Black henbane (Hyoscyamus niger L.), also referred to as common henbane, hogbean, hogbane, or insane root, is a member of the Solanaceae or nightshade family. Black henbane is an annual or biennial plant that can range in height from 1 to 3 feet tall. Rosette leaves are alternate and have petioles almost as long as the leaf blades. Stems of a mature plant are erect, leafy, thick, coarse, and widely branched.
Leaves are alternate, oblong to ovate, coarsely toothed to shallowly lobed, and grayish-green in color. Foliage is covered with fine, sticky hairs and has a foul odor. Flowers are funnel-shaped, 5-lobed, brownish-yellow with dark purple veins, and arranged in long, leafy, spike-like clusters. Fruit of the plant is pineapple-shaped, approximately 1 inch long, and contains hundreds of tiny, black seeds.
Isolation of chemical constituents
The psychoactive tropane alkaloids hyoscyamine, scopolamine, and atropine are present in all parts of the plant, but are concentrated in the seeds and roots (Nanjing University of Traditional Chinese Medicine, 2006; Prance and Nesbitt, 2005). In recent years, some non-alkaloids constituents, including withanolide steroids, lignanamides, tyramine derivative, steroidal saponins, glycosides, lignans, coumarinolignan, and flavonoids.
Side effects and toxic reactions
In the ancient Chinese monographs, H. niger was recorded to have drastic toxicity. Since H. niger contains tropines alkaloids, it has a narrow range of use safety. Excessive doses can cause poisoning and death. But there is insufficient reliable information available about the safety of the topical use of henbane (Jellin et al, 2000). When the water extract of H. niger seeds washig administered in mice to perform the acute toxicity experiment, none of the mice died due to intoxication (Wang et al, 2008).
The alkaloids like atropine, hyoscyamine, and scopolamine could cause permanent effect on brain development in inbred mice. They produce a typical antimuscarinic action by paralyzing the nerve endings of the parasympathetic system. The central anticholinergic syndrome is characterized by thought impairment, recent memory disturbance, hallucinations, hyperpyrexia, ataxia, excitement, drowsiness, coma, dry skin and flushing, tachycardia, mydriasis, and absence or reduction of bowel movements.
The therapy including gastrointestinal decontamination, gastric lavage, supportive therapy, and physostigmine, is recommended if tachycardia, somnolence, coma, and threatens respiratory arrest are developed (Longo, 1966).
H. niger intoxication includes the clinical signs of inappropriate speech, aggressiveness, nausea and vomiting, dilatation of pupils, flushing, somnolence, tachycardia, dizziness and ataxia, agitation, dryness of mouth, visual hallucinations, pyrexia, tremor and convulsion, dysphagia, distension of the bladder and abdomen, respiratory arrest, and coma, etc. And its therapy includes stomach lavage, supportive therapy, and physostigmine as a specific antidote (Doneray, Orbak, and Karakelleoglu, 2007). Administration of H. niger as anticholinergic agents in pregnancy could exert its permanent effect on brain development in inbred mice (Mahmoodi et al, 2004).
The anti-diabetic potential of methanolic leaves extract of Hyoscyamus albus (was evaluated in diabetic rats. Streptozotocin-induced diabetic rats, were administered (100 and 200 mg/Kg bw) for 30 days. The oral administration of both doses of methanolic leaves extract of Hyoscyamus albus significantly reduced the levels of blood glucose and glycosylated hemoglobin in diabetic rats. Determination of plasma insulin levels revealed that the extract possessed insulin stimulating action
The 11 compounds hyoscyamide, 1,24-tetracosanedioldiferulate, 1-O-(9Z,12Z-octadecadienoyl)-3-Ononadecanoyl glycerol, grossamide, cannabisin D, cannabisin G, N–trans-feruloyl tyramine, 1-O-octadecanoyl glycerol, 1-O-(9Z,12Z-octadecadienoyl) glycerol, 1-O-(9Z,12Z-octadecadienoyl)-2-O-(9Z,12Z-octadecadienoyl) glycerol, and 1-O-(9Z,12Z-octadecadienoyl)-3-O-(9Z-octadecenoyl) glycerol were subjected to ascreening test for cytotoxicity using human prostate cancer LNCaP cells. Grossamide, cannabisin G, and cannabisin D displayed low levels of inhibitory activity; Other compounds were inactive (Ma, Liu, and Che, 2002).
Relaxant effects on smooth muscle
The crude extract of H. niger seeds caused a complete concentration-dependent relaxation of spontaneous contractions of rabbit jejunum inhibited partially by atropine. It also could inhibit contractions induced by carbachol (l μmol) and K+ (80 mmol) in isolated rabbit jejunum, guinea-pig trachea, guinea-pig ileum, and rabbit urinary bladder tissues, which was similar to that of dicyclomine, but different from verapamil and atropine.
The extract shifted the Ca2+ concentration-response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca2+ channel-blocking mechanism in addition to an anticholinergic effect. In the guinea-pig ileum, it produced a rightward parallel shift of the acetylcholine curves, followed by a nonparallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine.
It exhibited antidiarrhoeal and antisecretory effects against castor oil induced diarrhoea and intestinal fluid accumulation in mice. In guinea-pig trachea and rabbit urinary bladder tissues, it caused relaxation of carbachol (1μmol) and K+ (80 mmol) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca2+ antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect.
Effects on central nervous system
Anxiolytic and sedative activity
H. niger leaves contain alkaloids, including scopolamine, which could relieve muscle tremors of central nervous system origin, inhibit central nervous system, and have a sedative effect (Jellin et al, 2000; Blumenthal et al, 1998).
The methanolic extract of H. niger (300 mg/kg ip) significantly delayed the onset of seizures induced by picrotoxin (12 mg/kg ip) in mice, which certificated its anticonvulsant activity. Antiseizure effect of H. niger may be partly related to the flavonoid, rutin in the extract (Ma, Lin, and Che, 2002). Animal experiments showed that flavonoids exerted their effects through the central benzodiazepine receptors (Reza et al, 2009).
Anti-inflammatory, analgesic, and antipyretic activities
The methanolic extract of H. niger seeds produced significant increase in hot-plate reaction time, while decreasing writhing response in a dose-dependent manner in mice indicated its analgesic activity. It has been assumed that both central and peripheral mechanisms are involved in the analgesic activity of the extract. It significantly inhibited carrageenin-induced paw edema and cotton pellet granuloma in rats.
The extract in dose of 800 mg/kg also exhibited antipyretic activity in yeast-induced rat’s pyrexia model. The bioactive extracts under chemical investigation showed that cleomiscosin A was an important constituent responsible for anti-inflammatory activity (Begum et al, 2010). Furthermore, the water decoction of H. niger seeds was also confirmed to have analgesic and anti-inflammatory function in mice (Wang et al
Cardiovascular inhibitory effects
It was studied that the methanol extracts of H. niger seeds exhibited hypotensive, cardiodepressantand vasodilator effects, causing a dose-dependent (10－100 mg/kg) fall in the arterial blood pressure (BP) ofrats under anesthesia. In guinea-pig atria, the extractexhibited a cardiodepressant effect on the rate and forceof spontaneous atrial contractions.
In isolated rabbitaorta, it (0.01－1.0 mg/mL) relaxed the phenylephrine(PE, 1 mmol) and K+ (80 mmol) induced contractionsand suppressed PE (1 mmol) control peaks obtained inCa2+ free medium similar to that caused by verapamil.Its vasodilator effect was endothelium-independent as itwas not opposed by Nω–N–L-arginine methyl ester inendothelium-intact rat aortic preparations and alsooccurred at a similar concentration in endothelium denudedtissues. These data indicated that H. niger lowered BP possibly through the inhibition of Ca2+influx and its release (Khan and Gilani, 2008).
Flavonoids have been shown to possess vasodilator effect through multiple mechanisms including Ca2+ channel blockade (Taggart et al, 1997; Ajay, Gilani, and Mustafa, 2003) and are considered protective against cardiovascular diseases such as hypertension and arrhythmias (Knekt et al, 1996; Pietta, 1998).
The antimicrobial effects of Hyoscyamus albus leaves extracts was studied against three reference strains (S. aureus ATCC 25923, E.coli ATCC 25922, P. aeruginosa ATCC 27853), four clinical strains (S.aureus, E coli P. aeruginosa, P. mirabilis) and Candida albicans. The results showed that the butanolic extract of Hyoscyamus albus possessed antibacterial effects against S. aureus ATCC 25923, S. aureus, E coli ATCC 25922, E coli, P. aeruginosa ATCC 27853, P. mirabilis with MIC values of: 8.30, 6.00, 6.93, 8.32, 7.63, 7.53 mg/ml respectively. (Prof Dr Ali Esmail Al-Snafi, 2018)
Methanolic extract also showed an antimicrobial activity against all the microbial strains except the Candida albicans(58) The diameters of inhibition zone of water, hot water and methanol extracts of the leaves of Hyoscyamus albus against Staphylococcus aureus were 17, 17, 32 mm, against Escherichia coli 19, 17, 26 mm; against Bacillus subtilis 15, 20, 18 mm and against Salmonella typhi 10, 18, 24 mm respectively.
The neuroprotective potential, of petroleum ether and aqueous methanol extracts of Hyoscyamus niger seeds was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice. Parkinsonian mice were treated twice daily with the extracts (125–500 mg/kg, po) for two days and motor functions and striatal dopamine levels were assayed. Administration of the aqueous methanol extract (containing 0.03% w/w of L-DOPA), but not petroleum ether extract, significantly attenuated motor disabilities (akinesia, catalepsy and reduced swim score) and striatal dopamine loss in MPTP treated mice.
The extract caused significant inhibition of monoamine oxidase activity and attenuated 1-methyl-4-phenyl pyridinium (MPP+)-induced hydroxyl radical (OH) generation in isolated mitochondria, Accordingly, the protective effect of the methanolic extract of Hyoscyamus niger seeds against Parkinsonism in mice could be attributed to its inhibitory effects on the increased ·OH generated in the mitochondria (Prof Dr Ali Esmail Al-Snafi, 2018)
Pharmacology of Tropane alkaloids
Tropane alkaloids are anticholinergic drugs, hyoscyamine (atropine), and scopolamine (hyoscine) act primarily by competitive inhibition of the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic neurons and in CNS, they produced wide range of pharmacological effects included:
Skin: inhibition of sweating (hyperpyrexia may result), flushing;
Visual: cycloplegia (relaxation of ciliary muscle), mydriasis (relaxation of sphincter pupillae muscle), increase in aqueous outflow resistance (increases intraocular pressure in many cases of glaucoma);
Digestive: decreased salivation, reduced tone and motility in the gastrointestinal tract, decrease in vagus-stimulated gastric, pancreatic, intestinal, and biliary secretions;
Urinary: urinary retention (relaxation of the detrusor muscle), relaxation of ureter;
Respiratory: bronchial dilation and decreased secretions;
Cardiovascular: bradycardia at low doses (may be a CNS effect) and tachycardia at higher doses (peripheral effect), increased cardiac output if patient is recumbent;
Central nervous system: decreased concentration and memory, drowsiness; sedation, excitation; ataxia, asynergia, decrease in alpha EEG and increase in low-voltage slow waves (as in drowsy state); hallucinations; coma
Hyoscyamine possesses many pharmacological effects, it has a high affinity for muscarinic receptors, acts both centrally and peripherally. Its general actions last about 4 hours except when placed topically in the eye, where the action may last for days. Its pharmacological effects included:
Eye: it produced persistent mydriasis (dilation of the pupil), unresponsiveness to light, and cycloplegia (inability to focus for near vision). In patients with narrow-angle glaucoma, intraocular pressure may rise dangerously.
Gastrointestinal: It reduced the motility of GI tract.
Urinary system: It reduced hypermotility states of the urinary bladder. It is still occasionally used in enuresis among children.
Cardiovascular: It produced divergent effects on the cardiovascular system, depending on the dose, at low doses, it decreased cardiac rate (bradycardia). With higher doses, the M2 receptors on the sinoatrial node were blocked, and the cardiac rate increased modestly. Arterial blood pressure was unaffected, but at toxic levels, it dilated the cutaneous vasculature.
Secretions: it blocked the salivary glands, producing a drying effect on the oral mucous membranes (xerostomia). Secretion of sweat and lacrimal glands were also decreased. Therapeutically, atropine was used in many disorders included:
Ophthalmic: exerted both mydriatic and cycloplegic effects, and it permited the measurement of refractive errors without interference by the accommodative capacity of the eye.
Antispasmodic: It was used as an antispasmodic agent to relax the GI tract and bladder.
Antidote for cholinergic agonists: It was used for the treatment of overdoses of cholinesterase inhibitor, insecticides and some types of mushroom poisoning (certain mushrooms contain cholinergic substances that block cholinesterases). Massive doses of the antagonist may be required over a long period of time to counteract the poisons. The ability of atropine to enter the central nervous system is of particular importance to minimize the CNS side effects of cholinergic drugs.
Antisecretory: The drug was used as an antisecretory agent to block secretions in the upper and lower respiratory tracts prior to surgery