Assessment of Plants for Anti Asthmatic Drugs

Assessment of Plants for Anti Asthmatic Drugs Introduction Asthma is a respiratory inflammatory disease characterized by narrowing of bronchial airway. There are changes in level of cytokines, eosinophils, lymphocytes, mast cells, and other inflammatory cell products. As high level of IgE binds to mast cell receptors, it interacts with antigen, resulting in inflammatory reactions, like the release of mediators (prostaglandins, histamines, and leukotrienes). Hence, bronchoconstriction is triggered. Asthma affects 300 million people across the world and an estimate of a further 100 million will suffer by 2025 (Taur D.J. and Patil R.Y., 2011). Now, there are more and more asthma patients and research teams looking for natural or complementary alternatives to treat asthma. This is because the modern asthma therapy has caused many adverse effects. The natural plant used to treat asthma should have immunomodulatory, smooth-muscle relaxants, antihistamine, anti-inflammatory and allergic activity. In the Ayurveda context, an anti-asthmatic plant drug should have anti-kapha and anti-vata properties (Taur D.J. and Patil R.Y., 2011). Countless natural plants are used as the natural source for anti-asthmatic drugs. After intense research, a particular molecule with good therapeutic properties is identified and extracted from the plants. Then, the molecule will undergo many modifications in the laboratories, be produced in large scale manufacture, put into various dosage forms and marketed to the public. The examples of such plant drugs are Aerva lanta Linn (Amaranthaceae), Cnidium monnieri (Umbelliferae), Euphorbia hirta (Euphorbiaceae), Mentha spicata L, and Olea europea (Oleaceae) (Taur D.J. and Patil R.Y., 2011). Selection of 4 plant drugs 4 drugs are being selected for their anti-asthmatic properties: Quercetin Ephedrine Cromolyn sodium Theophylline Drug Category Plant source Properties Quercetin (Yikrazuul, 2008) Flavonol Caper Quercetin potentiates ÃŽ ² receptor stimulation via phosphodiesterase inhibition of PDE4 and PLCÃŽ ². This relaxes airway muscles (Drug Bank, 2014). It is also an effective bronchodilator and it prevents release of histamine and other inflammatory chemicals (Drug Bank, 2014a). Ephedrine (NEUROtiker, 2008) Sympathomimetic amine Ma Huang As a bronchodilator and decongestant, ephedrine is a potent sympathomimetic that stimulates ÃŽ ± and ÃŽ ² receptors. It reduces swelling and vasoconstriction in lung airways. As your airway widens, you can breathe more easily (RxList, 2009). Cromolyn Sodium (Fvasconcellos, 2009) Chromone complex Khellin Cromolyn sodium inhibits mast cell degranulation, hence there is no release of histamine and slow-reacting substance of anaphylaxis. Type I hypersensitivity is ceased. Besides, cromolyn sodium may inhibit leukotriene release and calcium entry (Drug Bank, 2014b). Theophylline (Fuse809, 2014) Methylxanthine Cacao treeandcocoa tree Theophylline relaxes bronchial smooth muscles and reduces their responsiveness to allergen and histamine. It inhibits type III and type IV phosphodiesterase (PDE) which break downs cAMP, resulting in bronchodilation. It also blocks adenosine A2B receptor and subsequently, bronchoconstriction. Histone deacetylase is activated to prevent inflammatory gene transcription (Drug Bank, 2014c). Table 1: Drug, its category, plant source and properties. Plant Biological source Chemical constituents Family Scientific name Picture Caper bark,bud,leaves Rutin(Quercetin 3-Rutinoside),Quercetin 7-Rutinoside,Quercetin 3-Glucoside-7-Rhamnoside,Kaempferol-3-Rutinoside,Kaempferol-3-Glucoside, AndKaempferol-3-Rhamnorutinoside (Winter R, 1978). Capparaceae Capparis spinosa (Thomà © O. W., 1885) Ma Huang Stem Ephedrine, pseudoephrine Ephedraceae Ephedra sinica, Ephedra intermedia, Ephedra equisetina, Ephedra distacha, Ephedra trifurca (Climbjm, 2000) Khellin Seeds, fruits 1% of Khellin and 0.3% of visnagin are found in fruits (Drugs.com, 2009). Apiaceae Ammi visnaga (Sipler D, 2004) Cacao treeandcocoa tree Seeds The seeds contain about 2% of theobromine and 40-60% of solid fat (Grieve M, 2014). Malvaceae Theobroma cacao (Luisovalles, 2007) Table 2: Biological source, chemical constituent, family and scientific name of each plant. Different methods of screening The following two screening methods are done to uncover the chemical properties and effects of usage of drug quercetin. Method 1 is about using High-Performance Liquid Chromatography with electrochemical detection (HPLC-ED) to extract rutin out of plant extracts based on its chemical properties. Method 2 is the involvement of guinea pigs to compare anti-asthmatic effect of quercetin with other drugs like cromolyn sodium. Screening 1: â€Å"Bronchoprotective activity in mice against various mediators.† Mice were exposed to either 4% w/v acetycholine bromide in 5% NaHà ¢Ã¢â‚¬Å¡Ã¢â‚¬Å¡POà ¢Ã¢â‚¬Å¡Ã¢â‚¬Å¾ or 5% egg-albumin or 2% w/v histamine dihydrochloride aerosol in histamine chamber under constant pressure. Bronchospasm was then induced. The mice showed progressive dyspnea. The end point of PCD (pre-convulsive dyspnea) was identified from the time of exposure to the onset of dyspnea, leading to convulsion. When PCD started, the mice were removed from the chamber and be exposed to the fresh air for recovery (Bahekar R.H. et al., 2000). After 2 days, the mice were given different test drugs. The time for onset of PCD was measured against that induced by acetycholine bromide, egg-albumin or histamine dihydrochloride aerosol. The bronchoprotective effect of each drugs was calculated using the following formula (Bahekar R.H. et al., 2000): Tà ¢Ã¢â‚¬Å¡Ã‚  was a mean of control PCD time. Tà ¢Ã¢â‚¬Å¡Ã¢â‚¬Å¡ was a PCD time after drug treatment. Screening 2: â€Å"Quercetin inhalation inhibits the asthmatic responses by exposure to aerosolized-ovalbumin in conscious guinea-pigs.† Guinea pigs were actively sensitized with aerosolized-ovalbumin (AOA) (2w/v% in saline, inhalation for 3 min) in the double-chambered plethysmograph, triggering immediate (IAR), late phase (LAR) and late late phase (LLAR) asthmatic response. A doubling in skin thickness means a success in sensitization. Recruitment of histamine, leukocytes, and protein contents, specific airway resistance (sRaw), and phospholipase A2 (PLA2) activity in bronchoalveolar lavage fluid (BALF) were measured. After that, the guinea pigs were made to inhale different test drugs for 2 minutes. The effect was compared between the drugs (Moon H et al, 2008). The respiratory function of guinea pigs were measured using double-chambered plethysmograph. Tidal volume, respiratory rate, tidal airflow and sRaw were measured. Quercetin reduced sRaw by 57.15 +/- 3.82% in IAR; 57.72 +/- 7.28% in LAR as well as 55.20 +/- 5.69% in LLAR. Cromolyn sodium significantly reduced sRaw in all three phases (Moon H et al, 2008). Comparison between screening 1 and screening 2: Both screening methods use animals as the in vivo test system, inhalation as dosage form and chamber as the place for induction of asthma in animals. Both are used to measure the anti-asthmatic effects of different test drugs. Screening method 1 Difference Screening method 2 Mice Test animals Guinea pigs 4% w/v acetycholine bromide in 5% NaHà ¢Ã¢â‚¬Å¡Ã¢â‚¬Å¡POà ¢Ã¢â‚¬Å¡Ã¢â‚¬Å¾ or 5% egg-albumin or 2% w/v histamine dihydrochloride aerosol Chemical inducing asthma effects Aerosolized-ovalbumin (AOA) (2w/v% in saline, inhalation for 3 min) The time for onset of PCD Measure of drug effects Tidal volume, respiratory rate, tidal airflow and sRaw Bahekar et al. Researchers Hee Moon et al. Table 3: Differences between the screening methods. Side effect of the plant drugs Despite the popular claims that drugs from natural sources are safe and effective over the long-term, patients should not be fooled for thinking that natural drugs are safer than synthetic modern medicines. The same goes to the anti-asthmatic drugs. The side effects of the plant drugs are: Drugs Side effects Caution Solutions Quercetin Headacheor tingling in arms and legs, kidney damage (high doses) (WebMD, 2013a) Pregnant orbreastfeeding Interaction with antibiotics Cyclosporine,warfarin, or drugs (the function can be changed by theliver) (WebMD, 2013). Consult your doctor if the symptoms do not resolve within 2 or 3 weeks after starting taking this medicine. Ephedrine Dizziness, headache, nausea, allergic reactions, difficulty urinating (Drugs.com, 2014). Allergy to this medication Asthma Monoamine oxidase (MAO) inhibitor High blood pressure Heart disease (Drugs.com, 2014a). Consult your doctor if the symptoms do not resolve within 1 week after starting taking this medicine or you develop a high fever. Cromolyn sodium Nausea, joint pain, headache,mild stinging, burning ortrouble sleeping (WebMD, 2013b). Allergy to cromolyn sodium Kidney disease Liver disease (Drugs.com, 2014b). Consult your doctor if the symptoms do not resolve within 2 or 3 weeks after starting taking this medicine. Theophylline Chest pain, fainting, increase in urine volume, pounding or rapid pulse, persistent vomiting, seizures and shakiness (Drugs.com, 2014c). Breastfeeding (Theophylline can be present in breast milk, harming the baby) Anyone under 18 years old without medical advice (Drugs.com, 2014c). When your body gets used to the drug, the side-effects will disappear. Seek for professional health to reduce these side-effects. Table 4: Side-effects, cautions and solutions for each plant drug. Natural plant drugs do have their side-effects. Drug users have to be alert with the effects and take necessary precautionary steps or consult a doctor when any suspicious symptoms are detected. Conclusion Nowadays, you can find countless of prescriptions and over-the-counter medicines derived from plants. During the ancient times, plants have been the exemplary sources of drugs.They just do not get created entirely from zero in lab, but the researchers and scientists trawled through jungles, wetlands, rivers and grasslands they can find, searching for better compounds to test against asthma. Some of the natural anti-asthmatics underwent the most vigorous clinical trials imaginable, while some were not recognized for its functions due to lack of valid evidence. For example, the benefits of Quercetin in asthma are not known, while theophylline is the certified first line treatment for decades. There are many other plant drugs that have similar anti-asthmatic activity, like wild Licorice, Gingko Biloba, Anise (apinene and creosol), garlic and leaf of Parsley. All must undergo the most stringent quality control and quality assurance, together with firm uphold of Global Manufacturing Pract ice to ensure the quality, efficacy and safety of the plant drugs. So far, there is no cure for asthma. The effects of all the anti-asthmatic drugs and medicine, no matter which group it belongs, discovered has been limited to managing and controlling symptoms of asthma. However, there are more and more studies and researches, hoping to find a perfect drug to effectively and safely cure asthma (Taur D.J. and Patil R.Y., 2011). Reference Bahekar R.H. et al. 2000. New Bronchodilators 2: Synthesis Of 6-Alkylbenzimidazo [1,2-C] Quinazolines.Indian Journal of Pharmaceutical Sciences, [Online]. 62/1, 41-45. Available at: http://www.ijpsonline.com/article.asp?issn=0250-474X;year=2000;volume=62;issue=1;spage=41;epage=45;aulast=Bahekar;type=0[Accessed 17 November 2014]. Climbjm, (2000),Mormon Tea in Arches NP[ONLINE]. Available at: http://upload.wikimedia.org/wikipedia/commons/thumb/f/f2/Mormon_Tea_in_Arches_NP_-_July_2008.jpg/1024px-Mormon_Tea_in_Arches_NP_-_July_2008.jpg[Accessed 09 November 14]. Drug Bank. 2014a.Quercetin. [ONLINE] Available at:http://www.drugbank.ca/drugs/DB04216. [Accessed 20 November 14]. Drug Bank. 2014b.Cromoglicic acid.Available: http://www.drugbank.ca/drugs/DB01003. Last accessed 6th Nov 2014. Drug Bank. 2014c.Theophylline.Available: http://www.drugbank.ca/drugs/DB00277. Last accessed 6th Nov 2014. Drug Bank. 2014d.Ephedrine.Available: http://www.drugbank.ca/drugs/DB01364. Last accessed 6th Nov 2014. Drugs.com. 2009.Khella. [ONLINE] Available at:http://www.drugs.com/npp/khella.html. [Accessed 12 November 14]. Drugs.com. 2014a.Ephedrine.Available: http://www.drugs.com/ephedrine.html. Last accessed 7th Nov 2014. Drugs.com. 2014b.Cromolyn sodium. [ONLINE] Available at:http://www.drugs.com/mtm/cromolyn-sodium.html. [Accessed 20 November 14]. Fuse809, (2014),Structure of[ONLINE]. Available at: http://upload.wikimedia.org/wikipedia/commons/thumb/7/7f/Theophylline2DCSD.svg/612px-Theophylline2DCSD.svg.png[Accessed 20 November 14]. Fvasconcellos, (2009),Skeletal formula of cromoglicic acid (cromoglicate, cromolyn)[ONLINE]. Available at:http://upload.wikimedia.org/wikipedia/commons/thumb/1/10/Cromoglicic_acid.svg/970px-Cromoglicic_acid.svg.png[Accessed 20 November 14]. Grieve M. 2014.Cacao. [ONLINE] Available at:https://www.botanical.com/botanical/mgmh/c/cacao-02.html. [Accessed 12 November 14]. Luisovalles, 2007,Matadecacao[ONLINE]. Available at: http://upload.wikimedia.org/wikipedia/commons/thumb/5/5a/Matadecacao.jpg/640px-Matadecacao.jpg[Accessed 09 November 14]. Moon H. et al. 2008. Quercetin inhalation inhibits the asthmatic responses by exposure to aerosolized-ovalbumin in conscious guinea-pigs.Archives of Pharmacal Research. 31 (6), p771-772. NEUROtiker, (2008),Structure of (−)-Ephedrine[ONLINE]. Available at:http://upload.wikimedia.org/wikipedia/commons/thumb/9/91/(-)-Ephedrin.svg/207px-(-)-Ephedrin.svg.png[Accessed 20 November 14]. RxList. 2009.Ephedrine.Available: http://www.rxlist.com/ephedrine-drug/clinical-pharmacology.htm. Last accessed 6th Nov 2014. Sipler D, 2004,Ammi Visnaga[ONLINE]. Available at: http://upload.wikimedia.org/wikipedia/commons/thumb/1/15/Ammi_Visnaga_(289632722).jpg/800px-Ammi_Visnaga_(289632722).jpg[Accessed 09 November 14]. Taur D.J., Patil R.Y. (2011). Some medicinal plants with antiasthmatic potential: a current status.Asian Pac J Trop Biomed. 1 (5), p413–418. Thomà © O.W., 1885,Illustration Capparis spinosa0[ONLINE]. Available at:http://upload.wikimedia.org/wikipedia/commons/thumb/7/7c/Illustration_Capparis_spinosa0.jpg/640px-Illustration_Capparis_spinosa0.jpg[Accessed 11 November 14]. WebMD. 2013a.Quercetin.Available: http://www.webmd.com/vitamins-and-supplements/quercetin-uses-and-risks. Last accessed 7th Nov 2014. WebMD. 2013b.Mast Cell Stabilizers for Long-Term Control of Asthma. [ONLINE] Available at: http://www.webmd.com/asthma/mast-cell-stabilizers-for-long-term-control-of-asthma. [Accessed 20 November 14]. Winter R. 1978. A Consumers Dictionary of Food Additives. Crown Publishers, Inc., New York. Yikrazuul, (2008),Quercetin[ONLINE]. Available at: http://upload.wikimedia.org/wikipedia/commons/thumb/8/81/Quercetin.svg/800px-Quercetin.svg.png[Accessed 20 November 14].