Table of Contents
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FOREWORD
PREFACE
List of Contributors
Apium graveolens L. (Apiaceae)
Abstract
INTRODUCTION
MAJOR ACTIVE SUBSTANCES OF THE PLANT
BRIEF INFORMATION ON THE USAGE OF THE PLANT
CASE REPORTS ON THE PLANT
CONCLUDING REMARKS
REFERENCES
Cinnamomum sp. (Cinnamon and Cassia) (Lauraceae)
Abstract
INTRODUCTION
BOTANICAL SPECIFICATIONS
MEDICINAL USES
MAJOR ACTIVE SUBSTANCES
TOXICITY
Adverse Effects
Clinical Studies
Case Reports
International Reporting Data
Acute Toxicity
Coumarin Toxicity
Cinnamon Challenge
CONCLUDING REMARKS
REFERENCES
Datura spp. / Brugmansia spp. (Solanaceae)
Abstract
INTRODUCTION
MAJOR ACTIVE SUBSTANCE(S) OF THE PLANT SPECIES
BRIEF INFORMATION ON THE USAGE OF THE SPECIES
Traditional Uses
Illicit Uses
Medicinal Uses
TOXICITY
CASE REPORTS
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
REFERENCES
Gloriosa spp. /Colchicum spp. (Colchicaceae)
Abstract
INTRODUCTION
TRADITIONAL USES
ACTIVE SUBSTANCES
BIOLOGICAL ACTIVITY STUDIES PERFORMED ON THE SPECIES
CASE REPORTS
CONCLUDING REMARKS
REFERENCES
Glycyrrhiza glabra L. (Fabaceae)
Abstract
INTRODUCTION
PHYTOCHEMICAL COMPOSITION
Triterpene Saponins
Phenolic Compounds
Other Compounds
TRADITIONAL AND OTHER USES OF LICORICE
CASE REPORTS ON THE PLANT/PLANT PRODUCTS
CONCLUDING REMARKS
REFERENCES
Hedera helix L. (Araliaceae)
Abstract
INTRODUCTION
MAJOR ACTIVE SUBSTANCES
USAGE OF THE PLANT
CASE REPORTS ON THE PLANT/PLANT PRODUCT
CONCLUDING REMARKS
REFERENCES
Heracleum spp. (Apiaceae)
Abstract
INTRODUCTION
ACTIVE SUBSTANCES
BIOACTIVITY STUDIES PERFORMED ON THE SPECIES
ADVERSE EFFECTS
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
REFERENCES
Myristica fragrans Houtt. (Myristicaceae)
Abstract
INTRODUCTION
MAJOR ACTIVE SUBSTANCES
BRIEF INFORMATION ON THE USE OF M. fragrans
Ethnobotanical Use
Pharmacological Activities
CASE REPORTS ON M. fragrans
CONCLUDING REMARKS
REFERENCES
Nerium oleander L. (Apocynaceae)
Abstract
INTRODUCTION
MAJOR ACTIVE SUBSTANCES OF THE PLANT AND THEIR PHYSIOLOGICAL EFFECTS
ANTIDOTES OR TREATMENTS FOR OLEANDER POISONING AND REGULATIONS
Digoxin-Specific Antibody Fragments (Digoxin Immune Fab)
BRIEF INFORMATION ON THE USAGE OF THE PLANT/PLANT PRODUCT
CASE REPORTS ON THE PLANT/PLANT PRODUCT
CONCLUDING REMARKS
REFERENCES
Peganum harmala L. (Zygophyllaceae)
Abstract
BOTANICAL INFORMATION
MAJOR ACTIVE SUBSTANCES
Alkaloids
Fatty Acid Compositions
Volatile Components
Other Components
Traditional Uses in Türkiye
Bioactivity Studies
Antidepressant Effect
Antibacterial, Antifungal, and Antiviral Activities
Antioxidant Activities
Antitumor Effects
Other Pharmacological Activities
SIDE EFFECTS/ADVERSE EFFECTS
CASE REPORTS
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
REFERENCES
Rhododendron spp. (Ericaceae)
Abstract
INTRODUCTION
Name
Distribution
Botany
Mad Honey
ETHNOBOTANY
Use of Plant
Use of Mad Honey
PHYTOCHEMISTRY
TOXICOLOGY
General Information About Grayanotoxin Poisoning
History of Mad Honey Poisoning
Case Reports: Mad Honey
Non-Honey Poisonings of Humans
Non-Honey Poisoning of Animals
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
REFERENCES
Ricinus communis L. (Euphorbiaceae)
Abstract
INTRODUCTION
ACTIVE SUBSTANCES
Alkaloids
Flavonoids and Benzoic Acid Derivatives
Terpenoids
Fatty Acids
BRIEF INFORMATION ON THE USAGE OF THE PLANT/PLANT PRODUCT
PHARMACOLOGICAL ACTIVITIES
CASE REPORTS ON THE PLANT/PLANT PRODUCT
CONCLUDING REMARKS
REFERENCES
Poison or Remedy?
Case Reports on Selected Plants
Edited by
Ceyda Sibel Kılıç
Department of Pharmaceutical Botany
Ankara University Faculty of Pharmacy
Tandoğan, Ankara, Türkiye
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FOREWORD
This e-book comprising 12 chapters covers the topics of unwanted and sometimes unexpected effects of some plants that have been used by different populations throughout the world for various purposes. Though most of these plants have ethnobotanical, medicinal, and culinary usage, they can still be a threat to human and animal health due to the toxic secondary metabolites they contain. Chapters include not only case reports but also botanical information, photographs, structures of chemical compounds responsible for the adverse effects, and ethnobotanical and/or medicinal usages.
Chapters include celery plant that is used for culinary purposes but also containing phototoxic components: the spice cinnamon, which can lead to unwanted effects due to some species’ high coumarin content; Angel’s trumpet having tropane alkaloids; Gloriosa and Colchicum, two important genera containing colchicine-type alkaloids; licorice plant; common ivy; Heracleum spp. having phototoxic components; nutmeg, a spice and a medicinal plant; oleander plant having significant cardiotoxicity; Syrian rue with harmine and harmaline; rhododendron and its product mad honey and finally castor oil plant that also have uses in the cosmetic industry.
I would like to congratulate the authors and especially the editor, Prof. Dr. Ceyda Sibel Kılıç, who is a former PhD student of mine, for their efforts. They provided important and current details with respect to the adverse effects of some well-known and commonly used plants/plant products that should be kept in mind.
Maksut COŞKUN
Ankara University Faculty of Pharmacy
Ankara/TÜRKİYE
PREFACE
According to the data of World Health Organization (WHO), 80% of the population living in developing countries rely on herbal medicines for their health problems. It is known that plants contain hundreds of secondary metabolites resulting in various biological activities. However, they might also be responsible for various intoxications and/or adverse effects, either accidentally or on purpose, as many case reports confirm these occurrences.
Since plants can be our friends or foes, this book covers the unwanted effects of some plants (whether medicinal or not) in the form of case reports.We experience such side effects due to a lack of information about them and incorrect usage. Knowing these unwanted reactions will inform us about their adverse effects and will lead us to be cautious when we encounter/use these plants.
Each chapter contains botanical and phytochemical information related to the plant/plant product in question, including the structure of the common compounds responsible for the adverse effect(s). Case reports from different parts of the world are included along with the used parts and the intentions of the usage.
I would like to thank the authors for their contributions and would like to dedicate the book to Prof. Dr. Mekin Tanker from Ankara University (retired) for his contributions to the field of Pharmacognosy, who had passed away recently.
Ceyda Sibel Kılıç
Department of Pharmaceutical Botany
Ankara University Faculty of Pharmacy
Tandoğan, Ankara, Türkiye
List of Contributors
Alper GÖKBULUTDepartment of Pharmacognosy, Ankara University, Ankara, TürkiyeAslı CAN AĞCADepartment of Traditional, Complementary and Integrative Medicine, Ankara Yıldırım Beyazıt University, Institute of Public Health, Ankara, TürkiyeAyşe Esra KARADAĞDepartment of Pharmacognosy, Istanbul Medipol University, Istanbul, TürkiyeAyşe Mine GENÇLER ÖZKANDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeBüşra CUMHURAnkara University, Graduate School of Health Sciences, Ankara, TürkiyeBetül DEMİRCİDepartment of Pharmacognosy, Anadolu University, Eskisehir, TürkiyeCeyda Sibel KILIÇDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeDamla KIRCIDepartment of Pharmacognosy, İzmir Katip Çelebi University, İzmir, TürkiyeDerya ÇİÇEK POLATDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeFatih DEMİRCİDepartment of Pharmacognosy, Anadolu University, Eskişehir, TürkiyeGökalp İŞCANDepartment of Pharmacognosy, Anadolu University, Eskisehir, TürkiyeGülnur EKŞİ BONADepartment of Pharmaceutical Botany, İstanbul University-Cerrahpaşa, İstanbul, TürkiyeGülderen YILMAZDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeGözde ÖZTÜRKDepartment of Pharmacognosy, Anadolu University, Eskisehir, Türkiyeİlker ATEŞDepartment of Pharmaceutical Toxicology, Ankara University, Ankara, TürkiyeMuhammed Mesud HÜRKULDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeNagehan SALTANDepartment of Pharmaceutical Botany, Anadolu University, Eskişehir, TürkiyeÖzlem ATLI EKLİOĞLUDepartment of Pharmaceutical Toxicology, Anadolu University, Eskisehir, TürkiyeSinem ASLAN ERDEMDepartment of Pharmacognosy, Ankara University, Ankara, TürkiyeSafa GÜMÜŞOKDepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeŞeyda YAYLADepartment of Pharmaceutical Botany, Ankara University, Ankara, TürkiyeŞüheda Rumeysa OSMANLIOĞLU DAĞDepartment of Pharmaceutical Botany, Inonu University, Malatya, TürkiyeSelen İLGÜNDepartment of Pharmaceutical Botany, Erciyes University, Kayseri, TürkiyeYavuz Bülent KÖSEDepartment of Pharmaceutical Botany, Anadolu University, Eskişehir, Türkiye
Apium graveolens L. (Apiaceae)
Muhammed Mesud HÜRKUL1,*,Şeyda YAYLA1
1 Department of Pharmaceutical Botany, Ankara University, Faculty of Pharmacy, Tandoğan, Ankara, Türkiye
Abstract
Apium graveolens L. (Apiaceae; formerly Umbelliferae) is distributed from Europe to the Western Himalayas and from Micronesia to North Africa. The plant is called “celery” and is commonly consumed as a vegetable, also used as medicine, poison, and animal food. The plant has many pharmacological activities such as antioxidant, antimicrobial, hypocholesterolemic, cardiotonic, antidiabetic, antiulcer, hepatoprotective, antiplatelet, larvicidal, anti-spasmolytic, anti-inflammatory, anticancer, analgesic and anti-infertility. However, many important health problems have also been reported with the use of celery. Case reports indicate that important conditions like anaphylactic shock, food-dependent exercise-induced anaphylaxis, hyperthyroidism, bipolar disorder, phototoxicity, and acute irritant contact dermatitis may occur due to the use of celery.
Keywords:Apium graveolens, Apiaceae, Umbelliferae, Celery, Case reports.
*Corresponding author Muhammed Mesud HÜRKUL: Department of Pharmaceutical Botany, Ankara University, Faculty of Pharmacy, Tandoğan, Ankara, Türkiye; E-mail:
[email protected]INTRODUCTION
Apium graveolens L. (Apiaceae; syn.: Umbelliferae), celery is distributed from Europe to the Western Himalayas and from Micronesia to North Africa (Fig. 1) [1-3]. A. graveolens is cultivated and generally used as a vegetable and eaten boiled. Furthermore, it is also used as medicine, poison, and animal food [2-4]. In recent years, celery has gained interest with respect to its pharmacological effects and various biological activities of celery have been reported, such as antioxidant, antimicrobial, hypocholesterolemic, antidiabetic, cardiotonic, antiulcer, hepatoprotective, antiplatelet, larvicidal, anti-spasmolytic, anti-inflammatory, anticancer, analgesic and anti-infertility activities [5].
The plant is biennial, has a yellowish-green erect stem; angled, strongly sulcate, 30-100 cm, much branched above; leaflets (3-)5-7 per leaf, basal and lower cauline leaves deltate-rhombic, long-petiolulate, glabrous; greenish-white flowers up to 20 per umbellule having 4-12 unequal rays, without bracts and bracteoles;
fruit broadly ovoid, blackish when ripe; flowering in April-August, in damp places, at an altitude up to ± 500 m [1-3]. The leaf stalks of the A. graveolens have a broad, sheath base and mostly consist of parenchyma and collenchyma bundles. Vascular bundles beneath the epidermis layer are prominently ridged on the abaxial surface of the leaf. The fruit of A. graveolens is known as a schizocarp, which splits into two single-seeded mericarps when ripe. Mericarps remain attached by a filament called carpophore. Fruits usually contain essential oil and abundant endosperm [6].
A. graveolens, whose natural habitat is swamps, is suitable for growing in tropical wetlands with high soil moisture and shallow water tables. Deep, humus-rich, light clay soils are preferred. It is important that the soil is well aerated and well drained. The pH should be slightly acidic or neutral (6.0-7.5). Sites with full sun are ideal. Partial shade can be tolerated, but full sun is important for optimum growth. Cool and temperate climates provide the most suitable environment. The temperature should be between 15-21°C. It should be protected from frost [7, 8].
Fig. (1))Apium graveolens
MAJOR ACTIVE SUBSTANCES OF THE PLANT
Celery is rich in volatile oil and phenolic compounds [9-11] and the main component of the volatile oil is d-limonene (50-80%) along with high amounts of β-selinene (10%) [9, 12, 13]. Moreover, coumarins and furanocoumarins (bergapten) are other main compounds that the plant contains [9, 10]. The seeds are rich in vitamin B and contain proteins (8%), volatile oil (1.5-3%), and fixed oil (5.8-14.2%) [10-14]. Leaves and stems are rich in flavonoids and contain apiin and apigenin as main compounds [9, 10]. Celery root contains ferulic acid, caffeic acid, and p-coumaric acid derivatives; additionally, coumarin, scopoletin, and aescoumlic acid [10]. The chemical structures of some of these major components are given in Fig. (2).
Fig. (2))
Structures of (a) d-limonene, (b) β-selinene, (c) apiin; (d) bergapten, (e) apigenin (Structures are drawn with ChemDraw Ultra v. 12.0.2.1076)
Flavonoids such as apiin and apigenin have potent anti-inflammatory, antioxidant, anticarcinogenic, and neuroprotective properties. Apigenin and its derivatives stand out as potential therapeutic agents in the treatment of various inflammatory diseases such as rheumatoid arthritis and autoimmune diseases by inhibiting many of the molecular targets associated with inflammation. In addition, it shows chemopreventive effects in the treatment of various cancers and induces apoptosis in cancer cells. Its effects on neurodegenerative diseases are also remarkable; it shows promise in the treatment of Parkinson's and Alzheimer's diseases [15]. Essential oils have significant antimicrobial properties due to their generally hydrophobic nature, which allows them to disrupt bacterial cell membranes, causing increased permeability and leakage of cellular contents, potentially leading to cell death. These compounds can neutralize free radicals and break down peroxides, playing a role in preventing diseases such as brain dysfunction, cancer, heart disease, and immune system decline. Essential oils exhibit anti-inflammatory activity due to their ability to inhibit histamine release and reduce the production of inflammatory mediators [16]. As a natural product, d-limonene has broad therapeutic potential. It also has the potential for use in cosmetics, agriculture, food preservation, and other fields. D-limonene has potential therapeutic effects in inflammatory conditions such as colitis, pneumonia, and respiratory inflammation by controlling inflammatory signaling pathways and suppressing inflammatory factors. It also has broad-spectrum antibacterial properties against multidrug-resistant bacterial infections and is effective against various types of bacteria, fungi, and viruses. In addition, it has protective effects on the nervous system and preventive effects in various cancer models by reducing inflammatory responses and increasing the neurotrophic process, in the prevention and treatment of metabolic and cardiovascular diseases, such as liver protection, anti-obesity, and hypoglycemic effects [17].
BRIEF INFORMATION ON THE USAGE OF THE PLANT
Celery is known to have been used by ancient civilizations and reported to be cultivated even before 850 BC [4]. It is also used in various traditional medicine practices, for example, it was described in Materia Medica by Pedanius Dioscorides which has served as a pharmacy handbook for almost twenty centuries [18]. As for other traditional uses; celery is used in the treatment of stroke, epilepsy, and hot temper in Danish folk medicine [19]; for headaches in Persian traditional medicine [20]; as a diuretic and nephroprotective in Unani medicine [21]; for insanity in Traditional Indian Medicine [22]; and for rheumatism in Latvian folk medicine [23]. Also, the Chilandar Medical Codex of Serbian medicine reports that the plant was used for conditions affecting the spleen and the liver; and was effective against jaundice, passing stones, haematuria, and phlegmons [24]. Moreover, celery was used to strengthen eyesight and migraine and as a purgative in Cairo in medieval times [25]. Traditional uses of celery plants are summarized in Table 1 along with the countries that they are used in. Some extraction methods are applied in these traditional uses. Maceration is the process of keeping herbs (in raw or powdered form) in an airtight container filled with a solvent (menstruum). The samples are kept at room temperature for at least 3 days and stirred regularly until the solutes are completely dissolved. The resulting mixture is then filtered to remove impurities. Infusion is similar to maceration, but the plant material is immersed in cold or boiling water and the dissolved substances mix with the water. The maceration time is shorter with infusion. Decoction is the process of boiling the sample with a certain volume of water and is only suitable for the extraction of thermostable compounds, hard plant materials, and other substances. In this method, dissolved substances are transferred to water and then filtered [26, 27].
Table 1Traditional uses of A. graveolens (celery) in different countries.CountryPart UsedPreparation/AdministrationTraditional UsageRefs.AlgeriaLeavesInfusion, decoctionAgainst diabetes[28]Leaves, Seeds-Carminative, antispasmodic, diuretic[29]Seeds, Aerial partsDecoction, rawAgainst diabetes[30]ArgentinaLeavesDecoctionMenstrual disorders, dyspepsia, stomachache[31]Balearic IslandsLeavesInfusionHoarseness, antitussive, pharyngeal anti-inflammatory, urinary retention, diuretic, prostate anti-inflammatory[32]RootsInfusionDiureticWhole plantEaten rawAphrodisiacBolivia--Digestive system and liver ailments[33]Bosnia and HerzegovinaLeaves, Roots-Renal diseases, bladder stones, digestive disorders, loss of appetite, blood purification, ague, and diabetes.[34]BrazilWhole plantDecoction, poulticeInjuries, tetanus, infection, inflammation,[35]ChinaWhole plantDecoction, poultice, brothHigh blood pressure, urethritis, leucorrhea, injuries from falls, fracture, invigorate, adynamia[36]ColombiaAerial partsInfusion, soupStomach diseases, as digestive, carminative, good for the blood, to lose weight, hepatodepurative[37]Czech RepublicAerial partsExternal useRheumatism[38]internal useRenal stonesEcuadorStems, leavesInfusionAntiacid, stomachache, menstruation pain, diarrhoea, kidney problems[39]EgyptLeaves, fruit-Analgesic, sedative, relaxant, Antidepressant[40]GuatemalaLeavesInfusionDiabetes[41]IndonesiaLeaves-Hypertension[42]IranSeedsDecoctionLiver disorders, asthma[43]ItalyRootsDecoctionKidney stones[44][45]Stems-Diuretic, antiscorbutic[46]Eaten raw or taken as a decoctionMineralizing and anti-inflammatory for bones and joints[47]JordanSeeds-Diuretic, carminative, stomach strengthening[48]MalaysiaLeavesAsthma[49]MauritiusLeavesDecoction-drink 1 cup twice per weekDiabetes[50]MexicoAerial parts stemsInfusionCough, stomach pain[51]Leaves-Obesity[52]MoroccoFruits-Cardiac diseases[53]Whole plantDecoction-oralRenal problems[54]LeavesDecoction-oralKidney stones[55]PalestineAerial partsFresh juice- oral, 15 drops/every two hoursDiarrhea[56]PeruAerial partsInfusion-oralStomach infection, colic, gases[57]Saudi ArabiaLeavesjuice-oral ingestionNeurologic, cardiovascular, digestive, muscular diseases[58]SerbiaRootsEaten rawdiuretic[59]SpainAerial partsDecoction, macerationAntihemorrhoidal, dysmenorrhea, antispasmodic[60]Leaves-Digestive depurative, gastralgia, constipation, obesity[61]TürkiyeWhole plantInfusion, decoction-1 glass 3 times a day for 4 weeksRenal colic, diabetes, hypercholesterolemia, rheumatism, sexual inadequacy[62]Decoction- one teacup two times a day for a weekAbdominal pain, prostatitis[63]Leaves, seedsInternal useDiabetes, ringworm[64]
CASE REPORTS ON THE PLANT
Various health problems may occur as a result of celery use and utilization of its products as food or therapeutic. These have been reported as anaphylactic shock, food-dependent exercise-induced anaphylaxis, hyperthyroidism, bipolar disorder, phototoxicity and acute irritant contact dermatitis. Some case reports on the plant are summarized in Table 2.
Table 2Case reports on A. graveolens.ConditionAge/Sex/HistoryHistory of Presenting ConditionTreatmentRefs.Anaphylactic shock28/F
With a history of seasonal allergic rhinitis, burning, and swelling of the lips and cheeks, oral allergy syndrome (OAS) after eating raw apples.[Consumed raw celery]
Pain in the upper abdomen, generalized pruritic hives, swelling of the eyelids and lips, general weakness and shortness of breath, decrease in blood pressure to 60/40 mmHg, tachycardia (120/min.), tachypnea (25 breaths/min.)Epinephrine 1 mg IM, Dexamethasone 16 mg IM, Antazoline 100 mg IM, and 0.9% NaCl 500 ml[65]49/F
Seasonal rhinoconjunctivitis for 25 years[After eating celery]
Severe anaphylactic reactions with loss of consciousness, typical lesions of urticaria pigmentosaOral hyposensitization started with 0. 1ml of the celery juice five times on day 1, and then over 4 weeks, incremental doses of 5 ml were administered up to five times daily.[66]Food-dependent exercise-induced anaphylaxis (FDEIA)18/M
Allergic rhinitis, symptoms aggravate every spring and autumn.[Exercise for 30 min after ingestion of celery resulted in an anaphylactic reaction] Repeated anaphylactic reactionsInstructing to avoid exercise after ingestion of celery.[67]34/F
Mild springtime allergic rhinitis but no history of asthma, urticaria, eczema or food allergy[Eating (contains celery) before exercise within 2 h]
Cutaneous itching, hives, wheezing, abdominal cramping, dizziness, weaknessThree doses of 0.3 ml of 1:1000 subcutaneous epinephrine at 15-minute intervals.[68]20/M[Eating (contains celery) before exercise within 2 h]
Cutaneous itching, hives, angioedema, dizziness, weaknessThree doses of 0.3 ml of 1:1000 subcutaneous epinephrine at 15-minute intervals.[68]39/F
Mild seasonal allergic rhinitis and asthma[Eating celery before exercise within 2 hr]
Cutaneous itching, hives, abdominal cramping, dizziness, weaknessThree doses of 0.3 ml of 1:1000 subcutaneous epinephrine at 15-minute intervals.[68]28/F
Seasonal allergic rhinitis with peaks in spring and summer[Ingestion of a dish containing celery]
Acute urticaria, generalized facial swelling and tongue angioedema, dysphagia, shortness of breath, chest tightness, wheezing, palpitations, abdominal cramping, and syncopeEpinephrine, diphenhydramine, and prednisone.[69]22/F
Asthma and seasonal allergic rhinitis[Playing ball 1 hr after eating fresh celery]
Bronchial asthma and pollinosis, collapse, severe hypotension, dyspnea with wheezing, abdominal pain, nausea, hand numbness, angioedema, urticaria, generalized pruritus.-[70]Hyperthyroidism36/F
She experienced weight gain after her second delivery (primary weight: 107 kg).[She used 8 g/day of celery extract in powder form for weight reduction]
Blurred vision, palpitation, nausea, sweating, exophthalmos, skin rash on armsMethimazole 10 mg/day[71]48/M
No history of any thyroid diseases[Daily consumption of 4 g of dried celery leaves for 45 days] Weight loss, exophthalmos, and sweatingAfter cessation of consumption and treatment with methimazole, the symptoms remitted.[72]Bipolar disorder52/F
Major depressive disorder, hypertension, and dyslipidemia[Started taking herbal supplement celery root extract 1000 mg daily for menopause]
Confusion and speech abnormalities for 24 hours.Discontinuation of celery root extract, IV fluids at a rate of 110 ml/hour, haloperidol 0.5 mg twice a day, oral.[73]Phototoxicity56/F
Atopic eczema, PUVA for 9 months (40 mg 8-methoxy psoralen and 5 J/cm2 UVA dose), mild hypertension[She consumed soup containing celery, parsnip, and parsley the evening before and 2hr before PUVA]
Febrile (35.5°C) and in pain, generalized intense erythema with swollen and blistered face0.1% Betamethasone valerate cream[74]65/F[Consumption of a large quantity of celery root] Phototoxic reaction-[75]Acute irritant contact dermatitis69/F[Applied plant to her left knee and covered it with a cloth]
Erythema, edema, exudation, and bulla formationAntihistamines and systemic corticosteroids, topical fusidic acid cream, and Rivanol (ethracidinlactate-monohydrate)[76]
Epinephrine, dexamethasone, antazoline, diphenhydramine, prednisone, methimazole, haloperidol, and betamethasone are powerful medications commonly used to treat various medical conditions. While epinephrine is used in the emergency treatment of bronchospasm and anaphylactic reactions, dexamethasone, with its potent anti-inflammatory and immunosuppressive properties, is effective in the treatment of rheumatic, dermatologic and allergic diseases, as well as severe respiratory symptoms associated with COVID-19. Antazoline and diphenhydramine are used as histamine H1 receptor antagonists to relieve allergic reactions and symptoms, while diphenhydramine is also known for its antiemetic and sedative effects. Prednisone is widely used in the treatment of autoimmune and inflammatory diseases due to its immunosuppressive and anti-inflammatory effects. Methimazole acts as an effective antithyroid agent in the treatment of hyperthyroidism. Haloperidol exerts antipsychotic effects through dopamine receptor antagonism and is used in the treatment of schizophrenia and acute psychosis. Betamethasone, a long-acting corticosteroid, is used to treat skin conditions such as eczema and autoimmune diseases [77-79].
Studies on the toxicity of A. graveolens show that certain doses of the plant can cause various biochemical and physiological changes. Acute toxicity studies have shown that the plant is safe at doses above 2000 mg/kg, but may cause some discomfort. Subacute toxicity studies have shown that a dose of 200 mg/kg is safe for long-term use (28 days), but a dose of 400 mg/kg may cause significant changes in body weight and organ weight [80-82]. A. graveolens may be protective against valproic acid (VPA)-induced testicular toxicity. The previous studies investigated the protective effects of celery extract against VPA-induced testicular damage in male Wistar rats. Valproic acid is widely used to treat epilepsy and other conditions, but it can cause serious toxic effects on the testes. In the study, decreases in testicular weight, sperm count, and motility, decreases in testosterone levels, and increases in FSH levels were observed after VPA application. In addition, histopathologic studies reported degeneration of the seminiferous tubules and a decrease in germ cells. However, pretreatment with A. graveolens extract attenuated most of these effects [83].
CONCLUDING REMARKS
Apium graveolens is an important plant that has been cultivated and consumed as food since ancient times. However, celery is also used for medicinal purposes, as poison, and as animal feed. This plant, used in traditional medicine in many countries, has various biological activities. However, significant health problems have also been reported with the use of this plant. These problems include anaphylactic shock, food-induced exercise-induced anaphylaxis, hyperthyroidism, bipolar disorder, phototoxicity, and acute irritant contact dermatitis. These serious health problems that arise as a result of the use of plants for food or medicinal purposes show that plants are not innocent and should be used with caution. Long-term use of celery may cause various health problems. Consumption, especially in high doses and for long periods of time, may cause increases in liver enzyme levels, changes in markers of oxidative stress, and hormonal imbalances. This may lead to deterioration of liver function, adverse changes in lipid profile, and deterioration of kidney function. Hormonal imbalances and adverse effects on spermatogenesis in males have also been reported [84]. Long-term and high-dose consumption of celery should be used with caution and monitored by health professionals, especially in individuals with chronic medical conditions. Establishing safe doses and raising awareness among individuals is important to prevent potential toxic effects [81].
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