Naturally Occurring Small Molecules for Disease and Cancer Treatment

Therapeutic Benefits in Combination Therapy

Wing Shing Ho

• Publisher: WSPC
• Year: 2019
• ISBN:
  9789814525640
• Topic: Medicine
• Subtopic: Alternative & Complementary Medicine

Western drugs and target medicines for disease treatment come with undesirable side effects that have limited their use in patients for an extended period of time. It is warranted to develop a treatment strategy with alternative medicines to reduce toxicity relating to drugs, in particular, cancer drugs. Thus, a combination therapy with herbal medicines provides a more effective treatment method for hard-to-treat diseases. The recent breakthroughs in naturally occurring small molecules from herbal medicines have provided experimental evidence and are clinically significant in treatment strategies.

This unique volume presents the recent developments in the field of herbal medicines for the treatment of diseases and cancer. Recent progress on small molecules isolated from herbal medicines that exhibit therapeutic benefits in humans is highlighted. The book provides an overview of the significant discoveries and pioneering contributions of herbal medicines in combination with other drugs; the author's evaluation of the combination therapy in cancer treatment; and a recent discovery of crocodile tissue extract with pharmacological properties.

Contents:

• Principles of Pharmacology of Cancer Drug Treatment
• Plant Molecules
• Herbal Medicines
• Therapeutic Uses of Small Molecules
• Mechanism of Action
• Integration and Control of the Human Body During Treatment
• Cytotoxic Plant Molecules and Immunopharmacology
• Potential Beneficial Effects of Plant Products
• Adverse Drug Reactions
• Treatment of Cancer with Natural Products
• Pharmaceutical Development of Potential Cancer Drugs

Readership: Medical students, researchers in medicinal chemistry, pharmacologists and both undergraduate and postgraduate students in pharmacology and those working in herbal and alternative medicine.Therapeutic Benefits;Integrated Medicine;Anti-Cancer;Anti-Inflammatory;Small Molecules;Cancer Treatment;New Drugs;Combination Therapy;Natural Plant Products;Crocodile Tissue Extract0 Key Features:

• The book is unique in providing useful information for treatment of cancers and other diseases
• It is the first time that crocodile tissue extract has been shown to produce health benefits in humans
• Small naturally occurring molecules from herbal medicines provide insight into new drug development

1

Principles of pharmacology of cancer drug treatment

Introduction

Herbal medicines have been used for treatment of diseases in China for thousands of years. The composition of phytochemicals in herbal medicines varies among different plant species. Phytochemicals are useful to characterize their medicinal properties of herbs. Phytochemicals may have multi-arrays of other biological significance, e.g., polyphenols, flavonoids, saponins, or carotenoids. Some of these phytochemicals are established as essential nutrients in foods and has been reported in various plants. There are at least 150 kinds of naturally occurring saponins that have been found to possess anti-cancer properties and more than 11 distinguished classes of saponins including dammaranes, tirucallanes, lupanes, hopanes, oleananes, taraxasteranes, ursanes, cycloartanes, lanostanes, cucurbitanes, and steroids.¹ Due to differences in their chemical structures, saponins can display anti-tumorigenic effects on cancer cells yet active phytochemicals from herbal medicine are not easily identified. Although a number of active phytochemicals have been reported, their chemistry and reactivity and the pharmacological activities and mechanism of action and structure–function relationships at the molecular and cellular levels remain to be explored. Some special saponins with strong antitumor effects have been exhibited. Ginsenosides which are dammaranes are shown to exhibit anti-angiogenesis and inhibiting metastasis. In addition, Dioscin, one of the steroidal saponins, and its aglycone diosgenin are inducers of cell cycle arrest and apoptosis. Table 1.1 shows the medicinal properties of saponins.

Table 1.1 Medical application of selected saponins

Family	Species	Saponins	Cancer	Ref.
Agavaceae	Agave utahensis	Chlorogenin hexasaccharide	HL-60	Yokosuka et al.^2, Xu et al.^3
Alliaceae	Allium macrostemon Bunge	Macrostemo-noside O, P, Q, and R	HepG2, MCF-7	Yang et al.^4
Aslepiadceae	Cynanchum auriculatum	Wilfoside C3N	A549	Liu et al.^5, Kim et al.^6
Asparagaceae	Asparagus gobicus	Asparanin A	HepG2	Yang et al.^7, Wang et al.^8
Dioscoreaceae	Disscorea	(25S)-spirost- 5-en-3β	L929, HeLa	Liu et al.^9, Gonzalez et al.^10
Dracaenaceae	Nam ginseng	Namonins	HT-1080, BL6	^11, Tran et al.^12
Liliaceae	Polygonatum sibiricum Camassia cusickii	Neosibirico-sides A-D TGHS-1 and 2	MCF-7 P388	Sy et al.^13, Ahn et al.^14
Solanaceae	Solanum torvum Solanum indicum L.	Torvosides M Dioscin	HepG2, MCF-7, Colo-205, HSC-2, human fibroblasts	Nartowska et al.^15, Lu et al.^16

Infectious diseases which are infected by microorganisms such as protozoa are of major health concern worldwide. The incidence of the disease has increased since the emergence of AIDS and Ebola diseases. In the absence of a vaccine and satisfactory drugs, there is an urgent need for novel drugs to replace or to supplement those in current use. Herbal medicines are undoubtedly a valuable source of new medicinal agents. However, active phytochemicals remain to be identified and characterized. Herbal extracts and chemically defined molecules of natural origin show various medicinal activities. It also includes about three hundred compounds isolated from higher plants and microorganisms, which are classified into chemical groups with specific biologic activity.¹⁷

Many herbal medicine-derived compounds display significant effects on body functions. They can be good candidates for drug development for treatment of various diseases including rheumatism, asthma, and atherosclerosis. Many herbal extracts and the respective active compounds isolated from natural resources for the treatment of various diseases have been reported yet individual active compounds may not display the same activity in vivo. Herbal extracts are reported to exhibit anti-viral activity against herpes simplex virus (HSV), both the types 1 and 2.¹⁸ Therefore, medicinal plants can be a good source for drug development. However, the bioactive anti-HSV molecules from the plant extracts need to be identified and tested. The mechanism of actions of the potential active anti-HSV molecule(s) requires tedious research work. Similar methodology for isolation, purification, and characterization of potential phytochemicals from other herbal medicines can be used. The most potent molecule(s) and their analogues need to undergo preclinical and toxicity evaluations before synthesis of a large amount of the bioactive molecules for medical applications. In another approach such as genomics, gene expression profiling could help to identify molecular targets of the biological activity of the active natural products that would facilitate the gene-based drug development.

Sesquiterpene

Apart from this, another common class of phytochemicals, Sesquiterpene lactones have been reported as the major phytoconstituents of Saussurea costus. Different pharmacological experiments in a number of in vitro and in vivo models have demonstrated the medicinal properties of S. costus with anti-inflammatory, anti-ulcer, anti-cancer, and hepato-protective activities.¹⁹

Flavonoids

Flavonoids are a large family of polyphenols present in herbal medicines. Six major subclasses of flavonoids, namely anthocyanidins, flavan-3-ols, flavonols, flavanones, flavones, and isoflavones.^20,21 Table 1.2 shows the source of some common plant flavonols. Flavonols are the most commonly found in plants and vegetables and fruit. The biochemical properties of flavonoids influence their disposition. Their metabolites exert biological activities relevant to the health benefits in human health. Many of the biological effects of flavonoids are related to their ability to modulate cell-signaling processes and cell growth. In addition, flavonoids are shown to exhibit multi-arrays of pharmacologic activities including anti-inflammatory, anti-thrombogenic, anti-diabetic, and anti-cancer. Previous studies suggest that consumption of flavan-3-ols and anthocyanidins can exert therapeutic effects on cardiovascular disorders and type 2 diabetes mellitus. However, only a limited number of studies has reported the anti-cancer activities of flavonoids in humans but higher intake of soy isoflavones appeared to be associated with reduction in cancer risks of breast in women and prostate cancer in men. Yet the health benefits of flavonoids remain to be further investigated.

Table 1.2 Common plant flavonoids^20,21

Flavonoid Subclass	Dietary Flavonoids (aglycones)	Some Common Food Sources
Anthocyanidins	Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin	Red, blue, and purple berries; red and purple grapes; red wine
Flavan-3-ols	Monomers (Catechins): (+)-Catechin, (−)-Epicatechin, (−)-Epigallocatechin, (+)-Gallocatechin; and their gallate derivatives	Teas (white, green, and oolong), grapes, berries, apples
	Dimers and Polymers: Proanthocyanidins#	Apples, berries, cocoa-based products, red grapes, red wine
	Theaflavins, Thearubigins	Black tea
Flavonols	Isorhamnetin, Kaempferol, Myricetin, Quercetin	Onions, scallions, kale, broccoli, apples, berries, teas
Flavones	Apigenin, Luteolin, Baicalein, Chrysin	Parsley, thyme, celery, hot peppers
Flavanones	Eriodictyol, Hesperetin, Naringenin	Citrus fruit and juices, e.g., oranges, grapefruits, lemons
Isoflavones	Daidzein, Genistein, Glycitein, Biochanin A, Formononetin	Soybeans, soy foods, legumes

Phytochemicals from cruciferous vegetables

Cruciferous vegetables, such as broccoli and cabbage, contain various sulfur-containing compounds called glucosinolates. Isothiocyanates are biologically active products of glucosinolates.²² For example, broccoli is a good source of glucoraphanin, the glucosinolate precursor of sulforaphane (SFN), and sinigrin, the glucosinolate precursor of allyl isothiocyanate (AITC).^23–26 Glucosinolates are present in medicinal plants. Watercress is a rich source of gluconasturtiin, the precursor of phenethyl isothiocyanate (PEITC), while garden cress is rich in glucotropaeolin, the precursor of benzyl isothiocyanate (BITC). At pr...