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Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine

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Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine molecules Review Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine Letizia Polito †, Massimo Bortolotti †, Stefania Maiello, Maria Giulia Battelli * and Andrea Bolognesi Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy; [email protected] (L.P.); [email protected] (M.B.); [email protected] (S.M.); [email protected] (A.B.) * Correspondence: [email protected]; Tel.: +39-051-209-4700; Fax: +39-051-209-4746 † These authors contributed equally to this work. Academic Editor: Els Van Damme Received: 3 October 2016; Accepted: 9 November 2016; Published: 18 November 2016 Abstract: Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the position occupied in traditional medicine by plants from which RIPs have been isolated. The overview starts from the antique age of the Mediterranean area with ancient Egypt, followed by the Greek and Roman classic period. Then, the ancient oriental civilizations of China and India are evaluated. More recently, Unani medicine and European folk medicine are examined. Finally, the African and American folk medicines are taken into consideration. In conclusion, a list of RIP-expressing plants, which have been used in folk medicine, is provided with the geographical distribution and the prescriptions that are recommended by traditional healers. Some final considerations are provided on the present utilization of such herbal treatments, both in developing and developed countries, often in the absence of scientific validation. The most promising prospect for the medicinal use of RIP-expressing plants is the conjugation of purified RIPs to antibodies that recognise tumour antigens for cancer therapy. Keywords: ribosome-inactivating proteins; plant toxins; anticancer drugs; folk medicine; ethnopharmacology; ancient Egypt medicine; classic age medicine; traditional Chinese medicine; Ayurveda medicine; Unani medicine 1. Introduction Toxic substances, coming from either the mineral, vegetal or animal kingdom, have been frequently used for medical purposes since the earliest times. In particular, traditional medicine is based primarily on the use of plants, often taking advantage of those that are known for their toxicity, as a source of remedies for diseases that have always plagued humankind throughout the world. In addition, the knowledge of adverse events that arise from the consumption of some part of such toxic plants has its roots in very ancient time periods. This review is dedicated to the role in traditional medicine played by plants from which ribosome-inactivating proteins (RIPs) have been extracted. RIPs are enzymes that depurinate nucleic acids and are widely distributed in the plant kingdom and beyond, whose biological role is yet to be elucidated. RIPs can be divided into two main categories: type 1, consisting of a single enzymatically active polypeptide, and type 2, consisting of a polypeptide that is similar to the type 1 RIP and has a lectin chain that is held together by a disulfide bridge (reviewed in [1]). Molecules 2016, 21, 1560; doi:10.3390/molecules21111560 www.mdpi.com/journal/molecules Molecules 2016, 21, 1560 2 of 27 Table 1. Ethno-pharmacological uses of RIP-expressing plants. Plant Species, (Common Name), Geographic Area Therapeutic Application Plant Tissue(s) References Family and RIP Found Used as nervine, stomachic stimulant Abelmoschus esculentus (L.) Moench (okra) Africa Fruits, seeds [2,3] Malvaceae Used for the treatment of gastritis, spasms abelesculin India Used for the treatment of anaemia, cancer, diabetes, gastric ulcer, gonorrhoea, urethrorrhoea Fruits [4–6] Used for the treatment of asthma, bronchitis, cold, complaints, convulsion, cough, epilepsy, fever, Africa Leaves, roots, stems [7–12] malaria, sexual asthenia, stomach cramps, tetanus, tuberculosis, urinary schistosomiasis, wounds Abrus precatorius L. (jequirity) Used as abortifacient, analgesic, anthelminthic, anti-bacterial, anti-emetic, anti-pruritic, aphrodisiac, expectorant, hair growth-promoting, purgative, tonic Fabaceae Fruits, leaves, India, Southeast Asia Used for the treatment of amenorrhea, cancer, conjunctivitis, diabetes, diarrhoea, female fertility, [9,13–17] abrins roots, seeds fever, inflammation, intestinal problems, leucorrhoea, malaria, menstrual disorders, migraine, muscular skeletal disorders, postpartum complications, spasms, tetanus, urticaria Caribbean Used for the treatment of cold, consumption, cough, fever Leaves [18,19] Adenia digitata (Harv.) Engl. (modecca flower) South Africa Used for the treatment of knee swellings, leprosy, skin ailment, swollen legs, ulcers Roots [20] Passifloraceae modeccins Adenia volkensii Harms (kilyambiti plant) Used for the treatment of bronchitis, coughs, colds, fever, pneumonia, purgative, Passifloraceae Africa Leaves, rootstock [20] stomach ache, swelling volkensin Agrostemma githago L. (corncockle) Caryophyllaceae Mediterranean area Used for the treatment of skin outgrowths (warts, tumours) Seeds [21] agrostins Amaranthus viridis L. (amarant) Used as diuretic, laxative Leaves, roots, Amaranthaceae India, Pakistan [22] Used for the treatment of dysentery, inflammation, scorpion sting, snakebites whole plant amaranthin Aralia elata (Miq.) Seem. Used as anti-arrhythmic, tonic (japanese angelica-tree) China, India, Japan, Used for the treatment of arthritis, diabetes, gastritis, gastrospasm, hepatitis, Whole plant [23–27] Araliaceae Korea, Russia hypertension, neurasthenia aralin China, India, Used as emmenagogue Asparagus officinalis L. (asparagus) Flowers, leaves, seeds [4,23] Asparagaceae Japan, Korea Used for the treatment of arthralgia, diabetes, headache, urinary stones asparins Mediterranean area Used for the treatment of jaundice, sciatica, urinary and kidney dysfunctions Roots [21] Used as abortifacient, diuretic, emmenagogue, laxative, mucolytic Fruits, roots, seeds, Benincasa hispida (Thunb.) China, Korea Used for the treatment of dehydration caused by fever or great heat, diabetes, dropsy, [28–31] whole plant Cogn. (winter melon) hypertension, inflammation, liver and intestinal diseases, retention of placenta Cucurbitaceae [4,23] benincasins, hispin India Used for the treatment of diabetes, nervous diseases, peptic ulcers, urinary disorders Fruits, roots Molecules 2016, 21, 1560 3 of 27 Table 1. Cont. Plant Species, (Common Name), Geographic Area Therapeutic Application Plant Tissue(s) References Family and RIP Found Used as diuretic Beta vulgaris L. (beet) Turkey Leaves [32,33] Used for the treatment of diabetes, malaria Amaranthaceae beetins, betavulgin Jordan Used for the treatment of inflammation Leaves, roots [34] Mediterranean area Used as aphrodisiac, laxative Leaves, roots [21,35,36] Bryonia dioica Jacq. (bryony) Ancient Egypt Used for the treatment of polyuria Roots [37–39] Cucurbitaceae bryodins Mediterranean area Used as detoxifying, laxative Fruits [21,35,36] Used as anti-bacterial, aphrodisiac, diuretic India Used for the treatment of cancer, diabetes, eruptions, fever, gonorrhoea, healing of wounds, Leaves, seeds [4,40,41] Celosia argentea L. (cockscomb) inflammation, injuries, jaundice, metrorrhagia, mouth ulcers, skin sores, spasms, ulcers Amaranthaceae Used as ailment for eyes and liver, disinfectant CCPs Inflorescences, China Used for the treatment of blood diseases, broken bones, dysentery, dysuria, haematological and [42,43] leaves, seeds gynaecologic disorders, inflammation, mouth sore Chenopodium album L. (lamb’s quarters) Africa Used as anti-helminthic Leaves, stems [44] Amaranthaceae CAP30 India, Pakistan Used as anti-parasitic, diuretic, hepato-protective, laxative, sedative Whole plant [45] Used as anti-septic, suppressor of sexual behaviours Cinnamomum camphora (L.) J. Presl Persia Seeds [46,47] (camphorwood) Used for the treatment of boils, cold, sores, toothache Lauraceae Used for the treatment of asthma, boils, bronchitis, chills, colds, diarrhoea, hysteria, indigestion, China, Korea Not indicated [46,48] camphorins, cinnamomins muscle pains, nervousness, neuralgia, rheumatism, sores, sprains, toothache Cinnamomum porrectum (Roxb.) Kosterm. (yellow camphor) Leaves, stem bark, Malaysia Used for the treatment of wound infections [49] Lauraceae stem wood porrectin Used as abortifacient, analgesic, anti-parasitic, cathartic, diuretic, hair growth-promoting, purgative Iran, Jordan Fruits, roots, seeds [22,50–52] Used for the treatment of arthritis, diabetes, epilepsy, infections, inflammation, rheumatism Used as anti-bacterial, laxative India, Pakistan, Used for the treatment of abdominal worms, cancer, diabetes, gas troubles, gastroenteritis, liver and Fruits, roots [22,53–55] Sri Lanka respiratory diseases, toothache, tuberculosis Citrullus colocynthis (L.) Schrad (colocynth) Cucurbitaceae Used as abortifacient, analgesic, anthelminthic, anti-bacterial, anti-oxidant, carminative, colocins emmenagogue, immunostimulator, laxative, mucolytic Africa, China, Used for the treatment of cancer, cold, colic pain, cough, dehydration caused by fever or great heat, Fruits, roots, seeds [28,29,53,56–58] Middle East diabetes, dysentery, gastroenteritis, gynaecological-, respiratory-, skin- and urinary infections, hypertension, indigestion, inflammation,
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