**Abstract**

Natural products have been used in medicine right from the ancient civilisation. Natural products are used in many types of diseases, together with chemotherapy and radiotherapy. Many products are used against cancer. Many diseases are genetically derived. The drugs which have the capacity to act at genome level gains significant importance in any disease scenario. The genetic information essential for the identity and function of eukaryotic cells exist in DNA and during the lifetime of the cell DNA can be repeatedly damaged due to different factors. The stability and the fidelity of the replication process are meant to be the most remarkable features of the genetic material. The stability can be affected at any time. Compound which can enhance the DNA repair are applicable in many disease condition. Our study was focussed on the DNA repair enhancing property of a glucan from the macro fungi *Ganoderma lucidum*. Comet assay and chromosomal aberrations in mouse bone marrow were used as end points of study. Glucan was found to have DNA repair enhancing property in human lymphocytes.

**Keywords:** natural products, *Ganoderma lucidum*, glucan, mushroom, DNA repair

### **1. Introduction**

 The word 'Natural' has gained tremendous importance in the twenty-first century. Products obtained from nature are known to be natural. The Father of Medicine, Hippocrates has quoted that 'Let your food be our medicine and medicine be our food'. The incorporation of medicinal herbs and extract as food has been practiced long ago. In the present scenario, herbals are seen as potential medicine for a variety of diseases often viewed to super cede the pharmacological efficacy of allopathic drugs [1]. Natural products has become an extremely valuable commodity for the world today. The developing countries miss the modern medicine as they cannot afford it. Natural drugs were already there is use in Chinese medicine, Indian Ayurveda, Arabic Unani medicine and various other indigenous medicine. The two most important classics describing about more than 700 botanicals along with their classification, pharmacological and therapeutic properties are Charak Samhita and Sushrut Samhita (100–500 BC) [2, 3]. Recent reports have substantiated the general belief that traditional medicine is affordable as compared to modern medicine [4]. Natural products play a major role as 'drugs' and as 'lead structures' for the development of synthetic molecules [5]. Ancient people were fully aware of rich potential of herbs for curing different types of ailments. The twentieth century made invaluable contributions to the domain of medical sciences. The discovery of the fascinating molecule, DNA double helix and completion of human genome project were marvellous achievements that had no parallel.

 Different modalities of DNA repair mechanisms are offered by natural drugs in mammalian system like base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), SSB repair, which includes BER and DNA-PK-mediated ligation; DSB repair, which includes NHEJ and HR; inter-strand cross-link repair and DPCs (DNA-protein cross links) repair. The drugs act even as a biological catalyst where the rate of the repair process is enhanced [6]. An important cell pathology determinant is the rate of DNA repair. Shortened lifespan and increased cancer incidence has been observed in experimental animals with genetic deficiencies in DNA repair. Mice deficient in the dominant NHEJ pathway and in telomere maintenance mechanisms get lymphoma and infections more often, and consequently have shorter lifespans than wild-type mice [7]. Mice with deficient key repair mechanisms and DNA helices unwinding transcription protein have premature onset of aging-related diseases and shortening of lifespan [8]. Few natural products with DNA protective activity are phenolic compounds, essential oils, alkaloids, caratenoids, glutathione and glucans. Polyphenols and phenolic compounds have the capacity to donate electrons and scavenge free radicals [9, 10].

 Phenolic compounds have the capacity to donate electrons and directly scavenge free radicals [9, 10]. The extracts of *Geranium sanguineum* are rich with polyphenol compounds are found to exhibit anti-mutagenic and free radical scavenging capacities [11, 12]. Essential oils, are antioxidants. The essential oil from ginger is a natural antioxidant [13]. Alkaloids, are antioxidants. Carotenoids are lipophilic compounds. Lycopene present in tomatoes and other red fruits like red carrots, red bell peppers, watermelons, and papayas has good antioxidant capacity [14]. Glutathione is a free radical scavenger by either reacting directly with free radical molecules or by acting as proton donor for protection of active molecules as DNA [15]. Glucan is an important carbohydrate from plants, bacteria and fungi. It is discussed in detail here due to their diverse activity. Somehow the antioxidant activity is related to DNA repair mechanism as most of the compound which can repair DNA damage are found possess antioxidant capacity.

Macro fungi are distinguished as important natural resources with therapeutic potential. Studies were conducted on the glucan isolated from the medicinal mushroom and the macrofungi, *Ganoderma lucidum*. *Ganoderma* is popularly known as 'The mushroom of longevity and immortality'1. *Ganoderma lucidum*, commonly known as reishi, a mushroom like fungus which grows on logs or tree stumps is one of the most popular medicinal mushrooms in China, Japan and the United States (**Figure 1**). It has a shiny, hard, asymmetrical cap that ranges in colour from yellow to black. Species of the genus *Ganoderma* P. Karst (Ganodermatales) are important wood decaying mushrooms occurring throughout the world, mainly on tropical trees. Over 250 species of this mushrooms are known. The fruiting

**Figure 1.**  *Ganoderma lucidum growing in wild.* 

#### *Natural Drugs in DNA Repair DOI: http://dx.doi.org/10.5772/intechopen.86008*

 bodies of *Ganoderma lucidum* contain a variety of chemical substances. The polysaccharides of *G. lucidum* are the other major source of its biological activity and therapeutic use. This mushroom has attracted great attention owing to its antitumor and hypoglycemic activities [16]. Many fungal polysaccharides have been reported to be active in humans. More than 180 chemical substances have been isolated from *Ganoderma*, which include polysaccharides, triterpenes, nucleosides, ergosterols, fatty acids, proteins, peptides and trace elements. *Ganoderma* has been extensively used as mushroom of immortality in China and other Asian countries. *Ganoderma* has been reported to have numerous pharmacological effects including immunomodulating, anti-inflammatory, analgesic, anticancer, anti-lipidemic and hepatoprotective antihypertensive effects [8, 17]. It is widely accepted that pharmacological effects of *Ganoderma* depends on its colour, on the stage of development and the environment in which it grows. The fruiting bodies of *Ganoderma lucidum*, commonly known as reishi have long been prescribed in Chinese medicine as a tonic and sedative [18]. In Chinese folklore reishi has been regarded as a panacea for all types of diseases, perhaps owing to its demonstrated efficacy as a popular medicine. *Ganoderma* is also used in treating conditions of the nervous system. The ability of bioactive polysaccharides and polysaccharide-bound proteins to modulate immune cells can be due to the structural diversity and variability of these macromolecules. The bioactive glucanes and proteoglucans isolated from medicinal mushrooms are the most promising class of immunoceutics. Unlike proteins and nucleic acids, polysaccharides contain repetitive structural features which are polymers of monosaccharide residues joined to each other by glycosidic linkages. Glucan appear to be beneficial to humans with impaired immune systems, and those suffering from infectious diseases and cancer, as well as in helping patient recovery from chemotherapy and radiotherapy.

The basic mechanism of DNA replication, recombination and DNA repair are conserved throughout evolution. The complementarity of strands of DNA and the double stranded nature of DNA plays the major role in all the process. Damage to DNA by physical, chemical and biological factors influences the extraordinary accuracy of the entire process. At each cell division a handful of error is introduced per billion bp. Treatment modalities for cancer like chemo and radiotherapy affect DNA in many ways. Drugs of natural origin are capable of increasing the rate of DNA repair. The chapter will focus on the natural drugs and their influence on DNA repair mechanism. In the hierarchy of targets of reproductive death, DNA must be surely placed at the top, though membrane damage should be considered as the second important target with eukaryotic cells which contain their DNA in the nucleus, little lethal damage is observed as long as the radiation is absorbed only by the outer membrane and cytoplasm. There is a drastic increase as soon as the ionizing radiation reaches the nucleus and hence DNA. The DNA damages produced by ionizing radiation can be intra- or inter-strand cross linking and single and double strand breaks (**Figures 2** and **3**). The cellular reactions include halt in cell cycle, advancement at cell cycle checkpoints and the stimulation of DNA repair. An unrepaired or misrepaired DNA damage can result in genetic or genomic variability, changes in cellular individuality and role, cell death, and in multi-cellular organisms, neoplastic transformation.

Humanities use of mushrooms extends as early to 5000 B.C. About 2000 species of edible mushrooms are known all over the world. The total production of the edible mushroom is about 3.75 million tonnes. However they are rich source of high quality protein, vitamins and minerals. The average protein content is 10–40% on dry weight basis and low in fat content. Extracts and powders of mushrooms (mycelia and sporocarps) in the form of sugar coated tablets are being marketed on commercial scale for treatment of diseases such as diabetes, cancer, etc. Medicinal macro fungi modulate immune system and possess antitumor, antimicrobial,

**Figure 2.**  *Effect of radiation on cell.* 

#### **Figure 3.**

*Different types of damages in cell after radiation exposure.* 

anti-inflammatory activities. Attempts are done to explore the use of mushrooms and their metabolites for the treatment of a variety of human ailments [19]. More than 100 medicinal mushrooms have been identified.

#### *Natural Drugs in DNA Repair DOI: http://dx.doi.org/10.5772/intechopen.86008*

*Ganoderma lucidum*, commonly known as reishi, the mushroom of immortality is one of the most popular medicinal mushrooms. The fruiting bodies of *Ganoderma lucidum* contain a variety of chemical substances including polysaccharides, triterpenes, nucleosides, ergosterols, fatty acids, proteins, peptides and trace elements. The polysaccharides of *G. lucidum* are the other major source of its biological activity and therapeutic use. This mushroom has attracted great attention owing to its antitumor and hypoglycemic activities [6]. Many fungal glucan have been reported to be active in humans.
