Herbal Medicine: Back to the Future

The use of plant-derived medications in the treatment and prevention of diseases, i.e., phytotherapy, comprises the traditional knowledge of therapeutic advantages deriving from the use of herbal parts to prevent, protect against and cure several pathologic conditions, such as cancerous, metabolic and inflammatory diseases. Herbal medications are prevalent in countries with limited resources, but, recently, increasing attention is devoted to their exploitation in cancer management on the basis of their low cost and side effects absence compared to conventional radiation or chemotherapic cancer approach. Currently, about 114,000 herbal extracts have screened for anticancer activity and 60% of the commercially available and clinically used cancer drugs, such as vinblastine and vincristine, paclitaxel, campothecin and its derivatives, are from natural sources. These compounds are active against a number of cancer types (ovarian, breast, lung, colon, liver, blood, prostate cancer). There are many types of cancer elicited by several factors that still render this disease a major public health problem, almost everywhere in the world.

The human body is constantly exposed to free radicals arising from exogenous and endogenous origins, which cause oxidative stress. Oxidative stress is closely related to various diseases, including cancer. There are many evidences that ROS are pivotal in cancer progression (via damage of DNA leading to genomic instability) and regression (via cell death induction through oxidative stress burst). Antioxidants stabilize free radicals and, in turn, prevent the oxidative stress, playing a key role in protection of the body, In this context, natural plants-derived antioxidants are universally considered very important for the prevention and treatment of oxidative stress and cancer. However, a dual role of plants in ROS generation or scavenging is recognized as plants extracts can also increase ROS production in the cells. Consequently, the role of plant extracts in ROS balancing inside cancer cells is a very fascinating feature in phytotherapy.

Among the plants reported in traditional medicine as a very panacea in active compounds, Carica papaya and Azadiracta indica (also known as Neem) extracts from different parts (leaves, seeds, fruits, etc.) are scientifically validated in the treatment of several diseases, including cancer. In this context, the two plants have different impact on cancer cell lines. In particular hydro-alcoolic extract of Neem leaves shows a pro-oxidant activity in hepatoma HepG2 cells, whereas water extract of C. papaya seeds exerts an anti-oxidant activity in leukemia HL-60 cells. Neem extract is unable to quench oxidative stress induced on HepG2 and synergizes with hydrogen peroxide (H2O2) in inducing cell death. Conversely, C. papaya extract quenches ROS induced by H2O2 in HL-60 cells but at the same time negatively affects cell viability.

These evidences corroborate the idea that the extracts from plants could act in patients with cancer to modulate oxidative homeostasis and obtain benefit during cancer therapy.

An agent that causes irreversible and hereditary (mutation) changes in cellular genetic material, deoxyribonucleic acid (DNA) is defined as a mutagen. Changes in DNA caused by mutagens can damage the cells and cause certain diseases, such as cancer. Among the oldest and most recognized tests for the detection of mutagens we can mention those of Ames, which works with bacteria, and the test of the onion or Allium cepa test. One of the most effective ways to minimize the harmful effect of mutagenic substances is through the use of natural antimutagens. Natural antimutagenic substances, which may be present in plants, human diet and other sources have protective effects against mutagens. We showed that vitamin C and green tea infusions, in the Ames test, significantly mitigate the mutagenicity of sulfatiazole (a sulfa drug, an antibacterial commonly used) and nitrite (a food preservative and a normal body component) mixtures in acidic medium.

Cancer is one of the leading causes of death worldwide. There are many problems in cancer therapy due to the side-effects which limit its usage. Products derived from natural substances, particularly polyphenolic compounds which have very little toxic effects on normal cells, have gained a crucial interest as therapeutic weapon in clinical oncology due to their chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against different types of aggressive, recurrent and drugresistant cancers.

Especially now, polyphenols and their applications are one of the most studied topics in the literature due to their promising results against cancer cells. In many studies, it has been reported that, polyphenols inhibited the development of tumors through variety of mechanisms and reduce the tumor cell mass. However, with all the advantages of polyphenols, in the literature it is stated that, issues like poor solubility, high degradation rate and high dose requirement restrict the applications of polyphenols. Still, these obstacles can be overcome by using encapsulation and nano-drug delivery systems for plant-derived polyphenols. With the encapsulation techniques it is possible to increase their bioavailability, stability of the polyphenols and their uptake in the targeted cells. Encapsulated polyphenols have been used against cancer in various scientific studies. And the obtained results were promising. With the encapsulation methods, greater accumulation of polyphenols has been observed on the cell membrane and cytoplasm due to smaller size.

In this chapter, plant-derived polyphenols, their stabilities and encapsulation of polyphenols in order to increase their stability and their potential as cancer treatment agents will be explained.

World Health Organization (WHO) estimates that in 2015 cancer was the primary cause of death of 8.8 million people, which transfers to every sixth death globally. The number of newly diagnosed cancer cases annually is expected to reach more than 23 million over the next 2 decades. Cancer describes a large group of diseases originating in uncontrolled growth of abnormal cells in the body, debilitating for the patient and usually requiring complex long-term treatment. Surgery, chemotherapy and radiotherapy are considered as the most common conventional cancer therapies. These treatment strategies, however, are associated with limitations and clinical results are often unsatisfactory. Therefore, combined and more effective therapies in cancer treatment must be implemented.

Traditional herbal medicines (THM) have been used in treatment of cancer for thousands of years in majority of Asian countries. It is also a common practice nowadays to combine THM with Western cancer management schemes, consolidating a variety of natural agents into one treatment strategy. The use of herbal products in cancer therapy, over the last years, has received much attention also in Western countries becoming more popular among patients, with a prevalence reaching up to 80%. Large number of these medications is also widely approved as a form of complementary and alternative medicine in cancer treatment in both Europe and United States.

Clinical challenge in management of cancer is cancer-related fatigue (CRF), which is a persistent sense of tiredness associated with the treatment or the disease itself that cannot be eliminated by rest. THM in the recent years presents with a wide range of opportunities among which management of adverse treatment effects and fatigue emerge as worth investigating. Herbal medicines may be considered as an effective and safe treatment of CRF.

In conclusion, herbal medicines possess a wide range of activities in relation to cancer treatment. Natural medical agents may reduce cancer-related fatigue as well as damage to gastrointestinal, respiratory and nervous systems. However, considering, little scientific knowledge about efficacy and safety of herbal products consecutive controlled clinical studies are needed to fully verify this matter.

The traditional use of indirubin for the treatment of leukaemia has opened a vast field of research, studying the anti-tumor properties of indirubin and its derivatives (IRDs) against a wide range of malignancies. The cytotoxic effects of indirubin has been primarily attributed to its inhibitory function on a number of protein kinases, including cyclin-dependent kinases (CDKs), glycogen-synthase kinase 3 (GSK-3), and receptor tyrosine kinases (RTKs). In the past few decades, a lot of effort has been directed to the chemical modification of indirubin’s backbone towards better pharamcokinetic properties. This has led to the synthesis of various derivatives with new biological activities. We here review from the discovery of indirubin to the development of novel IRDs, and highlight the recent progress on how indirubins influence multiple cancer-associated signaling networks, leading to anti-proliferative and pro-apoptotic effects. Furthermore, we discuss the therapeutic use of indirubins in anti-cancer settings, as well as their potential for future clinical application.

Cancer is one of the deadliest diseases of the century. Though a lot is known about its pathogenesis, a cure for the disease is not yet available. The present therapies for cancer lack specificity and show various toxicities. Ayurveda is one of the oldest traditional systems of medicine along with the Chinese system of medicine, Siddha, and Unani. Cancer has been described as clinical entities arbuda and granthi in the famous ayurvedic text Sushrutha samhita centuries before the detection of cancer by modern medicine. In this chapter, we discuss the phytoconstituents of medicinal plants with anticancer properties as described in Ayurveda from ethnopharmacology and experimental pharmacology perspective. The chapter summarizes and emphasizes the importance of Ayurveda, a traditional system of medicine in the treatment of cancer.

Medicinal Plants have been known to be one of the oldest and most consistent sources for the production of novel drugs. Utilization of plant extracts as drugs can be attributed to their chemical and structural diversity along with their ability to interact with different biological targets in the cell. Moreover, they act as huge reservoirs for the phytochemicals which provide defense against a number of diseases. Cost effectiveness along with lesser adverse effects, allowed natural plants to be used as an alternative to conventional strategies for cancer treatment. Extracts from different natural plants have also been explored in the treatment of infectious diseases. The present chapter emphasizes on the use of plant extracts and their purified compound as cancer therapeutics. Cancer is one of the major causes of mortality worldwide. Owing to several limitations of current treatment regimens of cancer, the attention of researchers has been drawn towards exploration of natural sources. Herein, we will focus majorly on bioactive compounds as therapeutic agents for cancer treatment with emphasis on their other possible beneficiary roles.

Earth’s landform is highly rich in biodiversity holding thousands of flora exhibiting tremendous therapeutic potential which has been extensively used in traditional systems of medicine including Ayurveda, Unani, Siddha, Homeopathy and Tibb. However, due to the advancement in allopathic medicines, the use of herbs becomes shaded. Vitiligo is a skin depigmentation disease in which the loss of melanocytes results in the appearance of irreversible white patches on the body. As it is one of the most conspicuous traits, variation in skin color or spotted skin has led some societies to attach labels and fabricate myths about people having pigmented macules on their face and body. Therefore, several treatment modes have been unleashed. But the current treatments of vitiligo including phototherapy, surgery, use of topical corticosteroid and immune modulators come under increasing scrutiny due to their aftereffects, underscoring the requirement of such treatment strategies which have low or no side effects. Hence, the use of plants and their constituents for preparation of dermatological formulation for the treatment of vitiligo is highly recommended. In the present chapter, we have discussed the types and pathogenesis of vitiligo and the modern treatment modalities with the problems associated with them, with reference to the validated clinical use of herbal products. Furthermore, the results of our own studies and controlled clinical trials by other investigators enlighten the varying efficacies of different plants and their active components for melanocyte proliferation and regeneration which might be clinically used for the treatment of vitiligo, thus opening a platform for further research and development.