INTRODUCTION - AXIOLYTIC PROPERTY OF CAESALPINIA PULCHERRIMA LEAVES EXTRACTS IN EXPERIMENTAL ANIMALS

 

INTRODUCTION

 

            It’s normal to feel anxious when facing a challenging situation, such as a job interview, a tough exam, or a blind date. But if your worries and fears seem overwhelming and interfere with your daily life, you may be suffering from an anxiety disorder. There are many different types of anxiety disorders—and many effective treatments and self-help strategies. Once you understand your anxiety disorder, there are steps you can take to reduce your symptoms and regain control of your life.¹

 

            Anxiety is a normal reaction to stress and can actually be beneficial in some situations. For some people, however, anxiety can become excessive. While the person suffering may realize their anxiety is too much, they may also have difficulty controlling it and it may negatively affect their day-to-day living.²

 

            The first consideration is the possibility that anxiety is due to a known or unrecognized medical condition. Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse) is a diagnosis that often is missed.³

 

            Genetic factors significantly influence risk for many anxiety disorders. Environmental factors such as early childhood trauma can also contribute to risk for later anxiety disorders. The debate whether gene or environment is primary in anxiety disorders has evolved to a better understanding of the important role of the interaction between genes and environment. Some individuals appear resilient to stress, while others are vulnerable to stress, which precipitates an anxiety disorder.³

            In the central nervous system (CNS), the major mediators of the symptoms of anxiety disorders appear to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). Other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms.³

 

            Research and treatment trials suggest that abnormalities in serotonin neurotransmission in the brain are meaningfully involved in obsessive-compulsive disorder (OCD). This is strongly supported by the efficacy of serotonin reuptake inhibitors in the treatment of OCD.³

 

            Unlike the relatively mild, brief anxiety caused by a stressful event (such as speaking in public or a first date), anxiety disorders last at least 6 months and can get worse if they are not treated. Each anxiety disorder has different symptoms, but all the symptoms cluster around excessive, irrational fear and dread.² Despite their different forms, all anxiety disorders share one major symptom: persistent or severe fear or worry in situations where most people wouldn’t feel threatened.⁴ In addition to the primary symptoms of irrational and excessive fear and worry, other common emotional symptoms of anxiety include, feelings of apprehension or dread, trouble concentrating, feeling tense and jumpy, anticipating the worst, irritability, restlessness, watching for signs of danger, feeling like your mind’s gone blank.⁴

 

            Anxiety is more than just a feeling. As a product of the body’s fight-or-flight response, anxiety involves a wide range of physical symptoms. Because of the numerous physical symptoms, anxiety sufferers often mistake their disorder for a medical illness. They may visit many doctors and make numerous trips to the hospital before their anxiety disorder is discovered.⁴

 

            Anxiety related illnesses are bipolar disorder, eating disorder, headache, iiritable bowel syndrome (IBS), sleep disorder, substance abuse.⁵ In general, anxiety disorders are treated with medication, specific types of psychotherapy, or both. Treatment choices depend on the problem and the person’s preference. Antidepressants were developed to treat depression but are also effective for anxiety disorders. Although these medications begin to alter brain chemistry after the very first dose, their full effect requires a series of changes to occur; it is usually about 4 to 6 weeks before symptoms start to fade. It is important to continue taking these medications long enough to let them work. Some of the newest antidepressants are called selective serotonin reuptake inhibitors, or SSRIs. SSRIs alter the levels of the neurotransmitter serotonin in the brain, which, like other neurotransmitters, helps brain cells communicate with one another. SSRIs have fewer side effects than older antidepressants, but they sometimes produce slight nausea or jitters when people first start to take them. These symptoms fade with time. Some people also experience sexual dysfunction with SSRIs, which may be helped by adjusting the dosage or switching to another SSRI.²

 

            Tricyclics are older than SSRIs and work as well as SSRIs for anxiety disorders other than OCD. They are also started at low doses that are gradually increased. They sometimes cause dizziness, drowsiness, dry mouth, and weight gain, which can usually be corrected by changing the dosage or switching to another tricyclic medication.²

 

            The MAOIs most commonly prescribed for anxiety disorders are phenelzine (Nardil®), followed by tranylcypromine (Parnate®), and isocarboxazid (Marplan®), which are useful in treating panic disorder and social phobia. People who take MAOIs cannot eat a variety of foods and beverages (including cheese and red wine) that contain tyramine or take certain medications, including some types of birth control pills, pain relievers (such as Advil®, Motrin®, or Tylenol®), cold and allergy medications, and herbal supplements; these substances can interact with MAOIs to cause dangerous increases in blood pressure. The development of a new MAOI skin patch may help lessen these risks. MAOIs can also react with SSRIs to produce a serious condition called “serotonin syndrome,” which can cause confusion, hallucinations, increased sweating, muscle stiffness, seizures, changes in blood pressure or heart rhythm, and other potentially life-threatening conditions.²

 

            Anti-anxiety drugs like high-potency benzodiazepines combat anxiety and have few side effects other than drowsiness. Because people can get used to them and may need higher and higher doses to get the same effect, benzodiazepines are generally prescribed for short periods of time, especially for people who have abused drugs or alcohol and who become dependent on medication easily. One exception to this rule is people with panic disorder, who can take benzodiazepines for up to a year without harm.²

            Clonazepam (Klonopin®) is used for social phobia and GAD, lorazepam (Ativan®) is helpful for panic disorder, and alprazolam (Xanax®) is useful for both panic disorder and GAD.² Some people experience withdrawal symptoms if they stop taking benzodiazepines abruptly instead of tapering off, and anxiety can return once the medication is stopped. These potential problems have led some physicians to shy away from using these drugs or to use them in inadequate doses.² Buspirone (Buspar®), an azapirone, is a newer anti-anxiety medication used to treat GAD. Possible side effects include dizziness, headaches, and nausea. Unlike benzodiazepines, buspirone must be taken consistently for at least 2 weeks to achieve an anti-anxiety effect.²

 

            Antianxiety drugs, like other drugs used in psychiatry, can cause a wide range of adverse effects. All antianxiety drugs have the potential to produce untoward effects on higher cerebral functions, although the effect seen is also influenced by psychological and social factors. The most common effects is oversedation, which is a particular problem for the very young and the very old. It is also a serious problem for those who drive motor vehicles and may be a hazard when working in dangerous situations. Dependence on antianxiety drugs is well known, but only recently has it been recognised that dependence on benzodiazepines is a larger problem than previously realized.⁶   

 

            The increasing awareness of herbal medicine is acknowledged by WHO.  WHO estimate about three quarters of the world population currently used herbs and other forms of traditional  medicine  to  treat  there diseases.  WHO has  recently defined traditional medicine (including herbal drugs) as comprising therapeutic practices that have been in existence, almost for several hundred years. The traditional preparation comprises medicinal plants, minerals, organic matter, etc. Herbal drugs constitute only those traditional medicines which are primarily use medicinal plant preparation for therapy.⁷

 

            Natural drug from the plants are gaining popularity because of several advantages such as often fewer side effect, better patient tolerance, relatively less expensive and acceptance due to a long history of use, especially herbal medicines provide rational means for the treatment of many diseases that are obstinate and incurable in other system of medicine.⁸ The first point to make is that roughly half of today’s prescription and over-the-counter medicines are derived from plants. New drugs don’t just get created in the lab. Scientists trawl through jungles, rivers, wetlands and any other natural habitat they can find, looking for a new compound to test against all the sample viruses and bacteria they keep for this purpose. In other words, natural medicine really is the basis for modern medical practice, just a few steps back along the line of development. The difference is that you are taking a 100% natural product, rather than one that has been processed in a lab and lost much of its goodness along the way. Secondly, herbal medicine has gone through the most rigorous clinical trial imaginable! After thousands of years of regular use by a cross-section of the population, it’s safe to say that any side effects or interactions have been well documented and explored. Lastly, remember that natural supplements often bring other benefits beyond what you strictly expect. For example, you might take fever few to give relief from a migraine, then find that your stomach upset has also disappeared. These dual effects are what makes herbology so interesting.⁹

 

                There are several plants very effective in treating stress / anxiety; such plants include Passiflora incarnata (Passion flower) due to presence of bioactive phytomoiety (benzoflavone)¹⁰  and flavonoids in Dolichandrone falcata leaves.¹¹ One such plant Caesalpinia pulcherrima contains isoflavones, flavones,chalcones, flavanols, flavones, sterols and diterpenoids.¹² Recent study on anxiety claims that the flavonoids, alkaloids and terpenoids are responsible for anxiolytic (anti anxiety) and sedative activity^13,14,15.

 

                The literature reveals that the plant Caesalpinia pulcherrima possesses various bioactive compounds along with flavonoids (flavones) and there is no scientific data on anxiolytic activity of Caesalpinia pulcherrima leaves. In view of this, the primary aim of the present study is to investigate the possible anxiolytic activity of Caesalpinia pulcherrima leaves extract in laboratory animal.