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Traditional phytomedicines for gynecological problems used by tribal communities of Mohmand Agency near the Pak-Afghan border area

Abstract

Medicinal plants play a vital role in the human health care system of tribal communities and in the treatment of various gynecological problems. This study is an effort to document important medicinal flora used for the treatment of gynecological problems by indigenous people living in a tribal region near the Pak-Afghan border. The main objective of the study was to establish a clear profile of indigenous knowledge and practices from the unexplored tribal territory. Data were collected through semi-structured interviews and group discussions. The data were analyzed through Use Value and Factor of Informant Consensus. A total of 52 medicinal plants were recorded from the area; the most widely accepted were Withania somnifera (L.) Dunal (94 Use Value), Foeniculum vulgare Mill. (93 Use Value), Prunus domestica L. (91 Use Value), Myrtus communis L. (91 Use Value), Cannabis sativa L. (91 Use Value) and Nigella sativa L. (90 Use Value). A high consensus factor was recorded for menses-related problems (0.95). The root was the main part used (23% plants), followed by the leaves (20% plants), whole plant (18% plants), fruit (18% plants), and seed (13% plants). A total of 21 plants were used to treat menses-related problems, followed by sexual problems (ten plants), leucorrhea (nine plants), gastric problems (seven plants) and amenorrhea (seven plants). Knowledge related to ethnogynecological treatments is restricted to midwives and traditional healers. In conclusion, the documented flora that is particularly important to medicinal plants may be researched in the future to discover new pharmaceutical, neutraceutical and other pharmacological agents against gynecological complaints.

Keywords:
Ethnomedicines; Menstrual problems; Use value; Factor of Informant Consensus; Pharmaceuticals

Introduction

Ethnogynecology is a traditional approach that addresses women's health care problems. A number of medicinal plants are being used to cure women problems related to menses, abortion, menopause, gonorrhea, leucorrhoea, delivery complaints and infertility. It has been reported that sexual and other reproductive health issues account for 18% of the total global disease load (Kaingu et al., 2011Kaingu, C.K., Oduma, J.A., Kanui, T.I., 2011. Practices of traditional birth attendants in Machakos District Kenya. J. Ethnopharmacol. 137, 495-502.). Today, in modern societies, gynecological problems are usually treated with allopathic medicines, surgery, and non-steroidal anti-inflammatory drugs, which pose risks to the fetus at the gestation stage or the entire pregnancy period (Lawal et al., 2013Lawal, I., Amao, A., Lawal, K., Alamu, T., Sowunmi, I.L., 2013. Phytotherapy approach for the treatment of gynaecological disorder among women in Ido Local Government Area of Ibadan, Oyo State, Nigeria. J. Adv. Sci. Res. 4, 41-44.). Menstrual disorders are generally not perceived as major health concerns by global health organizations. These ailments require effective, safe medications because they can disrupt women's daily activities. Due to limited access to analgesics and sanitary facilities, women in various localities across the globe (Latin America, Africa or Asia) prefer traditional medicines (van Andel et al., 2014van Andel, T., de Boer, H.J., Barnes, J., Vandebroek, I., 2014. Medicinal plants used for menstrual disorders in Latin America, the Caribbean, sub-Saharan Africa, South and Southeast Asia and their uterine properties, a review. J. Ethnopharmacol. 155, 992-1000.).

The rural women of Pakistan frequently experience gynecological problems due to poor living standards, famine, and extensive physical work even during pregnancy. The country has a diversity of six thousand flowering plants, of which six hundred are used for medicinal purposes (Nasir and Ali, 1971–1991Nasir, E., Ali, S.I., 1971–1991. Flora of west Pakistan, Tech. Rep. 1-190. Pakistan Agriculture Research Council, Islamabad, Pakistan.). A local health practitioner known as "Daiya" possesses tremendous traditional knowledge to treat women problems. The "Daiya" primarily utilize medicinal plants and plant-derived medicinal products to treat the ailments (Tareen et al., 2010Tareen, R.B., Bibi, T., Khan, M.A., Ahmad, M., Zafar, M., 2010. Indigenous knowledge of folk medicine by the women of Kalat and Khuzdar regions of Balochistan, Pakistan. Pakistan J. Bot. 42, 1465-1485.). A traditional lifestyle and lack of proper access to modern health facilities motivate rural women to consult nearby midwives and traditional healers (Qureshi et al., 2009Qureshi, R.A., Ghufran, M.A., Gilani, S.A., Yousaf, Z., Abbas, G., Batool, A., 2009. Indigenous medicinal plants used by local women in southern Himalayan regions of Pakistan. Pak. J. Bot. 41, 19-25.). There is very little literature regarding ethnomedicinal uses by rural women for the treatment of gynecological disorders. Moreover, due to the introduction of allopathy and recent modernization, knowledge is decreasing rapidly because the younger generation is not taking an interest in learning these valuable practices and healing techniques. Hence, ethnogynecological knowledge may become extinct if not properly documented.

The current study was performed in Mohmand Agency, Federally Administrated Tribal Areas (FATA), Pakistan. The region is dominated by the Pashtun tribe, with low economic status, poor infrastructure and a lack of modern facilities (Murad et al., 2013Murad, W., Azizullah, A., Adnan, M., Tariq, A., Khan, K.U., Waheed, S., Ahmad, A., 2013. Ethnobotanical assessment of plant resources of Banda Daud Shah, District Karak Pakistan. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-77.
http://dx.doi.org/10.1186/1746-4269-9-77...
; Adnan et al., 2014aAdnan, M., Bibi, R., Mussarat, S., Tariq, A., Shinwari, Z.K., 2014. Ethnomedicinal and phytochemical review of Pakistani medicinal plants used as antibacterial agents against Escherichia coli. Ann. Clin. Microbiol. Antimicrob. 13, http://dx.doi.org/10.1186/s12941-014-0040-6.
http://dx.doi.org/10.1186/s12941-014-004...
). Many women in the area seek treatment from traditional healers for a variety of complications associated with the female reproductive organs. Such knowledge has not been documented previously from the study region. Hence, the present study was designed to document the ethnogynecological uses of medicinal plants and highlight candidate plants for further pharmacological investigations. The present research will provide baseline information for future research studies regarding phytochemistry, pharmacology, and the conservation of the plants used by the indigenous communities.

Material and methods

Study area

The Mohmand Agency is a part of FATA and is located near the Pak-Afghan border region (Fig. 1). The area is comprised of rugged mountains with barren slopes and extends along the Kabul river bank. The Agency shares its borders with Afghanistan (North-west), Khyber Pakhtunkhwa province (East), the Khyber Agency (North) and the Bajaur Agency (South). The area is populated by the Pashtun tribe, and due to their tribal nature, the economy is primarily pastoral and agrarian. The total irrigated land is approximately 1000 km2. FATA consists of a single university, which was recently established the requirements of the entire region. In the study area, there is one available bed in the hospital per 2179 persons, compared to one bed per 1341 persons in the settled areas of the country. A great proportion of the population is partially devoid of modern health facilities; however, a number of herbal practitioners known as "hakims" are located in the territory.

Fig. 1
Showing the location of Pakistan and the study area. Image courtesy of worldatlas.com.

Data collection

An ethno-gynecological survey was performed between June and October 2016. During this time, the identification of plant species is easy due to flowering. Regular field visits were conducted in June to target the informants, while ethnobotanical data were gathered in the other four months. Fieldwork was performed using a Participatory Rural Approach (PRA). PRA is considered an effective, popular approach in botanical studies. In the approach developed by Chambers (1992)Chambers, R., 1992. Rural Appraisal: Rapid, Relaxed and Participatory (IDS Discussion Papers 311). Institute of Development Studies, London., the indigenous population actively participates and describes the methodologies and patterns of their interaction with environmental and natural resources. The collection of indigenous knowledge and the survey were based on direct interactions with local respondents in the study area (Mahmood et al., 2013Mahmood, A., Rashid, S., Malik, R.N., 2013. Determination of toxic heavy metals in indigenous medicinal plants used in Rawalpindi and Islamabad cities, Pakistan. J. Ethnopharmacol. 148, 158-164.). Under PRA, information was gathered through semi-structured interviews, meetings and group discussions. Informants were selected through a snowball technique. Seventy-five key informants (50 males and 25 females, including house wives, midwives and traditional healers) were selected and belonged to different age groups (Table 1). Informants were selected based on their good reputation in the field of traditional medicine. Interviews were conducted in the local language, "Pashto". Mr. Amir Hasan Khan was the local resident of the study area familiar with the native dialect of the Pashto language.

Table 1
Demographic characteristics of the informants.

Prior to interviews, the main theme of the study was presented to each informant. Mr. Amir Hasan Khan stayed with the informants to document ethnogynecological medicinal practices. The ethnogynecological data were documented, including plant botanical name, local name, family name, part used, mode of preparation and drug administration method (e.g., juice, paste, decoction, powder). Through semi-structured interviews, information about gender, age, profession background and knowledge of the herbal recipes for gynecological problems were recorded. The initial documented results were recorded for each respondent for the possible feedback. Additionally, group discussions were arranged to clarify and validate the field data. Semi-structured questionnaires were subjected to harmonization using free interviews and informal conversation (Huntington, 2000Huntington, H.P., 2000. Using traditional ecological knowledge in science: methods and applications. Ecol. Appl. 10, 1270-1274.). Gender and age differences were considered, and interviews were taken individually and collectively. There were certain cultural barriers preventing females from participating in interviews, but the investigated female informants gave their consent. All respondents and focal individuals in the study area gave permission to publish and protect the data on traditional medicines that they provided. Ethical guidelines recommended by the International Society of Ethnobiology were firmly followed during the course of the survey.

Taxonomic verification

The documented medicinal plants were identified by Muhammad Adnan from the Department of Botany, Kohat University of Science and Technology, Kohat. The plants were mounted and preserved on herbarium sheets, assigned vernacular names and tagged with a voucher number for each species and were deposited at the Department of Botany, Kohat University of Science and Technology. Taxonomic problems regarding the correct name and updated systematic position were verified using "The Plant List" (www.theplantlist.org).

Data organization and analysis

Data were arranged and organized by using Microsoft Excel (2007). For each species, Use Reports (UR) were counted. UR can be defined as the utilized part of a plant species for a particular disease mentioned by an informant.

Use value (UV)

This index was used and applied to demonstrate the relative importance of each taxa used by local communities. The use value (UV) was calculated as:

U V = U i N

where Ui is the number of uses reported by each respondent for a given species, and N shows the total number of respondents taking part in the survey (Phillips and Gentry, 1993Phillips, O., Gentry, A.H., 1993. The useful plants of Tambopata Peru: I. Statistical hypotheses tests with a new quantitative technique. Econ. Bot. 47, 15-32.).

Factor of Informant Consensus (Fic)

Ethnobotanical data collected during field visits were evaluated and analyzed through UR and Factor of Informant Consensus (Fic), as described by Trotter and Logan (1986)Trotter, R., Logan, M., 1986. Informant consensus: new approach for identifying potentially effective medicinal plants. In: Etkin, N.L. (Ed.), Indigenous Medicine and Diet: Behavioral Approaches. Redgrave Publishers, New York, pp. 91–112.. Factor of Informant Consensus were calculated using the following formula:

F i c = N u r N t N u r 1

where Nur represents the number of use reports recorded from respondents for a particular disease category, while Nt refers to the number of taxa used for a particular illness by all informants. The maximum value for the index is 1 and the minimum value is 0.

Results and discussion

Ethnogynecological knowledge and indigenous communities

During the survey, it was found that ethnogynecological knowledge is restricted to older female community members, midwives and herbal practitioners locally known as Hakims. All female respondents reporting such knowledge were housewives, possibly because in remote areas of Pakistan, women are primarily confined to the home according to customs and religious restrictions. The female informants, including the midwives, were between 50 and 70 years old (Table 1). During informant selection, it was reported that the younger generation is completely unacquainted with traditional therapies and takes no interest in gaining the knowledge. The female informants selected for the study had no schooling. In rural areas, girls are expected to become wives, mothers, and housekeepers; hence, little attention is paid to their formal education, particularly higher education. Even at primary and secondary levels, access is restricted, retention rates are low, and facilities remain abysmal. However, traditional healers locally known as "hakims" have higher secondary and university levels of schooling (Table 1). The expertise of these hakims could be justified by their professional degrees, diplomas and experience gained from other hakims. Furthermore, the low literacy rate, lack of medical facilities, and poor economic status are the main factors for the locals' dependence on medicinal plants. It was specifically noted during the survey that people who do not use herbal therapies have a positive attitude toward ethno-gynecological knowledge. The women in the study area consider traditional therapies that are safer and more effective than modern drugs, which is why they generally consult traditional healers for gynecological problems rather than modern health practitioners. The pregnant women have more trust and faith in medicinal plants and often have concerns for their unborn child's well-being (Nordeng and Havnen, 2005Nordeng, H., Havnen, G.C., 2005. Impact of socio demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy. Acta Obstet. Gynecol. Scand. 84, 26-33.). In the case of emergency, women are also brought to nearby local dispensaries or shifted to other settled areas. Strikingly, knowledge related to the traditional remedies of gynecological problems is disappearing; in the event of the deaths of older community female members, the knowledge will be lost. Hence, there is a dire need to prioritize the conservation of this traditional knowledge from extinction in the near future (Mahmood et al., 2013Mahmood, A., Rashid, S., Malik, R.N., 2013. Determination of toxic heavy metals in indigenous medicinal plants used in Rawalpindi and Islamabad cities, Pakistan. J. Ethnopharmacol. 148, 158-164.).

Important medicinal plants

Tribal communities have diverse knowledge of traditional medicines related to plants for their basic healthcare needs (Rekka et al., 2013Rekka, R., Murugesh, S., Prabakaran, R., Tiruchengode, N.D., 2013. Plants used by Malayali tribes in ethnogynaecological disorders in Yercaud Hills, Southern Eastern Ghats Salem District, Tamil Nadu. Sci. Res. Rep. 3, 190-192.). In the current study, 53 medicinal plants were recorded that were used to treat gynecological ailments by indigenous communities in the study area (Table 2).

Table 2
Medicinal plants and their uses in the treatment of gynecological problems.

Medicinal plants were used against 28 health and pathological conditions in the study area. The most widely accepted medicinal plant species, indicated by the highest UV, were Withania somnifera (94), Foeniculum vulgare (93), Prunus domestica (91), Myrtus communis (91), Cannabis sativa (91) and Nigella sativa (90). To evaluate the local importance of any species, Phillips and Gentry (1993)Phillips, O., Gentry, A.H., 1993. The useful plants of Tambopata Peru: I. Statistical hypotheses tests with a new quantitative technique. Econ. Bot. 47, 15-32. proposed and devised the formula for UV. Higher UV implies the higher importance of specific plant species and vice versa. However, the use value cannot specify whether plant species is used for a single purpose or multiple purposes (Musa et al., 2011Musa, M.S., Abdelrasool, F.E., Elsheikh, E.A., Ahmed, L.A., Mahmoud, A.L.E., Yagi, S.M., 2011. Ethnobotanical study of medicinal plants in the Blue Nile State South-eastern Sudan. J. Med. Plants Res. 5, 4287-4297.). In the study area, W. somnifera is utilized to treat leucorrhea and fertility and as a sexual tonic. F. vulgare is widely used for vomiting during the initial period of pregnancy, menses pain, and vomiting, as well as to regulate the menses and lactiferous. Similarly, P. domestica is utilized to treat leucorrhea and irregular menstruation. M. communis is used to completely stop irregular menses and treat other reproductive ailments in women. C. sativa is used to cure abdominal pain, gonorrhea, pregnancy, and female impotency, while N. sativa is traditionally used as a lactiferous and sexual tonic. Previously, W. somnifera was used for leucorrhoea, abdominal pain, tonic, urinary disorders, sexual weakness, sterility in women, aphrodisiac, and menses pain (Adnan et al., 2014bAdnan, M., Ullah, I., Tariq, A., Murad, W., Azizullah, A., Khan, A.L., Ali, N., 2014. Ethnomedicine use in the war affected region of northwest Pakistan. J. Ethnobiol. Ethnomed. 10, http://dx.doi.org/10.1186/1746-4269-10-16.
http://dx.doi.org/10.1186/1746-4269-10-1...
; Ahmad et al., 2014Ahmad, M., Sultana, S., Fazl-i-Hadi, S., Ben Hadda, T., Rashid, S., Zafar, M., Khan, M.A., Khan, M.P.Z., Yaseen, G., 2014. An ethnobotanical study of medicinal plants in high mountainous region of Chail valley (District Swat-Pakistan). J. Ethnobiol. Ethnomed. 10, http://dx.doi.org/10.1186/1746-4269-10-36.
http://dx.doi.org/10.1186/1746-4269-10-3...
; Khan et al., 2015aKhan, R.U., Mehmood, S., Muhammad, A., Mussarat, S., Khan, S.U., 2015. Medicinal plants from Flora of Bannu used traditionally by North West Pakistan's women to cure gynecological disorders. Am. Eur. J. Agric. Environ. Sci. 15, 553-559.; Sher et al., 2016Sher, H., Bussmann, R.W., Hart, R., de Boer, H.J., 2016. Traditional use of medicinal plants among Kalasha, Ismaeli and Sunni groups in Chitral District, Khyber Pakhtunkhwa province Pakistan. J. Ethnopharmacol. 188, 57-69.). In other cultures, F. vulgare is reportedly used as a carminative and in urinary tract infections, laxative, abdominal pain, and menses pain (Akhtar et al., 2013Akhtar, N., Rashid, A., Murad, W., Bergmeier, E., 2013. Diversity and use of ethno-medicinal plants in the region of Swat, North Pakistan. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-25.
http://dx.doi.org/10.1186/1746-4269-9-25...
; Khan et al., 2015aKhan, R.U., Mehmood, S., Muhammad, A., Mussarat, S., Khan, S.U., 2015. Medicinal plants from Flora of Bannu used traditionally by North West Pakistan's women to cure gynecological disorders. Am. Eur. J. Agric. Environ. Sci. 15, 553-559.; Sher et al., 2016Sher, H., Bussmann, R.W., Hart, R., de Boer, H.J., 2016. Traditional use of medicinal plants among Kalasha, Ismaeli and Sunni groups in Chitral District, Khyber Pakhtunkhwa province Pakistan. J. Ethnopharmacol. 188, 57-69.). C. sativa is reportedly used as a sedative, analgesic, diuretic (Aziz et al., 2017Aziz, M.A., Khan, A.H., Adnan, M., Izatullah, I., 2017. Traditional uses of medicinal plants reported by the indigenous communities and local herbal practitioners of Bajaur Agency, Federally Administrated Tribal Areas Pakistan. J. Ethnopharmacol. 198, 268-281.), and male impotency treatment (Khan et al., 2015aKhan, R.U., Mehmood, S., Muhammad, A., Mussarat, S., Khan, S.U., 2015. Medicinal plants from Flora of Bannu used traditionally by North West Pakistan's women to cure gynecological disorders. Am. Eur. J. Agric. Environ. Sci. 15, 553-559.). N. sativa has reported uses as a sexual tonic, lactation, aphrodisiac, gestational diabetes, menstruation additive, abortion, and parturition uterus pain (Sadeghi and Mahmood, 2014Sadeghi, Z., Mahmood, A., 2014. Ethno-gynecological knowledge of medicinal plants used by Baluch tribes, southeast of Baluchistan, Iran. J. Rev. Bras. Farmacogn. 24, 706-715.; Aziz et al., 2017Aziz, M.A., Khan, A.H., Adnan, M., Izatullah, I., 2017. Traditional uses of medicinal plants reported by the indigenous communities and local herbal practitioners of Bajaur Agency, Federally Administrated Tribal Areas Pakistan. J. Ethnopharmacol. 198, 268-281.). It is generally noted that a single plant-based remedy is typically used, as indicated in the table (Table 2).

The biological efficacy of medicinal plants can be determined through the Fic value. The index is used to evaluate the consensus among the informants for traditional medications. To determine Fic, reported ailments were categorized into lactiferous, gastric, uterine infections, menses, backache, muscle contraction management, leucorrhea, sexual, and urinary problems, among others (Table 3).

Table 3
Showing diseases categories and the Factor of Informant Consensus (Fic).

In our study, Fic values ranged between 0.88 and 0.95 (Table 3). A high Fic value was recorded for menses problems (0.95), sexual problems and urinary problems (each 0.94) followed by leucorrhea (0.93), and gastric problems and uterine infections (each 0.92). In a study conducted by Sadeghi and Mahmood (2014)Sadeghi, Z., Mahmood, A., 2014. Ethno-gynecological knowledge of medicinal plants used by Baluch tribes, southeast of Baluchistan, Iran. J. Rev. Bras. Farmacogn. 24, 706-715., menses problems gave the highest Fic values. A high Fic value indicates that the information is shared among various informants and community members with consistency. Fic shows the homogeneity of the collected information and the consensus among various informants for a specific plant or part utilization for the treatment. A higher Fic indicates the sharing of knowledge or information, and vice versa.

Plant parts used to treat various ailments were the root (23%) followed by leaves (20%), whole plant (18%), fruits (18%), seeds (13%), gums (7%), and flowers (5%). In Traditional Chinese Medicine (TCM), the root is frequently utilized in herbal preparations (Ghorbani et al., 2011Ghorbani, A., Langenberger, G., Feng, L., Sauerborn, J., 2011. Ethnobotanical study of medicinal plants utilized by Hani ethnicity in Naban river watershed national nature reserve, Yunnan China. J. Ethnopharmacol. 134, 651-667.). The root is also the most commonly harvested plant part reported in other studies (Hussain et al., 2006Hussain, M., Shah, G.M., Khan, M.A., 2006. Traditional medicinal and economic uses of Gymnosperms of Kaghan valley, Pakistan. Ethnobot. Leaflets 10, 72-81.; Tolossa et al., 2013Tolossa, K., Debela, E., Athanasiadou, S., Tolera, A., Ganga, G., Houdijk, J.G., 2013. Ethno-medicinal study of plants used for treatment of human and livestock ailments by traditional healers in South Omo Southern Ethiopia. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-32.
http://dx.doi.org/10.1186/1746-4269-9-32...
), possibly because the roots remain in the soil and are easily accessible year-round. Another motif may be the easy harvest of herb roots by browsing out the whole plant. However, such harvesting activities (collected for both commercial and medicinal purposes) have a negative impact on the sustainability and conservation of medicinal plants. Previous research reports indicate that roots (30%) ranked second among the plant parts, which were frequently harvested (Lepcha and Das, 2011Lepcha, S.R., Das, A.P., 2011. Ethno-medico-botanical exploration along the international borders to Tibet Autonomous Region of China and the kingdom of Bhutanwith special reference to the Pangolakha Wildlife Sanctuary, East Sikkim. In: Gosh, C., Das, A.P. (Eds.), Recent Studies in Biodiversity and Traditional Knowledge in India. , pp. 257–270.). The unsustainable harvest of herbaceous roots is well recognized by conservationists, who have declared that such medicinal plants as highly threatened (Verma et al., 2007Verma, A.K., Kumar, M., Bussmann, R.W., 2007. Medicinal plants in an urban environment: the medicinal flora of Banares Hindu University, Varanasi, Uttar Pradesh. J. Ethnobiol. Ethnomed. 3, http://dx.doi.org/10.1186/1746-4269-3-35.
http://dx.doi.org/10.1186/1746-4269-3-35...
).

Herbal therapies used in the study area

The current investigations recorded various forms of herbal therapies in terms of their formulation and administration. Various recipes were used, mostly in powder form, and were ingested with ingredients such as milk, whey, water, honey, ghee and sugar. During the survey, it was found that women and traditional healers mostly use herbs to prepare ethnomedicines, while trees are very rarely used (Table 2). In remote areas, medicinal herbs are the main ingredients in local medicines and are considered the main rescue and first choice for medicines (Khan et al., 2011Khan, N., Ahmed, M., Ahmed, A., Shaukat, S.S., Wahab, M., Ajaib, M., Siddiqui, M.F., Nasir, M., 2011. Important medicinal plants of Chitral Gol National Park (CGNP) Pakistan. Pak. J. Bot. 43, 797-809.). The highest use of herbs indicates their high abundance in villages and the centuries-old traditional knowledge of the healers. The common use of herbaceous plants has also been reported in other regions of the world (Kala, 2005Kala, C.P., 2005. Ethnomedicinal botany of the Apatani in the Eastern Himalayan region of India. J. Ethnobiol. Ethnomed. 1, http://dx.doi.org/10.1186/1746-4269-1-11.
http://dx.doi.org/10.1186/1746-4269-1-11...
; Muthu et al., 2006Muthu, C., Ayyanar, M., Raja, N., Ignacimuthu, S., 2006. Medicinal plants used by traditional healers in Kancheepuram District of Tamil Nadu India. J. Ethnobiol. Ethnomed. 2, http://dx.doi.org/10.1186/1746-4269-2-43.
http://dx.doi.org/10.1186/1746-4269-2-43...
). Herbs can grow in roadsides, home gardens, farmland, and wild habitats, and are more common than other growth forms. In contrast, studies have also reported the highest uses of trees (Maroyi, 2013Maroyi, A., 2013. Traditional use of medicinal plants in south-central Zimbabwe: review and perspectives. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-31.
http://dx.doi.org/10.1186/1746-4269-9-31...
; Murad et al., 2013Murad, W., Azizullah, A., Adnan, M., Tariq, A., Khan, K.U., Waheed, S., Ahmad, A., 2013. Ethnobotanical assessment of plant resources of Banda Daud Shah, District Karak Pakistan. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-77.
http://dx.doi.org/10.1186/1746-4269-9-77...
) and shrubs in traditional medications (Moshi et al., 2012Moshi, M.J., Otieno, D.F., Weisheit, A., 2012. Ethnomedicine of the Kagera Region, North Western Tanzania. Part 3: Plants used in traditional medicine in Kikuku village Muleba District. J. Ethnobiol. Ethnomed. 8, http://dx.doi.org/10.1186/1746-4269-8-14.
http://dx.doi.org/10.1186/1746-4269-8-14...
; Padal et al., 2013Padal, S.B., Vijayakumar, Y., Butchi, R.J., Chandrasekhar, P., 2013. Ethnomedicinal uses of Shrub species by Tribals of Borra Panchayat, Ananthagiri Mandalam, Visakhapatnam district, Andhra Pradesh, India. Int. J. Pharm. Sci. Invent. 2, 10-12.). Variation in medicinal plants' growth form might be associated with different socio-cultural beliefs, ecological status, and variation in the practices of traditional healers across regions or countries.

Most remedies were based on a single plant application, due to palatability, non-toxicity and the high efficacy of certain plants (Tugume et al., 2016Tugume, P., Kakudidi, E.K., Buyinza, M., Namaalwa, J., Kamatenesi, M., Mucunguzi, P., Kalema, J., 2016. Ethnobotanical survey of medicinal plant species used by communities around Mabira Central Forest Reserve Uganda. J. Ethnobiol. Ethnomed. 12, http://dx.doi.org/10.1186/s13002-015-0077-4.
http://dx.doi.org/10.1186/s13002-015-007...
). However, some plants were used in combination with other plants to achieve the maximum therapeutic effect. This combination justifies the phenomenon of synergism, which could be explained by the better results of such plants products. Women from the studied regions reported medicinal plants for the treatment of 28 types of gynecological ailments. Menses was found to be the most treated ailment category in the studied regions. A total of 21 plants were used to treat menses-related problems, followed by nine plants for leucorrhea, seven each for amenorrhea, six for sexual tonic, five plants for backache and also five plants for lactiferous. The higher plant utilization for menses might be due to natural phenomenon associated with a variety of complications such as pelvic or abdominal cramps, bloating or sore breast, lower back pain, mood swings, food cravings, irritability, fatigue and headache(Sharma et al., 2008Sharma, P., Malhotra, C., Taneja, D.K., Saha, R., 2008. Problems related to menstruation amongst adolescent girls. Indian J. Pediatr. 75, 125-129.; Yamamoto et al., 2009Yamamoto, K., Okazaki, A., Sakamoto, Y., Funatsu, M., 2009. The relationship between premenstrual symptoms, menstrual pain, irregular menstrual cycles, and psychosocial stress among Japanese college students. J. Physiol. Anthropol. 28, 129-136.).

Traditional medicines for the treatment of women's diseases are taken in the form of decoctions, infusions, juices, extracts, suppositories, powders, and pills. These traditional medicines are typically mixed with honey or milk to improve the taste, depending on the ailment. Detailed methods for the preparation of herbal medicines have been described elsewhere (Mahmood et al., 2013Mahmood, A., Rashid, S., Malik, R.N., 2013. Determination of toxic heavy metals in indigenous medicinal plants used in Rawalpindi and Islamabad cities, Pakistan. J. Ethnopharmacol. 148, 158-164.). During the current study, different methods of preparation and administration were recorded for the herbal therapies from local herbalists (hakims) at various sites, but were quite simple. Orally, herbal recipes are ingested either as a plant powder (along with water), decoction, or rarely a juice extracts. This was indicated by researchers from different parts of the world (Abbasi et al., 2013Abbasi, A.M., Khan, M.A., Shah, M.H., Shah, M.M., Pervez, A., Ahmad, M., 2013. Ethnobotanical appraisal and cultural values of medicinally important wild edible vegetables of Lesser Himalayas-Pakistan. J. Ethnobiol. Ethnomed. 9, http://dx.doi.org/10.1186/1746-4269-9-66.
http://dx.doi.org/10.1186/1746-4269-9-66...
; Ridvan et al., 2015Ridvan, P., Ugur, C., Kaan, K., Denizhan, U.M., Zafer, T., 2015. An ethnobotanical study on medicinal plants in Espiye and its surrounding (Giresun-Turkey). J. Ethnopharmacol. 163, 1-11.). In contrast, paste and ground herbs were extensively used to treat dermal disease. It has been reported that grinding and boiling are the most effective methods and are common therapies for the extraction of biologically active compounds (Deeba, 2009Deeba, F., 2009. Documentation of Ethnoveterinary Practices in Urban and Periurban Areas of Faisalabad Pakistan. University of Agriculture, Faisalabad, Pakistan.). The majority of herbal preparations involve a single plant, while some remedies were prepared through the combination of various plants. For instance, Allium sativum is mixed with turmeric powder and used to stimulate uterine muscles. Similarly, gum powder from Acacia modesta is mixed with wheat flour and used for back pain after delivery. Moreover, decoctions are made from the leaves of Paeonia emodi in milk and mixed with flour, which is used during irregular menses and abdominal pain. The traditional healers in the study area have told that herbal remedies formed by the combination of two or more than two plants are more potent than single plant recipes.

Previous literature has revealed that the utilization of multiple traditional herbal formulations has shown efficacy in the current era due to synergism (Zonyane et al., 2012Zonyane, S., Van Vuuren, S.F., Makunga, N.P., 2012. Pharmacological and phytochemical analysis of a medicinal plant mixture that is used as a traditional medicine in Western Cape. In: Proceedings of the 38th Annual Conference of the South African Association of Botanist, University of Pretoria, Pretoria, South Africa, January, p. 124.; Sher et al., 2015Sher, H., Aldosari, A., Ali, A., de Boer, H.J., 2015. Indigenous knowledge of folk medicines among tribal minorities in Khyber Pakhtunkhwa, northwestern Pakistan. J. Ethnopharmacol. 166, 157-167.). Plant drug preparation for similar or different ailments varies from individual to individual and community to community, in many cases. For example, in a study conducted by Sher et al. (2015)Sher, H., Aldosari, A., Ali, A., de Boer, H.J., 2015. Indigenous knowledge of folk medicines among tribal minorities in Khyber Pakhtunkhwa, northwestern Pakistan. J. Ethnopharmacol. 166, 157-167., it was found that traditional practitioners recommended the decoction of leaves and roots of W. somnifera as an aphrodisiac while in our study the medicinal plants is used for the treatment of leucorrhea, to enhance fertility and as a sexual tonic.

Pharmacological profile of important medicinal plants

A literature survey was conducted to gain insight into the pharmacological profile of the most frequently used plants in traditional medicines to treat gynecological problems. For instance, studies of W. somnifera showed that the plant has several beneficial therapeutic effects, including sedative, general tonic, anti-inflammatory, diuretic, aphrodisiac and deobstruent properties (Chopra et al., 1980Chopra, R.N., Nayar, S.L., Chopra, I.C., 1980. Glossary of Indian Medicinal Plants, vol. 191. Council of Scientific & Industrial Research, New Delhi, pp. 258.; Nadkarni, 1982Nadkarni, A.K., 1982. Indian Materia Medica, 3rd ed. Popular Prakashan.; Kabiruddin and Mufradat, 1955Kabiruddin, M., Makhzan-ul-Mufradat, 1955. Nadeem University Printers, Lahore, pp. 75–76.; Ali, 1997Ali, S.S., 1997. Unani Advia-e-Mufradah, 8th ed. National Council for Promotion of Urdu Language (NCPUL), New Delhi, pp. 33.; Anonymous, 2007Anonymous, 2007. The Unani Pharmacopoeia of India. Part I, vol. I. Depart. of AYUSH, Ministry of Health & Family Welfare, Govt. of India, New Delhi, pp. 7–8.; Khare, 2007Khare, C.P., 2007. Indian Medicinal Plants – An Illustrated Dictionary. 1st Indian Reprint Springer (India) Pvt. Ltd, New Delhi, India, pp. 28.). One study indicated that it increases the production of semen and is utilized as a uterine tonic (Anonymous, 2007Anonymous, 2007. The Unani Pharmacopoeia of India. Part I, vol. I. Depart. of AYUSH, Ministry of Health & Family Welfare, Govt. of India, New Delhi, pp. 7–8.; Kabiruddin and Mufradat, 1955Kabiruddin, M., Makhzan-ul-Mufradat, 1955. Nadeem University Printers, Lahore, pp. 75–76.). Aqueous and alcoholic extracts of the plant have shown good activities against Proteus vulgaris, Bacillus subtilis, Salmonella typhimurium, Escherichia coli, Staphylococcus auerus and Pseudomonas aeruginosa as well as antihypercholesterolemic and diuretic activities (Ahmad et al., 1998Ahmad, I., Mehmood, Z., Mohammad, F., 1998. Screening of some Indian medicinal plants for their antimicrobial properties. J. Ethnopharmacol. 62, 183-193.; Srinivasan et al., 2001Srinivasan, D., Nathan, S., Suresh, T., Perumalsamy, P.L., 2001. Antimicrobial activity of certain Indian medicinal plants used in folkloric medicine. J. Ethnopharmacol. 74, 217-220.). The steroidal lactones and two basic withanolides, withaferin A and D, are considered responsible for the pharmacological actions of W. somnifera (Umadevi et al., 2012Umadevi, M., Rajeswari, R., Rahale, C.S., Selvavenkadesh, S., Pushpa, R., Kumar, K.S., Bhowmik, D., 2012. Traditional and medicinal uses of Withania somnifera. Pharm. Innov. 1, 102-110.).

Analyzing the pharmacological potential of C. sativa, Ali et al. (2012)Ali, E.M., Almagboul, A.Z., Khogali, S.M., Gergeir, U.M., 2012. Antimicrobial activity of Cannabis sativa L. Chin. Med. 3, 61-64. reported that the plant is biologically active against certain bacterial and fungal strains. It was observed that the plant extract has prominent activity against Salmonella typhii, which is a pathogenic bacterium responsible for paratyphoid fever, typhoid fever and food-borne illness. The plant is also active against both gram-positive and gram-negative bacteria and help to prevent urinary tract infections (UTI), cholecystitis, sepsis and food poisoning (Monika et al., 2014Kour, N., Kaur, M., 2014. Antimicrobial analysis of leaves of Cannabis sativa. J. Sci. 4, 123-127.). Researchers have found that the baste fibers of this plant have antibacterial potential (Hao et al., 2014Hao, X.M., Yang, Y., An, L.X., Wang, J.M., Han, L., 2014. Study on antibacterial mechanism of hemp fiber. Adv. Mater. Res. 887, 610-613.; Khan et al., 2015bKhan, B.A., Wang, J., Warner, P., Wang, H., 2015. Antibacterial properties of hemp hurd powder against E. coli. J. Appl. Polym. Sci. 132, http://dx.doi.org/10.1002/app.41588.
http://dx.doi.org/10.1002/app.41588...
). In a more recent study, plant powder has shown antibacterial effects against E. coli (Khan et al., 2015aKhan, R.U., Mehmood, S., Muhammad, A., Mussarat, S., Khan, S.U., 2015. Medicinal plants from Flora of Bannu used traditionally by North West Pakistan's women to cure gynecological disorders. Am. Eur. J. Agric. Environ. Sci. 15, 553-559., bKhan, B.A., Wang, J., Warner, P., Wang, H., 2015. Antibacterial properties of hemp hurd powder against E. coli. J. Appl. Polym. Sci. 132, http://dx.doi.org/10.1002/app.41588.
http://dx.doi.org/10.1002/app.41588...
), and this antibacterial effect is attributed to lignan and related compounds such as phenolics, alkaloids and cannabinoids (Appendino et al., 2008Appendino, G., Gibbons, S., Giana, A., Pagani, A., Grassi, G., Stavri, M., Smith, E., Rahman, M.M., 2008. Antibacterial cannabinoids from Cannabis sativa: a structure–activity study. J. Nat. Prod. 71, 1427-1430.; Khan et al., 2015aKhan, R.U., Mehmood, S., Muhammad, A., Mussarat, S., Khan, S.U., 2015. Medicinal plants from Flora of Bannu used traditionally by North West Pakistan's women to cure gynecological disorders. Am. Eur. J. Agric. Environ. Sci. 15, 553-559., bKhan, B.A., Wang, J., Warner, P., Wang, H., 2015. Antibacterial properties of hemp hurd powder against E. coli. J. Appl. Polym. Sci. 132, http://dx.doi.org/10.1002/app.41588.
http://dx.doi.org/10.1002/app.41588...
).

In the same way, the stem and leaves of F. vulgare are traditionally used to reduce the pyrexia headache, stomach pain, indigestion, diarrhea, and vomiting in our study, as well as in other cultures (Aziz et al., 2017Aziz, M.A., Khan, A.H., Adnan, M., Izatullah, I., 2017. Traditional uses of medicinal plants reported by the indigenous communities and local herbal practitioners of Bajaur Agency, Federally Administrated Tribal Areas Pakistan. J. Ethnopharmacol. 198, 268-281.). Important chemical compounds from this herb include fenchone, estragole, p-anisaldehyde and anethole, which may have estrogenic, acaricidal and antithrombotic potential. In multiple experiments, the plant has also shown antioxidant properties (Rather et al., 2012Rather, M.A., Dar, B.A., Sofi, S.N., Bhat, B.A., Qurishi, M.A., 2012. Foeniculum vulgare: a comprehensive review of its traditional use, phytochemistry, pharmacology, and safety. Arab. J. Chem., http://dx.doi.org/10.1016/j.arabjc.2012.04.011.
http://dx.doi.org/10.1016/j.arabjc.2012....
). The compound estragole has different effects in various species as well as gender specific effects (Miller et al., 1983Miller, E.C., Swanson, A.B., Phillips, D.H., Fletcher, L., Liem, A., Miller, J.A., 1983. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenyl benzene derivatives related to safrole and estragole. Cancer Res. 43, 1124-1134.; Paini et al., 2010Paini, A., Punt, A., Viton, F., Scholz, G., Delatour, T., Marin-Kuan, M., Schilter, B., van Bladeren, P.J., Rietjens, I.M., 2010. A physiologically based biodynamic (PBBD) model for estragole DNA binding in rat liver based on in vitro kinetic data and estragole DNA adduct formation in primary hepatocytes Toxicol. Appl. Pharmacol. 245, 57-66.). The plant is famous among indigenous communities for the production of breast milk in human females (Agrawala et al., 1968Agrawala, I.P., Achar, M.V., Boradkar, R.V., Roy, N., 1968. Galactagogue action of Cuminum cyminum and Nigella staiva. Indian J. Med. Res. 56, 841-844.; Mills and Bone, 2000Mills, S., Bone, K., 2000. Principles and Practice of Phytotherapy. Modern Herbal Medicine. Churchill Livingstone.; Abascal and Yarnell, 2008Abascal, K., Yarnell, E., 2008. Botanical galactagogues. Altern. Complement Ther. 14, 288-294.). The plant has been used as an estrogenic agent for many years and improves the libido, maximizes the reproductive cycle and facilitates delivery cases (Rather et al., 2012Rather, M.A., Dar, B.A., Sofi, S.N., Bhat, B.A., Qurishi, M.A., 2012. Foeniculum vulgare: a comprehensive review of its traditional use, phytochemistry, pharmacology, and safety. Arab. J. Chem., http://dx.doi.org/10.1016/j.arabjc.2012.04.011.
http://dx.doi.org/10.1016/j.arabjc.2012....
). Research has shown that the herb's extract can increase the concentration of the serum of follicle stimulating hormone and decreases the luteinizing hormone and testosterone (Karampoor et al., 2014Karampoor, P., Azarnia, M., Mirabolghasemi, G., Alizadeh, F., 2014. The effect of hydroalcoholic extract of fennel (Foeniculum vulgare) seed on serum levels of sexual hormones in female Wistar rats with Polycystic Ovarian Syndrome (PCOS). Arak Med. Univ. J. 17, 70-78.). The oil of the plant is considered very effective against dysmenorrhea (Khorshidi et al., 2010Khorshidi, N., Ostad, S.N., Mosaddegh, M., Soodi, M., 2010. Clinical effects of fennel essential oil on primary dysmenorrhea. Iran. J. Pharm. Res. 2, 89-93.). While analyzing the pharmacological potential of M. communis, it was found that the plant has antimicrobial and antioxidant potential (Cakir, 2004Cakir, A., 2004. Essential oil and fatty acid composition of the fruits of Hippophae rhamnoides L (Sea Buckthorn) and Myrtus communis L. from Turkey. Biochem. Syst. Ecol. 32, 809-816.). Important chemical compounds from this plant include linalool, 1,8-cineole, eugenol, terpinene, terpineol and essential oils, which are considered effective against both gram-positive and gram-negative bacteria (Oyedemi et al., 2009Oyedemi, S.O., Okoh, A.I., Mabinya, L.V., Pirochenva, G., Afolayan, A.J., 2009. The proposed mechanism of bactericidal action of eugenol, α-terpineol and β-terpinene against Listeria monocytogenes, Streptococcus pyogenes, Proteus vulgaris and Escherichia coli. Afr. J. Biotechnol. 8, 1280-1286.; Randrianarivelo et al., 2009Randrianarivelo, R., Sarter, S., Odoux, E., Brat, P., Lebrun, M., Romestand, B., Menut, C., Andrianoelisoa, H.S., Raherimandimby, M., Danthu, P., 2009. Composition and antimicrobial activity of essential oils of Cinnamosma fragrans. Food Chem. 114, 680-684.). Essential oil also possesses other effects, such as anti-diabetic, anti-inflammatory, anti-mutagenic, pro-apoptotic activity in cancer cells, cardiovascular and anti-atherogenicity activity against hepaticischemia, and molluscicidal, protozoicidal, and insecticidal effects (Aleksic and Knezevic, 2014Aleksic, V., Knezevic, P., 2014. Antimicrobial and antioxidative activity of extracts and essential oils of Myrtus communis L. Microbiol. Res. 169, 240-254.).

Investigating the pharmacological profile of the fruit of P. domestica reveals prominent activities against Staphylococcus aureus, Staphylococcus epidermidis, and Proteus mirabilis (Mehta et al., 2014Mehta, S., Soni, N., Satpathy, G., Gupta, R.K., 2014. Evaluation of nutritional, phytochemical, antioxidant and antibacterial activity of dried plum (Prunus domestica). J. Pharmacogn. Phytochem. 3, 166-171.). One study reports that the extracts and juices of P. domestica have the capacity to inhibit the oxidation of isolated human low-density lipoprotein (Qaiser and Naveed, 2011Qaiser, J., Naveed, A., 2011. The pharmacological activities of prunes: the dried plums. J. Med. Plant Res. 5, 1511-4508.). In vitro studies also reveal the antioxidant activity of P. domestica fruit peel and flesh with high content of total phenolics and flavonoids, suggesting its radical scavenging abilities (Mariäa et al., 2002Mariäa, I.G., Francisco, A.T., Betty, H.P., Adel, A.K., 2002. Antioxidant capacities, phenolic compounds, carotenoids, and vitamin C contents of nectarine, peach, and plum cultivars from California. J. Agric. Food. Chem. 50, 4976-4982.; Prakash et al., 2013Prakash, D., Upadhyay, G., Gupta, C., 2013. Total phenol and antioxidant activity of some fruits and their under-utilized parts. Int. Food Res. 20, 1717-1724.). Additionally, the plant has anti-hyperlipidemic activity, anticancer activity, blood-pressure lowering activity, activity against cognitive deficits related to age, anxiolytic activity, and beneficial activity related to constipation and liver disorders (Jabeen and Aslam, 2011Jabeen, Q., Aslam, N., 2011. The pharmacological activities of prunes: the dried plums. J. Med. Plants Res. 5, 1508-1511.).

The seed of N. sativa possesses insecticidal, anthelmintic, antimalarial, antitumor, antibacterial, antifungal, carminative, diuretic, antiseptic and digestive properties (Burits and Bucar, 2000Burits, M., Bucar, F., 2000. Antioxidant activity of Nigella sativa essential oil. Phytother. Res. 14, 323-328.; Ali and Blunden, 2003Ali, B.H., Blunden, G., 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res. 17, 299-305.; Saleh, 2006Saleh, S., 2006. Protection by Nigella sativa (Black seed) against hyperhomo-cysteinemia in rats vascular disease. Preventia 3, 73-78.; Abdulelah and Zainal-Abidin, 2007Abdulelah, H.A.A., Zainal-Abidin, B.A.H., 2007. In vivo anti-malarial tests of Nigella sativa (black seed) different extracts. Am. J. Pharmacol. Toxicol. 2, 46-50.; Ali et al., 2008Ali, A., Alkhawajah, A.A., Randhawa, M.A., Shaikh, N.A., 2008. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J. Ayub. Med. Coll. Abbottabad. 20, 25-27.). In the Middle East and some Mediterranean and European countries, the seed of the plant has been used for centuries to treat sexual disorders and has mainly been utilized as an abortifacient (Kanter, 2008Kanter, M., 2008. Effects of Nigella sativa and its major constituent, thymoquinone on sciatic nerves in experimental diabetic neuropathy. Neurochem. Res. 33, 87-96.; Iqbal et al., 2010Iqbal, M.S., Qureshi, A.S., Ghafoor, A., 2010. Evaluation of Nigella sativa L. for genetic variation and ex-situ conservation. Pak. J. Bot. 42, 2489-2495.). In vaginitis, the use of N. sativa capsules with clotrimazole vaginal cream was found to be more effective than clotrimazole vaginal cream alone. Therefore, N. sativa capsules are suggested for the treatment of Candida albicans vaginitis (Fard et al., 2015Fard, F.A., Zahrani, S.T., Bagheban, A.A., Mojab, F., 2015. Therapeutic effects of Nigella sativa Linn (black cumin) on Candida albicans vaginitis. Arch. Clin. Infect. Dis. 10, http://dx.doi.org/10.5812/archcid.22991.
http://dx.doi.org/10.5812/archcid.22991...
). All of the above-mentioned pharmacological studies suggest the potency of the reported species to combat gynecological problems.

Conclusions

Residents in the study area showed a positive attitude toward the utilization of medicinal plants. Midwives and traditional healers possess traditional knowledge related to gynecological problems. In the study area, 53 medicinal plants are used to treat 28 types of gynecological complaints. Most widely accepted medicinal plants are Withania somnifera, F. vulgare, P. domestica, M. communis, C. sativa and N. sativa. Roots are the main part used in the preparation of ethnomedicinal remedies for gynecological problems. Menstrual problems were the utmost prevailing disease category treated using 21 medicinal plants in the area. The current study provides a baseline for future pharmacological research in the field of gynecology. Therefore, it is necessary to focus on the reported plants to identify new pharmaceutical against gynecological diseases.

Ethical disclosures

  • Protection of human and animal subjects
    The authors declare that no experiments were performed on humans or animals for this study.
    Confidentiality of data
    The authors declare that no patient data appear in this article.
    Right to privacy and informed consent
    The authors declare that no patient data appear in this article.
  • Funding
    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this Research Group NO (RG-1435-014). The authors extend their appreciation and acknowledgment toward the local communities for their moral support to the authors.

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Publication Dates

  • Publication in this collection
    Jul-Aug 2018

History

  • Received
    28 Nov 2017
  • Accepted
    14 May 2018
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