**Abstract**

Also known as the Himalayan mayapple, *Podophyllum hexandrum* is a succulent erect herb, glabrous, up to 30 cm tall with creeping long knotty rhizome. The plant produces podophyllotoxin, an anticancer metabolite, and hence can also be used for the treatment of cancer. The roots have also reported anticancer lignans, including podophyllotoxin and berberine. The root is harvested in the autumn and either dried for later use or the resin is extracted. Due to the plant has been overexploited due to medicinal properties and is now enlisted as an endangered species. Therefore, there is a need to grow this plant at a greater scale so as to utilize its medicinal potential to the fullest. Unsuccessful attempts have been made to grow the pant in vitro. Hence, this problem needs to be countered and methods to increase the metabolite production by the plants are also needed in order to maximize the utilization of its medicinal properties. This review focuses on providing solutions to the researchers to develop new techniques to grow the plant in vitro as well as ex situ and also gives an insight on the various methods that have been proved fruitful for increasing the production of podophyllotoxin in *P. hexandrum*.

**Keywords:** *Podophyllum hexandrum*, anticancer, podophyllotoxin, in vitro propagation, ex situ propagation

## **1. Introduction**

The Himalayan range in India is recognized as a mega hotspot for biodiversity [1]. **Table 1** gives a list of the different types of plants found in this region, which helps to understand the importance of the Himalayan region in terms of endemism of plant species [2]. Of these floral collections, 1748 species have been identified to be of medicinal importance both traditionally and also as modern phytotherpeutics [3]. These 1748 species have been utilized for various purposes (**Table 2**) [3, 4], 121 of which have been categorized to be rare-endangered species [5]. Besides using these local floras for their own survival in form of food, medicine, agricultural tools, and fodder, the local communities also trade these endemic plant species and their traditional knowledge for generating income [3]. According to a survey conducted for the prioritization of medicinal plants by the All India Trade Survey, the demand of these plants for their medicinal value has increased by 50% while their availability has noted a decrease of 25% [6].


*The table also gives the percentage of different floras that are endemic to that area, thereby suggesting the importance of the Indian Himalayan region in terms of biodiversity.*

#### **Table 1.**

*List of different types of flora inhabiting the Indian Himalayan region.*


#### **Table 2.**

*The number of different species found in the Himalayan region has diverse uses which cater to the needs of both the traditional local communities and the industrially significant medicinal market.*

The term *Podophyllum* is derived from an ancient Greek word meaning foot leaf. It is also known as mayapple since the fruit ripens in the months of spring. The genus *Podophyllum* is globally represented by three species, the *P. hexandrum*, *P. peltatum*, and *P. sikkimensis*. The *P. hexandrum*, which grows in the Himalayan regions of Asian subcontinent, is commonly known as the Indian mayapple. *P. peltatum* is found distributed in regions of Atlantic North America and is popularly called as the American mayapple [7]. *P. hexandrum* is found to grow normally in the sub-Himalayan regions of India, Pakistan, Bhutan, Afghanistan, China, and Taiwan. In India, it largely covers the states from Jammu and Kashmir to Uttarakhand and some parts of Northeastern India due to its specific environmental requirements. **Table 3** gives a state-wise distribution of this plant species in India [8].

*Podophyllum* is a green herbaceous plant belonging to the family of Berberidacea of the order Ranunculales. Indian *Podophyllum* is a native of the Himalayan region and grows favorably in the temperate and subalpine regions having welldrained, humus-rich soil conditions. In Ayurvedic terminology, it is referred to as Vanyakarkati. The plant has a perennial rhizome and a succulent stem. The stem has a pair of leaves drooping down from the petiole like umbrellas. The stem grows to a height of approximately 30 cm before the complete development of the leaves. The leaves are generally spotted with a width of nearly 25 cm. The flower is pinkish white in color and appears in May. The fruit ripening occurs in August or September and the fruit is bright orange in appearance with a size comparable to that of a lemon.

Several studies have been conducted to identify the best possible methods of propagation of *P. hexandrum*. According to one such study, the propagation of the *Propagation of* Podophyllum hexandrum *Royale to Enhance Production of Podophyllotoxin DOI: http://dx.doi.org/10.5772/intechopen.93704*


**Table 3.**

*State-wise distribution of* P. hexandrum *in India.*

seeds of the plant in an off-site environment under controlled conditions allowed the seedlings to grow a year faster as compared to that when grown in field. The search is on to identify and establish such effective ex situ methods of propagation as these along with several other modes of propagation as in vitro and in vivo methods can help conserve the genetic diversity of the plant besides providing a substantial number of transplants to go back into the wild to combat the vulnerability of overharvesting without compromising on its industrial demand [9]. There is very less literature available showing the growth of *Podophyllum hexandrum* using micro-propagation techniques.

Use of bioreactors for the growth and production of podophyllotoxin has not yet been evaluated properly owing to the lack of genetic data about the plant's genes involved in metabolite production. The technical know-how about the factors affecting biosynthetic pathway and podophyllotoxin production has not been explored and no significant literature is available. This review focuses on the optimization of culture conditions for the propagation of *Podophyllum hexandrum* and obtains conditions for the enhanced production of podophyllotoxin (**Figure 1**).

**Figure 1.** *Taxonomic classification of* P. hexandrum*.*
