ANTIANXIETY PROPERTY OF BASELLA ALBA LINN LEAVES EXTRACT IN EXPERIMENTAL ANIMALS - INTRODUCTION

 

1. INTRODUCTION

 

            Anxiety disorders are marked by excessive fear (and avoidance), often in response specific objects or situation and in the absence too danger, and they are extremely common in the general population. According to a recent epidemiological study, the life time prevalence any anxiety disorder is 28.8%¹. Anxiety disorders are associated with impaired work place performance and hefty economic costs². Anxiety and stress related problems are so common today, that approximately 40 million Americans or 18 % adult population, suffer from anxiety disorders each year³.

         Anxiety disorders as recognized clinically include, generalized anxiety -GAD(an ongoing state of excessive anxiety lacking any clear reason or focus), panic disorders-PD (attacks of overwhelming fear occurring in association with marked somatic symptoms, such as sweating, tachycardia, chest pain, trembling, chocking, etc), phobias (strong fears of specific things or situations e.g. snakes, open spaces, flying, social interaction) post traumatic stress disorder-PTSD (anxiety triggered by insistent recall of past stressful experiences) ⁴. Anxiety is also an important component of many other psychiatric or medical conditions.

        Major drug classes for the treatment of anxiety disorders are Benzodiazepines (BZDs), Selective serotonin-reuptake inhibitors (SSRIs), Tricyclic antidepressant,          β-blockers, and Azapirones⁵. All this drug classes currently used are associated with side effects that very occurrence and severity. Effective treatment such as anxiolytic drug therapy or cognitive behavioural therapy exists but, many patients remain untreated, experience adverse effects of benzodiazepines, or do not benefit from full symptom control⁶. All this drug classes currently used are associated with side effects that very occurrence and severity. Like BZDs produce undesirable effects such as Benzodiazepines (e.g., diazepam, nitrazepam, lorazepam, alprazolam) are the most frequently prescribed synthetic chemical drugs for a variety of conditions, particularly anxiety, depression, epilepsy and insomnia^7,8. The prevailant prescription pattern of benzodiazepines is symptomatic which results in their potential overuse⁹. Chronic use of benzodiazepines causes deterioration of cognitive functioning¹⁰, physical dependence¹¹ and tolerance^{12, 13}. Besides addiction-liabilities, benzodiazepines adversely affect the respiratory, digestive and immune systems of the body¹⁴, drowsiness, ataxia, and sedation, muscle relaxation, hepatotoxicity and they adversely interact with other CNS depressants, particularly alcohol¹⁵. Since, the chronic treatment with benzodiazepines often proves more harmful in the longer run. the realization that benzodiazepines present a narrow safety margin between the anxiolytic effect and those causing unwanted side effects has prompted many researchers to evaluate new compounds in the hope that other anxiolytic drugs will have less undesirable effects.  Hence there is needed to look for more efficacious anxiolytic agents with lesser side effects. Many herbal plants are available to be best herbs for anxiety. It has been estimated that 43% of anxiety suffers use some form of complementary therapy. The most popular treatments include herbal medicines. Similarly, anxiety disorders are amongst the most common reason for people to try with herbal medicines ⁶.

        The use of the medicinal herbs for curing disease has been documented in history of all civilization. Man in the prehistoric era was probably not aware about the health hazards associate with the irrational therapy with the onset of research in medicine. It was concluded that plants contain active principles, which are responsible for the curative action of the herbs. The isolated active constituent of medicinal herbs and after testing some found to be therapeutically active¹⁶. Medicinal plants are now becoming more widely used by people all over the world. People understand the gentle strength of these natural remedies. Doctors and scientist are validating the wisdom of traditional use. Although a few of the remedies are strong, all can be used safely and without the side effects of drugs. Furthermore, these natural remedies can be used to cure problems rather than just mask symptoms. Much of the information about medicinal plant is in the form of actions. Rather than saying a plant is used for insomnia, many references will state that it has the action “sedative” or “hypnotic” properties and actions of medicinal plants describes the action of the plants on the body ¹⁷

          The increasing awareness of herbal medicine is acknowledged by WHO. WHO estimate about three-quarters of the world’s population currently use herbs and other forms of traditional medicines to treat their diseases. WHO has recently defined traditional medicine (including herbal drugs) as comprising therapeutic practices that have been in existence, almost for several hundred years, before the development and spread of modern medicine and are still in use today. The traditional preparations comprise medicinal plants, minerals, organic matter, etc. herbal dugs constitute only those traditional medicines, which are primarily use medicinal plants preparations for therapy ¹⁸.

           The development of new anxiolytic drug has been an area of interest. There is growing interest in the various types of herbs and herbal medicines being used as anxiolytic drugs. Ethnopharmacological studies and ethnobotanical surveys points to growing interest in the screening and understanding role of various herbs in CNS related disorders – especially on neuro and psychopharmacological aspects. There is a considerable popular interest in the use of natural remedies or herbal products.

           There are several plants very effective in treating stress / anxiety, such plants   include Matricaria chamomilla (chamomile), Hypericum perforatum (St.Jons wort), Piper methysticum (Kava kava)¹⁹, Scutellaria lateriflora ( Blue skullcap), Centella asiatica (Centella asiatica), Paullinia cupana (Guarana), Bacopa monniera (Keenmins), Cymbopogon citratus (Lemon grass), Valeriana officinalis (Valerian) ⁶.

 Pssiflora incarnate (Passion flower)²⁰. Dolichandrone falcata, contain chrysin flavones is subgroup of flavonoid present in bark²¹ and leaves also contain chrysin and Chrysin 7-rutinoside²². The active constituent mention above reported to have many biological activities, and one among them is for anxiolytic activity²³.There are herbal treatments that have been used in India for ages, including Brahmi and Shankhapushpi. After thousands of years of use in Indian Ayurvedic medicine, Brahmi has been proven to be an affective anxiolytic in over 30 clinical studies. There are no known side effects regarding the use of Brahmi and it does not contain any addictive ingredients. Shankhapushpi has also been used in India for hundreds of years for nervous disorders such as stress, anxiety and insomnia ²⁴. There are several plants reported to possess antianxiety activity due to presence of flavonoids like- Tilia americana^25,26, Dioclea grandiflor²⁷, Passiflora edulis²⁸, Passiflora coerulea²⁹. Basella alba L. is reported to contain a flavonoids^,31,32; more specifically kaempferol(kaempherol) type of flavonoid³². Kaempferol is reported to exert an anxiolytic (anti-anxiety) activity in plants like Tilia americana ^25,26 and apocynum venetum³³. which suggest that the Basella alba may possess antianxiety property.

 Basella alba is a fast-growing, soft-stemmed vine, reaching 10 m in length. Its thick, semi-succulent, heart-shaped leaves have a mild flavour and mucilaginous texture.

 

            The stem of the cultivar Basella alba is reddish-purple. Basella alba contains carbohydrates, glycosides, fixed oils, fats, flavonoids, mucilages, steroids and triterpenoids³⁰. Basella alba contains kaempferol type of flavonoid³². The paste of root of red Basella alba along with rice washed water is taken in the morning in empty stomach for one month to cure irregular periods by the rural people of Orissa, India ^34,35.Leaves of Basella alba is used for the treatment of hypertension by Nigerians in Lagos³⁶.Basella alba is used as antimalarial  in  cameroonian  folk  medicine³⁷.The daily consumption of Indian spinach has a positive effect on vitamin A stores in populations at high risk of vitamin A deficiency³⁸.The cooked roots and leaves have been reported to be used in the treatment of diarrhoea and as laxative, respectively³⁸The flowers are used as an antidote for poisons³⁸.It is also a safe aperient for pregnant women and its decoction has been used to alleviate labour³⁸.Basella alba traditionally claimed to increase libido³⁹Aqueous extract of Basella alba leaves increases red blood cell count in albino rats³⁸.Basella alba leaves extract possess anti inflammatory activity⁴⁰.Betacyanin present in Basella alba fruit gives antioxidant activity³¹.Basella alba extracts significantly enhances testosterone production in bull and rat Leydig cells in a concentration-dependent manner⁴¹.Extract of aerial parts of Basella alba shows CNS depressant activity³⁰.Basella alba leaves extract possess gastro protective action⁴². Review of literature, till date, regarding Basella alba is carried out by chemical abstract, biological abstract, medicinal abstract and other national and international scientific journals. The different parts of Basella alba have been screened for various pharmacological activities but there is no report regarding the anti anxiety activity of Basella alba leaves so far. Upon literature survey leaves of Basella alba is said to possess flavonoids^30,31,32 like kaempferol³² and kaempferol is  reported to be effective in treating stress / anxiety in plants like Tilia americana ^25,26 and apocynum venetum³³. Flavonoids have also been reported to exert wide range of biological activities. These includes: anti-inflammatory, antibacterial, antiviral, antiallergic^42,43,44, cytotoxic antitumor, treatment of neurodegenerative diseases, vasodilatory action^43,45,46,47. In addition flavonoids are known to inhibit lipid-peroxidation, platelet aggregation, capillary permeability and fragility, cyclo-oxygenase and lipoxygenase enzyme activities. They exert these effects as antioxidants, free radical scavengers, chelators of divalent cation^44,47,48. These are also reported to inhibit variety of enzymes like hydrolases, hyalouronidase, alkaline phosphatase, arylsulphatase, cAMP phosphodiesterase, lipase, α-glucosidase, kinase⁴⁹.

          Several flavones are present in are Basella alba plant which suggest that the leaves may possess antianxiety property. However, the literature survey has no scientific data on anxiolytic (anti-anxiety) activity on Basella alba leaves. In view of this, the primary aim of the present study is to investigate the possible antianxiety activity of Basella alba leaves extracts in laboratory animals.