Jordan University of Science and Technology Phytotherapy (PHMD431) Musculoskeletal System 2024 PDF

Jordan University of Science and Technology Faculty of Pharmacy Phytotherapy (PHMD431) THE MUSCULOSKELETAL SYSTEM Tamam M. El-Elimat, Ph.D. Natural Products Chemistry 2024, Irbid  The Musculoskeletal System The musculoske...

Jordan University of Science and Technology Faculty of Pharmacy Phytotherapy (PHMD431) THE MUSCULOSKELETAL SYSTEM Tamam M. El-Elimat, Ph.D. Natural Products Chemistry 2024, Irbid  The Musculoskeletal System The musculoskeletal system, which provides mechanical support and permits movement, is composed of skeletal muscle, tendons, bones, joints and ligaments. 2  Musculoskeletal Disorders Musculoskeletal disorders and diseases are the leading cause of disability in the US, and account for more than one-half of all chronic conditions in people over 50 years of age in developed countries. Approximately 1.71 billion people suffer from musculoskeletal disorders worldwide. Musculoskeletal disorder is characterized by acute or chronic pain that causes impairments in the functioning of bones, muscles, joints, ligaments, nerves, discs, or tendons. It restricts the sufferer’s mobility and ability to do work and participate in society. Common musculoskeletal diseases:  Tendinitis  Carpal tunnel syndrome  Osteoarthritis  Rheumatoid arthritis (RA)  Fibromyalgia  Bone fractures 3  Musculoskeletal Disorders Risk Factors of Musculoskeletal Disorders:  Age  Occupation  Activity level  Lifestyle  Family history Symptoms of Musculoskeletal Disorders:  Pain  Redness  Swelling  Muscle weakness  Muscle atrophy 4  Phytotherapeutics for the Musculoskeletal System Arthritis, Rheumatism, and Muscle Pain:  Turmeric  Willow bark  Glucosamine  Chondroitin Topical Anti-inflammatory Agents:  Capsicum 5  Phytotherapeutics for the Musculoskeletal System Arthritis, Rheumatism, and Muscle Pain:  Turmeric  Willow bark  Glucosamine  Chondroitin Topical Anti-inflammatory Agents:  Capsicum 6  Turmeric Latin Name: Curcuma longa L. (Zingiberaceae) Common Names: Turmeric, Curcuma, Indian saffron Part Used: Rhizomes Description: A perennial herb of the ginger family. It has a thick rhizome from which arise large, oblong, and long- petioled leaves. 7  Turmeric Chemical Constituents:  Curcuminoids: several phenolic diarylheptanoids including curcumin, monodemethoxycurcumin and bisdemethoxycurcumin.  Essential oil: an orange-yellow volatile oil that is composed mainly of turmerone, atlantone, and zingiberone.  Polysaccharides: such as glycans, the ukonans A–D. O O HO OH O O O Curcumin Turmerone 8  Turmeric: History and Folk Use Turmeric is the major ingredient of curry powder and is also used in prepared mustard. It is increasingly being used as a coloring agent because of the increased use of natural ingredients in foods. It is used in both the Chinese and Indian (Ayurvedic) systems of medicine for many conditions, including breathing problems, rheumatism, pain, and fatigue. Turmeric poultices are often applied locally to relieve inflammation and pain. 9  Turmeric: Therapeutic Uses and Available Evidence Turmeric has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of arthritis, skin disease, wounds, insect bites, allergies, inflammatory bowel disease, Alzheimer’s disease, prostate inflammation, renal disease, diabetes and many others. The most popular uses of curcumin are for three primary purposes:  General antioxidant: as an antioxidant to prevent heart disease and slow down the aging process.  Cancer Prevention and Treatment Adjunct  Inflammation: to reduce inflammation, particularly in osteoarthritis and inflammatory bowel disease. Anti-inflammatory properties have been documented in numerous pharmacological models, and the use of turmeric seems promising, despite the limited number of clinical studies and poor bioavailability. 10  Turmeric: Drug Interactions Curcumin may inhibit the following drug metabolizing enzymes: CYP3A4, CYP1A2, and CYP2A6. In one human study, 300 mg of curcumin reduced the absorption of the β-blocker talinolol by roughly 35%. Curcumin was also shown to downregulate intestinal P-glycoprotein levels. This action may have significance for other drugs influenced by intestinal P-glycoprotein downregulation, including:  Colchicine  Chemotherapy agents including etoposide, doxorubicin, and vinblastine  Digoxin  Immunosuppressive agents Pregnancy/Lactation  Unsafe for use during pregnancy in amounts greater than those commonly found in food.  Emmenagogue and abortifacient effects have been documented. 11  Turmeric: Dosage Turmeric is well tolerated but the bioavailability is poor and daily doses of at least 2 g are normally used. Because curcumin is so poorly absorbed, its clinical use should include something that may increase its absorption. This suggestion has meant using it in a lipid base, such as lecithin, fish oils, or essential fatty (with meals), or formulated in conjunction with piperine. Meriva: a phosphatidylcholine-bound curcumin formulation. The dosage of Meriva is 1000 to 1200 mg providing 200 to 240 mg of curcumin. Theracurmin: a surface-controlled particle dispersion, with an average particle size of curcumin of 0.19 μm compared with an average particle size of 22.75 μm in curcumin powder. the dosage of Theracurmin is 300 mg/day (providing 30 mg of curcumin). 12  Phytotherapeutics for the Musculoskeletal System Arthritis, Rheumatism, and Muscle Pain:  Turmeric  Willow bark  Glucosamine  Chondroitin Topical Anti-inflammatory Agents:  Capsicum 13  Willow Bark Latin Name: Salix alba L. (Salicaceae) Part Used: Bark Willow bark is a European phytomedicine with a long tradition of use for chronic forms of pain, rheumatoid diseases, fever and headache. 14  Willow Bark: Chemical Constituents Phenolic glycosides: salicin Phenolic acids, tannins: mainly dimeric and polymeric procyanidins Flavonoids The most commonly used willow bark dry extract has a salicin content of 15–18% OH O O HO HO OH OH salicin 15  Willow Bark: Therapeutic Uses and Available Evidence The effectiveness of an extract of willow bark (which is licensed as a medicine in Germany) has been shown to be superior to placebo for osteoarthritis and lower back pain, and with fewer side effects than, for example, aspirin. However, furthermore stringent clinical and mechanistic studies are needed. 16  Phytotherapeutics for the Musculoskeletal System Arthritis, Rheumatism, and Muscle Pain:  Turmeric  Willow bark  Glucosamine  Chondroitin Topical Anti-inflammatory Agents:  Capsicum 17  Osteoarthritis Osteoarthritis (OA), or degenerative joint disease, is characterized by joint degeneration, loss of cartilage, and alterations of the subchondral bone. It is by far the most common form of arthritis. It is estimated that more than 40 million Americans have OA, and OA is believed to be responsible for 25% of all office visits to primary care physicians. Whereas 80% of persons above 50 years of age will have x-ray evidence of significant OA, only 60% will experience symptoms. 18  Osteoarthritis Clinical symptoms: Clinical signs:  Mild early-morning stiffness  Local tenderness  Stiffness following periods of rest  Soft tissue swelling  Pain that worsens on joint use  Joint crepitus  Loss of joint function  Restricted mobility  Degenerative loss of articular cartilage 19  Osteoarthritis: Treatment Oral Medications Topical Injectables Medications Osteoarthritis CAM Devices/ Remedies Braces Lifestyle Interventions Modalities for Treatment of Osteoarthritis 20  Glucosamine Glucosamine is a simple molecule, manufactured in the body from fructose 6- phosphate and glutamine. OH O OH HO NH2 OH There are no food sources of glucosamine. Commercially available sources of glucosamine are derived from chitin; the exoskeleton of shrimp, lobsters, and crabs. 21  Glucosamine One of the primary physiologic roles of glucosamine is in the joints, where it stimulates the manufacture of glycosaminoglycans (GAGs), key structural components of cartilage. Glucosamine also promotes the incorporation of sulfur into cartilage. 22  Glucosamine: Osteoarthritis The primary use for GS is in the treatment of OA. This application has significant support in the medical literature. Numerous double- blind studies have shown GS to produce much better results compared with non- steroidal anti-inflammatory drugs (NSAIDs), placebo, or acetaminophen in relieving the pain and inflammation of OA. Although some of the studies comparing GS with NSAIDs or acetaminophen showed similar reduction in pain and symptom scores, only GS improved indexes of joint function or markers showing improvement of cartilage structure. Typically, the advantages of GS over these other treatments were seen after 2 to 4 weeks of use, but there is some evidence that the longer GS is used, the greater the therapeutic benefit. 23  Glucosamine: Side Effects and Toxicity GS has an excellent safety record in animal and human studies. On the basis of these studies, many experts have recommended that GS “be considered as a drug of choice for prolonged oral treatment of rheumatic disorders.” Side effects, when they do appear, are generally limited to light to moderate gastrointestinal symptoms, including stomach upset, heartburn, diarrhea, nausea, and indigestion. If these symptoms occur, GS should be taken with meals. Caution should be used in patients with a shellfish allergy, as glucosamine is derived from the exoskeletons of shellfish. 24  Glucosamine: Drug interactions Agents with antiplatelet properties: Glucosamine may enhance the antiplatelet effect of agents with antiplatelet properties. Monitor therapy. Warfarin: Glucosamine may enhance the anticoagulant effect of warfarin. Monitor therapy. 25  Chondroitin Sulfate Chondroitin sulfate is a sulfated glycosaminoglycan. It composed of repeating units of N-acetylgalactosamine and glucuronic acid. Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression. 26  Chondroitin Sulfate Although the absorption rate of glucosamine sulfate is 90% to 98%, the absorption of intact chondroitin sulfate is estimated to be anywhere from 0% to 13%. If chondroitin sulfate molecules were absorbed intact or partially digested, they would still be unlikely to produce any significant benefit, as the chondroitin sulfate molecules are too large to be delivered to cartilage cells. These absorption problems suggest that any direct effect of these compounds in OA is highly unlikely. 27  Chondroitin Sulfate Most likely any clinical benefit from chondroitin sulfate is due to the absorption of sulfur or smaller glycosaminoglycans molecules broken down by the digestive tract. However, even this is controversial, because in one human study, 1 g of chondroitin sulfate failed to increase serum glycosaminoglycans concentration at all, based on a highly sensitive measure of intact or depolymerized glycosaminoglycans absorption. These results prompted the researchers to conclude: “We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory”. Pooled literature on the biochemistry of chondroitin sulfate offers enough information to assert that neither intact nor polymerized chondroitin sulfate is absorbed by the mammalian gastrointestinal tract. Therefore, no direct action of orally administered chondroitin sulfate on cartilage or chondrocytes is possible. 28  Chondroitin Sulfate The clinical studies that have been done with orally administered chondroitin sulfate demonstrate that it is less effective than glucosamine sulfate. Furthermore, there is no evidence that using both glucosamine and chondroitin together is more effective than either alone. Nevertheless, given the safety record of chondroitin and the evidence of modifying joint-space pathology, chondroitin is a reasonable addition to an osteoarthritis patient’s glucosamine regimen. In addition, chondroitin sulfate may be acting in some indirect way in improving joint health. 29  Phytotherapeutics for the Musculoskeletal System Arthritis, Rheumatism, and Muscle Pain:  Turmeric  Willow bark  Glucosamine  Chondroitin Topical Anti-inflammatory Agents:  Capsicum 30  Capsicum Latin Name: Capsicum annum L. (Solanaceae) Common Names  Capsicum, Chilli Pepper, Hot Pepper, Red Pepper Botanical Description:  A shrubby, tropical plant  White flowers  A berry fruit Part Used: The fruit 31  Capsicum: Chemical Composition The most important constituents of capsicum are the pungent compounds, with capsaicin being the most prominent. Typically, capsicum contains about 1.5% capsaicin and related principles. Other active constituents present include carotenoids, vitamins A and C, and volatile oils. OH H N O O Capsaicin 32  Capsicum: Clinical Applications for Oral Preparations Thermogenic Aid:  Capsicum ingestion may also prove to be helpful in promoting weight loss in obese individuals.  Clinical studies showed capsicum increased the basal metabolic rate while reducing appetite and caloric intake. Atherosclerosis and the Metabolic Syndrome:  Capsicum exerts a number of effects beneficial in the prevention of atherosclerosis, including: o Inhibiting low-density lipoprotein cholesterol oxidation o Acting as an antioxidant o Inhibiting platelet aggregation 33  Capsicum: Clinical Applications for Topical Preparations Modern clinical use of capsicum has focused on the use of topical capsaicin- containing preparations. Commercial ointments containing 0.025% or 0.075% capsaicin are available over the counter. These preparations may offer significant benefits in a number of conditions:  Diabetic Neuropathy  Cluster Headaches  Osteoarthritis, and rheumatoid arthritis  Psoriasis 34  Capsicum Dosage:  Creams containing 0.025% or 0.075% capsaicin or poultices can be applied to affected areas up to four times daily. Side-Effects:  Capsicum contains pungent principles (capsaicinoids) that are strongly irritant to mucosal membranes.  Studies showed that consumption of 3 grams of red chilies per day during the postoperative period after hemorrhoidectomy or surgery for anal fissures increased the intensity of typical postoperative symptoms, stool frequency, and the consumption of analgesics. Drug Interactions:  The use of capsicum has been cautioned in patients on anticoagulants or antiplatelet therapy. 35 Thank You 36