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J Journal of Tropical Disease and Public Health

ISSN: 2329-891X Review Article

The Spongia somnifera: A Review Article Suleiman Olimat* Department of Medicinal Chemistry and Pharmacognosy, University of Science and Technology, Jordan

ABSTRACT Spongia somnifera is considered the most important formula used in anaesthesia and has been developed over centuries by different physicians. Medicinal being the anchor ingredients in the various formulas (, , hemlock, henbane, ivy, mulberry, hops, wide lettuce). The aim of the present review is to evaluate the medicinal plants used in different formulas of Spongia somnifera as agent with correlation with their modern applications, chemical compositions and pharmacology. Keywords: Spongia; Somnifera; Opium; Mandrake; Hemlock; Henbane; Ivy; Wide Lettuce; Mulberry; Hops

INTRODUCTION total anaesthesia, resorption/inhalation anaesthesia, and then local anaesthesia. Most of these sedative plants were members of Anaesthesia is a very essential performance of surgical and other a large botanical family, the family, Solanum nigrum, interventional procedures by rapidly, safely, and pleasantly , Cicuta minor, stramonium, and Lactuca producing analgesia, the primary goal of general anaesthesia is virosa, are gathered, and a sponge is plunged into their juice freshly rendering a patient unconscious and unable to feel painful stimuli expressed. The sponge is then dried in the sun, the process of while controlling autonomic reflexes. Anaesthesia introduced to dipping and drying is repeated two or three times, and the sponge modern medicine in 1846 and a new era started in the development is then laid up in a dry place [4]. Formula three used by the middle of that would not be possible without anaesthesia [1]. Spongia ages doctors used a Spongia somnifera (soporific-sponge), consisting somnifera is considered the oldest, most important formula used of a fresh seasponge soaked in opium, henbane, mulberry juice, in anaesthesia and has been developed over centuries by different lettuce seed, hemlock, mandrake and ivy, then dried in the sun. physicians. Medicinal plants being the only important ingredients When it was needed for pain-killing, it was reconstituted with water in the various formulas (e,g. opium, mandrake, henbane, ivy, inhaled or dripped into the mouth. Fennel root or vinegar was mulberry, hops, wide lettuce) [2]. Formula one consisted of three the antidote used to revive the patient. Formula four for Spongia plants (mandrake, opium, and henbane); it was introduced in somnifera was in the medieval medicine which is a combination medicine by the famous Arabian scientist Ibn Sina (980 to 1037 with mandrake, poppy, hops, henbane, lactuca (wild lettice) and CE), (), in his authoritative Canon of Medicine, he mulberry [5]. described the Spongia somnifera, put all the ingredients together in a bowl with water and dip the marine sponge to absorb the LITERATURE REVIEW dissolved water in which the recipe plants are placed, then place All the available information on Spongia somnifera was collected via the sponge on the patient's nostril and quickly fall asleep. The a library and electronic search (using Web of Science, Pubmed, second formula mentioned by Salernitan physicians. Michael Scot SciFindert, Scopus, Google Scholar…etc.). (1190 to 1250 CE), who recommends taking equal quantities of opium, , and hemp, grinding these plants and mixing Pharmacology and Chemical composition and mechanism of them with water. When you want to saw or cut someone, just dip a action of formulas one and two (mandrake, opium, and henbane). rag in the water and place it on his nostril, he will sleep deeply and Mandrake, Mandragora you can do with him whatever you wish [3]. The mandrake, mandragora is the common English name of Medieval medicine was highly innovative compared to ancient and Mandragora officinarum L. and M. automnalis L. perennial herb early modern medicine. It also pertains to anaesthesia, which in belonging to the family Solanaceae, the roots and rhizomes the Middle Ages was developed from ancient methods of sedation. are used in medicine, the is closely allied to the deadly Medieval scholars perfected the method into achieving the first nightshade, belladonna L. An old scholar book is known by

Correspondence to: Suleiman Olimat, Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, Jordan, Tel: +962 277 260 7116; Email: [email protected] Received: March 03, 2021; Accepted: April 05, 2021; Published: May 28, 2021 Citation: Olimat S (2021) The Spongia Somnifera: A Review Article. J Trop Dis 9: 282 Copyright: ©2021 Olimat S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

J Trop Dis Vol. 9 Iss. 5 No: 282 1 Olimat S. OPEN ACCESS Freely available online the name “Yabrouh”, believed it is a Syriani word meaning “I need codeine stem from its conversion to , about 10 percent a soul” because of the root and rhizome resembling the human of administered codeine undergoes O-demethylation to morphine, body, just needing a soul to be alive. The chemical composition which is predominately mediated by the polymorphic CYP2D6 of mandragora mainly and the sedative effect enzyme. Importantly, Codeine has an extremely low affinity for attributed to the presence of and alkaloids, standard CNS mu (μ), delta ( ), and kappa ( ) receptors. based on the actions of the juice of the mandrake plant, it must Thebaine has no medical applications, it occurs in opium extract contain an that is one of the most active , to the extent of 0.1-2.5 percentδ [11], is importantκ as a substrate mainly the alkaloid scopolamine [6]. Nowadays the plant is known in the semi-synthesis of other opium alkaloid. Thebaine alkaloid by different names like Tuffah el Majanin (Madmen’s Apple) and is an opioid analgesic, it is a partial mu (μ)-receptor agonist and Beid el Jinn (Eggs of the Jinn), this is due to the ability of the plant kappa ( )-receptor antagonist. It has a delayed onset of activity, and to invigorate and stimulate the senses even to the point of mental because of its property as a partial mu(μ)-opiate agonist. imbalance [7]. κ Poison hemlock, maculatum L. belonging to the family Mandragora extract was used as a juice, so the patient had to drink Apiaceae ( formerly Umbelliferae), known in English by the name it rather than inhalation, when the juice taken orally has to be hemlock or poisonous hemlock and in Arabic known as Shoukaran absorbed by mucus membranes, inhalation would be ineffective or Shykaran [12] It is a tall biennial, which typically forms a basal because atropine and scopolamine have a very low vapour pressure. rosette in the first year of growth. The hemlock species is native Mandragora was a common that has been used as a sedative to the Mediterranean region. It has leaves and white flower and to induce pain relief for surgical procedures; different dosage heads resembling those of parsnips, carrots; The long, fleshy, forms, tablets and friezes, had been developed since the 16th century. white taproot has a main stem with characteristic light red spots Mandragora anaesthesia acting to relieve pain by desensitizing the and a disagreeable smell, a dead rat smell. The flowers are small nerve endings [8]. with 5 white , numerous in compound flat-topped umbels at the ends of stems, produced from April to early July. All parts Henbane of hemlock are poisonous. The generic name of the plant-derived Hyoscyamus niger L. belongs to the family Solanaceae, its English from the Greek word “Konas”, meaning to whirl about, upon common name is henbane or black henbane, which refers to the consumption of the plant, causes vertigo and leading to death. black colour of the seeds, which are used in medicine. Known The species macualtum meaning (spotted) and referred to the dark in Arabic as “Banj”, refers to its anaesthetic effect [9]. Henbane spots on the stem. However, the common name hemlock is derived is rich in tropane alkaloids like other species belong to the from the Anglo-Saxonwords hem (border, shore) and leác (leek or family Solanaceae ( and Datura spp.) Atropine plant); other authors mentioned that the name (hemlock) was is a racemic mixture (containing equal amounts of the isomers derived from the word helm (straw), from which the word (haulm) (-)- and (+)-hyoscyamine, in addition to alkaloids was derived. Historical background, Socrates death. (-)-hyoscyamine, there is no difference in their pharmacological The juice of hemlock, hemlock cup, was administered in ancient activity, and (-)-scopolamine. Several tropane alkaloids are. Greek to criminals. The Greek philosopher Socrates is one of the Atropine, hyoscyamine, and scopolamine are muscarinic receptor most famous people who chose to be executed by drinking hemlock antagonists and used as powerful [9]. Tropane tea. The closing pages of Plato’s Phaedo provide a stunning picture alkaloids work by inhibiting the parasympathetic nervous system. is of the effects of poison upon the body of Socrates. Plato describes a a competitive antagonist of the actions of acetylcholine and other slowly ascending paralysis, beginning in Socrates’ feet and creeping muscarinic agonists. The alkaloids atropine and scopolamine are steadily up his legs toward his chest, with Socrates’ mind remaining qualitatively similar in their pharmacology, except atropine is CNS clear until the end. Death arrives calmly and peacefully [13]. After and scopolamine is a central and can act as Socrates drank the poison, he walked a few steps but felt that his a sedative. feet could not hold him, and one of his attendants advised him to Pharmacology of opium lie on his back, and the poison began to spread in his body from bottom to top until he felt the difficulty of breathing and his last The constituents of opium alkaloids (morphine, codeine, thebaine) words were ‘Crito, we owe a cock to Asclepius. Pay it and do not are exogenous opioid that produces analgesia, as a result of its neglect it. affinity to bind to receptors normally acted upon by endogenous . Morphine and close related alkaloids are biosynthesized Pharmacology and chemical composition from phenanthrene derivatives and include four or more fused Twelve piperidine alkaloids have been identified in C. maculatum, rings, morphine is the major active constituent in opium in a two of them, -coniceine and are generally the most concentration up to 20 percent. Morphinoid alkaloids and similar abundant and they account for most of the plant acute and chronic agonists have agonistic actions at the mu (μ), kappa ( ), toxicity. Coniineγ is the major alkaloid present in the plant, in a and delta ( ) receptors [10]. This drug produces the majority of its concentration of 2% in fruits and 0.5% in leaves, however, It is the analgesic effects by binding to the mu-opioid receptor within theκ first alkaloid the chemical structure of which was established (in Central Nervousδ System (CNS) and the Peripheral Nervous System 1881). Coniine provokes a skeletal muscle relaxation effect on the (PNS). The net effect of morphine is the activation of descending neuromuscular junction, whereas cicutoxin causes seizures. The inhibitory pathways of the CNS as well as inhibition of the general symptoms of hemlock poisoning are effects on the nervous nociceptive afferent neurons of the PNS, which leads to an overall system (stimulation followed by paralysis of motor nerve endings reduction of the nociceptive transmission. Codeine, the 3-methyl and CNS stimulation and later depression), vomiting, trembling, ether of morphine, is found in opium in a concentration range of 0.7 problems in movement, slow and weak later rapid pulse, rapid percent- 2.5 percent. Codeine possesses the same pharmacological respiration, salivation, urination, nausea, convulsions, coma and actions as morphine but is less potent. The analgesic properties of death. It is a nicotinic acetylcholine receptor antagonist, which

J Trop Dis Vol. 9 Iss. 5 No: 282 2 Olimat S. OPEN ACCESS Freely available online leads to inhibition of the nervous system, eventually causing death 3-O-rutinoside, quercetin 3-O-glucoside, kaempferol 3-O-glucoside, by suffocation in a mammal. quercetin, kaempferol, chlorogenic acid, neochlorogenic acid, 4,5-O-dicaffeoyl-quinic acid, 3,5- O-dicaffeoyl-quinic acid as well as E-Mulberry rosmarinic, caffeic, and protocatechuic acids. Juice of ivy was an Mulberry belongs to the Morus of the family Moraceae and ingredient in Spongia somnifera in medival times. The expectorant it is found in East, West and South-East Asia, South Europe, South effect of ivy is more complex (or more precisely described) than of North America, and some areas of Africa. There are 24 species those of other saponin-containing plants, due to the stimulation of Morus, the most commonly known species in the Morus genus of beta2-adrenoreceptors leads to increasing surfactant production. are white mulberry, known in Arabic as Toot Abiad, (Morus alba Flavonoids and caffeic acid derivatives with less pronounced L.), black mulberry, known in Arabic as Toot Aswad, (Morus nigra activity may also contribute to the effect54. Structure-related L.) and red mulberry, known in Arabic as Toot Ahmar, (Morus saponins like hederacoside C and hederagenin did not influence rubra L.) either the binding behavior of beta 2 AR or the intracellular cAMB Pharmacology and chemical composition of mulberry level [15]. I think the juice of wood-ivy in Spongia somnifera is due to its effect on the respiratory system. Mulberry species are rich in phenolic compounds mainly flavonoids, G-lettuce seeds flavonoid glycosides, phenolic acids and anthocyanidins. M. nigra main components are anthocyanins recognized as cyaniding The seeds of Lactuca scariola Linn belonging to the family 3-pelargonidin 3-O-glucoside, cyaniding 3-O-rutinoside, Asteraceae, is commonly known as “Prickly Lettuce” seeds or pelargonidin 3-O-glucoside and pelargonidin 3-O-rutinoside. M. “Wild Lettuce” seeds, in Arabic known as Buzrul khas. The species nigra showed higher amounts of phenolic compounds than M. Lactuca sativa L. is the common or garden variety, known in Arabic alba. Phytochemical analysis of M. alba showed that the abundant as Bustani Khas. The generic name Lactuca and the common name anthocyanins compounds which are cyanidin 3-O-rutinoside Lettuce derived from the Latin world lactus (milk), a milky fluid (60%) and cyanidin 3-O-glucoside (38%). The minor anthocyanins that flows from the stems when they break or are cut. The seeds (totally 2%) are pelargonidin 3-O-glucoside and pelargonidin medicinal properties were described by (430 BC). The 3-O-rutinoside. M. alba quercetin 3-O-glucoside, quercetin common reported pharmacological actions are anxolytic, sedative, 3-O-rutinoside, kaemferol 3-O-rutinoside, and 5-O-caffeoylquinic antipyretic, diuretic and analgesic. From the general properties of acid. Caffeic acid is considered the most abundant acid in Morus spp. the medieval general in general and the so-called Spongia somnifera in particular using lettuce seeds, I am with opinion that Caffeic acid, which selectively inhibits leukotriene biosynthesis Lactuca scariola is used in the formula [16]. Leukotrienes are significantly involved in immunoregulation Pharmacology and chemical composition of Lactuca scariola and a variety of diseases, including asthma, inflammation and various allergic conditions. They are initially biosynthesized Triterpenoid saponin, 3 -O-[ -l-rhamnopyranosyl]-30-norolean- by 5-lipoxygenase from arachidonic acid, which can also be 12,19-diene-28-oic acid 28-O-[ -d-glucopyranosyl-(1 4)-O- -d- metabolized to prostaglandin endoperoxide by cyclooxygenase. The galactopyranosyl]-ester has βbeenα isolated from the stems of L.a specific inhibitors for 5-lipoxygenase, caffeic acid, would be a useful scariola. Another triterpenoid saponin,β 3-O-[ -Dgalactopyranosyl-(1→ β tool for the regulation mechanism of leukotriene biosynthesis. I 3)-O- -D-xylopyranosyl-(1 4)-O- Lrhamnopyranosyl]- oleanolic think the role of mulberry is to regulate ale asthma in the patients acid; has been isolated from the seeds of L. scariolaβ . Oilseed lettuce due to the presence of caffeic acid [14]. →Becauseβ of the bitter taste →of its leaves,α- this is not eaten as a vegetable. Oilseed lettuce is characterized by a high percentage F-Ivy (35%) of oil in the seeds, which is used for cooking. The oil Ivy is Hedera helix L. belonging to Araliaceae family, known by contains Vitamin E, an essential nutrient. Seed oils of Lactuca English common name English ivy, common ivy, and in Arabic scariola Linn., L. sativa Linn., were found to contain epoxy acids known by the name Muddad. H. helix is an evergreen Climber in 10.0% (6.0% coronaric + 4.0% vernolic), 27.4% (16.9% growing to 15 m by 5 m at a medium rate. It is in leaf all year, coronaric + 10.5% vernolic) and 20.0% (16% coronaric + 4.0% in flower from October to November, and the seeds ripen from vernolic) amount, respectively, along with normal fatty acids. L May to June. Leaves and berries have been applied in medicine in sativa seed oil has demonstrated a pronounced sedative effect and ancient times for the treatment of various diseases (e.g. jaundice potentiated the effect of barbiturates in animal models. and dysentery). Nowadays, only the leaves are applied and only The alkaloid, lactucin, isolated from the seeds exhibited antipyretic in the treatment of respiratory diseases. According to European activity Methanolic extract of L. scariola can produce significant analgesic activity [17]. The alkaloids lactucine and its derivatives Pharmacopoeia, Hederae folium is the whole or cut, dried leaves of lactucopicrine and 11- , 13-dihydrolactucin, were evaluated for Hedera helix L. collected in spring, with a minimum hederacoside sedative and analgesic and sedative properties in animal model. content of 3.0%. Lactucopicrine alkaloidβ showed to be the most potent analgesic Pharmacology and chemical compositions of the tested compounds. Extract of L. scariola showed significant analgesic activity at low dose of 300 mg/kg. even better analgesic H.helix leaves contain 2.5%-6% triterpene saponins, based on the effect than the reference drug and the dose level of l000 mg/ aglycones hederagenin, oleanolic acid and bayogenin. The majority kg. The relaxation of airway muscles after the administration of of the saponins are bisdesmosides, with the main compound the methanol extract of L. scariola was found to be due to the hederacoside C (hederasaponin C). Monodesmosides (such as dual mechanism (i.e., muscarinic antagonist and Ca++ channel alpha-hederin) are present in smaller amounts. Further secondary blockade). The bronchodilator effect may possibly be mediated metabolites are caffeic acid derivatives, flavonoids, coumarins and through Ca++ channel blockade. Interestingly, muscarinic polyacetylenes. Phenolic constituents isolated from a commercial antagonists are today used in the treatment for the relief from dry extract of Hedera helix were included rutin, kaempferol asthma and similar diseases.

J Trop Dis Vol. 9 Iss. 5 No: 282 3 Olimat S. OPEN ACCESS Freely available online H-Hops henbane, ivy, mulberry, lettuce and hops; other plants are toxic not used anymore in medicine e.g. mandrake and hemlock. Hops is a dioecious perennial species the dried female inflorescence (strobili) of Humulus lupulus L. belonging to the family Canabinaceae, CONFLICT OF INTEREST it is known in English by the common name Hops and in Arabic known by the name Hashishat ed dinar. The female cones (stobili) The author has stated that there is no conflict of interest associated are widely used for beer brewing due to their bitter taste. with the publication and no financial support, which could have influenced the outcome. History REFERENCES Around 77-79 A.D, Humulus lupus became known as a plant grown in the wild. It wasn’t until around 736 A.D that they began 1. Berg M. An Introduction to anesthesia-related medications. Perianesth being cultivated by humans for use. 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