Medicinal Plants in Asia and Pacific for Parasitic Infections: Botany, Ethnopharmacology, Molecular Basis, and Future Prospect

Medicinal Plants in Asia and Pacific for Parasitic Infections

Botany, Ethnopharmacology, Molecular Basis, and Future Prospects

Christophe Wiart

School of Pharmacy, University of Nottingham Malaysia

Table of Contents

Cover image

Title page

Copyright

Dedication

Quote

Foreword by Robert Verpoorte

Foreword by Bruno David

Foreword by Maria de Lourdes Pereira and Veeranoot Nissapatorn

Foreword by Vu Thi Thom

Preface

Chapter 1. Antiparasitic Asian medicinal plants in the Clade Protomagnoliids

Abstract

1.1 Order Nymphaeales Salisb ex Bercht. & J Presl. (1820)

1.2 Order Austrobaileyales Takht. ex Reveal (1992)

1.3 Order Chloranthales R. Br (1835)

References

Chapter 2. Antiparasitic Asian medicinal plants in the Clade Magnoliids

Abstract

2.1 Order Piperales Bercht. & Presl. (1820)

2.2 Order Laurales Juss. ex Bercht. & Presl. (1820)

References

Further reading

Chapter 3. Antiparasitic Asian medicinal plants in the Clade Monocots

Abstract

3.1 Superorder Liliids

3.2 Superorder Commelinids

References

Further reading

Chapter 4. Antiparasitic Asian medicinal plants in the Clade Eudicots

Abstract

4.1 Order Ranunculales Juss. ex Bercht. & J. Presl. (1820)

4.2 Order Proteales Juss. ex Bercht. & Presl (1820)

References

Further reading

Chapter 5. Antiparasitic Asian medicinal plants in the Clade Core Eudicots

Abstract

5.1 Order Saxifragales Bercht. & Presl (1820)

Reference

Chapter 6. Antiparasitic Asian medicinal plants in the Clade Rosids

Abstract

6.1 Order Vitales Juss. Bercht. & Presl (1820)

Reference

Chapter 7. Antiparasitic Asian medicinal plants in the Clade Fabids

Abstract

7.1 Order Zygophyllales Link (1829)

7.2 Order Celastrales Link (1829)

7.3 Order Oxalidales Bercht. & J. Presl (1820)

7.4 Order Malpighiales Juss, ex Bercht. & J. Presl. (1820)

7.5 Order Cucurbitales Juss. ex Bercht. & J. Presl (1820)

7.6 Fabales Bromhead (1838)

7.7 Order Fagales Engl. (1892)

7.8 Order Rosales Bercht. & Presl. (1820)

References

Further reading

Chapter 8. Antiparasitic Asian medicinal plants in the Clade Malvids

Abstract

8.1 Order Myrtales Juss. ex Bercht. & J. Presl (1820)

8.2 Order Brassicales Bromhead (1838)

8.3 Order Malvales Juss. Ex Bercht. & J. Presl (1820)

8.4 Order Sapindales Juss. Ex Bercht. & J. Presl (1820)

8.5 Order Santalales R. Br. ex Bercht. & J. Presl (1820)

8.6 Order Caryophyllales Juss. ex Bercht. & J. Presl (1820)

References

Further reading

Chapter 9. Antiparasitic Asian medicinal plants in the Clade Asterids

Abstract

9.1 Order Cornales Link. (1829)

9.2 Order Ericales Berchtold et J. Presl (1820)

References

Chapter 10. Antiparasitic Asian medicinal plants in the Clade Lamiids

Abstract

10.1 Order Boraginales Juss. ex Bercht. & J. Presl (1820)

10.2 Order Gentianales Juss. ex Bercht. & J. Presl (1820)

10.3 Family Gentianaceae A.L. de Jussieu (1789)

10.4 Family Loganiaceae R. Br ex Mart (1827)

10.5 Family Rubiaceae A.L. de Jussieu (1789)

10.6 Order Lamiales Bromhead (1838)

10.7 Order Solanales Juss. ex Bercht. & J. Presl (1820)

References

Further reading

Chapter 11. Antiparasitic Asian medicinal plants in the Clade Campanulids

Abstract

11.1 Order Asterales Link (1829)

11.2 Order Dipsacales Juss. ex Bercht. & J.Presl (1820)

11.3 Order Apiales Nakai (1930)

References

Further reading

Bibliography

Classic texts

References

Index

Copyright

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Dedication

In memory of my grandmother Renée Monllor,

To my mother Flora Monllor,

To my wife Shirley Pita,

To my son Christophe Pita-Wiart

Quote

If you see what needs to be repaired and how to repair it, then you have found a piece of the world that G-d has left for you to complete.

Rabbi Menachem Mendel Schneerson

Foreword by Robert Verpoorte

The present pandemic COVID-19 viral disease shows that despite all our advanced science, still nature is able to show us that we might think that we have all under control, but in fact that is not true. During the million years of evolution and development leading to the present day’s society, there has been many other pandemic diseases caused by viruses, microorganisms, and various parasites that hit humans. Some have been eradicated, some we have learned to control by prevention, and others by medication or the combination of both measures. Besides hygiene, vaccination is the major preventive medical treatment. But still many tropical diseases lack proper medicines.

Present day pharmaceutical development is mainly focused on chronic lifestyle-related diseases, requiring strict regimens for the patients of taking several medicines for the rest of their life to treat the symptoms of the disease, like hypertension, high cholesterol, and/or high glucose. The business model is clear, identifies all patients who have symptoms and then prescribes the medication to be taken every day for the rest of your life. The other business model for the big pharma is cancer treatments that concern a disease that is potentially killing the patient. To save the patient’s life, the society accepts high costs for medicines that cure, or at least give the patients some extra time to live. This is a business model that is based on very expensive medicines to stop the growth of cancer cells and preferably kill these cells. For both business models, costs of development will be similar, but the earnings should be in the first case on chronic treatments over many years, in the second case intensive treatments in short time. What are missing in these two models are the medicines to treat infectious diseases caused by external organisms such as viruses, microorganisms, and parasites. For many of these illnesses, good medicines are available, like the antibiotics. But to develop novel drugs for these diseases, the business models mentioned do not work, as usually these illnesses are cured in a treatment of a week or so. That means the costs of developing a novel antibiotic or antiparasitic drug are difficult to earn back. Particularly for some of the more rare tropical diseases, big pharmaceutical companies do not have research programs for developing cures. The Nobel Prize 2015 shows two successful examples for parasitic diseases. This prize was for William C. Campbell and Satoshi Ōmura for their discoveries concerning a novel therapy against infections caused by roundworm parasites and the other half to Tu Youyou for her discoveries concerning a novel therapy against Malaria. The roundworms-caused diseases could be treated with a novel antibiotic Ivermectine that was developed and financed by the pharmaceutical company Merck.

So why did I write this long introduction about the economics of drug development? Because this makes clear that the development of medicines against infectious diseases has stalled at the level of the pharmaceutical companies, because of too high costs to develop this sort of medicines for a small market. Despite the warnings of the SARS and MERS, no major efforts were developed for medicines against diseases caused by Corona viruses. The result of this omission is visible in 2020. The already mentioned Nobel Prize 2015 shows three things. First that nature is full of molecules that could be used to treat any disease, second that our ancestors already developed medicines for many diseases, and third that this sort of research can successfully be done at academic institutions and governmental research institutions. The type of research necessary for developing drugs that cure infectious diseases can be done in any lab with no need for highly specialized equipment and facilities. What you need is to be a good observer like Alexander Fleming who discovered by chance penicillin in 1928, though it took more than 10 years before Florey and Chain developed it into a medicine. The three of them received the Nobel Prize for Medicine in 1945.

The development of an antibiotic or antiparasitic drug is very different from drug research that is aiming at treating symptoms of lifestyle diseases, where a pharmacological interference in the human metabolism is required. Antiviral drugs are an in-between hybrid case. A virus is not a living organism, so per definition, you cannot kill it. A virus uses part of the cellular system to infect an organism, so it requires interference in the normal homeostasis of the host’s cells.

Coming now to the crux of this preface, why is this book so interesting? I mentioned already the importance of nature and the knowledge of our ancestors about the use of plants and other materials from their environment as medicines. Artemisinin was discovered as an antimalarial drug from Artemisia annua in the 1970s. The use of this plant to treat fever and malaria has its roots in ancient times and earliest record dates back to 200 BCE. Artemisia annua was already mentioned in a Chinese pharmacopeia in CE 340. In fact many of the therapies in Western medicine are derived from Eurasian medicinal plants. It thus makes sense that we analyze in depth the use of medicinal plants in different cultures and regions for treatments of infectious and parasitic diseases. The symptoms are clear of most infectious diseases, and also the effect of the treatment is easy to see, which makes that chances that our ancestors have found interesting plants are good. The present book is particularly suited to learn more about plants used in Asia as antiparasitic drug. The various pharmacological effects are mentioned for all the reported plants, as well as the type of compounds present in the plants, and if known, what are the active compounds. Gathering this information helps in discovering hotspots of chemodiversity that are of interest for further research on activity and eventually confirming activity by isolation and identification of the active compounds. So rather than screening all plants for activity, it makes more sense to first focus on what our ancestors already have achieved in terms of therapies. The book formulates briefly the scientific questions that need to be addressed.

In the coming years there will be a lot of interest for developing antiviral drugs, but this pandemic shows how vulnerable our healthcare system is. New pandemics will occur, and worse, pathogenic microorganisms developing resistance against our major antibiotics and antiparasitic drugs is another major threat. In fact malaria is a major cause of death in the world (about 435,000 per year worldwide). Climate change will result in further spreading of (tropical) diseases. Ticks spreading Lyme disease and encephalitis, mosquitos spreading malaria in new areas, are just some other examples that should make us aware of the need to really make a major effort in developing novel drugs for this sort of diseases. So finally the question why nature as source and not synthesis? In Nature, all kind of organisms use chemistry to defend themselves against other organisms; thus nature is the place to find compounds that are able to selectively kill microorganisms or parasites and are not very toxic for humans. Chemical synthesis can then be of help to produce these compounds and make new analogues that might be more effective.

In conclusion, this book is at the basis of drug development from Nature and from our ancestors knowledge. The development of novel drugs to treat infectious and parasitic diseases is a major challenge for academic institutions and public research institutes. On the one hand, it will help to identify the locally known treatments that can be used safely and sort out those that have no activity at all, or/and are potentially toxic. Clinical trials will be an important tool in this. For the materials that have shown interesting activities, one can do further research on the active compound(s), which may result in leads for further drug development, and which can be used for standardizing local preparations. This book will be of great help to select the most promising plants for further research that may lead to novel drugs for some major killing diseases. So I want to congratulate Dr. Christophe Wiart for his excellent contribution to enable the further exploration of Asian traditional knowledge on medicinal plants for developing novel drugs.

Robert Verpoorte, Natural Products Laboratory, IBL, Sylvius Laboratory, Leiden University, Leiden, The Netherlands

Foreword by Bruno David

It gives me great pleasure to introduce this Medicinal Plants in Asia and Pacific for Parasitic Infections: Botany, Ethnopharmacology, Molecular Basis, and Future Prospects—an essential contribution to our scientific knowledge of antiparasitic medicinal plants from that important part of the world. Dr. Wiart is a renowned expert in the phytochemistry of medicinal Asian-Pacific plants and already has a long list of excellent books to his name.

I have known Dr. Christophe Wiart for quite some time as I welcomed him at the end of his Pharmaceutical studies in 1995 for a 6-month internship at the Pierre Fabre Phytochemistry Research Laboratory near Toulouse (France). Christophe moved from his native Brittany to South-West France where Pierre Fabre has most of its facilities. Pierre Fabre Laboratories is a 60-year-old medium-sized French pharmaceutical company with 11,000 employees worldwide specialized in the development of plant-based ethical drugs and dermocosmetic products sold all over the world. Christophe impressed me so much and was so interested in the fields of phytochemistry and botany that I encouraged him to apply for a position of Pensiarah Pelawat at Malaya University (Petaling Jaya, Malaysia) as part of a collaboration with the French National Center of Scientific Research (CNRS). Since then, he has devoted his career and his life to the study of Malaysian plants and bioactive natural products from regions beyond South-East Asia.

Since biodiversity together with associated traditional knowledge are disappearing everywhere at an alarming rate, and particularly in the Asia-Pacific region, it is vital to inventory, value and preserve this precious ethnobotanical know-how. The book’s presentation, based on botanical taxonomy, is a very relevant approach as it is usefully correlated with the latest scientific information including pharmacology at molecular level.

Parasitic infections are a major socioeconomic issue in terms of public health. As the pharmaceutical industry is mainly profit-driven, scant attention is paid to research and development of new parasitic agents. Such research is important since resistance has appeared in parallel to the long and continuous use of old molecules. The most successful approach historically, and still valid in antiparasitic research, is the bioguided isolation of bioactive natural products from genetic resources followed by optimization of therapeutic properties by medicinal chemistry.

Interest in antiparasitic agents should be renewed at an international level in both academic and private research sectors as the global warming, tropicalization of temperate areas, the migrations that this generates, and the anthropic pressure on ecosystems are prone to the resurgence of old pathogens and emergence of new ones. The recent pandemic of SARS-CoV-2 is unfortunately a significant illustration of the recrudescence of parasitic infections in a fully globalized world. In addition to the obvious issue of global health in the tropical source countries of these diseases, globalization and rapid exchanges swiftly turn these pathologies into a mass phenomenon relevant for researchers and for the international pharmaceutical industry…

There is no doubt whatsoever that this new release, carefully composed and covering all aspects of the subject, will provide inspiration to anyone—from academic and industrial researchers to students, administrators, civil servants, conservationists, and NGOs—interested in antiparasitic plants. We wish Dr. Wiart’s new book all the success that it deserves.

Bruno David Dr. , DPharm, PhD, HDR

Ex-Director of Phytochemistry Research

Pierre Fabre Laboratories

Toulouse (France), June 2, 2020

Foreword by Maria de Lourdes Pereira and Veeranoot Nissapatorn

Parasites, a group of infectious agents, cause a significant devastating impact on humans worldwide. Since parasites play a critical role in public health concerns, these tropical diseases have been reported to increase morbidity and mortality in developing countries, particularly in Africa and Asia. As of now, the impact of parasites can be witnessed in the high rate of infection and disease burden in marginalized people (adults and children) across the world.

Parasites are divided into two main groups: (1) protozoa which are vectors, food and/or water-borne parasites. Vector-borne includes blood sucking parasites, like Plasmodium spp. causing malaria, Trypanosoma spp. causing trypanosomiasis, and Leishmania spp. cause leishmaniasis while food and/or water-borne consists of Toxoplasma gondii (toxoplasmosis), free-living amoebae (e.g., Acanthamoeba spp. and Naegleria fowleri), Giardia lamblia (giardiasis), Cryptosporidium parvum (cryptosporiasis), and Entamoeba histolytica (amoebiasis). While helminths are divided into three groups: nematodes (roundworms) mainly involve soil-transmitted helminths, cestodes (flatworms) are vertebrate parasites, with each species infecting a single definitive host or group of closely related host species, and trematodes (flukes) include internal parasite flatworms of molluscs and vertebrates, with a complex life cycle of at least two hosts. Parasite causes infectious, but some remain neglected diseases. Thus, malaria is considered the most common killer disease followed by leishmaniasis found in the tropics. Among children, parasitic diseases like giardiasis, cryptosporidiosis, amoebiasis, and soil-transmitted helminthiases are the main source of illnesses ranging from mild to moderate and severe conditions, depending on geographical areas, social contact, as well as behavioral practices.

Though drugs are currently available used in the form of single and/or combined therapy; however, the partial effective of treatment has been recorded in many parasitic diseases, such as cryptosporidiosis, toxoplasmosis, and acanthamoebiasis due to the thick wall of (oo)cysts. At the same time, drugs resistant has been constantly emerged and has caused a remarkable economic and public disaster, especially related to noneradicable diseases, as is always seen among all, like malaria and leishmaniasis. Furthermore, novel drugs are also in the pipeline to combat the long-standing parasitic diseases, like Chagas disease or sleeping sickness. Unfortunately, there is limited funding for discovery, development, and delivery (3D) of new therapeutic agents for parasitic diseases. In fact, chemotherapy is the major modality considered not only for the treatment, but also for the control of these parasitic diseases in the infected individuals, especially in areas with endemicity. There is no doubt that these modern drugs are periodically reported on the adverse side effects, low efficacy, high toxicity, long-course treatment regimen, induction of parasite resistance, and cost effectiveness. Therefore it is timely that an alternative therapy based on natural products is considered as the other opportunity to play its role in the therapeutic advance of antiparasitic diseases. Plant-based therapy has long been used as folklore and traditional healer as far back the human ancient civilization.

This book Medicinal Plants in Asia and Pacific for Parasitic Infections: Botany, Ethnopharmacology, Molecular Basis, and Future Prospects underscores several aspects on the use of medicinal plants in Asia-Pacific region that are useful in treating parasitic diseases. Prof. Christophe Wiart, an expert in vivid and enigmatic plants in Asia, is the author of several books related the medicinal plants used in Asia and the Pacific for antimicrobial activities. He has again penned down this book with all his vast knowledge and efforts to investigate how the effectiveness of plant-based therapy can help to reduce the suffering among affected individuals. This book covers all medicinal plants used for the treatment of parasitic infections in a geographical zone ranging from Turkey to Pacific islands. The plant is described, uses given local names, and pharmacological effects against amoeba, protozoa, nematodes, and helminths. Therefore it is highly appreciated the efforts of Prof. Wiart to compile this historical and scientific document in a systematic manner, which I am sure that this book will be useful for students, teachers, researchers, and all users of natural and traditional medicine to experience deeper to their therapeutic potentials.

Maria de Lourdes Pereira, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal

Veeranoot Nissapatorn, School of Allied Health Sciences, Walailak University, Thammarat, Thailand

Foreword by Vu Thi Thom

Mother nature is a source of plants that have been used by humans since time immemorial for food and medicines. Vietnam is a tropical country with plenty of parasitic infections such as malaria, fasciolosis, hookworm, Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Enterobius vermicularis, Strongyloides stercoralis, Fasciolopsis buski, Fasciola hepatica, Clonorchis sinensis, and Paragonimus westermani. It is found in community studies that more than 80% of stool samples contained at least one parasite species and the most common species were hookworm, Trichuris trichiura, and Ascaris lumbricoides. Vietnamese traditional medicine recommends plants with potentials of antiparasitic infection such as Diospyros mollis, Cyrtomium fortune, Mallotus philippinensis, Punica granatum, Areca catechu, Combretum quadrangulare, Chenopodium ambrosioides, Cucurbita pepo, Stemona tuberosa, Artemisia annua, Dichroa febrifuga, Tinospora crispa, and Aglaia merostele. This traditional knowledge has been mentioned in the present book written by Christophe Wiart who has dedicated his life to the study of medicinal plants in Asia. It is my belief that the present book will be an uncontournable reference and a precious tool for the discovery of lead antiparasitic compounds from medicinal plants in Asia-Pacific.

Vu Thi Thom, PhD, Department of Science & Technology, International Cooperation, Vietnam, Department of Basic Science in Medicine and Pharmacy, School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam

Preface

The intention behind the writing of this book is to offer a comprehensive set of interrelated botanical, ethnopharmacological, phytochemical, and molecular data to students, scholars, and researchers looking forward to discovering antiparasitic agents from the medicinal plants of Asia and the Pacific. This book is a simple and humble attempt to grasp and understand a very vast, yet fascinating, topic. It is becoming more and more apparent over the years that a logic exists behind pharmacological activities of medicinal plants. In simple words, the botanical classification of a plant is correlated with certain classes of natural products which themselves have the tendency to have either antiamoebic, antiplasmodial, antileishmanial, antitrypanosomal, or anthelminthic properties. The same is true for other activities including antimicrobial, anticancer, etc., but these are not treated here.

This book consists of chapters corresponding to the major angiosperm clades as per the Angiosperm Phylogeny Group classification III (Angiosperm Phylogeny Group, 2009. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG III. Botanical Journal of the Linnean Society, 161(2), pp. 105–121). Within each major clade, medicinal plants are presented according to the order and families they belong to. For each plant is given its scientific name, subfamily and tribe (if relevant), synonyms, local names, detailed botanical description (to allow the reader to recognize it), as well as medicinal uses, pharmacological properties, and commentaries. Thousands of carefully selected publications are cited and self-made botanical plates available. It is my dear hope that this book will contribute to further antiparasitic evaluation of medicinal plants leading to the isolation of drugs.

This book could not have been written without the moral support of my mother, my wife Shirley, and my dear friends Khoo Teng Jin, Thomas Maul, Mohammed Rahmatullah, Christopher Jesudason, Hazem Demrdash, Frederic Weber, Neil Russel Mennie, Blandine Louapre, Pierre Monnier, Alejandro Estudillo, and Marc Archer.

Christophe Wiart, Kuala Lumpur, Malaysia

March 31, 2020

Chapter 1

Antiparasitic Asian medicinal plants in the Clade Protomagnoliids

Abstract

Medicinal plants in Asia and the Pacific in the Clade Protomagnoliids are few and mainly used for the treatment of malaria and dysentery. Most of these plants have not been examined for their antiparasitic properties in vitro and in vivo. Plants in this Clade are sisters of all the other Clades of Angiosperms. They produce tannins, lignans, and sesquiterpenes.

Keywords

Protomagnoliids; Antiparasitic; Malaria; Dysentery

1.1 Order Nymphaeales Salisb ex Bercht. & J Presl. (1820)

1.1.1 Family Nymphaeaceae R. A. Salisbury (1805)

The family Nymphaeaceae consists of 5 genera and 75 species of ancient and often magnificent aquatic herbs. The leaves are simple, spiral, stipulate or exstipulate, floating, cordate, or peltate. The petiole is long and spongy. The flowers are showy and solitary. The calyx comprises four sepals. The corolla consists of up to 70 petals. The androecium includes up to hundreds stamens. The gynoecium includes up to 35 carpels free or partially united. The fruits are fleshy berries. Members of this family have the tendency to elaborate flavonols (kaempferol, quercetin, and myricetin), flavone-C-glycosides, ellagic, and gallic acid, gallo- and ellagitannins, proanthocyanidins, and unique series of sesquiterpene thioalkaloids.

1.1.1.1 Nymphaea pubescens Willd.

Synonyms: Nymphaea lotus var. pubescens (Willd.) Hook. f. & Thomson, Nymphaea rubra Roxb. ex Salisb.

Subfamily: Nymphaeoideae

Tribe: Nymphaeaceae

Common names: Hairy water lily; lal saluki, nal, raktahola, lal hapla, lal sapla (Bangladesh); apulbaha (India)

Botanical description: It is an aquatic herb developing from a rhizome. The leaves are simple, alternate, and exstipulate. The petiole is long and slender. The blade is floating, 14–28 cm×8–26 cm, orbicular, sagittate to cordate, hairy below, serrate at margin, and fleshy. The flowers are graceful, solitary, above the water surface, and 8–15 cm across. The calyx comprises four sepals, which are up to 7 cm long and oblong. The corolla comprises numerous petals, which are pure white or light pink, and up to about 7 cm long. The androecium comprises numerous stamens, which are up to 3.5 cm long. The gynoecium includes a syncarpous, many locular ovary developing 15–30 club-shaped stigmas. The fruit is a globose berry, which is about 5 cm in diameter, enclosed by persistent sepals, and containing numerous minute seeds.

Medicinal use: Dysentery (India)

Antiparasitic pharmacology: The plant has not apparently been subjected to any antiparasitic investigations. Its antidysenteric activity may be due, at least partially, to tannins.

1.2 Order Austrobaileyales Takht. ex Reveal (1992)

1.2.1 Family Schisandraceae Blume (1830)

The family Schisandraceae consists of 2 genera and about 40 species of aromatic woody climbers. The leaves are simple, alternate, entire, and without stipules. The flowers are small, solitary, axillary, regular, hypogynous, and with somewhat an elongate receptacle. The perianth consists of 5–24 tepals spirally arranged. The androecium includes up to 80 stamens, which are spirally arranged. The gynoecium comprises numerous carpels, which are free and spirally arranged. Each carpel contains two to five marginal ovules. Members of this family produce tannins and unusual series of dibenzocyclooctadiene lignans, as well as myricetin.

1.2.1.1 Schisandra chinensis (Turcz.) Baill.

Synonyms: Kadsura chinensis Turcz., Maximowiczia amurensis Rupr., Maximowiczia chinensis (Turcz.) Rupr., Schisandra chinensis var. leucocarpa P. H. Huang & L. H. Zhuo

Common names: Schisandra; wu wei zi (China); gomishi (Japan); nam o mi ja (Korea)

Botanical description: It is a graceful climber which grows up to a length of 4 m long. Latex present. The fresh leaves release a lemony smell when crushed. The petiole is 0.9–4 cm long and glabrous. The blade is elliptic, 4.5 cm×2.5 cm–8 cm×6.5 cm, membranaceous, and with four to six pairs of secondary nerves. The blade is cuneate at base, serrulate, and shortly acuminate at apex. The flowers are axillary and solitary. The perianth includes five to nine tepals, which are white, 0.6 cm×0.2 cm–1.1 cm×0.5 cm, and glabrous. The male flowers present five stamens. The female flowers include 14–40 carpels. The fruits are edible, pinkish red, globose, glossy, fleshy, 0.5 cm×0.4 cm–0.75 cm×0.6 cm, and grouped into a sort of grape.

Medicinal use: Dysentery (China)

Antiparasitic pharmacology: The plant has not apparently been subjected to any antiparasitic investigations. Its antidysenteric activity may be due, at least partially, to cytotoxic lignans (Chen et al., 2005).

1.3 Order Chloranthales R. Br (1835)

1.3.1 Family Chloranthaceae R. Brown ex Sims (1820)

The family Chloranthaceae comprises 5 genera and about 75 species of herbs. The leaves are simple, opposite, and stipulate. The inflorescences are axillary or terminal compound spikes, panicles, or heads. The perianth is very much reduced. The androecium consists of one to three fused stamens. The gynoecium comprises a single carpel. The stigma is sessile, the style is short, and the ovule is solitary and orthotropous. The fruits are small berries. Members of this family produce pentacyclic triterpenes such as betulinic acid as well as sesquiterpenes.

1.3.1.1 Chloranthus eliator R. Br. ex Link

Synonym: Chloranthus officinalis Bl.

Common names: Chloranthus; sigeh putih, sambau paya (Malaysia)

Botanical description: It is an aromatic herb, which grows to a height of 60 cm. The leaves are simple, opposite, and stipulate. The blade is serrate, elliptic, lanceolate, 15 cm×6 cm, acuminate, dark green, glossy, and membranaceous. The inflorescences are terminal 4-cm-long spikes. The flowers are tiny and white. The androecium consists of fused three stamens. The gynoecium consists of a one-celled ovary, a very short and thick style, and a subsessile and a truncate stigma. The fruits are fleshy, up to about 1 cm long, pulpy, and white berries.

Medicinal use: Malarial fever (Malaysia)

Antiparasitic pharmacology: The plant has not apparently been subjected to any antiplasmodial investigations. Ethanol extract of the plant was cytotoxic for P388 cells (Kambara et al., 2006). Are antiplasmodial sesquiterpenes present in this plant?

1.3.1.2 Chloranthus spicatus (Thunb.) Nak.

Synonyms: Chloranthus inconspicuus SW., Nigrina spicata Thunb.

Common name: Jin su lan (China)

Botanical description: It is an aromatic herb, which grows to a height of 60 cm. The stems are terete and glabrous. The leaves are simple, opposite, and stipulate. The petiole is up to about 1.8 cm long. The blade is elliptic, obovate, 5–11 cm×2.5–5 cm, cuneate at base, with up to eight pairs of secondary nerves, serrate at margin, acuminate, and acute at apex. The inflorescences are terminal spikes. The flowers are tiny and yellowish. The androecium consists of fused three stamens. The gynoecium includes an obovoid ovary. The fruits are berries.

Medicinal use: Malaria (China)

Antiparasitic pharmacology: The plant has not apparently been subjected to any antiplasmodial investigations. The plant produces series of lindenane sesquiterpenes lactones (Kim et al., 2011) which may, at least partially, be involved in the antimalarial properties.

References

Chen et al., 2005 Chen YG, Wu ZC, Gui SH, Lv YP, Liao XR, Halaweish F. Lignans from Schisandra hernyi with DNA cleaving activity and cytotoxic effect on leukemia and Hela cells in vitro. Fitoterapia. 2005;76(3–4):370–373.

Kambara et al., 2006 Kambara H, Yamada T, Tsujioka M, et al…. A study on medicinal plants from Malaysia focused on Acalypha siamensis Oliv ex Gage isolation and structure of a new tetraterpene, acalyphaser A. Chemistry & Biodiversity. 2006;3(12):1301–1306.

Kim et al., 2011 Kim SY, Kashiwada Y, Kawazoe K, et al. Spicachlorantins G-J, new lindenane sesquiterpenoid dimers from the roots of Chloranthus spicatus. Chemical and Pharmaceutical Bulletin. 2011;59(10):1281–1284.

Chapter 2

Antiparasitic Asian medicinal plants in the Clade Magnoliids

Abstract

Medicinal plants in Asia and the Pacific in the Clade Magnoliids are mainly used for the treatment of malaria and helminthiasis and to a lesser extend dysentery. Few of these plants have been examined for their antiparasitic properties both in vitro and in vivo. Plants in this Clade, are sisters to the Clade Monocots. They produce lignans, phenylpropanoids, diterpenes, sesquiterpenes, triterpenes, aristolactam and isoquinoline alkaloids, acetogenins.

Keywords

Magnoliids; Antiparasitic; Malaria; Helminthiasis

Magnoliids and Protomagnoliids are expansion of a common, yet unknown primitive archeomagnoliid ancestor.

2.1 Order Piperales Bercht. & Presl. (1820)

2.1.1 Family Aristolochiaceae A.L. de Jussieu (1789)

The family Aristolochiaceae consists of about 9 genera and 600 species of mostly poisonous climbers, herbs, or shrubs. The leaves are simple, alternate, and exstipulate. The flowers are solitary or cymose and terminal or axillary. The calyx is three-lobed and often very characteristically and gracefully pipe-shaped. The androecium includes 6–12 stamens. The gynoecium includes fused four to six carpels with three to six lobes. The fruits are capsules containing minute flat-winged seeds. Members of the family Aristolochiaceae produce a fascinating array of phenanthrene alkaloids (aristolactam-type alkaloids and aristolochic acids) and 4,5-dioxoaporphines (derived from aporphines), essential oils (monoterpenes and phenyl propanoids), amide alkaloids, and furanolignans.

2.1.1.1 Aristolochia bracteata Retz

Subfamily: Aristolochioideae

Tribe: Aristolochieae

Synonym: Aristolochia bracteolata Lam.

Common names: Bhringi, keeramar (India)

Botanical description: It is a prostrate, somewhat glaucous, and smelly herb. The stems are terete and striate. The leaves are simple, spiral, and exstipulate. The petiole is up to 3 cm long. The blade is ovate, sagittate wavy, 3–7 cm×3–7 cm, with up to three pairs of secondary nerves, and acute at apex. The flowers are solitary and axillary. The perianth is pipe-shaped, up to 4 cm long, greenish, and dark purple at apex. The androecium includes six stamens. The ovary is oblong and ribbed. The fruits are capsules which are ribbed, up to about 3 cm long, and containing numerous seeds which are flat, blackish, and up to 7 mm long.

Medicinal use: Roundworms (India)

Antiparasitic pharmacology: The plant is poisonous, which is a strong indication that it may hold potential effects against Ascaris lumbricoides. It produces aristolochic acid-I, aristolactam (Mix, Guinaudeau, & Shamma, 1982), nitrophenanthrene derivatives, magnoflorine, and (-)-N-acetyl-nornuciferine which are possibly involved in the medicinal use. Note that hexane extract of the whole plant inhibited the growth of Plasmodium falciparum (MRC-2) and P. falciparum (RKL-9) with the IC50 values of 15.9 and 22.1 µg/mL, respectively (Rana, Mehta, Desai, Highland, & George, 1979). Aristolochic acid is a DNA alkylating agent and as such potentially antiparasitic (Wink, 2012).

2.1.1.2 Aristolochia indica L.

Subfamily: Aristolochioideae

Tribe: Aristolochieae

Common names: Indian birthwort, Dutchman’s pipe; isharmul (Bangladesh); eeswaramooli (India)

Botanical description: It is a climber which grows to 5 m long. The stem is angled and glabrous. The leaves are simple, alternate, and exstipulate. The petiole is 1–1.5 cm long. The blade is oblong, somewhat cordate at base, acuminate at apex, dull dark green, 5–10 cm×2–4 cm, and fleshy. The inflorescences are axillary racemes. The perianth is tubular, greenish, curved, globose at base, about 1 cm in diameter, and develops a tube which reaches 2.5 cm long. The androecium includes six stamens in a column. The ovary is cylindrical and ribbed. The fruits are pendulous and dehiscent capsules which are six-valved and containing deltoid seeds.

Medicinal use: Malaria (Myanmar)

Antiparasitic pharmacology: Methanol extract of flowers had no activity against P. falciparum (3D7) (Kamaraj, Kaushik, Mohanakrishnan, et al., 2012). The plant has been assessed for its anthelminthic properties (Mini, Ventkateswaran, Gomathinayagam, Selvasubramanian, & Bijargi, 2013). The antiparasitic activity is, at least partially, due to aristolochic acids (Mix et al., 1982) which are cytotoxic (Wink, 2012). Further, the plant produces isoquinoline alkaloids (Shamma & Guinaudeau, 1985). Note that isoquinoline alkaloids, which are not uncommon in the genus Aristolochia L., have the tendency to inhibit the survival of P. falciparum (Wright et al., 2000).

2.1.1.3 Aristolochia debilis Siebold & Zucc.

Subfamily: Aristolochioideae

Tribe: Aristolochieae

Synonyms: Aristolochia longa Thunb., Aristolochia recurvilabra Hance, Aristolochia sinarum Lindl.

Common names: Ma dou ling, ch’ing-mu-hsiang, pai-shu, ma dou ling, sam pai liang yin yao (China)

Botanical description: It is a graceful climber. The stem is terete, smooth, and glabrous. The leaves are simple, alternate, and exstipulate. The petiole is up to 2 cm long. The blade is ovate, oblong, or sagittate, 3–6 cm×1.5–3.5 cm, with two to three pairs of secondary nerves, acute to round at apex, and membranaceous. The inflorescences are axillary and solitary on a peduncle, which is up to about 1.5 cm long. The perianth is tubular, beautiful, greenish yellow, curved, globose at base, and about 1 cm in diameter and develops a tube which reaches 2.5 cm long ending into a dark purple throat with a lobe, which is up to about 3 cm long. The androecium includes six stamens in a column. The ovary is cylindrical and ribbed. The fruits are pendulous and dehiscent capsules, which are up to about 6.5 cm long and containing deltoid and 4mm-long seeds.

Medicinal use: Dysentery (China)

Antiparasitic pharmacology: The plant produces series of aristolochic acids as well as aristolactam (Mix et al., 1982) which, at least partially, may contribute to the antidysenteric use. Also found in this plant is a sesquiterpene ketone (Nishida & Kumazawa, 1973) as well as the isoquinoline alkaloid magnoflorine (Li & Wang, 2014). Note that isoquinoline alkaloids have the tendency to inhibit the survival of amoebas, for instance, magnoflorine inhibited the growth of Entamoeba histolytica with the IC50 value of 111 µM (Wright et al., 2000).

2.1.2 Family Piperaceae Giseke (1792)

The family Piperaceae comprises 10 genera and about 2000 species of herbs, climbers, or treelets. The stems are smooth terete, articulate, and often swollen at nodes. The leaves are simple, alternate, and stipulate or not. The inflorescence are axillary spikes. The flowers are tiny and without perianth. The androecium comprises 1–10 stamens. The gynoecium comprises a unilocular ovary containing a single orthotropous ovule. The fruits are capsular or drupaceous. Members of this family produce isoquinoline and piperidine alkaloids, essential oils, as well as styryl lactones.

2.1.2.1 Piper betle L.

Synonym: Chavica betle Miq.

Common names: Betel pepper, betel vine; lou ye (China); pan (Bangladesh); kun ya (Myanmar); plu (Thai); trâu luong (Vietnam)

Botanical description: It is a climber which grows up to about 3 m long. The stems are articulate, swollen, at nodes, and woody. The leaves are simple, spiral, and stipulate. The petiole is 5 mm long, channeled, and pubescent. The blade is 10 cm×6 cm–9.5 cm×5 cm, ovate to ovate-oblong, light green below, glossy above, with two to three pairs of secondary nerves, cordate and not uncommonly asymmetrical at base, and acuminate at apex. The androecium includes two stamens. The gynoecium develops four to five stigmas. The inflorescences are axillary and cylindrical whitish spikes, which are up to about 5.5 cm long. The fruits are globose drupes, which are about 3 mm diameter and greenish.

Medicinal use: Malaria (China)

Antiparasitic pharmacology: Essential oil of the plant evoked anthelminthic activity (Ali & Mehta, 1970). The phenylpropanoids chavicol, allylpyrocatechol, chavibetol, and chavibetol acetate isolated from the leaves abrogated the survival of Caenorhabditis elegans (Evans, Bowers, & Funk, 1984). Chloroform extract of leaves inhibited the survival of E. histolytica (strain HTH-56:MUTM) with the IC50 value of 91.1 µg/mL (Sawangjaroen et al., 2006). Ethanol extract of leaves inhibited Leishmania donovani promastigotes with the IC50 value of 9.8 µg/mL (Sarkar et al., 2008). Methanol extract of leaves given orally to mice (BALB/c) at a dose of 100 mg/kg/day for 14 days evoked a reduction of human lymphatic filarid Brugia malayi (Singh, Shakya, et al., 2009). Methanol extract of leaves given orally at a dose of 400 mg/day for 4 days to mice infected with Plasmodium berghei decreased parasitemia from 5.1 to 0.9% (Al-Adhroey, Nor, Al-Mekhlafi, Amran, & Mahmud, 2011). Note that the fruits contain about 0.06 mg/g of piperine (Bao, Ochir, Sun, Borjihan, & Yamagishi, 2014), which has antiplasmodial properties (Thiengsusuk, Muhamad, Chaijaroenkul, & Na-Bangchang, 2018). Ethanol extract of fruits of P. betle inhibited Neospora caninum (NC1) growth at the IC50 value of 22.1 μg/mL (Leesombun, Boonmasawai, & Nishikawa, 2017). This extract given intraperitoneally at 400 mg/kg/day for 7 days evoked an 83.3% survival rate of BALB/c mice infected with N. caninum (NC1) (Leesombun et al., 2017). Aqueous extract of leaves given orally to Mongolian gerbils at the dose of 40 mg/100 g body weight, twice a day, for 9 days evoked a significant decline in Giardia intestinalis cyst (Pecková et al., 2018).

Piper betle L.

Ethanol extract of fruits inhibited the survival of Toxoplasma gondii (RH-GFP) with the IC50 value of 23.2 µg/mL (Leesombun, Boonmasawai, Shimoda, & Nishikawa, 2016). This extract given to C57BL/6 mice experimentally infected with T. gondii (PLK strain) for 7 days at a dose of 400 mg/kg/day intraperitoneally evoked a 100% survival rate (Leesombun et al., 2016).

Commentary: This plant may hold potentials for the development of antimalarial and antiamoebic phytomedications. Clinical trials are warranted.

2.1.2.2 Piper chaba Hunter

Synonyms: Chavica officinarum Miquel, Piper officinarum (Miquel) DC., Piper retrofractum Vahl.

Common names: Jia bi ba (China); chavika, chevuyam; chavana (India)

Botanical description: It is a climber that grows wild in India, Indonesia, Malaysia, Philippines, Thailand, and Vietnam. The stems are terete and swollen at nodes. The leaves are simple, alternate, and stipulate. The petiole is 0.5–1 cm long and sheathed at base. The blade is dark green, glossy, broadly elliptic, 8–15 cm×3–8 cm, papery, cordate and asymmetrical at base, acute at apex, and with 9–12 pairs of longitudinal secondary nerves. The inflorescence is a conical spike, which is 5 cm long and opposite the leaves. The fruits are drupaceous.

Medicinal use: Worms (India)

Antiparasitic pharmacology: Ethanolic extract of fruits inhibited the growth of P. falciparum (K1) and P. falciparum (3D7) with the IC50 values of 5.3 and 4.1 µg/mL, respectively (Thiengsusuk, Chaijaroenkul, & Na-Bangchang, 2013). Piperine isolated from the fruits inhibited the survival of P. falciparum (3D7) and P. falciparum (K1) with the IC50 values of 111.5 and 59 µg/mL, respectively (Thiengsusuk et al., 2018).

Piper chaba Hunter

Methylene chloride extract of fruits inhibited the survival of Schistosoma mansoni with the IC50 value of 0.7 µg/mL (Atjanasuppat et al., 2009). Chloroform extract of fruits inhibited the growth of E. histolytica (HM1:IMSS) with the IC50 of 71.4 µg/mL (Sawangjaroen et al., 2006) and Giardia intestinalis with the IC50 of 250 µg/mL (Sawangjaroen et al., 2005).

Commentary: According to Philippe et al. (2005) and Pink, Hudson, Mouriès, and Bendig (2005) the antiplasmodial activity of plant extract is classified as follow: highly active at IC50<5 μg/mL, promising at 5–15 μg/mL, low at 15–50 μg/mL, and inactive at >50 μg/mL. What is the antiplasmodial mode of action of piperine? Preclinical trials for the development of antiplasmodial or anti-schistosomal phytomedications are warranted.

2.1.2.3 Piper cubeba L. f.

Common names: Java pepper, cubebs, tailed pepper; lada berekur (Malaysia); tieu (Vietnam); thippli (India); sayo pin. (Myanmar)

Botanical description: It is a climbing shrub which grows to a length of 1 m in tropical Asia. The plant is native to Indonesia and Malaysia. The stems are glabrous, articulate, and succulent. The leaves are simple, alternate, and stipulate. The petiole is about 1.5 cm long, velvety, and channeled. The blade is broadly elliptic, velvety below, membranaceous, and 11 cm×6.4 cm–8.5 cm×4.8 cm. The margin is wavy, the apex of the blade is acuminate, and the base is asymmetrical and cordate. The blade shows five to seven pairs of secondary nerves which are raised on both surface. The inflorescences are 4 cm×3 mm spikes.

Medicinal uses: Dysentery (Indonesia); malaria (Myanmar)

Antiparasitic pharmacology: The dibenzylbutyrolactone lignan cubebin from the fruits given orally to BALB/c mice at a dose of 50 mg/kg afforded protection against Trypanosoma cruzi (B5 CL Brener clone) (Esperandim da Silva Ferreira, Rezende, Cunha et al., 2013). Essential oil of fruits inhibited the survival of T. cruzi promastigotes with the IC50 of 45.5 µg/mL and amastigotes, with the IC50 value of 87.9 µg/mL (Esperandim da Silva Ferreira, Rezende, Magalhães, et al., 2013). Cubebin, dihydrocubebin, and hinokinin isolated from the fruits exhibited ovicidal activities against fecal isolates of both Haemonchus contortus and Trichostrongylus sp. with the EC50 values of 150, 186.7, and 68.3 μg/mL, respectively (de Paula Carlis et al., 2019). Hinokinin, cubebin, yatein, and 5-methoxyyatein from the fruits at the concentration of 50 µM inhibited the motility of S. mansoni by 75%, 75%, 75%, and 100%, respectively (Parreira et al., 2019). Essential oil of fruits at 50 µg/mL inhibited the survival of S. mansoni (Magalhães et al., 2012). The fruits could be used as phytomedication against trypanosomiasis and schistosomiasis. What is the antiparasitic mode of action of cubebin?

Piper cubeba L. f.

2.1.2.4 Piper longum L.

Synonym: Chavica roxburghii Miquel.

Common names: Indian long pepper; bi ba (China); peik chin, nga yok kaung, tanwhite (Myanmar); chapala, argadi (India)

Botanical description: It is climber that grows wild in India, Malaysia, Nepal, Sri Lanka, and Vietnam. The stems are flexuous, pubescent, and terete. The leaves are simple, alternate, and exstipulate. The petiole is grooved, of variable length, and can reach 10 cm long. The blade is ovate, 6–12 cm×3–12 cm, papery, the base is cordate and asymmetrical, the apex is acuminate, and two to three pairs of secondary nerves arising from the base are observable. The inflorescence is a cylindrical and slightly curved spike, which is 1.5–5 cm long, and opposite to the leaves. The fruits are drupaceous, globose, and 2 mm in diameter.

Medicinal uses: Malaria and worms (Myanmar)

Antiparasitic pharmacology: The fruit contain up to 33.2 mg/g of piperine (Bao et al., 2014) which is antiplasmodial (Thiengsusuk et al., 2018). Essential oil of the fruit elicited a paralytic effect on A. lumbricoides (more potently than piperazine) (D’Cruz, Nimbkar, & Kokate, 1980). The essential oil at 3 mg/mL paralyzed Fasciola gigantica (Singh, Kumar, Tandan, & Mishra, 2009). Ethanol extract of fruits at 3 mg/mL paralyzed Gigantocotyle explanatum (Singh, Kumar, & Tandan, 2008). At an oral dose of 1000 mg/kg/day for 5 days, the methanol extract of fruit exhibited the curative rate of 100%, against E. histolytica in Swiss albino mice (Sawangjaroen, Sawangjaroen, & Poonpanang, 2004). Clinical examination of this plant against E. histolytica is warranted.

Piper longum L.

2.1.2.5 Piper nigrum L.

Common names: Black pepper, white pepper; hu jiao (China); lada hitam, lada puteh (Malaysia); kurumilagu (India); kalomorich (Bangladesh); burakku (Japan); phrik thai (Thailand); trieu (Vietnam)

Botanical description: It is a climber native to India, which is stout and rooting at nodes. The stems are terete, smooth, and articulated. The leaves are simple, spiral, and exstipulate. The petiole is about 1.5 cm long. The blade is ovate to elliptic, glossy, coriaceous, 4–6 cm×9–11 cm, acuminate at apex, rounded to oblique at base, and with three pairs of longitudinal secondary nerves. The inflorescences are spikes opposite to the leaves and up to about 13 cm long. The androecium includes two stamens. The gynoecium includes an ovary which is ovoid and three stigma. The fruits are globose drupes which are about 8 mm in diameter, yellowish-red, glossy, and sessile on a pendulous infructescence which is about 10 cm long.

Medicinal uses: Dysentery (Bangladesh); malaria (India)

Antiparasitic pharmacology: Ethyl acetate extract of seeds inhibited the survival of chloroquine-sensitive P. falciparum (3D7) and chloroquine-resistant P. faciparum (INDO) with the IC50 values of 12.5 and 12 μg/mL, respectively (Kamaraj, Kaushik, Rahuman, et al., 2012). Methanol extract of fruit inhibited schizont maturation of P. falciparum (chloroquine-sensitive strain FCK2) and P. falciparum (chloroquine-resistant strain INDO) with the IC50 values of 39.5 and 41.2 µg/mL, respectively (Biradar, Bodupally, & Padh, 2019). Note that the fruits contain about 42.6 mg/g of piperine (Bao et al., 2014) which is antiplasmodial (Thiengsusuk et al., 2018). Piperine acts synergistically with meglumine antimoniate against Leishmania infantum (strain IOC/L0579) (Vieira-Araújo et al., 2018). Essential oil at 50 mg/mL abrogated the survival of Acanthamoeba sp. (Sanguan et al., 2018). The IC50 values of piperine against Leishmania amazonensis promastigotes and amastigotes were 14.2 and 28 μM, respectively (Ferreira et al., 2011). Piperine inhibited the survival of L. donovani amastigotes and amastigotes with the IC50 values of 0.7 and 2.5 mM, respectively (Singh et al., 2010). Aqueous extract of fruits at the concentration of 0.1 mg/mL decreased the growth of Blastocystis hominis (Yakoob et al., 2011).

2.1.3 Family Saururaceae Martynov (1820)

The family Saururaceae consists of four genera and seven species of beautiful rhizomatous, aromatic, and often stoloniferous herbs which at first glance look like Monocots. The leaves are simple, alternate, and stipulate. The stipules form a sheath. The inflorescences are spikes or racemes. Flowers in this family do not have a perianth. The androecium includes three to eight stamens. The gynoecium includes two to four carpels and free styles. The fruits are schizocarps or apically dehiscent capsules containing one to many seeds. Members of this family elaborate lignans and flavonoids.

2.1.3.1 Houttuynia cordata Thunb.

Common names: Chameleon plant, heartleaf, bishop’s weed; ji cai (China); dokudami (Japan); yak mo mil (Korea)

Synonyms: Polypara cochinchinensis Lour., Polypara cordata Kuntze

Botanical description: It is a graceful herb which grows up to a length of 60 cm long from a creeping, thin, and edible rhizome. The stems are stoloniferous. The leaves are simple, alternate, and stipulate. The stipules are sheathing and 1–2.5 cm long. The fresh leaves have a peppery scent when crushed. The petiole is up to about 3.5 cm long. The blade is edible, broadly ovate, 2.5 cm×6 cm, papery, densely glandular, purplish below, cordate at base, and shortly acuminate at apex. The blade shows five to seven pairs of secondary nerves. The inflorescence is a spike which is somewhat cylindrical, up to 4 cm long, and presenting at base 4 petal-like bracts, which are pure white, about 1.5 cm long, and obovate. The flowers are minute. The fruit is a capsule which is about 0.3 cm long and presenting at apex vestige of styles.

Medicinal uses: Worms (China); dysentery (Cambodia, Laos, and Vietnam)

Antiparasitic pharmacology: Methanol extract of leaves given to Wistar rats at the dose of 800 mg/kg/day orally decreased the count of eggs of Hymenolepis diminuta per gram of feces by 57% (Yadav, 2011). The plant is known to produce aristolactams, isoquinolines such as cepharadione B and norcepharadione B, flavonoid glycosides, phytosterols, and triterpenes (Chou, Su, Ku, & Wu, 2009). One one could suggest that cytotoxic aristolactams and isoquinolines may, at least partially, account for the anthelminthic and antiamoebic use of this plant. Further investigations are needed.

Commentary: One could have some interest to look into the potential antiamoebic activities of this plant.

2.1.3.2 Saururus chinensis (Lour.) Baill.

Synonyms: Saururopsis chinensis (Lour.) Turcz., Saururopsis cumingii C. DC., Saururus cernuus Thunb., Saururus loureiri Decne., Spathium chinense Lour.

Common names: Chinese lizard’s tail; san bai cao (China); hangesho (Japan); sam baek cho (Korea)

Botanical description: It is a beautiful herb (with somewhat a Monocot appearance) which grows to about 1 m tall from a creeping, white, and thick rhizome. The stems are creeping at base and erect at apex. The stipular sheath is 0.2–1 cm long and slightly clasping. The petiole is 1–3 cm long and glabrous. The leaves are simple and alternate. The blade is ovate, 10 cm×5 cm–20 cm×10 cm, papery, densely glandular, cordate at base, and acute at apex. The blade shows five to seven pairs of secondary nerves and a whitish patch at base. The inflorescence is an elongated, curved, 12–20 cm long, tail-like, and whitish spike. The flowers are minute and innumerable. The fruits are subglobose, about 3 mm in diameter, and tuberculate.

Medicinal uses: Malaria and worms (China)

Antiparasitic pharmacology: The plant contains series of lignans such as sauchinone, saucernetin-7, saucerneol D, 2′-hydroxydihydroguaiaretic acid, machilin D, and manassantin A (Sung, Lee, Cho, Kim, & Kim, 2000), as well as unique series of cyclic diterpenes (Gao et al., 2017). Saucerneol D is a potent inhibitor of topoisomerases I and II (Lee et al., 2009). Topoisomerases I and II (Wink, 2012) may provide suitable target for antimalarial, trypanocidal (Figgitt, Denny, Chavalitshewinkoon, Wilairat, & Ralph, 1992), antileishmanial (Ray et al., 1996), and anthelminthic drugs. Threo, threo-manassantin A and threo,erythro-manassantin A inhibited the survival of L. amazonensis promastigotes (EC50=35.4 and 17.6 μM, respectively) and amastigotes (EC50=20.4 and 16 µM, respectively), and this more potently than miltefosine (EC50=28.7 μM) (Brito et al., 2019). Saucerneol D, manassantin A, and manassantin B, inhibited Trypanosoma brucei (strain 427) with the IC50 values of 5.6, 5.4, and 3.5 µM, respectively (Sun et al., 2016).

Commentary: One could have some interest in assessing the antiplasmodial properties of saucerneol D, manassantin A, and manassantin B. Should such lignans be non-toxic in rodent, clinical trials as antitrypanosomal or antimalarial agents would be warranted.

2.2 Order Laurales Juss. ex Bercht. & Presl. (1820)

2.2.1 Family Lauraceae A.L de Jussieu (1789)

The family Lauraceae consists of about 50 genera and 2000 species of graceful trees, shrubs, climbers, and herbs. The leaves are simple, opposite, spiral, whorled or alternate, and without stipules. The inflorescences are racemes or clusters. The flowers are actinomorphic, small, and with a perianth that includes two series of three tepals. The androecium comprises about 12 stamens with characteristic poricidal anthers. The gynoecium consists of a carpel forming a unilocular ovary. The fruits are drupes or berries characteristically seated on the persistent perianths. Plants in this family produce isoquinoline alkaloids (benzylisoquinoline and oxoaporphine alkaloids), phenylpropanoids (safrole and cinnamic acid), essential oils, lignans, and terpenes (mono- and sesquiterpenes).

2.2.1.1 Cassytha filiformis L.

Subfamily: Cassythoideae

Synonyms: Calodium cochinchinense Lour., Cassytha americana Nees, Cassytha aphylla (Forssk.) Raeusch., Cassytha brasiliensis Mart. ex Nees, Cassytha cuscutiformis F. Muell., Cassytha dissitiflora Meisn., Cassytha guineensis Schumach. & Thonn., Cassytha paradoxae Proctor, Cassytha zeylanica Gaertn., Ocotea cuneata (Griseb.) M. Gómez, Volutella aphylla Forssk.

Common names: Dodder-laurel, snotty-gobble, devil’ gut, love-vine; wu gen teng (China); chemar batu (Malaysia)

Botanical description: It is a slender tropical parasitic plant which scrambles over bushes and trees along the seashores and roadsides of Asia-Pacific. The stems are pale green, succulent, terete, soft, thread-shaped, and without leaves. The flowers are 2–3 mm long, white, yellowish, and globose. The perianth consists of six tepals, the three outer ones smaller than the inner ones. The androecium includes nine or six stamens, in three whorls. The ovary is superior. The fruits are berries which are about 5 mm diameter and enclosed in an enlarged, succulent, pale, and persistent perianth.

Medicinal use: Worms (Indonesia, India)

Antiparasitic pharmacology: The plant accumulates series of poisonous isoquinoline alkaloids including cassythic acid, cassythine, neolitsine, and dicentrine which relaxed precontracted rat aortic preparations with IC50 values ranging from 0.08 and 2.4 µM (Tsai, Wang, & Lin, 2008) and are cytotoxic. Note that dicentrine inhibited the larval mobility of H. contortus with the EC90 value of 6.3 μg/mL. In mice, administration of dicentrine orally at a dose of 25 mg/kg resulted in 67% reduction of Heligmosomoides polygyrus counts (Ayers et al., 2007). Alkaloid fraction inhibited T. brucei brucei (strain 427) with the IC50 value of 2.2 µg/mL (Hoet et al., 2004). From this extract, the aporphine alkaloids actinodaphnine, dicentrine, and cassythine inhibited the survival of T. brucei brucei (strain 427) with the IC50 values of 3.2, 14.6, and 6 µg/mL, respectively via inhibition of topoisomerase I (Hoet et al., 2004).

Commentary: Natural products with anthelmintic activity act on (1) membrane ion channels (nicotinic receptors, GABA receptors, and calcium channels) or (2) non-ion channels (β-tubulin, malate metabolism, phosphoglycerate mutase and kinase, and arachidonic metabolism) (Martin, Robertson, & Bjorn, 1997). One could therefore draw the inference that isoquinolines produced by this plant may act, at least partially, via ion channels inhibition. It also implies that natural products with agonistic or antagonistic effects on GABA, acetylcholine, adrenaline, or serotonin have potentials as anthelminthics. Nicotinic acetylcholine receptor agonist used as anthelminthics are levamisole and pyrantel (Keiser & Utzinger, 2008).

Cassytha filiformis L.

2.2.1.2 Cinnamomum bejolghota (Buch.-Ham.) Sweet

Subfamily: Lauroideae

Tribe: Cinnamomeae

Synonyms: Cinnamomum obtusifolium (Roxb.) Nees, Laurus bejolghota Buch.-Ham., Laurus obtusifolia Roxb.

Common names: Wild cassia; dun ye gui (China); na-lin-gyaw, maza, nakzik, hman-thein, lulingyaw, tauku-ywe, thit-kyabo (Myanmar)

Botanical description: It is a handsome tree which grows in India, Nepal, Bangladesh, Myanmar, Thailand, and Vietnam to a height of 25 m. The stems are terete or angular. The leaves are simple, exstipulate, and subopposite. The petiole is stout and up to about 1.5 cm long. The blade is elliptic to oblong, aromatic, somewhat coriaceous, with a pair of secondary nerves, glaucous below, 12–30 cm×4–9 cm, attenuate at base, and obtuse at apex. The inflorescences are axillary panicles which are up to 16 cm long. The flowers are white to pale yellowish. The perianth produces six lobes which are oblong and about 5 mm long. The androecium includes nine stamens. The ovary is oblong and minute. The fruit is oblong, 1.3 cm×0.8 cm, and seated on a cup-shaped somewhat purplish persistent perianth.

Medicinal uses: Malaria and worms (Myanmar)

Antiparasitic pharmacology: Aqueous extract of bark at 100 mg/mL evoked the death of Pheretima posthuma after 74.7 minutes (Gogoi, Kakoti, Bora, & Yadav, 2014). Note that essential oil of bark shelters principally 1,8-cineole, α-terpineol, and linalool (Choudhury, Ahmed, Barthel, & Leclercq, 1998). 1,8-Cineole has affinity for GABA receptor (Tong & Coats, 2012) and as such has potentials as anthelminthic. Further, 1,8-cineole inhibited the growth and development of chloroquine-resistant and chloroquine-sensitive strains of P. falciparum (Su, King, Woodrow, McFadden, & Gleadow, 2008). Linalool inhibited the survival of P. falciparum (NF54, clone 3D7) with the IC50 value of 0.2 mM by interfering with parasitic isoprenoid metabolism (Goulart et al., 2004). Linalool inhibited the growth of H. contortus with a LC50 value of 290 µg/mL (Katiki et al., 2014).

Commentary: The principle(s) responsible for the antimalarial and antiplasmodial properties of the plant remain to be isolated and their mechanisms understood.

2.2.1.3 Cinnamomum eugenoliferum Kosterm.

Subfamily: Lauroideae

Tribe: Cinnamomeae

Synonyms: Cinnamomum gigaphyllum Kosterm., Cinnamomum hentyi Kosterm.

Common names: Insan, timipikiri (Papua New Guinea)

Botanical description: It is buttressed tree which grows on the seashore and forests of Papua New Guinea to a height of 40 m tall. The bark is smooth, lenticelled, and aromatic. The stems are terete or angular. The leaves are simple, exstipulate, and subopposite. The petiole is stout and up to about 1.8 cm long. The blade is elliptic to oblong, aromatic, somewhat coriaceous, with a pair of secondary nerves, glaucous below, 10–35 cm×5–20 cm, rounded at base, and obtuse at apex. The inflorescences are axillary panicles which are up to 8 cm long. The flowers are white to pale yellowish. The perianth produces six lobes which are hairy within. The androecium includes nine stamens. The ovary is minute. The fruits are ellipsoid, up to about 1.5 cm long, seated on funnel-shaped persistent perianths.

Medicinal use: Dysentery (Papua New Guinea)

Antiparasitic pharmacology: The plant has apparently not been studied for its possible antiamoebic activities. One could draw an inference that essential oil components may have some activity against E. histolytica.

2.2.1.4 Cinnamomum javanicum Blume

Subfamily: Lauroideae

Tribe: Cinnamomeae

Synonyms: Cinnamomum sulphuratum C. Nees, Cinnamomum neglectum Blume

Common names: Phua wa rou gui (China); kayu tuha, huru gading, sintok lancang (Indonesia); medang wangi, medang teja, kulit lawang kechil (Malaysia)

Botanical description: It is a tree which grows up to 25 m tall in the rainforest of Malaysia, Indonesia, Vietnam, and South China. The stem is angled and hairy at apex. The leaves are simple, opposite, and exstipulate. The petiole is stout, up to 1.2 cm long, and hairy. The blade is elliptic to ovate, 11–22 cm×5–6.5 cm, hairy below, with one pair of secondary nerves, round at base, and caudate at apex.