Indigenous medicinal plants of Pakistan used to treat skin diseases: a review

Ethno-pharmacological relevance Plants are providing reliable therapy since time immemorial. Pakistan has a great diversity in medicinal flora and people use these ethno-medicines to deal with many skin problems. This review explores the fundamental knowledge on various dermatological properties of medicinal plants of Pakistan and is aimed to provide a baseline for the discovery of new plants having activities against skin issues. Material and method A total of 244 published articles were studied using different research engines like PubMed, Google, Google-scholar and science direct. Results Review of literature revealed ethno-pharmacological use of 545 plant species, belonging to 118 families and 355 genera, to combat various skin ailments. Out of these, ten most commonly used plant species belonging to ten different families are documented in this review. It was also found out that ehno-medicines are prepared using various parts of the plants including leaves (28.32%), whole plant and roots 13.17% and 10.97% respectively, in the form of powder (23.5%) and paste (22.75%). A total of 13 endangered plant species and ten commercially important plants were recorded. Conclusion Medicinal plants of Pakistan have therapeutic effects against several skin problems; however most of medicinal plants are still not evaluated scientifically to support their ethno-pharmacological claim on skin. Dermatological pathogens are recommended to study. Further, the conservational programs should be established for endangered species.


Background
History of natural products is as old as human civilizations and so is the Indigenous knowledge, which is handed down to the people from their ancestors through verbal communication; people have been living in close association with plants since time immemorial [1]. The purpose of standardizing traditional remedies is, obviously, to ensure therapeutic efficacy of medicinal plants; whereas the value of ethno-medicinal information in modern pharmacology lies in the development of new drugs. Some modern drugs have been deducted from folklore and traditional medicines [2]. The origin of the word "Ethnobotany" is accredited to US ethnobotanist "John Harshberger" who described and explained the relationship between people and plants they use in a culture in 1895 [1,3]. In Sub-continent, Rig Veda (4500-1600 BC) compiled first record of ethno-medicine [4].
In ancient times, natural products were successfully used to treat different ailments owing to their enhanced acceptability in human society, better compatibility with the body and their natural power to treat ailment via synergistic effects and neutralizing combinations to lessen adverse effects [5]. Medicinal plants are better as compared to synthetic drugs because of minimal adverse reactions [6,7]. Medicinal plants (trees, shrubs, grasses or vines) can be used in different forms [8] like extracts, in fresh or powdered form, seeds, fruits, vegetable mixtures, etc. [9].
According to an estimate, earth carries 265,000 species of plants but only half of these are yet investigated for their medicinal values and chemical composition. In developing countries, around 80% of the population depends upon medicinal plants for combating different diseases but this was estimated about a decade ago [10,11] while in developed countries, 60% of the population uses these plants [6], 40-50% of the population in Germany, 42% in the USA, 48% in Australia and 49% in France depends upon plants for different health issues [12]. Importance of these medicinal plants can be judged by the fact that at least 25% of the drugs enlisted in modern Pharmacopoeia are of plant origin [5]. Also about 25% of the medical prescriptions are based on the substances or analogs of the substances of plant origin [13].
Pakistan occupies 80,943 km 2 area and lies between 60°55′ to 75°30′ E longitude and 23°45′ to 36°50′ N latitude [14], and has altitude ranges from 0 to 8611 m with a mixed climate zones; has a large biodiversity of the medicinal plants. Pakistan is blessed with 6000 species of higher plants, of which 600-700 are used medicinally [15], out of these 6000 species, half (3000 species) are reported from Northern areas out of which 124 species have medicinal importance [16,17], 4940 flowering plants are native to Pakistan (if cultivated flowering species are included figure turns 5738) [14]. Unfortunately only 10% of the total plant species in Pakistan have reported medicinal values [18].
In Pakistan, a large population uses folk medicines and it has become a definite part of its cultural heritage [19]. In early 1950s, most of the health concerned issues were treated using traditional indigenous experiences by more than 84% of the population of Pakistan but now this practice is limited to only remote areas of the country [6,20,21]. In 1958, Hocking also reported same percent (84%) of Pakistan population depending upon traditional medicinal plants for treating different ailments. In 1983, 63% of the population in Pakistan, especially in villages, was reported to use herbal medicines prescribed by the traditional prescribers [22]. Knowledge on the use of medicinal plants is enormous but if this traditional knowledge is not rapidly researched and recorded, indications are that it will be lost with succeeding generations [23].
Skin, the most diverse organ of the human body, is very important for aesthetic reasons and health issues. Skin diseases not only give unfavorable looks but also pushes the patient into psychic conditions [24]. It has been estimated that skin diseases account for 34% of all occupational disease [25]. Despite of all the developments in the medical science, it is still complicated to manage skin diseases specifically in developing countries, due to the fact that health care workers lack training in skin care and skin diseases, which have been of major concern, recently, due to their association with the Human Immunodeficiency Virus and Acquired Immunity Deficiency Syndrome (HIV/AIDS) [26]. Since human civilization, plants are used to treat major skin issues like wounds, cuts and burns [27]. In a study, it was documented that 80% of the Indian population uses ethno-medicines to deal with skin problems and 50% of the medicinal plants used against skin problems are restricted to forest [28].
This review is an attempt to summarize utmost possible information on ethno-medicines and pharmacology of the plants used in Pakistan to cure skin diseases. This study was aimed to investigate the ethno-medicinal uses of the plants of Pakistan to treat various skin conditions. We were interested in gathering the answers of the following questions in particular: Which plant species are most commonly used traditionally for skin problems? Which skin conditions are most commonly treated using ethno-medicine? Which parts of medicinally important flora of Pakistan are used against skin diseases? What are the recipes for preparing and applying the ethno-medicines? Above all, the review will identify gaps in the current knowledge that will provide a baseline for further research activities. Also, the review is aimed to highlight the area of Pakistan still need to be investigated. As this review is written after consulting a large number of articles, only references are provided in it due to vey diversified data.

Data collection and analysis
The data collected were grouped into 26 categories on the basis of skin conditions; 28 categories based on families plant belong to; 7 categories based on mode of preparation of medicine, 30 categories based on the part used, 9 categories based on habit of plants and 6 categories based on the region the plant grows.
Plants reported in more than one region of Pakistan were enlisted only once for making the final list of medicinal plants. Conservation status was evaluated following IUCN red list categories version 3.1 and the herbal products registered in Pakistan and economical importance of the plants was estimated by consulting druginfosys.com and scientific literature respectively.

Taxonomic problems
Several taxonomic problems were observed in the development of this manuscript. Entirely, we documented 10 plant species most frequently used by the people of Pakistan against skin diseases, there were some spelling mistakes in family names, botanical names, publication and authors, which were also verified according to "http:// www.googl e.com", "http://www.tropi cos.org" and "http:// www.plant list.org".

Results and discussion
The present review revealed ethno-medicinal use of 545 plant species belonging to 118 families and 355 genera to cure various skin diseases, 10 plant species belonging to different genera and families which were most commonly used in different regions of Pakistan against several skin ailments are documented in this review ( Table 1).  Table 2. Many of the plants and hence families were used in more than one region; those plants and their families were counted just one time when enlisting for overall plants of Pakistan. The distribution of plants and their families in different regions of Pakistan, according to their use in skin conditions is shown in Fig. 1.

Medicinally important families and genus against skin ailments
A total number of 118 families were studied and out of them 10 families were documented in this review. Among these families, Asteraceae (8.99%) is the most commonly used family followed by Fabaceae (4.58%), Poaceae ( The results, in terms of percentage, of commonly used families are represented in Fig. 2.
Asteraceae holds the top position among the families used in ethno-medicines which indicates the presence of effective bioactive ingredients in the members of this family [29]. Lamiaceae and Asteraceae are the most frequently used families in ethno-medicine [30]. It was reported that Asteraceae family is the most diverse family found in all the habitat and regions except in Antarctica and it was not a new finding about Asteraceae family holding highest position among the traditionally important families, it was further concluded that this prevalence is due to high quantities of active secondary metabolites present in this family and also because this family includes a large number of species [31].
Medicinally important genera along with the number of species used effectively against skin ailments in terms of percentage are graphically represented in Fig. 3.

Common skin diseases in Pakistan
In this review, it was found out that most of the plant species were used to treat more than 1 disease/condition of skin. Total 26 skin conditions were reviewed which were treated using ethno-medicine. Most common of them was wound healing (17.064%) followed by boil healing (8.72%), postules or pimples (5.83%), eczema (5.01%), ulcer (4.579%), burn (4.51%), Ringworm (3.889%) and scabies (3.889%).
These most commonly treated skin conditions mentioned above are represented graphically in Fig. 4 and total of all the skin conditions treated traditionally are represented in Fig. 5.
Burn, which accounts 4.51% of the skin conditions treated traditionally in Pakistan is a serious issue globally, De Wet et al. reported increased mortality rate due to burn which has contributed to a serious health concerned issue globally. In South Africa, burn is one of the major reasons of deaths among 5-29 years individuals. Ethno-medicines have great potential to cure different kind of skin diseases [25,137].
Some plants cure more than one skin disease, Curcuma longa and Melia azaderach are the natural resources for curing multiple skin diseases [33,138].
Tabassum and Hamdani concluded that skin conditions can be of thousand types but are categorized into nine categories based on common diseases; rashes, viral infections, bacterial infections, fungal infections, parasitic infections, pigmentation disorder, tumor and cancer, trauma and other conditions (Wrinkles, spider veins and varicose veins) [28]. This review revealed that all these skin conditions are treated traditionally using etho-medicines. Mabona and Vuuren reported wound healing as a most frequently treated skin condition using ethno-medicine, followed by sores or ulcers. Among the medicinal plants used to combat wounds, Erythrina genus is used most frequently in South Africa with 120 species having their space in the traditional usage against skin conditions particularly in disinfection of wounds. Traditional plants are also used to combat associated condition of wounds including inflammation, urticaria, skin allergies, acne, eczema and psoriasis. Among these associated conditions, eczema is most commonly diagnosed in South Africa and thus most frequently treated with ethno-medicines [34].

Habit
Growing habits of 42.23% plants were not available in the previous articles. Common life forms used by traditional healers for the preparation of ethno-medicines include Trees 9.68%, Shrub 11.52%, Herb 34.72%, Creepers and Climbers 0.5% each, Grass 0.5% (only 3 plants were a grass), Sedges 0.1% (only 1 plant was from sedges) as shown in Figs. 6 and 7.
Trees and shrubs are used to prepare majority of herbal recipes as they are accessible round the year, followed by utilization of herbs which might be related to their easy collection methods, higher abundance and efficacy in curing ailments as compared to other life forms [30]. Khan et al. reported shrubs and trees as most commonly used life forms in ethno-medicines due to the their availability around the year with the minimum seasonal variation [35]. Ahmad et al. stated that herb is used in ethno-medicines due to their abundance and easy availabilty in most of the aresa of the world [36].
Leaves were the most commonly used plant part in ethno-medicine, this is due to the ease of processing them into a digestible paste and have less conservational issues than the collection of roots, bark, stem or the whole plant and also because leaves does not affect the   [29], further the life form of the plant is not effected by the collection of leaves [37] and also due to the reason that leaves contain photosynthate which might have some medicinal value [38]. Ayyanar and Ignacimuthu reported leaves as most frequently used plant part (accounting 50%) to prepare ethno-medicines in Kani Tribes, India [39].
Whole plant and roots are other frequently used plant parts probably due to bioactive components enriched in these parts. However, their excessive use is detrimental for their survival since whole plant has to be uprooted. Not only roots, even the use of more than one plant part for medicinal purpose has put these plants to extinction risk owing to damage inflicted on the plants [40].

Mode of preparation
Herbal preparation is made by using different plant parts like whole plant, leaves, roots, stem, fruits, flowers, barks, berries and seeds. Different modes of preparation are used for different plants by using various parts by the native people; this study showed 23.5% ethno-preparations were used in powdered form, 22.7% paste, 16.37% decoction, 12.62% juice, 8.75% poultice, and 8% each extract and infusion and 16.25% were not mentioned in literature.
Different modes of preparation of the plants are shown in Fig. 9.
The missing information regarding mode of preparation of the ethno-medicine was also reported by   Farnsworth who indicated the published studies include raw list of plants and only a small number of manuscripts reports the mode of preparation while the rest indicates the part used in treating a particular ailment [41]. Literature revealed that plants can be used in different ethno formulations depending upon the sort of skin disease to be treated and the type and part of plant selected to treat the disease. The ethno-formulation used for skin condition may include powder, paste, plant juice, ointment, poultice, extract, decoction or infusion [42,43].

Frequency of Part used by tradiƟonal healers
Decoction and infusion are frequently used in ethnomedicine due to the ease of preparation and because water is used as a solvent in these formulations, which is easily available [34]. Felhaber reported that ethno-medicines can be given orally or applied topically. Though both the routes can be used but topical application is common as well as effective as it ensures direct contact of active constituents of plant with the site of action (skin) and also because it gives a quick relief [44].

Combined ethno-preparation
Medicinal plants are used in combination with other medicinal plants, with vegetable oils (mustard oil, apricot oil etc.) and/or with the nutrients (milk, ghee etc.). People of Pakistan still rely on synergistic interactions of plants and supportive components like oil and milk to treat skin diseases.
These supplement ingredients may be used to enhance the effect of the herbal preparations or are simply used to make the preparations palatable. And on the other hand they improve the healing conditions; however, the exact role of these materials in curing the diseases is not clearly known [29].
A number of plant combinations used to treat skin conditions have been reported. The synergistic interaction of medicinal plants have been used since antiquity. Mabona and Van Vuuren reported that medicinal plants are used alone as well as in combination with other plants without any adequate validation of the combination. Plant species like Acorus calamus, Cyathula natalensis, Cyanella lutea, Hypoxis latifolia, Momordica foetida, Pittosporum viridiflorum and Vernonia natalensis have effects on skin when used in combination with other plants but if used alone, they do not have any dermatological effects; they may have potential to treat the additional symptoms associated with skin conditions like fever in skin infection [34].
Plants used in combination with other plants are given in Table 3, plants used in combination with different oils in Table 4 and plants used in combination with nutrients are given in Table 5.

Endangered species
Endangered medicinal plants of Pakistan that have got their role in treating skin conditions are discussed in Table 6.
Using the part like roots, rhizomes or bulbs could be a severe threat for reproduction of medicinal plants of the area. The plants collected by using these methods, especially those propagated through rhizome, bulb or corm, need sustainable utilization and conservation strategies. Un-sustainability of harvesting of herbaceous roots is well recognized by conservationists and termed such medicinal plants as highly threatened [40]. Uprooting a plants is the most detrimental method of plant collection, if the roots are not removed completely it can also result in destruction by decreasing water upset and increasing susceptibility of fungal infection. Commercialization is the major cause of extinction of medicinal plants in South Africa which demands over harvesting and thus has taken natural medicinal resources to near extinction [45].
Shanwari suggested to establish protocols to interpret the pattern of plant growth and to accelerate the knowledge about propagation of medicinal plants and avoiding harvesting of wild species in order to save endangered species [15].
Aconitum chasmanthus, A. heterophyllumand, A. violaceum, which are native to Pakistan, India and Nepal [46][47][48], are harvested for their tubers which constitute Ayurveda drug and for this reason whole plants are uprooted. In 2003 in a CAMP workshop organized at India (Shimla), experts agreed that 80% of the wild population of Aconitum chasmanthus had declined and therefore it is assessed as "critically endangered species", 70% of that of A. heterophyllum had declined and it is assessed as "endangered" while 40% decline of the population of A. violaceum has made it a "vulnerable" specie to become endangered. This decline is over a decade but the situation has not improved and therefore the status id still valid [49]. It was observed in a survey in India that collection amount of A. heterophyllum has dropped down from 200 g per person per day to 70-100 g per person per day in 5 years [50]. Moreover, illegal collection of this specie has let it threatened [51].
Reddy et al. reported that oleo-gum resin tapped from the stems of Commiphora wightii constitutes the wellknown Ayurvedic drug "Guggul" which is consumed in high volumes by the herbal industries of Sub-continent. Field observations over the last several decades have confirmed a severe decline in its wild population, as the shrubs tapped for oleo-gum resin die within 2-3 years. Over the past 84 years (three generation lengths) there has been a decline of more than 80% in the wild population as a result of habitat loss and degradation, coupled  Polygonum tataricum L.

Bro Kho-Bro
Polygonaceae L, Sd The flour is mixed with apricot oil in boiling water; paste is formed and applied to skin overnight.

Panzpatar, Rattenjot
Rosaceae L, R The leaves are boiled in milk and applied/powder (ashes) is being applied with oil Boil healing, burns and bruises [22] Sporobolus ioclados (Trin.)

Ganri
Poaceae Sd, L Mixed with oil and applied Scabies [129]     CR, critically endangered; EN, endangered; LC, least concern; NT, near threat; VU, vulnerable with unregulated harvesting and tapping of oleo-gum resin. This species is therefore assessed as Critically Endangered [52]. Soni identified a number of relevant activities within the study area under the theme 'Guggal Bachao Abhiyan' (Save Guggal Movement). These were conducted through the close co-operation of the village level communities, who depend on local biodiversity for their livelihoods in the Aravali Hills of Rajasthan [53]. Gentiana kurroo is mainly collected from the wild and there is no information regarding its cultivation.
Hence, the species is under severe threat of extinction. This assessment was primarily based on the very limited reported presence of the species in wild and the high demand and prices for the dried roots of this plant. The wild population in IndoPak region is inferred to have declined by 80% in a 10 years time period. The recent CAMP assessment also agrees with the trend of population decline of more than 80% in India. Therefore, the species is assessed as Critically Endangered [54,55].

Commercially available important plants
Plants that are available commercially in Pakistan in different formulations are enlisted in Table 7. Worth and number of herbal industries is increasing day by day in Pakistan due to the trust of people on traditional medicines [56].
Ethno-medicines has a vital role in the industrialization [57]. Vivienne et al. stated commercial importance of medicinal plants in South Africa and reported 11 species of medicinal plants that are imported from India and other countries including Cinnamommum camphora. They also concluded that the size of the regional market of medicinal plants can be assessed by knowing the number of species traded. Commercial utilization of the medicinal plant is directly related to the degree of extinction [45].

Future considerations
The review revealed that many of the important information like ethno preparation, habit and part used, of many important medicinal plants were not available in previous articles which can be due to the lack of interest of local youth to acquire the traditional knowledge from the ancestors and thus provision of incomplete information to the previous articles, further ethno-pharmacological research should be carried out to save the traditional knowledge and to take it to the light of science.
Medicinal plants in Pakistan contain great variety which can be used against a large number of skin ailments. Leaves, whole plant and roots are the most widely used parts in different ethno-medicinal preparations. Whole plant and root harvesting are the destructive type of techniques, it is important to protect the medicinal plants from exploitation. Although in Pakistan there is a strong traditional background supporting the use of these ethno-medicines against skin ailments but detailed ethno-pharmacological studies are not enough to support the folk claim. Majority of the studies have not documented other information regarding mode of preparation and dose of ethno-medicine. Therefore it is necessary to carry out a comprehensive study on ethno-pharmacology in Pakistan. It is important as the folk knowledge supplements a scientific investigations and penetrations with the primary information. Very limited number of studies provides toxic profile of these medicinal plants, toxicity studies should be carried out for these medicinal plants in animal system to establish a safe dose range.
More pharmacological studies (in vitro and in vivo) should be carried out on medicinal plants of Pakistan that are relatively unexplored or less explored. Mostly, the extracts were tested against different pathogens, for wound healing properties and for other skin conditions. However, very few classes of secondary metabolites and pure isolated components were tested. Therefore, it is imperative to conduct detailed phytochemical studies for the isolation of novel compounds.