**1. Introduction**

Traditional medicine is a popular treatment method for a wide range of diseases in many countries due to its claims of therapeutic activity by patients. The knowledge handed over from generation to generation since ancient ages is the foundation of traditional medicine; hence, the methods of treatment vary depending on the country and the region of origin.

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In addition, a single region may use different types of traditional medicine due to different ethnic backgrounds of its citizens migrated from different regions of the world.

In order to investigate the different activities of plant-derived extracts, the use of experimental platforms is important prior to clinical trials. Human stem cells are one such experimental platform to investigate therapeutic activities of herbal extracts *in vitro.* Stem cells with the ability to self-renew and differentiate into many cell lineages have been accepted and extensively used by scientists globally as a reliable tool in their research. Of the many different sources of stem cells, bone marrow stem cells have been used widely in research due to their well-explained characteristics, but the usage paradigm is shifting towards umbilical cord- and cord blood-derived stem cells due to the advantages such as minimum ethical issues, high availability and easy isolation methods of the latter [15]. Since stem cells possess multi-lineage differentiation ability, stimulated differentiation of stem cells could be used to investigate on therapeutics applicable to different types of diseases. For example, human mesenchymal stem cells (hMSCs) could be differentiated into osteocytes, adipocytes and chondrocytes; hence, herbal extracts could be used to investigate the suppression or the stimulation of adipogenic, osteogenic and chondrogenic differentiation properties of stem cells and therefore used to investigate the therapeutic possibilities of diseases related to the above cell lineages *in vitro*. Human haematopoietic stem cells are the progenitors of cells of blood tissue; hence, those can be differentiated into different blood cell types, and herbal extracts could be used in the above manner to search for therapeutic agents for blood cell-related disorders. Induced pluripotent stem cells (iPSCs), a group of adult somatic cells which are genetically engineered to function as embryonic-like stem cells, are also widely used as disease model stem cell lines in investigations of therapeutic candidates for different disease targets [16]. iPSC-derived cardiomyocytes from patients with cardiovascular diseases and iPSC-derived neurons from patients with neurodegenerative disorders are currently used in high-throughput drug screening [17]. Undifferentiated stem cells are transplanted in order to regenerate tissue *in vivo*; hence, stimulation factors are important to increase the regeneration speed. The issues of synthetic growth factors and stimulants, i.e. possible side effects, high costs and low availability, remain unchanged; therefore, natural stimulants are preferred. Hence, research is ongoing in search of natural stimulants for stem cells [8]. Furthermore, growth factors, cytokines and vesicles secreted by hMSCs are known as the secretome of hMSCs, and these bioactive factors isolated singly or as a mixture are investigated as potential therapeutic agents, which could reduce the complexities

Application of Herbal Medicine as Proliferation and Differentiation Effectors of Human Stem Cells

http://dx.doi.org/10.5772/intechopen.72711

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Although it is reported that over 53,000 plant species are used in herbal medicine globally [2], only a few are being tested and reported with scientific proof of their biological activities. The need for merging of traditional herbal medicine knowledge and cutting-edge scientific techniques is essential to produce novel drugs for the benefit of patients. Investigation of mechanisms of actions and pathways, stimulated by herbal extracts, is critical as this would support the scientific validation of such products prior to their market launch. Therefore, this chapter aims to elaborate such research published in the recent decade, in which herbal preparations, extracts and plant-derived bioactive compounds were utilized to produce scientific proof of anti-disease activity, proliferation stimulant activity and differentiation stimulation or suppression of stem cells and their related plausible mechanisms of action. Also, the chapter would identify research gaps related to effects of herbal extracts on stem cells for use in clinical therapy. This chapter harps on the potential of commercializing herbal-based stem

of therapy using cell transplantations [18].

cell therapy, which will also be affordable to the developing world.

As the World Health Organization (WHO) defines 'Traditional medicine is the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness [1]'.

Herbal medicine is one of the main streams of every traditional medicine practice regardless of the different types such as Indian traditional medicine (ITM), Sri Lankan traditional medicine (SLTM), traditional Chinese medicine (TCM), Arabic traditional medicine (ATM), African traditional medicine and South American traditional medicine. According to the WHO, medicinal ingredients of herbal medicine include herbs, herbal materials, herbal preparations and finished herbal products that contain active ingredients as parts of plants or other plant materials or combinations; also, 75% of the world's population use herbs for their basic healthcare needs [2]. Archaeological proof of history in the use of herbal medicine dates back to more than 5000 years [3], along with evidence from ancient literature such as *Arkaprakasa* (pharmacology and pharmacy) and *Kumaratantra* (paediatric diseases and management) claimed to be written by the great king Ravana of Sri Lanka where different herbal preparations were introduced for treatment and management of different types of diseases [4]. An in-depth account of the historical events on the use of herbals is reviewed by Petrovska [5]. The same disease could be treated in different countries, with different types of plant-based remedies mainly depending on their indigenous plant varieties and traditional knowledge handed down to generations through thousands of years [6, 7].

Even though history strongly supports the use of herbal medicine, over the last century, traditional knowledge and its effective uses were challenged by Western medical practitioners due to lack of scientific validation of these claims and evidence [2]. However in the recent decades, perspectives on herbal medicine had been evolving into positive thoughts with the isolation of many different effective drugs from plant materials. Existing synthetic drugs are highly expensive, and most of these are required to be replaced due to their instability *in vivo* [8]. Continuous synthetic drug doses may cause side effects and toxicity [9]; hence, these disadvantages accelerated the search for alternatives derived from natural products. With the technological advances in health and basic sciences, multi screening drug facilities to investigate specific therapeutic activities was made possible. Isolated chemicals and bioactive compounds from plant materials are the main source of modern pharmaceutical drugs, which are either naturally derived or synthetic analogues of existing natural compounds [10]. Among the many different approved drugs derived from herbal material, anticancer drugs [11], antidiabetic drugs [12] and skin care products [13] have maintained topmost status in this long list. In cancer therapy, 25% of the drugs used in the last 20 years are directly derived from plant material [11], and 49% of the antidiabetic drugs approved in the last 10 years were plant derived [12]. Both in developing and developed countries, obesity is becoming a socio-economic burden rendering global populations unhealthy, leading to many non-communicable diseases [14]. There are many weight-reducing supplements prepared by herbal extracts selling in an increased rate in the local markets, even without clinical approval, due to the popularity of the products among the users. Hence, researches are in the timely search of antiobesity herbal preparations [14] as these would flourish as multimillion dollar businesses in the global market.

In order to investigate the different activities of plant-derived extracts, the use of experimental platforms is important prior to clinical trials. Human stem cells are one such experimental platform to investigate therapeutic activities of herbal extracts *in vitro.* Stem cells with the ability to self-renew and differentiate into many cell lineages have been accepted and extensively used by scientists globally as a reliable tool in their research. Of the many different sources of stem cells, bone marrow stem cells have been used widely in research due to their well-explained characteristics, but the usage paradigm is shifting towards umbilical cord- and cord blood-derived stem cells due to the advantages such as minimum ethical issues, high availability and easy isolation methods of the latter [15]. Since stem cells possess multi-lineage differentiation ability, stimulated differentiation of stem cells could be used to investigate on therapeutics applicable to different types of diseases. For example, human mesenchymal stem cells (hMSCs) could be differentiated into osteocytes, adipocytes and chondrocytes; hence, herbal extracts could be used to investigate the suppression or the stimulation of adipogenic, osteogenic and chondrogenic differentiation properties of stem cells and therefore used to investigate the therapeutic possibilities of diseases related to the above cell lineages *in vitro*. Human haematopoietic stem cells are the progenitors of cells of blood tissue; hence, those can be differentiated into different blood cell types, and herbal extracts could be used in the above manner to search for therapeutic agents for blood cell-related disorders. Induced pluripotent stem cells (iPSCs), a group of adult somatic cells which are genetically engineered to function as embryonic-like stem cells, are also widely used as disease model stem cell lines in investigations of therapeutic candidates for different disease targets [16]. iPSC-derived cardiomyocytes from patients with cardiovascular diseases and iPSC-derived neurons from patients with neurodegenerative disorders are currently used in high-throughput drug screening [17]. Undifferentiated stem cells are transplanted in order to regenerate tissue *in vivo*; hence, stimulation factors are important to increase the regeneration speed. The issues of synthetic growth factors and stimulants, i.e. possible side effects, high costs and low availability, remain unchanged; therefore, natural stimulants are preferred. Hence, research is ongoing in search of natural stimulants for stem cells [8]. Furthermore, growth factors, cytokines and vesicles secreted by hMSCs are known as the secretome of hMSCs, and these bioactive factors isolated singly or as a mixture are investigated as potential therapeutic agents, which could reduce the complexities of therapy using cell transplantations [18].

In addition, a single region may use different types of traditional medicine due to different

As the World Health Organization (WHO) defines 'Traditional medicine is the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness [1]'.

Herbal medicine is one of the main streams of every traditional medicine practice regardless of the different types such as Indian traditional medicine (ITM), Sri Lankan traditional medicine (SLTM), traditional Chinese medicine (TCM), Arabic traditional medicine (ATM), African traditional medicine and South American traditional medicine. According to the WHO, medicinal ingredients of herbal medicine include herbs, herbal materials, herbal preparations and finished herbal products that contain active ingredients as parts of plants or other plant materials or combinations; also, 75% of the world's population use herbs for their basic healthcare needs [2]. Archaeological proof of history in the use of herbal medicine dates back to more than 5000 years [3], along with evidence from ancient literature such as *Arkaprakasa* (pharmacology and pharmacy) and *Kumaratantra* (paediatric diseases and management) claimed to be written by the great king Ravana of Sri Lanka where different herbal preparations were introduced for treatment and management of different types of diseases [4]. An in-depth account of the historical events on the use of herbals is reviewed by Petrovska [5]. The same disease could be treated in different countries, with different types of plant-based remedies mainly depending on their indigenous plant varieties and traditional knowledge handed down to

Even though history strongly supports the use of herbal medicine, over the last century, traditional knowledge and its effective uses were challenged by Western medical practitioners due to lack of scientific validation of these claims and evidence [2]. However in the recent decades, perspectives on herbal medicine had been evolving into positive thoughts with the isolation of many different effective drugs from plant materials. Existing synthetic drugs are highly expensive, and most of these are required to be replaced due to their instability *in vivo* [8]. Continuous synthetic drug doses may cause side effects and toxicity [9]; hence, these disadvantages accelerated the search for alternatives derived from natural products. With the technological advances in health and basic sciences, multi screening drug facilities to investigate specific therapeutic activities was made possible. Isolated chemicals and bioactive compounds from plant materials are the main source of modern pharmaceutical drugs, which are either naturally derived or synthetic analogues of existing natural compounds [10]. Among the many different approved drugs derived from herbal material, anticancer drugs [11], antidiabetic drugs [12] and skin care products [13] have maintained topmost status in this long list. In cancer therapy, 25% of the drugs used in the last 20 years are directly derived from plant material [11], and 49% of the antidiabetic drugs approved in the last 10 years were plant derived [12]. Both in developing and developed countries, obesity is becoming a socio-economic burden rendering global populations unhealthy, leading to many non-communicable diseases [14]. There are many weight-reducing supplements prepared by herbal extracts selling in an increased rate in the local markets, even without clinical approval, due to the popularity of the products among the users. Hence, researches are in the timely search of antiobesity herbal preparations [14] as these

ethnic backgrounds of its citizens migrated from different regions of the world.

generations through thousands of years [6, 7].

88 Herbal Medicine

would flourish as multimillion dollar businesses in the global market.

Although it is reported that over 53,000 plant species are used in herbal medicine globally [2], only a few are being tested and reported with scientific proof of their biological activities. The need for merging of traditional herbal medicine knowledge and cutting-edge scientific techniques is essential to produce novel drugs for the benefit of patients. Investigation of mechanisms of actions and pathways, stimulated by herbal extracts, is critical as this would support the scientific validation of such products prior to their market launch. Therefore, this chapter aims to elaborate such research published in the recent decade, in which herbal preparations, extracts and plant-derived bioactive compounds were utilized to produce scientific proof of anti-disease activity, proliferation stimulant activity and differentiation stimulation or suppression of stem cells and their related plausible mechanisms of action. Also, the chapter would identify research gaps related to effects of herbal extracts on stem cells for use in clinical therapy. This chapter harps on the potential of commercializing herbal-based stem cell therapy, which will also be affordable to the developing world.
