PHYTOPHARMACOLOGY OF AN IMPORTANT UNANI DRUG BAZR-UL-BANJ (HYOSCYAMUS NIGER LINN.) – REVIEW

Objective: Bazr-ul-Banj syn. Ajwain khurasani ( Hyoscyamus niger Linn.) is one of the important drug mentioned in Unani literature. It mentioned by the great Unani philosopher Dioscorides (first century AD) in his treatise Kitab-al-Hashaish . According to Unani philosophy, Bazr-ul-Banj is in third-degree category according to its temperamental nature. H. Linn. contains tropane alkaloids in good quantity, mainly hyoscyamine and scopolamine. Methods: Unani classical literature was searched from recent to past available in different libraries. For phytochemistry, pharmacology, and clinical studies to prove, the importance computerized databases such as Medline, PubMed, Ovid SP, Google Scholar, and Science-direct were searched. All the information of plant available in Urdu, Persian, Arabic, and studies published abstract were included in the study. Results: Fourteen Unani books were referred and 18 pharmacological studies were recognized. The action of Bazr-ul-Banj mentioned in Unani classical literature are Hazim (Digestive), Mudammil (Cicatrizant), Mujaffif (Dessicant), Mukhaddir (Anesthetic), Munashshi (Narcotic), Munawwim (Hypnotic), Musakkin (Sedative), Musakkin-e-Alam (Analgesic), Raade (divertive), Qabiz (Astringent), etc., and useful in Amraz-e-asbania (nervous affections), Amraz-e-Raham (uterine spasm and pain), Dard wa Alam (pain), Ikhtelaj-e-Qalb (palpitation), Junoon (mania), Niqras (Gout), Zeequn Nafas (Bronchial asthma), etc. H. niger Linn. showed many pharmacological effects included antimicrobial, anticancer, analgesic, anti-inflammatory, antipyretic, antihypertensive, and antidiarrheal activities in different clinical and experimental studies. Conclusion: This presentation is an attempt to showcase the action, uses mentioned in Unani literature, chemical constituent, and pharmacological and toxicological effects at one place. It may also observe that the drug is having many actions which may be beneficial in cases of COVID-19. It may be concluded this should be tested as adjuvant medicine in cases of COVID-19. Unani


INTRODUCTION
Unani system of medicine (USM) is one of the oldest systems of medicine based on Hippocratic theory of Akhlat-e-arba (four humors). In this system the drugs are used from three sources, plant, animal, and minerals origin; however, the main source is plants and their products. According to the World Health Organization presently, 80% of the world population depends on herbal medicine for some aspect of primary health care. However, plants still provide some of our most valuable medicines [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].
Bazr-ul-Banj (Hyoscyamus niger Linn.) [16] is a native of Himalaya, but in use since a long time in USM. Dioscorides (first century AD) the great Unani physician and philosopher has mentioned the preparation of a sun-dried extract from the juice of the fresh whole plants or seeds is useful for the treatment of sleeplessness and pain [17]. He says that the dried aqras (pills) prepared from the extract pounded with flour, can retain their medicinal properties for 1 year [18]. Probably, the ancient ayurvedic physicians were not aware of it. It was introduced to India during 9 th century [19]. Henbane is literally translate "Hen Killer" [20] and its name derived from the anglo-saxon (hen (chicken) and bana (Murderer) because when fowls eat its seeds, they become paralyze and die [21]. It grows in two distinct forms annual and biennial. Stem is simple thick and about 0.5 m high leaves are dark in color, hairy with an irregular border, the fruits like that of pomegranate full of seeds resembling poppy seeds. Flowering time is during July and August corolla is paler in color and deeply veined. It is also found in Europe, Sabaria, Egypt, and Iran. Its taste is bitter. Unani scholars describe its three varieties according to color of its flowers, for example, white, black, and red. White flower is considered best for medicinal purposes. Extract of henbane seed, leaves, and root are used by some witches to run or fly on fire and when thieves come to rub them [22]. It is toxic plant exposure to potentially either intentionally or accidentally could induce toxic manifestation [23][24][25]. Nearly 900 patients during 1981-1991 were referred to the poison center of Imam Reza of Mashhad of Iran due to its poisoning [26,27].

METHODS
Unani classical literature was searched from recent to past available in different libraries. For phytochemical, pharmacological activities, and clinical trials carried out to prove the importance of Bazr-ul-Banj (H. niger Linn.), computerized databases such as Medline, PubMed, Ovid SP, Google Scholar, and Science-direct were searched. All the information of plant available in Urdu, Persian, Arabic, and studies published abstract were included in the study. Fourteen Unani books were referred and 18 pharmacological studies were recognized.

Temperament
The USM describes the general character of a drug in terms of its temperament. According to Unani philosophy, drugs are classified as per the specific temperament (Mizāj) and are graded in the first, second, third, and fourth-degree according to their potency. According to this philosophy of Unani system, Bazr-ul-Banj is cold and dry in the third degree of temperament [28][29][30][31][32][33][34][35].

Part used
As per Unani classical literature, seeds and leaves are used for various therapeutic purposes.

Pharmacological studies
Many pharmacological studies were conducted on the plant in different experimental models. These pharmacological activities are alphabetically arranged here.

Analgesic activity
The methanolic extract of seeds of H. niger and leaves of H. albus showed analgesic activity in experimental animal models at different doses in hot plate reaction time and writhing response [51][52][53]. Hydroalcoholic extract of seeds decreased the formalin-induced acute and chronic pain significantly through parental and oral route relative to the control group [54,55]. Methanolic extract of H. reticulatus L. possesses a significant antinociceptive activity in both central and peripheral pain models in mice [56]. The crude extract of H. niger reduced the numbers of acetic acid-mediated writhes in mice in dosedependent manner [57].

Anticancer activity
Alkaloidal extract showed anticancer activity by reducing the spontaneous frequency of chromosomal aberrations, micronuclei assay, and increased the mitotic index in mice bone marrow cells. Alkaloidal extract also induced apoptosis activity rather than cytotoxic activity against cancer cell lines (A549, PC-3) [27]. Compounds grossamide, and cannabisins D, and G isolated from H. niger seeds exhibited moderate cytotoxicity in cultured LNCaP human prostate cancer cells [59].

Anticonvulsant activity
Methanolic extract of H. niger L. possess the anticonvulsant activity against picrotoxin-induced seizures in mice by increasing latency and duration of seizure also delayed the death as compared to control [60]. Alcoholic seed extract of H. niger has markedly alleviated pentylenetetrazol-induced seizure phases in male mice [61].

Antidepressant effect
H. niger leaves ethanolic extract significantly reduced immobility duration of mice in forced swim test and tail suspension test in higher dose; it also showed anxiolytic activity [62].

Antidiabetic activity
Calystegines, polyhydroxylated alkaloids extracted from H. albus seeds showed antidiabetic effect on streptozotocin-induced diabetes in mice by markedly reducing blood glucose levels and minimized damages on β-cells of islets of Langerhans, also stimulated β-cells regeneration, and improved insulin secretion [63]. The oral administration of methanolic extract of leaves of H. albus significantly reduced the levels of blood glucose and glycosylated hemoglobin in streptozotocin-induced diabetic rats [64].

Antidiarrheal activity
The crude extract of H. niger seeds exhibited antidiarrheal and antisecretory effects against castor oil-induced diarrhea and intestinal fluid accumulation in mice [65].

Antihypertensive
H. niger crude extract lowers blood pressure through a Ca(++)antagonist mechanism in dose-dependent manner in rats and guinea pig models, also exhibited a cardio depressant effect on the rate and force of spontaneous atrial contractions [66].

Antihyperuricemic activity
Aqueous extract showed an inhibitory effect on xanthine oxidase activity, oral administration of the aqueous extract significantly reduced serum urate levels in hyperuricemia induced in mice in a dosedependent manner [67,68].

Anti-inflammatory activity
The methanolic extract of seeds of H. niger showed an anti-inflammatory effect in carrageenin-induced paw edema and cotton pellet granuloma methods [51].

Antipyretic activity
H. albus methanolic extract showed a dose-dependent lowering effect of the body temperature up to 3 h in comparable to paracetamol [52,53]. Methanolic extract of seeds of H. niger exhibited antipyretic activity in yeast-induced pyrexia model [51].

Antispasmodic activity
The crude extract of H. niger seeds inhibited contractions induced by carbachol and potassium in a pattern similar to that of dicyclomine, but different from verapamil and atropine [65].

Bronchodilatory effect
The crude extract of H. niger exhibits airways relaxation, inhibition of the CCh-induced increase in the inspiratory pressure of anesthetized rats [57].

Cardioprotective activity
Oral administration of crude powder of the H. niger protected rats from the cardiac damage induced by lipid peroxidation and activation of antioxidant enzymes. It protected from cardiac necrosis as evidenced by the inhibitory activity on CK-Mb and TGL [80].

Insecticidal effect
Methanol extract of aerial parts and flower of H. niger had destroyed the mosquitoes Anopheles spp. larvae [81].

Unani formulations
According to USM, the choice of drugs for treatment is governed by three laws: (i) Quality of drug in terms of temperament, (ii) quantity of drug in terms of its weight and potency, and (iii) time of administration. The selection of drug depends on the nature and type of the disease. To achieve the target, single and compound formulations were prescribed. The Unani Drugs are being manufactured mostly in the classical form. Modern instruments are used in the preparation of drugs. Sometimes,

Azhar and Mustehasan
minor alterations are made in the dosage forms, and due care is taken not to depart from the essence. The Unani Drug Industry is preparing and marketing two types of drugs: (i) Classical Unani formulations and (ii) patent and proprietary products. Good manufacturing practices are followed to ensure quality control of these drugs. Some important classical Unani formulations in which Ajwain khurasani is one of the ingredients mentioned in National Formulary of Unani Medicine.