Herbal Drugs for the Treatment of Mental Disorders
By - 01/11/2008
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Mr. Santosh S. Bhujbal
The prevalence of mental health problems, particularly depression and anxiety, in the general population is around one in six people, and around 40% of people with mental health problems will have symptoms of both anxiety and depression. Drug acting on the central nervous system (CNS) include the centrally acting (mainly opoid) analgesics, anti-epileptics and anti-Parkinson agents, as well as those for psychiatric disorders. Many of such herbal drugs have reached to the stage of clinical trials. The current review is focused on various herbs, which can be used in treatment of various mental disorders along with their pharmacological and clinical evidences.
Introduction:
The prevalence of mental health problems, particularly depression and anxity, in the general population is around one in six people, and around 40% of people with mental health problems will have symptoms of both anxiety and depression.
Drug acting on the central nervous system (CNS) include the centrally acting (mainly opoid) analgesics, anti-epileptics and antiparkinsonian agents, as well as those for psychiatric disorders.
Drugs of plant origin are important in all these areas, although not usually for self-medication. They are also of historical interest; for example, the antipsychotic drug reserpine, isolated from Rauvolfia species, revolutionized the treatment of schizophrenia and enabled many patients to avoid hospitalization before the introduction of the phenothiazines and the newer atypical antipsychotics, in the same way Phytotherapy has a role in helping to re-establish a regular pattern of sleep which was disturbed by depression and anxiety.
Botanicals used in treatment of mental disorders
Hypericum perforatum (St. John’s Wort) :
Hypericum perforatum belonging to family Hypericaceae(St. John’s Wort) has a history of medicinal use, particularly as a ‘nerve tonic’ and in the treatment of nervous disorders.0 It is an aromatic perennial native of Europe. It’s use can be traced back to the texts of ancient Greek physicians Hippocrates and Galen. It has become the second most commonly used herbal remedy in Germany and is currently used in that country for treatment of depression four times more often than the most commonly used antidepressant.6
Constituents:
Initially, hypericin (a naphthodianthrone) was considered to be the antidepressant constituent of St. John’s wort, although experimental and clinical evidence has now emerged that hyperforin (a prenylated phloroglucinol) is a major constituent required for antidipressant ctivity.
Pharmacological effects and clinical efficacy:
The German monograph for St. John's wort identifies hypericin, a purported monoamine oxidase (MAO) inhibitor, as the active ingredient in the herb. The hypericin content of St. John's wort is used as the basis for dosing. However, one U.S. studyshowed that pure hypericin does not bind to MAO. In this study, a crude St. John's wort extract exhibited significant receptor affinity for MAO, but the investigators stated that concentrations of the crude extract required for this activity are unlikely to be achieved after oral administration.8Hypericin, in a standardized extract has shown a significant antidepressant activity by inhibiting the enzyme mono amino oxidase (MAO). 9
The antidepressant activity of Hyperforin is attributed to its inhibition of neuronal uptake of serotonin, norepinephrine and dopamine like many other antidepressants and also inhibits GABA and glutamate uptake. 10
The antideprerssant activity of hypericum is not only limited to hypericin and hyperforin, xanthones of the plants are also reported to exhibit this property. 12,13
A few studies have found St. John’s Wort somewhat more effective than a standard antidepressant. However, none of these studies lasted more than six weeks, which is not long enough to determine how long the herb would be effective or to detect any long-term adverse effects.11
When the aqueous methanolic extract of the herb was administered in the dose of 900 mg per day, for the duration of atleast four weeks, the Hamilton Rating Scale for Depression (HRSD) was used as an outcome measure, slightly greater improvement in HRSD scores was obtained. 14
When the St. John Wort in the dose of 900 mg per day was compared against low dosages of maprotiline, imipramine and amitriptyline in case of mild to moderate depression 15-18 no significant differences in response were found.
Studies involving small no of healthy male volunteers have indicated that St. John's wort extracts may have dopaminergic activity and effect on cortisol, which may influence concentration of certain neurotransmitter.
Evidence from randomized controlled trials indicates that preparation of St. John's Wort extracts are more effective than placebo, and as effective as conventional antidepressant, in the treatment of mild to moderate depression.
Toxicity:
St. John’s Wort has long been considered safer than the conventional pharmaceutical agents. However its ability through its active constituents hypericin, pseudohypericin and hyperforin, to induce P – glycoprotein/ MRD1 and both intestinal and hepatic CYP3A4 enzyme, could markedly reduce the distribution and disposition of their co-substrates. St. John’s Wort is a potent uptake inhibitor of neurotransmitters serotonin, norepinephrine and dopamine all of which have a role in mood control. 19
No serious side effects are reported, but minor side effects include gastrointestinal discomfort, fatigue, dry mouth, dizziness, skin rash, and hypersensitivity to sunlight. However, in February 2000, British journal Lancet carried reports that St. John's wort could interfere with the effectiveness of an AIDS remedy (indinavir) 20; an immunosuppressive drug (cyclosporin) used to protect patients after heart transplantation 21; and an anticoagulant (warfarin). 22
It has been reported that St. John’s wort may be toxic during pregnancy and lactation in mice.23 St. John's wort should not be used by women who are pregnant or are breastfeeding. Nor should it be used together with standard antidepressants. 24
No significant side effects have been reported in the numerous double-blind studies, but perhaps the best demonstration of the excellent safety record of St. John's wort extract is a large-scale study involving 3,250 patients conducted in Germany. Results were analyzed by means of a patient questionnaire. Pooled data indicated that symptoms of depression were reduced in frequency and intensity by approximately 50%. The frequency of undesired side effects were reported in 79 patients (2.43%) and 48 (1.45%) discontinued therapy. The most frequently noted side effects were gastrointestinal irritation (0.55%), allergic reactions (0.52%), fatigue (0.4%), and restlessness (0.26%). 25
The frequency and severity of side effects with St. John's wort extract are clinically insignificant, especially when compared to the well-known side effects of tricyclics and other antidepressants. There have been no deaths due to St. John's wort toxicity, a stark contrast to the 31 deaths per one million prescriptions produced by synthetic antidepressants. 26
There is considerable evidence that St. John's Wort can cause severe photosensitivity in animals grazing extensively on the plant. In fact, the term "hypericism" has been used to describe a skin disease found in animals that graze on large quantities of St. John's Wort. 27
Because of the possibility of photosensitivity, it is often recommend that individuals, especially those with fair skin, avoid exposure to strong sunlight and other sources of ultraviolet light when using St. John's Wort. However, while this recommendation may be appropriate it must be pointed out that the therapeutic dosage of 2.7 mg hypericin per day is about 30 to 50 times below the level required to produce phototoxicity. 28 Reports of photosensitivity in humans have been rare and have been limited to those taking excessive quantities for HIV infection. St. John's Wort is unlikely to be toxic to humans when used at recommended medicinal doses. However, individuals with AIDS taking larger amounts of St. John's wort extracts (or hypericin) have developed photosensitivity. 29
Quality assurance and analysis:
St. John's wort is included in the Eur. Ph., which states that the drug should contain not less than 0.08% of total hypercins, expressed as hypericin, calculated with reference to the dried drug. Analysis is usually by High performance liquid chromatography (HPLC). Most products containing standardized extracts of St. John's wort are still standardized on hypercin content, as hyperforin is fairly unstable.
Bacopa monnieri L. (Brahmi)
Bacopa monnieri L belonging to family Scrophulariaceae (Brahmi) is a annual creeping plant found throughout India in wet, damp and marshy areas. It is the important drug in Ayurveda for improvement of intelligence and memory and revitalizing of sense organs.
Constituents:
The main constituents present in Bacopa monnieriare saponins, bacoside A, bacoside B, monnierin and hersaponin, which are also responsible for the biological activity. Most of the work reported is on the alcoholic extract of the plant.
Pharmacological effects and clinical efficacy:
This plant has been extensively investigated for memory enhancing effects. Ethanolic extract of B. monnieri was demonstrated to facilitate acquisition, consolidation and retention of memory in animal models.
Bacosides A and B (Saponins) were identified as active principles. Administration of bacosides attenuated the retrograde amnesia produced by immobilization induced stress, electroconvulsive shock and scopolamine.
Treatment with the plant extract for one month reduced levels of anxiety, adjustment disability leading to improved mental functions. The protective action of B. monnieri was demonstrated against phenytoin induced cognitive deficit. Phenytoin (25 mg/kg orally for 14 days) adversely affected the passive avoidance task in mice. An extract of this plant (40 mg/kg orally for 7 days along with phenytoin in the second week of the 2-week regimen) significantly revised phenytoin induced impairment without affecting its anticonvulsant efficacy. The observed cognitive effects of phenytoin and the plant extract were found to be independent of motor stimulation. 30-35
One of the marketed preparation contains the novel drug molecules, in experimental models increased protein kinase activity and new protein synthesis specifically in brain cells that are concerned with alertness, briskness and long term memory thereby resulting in the reduction of learning process.
Another commercial preparation in a capsule form containing 500 mg of leaf powder is also claimed to improve the brain function and memory power in elderly people. 36
In a double blind randomized controlled clinical trial in 76 subjects, B. monnieri showed significant effect on the retention of new information. Follow – up tests showed that the rate of learning was unaffected, suggesting that B. monnieri decreases the rate of forgetting newly acquired information. 37
Toxicity:
Therapeutic doses of Bacopa monnieri are not associated with any known side effects, and Bacopa monnieri has been used safely in Ayurvedic medicine for several hundred years. A double blind, placebo controlled clinical trial of healthy male volunteers investigated the safety of pharmacological doses of isolated bacosides over a four-week period. Concentrated bacosides given in single (20-30 mg) and multiple (100-200 mg) daily doses were well tolerated and without adverse effects.38
The LD-50 of Bacopa extracts administered orally to rats was 5 g/kg for aqueous extracts and 17 g/kg of the alcohol extract. Neither extract resulted in gross behavioral changes at these concentrations. 39
Centella asiatica L (Mandukaparni)
Drug consist of the dried aerial parts, preferably leaves of Centella asiatica (Linn.) Urban belonging to family Apiaceae., (Mandukaparni). It is distributed throughout the tropical and subtropical regions of India.
The plant is traditionally considered as a tonic in diseases of nerves and blood and for improving memory. The plant is especially used in the treatment of amnesia and hysteria; it has beneficial effect on behavior learning and memory.
The plant is a ‘rasayana’ in Ayurvedic medicine; it enhances the immune system and is considered to have a rejuvenating, neurological ‘tonic’ and mild sedative effect.
Constituents:
Triterpenoid saponins viz., madecassoside and asiaticoside and their aglycones viz., Asiatic acid and madecassic acid. Madecassoside 0.7 – 5.0 %; Asiaticoside 0.1 – 0.6 %; Asiatic acid 0.1 – 0.5 % and Madecassic acid 0.5 – 0.8 % are major constituents.
While saponins viz., asiaticoside B, brahminoside, centelloside, indeentelloside, thankuniside and isothankuniside; triterpenoid acids viz., brahmic acid, isobrahmic acid, betulic acid, centic acid and centoic acid; flavonoid glycosides viz., 3-glucosylquercetin and 3-glucosylkaempeferol; and an alkaloid hydrocotyline are some of the minor constituents.
Pharmacological effects and clinical efficacy:
Aqueous extract of fresh leaves has effect on learning, memory and biogenic amine turnover in albino rats and the effect is dose dependent. In double blind clinical trial conducted on 30 mentally retarded children who were free from epilepsy and other neurological conditions to study effects of C. asiatica on general mental ability, significant improvement in general ability and behavior pattern was observed after administering the drug for a period of 6 weeks. 36
Aqueous extract of this plant was shown to improve learning and memory in shuttle box, stepdown paradigm and elevated plus maze in rats. When tested on oxidative stress parameters, it decreased brain levels of malondialdehyde (MDA) with a simultaneous increase in the level of glutathione. The drug also increased catalase levels.2
For studying general ability of mentally retarded children, a double blind trials using whole herb powder was conducted. The results showed that, with the treatment period of three months, the drug produced a significant intellectual improvement and behavioral changes. The IQ of children increased by 7.6% as compared to 3.0% increase in the placebo group. The drug increased power of concentration and attention in children. The behavioral improvement compared favorably with that noticed with Glutamic acid and vitamins or Encephabol. The study concluded that the drug could be used for routine treatment of mental retardation.
The indigenous drug Geriforte (brand name) contain C. asiatica as one of the constituents, has been found to impart protective and antifatigue effects on stressed rats and also an excellent nervine tonic in decline age.
Toxicity:
Contact dermatitis has been observed due to madecassol (an extract of C.asiatica). Triterpene glycosides have been identified as having oncogenic activity and asiaticoside has been implicated as a possible carcinogen where repeated applications are used.
In most cases, the herb, its extract or its preparations are not recommended for use in the children under age 12, pregnant or lactating women.
Valeriana officinalis (Valerian)
The root of Valerian has served thousands of years as a mild sedative. From 1820 until 1942, it was listed in the U.S. Pharmacopoeia as a tranquilizer. It’s widely used and approved in Europe as a mild hypnotic to induce sleep and relieve anxiety. In the United Kingdom, Valerian is also a popular and government approved sleep aid. Valerian targets the same neuroreceptars as benzodiazepines. As per the study in 1993, Valerian and Humulus lupulus (Hops) are calming to the central nervous system and reduce depression and anxiety. It has lesser side effects.40
The mechanism of Valerian tends to sedate by stimulating activity of the nerve transmitter GABA that dampens the brain’s arousal system. Perhaps, Valerenic acid and Valepotriates, chemicals unique to Valerian sedate the brain cells responsible for arousal.41 Valerian extract in the dose of 400 to 900 mg decreases sleep latency and nocturnal awakenings and improved subjective sleep quality. 42-44
Adverse effects of valerian are rare but include gastrointestinal upset, contact allergies, headache, restless sleep and mydriasis. 45 Valerian appears to be relatively safe in overdose46 with the major effect being central nervous system depression. 47
Withania somnifera (Ashwagandha)
The plant is used as adaptogen since long time.36 It has been extensively investigated. The root is a nervine sedative and is used in doses of one gram in all cases of general debility nervous exhaustion, brain – fatigue and loss of memory.48
When the anxiolytic and antidepressant activity of W. somnifera (dose 20 and 50 mg/ kg) was compared with that of Lorazepam (0.5 mg/kg i.p.) and also with Imipramine (10 mg/kg i.p.), the herbal drug showed comparable results. Thus, W. somnifera is a effective mood stabilizer in clinical conditions of anxiety and depression. 49
In an animal study assessing the anxiolytic and antidepressive actions of ashwagandha compared to commonly prescribed pharmaceuticals, an extract of the root was administered orally to rats once daily for five days. The results were compared to a group administered the benzodiazepine lorazepam for anxiolytic activity, and the tricyclic antidepressant imipramine for antidepressant investigation. Both the ashwagandha group and the lorazepam group demonstrated reduced brain levels of a marker of clinical anxiety. Ashwagandha also exhibited an antidepressant effect comparable to that induced by imipramine in the forced swim-induced “behavioral despair” and “learned helplessness” tests. Other similar studies confirm these results, lending support to the use of ashwagandha as an antistress adaptogen.50-53
Ashwagandha is generally safe when taken in the prescribed dosage range. Large doses have been shown to cause gastrointestinal upset, diarrhea, and vomiting.54
A typical dose of ashwagandha is 3-6 grams daily of the dried root, 300-500 mg of an extract standardized to contain 1.5 percent withanolides, or 6- 12 ml of a 1:2 fluid extract per day. Large doses of ashwagandha may possess abortifacient properties; therefore, it should not be taken during pregnancy. Since ashwagandha acts as a mild central nervous system depressant, patients should avoid alcohol, sedatives, and other anxiolytics while taking ashwagandha. 55
At the University of Texas Health Science Center, in 1991, the study indicated that extracts of Ashwagandha had GABA – like activity. 56
Piper methysticum (Kava)
It is a shrub, native to Polynesia and it has traditionally been taken by pacific Islanders as a beverage mixed with coconut milk and water. Most medicinal forms are either ethanol – water or acetone – water extracts. 57
Kava is marketed as a mild anxiolytic in European countries. In the United States, kava is sold in health food stores as a natural alternative to antianxiety drugs and sleeping pills. 58
The active constituents in Kava known as Kavapyrones have a variety of actions like inhibition of voltage – dependant sodium channels, increasing GABA-A receptor density, blocking norepinephrine reuptake and suppressing the release of glutamate.59,60-62 Kavalactones, the active principles in kava, are potent inhibitors of several of the CYP 450 enzymes, suggesting a high potential for causing pharmacokinetic interactions with drugs and other herbs which are metabolized by the same CYP 450 enzymes. Furthermore, some kavalactones have been shown to possess pharmacological effects, such as blockade of GABA receptors and sodium and calcium ion channels, which may lead to pharmacodynamic interactions with other substances, which possess similar pharmacological proprieties. 19
In a study conducted in Germany in which Kava was given to women suffering from anxiety, depression and other symptoms associated with menopause, the symptoms were relieved and sense of well – being was enhanced. According to some German scientists, Kava is as effective in treating forms of anxiety ad the powerful tranquilizers known as benzodiazepines. Kava is not habit forming and does not reduce alertness. 41
The side effects included oral and lingual dyskinesia, torticollis, painful twisting movements of the trunk, oculogyric crisis and exacerbation of Parkinson's disease. Kava has also been shown to have additive effects with central nervous system depressants. A patient who was taking alprazolam (Xanax), cimetidine (Tagamet) and terazosin (Hytrin) became lethargic and disoriented after ingesting kava.63
The investigationalstudies suggest that kava might have additive effects with benzodiazepines,given that they act on the same receptor and on the same areasof the central nervous system with increased GABA receptors. 64
Ginkgo biloba(Ginkgo)
It is an ancient Chinese medicinal plant, which is now being cultivated in several countries including India. A standard Ginkgo biloba extract of leaves contain 24 percent flavonoids and 6 per cent terpenes, increases cerebral blood flow, especially in geriatric patients whose conditions include short-term memory loss. The extracts of Ginkgo biloba has anti – free radical properties in various in – vitro systems that may contribute to its efficacy in free radical induced cerebral insufficiencies.36
In a review of more than 40 controlled trial of Ginkgo showed that all but one found clinically significant improvements in symptoms such as memory loss, concentration difficulties, fatigue, anxiety and depressed mood.65
In a 52 – week, randomized, double blind, placebo controlled, multi-center study of more than 300 patients with Alzheimer’s disease or vascular dementia used the extract at a dosage of 120 mg a day33 The group taking Ginkgo extract showed significantly less decline on two of the three standardized rating scales.66
Side effects of Ginkgo extract are uncommon but include headache, gastrointestinal upset and allergic skin reactions65 and rarely cerebral hemorrhage.67
Panax ginseng (Ginseng)
It is a commonly used herb in maintaining emotional balance. In a study conducted in 1982, nurses who switched from a day to a night shift were tested to see how efficient they were and how they reacted psychologically as they struggled to adjust to their new routine. Some of them were given ginseng to help them maintain emotional balance; another group was not given anything. Those who took ginseng felt less moody and were emotionally steadier than those who did not take the herb.41
Several studies have found indications that Panax ginseng might enhance mental function. However, the specific benefits seen have varied considerably from trial to trial, tending to make the actual cognitive effects of ginseng (if there are any) difficult to discern. A double blind, placebo-controlled study found that Panax ginseng could improve some aspects of mental function.68 Over a period of 2 months, 112 healthy, middle-aged adults were given either ginseng or placebo. The results showed that ginseng improved abstract thinking ability. However, there was no significant change in reaction time, memory, concentration, or overall subjective experience between the two groups. Another double-blind, placebo-controlled study of 50 men found that 8-week treatment with a Panax ginseng extract improved ability in completion of a detail-oriented editing task.69Also, a double-blind trial of 16 healthy males found favorable changes in ability to perform mental arithmetic in those given Panax ginseng for 12 weeks.70
A double-blind, placebo-controlled trial of 60 elderly people found that 50 or 100 days of treatment with Panax ginseng produced improvements in numerous measures of mental function, including memory, attention, concentration, and ability to cope.71 Benefits were still evident at the 50-day follow-up. However, virtually no improvement was seen in the placebo group, a result that is highly unusual and raises doubts about the accuracy of the study. In addition, three double blind, placebo-controlled studies evaluated combined treatment with Panax ginseng and ginkgo and found some evidence of improved mental function.72-74
Ginseng appears to be nontoxic, both in the short and long term, according to the results of studies in mice, rats, chickens, and dwarf pigs.75-78 Reported side effects with either type of ginseng are rare. There are a few case reports of breast tenderness, postmenopausal vaginal bleeding, and menstrual abnormalities associated with Panax ginseng use.78-83 Two reports indicate that combination treatment with Panax ginseng and antidepressant drugs may result in a manic episode.84, 85
Leonurus cardiaca (Motherwort)
It is also known as ‘heart herb’. It increases blood circulation in the brain. In the 17th century, it was recommended by the herbalist Nicholas Culpeper to prevent melancholy. In modern time, it has been studied in Germany where it was recognized as having a mild sedative effective for treating anxiety and sleep disorders. Modern herbalists report that it helps to alleviate depression especially when combined with other antidepressant herbs.41
A single application of motherwort extract (concentration not reported) in excess of 3 grams may cause diarrhea, uterine bleeding, and stomach irritation. 86 It should be avoided in pregnancy as large amounts may cause uterine contraction and potential miscarriage. 87
Other herbs used in mental disorders
Japanese formulations like Sho – ju – sen88 [Kumazasa leaf (Sasa kurinensis makino et Sibata), Japanese red pine leaf (Pinus densiflora Sieb et Zucc) and Ginseng radix (Panax ginseng c.A. Mayer)], Chinese formulation Suanzaoentang [Zizyphi Legustrum with liquorice, Chinese herbs Poria and Bung root] have been studied for their effect on depression and anxiety where they were found effective against the conventional drugs like Diazepam41. Plantago asiatica, Scruphularia ningpoensis, Ilex pubescens are the traditional Chinese medicines prescribed for treating depression like ailments in Chinese medical practice. 89Peaonia emodi Wall. is an ingredient of Shimotsu –to, a traditional Chinese medicine shown to improve spatial working memory in rats. 2
Some other herbs like Passiflora incarnata (Passion flower) 89, Evolvulus alsinide36 Scutellaria lateriflora (Scullcap herb) 89 are studied for their activity against irritation of brain, nervousness, restlessness; sleeplessness. Some other herbs including Humulus lupulus (Hops Strobile) 90, Convolvulus pluricaulis Choisy36 are considered for their activity against mild to moderate anxiety.
The herbs like Celastrus paniculatus Wild., Acorus calamus Linn., Piper longum Linn. are claimed as brain tonics. Clitoria ternatia Linn. is used as memory stimulant36. The herbs Eugenia caryophyllus Spl., Glycyrrhiza glabra Linn. Tinnospora cordifolia F. Vill exhibit their activity in mental disorders by acting on Acetalcholine content. Lawsonia inermis Linn, Nardostachys jatamansi DC are also important herbs used in mental disorders2.
Role of essential oils
The essential oils can be used in an aromatherapy room diffuser to reduce depression, anxiety and stress to enhance mood. The oils like that of Citrus bergamia (Bergamot), Juniperus virginiana (Cedarwood), Anthemis nobilis (Chamomile), Lavendula officinalis (Lavender), Citrus limon (Lemon), Rosa centifolia (Rose), Santalum album (Sandalwood) etc are mainly used in treatment of mild to severe depression, anxiety and stress. These oils are mainly used in the form of inhalation, bath, massage or steam treatments. However their use is limited to external application. Some of them may cause phototoxicity (eg Bergamot oil), some of them may result in skin irritation and rashes (eg. Lavender oil). Use of few oils is restricted during pregnancy (eg Cedarwood oil, Chamomile oil etc). 91
Conclusion
Increasing number of patients express a preference for the use of remedies they perceive to be natural and Physicians recommend herbal remedies in the selected cases. It is becoming increasingly important for physician to be familiar with the herbal remedies commonly used in the patient problems they serve.
Since the mental illness are diverse and individual patients are biochemically unique, a larger number of drugs will increase the likelihood of finding a beneficial medication, Hence in future times psychiatric patients will probably have medications with improved effectiveness and with less side effects.
Although evidence of the efficacy of the herbal preparation in treating psychiatric conditions is growing translating the results of efficacy studies into effective treatment for patients is hampered by the chemical complexity of the products. The lack of standardization of commonly available preparation and the paucity of well-controlled studies. This reveals that number of herbal drugs are available for the treatment of various mental disorders but there is a need to explore efficacy of many of them. For this a rigorous study of various traditionally but not scientifically proved herbs must be carried out at the pre-clinical and clinical levels.
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About Authors:
Mr. Santosh S. Bhujbal
Asst. Professor of Pharmacognosy,Dr. D.Y. Patil Pratisthan’s, Padmashree Dr. D.Y. Patil College of Pharmacy, Akurdi, Pune (MS) 411044, India.
Dr. Manohar J. Patil
Professor and Principal, Marathwada Mitramandal’s College of Pharmacy, Kalewadi,Pune(MS) – 411018 India
Mr. Sohan S. Chitlange
Asst. Professor of Pharmaceutical Chemistry, Dr. D.Y. Patil Pratisthan’s, Padmashree Dr. D.Y. Patil College of Pharmacy, Akurdi, Pune (MS) 411044, India.
Mr. Parag A. Kulkarni
Lecturer of Pharmaceutics, Dr. D.Y. Patil Pratisthan’s, Padmashree Dr. D.Y. Patil College of Pharmacy,Akurdi, Pune (MS) 411044, India.