LITERATURE REVIEW. Chapter-2

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1 Chapter-2 LITERATURE REVIEW Some national and international researchers have studied on hair growth mechanism and hair growth potential of various drugs obtained from natural and synthetic sources, which are summarised as follows: Jain et.al., (2016) studied and recognized a new molecule which can be utilized to treat Alopecia. With the aid of changing the induction of androgen-sensitive genes in the course of AGA that are brought on by the over-creation of 5α-DHT with the aid of the 5α-reductase (5α-R) enzyme; consequently one possible process to treat AGA is to inhibit this enzymatic response. RT-PCR was used to identify the presence of the 5α-R and AR within HHDPCs. Therefore a newly developed AGA-central HHDPC-established assay when combined with non-radioactive thin layer chromatography (TLC) this procedure was used for screening crude plant extracts for the identification of recent 5α-R inhibitors. HHDPCs expressed both 5α-R type 1 isoform of the enzyme (5α-R 1) and AR in the entire passages used on this study. Among the thirty validated extracts, Avicennia marina (AM) displayed the perfect inhibitory undertaking at the ultimate awareness of 10 µg/ml, because the creation of 5α-DHT reduced by using 52 % (IC50 = 9.21 ± zero.38µg/ml). Avicennia marina (AM) was once recognized as a potential herb for the cure of AGA based on its 5α-R 1-inhibitory activity. Patel et.al., (2015) worked and investigated the potential of Phyllanthus niruri (P. niruri) extracts for promotion of hair growth. The hair growth promoting activity of petroleum ether extract of P. niruri was shown by its topical administration. Alopecia was induced in albino rats by subcutaneous administration of testosterone for 21 days. Evaluation of hair loss inhibition was done by concurrent administration of petroleum ether extract of P. niruri and monitoring parameters were observed like follicular density, anagen/telogen (A/T) ratio and histological observation of animal skin sections. Finasteride solution was applied topically as standard. In vitro experiments were also performed in order to study the effect of extract on the activity of 5α-reductase enzyme. Albino rats were grouped and treated with petroleum ether extract of plant were hair regrowth activity was observed by studying the following parameters - follicular density, 25

2 (A/T) anagen / telogen ratio and skin biopsy. Histopathological and morphologic observations of hair re-growth at shaved sites showed active follicular proliferation. In vitro experiments results showed inhibitory activity of petroleum ether extract on type-2 5α-reductase enzyme and an increase in the amount of testosterone concentrations. Semwal et.al., (2015) reviewed on alopecia and suggested that Alopecia is a dermatological disease which frequently known as hair loss. Numerous medicinal techniques incorporate therapeutic retailers for alopecia but very few of them are promising. Makes use of herbs and medicinal plants for the medication of alopecia are very well identified by folklore followers. The conventional synthetic medicinal drugs are associated with one or more gigantic aspect effects when used for long term for alopecia medication. The herbal medicinal drugs obtained from herbs can furnish a safer and more potent replacement to treat alopecia. Grace et.al., (2014) have reviewed and stated that natural formulated oil when evaluated for its organoleptic character, acid value, saponification value, refractive index and ph and so on. All the parameters were observed to be excellent and correlate with that of standard values. Mankind makes use of various merchandise to enhance beauty and elegance to appear more youthful and charming. Cosmetics accordingly play a vital position in human life. Now days, natural or herbal cosmetic are largely used seeing that of the perception that they've fewer side and better protection. Hair is one of the important ingredients of the physique which acts as a protecting appendage. Nita et.al., (2014) studied and developed hair oil formulation of Eclipta alba 10%, Bacopa monnieri 10% and Trigonella foenugraecum 5% w/v respectively in the form of herbal oil which have excellent hair growth activity with standard (2% minoxidil ethanolic solution) in wister albino rats. Hair growth initiation time was remarkably changed to half on treatment with the oil, as compared to control animals. The time required for complete hair growth was also significantly reduced. Quantitative analysis of hair growth after treatment with oil exhibited greater number of hair follicles in anagenic phase i.e. 82 which were higher as compared to control. The results of treatment with oil were better than the positive control minoxidil 2% treatment. Hence Eclipta alba, Bacopa monnieri & Trigonella foenugraecum holds the promise of strong natural substitute for minoxidil. 26

3 Palanisamy., (2014) Investigated that Androgen-dependent methods are predominantly as a result of the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). The predisposed scalp exhibits high stages of DHT, and raised expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a principal role, at the same time androgen-regulated explanations deriving from dermal papilla cells are believed to have an effect on the development of other hair cells, components & hair follicle. Minoxidil, an anti-hypertensive agent is being used for treating AGA for more than 30 years. The inconsistencies within the outcome shown for hair follicle response to minoxidil mediated through its sulphate form which acts as potassium channel opener, query the evidences. Hair Cell cultures describe a kind of response to minoxidil and some of these would promote hair growth. Jegan et.al., (2014) worked and investigated that Benincasa hispida, extract shows desired pharmacological activity for treating and evaluating alopecia. Chemical test of extract confirm chemical constituents present in the extracts and the plant extract has significant social and psychologic consequences on androgen induced alopecia in animal models. Punasiya., (2014) studied on hair growth promoting activity of Hibiscus syriacus L. leaves extract with different solvent like petroleum ether, benzene, chloroform, methanol, and water. The phytochemical screening was done in order to study the bioactive compounds of the dry extract. The leaves of Hibiscus genus are traditionally acclaimed as hair tonic in the Indian system of medicine. Studies were therefore undertaken in order to evaluate petroleum ether, benzene, and chloroform, methanol, and water extract of Hibiscus syriacus L. leaves for its effect on hair growth in albino mice. The 10% extracts was incorporated into liquid paraffin base and was applied topically on shaved denuded skin of albino mice. The time required for initiation of hair growth as well as completion of hair growth cycle was recorded. The results of treatment with 10% petroleum ether, benzene, chloroform, methanol, and water extracts were comparable to the control. Rabinarayan et.al., (2014) investigated that the topical gel of minoxidil prepared by polymers comparable to hydroxypropyl methylcellulose K4M (HPMC K4M) and hydroxypropyl cellulose (HPC) in various concentrations (1, 2 and 3%) were used individually and in combination. The effectiveness of drug and polymers compatibility 27

4 had been done by adopting FTIR method. The gels had been evaluated for drug content material, viscosity, ph, homogenity, grittiness and in vitro drug release. The FTIR spectra of drug alone and in physical blend with polymers did not exhibit any shift in essential peaks, which indicates that there was no drug-polymer interaction. The entire information bought from above physicochemical parameters had been satisfactory enough. In vitro drug release of gels was carried out using Franz diffusion cell of 25 ml capacity with cellulose acetate membrane in phosphate buffer ph 6.8 as receptor medium. According to the release study, the drug release was decreasing with the increasing polymer concentration in each formulation. The correlation coefficient (r 2 ) values demonstrate that the drug release sample followed Higuchi model and the release exponent (n) values were within 0.45 to 0.85 for all formulations besides FG3, FG4 and FG7. The above results showed that swelling and diffusion (Non-Fickian diffusion) have been the drug release mechanism. Wani Snehal., (2014) worked and developed ayurvedic preparationsin formulation form for various hair disorder including dandruff.this natural shampoo was formulated using common herbal ingredient like Fenugreek (methi), Azadirachta indica (neem), Acacia concinna (shikakai), Sapindus mukorossi (reetha), Ocimum sanctu (tulsi) with standard established efficacy of hair care formulation. The blend of a few such powdered ingredient of natural foundation has made it feasible to secure and prepare tremendously potent dry powder shampoo. Although this formulation was prepared at laboratory scale and had been evaluated for its quality control aspect so that its safety and efficacy is ensured. Rajesh et.al., (2014) investigated and reported that herbal cosmetics are formulations by utilizing various natural coloring agents and are known as herbal Cosmetics. The therapeutic usages of herbal cosmetics are growing swiftly because of their least side effects. Because of this such Herbal drugs constitute a major part in any of the traditional system of treatment. As per one approximation there are about 1250 Indian medicinal plants, which are comprehensively used in preparation of various therapeutics preparations. In case of preparation of hair dying formulations the commonly said plants are Pterocarpus santalinus, Eclipta alba, Lawsonia innermis, Phyllanthus emblica, Centella asiatica and Acacia catechu. Investigation of these plants in terms of their formulations through utilizing special concentrations of extracts was developed and the affectivity in term of quality for higher colourantion on sheep wool threads. Results of 28

5 reports showed that three hair colorant formulations viz. PF-7, PF-5, PF-3, out of eight formulations of both aqueous and alcoholic extract, blackened better colorless sheep wool threads. The black colouring ability of the formulation PF-7 was found to maximum. It was also observed that the duration of black colour on the applied hairs was for longest period when the threads stored at room temperature, but under the influence of sunlight and washing of hairs with common detergents, the order of blackening of hair can be summarized as PF-7 >PF-5 >PF-3 >PF-4 >PF-6 >PF-2 >PF-8 >PF-1. The colouring effect of alcoholic extract formulation was significantly much higher than aqueous extract formulation. Eby George., (2014) worked and developed and assessed Minoxidil emulgel and compare its activities with Minoxidil gels. When gel and emulsion are utilized in combined the dosage form this is known as Emulgel. For preparing this emulgel, first, Minoxidil was dissolved in solvent system comprising of water and propylene glycol in ratio of 35:15 with liquid paraffin as oil phase. The prepared w/o emulsion was then combined with carbopol gel solution in ratio of 1:1 and finally neutralized with triethanolamine to form emulgel. Total eight formulations have been prepared out of which four have been gels and other four have been Emulgels. The gels had been evaluated for physicochemical parameters, In-vitro drug liberate and Ex-vivo permeation study. Rakesh et.al., (2013) had under taken a studies related to the hair growth development in experimental rats by using the Methanolic extract of Elephantopus scaber leaves. The methanolic extract of 2 % and 5% solutions were prepared for studying hair growth development in wistar rats for 30 days. Minoxidil (2% solution) was taken as a reference. It was observed that the formulation prepared from methanolic extract indicates drastically (p<0.01) potentiated result for onset of hair growth initiation and completion time with dose dependent manner. A significant improvement in epidermis biopsy, hair size and hair weight was also observed. The improvement in the initiation of new hair follicle was clearly observed In vitro studies (p<0.05). Kaur et.al., (2013) reviewed that the common problem associated with hair are depigmentation, dandruff and hair shedding. Conventional treatments for hair aliments include the drug therapy and hair transplantation. At present Minoxidil and Propecia (Finasteride) are the only two drugs are in use for hair growth in men. Minoxidil is 29

6 therapeutically used in to treat females with androgenetic alopecia. Although these two drugs are approved by FDA and are quite effective but considering their major side effect have resulted their limited use and the increase in the interest in the uses of herbal cosmetics. Soni et.al., (2013) studied and suggested that gigantic quantity of people around the globe is affected by hair loss (alopecia) or hair thinning. Hair loss is not a life threatening wellness problem it could possibly make existence distressful and might thereby affect bodily and intellectual health of man or women. To get to the bottom of such issues, an attempt has been made to evaluate the hair progress promoting endeavor of a herbo-mineral Ayurvedic formula, Trichup capsule. Safety of drug was additionally evaluated by means of conducting acute toxicity study as per OECD guiding principle. For analysis of hair progress activity, animals had been chosen and divided in to three groups and each group contains six animals. TED and TED X 2 groups were treated with Trichup capsule at the dose of 171 mg/kg/day and 342 mg/kg/day, orally for 30 days respectively. Visible parameters, hair size, hair diameter and serum total protein had been estimated. There have been no signs of toxicity or mortality for the duration of the treatment period. Therapy of Trichup capsule confirmed tremendous influence on all visible parameters. Size and diameter of hairs have been vastly increased in both groups. Total Serum protein was also increased in both groups as compared to control group. Anusha et.al., (2013) have undertaken the studies and concluded that dandruff is a common hair disorder which affect the scalp condition caused by yeast Pityrosporum. For the treatment of Dandruff many anti-fungal drugs are used in hair care formulation. But because of their major side effects including loss of hair, an attempt was made to formulate the anti-dandruff shampoo. The herbal anti-dandruff shampoo was formulated using herbal based ingredient like Lemon Grass Oil, Neem oil, Henna, Aloe Vera gel and other elements. Such shampoo was subjected to safety studies on albino rats on the aspect like eye irritation and skin sensitivity. The results obtained were good enough without any irritation and sensitivity. The stability studies for a period of three month yielded negligible changes in their physio-chemical properties. J Prasad., (2012) worked on 28 volunteers suffering from hair losses which varied from small patch to more diffused pattern.all the patient applied a gentle massage of the solution covering the whole area of the affected part and rinse in the morning. The 30

7 response to this therapy was evaluated at monthly intervals for a period of six month. The study clearly demonstrated the beneficial effect of Hairzone solution. The hair loss was reduced in 21 out of 28 patients. Sandhya et.al., (2102) carried out on the preclinical studies of a polyherbal phyto-chemical hair growth promoting cream blended with aqueous extracts of Trichosanthes cucumerina (T. Cucumerina) Linn and Abrus precatorius (A. Precatoius) Linn on accelerating the hair growth. Leaves of T. Cucumerina and A. Precatoius were individually extracted with distilled water and then subjected to primary chemical examinations and finally a hair cream was prepared. The formulated cream was subjected to evaluation of parameters like organoleptic characters, presence of overseas particles/grittiness, decision of ph, irritancy, partition coefficient, drug content material, diffusion studies, stability reports, sterility scan, SEM, FT-IR, solubility and hair growth promoting undertaking. The preclinical studies concluded that the 2% polyherbal phytocomplex hair development promoting cream was at par with the result obtained from minoxidil 2%. The percentage of hair follicles in the anagen phase was increased extensively which predicts that the formulation can be used in alopecia. As the 2% polyherbal phyto-complex hair cream didn't exhibit any kind of irritancy or toxicity to the experimental animals. Sukirti et.al., (2012) worked on Glycyrrhiza glabra root extract, the hair development promotion reports were carried out on three groups of female Wistar rats (n = 6) and the dorsal skin of selected animals was thoroughly denuded for complete elimination of hair. Paraffin oil (control), 2 % minoxidil solution (reference) & petroleum ether ( C) root extract of G. Glabra (2%), used to be applied to the denuded epidermis once daily for 30 days. The pattern of Hair growth was visually observed and subsequently the follicular density for hair follicle was performed by skin biopsy. It was seen that the animals treated with petroleum ether extract of G. Glabra roots indicated a longer pattern of hair growth as compared to those treated with either minoxidil or control. The onset time for hair growth was recorded (5 to 13 days) as compared to the time span of (6-19 days) by those animals treated with minoxidil. Also the of 76 % of hair follicles were found in anagenic phase (energetic growth section of hair) among the extract-treated compared to 66 % and 45 % respectively minoxidiltreated and control group. 31

8 Jain & Jain., (2012), reviewed that herbs & herbal drugs are clinically proved for hair growth. Hair loss problem is of great concern to both males & females. The main problems associated with hair loss are hair fading, dandruff & falling of hair. Various synthetic medicines are available for hair loss which does not treat permanently & also shows severe side effects. This problem could be solved by the use of herbal medicines. About 1000 kinds of herbal plant extracts have been examined for hair growth. Sapna et.al., (2012) aimed to prepare a formulation of herbal oils by using various herbs this formulation was evaluated for different physical parameters such as viscosity, saponification worth, ph, etc. Bhaiji et.al., (2012) carried out the experiments related to the hair gwoth in albino rats by using petroleum ether and methanolic extracts of Evolvulus alsinoides. The extracts so obtained was mixed with oleaginous base and applied topically on shaved denuded dermis of albino rats for thirty days. The time required for hair growth initiation and completion was drastically (P < 0.01) lowered. In this experimental model Minoxidil 2% solution was adopted as positive control. This treatment result in bringing 73% of hair follicles in anagenic phase which was comparable with the standard. Sivapalan., (2012) carried out the work on Cyperus rotundus L., which is a perennial weed and significant and specific plant which is commonly used as a traditional medicine throughout the world for treating indigestion, constipation, dysentery, stomach distention, neurogenic gastralgia, chest pains, irregular menstruation, painful menstruation, epidermis ailments, furuncle infections, leprosy, sprains and bruises, and fever. It also possess the significant therapeutic aspect as analgesic, alternative, astringent, antispasmodic, antibacterial, carminative, contraceptive, demulcent, emmenagogue, emollient, febrifuge, immunostimulant, laxative, tonic, vermifuge. Pharmacognostical investigations are performed to investigate macroscopy, microscopy, physicochemical parameters, and preliminary phytochemical screening and fluorescence characteristics. The findings provide priceless information with regard to its identification and standardization parameters. Sanjay et.al., (2011) reviews and stated that ethanolic extract of Nardostachys jatamansi (Valerianaceae) and Cyperus rotundus (Cyperacae) was evaluated for hair growth on albino rats. The result of his studiers suggested that both of the extracts are having a substantial hair growth activity the hair growth potential activity had been 32

9 observed on Chemotherapy induced alopecia model and investigation was achieved making use of various parameters like hair density, lymphocyte depend and testosterone stage along with histopathological. Jain et.al., (2011) have formulated and evaluated herbal formulation containing the extract of Emblica officinalis (Fruits) extract (5% w/w), Centella asiatica leaf, Aloe vera leaf extract (5% w/w), Ocimum sanctum leaf extract (5% w/w), Eclipta alba extract (5% w/w) in hydrophilic USP base in various ratios.the extract obtained so was converted into ointment which was topically applied on shaved skin of rats.the combined effect of such formulation on hair growth was much significant as compared to the application of single extracts of Emblica officinalis, Centella asiatica, Aloe vera, Ocimum sanctum and Eclipta alba. Semwal et.al., (2011) reviewed that Alopecia is most severe scientific situation and the lack of hair from some or all areas of body, commonly scalp was found. There are various types of alopecia similar to diffuse alopecia areata, alopecia areata monolocularis, alopecia areata barbae, and alopecia areata totalis. It occurs in 0.1%-0.2% of person of any age group or any person irrespective of age and sex like late teenage, early childhood, young grownup hood. There will also be distinct factors of alopecia like genetic, drug precipitated, and environmental, emotional stress and so on. It's an embarrassing for any one, as he/she appears extra aged than average. To prevent or cut down unwanted side effects of allopathic drugs most of effective persons would like to switch over to herbal medicine. More than a few herbs are getting used to restrict the hair loss and regrowth of hairs together with aloe vera, amla, bhringraj, brahmi, etc. Sundberg et.al., (2011) stated that primary follicular dystrophy with scarring dermatitis in c57bl/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans. A number of C57BL/6 (B6) substrains were commonly used by the researcher. One of several B6 strain-specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis. Clinical and progressive histological changes of skin disease commonly observed in C57BL/6J and preliminary studies in other closely related substrains were presented. Lesions were developed due to a primary follicular dystrophy with rupture of severely affected follicles leading to formation of secondary foreign body granulomas in affected B6 substrains of mice. Histologically, these changes resemble the human disease called 33

10 central centrifugal cicatrical alopecia (CCCA). Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affect removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected, which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these 2 defects has the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains. Gholamreza et.al., (2011) reported that various conditioners, hair toner and formulation containing herbal extract can effectively reduce the loss of hair. The 50% ethanolic extract of seeds of fenugreek have been prepared by maceration system, and then were freeze dried. The product so obtained was used in the formulation of shampoo. This shampoo was having the excellent thiotropy property. Based on some specific data and its performance with other market shampoo it was inferred that this formulated shampoo was having a better quality.than the other marketed ones. Hanna et.al., (2010) reviewed that the pilosebaceous unit is a structure which passes through a hair growth cycle and contains a number of principal drug targeting sites. Via this procedure medicines can also be distinctive to the bulge area with stem cells or to the sebaceous glands. Curiosity in pilosebaceous units is directed towards their utilization as reservoirs for localized medication and also as a transport pathway for systemic drug supply. Advanced investigative methods, corresponding to differential stripping, are being evolved as a way to determine follicular penetration. These findings review the concern aspects of comprehensive follicle-targeting formulations and delivery system including the activity stage of hair follicles, and variants in follicle size and distribution. Patil et.al., (2010) stated that the hair loss (alopecia) is not the disease which is life threatening. It is only the thought of baldness which can result to the emotional and traumatic experience. Such person may try all the possible aspect to regain their hairs. Although the common treatment of hair thinning is the hair transplant but there are medicine namely Minoxidil and Propecia (Finasteride) which have been approved by FDA for hair growth in men. Both of these drugs have been proved to have the positive outcome for balding condition on the vertex region of the scalp.but despite this the 34

11 herbal medicines are used as a alternative drugs because of the side effect caused by the aforementioned two drugs. Yoon et.al., (2010). Carried out the studies related to the efficacy of essential oil obtained from seeds of Zizyphus jujuba for its hair growth promotion activity in vivo. The essential oil obtained so was applied topically on the shaved skin onto the backs of BALB/c mice and observed for 21 days. The concentrationsof the applied oil was (01%, 1% and 10%) respectively. After 21 days it was observed that those mice treated 1% and 10% of essential oil produced a substantial effect on the length of hair which were measured to 9.96 and mm, respectively. These result are quite encrougeing considering the length of hair 8.94mm only among the control lots. The overall finding was such that the mice treated with 1% essential oil produced the optimum result. Ghosh et.al., (2010) had also reported that Alopecia is a dermatological disorder which is more concern with the psychosocial implications on patients with hair loss. During his studies he tried Arnica mon-tana, Aloesocotrina, Emblica officinalis, terminalia chebula, Nyctanthes arbor-tristis, Pilocarpus jaborandi and formulated 5% herbal cream from the above mentioned herbs and concluded that the excellent hair growth activity was observed which was comparable with the rate of hair growth by applying standard 2% minoxidil ethanolic solution in wister albino rats. In addition to above the hair growth initiation time has been found to be significantly reduced to 50 % on treatment with the formulation as compared to control animals. The total time required to for complete hair growth was also substantially reduced. Barahmani et.al., (2010) suggested that the serum cytokine profiles mentioning the severity of the Alopecia areata (AA) phenotype or are affected by co-existent atopy. Alopecia areata is an organ particular autoimmune ailment characterized by folliculotropic T-cell infiltrates around anagen stage hair follicles. In this expeirment 17 serum cytokines have been measured and when compared in 269 individual sufferers having AA of varying severity with and without atopy and 18 unrelated controls. Among the 269 individual sufferers, 96% had active sickness and 54% have been a topic. Levels of Thl, interleukin (IL)-l receptor antagonist (ra) and IL-8 levels have been larger in all patients with AA than in controls. IL-la, IL-12 and tumour necrosis aspect-a stages were larger in individual sufferers with AA and atopy than in patients with AA without atopy. It was once consequently concluded that increase Thl 35

12 serum cytokines (IL-2, IL-12 and interferon-y) and IL-lra levels are associated with AA in spite of disease severity or the presence of atopy. Petukhova et.al., (2010) studied genome-wide collaboration in alopecia areata and observed that it implicates each innate and adaptive immunity. Alopecia areata (AA) is one of the most extremely typical human autoimmune disorder, it leads to hair loss due to the deficiencies of immune privilege of the hair follicle and subsequent autoimmune assault. A genome - wide collaboration gain knowledge of (GWAS) in a pattern of 1,054 case and 3,278 controls were conducted and 139 single nucleotide polymorphisms were recognized which might be tremendously associated with AA. Right here an association with genomic regions containing several genes controlling the activation and proliferation of regulatory T cells (T,eg cells), cytotoxic T lymphocyteassociated antigen 4 (CTLA4), interleukin IL)-2/IL-21, IL-2 receptor A IL-2RA; CD25) and Eos as good as the human leukocyte antigen (HLA) region was once studied. These observations have furnished proof for the involvement of each innate and acquired immunity in the pathogenesis of AA. The genetic underpinnings of AA had been succinctly outlined, and positioned within the context of shared pathways among autoimmune ailments, and a novel disorder mechanism, the upregulation of ULBP ligands, in triggering autoimmunity has been uncovered. Abdullah et.al., (2010) reviewed alopecia areata (AA) as autoimmune ailment that symbolize as nonscarring hair loss, although the detailed pathogenesis of the disease is yet unknown. Disease incidence rates ranges from 0.1% to 0.2% which had been estimated for USA. Alopecia areata can impact any hair-bearing part of the body. It most commonly visualized by well demarcated patches of nonscarring alopecia on dermis /skin. Alopecia areata points are good known with poor diagnostic signs, the path of the ailment is unpredictable and the response to treatment varies with age and sex.. Semalty et.al., (2010) worked on herbal formula containing three herbal drugs namely Semecarpus anacardium, Trigonella foenumgraecum and Trigonella corraculatc and reported that hair growth promoting activity. Petroleum ether and ethanolic extracts of all three herbs was prepared. Aloe veragel (prepared with recent Aloe vera leaves) based herbal formulations have been prepared with both varieties of extracts. The formulations was subjected to characterization of ph, texture, odour and toxicity reports. 36

13 Hair growth activity of the formulations was studied with 2% minoxidil solution (positive control) in albino rats for 30 days. Krishnamoorthy et.al., (2010) worked and stated that the hair growth enhancing property of a poly herbal preparation in comparison with 2% Minoxidil ethanolic solution in an experimental animal model. The investigated report shows that in gel form containing extracts of medicinal herbs stated in Siddha system of traditional Medicine was found to have statistically significant influence on promoting hair growth and its outcomes had been in relative comparison with Minoxidil solution. Deependra Singh Dangi., (2010) worked on epilation induced alopecia and reported that this model is best for studying alopecia and the hair growth activities are trustworthy, fast, economical and reproducible for any type of test compound. Epilation means uprooting of hair follicles, rendering the synchronized hair growth in the experiment field, which can also be altered via the topical application of experiment compound under test. Changes within the qualitative as well as quantitative standards estimate the hair growth promoting activities. Positive control group receiving 2% minoxidil solution topically has proven higher qualitative parameters i.e. Hair growth initiation and completion time and other good quantitative parameters like hair size, hair growth rate, follicle width, thickness, percent anagen induction, and many others as in comparison with control group. Ashlesh et.al., (2010) investigate and stated that numerous researches are going to explore the safe and effective drug for their hair growth Tobacco leaves have been mentioned in old Indian literature for hair promoting activity. Hence, the main purpose of present study is to formulate and evaluate the microbial bio transformed extract of tobacco leaves for hair growth activity in male albino Wister rats. The extract was prepared via microbial biotransformation of tobacco leaves in cow urine for 28 days. The herbal formulations (lotion) were formulated by common system of making emulsion oil in water (o/w) base in various proportions or concentrations of 10%, 20% and 30% of extract. These lotions were applied on shaved dermis area of rats for 30 days and the fix quantity of this lotion is applied on denuded skin once a day and hair size, total serum protein, and total testosterone were calculated for the result estimation. Nema et.al., (2009) worked and reported that herbal formulations prepared from fruits of Embelica officinalis, flowers of Hibiscus rosa sinensis, leaves of Bacopa 37

14 monnieri and seeds of Trigonella foenumgraecum in form of herbal oil by various techniques prescribed in Herbal and Ayruvedic Pharmacopeia shows good result for hair growth activity. The oil of different concentrations had been characterized for proximate analysis including moisture content, total ash, acid insoluble ash, water soluble ash, water insoluble ash, sulphated ash, they were also subjected to chromatographic studies and chemical test to determine various phyto-constituents The formulation containing 7.5% of each drug used for the study and showed excellent hair growth activity with standard (2% minoxidil ethanolic solution) by an enlargement of follicular size and prolongation of the anagen phase. It holds the promise of potent herbal alternative for minoxidil. Lew et.al., (2009) determined the new clinical approach and prognosis of acute diffuse and total alopecia (ADTA) by means of specified clinical observations. The histopathology of lesion revealed infiltration of mononuclear cells round the hair follicles and outstanding pigment incontinence. Individuals experience hair regrowth in them in about 6 months, without regard to the approach of treatment. These cases can also be categorized as having a new subtype of AA that is related to a good prognosis and speedy spontaneous restoration even without medication. Barahmani et.al., (2009) investigated the symptoms associated between history of atopy or autoimmune ailments and hazard of alopecia areata AA. The evaluation showed that a historical past of atopy and autoimmune ailment was once associated with an enhanced chance of AA and the result of that outcome had been consistent for each the severe subtype of AA (i.e. Alopecia totalis and alopecia universalis) and the localized subtype (i.e. AA chronic). Duque- Estrada et.al., (2009) studied the possible hazards risk of mesotherapy as a therapeutic procedure for hair loss. Mesotherapy has just lately turn out to be an advertised method for the therapy of exceptional types of hair loss regardless of the lack of any information regarding its efficacy and feasible part effects. The substances injected into the scalp include "the mixture " of traditional plant extracts, homoeopathic drugs, nutrition, vasodilators, and medicinal drugs that may stimulate hair growth potential, such as finasteride and minoxidil. In one individual, hair loss took place after injections of the heparinoid vasodilator mesoglycan; the threemonth follow up examination revealed a small residual field of cicatricial alopecia. 38

15 Yet another individual homeopathic agents. developed reversible alopecia after multiple scalp injections of Welsh N, guy A, (2009) explored experiences of patients suffering from alopecia areata and alopecia universalis and studied their problem owed of adjusting to, and dealing with such situation. Whilst earlier studies and their observations has focused on the antagonistic psychosocial have an impact of alopecia, this investigation used Interpretive Phenomenological analysis to provide a extra holistic perspective, results showed that techniques used by participants evolved over time and that there have been clear gender differences. Within the early levels, patient did not want to consider that their hair loss can be lasting and managed through concealment. Later coping techniques reflected an embodied acceptance with contributors managing the effects of AA/AU and becoming extra optimistic about surviving with the circumstances. Harries et.al., (2009) studied about fundamental of cicatricial alopecia (PCA) representing distinguished inflammatory ailment that results in everlasting loss of scalp hair. Cutaneous autoimmunity, most prominently persistent cutaneous lupus erythematosus (CCLE), can result in this type of abnormal hair loss. Hair follicle (HF) cycling and regeneration are disturbed in PCA as a result of irreversible, epithelial hair follicle stem cell (ehfsc) damage, influenced by critical, but doubtful pro-inflammatory events (such as : Type I interferon-related cytotoxic inflammation, loss of HF immune privilege, loss of immunosuppressive with "no danger " alerts). Thus, immuno-safety parameters of ehfsc and restructure of their immune privilege are appealing future therapeutic approaches in PCA. Chronic cutaneous lupus erythematosus-associated PCA is also served as a model system for other diseases where epithelial stem cells undergo immuno-destruction. Suraj et.al., (2009) carried out the research work on seeds of Prunus dulcis which had been traditionally identified for its hair promoting effect. The efficacy of the extract P. dulcis was investigate hair growth potential effect. Petroleum ether, methanol, chloroform and water extracts of P. dulcis seeds were mixed in oleaginous ointment base have been utilized topically on shaved denuded epidermis of albino rats and screened for hair growth potential effect. Petroleum ether extract confirmed consistent and significant increase in the length of hair (p<0.001) with good % of hair follicles 39

16 within the anagen phase were recorded. The study was completed within 24 days for petroleum ether used to be 24 where as for methanol, water and chloroform extracts had been 28, 29 and 30 respectively. Thorat et.al., (2009) worked and formulated an hair oil formulation of Eclipta alba Hassk (Asteraceae) 10% w/v, Hibiscus rosa sinensis (Malvaceae) 10 % w/v, Nardostachys jatamansi (Valerianceae) 5 % w/v in the form of herbal oil. The prepared formulation was evaluated for three month in comparison with coconut oil was carried out on human volunteers who are suffering from hair fall problem. The prepared formulation was evaluated suing Combing assay to assess the efficacy of the prepared herbal hair oil. The findings of the research show that the formulated oil was effective and capable to reduce the hair fall rate. Datta et.al., (2009) studied on Eclipta alba and reported that the methanolic extract of Eclipta alba was used as hair growth promoter. A species of Pigmented C57/BL6 mice were preselected for study of telogen phase for hair growth. The truncal epidermis lacks melanin-producing melanocytes and melanin production is exactly to anagen phase of hair growth. The extract was applied topically to assess telogen to anagen transition. Antigen specificitytest was performed by Immuno histochemical investigation. Animals in anagen phase of hair growth have been positive for FGF-7 and Shh and negative for BMP4, whereas the animals in telogen phase had been positive only for BMP4 antigen. The methanolic extract was evaluated for hair growth promoting activity, exhibited dose elegant activities in C57BL6 mice. The preparation was evaluated for the melanogenesis in resected dermis, follicle count in the subcutis, skin thickness and surrogate markers in vehicle control and extracts handled animals. These findings advise that methanolic extract of Eclipta alba can have competencies as a hair development promoter. Thorat et.al., (2009) worked and stated that alopecia is a dermatological disorder with psychosocial implications on patients with hair loss. Eclipta alba Hassk (Asteraceae), Hibiscus rosa sinensis Linn (Malvaceae), Nardostachys Jatamansi (Valerianaceae) is a good known Ayurvedic herb with purported claims of hair growth promoting. Hair preparation of Eclipta alba Hassk ( Asteraceae ) 10% w/v, Hibiscus rosa sinensis Linn ( Malvaceae ] 10 % w/v, Nardostachys jatamansi ( Valerianceae ) 5 % w/v were prepared in form of herbal oil to evaluate hair growth and compared with 2 % 40

17 minoxidil ethanolic solutionas positive control in Wister albino rats. Hair growth initiation time used to be significantly decreased to 1/2 on treatment with formulated oil, as in comparison with control animals. The time required for complete hair growth was greatly lowered. Quantitative evaluation of hair growth formulation after treatment with herbal oil exhibited better result as hair follicles in anagenic phases which have been 82 as compared to control which were 52. The results of herbal oil have been better than the constructive control minoxidil 2 % remedy. It holds the promise of robust herbal substitute for minoxidil. Talpur et.al., (2009) studied the safety aspect together with the dose-limiting toxicities with side effect, and efficacy, i.e., to record the response rate of bexarotene in hair loss or alopecia areata. Hair loss may be due to perifollicular T-cell infiltrates, which may be refractory to treatment. The Bexarotene, is a retinoid X receptor, which is a selective retinoid and induces T-cell apoptosis. This design could now not differentiate between drug-induced and spontaneous regrowth. Arslan et.al., (2009) experimented and reported that the effects of biotin supplementation on serum and liver tissue biotinidase enzyme endeavor and hair loss in rats which were administrated to valproic acid, Valproic acid (VPA) is a generally used and well-tolerable antiepileptic drug in epileptic patients. Nevertheless, VPA has many facet effects associated with dose-elegant and non dose-dependent. It has been observed that VPA therapy may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Experiments have been performed to observe the biotin deficiency which may be seborrheic dermatitis, dry skin, excellent and brittle hair, and hair loss. The results of biotin supplementation on serum and liver tissue BEA and hair loss for the duration of VPA remedy had been investigated. There were significant loss within the stages of serum and liver tissue BEA of the be examined group compared with the control one. It was inferred that VPA usage loweres the serum and liver tissue BEA and impaired the biotin utilization by using affecting the liver. Partial biotinidase deficiency may just lead to hair loss. Thus biotin supplementation may be avoided in the patients receiving VPA therapies. Wiliemsen et.al., (2009) studied the multiplied history of childhood and lifetime demanding events among adults with hair loss. Whither adult hair loss is related with childhood or total lifetime demanding activities is no longer identified. 41

18 Prior reviews have reported most effective on the relationship with up to date traumatic hobbies. It was once discovered that sufferers or patients with hair loss experienced extra emotionally and bodily demanding activities. The trained documents revealed an expanded history of childhood trauma in patients with hair loss when compared with manipulate topics. Humbert, (2009) pronounced that hair loss is one of the most dreaded aspect results of chemotherapy, specifically with the aid of females with breast melanoma. It suggests a deterioration of body ensuing in a poor selfimage due to which woman s femininity suffers. Present methods to restrict chemically caused hair loss are insufficiently mighty and inconvenient. It has recently been shown that the oral administration of L-cystine mixed with pyridoxin would avoid hair loss triggered through tobacco in mice. The hair loss induced by tobacco involves apoptosis mechanisms as in drug-triggered hair loss. This be study confirmed that the apoptosis prompted via doxorubicin was once vastly diminished in presence of the cystine + pyridoxin and accordingly the glutathione was once significantly higher in presence of cystine. Garg et.al., (2009) described lack of hair as a usual condition causing nonscarring alopecia. Usually the patchy involving the entire scalp (alopecia totalis) or whole body (alopecia universalis). Hair loss could motive great psychological distress, and the predominant aspect of administration is counselling the patient about the unpredictable nature and course of the condition as well as the available therapies, with important points of their adverse effects. Although many therapies were proven to stimulate hair progress in alopecia areata, there are limited knowledge on their lengthyterm efficacy and affect on excellent of existence. The proof for the following used treatments: corticosteroids (topical, intralesional, and systemic), topical sensitizers (Diphenyl cyclopropenone), psoralen and ultraviolet A phototherapy (PUVA), minoxidil and dithranol was reviewed. Triieb, (2009) studied the emotional misery observed on by chemotherapyinduced- alopecia (CIA). The incidence and severity of CIA are variable and related to the certain chemotherapeutic protocol. CIA is mainly categorized as acute diffuse hair loss brought on by dystrophic anagen effluvium; nonetheless, CIA grants with one of a kind medical patterns of hair loss. When an arrest of mitotic exercises occurs, 42

19 undoubtedly countless and interacting motives influences the shedding sample. The main process to slash CIA is by way of scalp cooling. A couple of experimental approaches to the progress of pharmacologic models are underneath evaluation and comprise drug-specific antibodies, hair growth cycle modifiers, cytokines and growth motives, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Among the few molecules which were evaluated so far in humans, AS 101 and minoxidil had been able to diminish the severity or shorten the length of CIA, however would now not preclude CIA. Biro et.al., (2009) explored the endocannabinoid method of the skin in healthy and diseased volunteer. The newly discovered endocannabinoid approach (ECS; comprising the endogenous lipid mediators' endocannabinoids present in almost all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in a couple of regulatory services each in healthy and diseased volunteer. Latest investigation and researches have apparently shows the existence of a functional ECS in the skin and implicated it in more than a few biological methods (e.g. Prolitferation, growth, differentiation, apoptosis and cytokine, mediator or hormone construction of various cell forms of the skin and appendages, such as the hair follicle and sebaceous gland). It appears that the essential physiological perform of the cutaneous ECS is to constitutively control the right and good-balanced proliferation, differentiation and survival, as good as immune competence and/or tolerance, of skin cells. The disruption of this gentle steadiness might facilitate the progress of more than one pathological stipulations and ailments of the dermis (e.g. Pimples, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth problems, systemic sclerosis and melanoma). Awe., (2009) worked and stated that traditional extracts for hair growth corresponding to methanolic extract of the whole plant of Russelia equisetiformis (MERE) (Family - Scrophulariaceae) has hair growth promoting effect. Topical application of MERE onto a known diameter of shaved field of the back of albino Wistar rats, produced a significant increase in the rate of hair growth (P<0.05), in a concentrated manner. The influence was shown with the aid of reduction in the diameter of the shaved area. Formulation of R. Equisetiformis has hair promoting advantage, the outcome of which is also due to the presence of triterpenes and flavonoids within the plant extracts. 43

20 Vaishali Rathi., (2009) worked and stated that hair growth promoting effect of three polyherbal formulations. Polyherbal formulations were formulated using extract of Cicer arietinum Linn., Ocimum sanctum Linn. and Cyperus rotundus Linn. in different ratios to acquired the quality components The extract integrated into cream were applied topically on shaved skin of rats and primary skin infection test, hair growth initiation time, completion time, hair length and diameter were observed. The ratio of Cicer arietinum Linn., Ocimum sanctum Linn. and Cyperus rotundus Linn. in 1:2:3 confirmed best hair growth promoting effect comparable to standard. Gupta et.al., (2008) worked and developed the hair formulation from herbs of Emblica officinalis (Euphorbiaceae), Bacopa,monnieri (Scrophulariaceae), Trigonella foenumgraecum (Leguminosae),Murraya koenigii (Rutaceae) in various concentrations in the form of herbal oil for evaluating hair growth potential of the prepared formulation. Every drug has been tested individually for its activity in ratio of 1-10%. Established on these outcome blend of herbs Murraya koeniigi, leaf (Rutaceae), Bacopa monnieri, leaf (Scrophulariaceae), Trigonella foenumgraecum (Leguminosae),Murraya koenigii (Rutaceae) have been prepared in various concentration in form of herbal hair oil.the result shows that the hair growth activity of every drug used to be determined proportional to the concentration variety validated. In a similar fashion greater concentrations of drug in the system were observed to have higher hair growth activities. The formulation containing 7.5% of each drug used for the study and confirmed fine hair development in comparison with standard (2% minoxidil ethanolic solution) by an expansion of follicular size and prolongation of the anagen phase. It holds the promise of potent herbal alternative for minoxidil. Randall, (2007) evaluated hormonal control of hair follicles. Hair's importance for insulation and camouflage or human communique signifies that hairs ought to change with season, age or sexual growth and development. Common, regenerating of hair follicle cycles produce new hair follicle which may just vary in colour and size, e.g., beard growth. Hormones of the pineal-hypothalamus-pituitary axis coordinate seasonal changes, simultaneously androgens regulate most sexual aspects with satirically specific results depending on body site; examine beard growth and balding. Hormones have an effect on follicular mesenchymal- epithelial interactions altering growing time, dermal papilla size and dermal papilla cell, keratinocyte and melanocyte endeavor. These 44