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Harmal

Harmal

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Harmal is a plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

 of the family
Family (biology)
In biological classification, family is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, class, order, genus, and species, with family fitting between order and genus. As for the other well-known ranks, there is the option of an immediately lower rank, indicated by the...

 Nitrariaceae
Nitrariaceae
Nitrariaceae is a family of flowering plants in the order Sapindales. It comprises three genera, Nitraria, Peganum and Tetradiclis, totalling 16 species....

, native from the eastern Mediterranean region east to India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

. It is also known as Wild Rue or Syrian Rue because of its resemblance to plants of the rue
Rue
Rue is a genus of strongly scented evergreen subshrubs 20–60 cm tall, in the family Rutaceae, native to the Mediterranean region, Macaronesia and southwest Asia. There are perhaps 8 to 40 species in the genus...

 family.

It is a perennial plant which can grow to about 0.8 m tall, but normally it is about 0.3 m tall. The roots of the plant can reach a depth of up to 6.1 m, if the soil it is growing in is very dry. It blossoms between June and August in the Northern Hemisphere
Northern Hemisphere
The Northern Hemisphere is the half of a planet that is north of its equator—the word hemisphere literally means “half sphere”. It is also that half of the celestial sphere north of the celestial equator...

. The flowers are white and are about 2.5–3.8 cm in diameter. The round seed capsules measure about 1–1.5 cm in diameter, have three chambers and carry more than 50 seeds.

Peganum harmala was first planted in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 in 1928 in the state of New Mexico
New Mexico
New Mexico is a state located in the southwest and western regions of the United States. New Mexico is also usually considered one of the Mountain States. With a population density of 16 per square mile, New Mexico is the sixth-most sparsely inhabited U.S...

 by a farmer wanting to manufacture the dye "Turkish Red" from its seeds. Since then it has spread invasively to Arizona
Arizona
Arizona ; is a state located in the southwestern region of the United States. It is also part of the western United States and the mountain west. The capital and largest city is Phoenix...

, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

, Montana
Montana
Montana is a state in the Western United States. The western third of Montana contains numerous mountain ranges. Smaller, "island ranges" are found in the central third of the state, for a total of 77 named ranges of the Rocky Mountains. This geographical fact is reflected in the state's name,...

, Nevada
Nevada
Nevada is a state in the western, mountain west, and southwestern regions of the United States. With an area of and a population of about 2.7 million, it is the 7th-largest and 35th-most populous state. Over two-thirds of Nevada's people live in the Las Vegas metropolitan area, which contains its...

, Oregon
Oregon
Oregon is a state in the Pacific Northwest region of the United States. It is located on the Pacific coast, with Washington to the north, California to the south, Nevada on the southeast and Idaho to the east. The Columbia and Snake rivers delineate much of Oregon's northern and eastern...

, Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

 and Washington. "Because it is
so drought tolerant, African rue can displace the
native saltbushes and grasses growing in the salt-desert shrub lands of the Western U.S."

Common names:
  • African rue
  • Esphand (Persian, اسپند - سپند)
  • Harmal peganum
  • Harmal shrub
  • Harmel
  • Isband
  • Ozallaik
  • Peganum
  • Steppenraute
  • Syrian rue
  • Yüzerlik, üzerlik (Turkish)
  • Üzərlik
  • Luotuo-peng (Chinese, 骆驼篷)

Traditional uses


In Turkey Peganum harmala is called yüzerlik or üzerlik. Dried capsules from this plant are strung and hung in homes or vehicles to protect against "the evil eye
Evil eye
The evil eye is a look that is believed by many cultures to be able to cause injury or bad luck for the person at whom it is directed for reasons of envy or dislike...

."


In Afghanistan, Azerbaijan
Azerbaijan
Azerbaijan , officially the Republic of Azerbaijan is the largest country in the Caucasus region of Eurasia. Located at the crossroads of Western Asia and Eastern Europe, it is bounded by the Caspian Sea to the east, Russia to the north, Georgia to the northwest, Armenia to the west, and Iran to...

, Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...

, Iraq
Iraq
Iraq ; officially the Republic of Iraq is a country in Western Asia spanning most of the northwestern end of the Zagros mountain range, the eastern part of the Syrian Desert and the northern part of the Arabian Desert....

, Turkey
Turkey
Turkey , known officially as the Republic of Turkey , is a Eurasian country located in Western Asia and in East Thrace in Southeastern Europe...

, Uzbekistan
Uzbekistan
Uzbekistan , officially the Republic of Uzbekistan is a doubly landlocked country in Central Asia and one of the six independent Turkic states. It shares borders with Kazakhstan to the west and to the north, Kyrgyzstan and Tajikistan to the east, and Afghanistan and Turkmenistan to the south....

 and Tajikistan
Tajikistan
Tajikistan , officially the Republic of Tajikistan , is a mountainous landlocked country in Central Asia. Afghanistan borders it to the south, Uzbekistan to the west, Kyrgyzstan to the north, and China to the east....

, dried capsules (known in Persian
Persian language
Persian is an Iranian language within the Indo-Iranian branch of the Indo-European languages. It is primarily spoken in Iran, Afghanistan, Tajikistan and countries which historically came under Persian influence...

 as اسپند espænd or اسفنددانه esfænd-dāneh and испанд ispand or испандут ispandut by Tajiks
Tajiks
Tajik is a general designation for a wide range of Persian-speaking people of Iranic origin, with traditional homelands in present-day Afghanistan, Tajikistan, and Uzbekistan...

 and Bukharian Jews of Central Asia) mixed with other ingredients are placed onto red hot charcoal
Charcoal
Charcoal is the dark grey residue consisting of carbon, and any remaining ash, obtained by removing water and other volatile constituents from animal and vegetation substances. Charcoal is usually produced by slow pyrolysis, the heating of wood or other substances in the absence of oxygen...

, where they explode with little popping noises, releasing a fragrant smoke that is wafted around the head of those afflicted by or exposed to the gaze of strangers. As this is done, an ancient prayer is recited. This prayer is said by Jews (more specifically, Bukharian Jews) and Muslims as well as by Zoroastrians. This Persian
Persian people
The Persian people are part of the Iranian peoples who speak the modern Persian language and closely akin Iranian dialects and languages. The origin of the ethnic Iranian/Persian peoples are traced to the Ancient Iranian peoples, who were part of the ancient Indo-Iranians and themselves part of...

 practice dates to pre-Islamic, Zoroastrian times. In Iran, this ritual is sometimes performed in traditional restaurants, where customers are exposed to the eyes of strangers.

Harmal has been used as an entheogen
Entheogen
An entheogen , in the strict sense, is a psychoactive substance used in a religious, shamanic, or spiritual context. Historically, entheogens were mostly derived from plant sources and have been used in a variety of traditional religious contexts...

 in the Middle East, and in modern Western culture, it is often used as an analogue of Banisteriopsis caapi
Banisteriopsis caapi
Banisteriopsis caapi, also known as Ayahuasca, Caapi or Yage, is a South American jungle vine of the family Malpighiaceae. It is used to prepare Ayahuasca, a decoction that has a long history of entheogenic uses as a medicine and "plant teacher" among the indigenous peoples of the Amazon Rainforest...

to create an ad hoc
Ad hoc
Ad hoc is a Latin phrase meaning "for this". It generally signifies a solution designed for a specific problem or task, non-generalizable, and not intended to be able to be adapted to other purposes. Compare A priori....

Ayahuasca
Ayahuasca
Ayahuasca is any of various psychoactive infusions or decoctions prepared from the Banisteriopsis spp. vine, usually mixed with the leaves of dimethyltryptamine-containing species of shrubs from the Psychotria genus...

, the South American mixture of phytoindoles including DMT
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...

 with β-carbolines. However, Harmal has distinct aspects from caapi (notably, lacking DMT) and a unique entheogenic signature. Some scholars identify Harmal with the entheogenic haoma
Soma
Soma , or Haoma , from Proto-Indo-Iranian *sauma-, was a ritual drink of importance among the early Indo-Iranians, and the subsequent Vedic and greater Persian cultures. It is frequently mentioned in the Rigveda, whose Soma Mandala contains 114 hymns, many praising its energizing qualities...

 of pre-Zoroastrian Persian religions.

A red dye, "Turkey Red", from the seeds (but usually obtained from madder
Madder
Rubia is a genus of the madder family Rubiaceae, which contains about 60 species of perennial scrambling or climbing herbs and sub-shrubs native to the Old World, Africa, temperate Asia and America...

) is often used in Western Asia to dye carpets. It is also used to dye wool
Wool
Wool is the textile fiber obtained from sheep and certain other animals, including cashmere from goats, mohair from goats, qiviut from muskoxen, vicuña, alpaca, camel from animals in the camel family, and angora from rabbits....

. When the seeds are extracted with water, a yellow fluorescent dye is obtained. If they are extracted with alcohol, a red dye is obtained. The stems, roots and seeds can be used to make inks, stains and tattoos.

Medicinal uses


Peganum harmala is used as an analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 and antiinflammatory agent.

In Yemen
Yemen
The Republic of Yemen , commonly known as Yemen , is a country located in the Middle East, occupying the southwestern to southern end of the Arabian Peninsula. It is bordered by Saudi Arabia to the north, the Red Sea to the west, and Oman to the east....

 it was used to treat depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, and it has been established in the laboratory that harmaline
Harmaline
Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the reduced hydrogenated form of harmine.-Occurrence in nature:...

, an active ingredient in Peganum harmala, is a central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

 and a "reversible inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

 of MAO
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

-A (RIMA
Rima
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel Green Mansions: A Romance of the Tropical Forest. In 1974, she was adapted into a comic book character and featured in the short-lived monthly series Rima the Jungle Girl, published by DC Comics...

)," a category of antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

.

Smoke from the seeds kills algae
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...

, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, intestinal parasite
Intestinal parasite
Intestinal parasites are parasites that populate the gastro-intestinal tract in humans and other animals. They can live throughout the body, but most prefer the intestinal wall. Means of exposure include: ingestion of undercooked meat, drinking infected water, and skin absorption...

s and mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

s. Peganum harmala has "antibacterial activity," including antibacterial activity against drug-resistant bacteria.

The "root is applied to kill lice" and when burned, the seeds kill insects. It also inhibits the reproduction of the Tribolium castaneum beetle.

It is also used as an anthelmintic
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...

 (to expel parasitic worms). Reportedly the ancient Greeks used powdered Peganum harmala seeds to get rid of tapeworms and to treat recurring fevers (possibly malaria).

Peganum harmala is an abortifacient
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....

, and, in large quantities, it can reduce spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...

 and male fertility in rats.

Antiprotozoal


It is fairly effective against protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...

 including malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

. There is evidence that it may be effective against drug-resistant protozoa. It is given in a decoction
Decoction
Decoction is a method of extraction, by boiling, of dissolved chemicals, or herbal or plant material, which may include stems, roots, bark and rhizomes. Decoction involves first mashing, and then boiling in water to extract oils, volatile organic compounds, and other chemical substances...

 for laryngitis
Laryngitis
Laryngitis is an inflammation of the larynx. It causes hoarse voice or the complete loss of the voice because of irritation to the vocal folds . Dysphonia is the medical term for a vocal disorder, of which laryngitis is one cause....

.

One of the compounds found in Peganum harmala, vasicine (peganine) has been found to be safe and effective against Leishmania donovani
Leishmania donovani
Leishmania donovani is a species of Leishmania. It is an important cause of visceral leishmaniasis. The reference genome of L. donovani extracted in the south eastern Nepal was published in 2011...

, a protozoan parasite that can cause potentially "fatal visceral leishmaniasis
Leishmaniasis
Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...

." "Peganine hydrochloride dihydrate, besides being safe, was found to induce apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 in both the stages of L. donovani via loss of mitochondrial transmembrane potential."

Another alkaloid harmine
Harmine
Harmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant harmal or Syrian rue and the South American vine Banisteriopsis caapi...

 found in Peganum harmala, ". . .because of its appreciable efficacy in destroying intracellular parasites as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be considered for clinical application in humans."

One study using the medicinal plant Peganum harmala showed it to have a lifesaving effect on cattle infected with the protozoal East Coast fever
East Coast fever
-Introduction:East Coast fever is a disease of cattle, sheep and goats caused by the protozoan parasite Theileria parva. The term excludes diseases caused by other Theileria, such as tropical theileriosis , caused by T. annulata, and human theileriosis, caused by T...

, which can be 100% fatal and killed 1.1 million cattle in Africa in 1992.

Anticancer


"The beta-carboline alkaloids present in medicinal plants, such as Peganum harmala and Eurycoma longifolia
Eurycoma longifolia
Eurycoma longifolia is a flowering plant in the family Simaroubaceae, native to Indonesia, Malaysia, and, to a lesser extent, Thailand, Vietnam, and Laos...

, have recently drawn attention due to their antitumor activities. Further mechanistic studies indicate that beta-carboline derivatives inhibit DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 topoisomerase
Topoisomerase
Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double helical structure. For example, during DNA replication, DNA becomes overwound ahead of a replication fork...

s and interfere with DNA synthesis."

Peganum harmala has antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

 and antimutagenic properties.

Peganum harmala as well as harmine exhibit cytotoxicity
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...

 with regards to HL60
HL60
The HL-60 cell line is a leukemic cell line that has been used for laboratory research on how certain kinds of blood cells are formed. HL-60 proliferates continuously in suspension culture in nutrient medium supplemented with fetal bovine serum, L-glutamine, HEPES and antibiotic chemicals. The...

 and K562 leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 cell lines. Ground Peganum harmala seeds have been used occasionally to treat skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...

 and subcutaneous cancers traditionally in Morocco
Morocco
Morocco , officially the Kingdom of Morocco , is a country located in North Africa. It has a population of more than 32 million and an area of 710,850 km², and also primarily administers the disputed region of the Western Sahara...

. Seed extracts also show effectiveness against various tumor cell lines both in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

.

Alkaloids


The active alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

s of Harmal seed
Seed
A seed is a small embryonic plant enclosed in a covering called the seed coat, usually with some stored food. It is the product of the ripened ovule of gymnosperm and angiosperm plants which occurs after fertilization and some growth within the mother plant...

s are the MAOI-A (monoamine oxidase inhibitor A) compounds:
  • Harmane, 0.16%

  • Harmine
    Harmine
    Harmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant harmal or Syrian rue and the South American vine Banisteriopsis caapi...

    , 0.44–1.84%–4.3%
The coatings of the seeds are said to contain large amounts of harmine.
  • Harmaline
    Harmaline
    Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the reduced hydrogenated form of harmine.-Occurrence in nature:...

    , 0.25%–0.79%–5.6%
  • Harmalol, 0.6%–3.90%
  • Tetrahydroharmine, 0.1%
Total harmala alkaloid
Harmala alkaloid
Several alkaloids that function as monoamine oxidase inhibitors are found in the seeds of Peganum harmala , including harmine, harmaline, and harmalol, which are members of a group of substances with a similar chemical structure collectively known as harmala alkaloids...

s were at least 5.9% per dried weight, in one study.
  • Vasicine (peganine), 0.25%
  • Vasicinone, 0.0007%

The stems of the plant contain about 0.36% alkaloids, the leaves about 0.52%, and the roots up to 2.5%.

Harmine and harmaline are reversible inhibitors of MAO-A (RIMA
Rima
Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel Green Mansions: A Romance of the Tropical Forest. In 1974, she was adapted into a comic book character and featured in the short-lived monthly series Rima the Jungle Girl, published by DC Comics...

).

External links