving of GERD during early stages of pregnancy. GERD commonly known as heartburn, is common in pregnancy and is experienced by 45-80% of pregnant women. GERD has 3 grades: First grade is non-erosive esophageal reflux disease (NERD), It accounts for up to 70% of patients. Mechanism: it is proposed that one way is the essential oils relax the esophageal sphincter, which then releases the gas. Active constituents: peppermint oil contains menthol, menthone, and menthyl acetate as main components.  Basil (Ocimum Basilicum) In a 2005 clinical study, Patients with dyspepsia consumed 30 drops of prescribed medications (placebo or the extract, equal to 1.5 gm leaves powder) daily at 30 min before lunch and dinner for one month. Result: The plant extract relieved the symptoms of functional dyspepsia especially in female and young patients with dysmotility. Active constituents: Volatile oil contains β- Linalool, Cineole, nerol, methyl cinnamate. Mechanism of action: increase gastric emptying rate with carminative effect. Basil herb and basil oil contain estragole. Estragole is a chemical that might increase the risk of getting liver cancer (proved in mice studies).  Ginger (Zingiber officinale) In a 2011 clinical study, eleven patients with functional dyspepsia were studied in a randomized double-blind manner. patients ingested three capsules that contained ginger (total 1.2 g) or placebo. Result: Ginger successfully stimulated gastric emptying rate in patients with functional dyspepsia. Active constituents: main terpene component is zingiberene, while main phenolic components are gingerols and shogoals.  Anise A 2015 clinical study on 107 patients with dyspepsia, in which patients received 3 g after each meal (3 times/day) for 4 weeks. Results: Total scores of dyspepsia severity scale in the anise group dropped from 10 to 2 after 4 weeks. Epigastric fullness, discomfort, burning/pain, early satiety, bloating, and loss of appetite decreased significantly. Mechanism of action: Carminative, Antispasmodic and anti-inflammatory which inhibits gastric mucosal inflammation. Active constituents: trans-anethole, estragole, p-anisaldehyde, and methyl chavicol.  B- Bitters (Digestives): Boldo leaves (Peumus boldus): Boldo is officially listed as phytotherapy as cholagogue & choleretic, for treatment of mild dyspepsia in Brazilian pharmacopoeia. Active constituents: Boldo leaf contains the alkaloid boldine. Boldo leaf also contains 2-4% of volatile oil. Major constituents reported as: ascaridole (16-38%), 1,8- cineole (11-39%) and p-Cymene (9-29%).  IV- Antispasmodic Hyoscine butylbromide (Buscopan®) Hyoscine butylbromide is a salt of the alkaloid hyoscine isolated from Hyoscyamus muticus. It is one of the WHO essential drug list. Uses: Hyoscine butylbromide is available in the international market as potent general antispasmodic drug for IBS spasms, gastric spasms, menstrual spasms, bladder spasms and renal colic. It is available as tablets and injection. Mechanism of action: It is an anticholinergic drug; it blocks the action of the neurotransmitter acetylcholine at synapses in the central and peripheral nervous system, thus inhibiting the parasympathetic system. Side effects: As an anticholinergic, it may cause dry mouth, tachycardia, and blurred vision. It is contraindicated in patients with closed-angle glaucoma and myasthenia gravis.  V- Gastric ulcer The cause of ulceration in patients is mainly due to hyper-secretion of gastric juice, and due to hypersecretion of pepsin. An ulcer is basically an inflamed break in the skin, or the mucus membrane lining the alimentary tract in stomach or duodenum. Ulceration occurs when there is a disturbance of the normal equilibrium caused by either enhanced aggression or diminished mucosal resistance. Various factors that disrupt the balance your stomach’s environment can cause them. The most common causes are hyper-secretion of gastric juice, Helicobacter pylori bacteria and overdoses of N-SAIDS. Other common causes include stress, smoking, excess alcohol consumption and the overuse of anti-inflammatory medications, such as aspirin and ibuprofen.  1- Cabbage (Brassica oleracea) Cabbage, like other cruciferous vegetables, is famous of sulfur compounds, potent antioxidant beta carotene, high percentage of phenolics; flavonoids (kaempferol, quercetin, and apigenin), vitamins and minerals. Earlier clinical studies in the last century reported rapid healing of peptic ulcer in 13 patients after ingestion of fresh cabbage juice daily for one month. Other studies reported symptoms decrease after 10-14 days.  2- Licorice (Glycyrrhiza glabra) The licorice extract can be used as a sugar substitute as it contains glycyrrhizin, which is 50 times sweeter than sugar. Active constituents: Flavonoids. (Deglycyrrhizinated licorice) Anti-peptic ulcer activity: One of the most common folk uses of licorice in Europe has been in the treatment of gastric ulcer. Its supposed mechanism of action includes: 1- has potent demulcent effect, promote mucus secretion from the stomach and prolongs the life span of surface cells in the stomach. 2- It has an anti-pepsin effect. 3- Many in-vitro studies showed the anti-H. pylori activity of licorice extract and its isolated active constituents.  3- Turmeric (Curcuma longa) In GIT disorders, it has a choleretic action, causing increased flow of bile into the intestine and is a remedy for dyspepsia and diarrhea. Active constituents: Curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin). 2001 clinical study was done on 25 patients with gastric & duodenum ulcers. Treatment: capsule-filled turmeric orally in the dose of 2 capsules (300mg) five times daily, one half to an hour before meals. Results: the complete cure of ulcers in 48% of patients in the first month, raised to 72% in the second month and 76% in the third with no significant changes in hematological system, liver and renal functions during treatment. Proposed mechanism: As explained in previous studies, turmeric had local anesthetic action and inhibit gastrin hormone secretion from the antrum of the stomach; responsible for gastric acid HCL secretion.  4- Black seed (Nigella sativa) in-vitro study showed that N. sativa extract produced a 100% inhibition of the growth of all the strains of H. pylori that were tested within 60 minutes. Previously, extracts of N. sativa has been reported to inhibit gram-positive and gram-negative bacteria. Many In-vivo studies showed anti-peptic ulcer of NS extracts. 2010 clinical study on 88 dyspeptic patients with H.Pylori infection. Treatment: one group received 2 gm NS + 40 mg omeprazole daily, and the other group received standard triple therapy of comprising of clarithromycin, amoxicillin, omeprazole. Results: 2 gm NS showed anti-H.pylori activity comparable to standard triple therapy. It improved all the dyspepsia symptoms.  2020, England, Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis There is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality. 2021, China, Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR-30a to regulate COX-2/BCL9 pathway Gastric cancer is one of the most frequently diagnosed digestive cancers, accounting for over million new cases globally in 2018. Incidence rates of gastric cancer are markedly elevated in Asian countries, especially in China. Evidence supports that Helicobacter pylori (H. pylori) is a first-class carcinogen leading to gastric adenocarcinoma and is directly linked to the development of gastric cancer. Early-stage gastric cancer is asymptomatic. So, most gastric cancer patients are diagnosed at an advanced stage.  Phytotherapy for Helicobacter pylori 2020, Egypt, Plants against Helicobacter pylori to combat resistance: An ethnopharmacological review Helicobacter pylori is a spiral-shaped Gram-negative bacteria colonized in the gastrointestinal tract. leading to gastritis, peptic ulceration, and gastric carcinoma. About 50 % of the world population is estimated to be infected by this bacterium. The mechanisms of action of herbs include urease inhibition, DNA damage, protein synthesis inhibition, and anti-inflammatory effects. Urease inhibitors: Green tea, chamomile, Cranberries and oregano, resveratrol, red grape juice and red wine. Anti-adhesion activity: Licorice, parsley, and turmeric water extracts are found to be able to decrease adhesion of H. pylori. Garlic disrupts bacterial cell wall while aloe vera increases mucous.  VI- Irritable Bowel Syndrome Irritable bowel syndrome (IBS) is a chronic condition of functional gut disorder characterized by abdominal pain or discomfort, bloating, and bowel disturbances in the absence of any known mechanical, inflammatory, or biochemical explanation for these symptoms. It can be accompanied by an array of symptoms including increased or decreased bowel movements, hard or loose stools, passage of mucus or extensive gas, urgency of defecation, straining during a bowel movement, feeling of incomplete evacuation and abdominal fullness or bloating. Statistically, it affects up to 20% of the general population with a higher prevalence ratio of women to men (ratio of 2:1).  1- Peppermint A 2010 clinical trial was done on 90 patients with IBS Treatment: one capsule of enteric-coated, delayed- release peppermint oil 3 times daily for 2 months. Results: The severity of abdominal pain was reduced significantly in the Peppermint oil group as compared to controls with significant improvement in quality of life without any significant adverse reaction. Mechanism of action: Peppermint oil, and its major constituent, menthol, also has relaxing effects on gastrointestinal smooth muscle by blocking Ca2+ channels in the gut, which may be useful in improving IBS symptoms. Active constituents: Menthol, Menthone, and 1,8-Cineole, menthyl acetate and Isovalerate, Pinene, Limonene and other constituents.  2- Turmeric (Curcuma longa) A 2004 clinical study was done on one hundred IBS patients Treatment: two tablets (144 mg) of a standardized turmeric extract daily for 2 months. Results: IBS prevalence decreased significantly by 60% between baseline & after treatment. Abdominal pain/discomfort score reduced significantly by 25%. two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. Mechanism of action: Recent evidence has shown that turmeric inhibits the expression of inflammatory mediator cyclooxygenase-2.  3- Curcumin and Fennel Essential Oil The anti-inflammatory property of curcumin and the antispasmodic and carminative effect of fennel suggests that this combination would be useful in IBS. A 2014 clinical study was done on 121 patients with mild-to-moderate symptoms of IBS with abdominal pain score 30-70 on a 100 mm. Treatment: 2 capsules of CU-FEO (Curcumin 42 mg and Fennel essential oil 25 mg) for 30 days. Results: 25% of patients were symptom-free, and the other 75% reported decrease in abdominal pain with all IBS symptoms. Mechanism of action: the fennel reduced abdominal pain by the anethole-dependent relaxation of intestinal smooth muscle.  4- Psyllium In the management of irritable bowel syndrome, most general practitioners recommend an increase in the fiber content of the daily diet. Many studies suggest that soluble fibers like psyllium improve the symptoms while insoluble fibers (bran) can worsen the symptoms. A clinical study employed 180 IBS patients. Treatment: 10 g psyllium (soluble fiber), 10g bran (insoluble fiber), or placebo (rice flour) twice daily, taken with meals by mixing with food, preferably yoghurt. Results: Improvement of symptoms was significantly greater in the psyllium group than in bran and placebo group from the first month. Early dropout was most common in bran group; due to worsened symptoms of IBS. THANK YOU