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Pharmacognosy Communications

An Official Publication of Pharmacognosy Network Worldwide [Phcog.Net] www.phcogcommn.org | www.phcog.net

Editor-in-Chief

Dr Ian Cock

Biomolecular and Physical Sciences Griffith University, Nathan campus,

170 Kessels Rd, Nathan, Queensland 4111 Australia

Editorial Board Members Dr. William N. Setzer, Professor and Chair

Department of Chemistry The University of Alabama in Huntsville

Huntsville, AL 35899, USA

Dr. Khuraman MUSTAFAYEVA

Pharmaceutical faculty Azerbaijan Medical University

Dr David Ruebhart HydroTox Services Melbourne Australia Dr. Omayma A. El Dahshan, Ph D Pharmacognosy Dept., Faculty of pharmacy, Ain shams University,

Cairo, Egypt

Dr. Michał Tomczyk

Medical University of Białystok, Faculty of Pharmacy, Department of Pharmacognosy,

ul. Mickiewicza 2a, 15-089 Białystok, Poland

Prof. Ameenah Gurib-Fakim,

CEPHYR Ltd (Centre for Phytotherapy and Research) 7th Floor, Cyber Tower 2

Ebene, Mauritius

Dr. Philip G. Kerr PhD

School of Biomedical Sciences Charles Sturt University Wagga Wagga NSW 2678

Australia

Prof. Dr. Rimantas Venskutonis

Department of Food Technology Kaunas University of Technology Radvilenu pl. 19, Kaunas LT-50254, Lithuania

Editor - Publications Dr. Mueen Ahmed KK

Aim and Scope

Phcog Commn. is aimed at a broad readership, publishing articles on all aspects of pharmacognosy, and related fields. The journal aims to increase understanding of pharmacognosy as well as to direct and foster further research through the dissemination of scientific information by the publication of manuscripts.

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Editorial

*Correspondence: Tel.: +61 7 37357637; fax: +61 7 37355282 E-mail: [email protected] (I. E. Cock).

DOI: 10.5530/pc.2011.1.1

Pharmacognosy Communications:

The Scope of Pharmacognosy

I. E. Cocka,b_*

a_{Biomolecular and Physical Sciences, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, Brisbane, Queensland 4111, Australia.} b_{Environmental Futures Centre, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, Brisbane, Queensland 4111, Australia}

Pharmacognosy is the branch of pharmacology that studies drugs in their crude and/or natural states.[1]_{In general, when} we describe pharmacognosy, we are usually referring to plant based medicinal systems. However, it is important to note that medicinal preparations may also be derived from animal sources as well as from fungi and microorganisms. Indeed, the discovery of the fungal antibiotic agent penicillin (from Penicillinum spp.) [2] is one of the most important medicinal findings to date. Many other useful medicinal products are also derived from fungi including the immunosuppressant mycophenolic acid (also from Penicillinum spp.)[3]_{and purgative anthraquinone emodin (from} Penicillium islandicum).[4]_{Also, numerous hallucinogenic substances} (eg. psilocin and psilocybin) are produced by Psilocybe spp. (family Tricholometaceae) of fungi.[5]

Similarly, numerous medicinal agents are produced by bacteria, especially further antibiotic agents. Very early studies demonstrated the antibiotic potential of bacteria towards other bacterial species. In 1887 it was accidently discovered that prior injection of Streptococcus erysipelatis protected guinea pigs from developing cholera when injected with Vibrio cholera.[6]_{Furthermore, it was} also shown that previous injection of either Streptococcus erysipelatis or Pseudomonas aeruginosa also prevented the development of anthrax in experimental animals injected with Bacillus anthracis[6] and that pre-injection of sterilised cultures of the protective bacteria have the same protective effect as live bacteria.[7]_This discovery stimulated further studies into the antibiotic activity of bacteria, resulting in the discovery of streptomycin, chloramphenicol, chlortetracycline, tetracycline, erythromycin, neomycin and numerous other antibiotics, especially from Streptomyces spp. (family Streptomycetaceae). Other bacteria, particularly Bacillus spp., are noted for their production of antibiotic polypeptides such as actinomycin,[8]_bacitracin,[9] tyrothrycin[10]_{and polymixin.}[10]_{These antibiotic polypeptides} were initially not widely used as they also display strong cytotoxic

properties. More recently, there is renewed interest in their use due to their antitumor potential. Indeed, the bacterial antibiotic polypeptides doxorubicin, daunorubicin and actinomycin D are now routinely used in the treatment of a variety of cancers.[11,12] Although the number of animal derived pharmacognostical agents is small when compared to fungi, bacteria and plants, there has recently been an increase in interest in marine creatures as a source of new drugs. Marine invertebrates in particular, account for much of the recent publications describing animal pharmacognosy. Some species of sponges have been found to have antibacterial, antifungal, antimalarial, cytotoxic and anticancer bioactivities.[13]_{Furthermore, sponges produce interesting} metabolites including bromophenols, cyclic peroxides, peroxyketals and modified sesquiterpenes which warrant further investigation. [13] The soft coral Sarcophyton glaucum produces the diterpenoids sarcophytol A and sarcophytol A, which have tumour inhibiting bioactivity.[14]

Whilst marine animals are receiving much recent interest, there are also many examples of pharmacognostical agents derived from terrestrial animals. For examples, bees (Apis mellifica) provide us with multiple useful medicinal properties. The antimicrobial activity of honey produced by bees feeding on some plant species is known to be exceptionally good. Manuka honey (made by bees feeding on the Eastern Australian/New Zealand plant Leptospermum scoparium) is an especially good antimicrobial agent. [15] Additionally, beeswax and royal jelly are also reported to have therapeutic properties.[16]_{Toad skins contain cardioactive agents} and were used to treat oedema prior to the development of more effective agents.[17]_{Pharmacognostic agents produced by} vertebrates include lanolin from wool, gelatine and musk. In my own region of the world (Australia) there is also much interest in oils obtained from emu for its many therapeutic properties. [18] Inorganic chemicals may also have important medicinal properties. Silver is particularly well known for its antibacterial activity[19] and has been used since the times of ancient Greece. Silver nanoparticles have also been shown to have a potent cytoprotective bioactivity towards HIV infected cells.[20]_{Gold thiolates have been}

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• Natural product discovery and evaluation

• Mechanistic studies

• Method and technique development and evaluation

• Isolation, identification and structural elucidation of natural products

• Synthesis and transformation studies

We look forward to receiving your valuable pharmacognosy communications.

REfEREnCES

1. The American Heritage Medical Dictionary, 2007, Houghton Mifflin Company, USA. 2. Fleming A, 1928, On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B. Influenza. British Journal of Experimental Pathology, 10, 216-226.

3. Florey HW, Gilliver K, Jennings MA, Sanders AG, 1946, Mycophenolic acid, an antibiotic from Penicillium brevi-campactum Dierckx. Lancet, 1, 46-49.

4. Ghosh AC, Manmade A, Demain AL, 1977, Toxins from Penicillium islandicum Sopp. In Mycotoxins in Human and Animal Health, Edited by Rodricks JV, Hesseltine CW, Mehlman MA, Pathotox, Chicago, USA, 625-638.

5. Hofmann A, Heim R, Brack A, Kobel H, 1958, Psilocybin ein psychotroper Wirkstoff aus dem moscikanischen Rauschpilz Psilocybe mexicana Heim. Experientia, 14, 107.

6. Bouchard C, 1889, Influence qu’exerce sur la maladie charbonneuse l’inoculation du bacilli pyocyanique, Comptes Rendus de l’Académie des Sciences, 108, 713-714.

7. Woodhead GS, Wood C, 1889, De l’action antidotique exercée par les liquids pyocyaniques sur le cours de la maladie charbonneuse. Comptes Rendus de l’Académie des Sciences, 109, 985-988.

8. Waksman SA, Woodruff HB, 1940, Bacteriostatic and bactericidal substances produced by soil actinomycetes. Proceedings of the Society for Experimental Biology and Medicine, 45, 609-614.

9. Johnson BA, Anker H, Meleney FL, 1945, Bacitracin: a new antibiotic produced by a member of the B. Subtilise group. Science, 102, 376-377.

10. Dubos RJ, Hotchkiss RD, 1941, The production of bactericidal substances by aerobic sporulating Bacilli. Journal of Experimental Medicine, 73, 5, 629-640. 11. Lasek W, Giermasz A, Kuc K, Wańkowicz A, Feleszko W, Golab J, Zagozdzon R,

Stoklosa T, Jakobisiak M, 1996, Potential of the anti-tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results. International Journal of Cancer, 66, 374-379.

12. Weiss RB, 1992, The anthracyclines: will we ever find a better doxorubicin? Seminars in Oncology, 19, 6, 670-686.

13. Fusetani N, Matsunaga S, 1993, Bioactive sponge peptides. Chemistry Reviews, 93, 1793-1806.

14. Wei H, Frenkel K, 1992, Suppression of tumor promoter-induced oxidative events and DNA damage in vivo by sarcophytol A: A possible mechanism of antipromotion. Cancer Research, 52, 2298-2303.

15. Brophy JJ, Goldsack RJ, Bean AR, Forster PI, Lepschi BJ, 1991, Leaf essential oils of the genus Leptospermun (Mytaceae) in Eastern Australia. Part 5,

Leptospermum continentale and its allies. Flavour and Fragrance Journal, 14,

98-104.

16. Fujii A, 1995, Pharmacological effect of royal jelly. Honeybee Science, 16, 97-104. 17. Chen KK, Kovariková A, 1967, Pharmacology and toxicology of toad venom.

Journal of Pharmaceutical Sciences, 56, 12, 1535-1541.

18. Whitehouse MW, Turner Ag, Davis CKC, Roberts MS, 1998, Emu oil(s): A source of non-toxic transdermal anti-inflammatory agents in Aboriginal medicine, Inflammopharmacology, 6, 1-8.

19. Feng QL, Wu J, Chen GQ, Cui FZ, Kim TN, Kim JO, 2000, A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus, Journal of Biomedical Materials Research, 52, 662-668.

20. Sun RWY, Chen R, Chung NPY, Ho CM, Lin CLS, Che CM, 2005, Silver nanoparticles fabricated in Hepes buffer exhibit cytoprotective activities towards HIV-1 infected cells. Chemistry Communications, 40, 5059-5061.

21. Parish RV, Cottrill SM, 1987, Medicinal gold compounds, Gold Bulletin, 20, 3-12. 22. Easmon J, Pürstinger G, Heinisch G, Roth T, Fiebig HH, Holzer W, Jäger W, Jenny

M, Hofmann J, 2001, Synthesis, cytotoxicity, and antitumor activity of copper(II) used in the treatment of rheumatoid arthritis and as anti-tumour

agents (as reviewed in Parish and Cottrill).[21]_{A variety of copper} and iron complexes demonstrate potent cytotoxic activities against human cancer cells.[22]_{Recent studies have highlighted the} importance of selenium in blocking the production of reactive oxygen species (ROS) and thus blocking oxidative stress and its associated disease states and medical conditions. [23]_{A variety of} other inorganic molecules and ions also have medicinal promise, possibly also through their maintenance of cellular redox state. Despite the importance of pharmacognostic agents from fungi, microorganisms and animals, plants provide us with the greatest variety of medicinal agents and arguably hold the most promise for future drug discovery. Asian medicinal botany in particular has been especially well documented. Traditional Chinese Medicinal (TCM) systems and Indian Ayuverda are widely practiced with approximately 85% of Indians regularly using crude plant formulations for the treatment of various diseases and ailments.[24]_{Similarly, African and Middle Eastern medicinal} ethnobotanies are also widely practiced well documented. Even allopathic/Western medicine practiced in developed countries owes much to our understanding of plant based remedies. Indeed, it has been estimated that approximately 25% of all prescription drugs currently in use are originally derived from plants.[26,27] Furthermore, approximately 75% of new anticancer drugs marketed between 1981 and 2006 are derived from plant compounds.[26]_{Recently, there has been an increase in interest} in pharmacognosy and natural therapies due to the perception that natural therapeutics offer a safer alternative than synthetic formulations due to their organic origin. This is reflected in the dramatic increase in publications in pharmacognosy journals over the period 2005-2010.[28]_{It is evident that a further publication} outlet is required to accommodate this expanding field. Pharmacognosy Communications is a new journal published by Pharmacognosy Network Worldwide [www.phcog.net]. We aim to publish high quality original research articles, methods, techniques and evaluation reports, critical reviews, short communications, commentaries and editorials of all aspects of pharmacognosy research. The journal is aimed at a broad readership, publishing articles on all aspects of pharmacognosy, and related fields. The journal aims to increase understanding of pharmacognosy as well as to direct and foster further research through the dissemination of scientific information by the publication of manuscripts. The submission of original contributions in all areas of pharmacognosy are welcomed. The journal aims to cater the latest outstanding developments in the field of pharmacognosy and natural products and drug design covering but not limited to the following topics:

• Pharmacognosy and pharmacognistic investigations

• Research based ethnopharmacological evaluations

• Biological evaluation of crude extracts, essential oils and pure isolates

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25. Newman DJ, Cragg GM, Snader KM, 2000, The influence of natural products on drug discovery. Natural Product Reports, 17, 215-234.

26. Hostettmann K, Hamburger M, 1993, Search for new lead compounds of natural origin. In Perspectives in Medical Chemistry, Testa B, Kyburz E, Fuhrer W, Giger R (eds), Verlag Helvitica Acta, Basel.

27. Ahmed MKK, 2011, New challenges in the new year for Pharmacog Mag.: 5 years of quality publication. Pharmacognosy Magazine, 7, 25, 1-3.

and iron(II) complexes of 4_{N-azabiclo[3.2.2]nonane thiosemicarbazones derived} from acyl diazines, Journal of Medicinal Chemistry, 44, 13, 2164-2171. 23. Venardos K, Harrison G, Headrick J, Perkins A, 2004, Effects of dietary selenium

on glutathione peroxidise and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion, Journal of Trace Elements in Medicine and Biology, 18, 1, 81-88.

24. Kamboj VP, 2000, Herbal medicine. Current Science, 78, 35-39.

AbouT jouRnAl

P h a r m a c o g n o s y Communications [Phcog Commn.] www.phcogcommn. org is a new journal published by Pharmacognosy Network Worldwide [www.phcog.net]. It is a peer reviewed journal aiming to publish high quality original research articles, methods, techniques and evaluation reports, critical reviews, short communications, commentaries and editorials of all aspects of medicinal plant research. The journal is aimed at a broad readership, publishing articles on all aspects of pharmacognosy, and related fields. The journal aims to increase understanding of pharmacognosy as well as to direct and foster

further research through the dissemination of scientific information by the publication of manuscripts. The submission of original contributions in all areas of pharmacognosy are welcome. The journal aims to cater the latest outstanding developments in the field of pharmacognosy and natural products and drug design covering but not limited to the following topics:

• Pharmacognosy and pharmacognistic investigations

• Research based ethnopharmacological evaluations

• Biological evaluation of crude extracts, essential oils and pure isolates

• Natural product discovery and evaluation

• Mechanistic studies

• Method and technique development and evaluation

• Isolation, identification and structural elucidation of natural products

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Invited Review

*Correspondence: [email protected]; [email protected] Tel.: +91-9872981142, +91-9815916142

DOI: 10.5530/pc.2011.1.2

Plant Drugs Used to Combat Menace of Anxiety Disorders

Reecha Madaan*1_{, Suresh Kumar}2_{, Gundeep Bansal}2_{, Anupam Sharma}3

1_{Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India ([email protected]).}2_{Department of Pharmaceutical Sciences}

and Drug Research, Punjabi University, Patiala- 147 002, Punjab, India ([email protected]). 3_{Pharmacognosy Division, University Institute of}

Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, India ([email protected])

INTRODUCTION

Anxiety Disorders: An Overview

Global scenario of persons afflicted by mental disorders is alarming.[1]_{About 500 million people suffer from neurotic, stress} related and somatoform problems, 200 million from mood disorders, 83 million from mental retardation, 30 million from epilepsy, 22 million from dementia, and 16 million from schizophrenia. Anxiety disorders are serious medical illnesses that have affected 1/8th_{of total population worldwide irrespective} of gender, age, religion, nationality and profession.[2]_Anxiety Disorders Association of America (ADAA) described anxiety disorders as the most common mental illness in the US, that have affected 19.1 million (13.3%) of the adult (18-54 years) US population.[3]_{A study commissioned by ADAA on ‘The Economic} Burden of Anxiety Disorders’ revealed that anxiety disorders cost the US more than $42 billion a year, almost one-third of the $148 billion total mental health bill for the US. In India, prevalence rate for all mental disorders is 65.4 per 1000 population, and that for anxiety neurosis is 18.5 per 1000 population.[4]_The Global Research on Anxiety and Depression (GRAD) network, a consortium of world’s leading psychiatric epidemiologists and clinical researchers, during the 154th_{annual meeting of ‘American}

Psychiatric Association’ (APA) has observed that, “a significant number of world’s population is plagued by chronic and excessive anxiety, also known as generalized anxiety disorder (GAD), which is more serious than those of lung disease, sleep disorders and major depression, and affects more than 5% of the world population”.[5]_{Following is the categories of anxiety disorders.}[3,6]

1. Panic disorder (PD) is characterized by panic attacks, sudden feeling of terror that strike repeatedly and without warning. Physical symptoms include chest pain, heart palpitations, sweating, trembling, shortness of breath, dizziness, abdominal discomfort, fear of losing control, fear of dying, tingling sensations, and hot flushes. Panic disorders have affected 6 million (2.7%) adult US population. Women are twice more likely to be afflicted than men.

2. Obsessive–compulsive disorder (OCD) is characterized by uncontrollable obsessions (recurring thoughts or impulses that are intrusive or inappropriate and cause the sufferer anxiety) and compulsions (repetitive behaviours or rituals). It has affected 2.2 million (1%) adult US population. It is equally common among men and women.

3. Post-traumatic stress disorder (PTSD) is characterized by persistent symptoms (nightmares, flashbacks, numbing of emotions, depression, feeling angry and irritable) that occur after experiencing a traumatic event such as war, rape, child abuse and natural disaster. It has affected 7.7 million (3.5%) adult US population. Women are more likely to be afflicted by this disorder.

ABSTRACT: In present era, a sudden holocaust of mental disorders, and recognition of severe side effects and addiction liabilities associated with long term administration of widely prescribed synthetic drugs have aroused the attention of researchers towards natural resources. This review includes 351 references, and emphasizes pharmacological reports on anxiolytic plant products and formulations. Various chemical constituents (with structures), isolated from different plants, responsible for antianxiety activity, and their possible mechanism of actions have been incorporated in this review.The review has been compiled using references from major databases like Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, Scirus, Science Direct and Online Journals. It has been concluded that preliminary antianxiety activity studies have been carried out on crude extracts of most of traditonally used and clinically potential plants. Such plantsneed to be explored properly with a view to isolate anxiolytic constituents, and to evaluate their possible mode of actions.

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Invited Review

Thought patterns

Negative thoughts can actually create physical symptoms of anxiety.

Management of anxiety disorders

Such a horrid emergence of mental disorders has attracted the attention of researchers towards various pharmacotherapeutic approaches for the management of these ‘modernization borne diseases’.[10]_{Barbiturates, benzodiazepines (BZDs), azaspirones,} norepinephrine and serotonin-reuptake inhibitors, monoamine oxidase inhibitors and phenothiazines are some of the commonly used psychotropic drugs.[10]_{Among these, BZDs are the most} widely prescribed synthetic chemical drugs for the treatment of anxiety, insomnia, epilepsy, and stress. Regular use of BZDs causes deterioration of cognitive functioning, addiction, physical dependence and tolerance.[10-12]_{Abrupt cessation of chronic} treatment with BZDs causes the appearance of withdrawal effects comprising re-bound anxiety, restlessness, epilepsy, and motor agitation.[13,14]_{In the light of adverse effects associated with the} synthetic drugs, researchers have been exploring natural resources to find out safer and effective drugs. Investigating plants, based on their use in traditional systems of medicine, is a sound, viable and cost effective strategy to develop new drugs.[15]_{Plants like} Valeriana officinalis, Nardostachys jatamansi, Withania somnifera and Panax ginseng have been used extensively in various traditional systems of therapy because of their adaptogenic and psychotropic properties. Inclusion of these well-established CNS affecting plants in the arsenal of modern therapeutics has revived the faith of researchers in the plants.[16]

Targets for Treatment of Anxiety

With anxiety, various brain neurotransmitters and hormones levels change immediately. In particular, monoamines, such as norepinephrine, serotonin and dopamine, are involved in mood, stress and other physical homeostasis.[17]_{Serotonin and}

norepinephrine mainly regulate stress and negative mood in the mammalian brain, and their dysfunctions cause various mood disorders, such as social anxiety disorder and depression.[18] Dopamine also regulates mood and emotion-related behaviors and has a motivation/reward function and conditional fear responses.[19,20]_{Various anxiolytics and antidepressants aim} at monoamine neurocircuitry, such as their receptors and transporters.[21]

The 5-hydroxytryptamine 1A (5-HT_1A) receptor is viewed as a relevant target for the treatment of psychiatric disorders, notably anxiety and depression.[22]_5-HT

1A receptors are located at the presynaptic and postsynaptic sites.[23]_{The somatodendritic} autoreceptor, when activated by systemic stimulation, is believed to exert anxiolytic-like effects and to reduce 5-HT release both in the cell body and in the terminal regions of the serotonergic neurons.[24]_{The other 5-HT}

1A receptor is localized postsynaptically to the serotonergic neurons in the hippocampus, septum, amygdala, and cortex, where it increases signal transfer, which leads to an inhibition of the firing activity.[25]

4. Social phobia or Social anxiety disorder (SAD) is characterized by an intense fear of situations where embarrassment may occur. Physical symptoms include palpitations, tremors, sweating, diarrhoea, confusion and blushing. It has affected 15 million (6.8%) US adult population. It is equally common among men and women.

5. Specific phobia (SP) is characterized by the excessive fear of an object or a situation, exposure to which causes an anxious response. Specific phobias affect an estimated 19 million (8.7%) US adult population and are twice as common in women as in men.

6. Generalized anxiety disorders (GAD) are characterized by chronic, exaggerated worry about everyday routine life events and activities, lasting at least six months. Physical symptoms include fatigue, trembling, muscle tension, headache or nausea. It has affected an estimated 6.8 million (3.1%) US adult population and is twice as common in women as in men. Though, GAD is the most frequent anxiety disorder, yet only 20% of patients receive proper treatment.[7]_GAD results loss of 6 for every 30 work-impairment days.

Causes of Anxiety Disorders

Various factors causing anxiety disorders are described below. [8-9]

Heredity/Genetic factors

Anxiety disorders (PD and OCD) tend to run in families. Studies have shown that if one of the twins has an anxiety disorder, the second is more likely to have an anxiety disorder.

Brain chemistry

The symptoms of long term social anxiety disorder can be attributed to the improper chemical balance in the brain. Several neurotransmitters namely serotonin, norepinephrine, gamma-amino butyric acid (GABA), which are produced in the brain, directly affect one’s feelings about a given situation. Thus brain, too, appears to play a role in the onset of anxiety disorders because symptoms of anxiety disorders are often relieved by medications that alter the level of chemicals in the brain.

Personality

People with low self-esteem and poor coping skills are more prone to anxiety disorders. Conversely, an anxiety disorder that begins in childhood may itself contribute to the development of low self-esteem.

Life experiences

Long term exposure to abuse, violence, poverty or stressful experiences (the early death of a parent, bad marital or family relationships, or traumatic experiences) may affect individual’s susceptibility to anxiety disorders.

Stress overload/Lifestyle factors

Excessive stress over time, and poor lifestyle habits such as overwork, lack of sleep, poor diet and lack of regular exercise promote anxiety.

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In brain, Nitric oxide synthase (NOS) has been localized in regions involved with anxiety, such as hypothalamus, amygdala and hippocampus.[36,37]_{Inhibition of NOS by nonselective or}

by relatively selective inhibitors of nNOS produced antianxiety-like effect. Neurosteroids can rapidly alter the excitability of central nervous system by modulating neurotransmitter-gated ion channels such as GABA_A and N-methyl-D-aspartate receptors.[38]_{Anxiolytic, anticonvulsant and anaesthetic effects} of neuroactive steroids are mediated by their capacity to positively modulate GABA_Areceptor. 5-alpha reductase, the enzyme that converts into 5-alpha-reduced metabolites like the GABA_A positive neuroactive steroid 3-alpha-hydroxy-5-alpha-pregnan-20-one, thus, few drugs exhibits anxiolytic action via an indirect activation of the GABA-ergic system through neuroactive steroids.[39]

PLANTS HAVING ANTIANXIETY ACTIVITY

Antianxiety activity reports of various plants, and plant constituents and formulations have been presented in tables 1 and 2. Various patented formulations of anxiolytic plant drugs have been depicted in table 3. Various review articles published on anxiolytic plants are shown in table 4.

GABA is a major inhibitory transmitter in the central nervous system. The γ-aminobutyric acid type A (GABA_A) receptor, the chloride ion channel complex and the central benzodiazepine receptors located on the neuronal membranes within this complex have been suggested to play an important role in the regulation of the stress and anxiety states.[26,27]_{The benzodiazepine binding} site and GABA_A receptor are structurally and functionally coupled. [28] Benzodiazepines (BZDs) have become the primary pharmacological treatment for generalized anxiety disorder. However, BZDs are often associated with tolerance development and withdrawal symptoms, which pose a risk of relapse upon discontinuation.[29,30] Monoamine oxidase (MAO) catalyzes the oxidative deamination of a variety of monoamines such as dopamine, norepinephrine and serotonin. The MAO reaction yields aldehydes and hydrogen peroxide (H₂O₂), which induces apoptosis.[31]_{Increased endogenous} MAO inhibitory activity (tribulin activity) is associated with conditions associated with stress and anxiety, both in animals and in man. [32]_{Rat brain tribulin activity is significantly augmented by} anxiogenic agents like pentylenetetrazole, and this effect can be prevented by anxiolytic agents.[33]_{Inhibition of MAO and subsequent} H₂O₂ generation effectively prevents depression and various oxidative stresses in the brain.[34]_{The presence of plant-derived MAO} inhibitors suggests that such plant extracts could be useful as potential neuroprotectants in the treatment or prevention of depression.[35]

OH O (1) O O O O O (2) N H O R₁ R2 R1 R2 (3) OH (4) H OH H O O (5)

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O HO O OH OH OH (6) O OH OH HO O OH OH (7) N HO O NH2 O (8) H OH HO H (9) O O OH HO (10) CH3 O CH3 OH OHOH O O CH2OH OH OH O HO HOH2C CH3 H3C C HO CH3 O O CH2 OH OH OH (11) CHO CH2OOCCH2CH(CH3)2 (12)

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O R O R O O (13), R = β-Gentiobiosyl O (14) O OH HO OH OH OH (15) HO CH3 H3CO (16) OH HO O OH OCH3 H3CO (17) O (18) N RO R' CH3O CH3O R R’ (19) CH3 OH (20) H H (21) H OH N RO H3CO H3CO R (22) H (23) CH₃ N N N N O NH2 OH HO HO (24)

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O R₃O H _H O OH OR2 R₁ H3CO2C R₁ R₂ R₃ (25) (26) H H H H OH H O OH OH (27) O O O O OH O O OH O R₁ R₂ H3C C(CH3)3 R1 R2 (28) H H N OCH3 OCH3 (29) O OH CH3 HO R O OH HO OH OH (30), R=CH3 (31), R =CH2OH O OH HO O OH O HO HOHO CH2OH (32) O OH HO O OH OH R₁ R2 R₂ (33) -Glc (34) H H -Glc R₁ O O O O O HO CH3O (35) β β

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OH OH (36) O OH CH2 H2C OH (37) O OH HO OH O (38) N O N H HO CH3 H3C H OCH3 OCH3 OCH3 H3CO (39) O O O OH HO H OH OH OH OH OH OH OH OH HO HO HO HO HO H O O O O O H H H H (40)

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O O HO OH OR HO OHHO R (41) D-glucose (42) H O HO O OH (43) O OH HO O OH OH (44) O O OH HO O OH OH OH (45) CH COOH OH OH CH (46) O 2 3 4 5 6 O 7 8 9 10 1 11 12 13 14 OCH3 R₁ R₂ R₃ R₄ R₅ R1 R2 R3 R4 R5 C5-C6 (47) H OCH2OH H = (48) H OCH2OH H (49) H H H H H H (50) H H H H H = (51) H H H H H = H (52) H OCH₃ H H H = H C7-C8 O O O N O O (53)

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O 2 3 4 5 6 _O 7 8 9 10 1 11 12 13 14 OCH3 R1 R₂ R₃ R₄ R₅ R₃ (54) (55) (56) (57) (58) (59) (60) R₁ R₂ R₄ R₅ C5-C6 C7-C8 OCH2O OCH₂O OCH2O OCH₂O OCH₂O OCH2O H H H = H H = H H = H H H = = H H = = H H H = = OCH₃O CH₃ OCH₃ OCH₃ OCH3 OCH₃ H H H = H H H HO (61) H H H HO (62) OH O OH OH OH OH HOOC (63) O O O O O O O O H H H (64) O O (65) O HO O OH OCH3 (66) O H H OH H OH OH H H O O COOH HO OH O (67)

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O HO OH O HO (68) HO (69) O OH HO OH O H3C (70) O O O O O OH HO _O OH OH OH OH OHHO H3C OCH3 (71) O O OH HO O O O O OH OH OH HO HO H3C OCH3 (72) CH3 COOH H CH3 CH3 (73) N H O HN N H N O O O CH3 CH3 (74) O (75)

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O CH3 CH₃ CH3 (76) O (77) O (78) CH3 H2C H H CH3 CH3 (79) OH (80) OH (81) OH (82) N N O O O H H H (83)

CONCLUSION

In present era, a sudden holocaust of mental disorders, and recognition of severe side effects and addiction liabilities associated with long term administration of widely prescribed synthetic drugs have aroused the attention of researchers towards natural resources. Plants like Valeriana officinalis, Nardostachys jatamansi, Withania somnifera and Panax ginseng have been used extensively in various traditional systems of therapy because of their adaptogenic and psychotropic properties. Inclusion of these well-established CNS affecting plants in the arsenal of

modern therapeutics has revived the faith of researchers in the plants.

In present review article, amongst 143 plants reported to possess antianxiety activity (Table 1):

(a) only 07 plants have been tested clinically,

(b) preliminary antianxiety activity screening on crude extracts has been carried out on 90 plants. Such plants need to be explored with a view to isolate active constituents and their mode of actions,

(18)

Tab

le 1:

List of v

arious plants repor

ted to possess antianxiety activity

. S. _No. Biological sour ce Extract/Fraction/Isolate Dose Animal/ Human being

Experimental model/ _{Assessment of c}

linical parameter s Mec hanism of action Activity Ref . 01 Abies pindro w R oyle (Pinaceae) Talispatra, Silver Fir , Pindr o w Fir Ethanol e xtr act of lea ves 50 and 100 mg/kg , or ally once daily f or 3 da ys Wistar r ats Ele va

ted plus maz

e (EPM),

Open field test (OFT),

Ele va ted zero maz e (EZM) — Anxiolytic [40] 02 Achillea millef olium Linn. (Compositae) Yarr o w , Milf oil Aqueous e xtr act of flow er s 12 mg/kg , p .o . Female Wistar r ats Conflict beha viour — Anxiolytic [41] 03 Acor us calam us Linn. (Ar aceae) Bac h /Bacopa monnier i Linn. (Scrophulariaceae) Brahmi P ow der of whole plant 500 mg TDS for 6 w eeks 81 P atients suf fering from anxiety disorder Electroph ysiolo gical par ameter s lik e EEG , ECG — Impro vement in ner vousness , restlessness , ir rita bility , poor concentr ation,

sleep and loss of a

ppetite [42] 04 Actaea spicata Linn. (A piaceae) Baneberr y, Grape w or t F la vonoidal moiety 2 mg/kg , p .o . Laca mice EPM — Anxiolytic [43] (a) Methanol e xtr act (b) P olyphenol fr action (a) 100 mg/kg , p.o . (b) 50 mg/kg , p.o . Laca mice EPM — Anxiolytic [44] 05 Adiantum tetr aph yllum Humb . & Bonpl. e x Willd.

(Adiantaceae) Fourleaf maidenhair

Ethanol e xtr act (95%) of lea ves 200 mg/kg , p.o . Male Spr ague Dawle y ra ts OFT , EPM, Acoustic star tle response test — Anxiolytic [45] 06

Aethusa cynapium Linn.

(A piaceae) Fool’ s P ar sle y Fa tty acid: trideca-7,9,11-trienoic acid (1) isola

ted from methanol

extr act of aerial par ts 20 mg/kg , p .o .

Swiss albino mice

[1-(3-c hlor phen yl)piper azine] induced h ypolocomotion test — Anxiolytic [46] 07 Albizzia julibr issin Dur azz . ( Fa baceae ) Silktree , Mimosa, Nem unoki Aqueous e xtr act of stem bar k 100 and 200 mg/kg , p .o . Male SD r ats EPM Serotonergic system Anxiolytic [47] Aqueous e xtr act of bar k 200 mg/kg , p.o . f or se ven da ys Male SD r ats EPM Inter action with 5-HT 1A receptor Anxiolytic [48] 08 Albizzia leb bec k Benth. ( Fa baceae ) Siris tree , Albizia Sa ponins ric h n-b utanolic fr action of petroleum ether e xtr act from lea ves 25 or 50 mg/ kg, p .o .

Albino Swiss mice

EPM

Inhibition of GAB

Aergic

tr

ansmission

Anxiolytic and nootropic

(19)

Tab le 1: Contin ued S. _No. Biological sour ce Extract/Fraction/Isolate Dose Animal/ Human being

linical parameter s Mec hanism of action Activity Ref . 09 Alo ysia polystach ya Griseb . (V erbenaceae) Burrito Hy dro-alcoholic e xtr act (60% ethanol) of lea ves 1.56 to 50 mg/ kg, i.p . Female Spr ague Dawle y ra ts EPM, F orced Swimming Test (FST) —

Anxiolytic and antidepressant

[50] Ethanol e xtr act of aerial par ts 1.0,10.0 and 100.0 mg/kg , p.o .

Swiss albino male mice

EPM Other mec hanism than BZD-bs modula tion a t the GAB AA receptor s

Anxiolytic without seda

tiv e ef fects [51] 10 Alpinia zer umbet (P er s.) Bur tt & RM (Zingiber aceae) Shell flo wer , Pink por celain lil y

Essential oil from lea

ves

Inhala

tion 3.5

mg/L air

Male ICR mice

Light/Dar k model (LDM) , OFT , EPM — Anxiolytic [52] 11 Ang elica Essential oil 30.0 mg/kg , p.o .

Male Swiss mice

EPM, LDM — Anxiolytic [53] Essential oil 21 mg/kg , p .o . Male Wistar r ats Social inter action in r ats (SI), Hole Board Test (HBT) — Anxiolytic [54] 12 Angelica dahur ica (Fisc h. e x Hof fm.) Benth. (A piaceae) Dahurian ang elica Fur anocoumarin – Phellopterin (2) isola ted from methanol e xtr act of roots IC50 = 0.36 microM In vitro — BZD receptor s agonist Anxiolytic [55] 13 Aniba r ipar ia (Nees) Mez (Laur aceae) Rose w ood Riparin III (3) isola ted from unripe fr uits 25 and 50 mg/ kg, i.p .

Male Swiss mice

EPM, FST — Anxiolytic , antidepressant [56] Riparin I (4) isola ted from unripe fr uits 25 and 50 mg/ kg, i.p .

Male Swiss mice

EPM, OFT , HBT — Anxiolytic [57] Riparin- III (3) isola ted from unripe fr uits 25 and 50 mg/ kg, p .o .

Male Swiss mice

OFT , EPM, HBT — Anxiolytic b ut de void of seda tiv e acti vity [58] 14 Annona cher imolia Mill. (Annonaceae) Cherimo ya, Custar d apple He xane e xtr act of lea ves 6.25, 12.5, 25.0 and 50.0 mg/kg , p .o . Albino mice Mouse a voidance e xplor ator y beha vior , Marble b ur ying test (MBT) GAB A/BZD receptor comple x Anxiolytic [59] 15 Annona div ersif olia Saf f. (Annonaceae) Llama, Anona b lanca P almitone (5) isola ted from he xane e xtr act of lea ves 0.3, 1, 3, 10 and 30 mg/kg i.p. Albino mice EPM — Anxiolytic [60]

(20)

16 Apocyn um v enetum Linn. (A pocynaceae) Dogbane Ethanol e xtr act of lea ves 30 and 125 mg/kg , p .o . Male C75 BL/6 mice EPM In volv ement of GAB Aergic system Anxiolytic [61] Kaempf erol (6) isola ted from h ydro-alcoholic extr act (70% ethanol) of lea ves >0.02 mg/kg , p.o . Male BL6/C57J mice EPM BZD receptor inter action Anxiolytic [62] 17 Aronia melanocar pa Mic hx. (R osaceae) Blac k c hokeberr y Fr uit juice 5 and 10 ml/ kg, p .o . Wistar r ats SI, OFT — Anxiolytic [63] 18 Azadir achta indica A. J uss . (Meliaceae) Neem tree Aqueous e xtr act from lea ves 10, 20, 50, 100 and 200 mg/ kg, p .o . Wistar r ats EPM, OFT — Anxiolytic [64] Aqueous e xtr act from lea ves 500 mg/kg/ day × 15 da ys Male Char les-F oster albino ra ts

OFT and Mor

ris w

ater maz

e

Increase in ascorbic acid level of

br ain whic h falls during br ain isc hemia Anxiolytic [65] 19 Baphia nitida Lodd. (F abaceae) African sandal w ood, Barw ood Eth yl aceta te e xtr act of lea ves 100-400 mg/ kg, p .o .

Adult albino mice of

either se x EPM, Y maz e — Anxiolytic [66] 20 Byrsocar pus coccineus Sc hur n. and Thonn. (Connar aceae) Kimbar mahalba Aqueous e xtr act of lea ves 200 and 400 mg/kg , p .o . Albino mice of either se x He

xobarbitone induced sleeping

time , Y -maz e, EPM, HBT —

Anxiolytic and seda

tiv e [67] 21 Calluna vulgar is Linn. (Hull) (Ericaceae) Heather Quercetin (7) isola ted from methanol e xtr act of aerial par ts 41µg/mg — In vitro Inhibition of MA O-A Anxiolytic [68] 22 Calotropis gigantea (L.) Dr yand. (A pocynaceae) Giant Milkweed, Cro wn Flo wer , Aak Alcoholic e xtr act of peeled roots 250 and 500 mg/kg , p .o . Albino r ats of either se x EPM, Hot pla te method, Acetic

acid induced writhing

,

Assessment of

locomotor

acti

vity

, rota rod and PTZ-

induced con vulsions — Anxiolytic , anticon vulsant, analg esic and seda tiv e [69] 23 Camellia sinensis (L.) O . K untz e

(Theaceae) Green tea

L-theanine (8) 10 mg/kg , p .o . Spr ague Dawle y r ats EPM

Increase in dopamine levels b

ut not GAB AA receptor inter action Anxiolytic [70]

(21)

linical parameter s Mec hanism of action Activity Ref . 24 Cannabis sativ a Linn. (Canna baceae) Bhang Canna bidiol (9) 15, 30 and 60 nmol, intr a-dlP A G (Dor sola ter al

peri aqueductal gray)

Male Wistar r ats EPM, V og el conflict test Canna bidiol inter action with 5HT 1A receptor s in dIP A G in br ain Anxiolytic [71] Canna bidiol (9) 15, 30 and 60 nmol, intr a-BNST bila ter al injections Male Wistar r ats EPM, V og el conflict test Facilita tes local 5-HT 1A receptor -media ted neuro- transmission Anxiolytic [72] 25

Casimiroa edulis Lla

ve & Le x. (R utaceae) White Sapote , Zapote b lanco Aqueous e xtr act of Lea ves 25 and 35 mg/ kg, i.p . Wistar r ats EPM, OFT — Anxiolytic [73] Hy dro-alcoholic (60% ethanol) e xtr act of lea ves 40, 80, 160, and 320 mg/ kg, p .o . in mice , or 1.56, 3.12, 6.25,12.5 and 50 mg/kg , i.p . in r ats Male and f emale Spr ague-Dawle y r ats

Spontaneous motor acti

vity , EPM, FST , HBT , MBT — Anxiolytic ,

antidepressant and seda

tiv e [74] 26 Casimiroa pr inglei (S . W atson) Engl. (R utaceae) Pringle’ s Zapote

ves 795 and 1000 mg/kg , p .o . Wistar r ats EPM, OFT , HBT —

Anxiolytic and seda

tiv e [75] 27 Cassia siamea Lam. (F abaceae) Kasod, Siamese cassia Bar ak ol (10) 10 mg/kg , i.p . Male wistar r ats EPM — Anxiolytic [76, 77] 28

Cecropia glazioui Sneth (Ur

ticaceae) Embauba, Y arumo (a) Aqueous e xtr act of lea ves (b) Butanolic fr action of aqueous e xtr act of lea ves (a) 0.5 and 1.0 g/kg , p .o . (b) 25-100 mg/kg , p .o .

Male adult Swiss mice

EPM — Anxiolytic [78] 29 Celastr us paniculatus Willd. (Celastr aceae) Jy otishmati, Maak kangni P etroleum ether e xtr act of seeds 3.2 g/kg/da y for 5 da ys Albino mice Beha viour al disinhibition model — Anxiolytic [79] Oil of seeds 1 and 1.5 g/kg , i.p . Wistar r ats OFT , EPM, Thir sty r at conflict par adigm Serotonergic mec hanism Anxiolytic [80]

(22)

30 Centella asiatica (L.) Urb . (Umbellif er ae) Gotu K ola P ow dered dr ug 12 g/da y, p .o . Double-blind, placebo-controlled stud y in 20 subjects Significantly a ttenua ted the peak of acoustic star tle response amplitude — Anxiolytic [81] (a) Mar keted for mula tions (b) Methanol e xtr act (c) Eth yl aceta te e xtr act (d) Asia ticoside (11) (a) 500 mg/kg , p.o . (b) 3047 mg/ kg, p .o . (c) 111 mg/kg , p.o . (d) 3 mg/kg , p.o . Male Spr ague-Dawle y (SD) r ats EPM, OFT , SI, locomotor acti vity , punished drinking , no vel ca ge test — Anxiolytic [82] 31 Centr anthus r uber (L.) DC (Valerianaceae) Red v alerian V alepotria te – valtr ate (12) 5 mg/kg , p .o . Wistar r ats Inhibition of orienta tion refle xes

and motor acti

vity — Anxiolytic [83] 32 Cer atonia siliqua Linn. (F abaceae) Car ob tree Methanol e xtr act of lea

ves and pods

P ods - 12.17 ng and Lea ves - 18.7 ng diaz epam equi valent In vitro — BZD receptor inter action Anxiolytic [84] 33 Cinnamom um cassia Blume . (Laur aceae)

Cassia Bark, Chinese cinnamon

50% Ethanol e

xtr

act

from stem bar

ks

750 mg/kg

,

p.o

.

Male ICR mice

EPM R egula tion of 5-HT 1A and GAB A receptor system Anxiolytic [85] 34 Cissus sicy oides Linn. (V itaceae) P

ossum grape _vine

, Princess vine Hy dro-alcoholic e xtr act (70% ethanol) of lea ves 300, 600 and 1000 mg/kg , i.p . Male and f emale Swiss albino mice EPM, HBT , MBT , Sodium P

entobarbital-induced sleeping _time

, PTZ-induced con vulsion — Anxiolytic , anticon vulsant [86] 35 Citr us aur antium Linn. (R utaceae) Bitter Orang e

Essential oil from peel (EOP) of

lea ves 1 g/kg , p .o .

Male Swiss mice

EPM,

OFT

—

Anxiolytic

[87]

Essential oil from fr

uits

0.5 and 1.0 g/ kg, p

.o

.

Male Swiss mice

LDM, MBT — Anxiolytic [88] 36 Citr us sinesis Linn. (R utaceae) Sweet Orang e, Blood Orang e Essential oil 100, 200 and 400 µl Wistar male r ats EPM, LDM — Anxiolytic [89] 37 C lit or ia te rn at ea Li nn . ( P ap ili on ac ea e) B u tt er fly p ea Methanol extr act of roots 100-400 mg/ kg, p .o .

Male Swiss albino mice and Wistar r

ats EPM, LDM — Anxiolytic [90] 38 Con vulvulus plur icaulis Choisy . (Con volvulaceae) Shankhpuspi Eth yl aceta te fr action of ethanol e xtr act of the aerial par ts 100 mg/kg , p .o . Spr ague-Dawle y r ats and

Swiss albino mice

EPM,

OFT and rotarod

perf or mance — Anxiolytic [91] 39 Copaif er a reticulata Duc ke

(Leguminosae) Brazilian copaiba

Essential oil 100, 400 and 800 mg/kg , i.p . Wistar r ats EPM — Anxiolytic [92]

(23)

linical parameter s Mec hanism of action Activity Ref . 40 Cor iandr um sativum Linn. (Umbellif er ae) Coriander , Dhaniy a Aqueous e xtr act of seeds 100 mg/kg , p.o .

Male albino mice

EPM — Anxiolytic [93] 41 Crocus sativus Linn. (Liliaceae) Saffr on, A utumn cr ocus Crocin (13) isola ted from aqueous e xtr act of red dried stigmas 50 mg/kg , i.p . Wistar r ats LDM — Anxiolytic [94] (a) Aqueous e xtr act of stigmas (b) Crocin (13) (c) Safr anal (14) (a) 56, 80, 320 and 560 mg/ kg, i.p . (b) 50, 200 and 600 mg/ kg, i.p . (c) 0.05, 0.15 and 0.35 ml/ kg, i.p . R

azi male mice

EPM, OFT , P entobarbital sleeping time , R otarod test —

Anxiolytic (At low

er dose),

hypnotic (At higher dose)

[95]

42

Croton celtidif

olius

Baill. (Euphorbiaceae) Sangue-de-ada

ve Proanthocy anidin (15) ric h fr action isola ted from aqueous e xtr act of bar k 3 mg/kg , i.p . Wistar r ats EPM — Anxiolytic [96] 43 Croton z ehntner i P ax & Hof fman

(Euphorbiaceae) Canela de Cunha

Meth yl eug enol (16) from essential oil 1, 3 and 10 µl/100 g , p .o . Male Wistar r ats OFT , SI, EPM, HBT , FST —

Antidepressant and mild anxiolytic

[97] 44 Curcuma longa Linn. (Zingiber aceae) Cur cuma, T urmeric Curcumin (17) 20 mg/kg , i.p .

Swiss albino mice

EPM, OFT , LDM, SI In volv ement of inducible NOS Anxiolytic [98] 45 Cymbopogon citr atus (DC .) Sta pf (P oaceae) Lemongrass, Ging er grass Citr al (18) or tea abafado 200 mg/kg , i.p .

Male albino Swiss mice

OFT , R ota-rod test, Spontaneous motor acti vity , Barbitur ate sleeping-time , T ranscor neal electroshoc k, PTZ-induced con vulsions , Punished response test — Centr al Ner vous depressant [99] Essential oil 0.5 and 1.0 g/ kg, i.p .

Swiss male mice

EPM, LDM — Anxiolytic [100] 46 Da villa r ugosa P

oiret (Dilleniaceae) _Cipo-Caboc

lo, Fire vine Hy dro-alcoholic e xtr act (70% ethanol) of stems 15 mg/kg , p .o . Male Wistar r ats EPM, OFT — Anxiolytic [101] 47 Dr ymar ia cordata (L.) Willd. e x R oem. & Sc hult. (Car yoph yllaceae) Tr opical c hic kweed Hy dro-alcoholic e xtr act (50% ethanol) of lea ves 100 mg/kg , p.o .

Swiss albino mice

EPM, LDM, OFT , HBT — Anxiolytic [102]

(24)

48 Ducrosia anethif olia Boiss . (A piaceae) Hazza, Hazzaz Essential oil 25, 50, 100, 200 and 400 mg/kg , p .o .

Swiss albino mice

EPM, Spontaneous motor acti vity , K etamine-induced sleep time — Anxiolytic b ut not seda tiv e [103] 49 Echinacea pur purea (L.) Moenc h. (Aster aceae) Cone flo wer (a) E. pur purea root extr act (ethanol 4% v/v; Ec hinacoside 4%) (b) E. pur purea herb extr act (ethanol 60% m/m; total phenols 4%) (c) E. angustif olia root extr act (ethanol 85% v/v; Ec hinacoside 4%) (d) E. pur purea root extr act (ethanol 70% v/v) 3-7 mg/kg , p .o . Male Wistar r ats EPM, SI, shoc k induced social av oidance test, OFT — Only e xtr act (d) show ed anxiolytic acti vity [104] 50 Echium amoen um Fisc h. Et Me y. (Bor aginaceae) Viper’ s b ugloss, Red f eather s Aqueous e xtr act of flow er s 5, 10, 30, 62.5, 80 and 125 mg/kg , i.p .

Male NMRI albino mice

EPM — Anxiolytic [105] Hy dro-ethanol e xtr act (80%) of the plant flow er s 50 mg/kg , i.p . Male TO mice EPM — Anxiolytic [106] 51 Eclipta alba Linn. (Aster aceae) Bhringaraj, F alse daisy (a) Aqueous , h ydro-alcoholic e xtr acts (b) Hy drolyz ed fr action

obtained from whole plant (a) 150 and 300 mg/kg , p.o . (b) 30 mg/kg , p.o . Wistar r ats Locomotor acti vity , EPM, HBT , Cold restr aint induced g astric

ulcer and white blood cell count in the milk induced leuk

ocytosis challeng e Nootropic , seda tiv e,

anxiolytic and antistress

[107] 52 Er ythr ina m ulungu Mar t. (P apilionaceae) Mulungu, Cor ticeira Hy dro-alcoholic e xtr act

(70% ethanol) from the inflorescence Acute (200 mg/kg , p .o .) chronic (50 mg/kg , p .o . f or 7 da ys) Male Wistar r ats Ele va ted T maz e (ETM), LDM, Ca t odor test — Anxiolytic [108, 109] W ater : Alcohol (7:3) extr act of inflorescence Acute stud y 200 and 400 mg/kg , p .o . and c hronic stud y f or 21 da ys , 50 and 200 mg/kg , p.o . Male Wistar r ats ETM — Anxiolytic [110] Er

ythrinian alkaloids i.e

(+)-α– hy dro xy er sotrine (19) , er ythr avine (20) and (+)-11-α–h ydro xy er ythr avine (21) isola ted from h ydro-alcoholic extr act of flow er s 3 and 10 mg/ kg, p .o .

Male Swiss Mice

EPM,

LDM

—

Anxiolytic

(25)

linical parameter s Mec hanism of action Activity Ref . Cr ude e xtr act (CE), Er ythrinian alkaloids: (+)-α– hy dro xy er sotrine (19) , er ythr avine (20) and (+)-11-α–h ydro xy er ythr avine (21) isola ted from h ydro-alcoholic extr act of flow er s 3-10 mg/kg , p.o . CE (50, 100, 200 and 400 mg/kg , p .o .)

Male Swiss mice

T-maz e, Locomotor acti vity test — Anxiolytic [112] 53 Er ythr ina suberosa R oxb . (F abaceae) Coral tree Alkaloids – Erysodine (22) and er ysothrine (23) isola ted from h ydro-alcoholic extr act of flow er s 3 and 10 mg/ kg, p .o .

Male albino mice

EPM, LDM — Anxiolytic [113] 54 Er ythr ina v elutina Willd. (F abaceae) Bico-De-P apa gaio W ater : Alcohol (7:3) extr act of stem bar k Acute stud y - 200 and 400 mg/kg , p .o ., and c hronic stud y - 50 and 200 mg/kg , p.o . Male Wistar r ats ETM — Anxiolytic [110] Hy dro-ethanol e xtr act of stem bar k 50 and 100 mg/kg , p .o . f or 23-26 da ys

Adult male Swiss albino mice

EPM — Anxiolytic [114] 55 Eschscholzia calif or nica Cham. (P apa ver aceae) Calif ornia popp y, Gold popp y Hy dro-alcoholic e xtr act (60% ethanol) of aerial par ts 25 mg/kg , i.p .

Male Swiss mice

LDM BZD receptor inter action Anxiolytic [115] 70% ethanol e xtr act of aerial par ts 100 to 300 mg/kg , i.p . Male Wistar r ats CCl 4 induced neuropa thic pain, hot pla te and car ra geenan induced pain —

Anxiolytic and anti- neuropa

thic pain [116] 56 Euphorbia hir ta

Linn. (Euphorbiaceae) Asthma weed

Aqueous e xtr act of whole plant 12.5 and 25 mg/kg , i.p .

Swiss albino mice

Stair case test,

LDM — Anxiolytic [117] 57 Euphor ia longana Lamarc k (Sa pindaceae) Longan Arillus (a) Methanol e xtr act (b) adenosine (24) isola

ted from pulp or

flesh (a) 2 g/kg , s .c . (b) 30 mg/kg , s.c .

Male ddY mice

V

og

el type anti-conflict method

— Anxiolytic [118] 58 Euphorbia nerr ifolia

Linn. (Euphorbiaceae) Indian spur

g e tree , Oleander spur g e Hy dro-alcoholic (50% ethanol) e xtr act of lea ves 400 mg/kg , p.o .

Swiss albino mice

EPM

—

Anxiolytic

(26)

59 Eur ycoma longif olia Jac k

(Simaroubaceae) Tongkat ali, Pena

war bias Chlorof or m, n -b utyl alcohol and w ater fr

actions obtained from _methanol

extr act of roots 0.3 g/kg , p .o . for 5 da ys twice daily Albino mice EPM, OFT , F oot shoc k induced flighting beha viour — Anxiolytic [120] 60 Ev olvulus alsinoides Linn. (Con volvulaceae) Shankhpushpi Eth yl aceta te fr action of ethanol e xtr act of the aerial par ts 100 mg/kg , p .o . Spr ague-Dawle y r ats and

Swiss albino mice

EPM,

OFT and rotarod

perf or mance — Anxiolytic , neuromuscular coordina tion and antio xidant [91] 61 Galphimia glauca Ca v. (Malpighiaceae) Calder ona amarilla Galphimine B (25) , galphimine A (26) and galphimine ric h fr actions

(GRFs) obtained from methanol e

xtr act of aerial par ts 15 mg/kg , i.p .

Male ICR mice

EPM — Anxiolytic [121] Methanol e xtr act of aerial par ts 125, 250, 500, 1000 and 2000 mg/kg , p.o .

ICR albino mice

EPM,

LDM,

FST

—

[122] Ca psules containing 310 mg of aqueous e xtr act of aerial par ts 310 mg twice daily f or 4 w eeks A controlled r andomiz ed double blind c linical trial HAMA scale , the c linical global

impression scale and pa

tient global e valua tion — Anxiolytic [123] 62 Gardenia jasminoides Ellis (R ubiaceae) Cape jasmine Kamisho yosan 50-200 mg/kg , p.o .

Male ddY mice

SI

—

Anxiolytic

[124]

63

Gastrodia elata Blume (Orc

hidaceae)

Tian ma (China); Gastr

odia Tuber(English name) (a) Aqueous e xtr act of rhiz omes (b) Phenolic constituents: 4-h ydro xyl-benzyl alcohol, and benzaldeh

yde and its

phenolic constituents (a) 400 mg/kg , p.o . (b) 50 and 100 mg/kg , i.p .

Male ICR mice

EPM Inter action with 5-HT (1A) receptor Anxiolytic [125] 64 Gelsemium semper virens (L.) Ait. (Lo ganiaceae) Car olina y ello w Jasmine Methanol extr act of roots and rhiz omes 150 mg/kg , p.o .

Swiss albino mice

EPM

—

Anxiolytic

[126]

Centesimal dilutions of hydro-alcoholic e

xtr act of plant as in homeopa thic system 5C , 9C and 30C dilutions

ICR-CD1 male mice

LDM,

OFT

—

Anxiolytic

(27)

linical parameter s Mec hanism of action Activity Ref . 65 Ginkgo biloba Linn.

(Ginkgoaceae) Ginkgo, Maidenhair tree Aqueous and ethanol extr

acts of lea ves 5 and 10 mg equi valent In vitro using r at br ain mitocondrial e xtr act —

Inhibition of monoamine oxidase (MA

O A and B) Anxiolytic [128] Ginkgo biloba e xtr act (EGb-761) 8-16 mg/kg , i.p . Wistar AF r ats SI GAB A/ BZD/ Cl - channel receptor inter action Anxiolytic [129] Ginkgolic acid (27) conjug ates (GA C) isola ted from c hlorof or m: methanol e xtr act (2:1) of the lea ves 0.6 mg/kg , p .o . Char les F oster r ats EPM, OFT , no velty-induced feeding la tency and SI — Anxiolytic [130] G. biloba e xtr act (GBE), standardiz ed to contain 24% ginkgo- flavo gly cosides and 6% ginkgo-ter penoid lactones or ginkgolide A(28) 0.5 and 1.0 g/ kg, p .o . f or 7 da ys; 1 and 2 mg/kg , p.o . f or fi ve da ys

Male ddY mice

EPM

Other mec

hanism

but not through GAB

A/ BZD/ Cl - channel receptor inter action Anxiolytic [131] 66 Glycyrrhiza glabr a Linn. (Leguminosae) Licorice , Mulethi Hy dro-alcoholic e xtr act of

roots and rhiz

omes

10-300 mg/kg

,

i.p

.

Swiss albino mice

EPM, foot shoc k induced ag gression — Anxiolytic [132] 67 Hedy osm um br asiliense Mar t. (Chlor anthaceae) Cha de b ugre Ethanol e xtr act of aerial par ts 100 mg/kg , i.p .

Male Swiss albino mice

EPM,

OFT

, Barbitur

ate-induced

sleeping time test

—

Anxiolytic and seda

tiv e [133] 68 Heteropter ys glabr a Hook. & Ar n. (Malpighiacae) Red wing Ethanol e xtr act of fr uits 350 mg/kg , p.o . DB A/2J mice Sleep w ak efulness cy cle , electroencephalo gr am (EEG) and visual e vok ed potentials (VEP) —

Anxiolytic and seda

tiv e [134] 69 Hibiscus sabdar iff a Linn. (Malvaceae)

Jamaica sorrel, Red sorrel

Aqueous , h ydro-alcoholic , and ethanol extr act of calyx es of plant 300 mg/kg , p.o . Wistar r ats EPM, k

etamine- induced sleep

—

Anxiolytic and seda

tiv e (a t multiple doses) [135] 70 Hippeastr um vittatum (L ’Herit) Herber t (Amar yllidaceae) Amar yllis

Isoquinoline alkaloid: Montanine

(29) isola ted from ethanol e xtr act of bulbs

Anxiolytic and seda

tiv e (1-10 mg/kg , i.p .), anticon vulsant (30 and 60, mg/kg , i.p .)

Swiss albino mice

EPM, Sodium pentobarbital-induced sleep , PTZ-pro vok ed con vulsions , FST — Anxiolytic , mild seda tiv e and anticon vulsant

but not antidepressant

(28)

71 Hyper icum perf or atum Linn. (Guttif er ae) St John’ s w or t H. perf or atum extr act LI60 — In vitro — β receptor acti va tion Anxiolytic [137] Standardiz ed e xtr act of

the whole plant, containing 0.54% total hypericins [0.11% hypericin

(30) and 0.43% pseudoh ypericin (31) ]and 0.09% protof or ms 2778 and 1852 mg/kg , p.o . Male Spr ague–Dawle y r ats OFT , LDM Inhibitor y influence on glutama tergic tr ansmission _media ted b y NMD A receptor s Anxiolytic [138] Ly ophiliz ed aqueous extr act 5 mg/kg , p .o .

EPM — Anxiolytic [139] Hy dro-alcoholic e xtr act of whole plant 100 or 200 mg/kg , p .o . OD for 3 da ys Wistar r ats EPM, OFT , EZM, no velty-induced suppressed f eeding la tency , SI Af fect monoamines concentr ation in ra ts’ br ain Anxiolytic [140] H. perf or atum extr act LI 160 300 mg/kg , p.o . f or 21 da ys

Mouse def ense test ba tter y — Anxiolytic [141] H. perf or atum extr act LI 160 300 mg/kg , p .o

ETM — Anxiolytic [142] H. perf or atum extr act LI 160 380 mg/kg/ day c hronic administr ation C57BL/6J Mice OFT , LDM, FST —

[143] H. perf or atum extr act LI 160 150 and 300 mg/kg , p .o .

Swiss albino mice

MBT

, FST

—

[144] Hy dro-alcoholic e xtr act of whole plant 200-400 mg/ kg, p .o .

Male Laca mice

Mir rored c hamber , EPM, EZM — Anxiolytic [145] 72 Jatropha ciliata M. Arg . (Euphorbiaceae) Huanarpo V ite xin (32) , iso-orientin (33) and orientin (34) from methanol e xtr act of Stems 40 mg/kg , s .c .

Male ddY mice

V og el type Anticonflict ef fect in mice — Anxiolytic [146] 73 Kielme yer a cor iacea Mar t. (Clusiaceae) P áu santo Ethanol e xtr act of lea ves 120 mg/kg/ day, p .o . Male Wistar r ats EPM — Anxiolytic [147]

(29)

linical parameter s Mec hanism of action Activity Ref . 74 La vandula angustif olia Miller (Lamiaceae) English La vender

ves Inhala tion 0.1-1.0 ml Adult male Spr ague-Dawle y albino r ats

Open field beha

vior test La vender oil potentia tes the responses of GAB A receptor s at low concentr ations

and inhibits responses of GAB

A receptor s at high concentr ations in vitro Anxiolytic [148, 149] La vender oil I ml/100 g , i.p .

Male ICR Mice

Galler type conflict test

— Anxiolytic [150] La vender odour — Ma

ture male and f

emale gerbils EPM — Anxiolytic [151] 75 Leptosper m um scopar ium J .R. et G . For st. (Myr taceae) Man uka or Tea tree (a) Hy dro-alcoholic extr act (70% ethanol) (b) 5,7-dimetho xyfla vone (1), 5,7-dimetho xy-6-meth ylfla vone (2), 5-h ydro xy-7-metho xy-6-meth ylfla vone (3) and 5-h ydro xy-7-metho xy-6,8-dimeth ylfla vone (4) (a) 250 mg/kg , p.o . (b) IC50- values of 2.1 microM (1), 45

microM (2), 3.3 microM (3) and 40 microM (4)

(a) R ats (b) In vitro r adio receptor assa y with [3H] F lunitr az e-pam Locomotion stud y Inter action with GAB AA /BZD receptor Anxiolytic [152, 153] 76 Lippia alba (Mill.) N.E. Brown (V erbenaceae) Cidreira, Bush y matgrass Three c hemotypes of

essential oil (EO1,

EO2,

EO3) from lea

ves

EO1 and EO3 (100 mg/kg

, i.p .) and EO2 (25 mg/kg , i.p .)

Male Swiss Mice

EPM,

OFT and rotarod

—

Anxiolytic and myorelaxant

[154] 77 Loeselia me xicana Br and (P olemoniaceae) Me xican false calico, Espinosilla Da phnoretin (35) isola ted from h ydro-alcoholic extr act (60% ethanol) of whole plant 1.8, 3.7, 7.5 and 15.0 mg/ kg, i.p .

Male ICR mice

OFT , EPM — Anxiolytic [155] 78

Magnolia dealbata Zucc

. (Ma gnoliaceae) Elo xoc hiti Ethanol e xtr act of lea ves 100 and 300 mg/kg , p .o .

Male Swiss albino mice

EPM, HBT , e xplor ator y rearings ,

Sodium pentobarbital-induced hypnosis

, PTZ-induced seizures — Anxiolytic , seda tiv e and anticon vulsant [156]

38 - pc_1_1_Jul_Sep_2011

Pharmacognosy Communications

Contents

Editorial

Pharmacognosy Communications:

The Scope of Pharmacognosy

REfEREnCES

AbouT jouRnAl

Invited Review

Plant Drugs Used to Combat Menace of Anxiety Disorders

INTRODUCTION

Invited Review

PLANTS HAVING ANTIANXIETY ACTIVITY

CONCLUSION