CII3CI Icilj

Halki Diabetes Remedy

Quick Diabetes Cure

Get Instant Access

Fig. 5.64 Structure of Cocaine.

Conium alkaloids

The major alkaloid (about 90%) is the volatile liquid coniine, with smaller amounts of structurally related piperidine alkaloids, including N-methylconiine and y-coniceine. Coniine contributes to the foul smell of hemlock. It is a neurotoxin, causes respiratory paralysis and is toxic to all classes of livestock and humans. In 399 BC, Socrates was put to death by this poison (Fig. 5.65).

Fig. 5.65 Structure of Conium alkaloids.

y-coniceine

Curare alkaloids

These are obtained from Chondrodendron tomentosum. (+) tubocurarine (Fig. 2.6) is the principal alkaloid. In addition, it contains chondrocurarine, isochondrodendrine, curine, curarine, cylleanine and tomentocurarine. (+) tubocurarine is a strong neuromuscular blocking agent.

Iboga alkaloids (Terbernanthe iboga)

The root bark contains up to 6% indole alkaloids, the principal component of which is ibogaine. Ibogaine is a CNS stimulant, and is also psychoactive. In large doses, it can cause paralysis and respiratory arrest. Ibogaine is of interest as a potential drug for relieving heroin craving in drug addicts (Fig. 5.66).

Ipecac Structure
Fig. 5.66 Structure of Ibogaine.

Ipecac alkaloids

These are obtained from dried root of Cephalis ipecacunaha. The chief alkaloids are emetine, cephaline and psychotrine (Fig. 5.67). Cephaline is a reduction product of psychotrine. The actions of emetine, cephaline are similar; psychotrine is inert. Emetine is specific for amoebic dysentery.

Structure Adhatodine
Fig. 5.67 Structure of Cephaline and Emetine.

Nux-vomica alkaloids

These seeds contain 1.5-5% of alkaloids, chiefly strychnine (about 1.2%) and brucine (about 1.6%). Strychnine (Fig. 2.6) is very toxic, affecting the CNS and causing convulsions. This is a result of binding to receptor sites in the spinal cord that normally accommodate glycine. Its only medicinal use is in very small doses as an appetite stimulant and general tonic, sometimes with iron salts if the patient is anaemic. Brucine (Fig. 5.14) is considerably less toxic. Distribution of strychnine and brucine in various species of Strychnos is tabulated below.

Table 5.1 It shows alkaloid % in various species of Strychnos.

Species

Strychnine

Brucine

Strychnos nux-blanda

x

x

Strychnos tieute

1.4%

traces

Strychnos nux-vomica

1.23%

1.55%

Strychnos lucida

0.3%

1.5-2.4%

Strychnos ignatii

1.23%

These are obtained from Holarrhena antidysenterica. They include connesine (Fig. 5.68), holarrhenine, kurchine, kurchicine conkurchine, conesimine, holarrhine, holarrhimine, conimine and isoconessimine. Steroidal alkaloids, antidysentericine, reghloarrhenine-A, reghloarrhenine-B and reghloarrhenine- C have been isolated from H. antidysenterica. In castor oil-induced diarrhea, the alkaloids reduced the diarrhea.

Fig. 5.68 Structure of Conessine.

Opium alkaloids

Although the ripe poppy (Papaver somniferum) capsule can contain up to 0.5% total alkaloids, opium represents a much more concentrated form and up to 25% of its mass is composed of alkaloids. Of the 40 alkaloids identified, about 6 represent almost all of the total alkaloid content. A typical commercial sample of opium would probably have a morphine content of about 12%. Powdered opium is standardized to contain 10% of anhydrous morphine.

Morphine (Fig. 2.6) is a powerful analgesic and narcotic, and remains one of the most valuable analgesics for relief of severe pain. Codeine (Fig. 5.5) is a relatively safe non-addictive medium analgesic, but is too constipating for long-term use. Codeine also has valuable antitussive action, helping to relieve and prevent coughing. It effectively depresses the cough center, raising the threshold for sensory cough impulses.

Papaverine (Fig. 5.6) possesses spasmolytic and vasodilator activity. Noscapine has good antitussive and cough suppressant activity comparable to that of codeine, but no analgesic or narcotic action.

Pilocarpus alkaloids

Pilocarpus microphyllus is currently the main source. The alkaloid content (0.5-1.0%) consists principally of the imidazole alkaloid pilocarpine; together with small amounts of pilosine (Fig. 5.69). Pilocarpine salts are valuable in ophthalmic practice and are used in eyedrops as miotics and for the treatment of glaucoma. Pilocarpine is a cholinergic agent and stimulates the muscarinic receptors in the eye, causing constriction of the pupil and enhancement of outflow of aqueous humour.

Pilocarpine

Pilocarpine

"O

Isopilocarpine

C5H5-CH-

o"

N CH3

Pilosine

Fig. 5.69 Structure of Pilocarpus alkaloids.

Psilocybe alkaloids (Psilocybe maxicana)

The active hallucinogens, present at about 0.3%, are the tryptamine derivatives psilocybin and psilocin, which are structurally related to the neurotransmitter, 5-hydroxytryptamine, the factor contributing to their neurological effects (Fig. 5.70).

Psilocin

Psilocin

Fig. 5.70 Structure of Psilocybe alkaloids.

Psilocybin

Resperine alkaloids (Rauwolfia serpentina)

Reserpine and deserpidine (Fig. 5.71) have been widely used as antihypertensive and mild tranquillizers. They act by interfering with catecholamine storage, depleting levels of available neurotransmitters. Prolonged use of reserpine has been shown to lead to severe depression in some patients, a feature not so prevalent when the powdered root was employed. Both ajmalicine (Fig. 5.71) and ajmaline are used clinically in Europe. Ajmalicine is employed as an antihypertensive, whilst ajmaline is of value in the treatment of cardiac arrhythmias.

Reserpine Root
Reserpine
Desperidine

Ajamalicine Ajmaline

Fig. 5.71 Structure of Resperine alkaloids.

Ajamalicine Ajmaline

Fig. 5.71 Structure of Resperine alkaloids.

Tobacco alkaloids

Tobacco is the cured and dried leaves of Nicotiana tabacum. Tobacco leaves may contain from 0.6-9% of (-)-nicotine, an oily, volatile liquid alkaloid, together with smaller amounts anabasine and nornicotine (Fig. 5.72). It also contains N-formyl nor-nicotine, cotinine, myosmine, nicotyrine, anabasine and nicotelline.

In lower concentrations, nicotine is a stimulant, i.e. it increases activity, alertness and memory, and this is one of the main factors that contribute to the dependence-forming properties of tobacco smoking. Nicotine increases the heart-rate and blood pressure, and reduces appetite. In higher doses, nicotine acts as a depressant.

Crystalline Alkaloid Alkaloid
Fig. 5.72 Structure of Tobacco alkaloids.

Vasaka alkaloids

These are obtained from Adhatoda vasica. They include vasicine (Fig. 5.6), adhatodine, and vascinone (Fig. 5.73). Vasicine is a quinazoline alkaloid, bitter in taste and occurs in crystalline form. It is soluble in chloroform. Oxidation of vasicine leads to formation of vascinone. Other alkaloids include anisotine, 3-hydroxyanisotine, vanestine, desmethoxyaniflorine and desmethoxyvascinone. Vasicine reduces ovalbumin and platelet activating factor induced allergic reactions. Vasicine has significant antiinflammatory and abortifacient activity.

HO
Structure Vasaka
Vasicinone Fig. 5.73 Structure of Vasaka alkaloids.

Vasicine yield from various samples in India ranged from 0.541 to 1.105% on a dry basis. Yeild as high as 2.18% was reported from a foreign sample of which more than half was the l-form and remainder dl-form of the alkaloid. The plant shows wide seasonal variation in vasicine content in its leaves. High concentration is attained twice in a year (3% in March and 1.4% in September), which concides with the flowering stage of the medicinal plant. During the vegetative stage, the plant contained very low concentration of the alkaloid.

Caltha alkaloids

Cathine and cathionine are obtained from Caltha edulis (Fig. 5.74). Cathine is analeptic and bronchodilator.

oh o nh2

ch, nh2

Cathlne Cathionine

Fig. 5.74 Structure of Cathine and Cathionine.

Gelsemium alkaloids

Gelsemine and gelseminine are obtained from Gelsemium semepervirens (Fig. 5.75). They act like strychnine. Other alkaloids include 21-oxygelsemine, gelsemicine, gelsidine, gelsevirine, and sempervirine.

Fig. 5.75 Structure of Gelsemine and Gelseminine.

Harmal alkaloids

Harmaline (harmidine), harmine (banisterine) and harmalol are obtained from Peganum harmala (Fig. 5.76). They are oxytocic in action.

h3co h h3co

Harmaline h3co h h3co

Harmaline

Harmine

Harmine

Harmalol

Fig. 5.76 Structure of Harmal alkaloids.

Harmalol

Fig. 5.76 Structure of Harmal alkaloids.

Jasminum alkaloids

Jasminine and jasminidine are obtained from Jasminum grandiflorum (Fig. 5.77).

Fig. 5.77 Structure of Jasminine and Jasminidine.

Vinca alkaloids

Catharanthus roseus is known as the common or Madagascar periwinkle. Formerly, it was classified as Vinca rosea. It is a perennial evergreen herb in Apocynaceae and originally native to the island of Madagascar. In all 70 alkaloids have been identified in periwinkle. Some have anticancer and hypoglycemic properties. Some act as hemostatics (arrest bleeding).

Two groups began working independently on periwinkle in 1950s when they heard of a tea which Jamaicans drank to treat diabetes. Beer and Noble from the University of Western Ontario became interested in the plant as a possible 'oral insulin'—they isolated alkaloid—vinblastine.

Svoboda injected a crude extract of the whole periwinkle plant into mice that were infected with P-1534 leukemia. The mice (60-80%)

experienced a prolonged life. Lilly produced vinblastine as the drug Velban and also synthesized another alkaloid, vincristine (Fig. 5.78). In the first human test in 1960, a 49 yr old man dying of Hodgkin's disease, was walking within a week and 4 mon later the tumor disappeared.

Vinblastine (Fig. 5.78) has been especially effective for treating Hodgkin's disease. It is the first drug of choice in the treatment of many forms of leukemia and since the 1950's it has increased the survival rate of childhood leukemias by 80%. Vincristine has been especially effective for treating acute childhood leukemia, often with 99% remission rates.

Vinblastine, vincristine, and two semi-synthetic derivatives (vindesine and vinorelbine) all have the same mode of action. They inhibit mitosis in metaphase by binding tubulin. Vinblastine binds to tubulin dimmers in a 1:1 ratio and prevents microtubule formation. Other alkaloids which bind to tubulin include colchicine, maytansine and mescaline, but they have been studied much less than Vinblastine.Vinblastine also seems to fight cancer by interfering with glutamic acid metabolism. They are all administered intravenously once a week. The compounds can be fatal if they are administered any other way, and can cause a lot of tissue irritation if they leak out of the vein.

oh oh

Vinblastine

Vincristine Fig. 5.78 Structure of Vinca alkaloids.

Vincristine Fig. 5.78 Structure of Vinca alkaloids.

Cepharanthine makes memberane more stable by inhibiting peroxidation of their lipids.

Carbazole alkloids, glycoborinine, glycozoline and glycozolidine are reported from roots of Glycomis arborea (Fig. 5.79).

Fig. 5.79 Structure of Glycozoline and Glycozolidine.

Lunasia amara contains quinoline alkaloids, such as lunacridine, which would be worth investigating for pharmacology (Fig. 5.80).

och3

och3

Fig. 5.80 Structure of Lunacridine.

och3

Fig. 5.80 Structure of Lunacridine.

Buchanine, a novel pyridine alkaloid has been reported from Cryptolepis buchanani. Boldoa fragrans contains isolqinoline alkaloid, boldine (Fig. 5.81). Tribulus terrestris contains ß-carboline alskloid, tribulusterine (Fig. 5.82).

Structure Buchanine

Fig. 5.81 Structure of Boldine. Fig. 5.82 Structure of Tribulusterine.

Crinasiatine, crisiaticidine-A, isocraugsodine, lycoriside and palmilycorine have been reported from Crinum asiaticum (Figs. 5.83, 5.84). The plant also contains lycorine.

Fig. 5.83 Structure of Crinasiatine.

Fig. 5.84 Structure of Crisiaticidine-A.

Fig. 5.83 Structure of Crinasiatine.

Fig. 5.84 Structure of Crisiaticidine-A.

5-hydroxymethyl-1-1 (1, 2, 3, 9-tetrahydro-pyrrolo [21-b] quinazolin-1-yl)-heptan-1-one is reported to be the bioactive alkaloid of Sida cordifolia (Fig. 5.85). It has analgesic and anti-inflammatory activites.

ch2-ch2-ch2-ch-ch2-oh ch2

ch2-ch2-ch2-ch-ch2-oh

Fig. 5.85 Structure of bioactive alkaloid of Sida cordifolia.

Wilfordine, wilfortrine, wiforgine and wilforine are major alkaloids of immunomodulator Chinese drug, Triptergyium wilfordi. Chakranine is an alkaloid isolated from Bragantia wallichii. Colycotomine is alkaloid of Acacia sinuata. A great variety of isoquinoline alkaloids like protopine and stypoline have been isolated from Corydalis govaniana (Fig. 5.86). The plant also contains corydaline.

Fig. 5.86 Structure of Protopine and Stypoline.

Jateorrhiza columba (Cocculus palmata) contains several isoquioniline alkaloids including cocculine, columbamine, jatorrhizine, plamatine and umbellatine (Fig. 5.87). Cocculus hirsutus is reported to contain cohirstine, cohirsitinine, cohirsinine, jamatinine and haiderine. Cosculine from the stem and leaves of Cocculus pendulus, is active against the cells derived from human epidermoid carcinoma of nasopharynx.

Bragantia Willichii Leaves

Columbamine

Jatorrhizine

Cocculine o ch

Columbamine

Jatorrhizine

Cocculine o

ch3 o ch ch3 o ch3

Palmatine Umbellatine

Fig. 5.87 Structure of alkaloids of Jateorrhiza columba.

Ricinine (Fig.5.88) and N-demethyl-ricinine, isolated from leaf extract of Ricinus communis have significant hepatoprotective, choleretic and anticholestatic activity.

Fig. 5.88 Structure of Ricinine.

Major alkaloids of Fumaria parviflora include protopine, cryptopine, sanguinarine, fumaridine, fumaramine, parfumine and fumariline. Sanguinarine is antimicrobial. Theobromine and theophylline from Theobroma cocoa are well-reputed bronchodilators (Fig. 5.89). Voacangine n

Fig. 5.88 Structure of Ricinine.

and mitragynine, isolated from Voacanga africana and Mitragyna cilita, respectively, are potential analgesic agents. Nitidine isolated from Toddalia asiatica has potential antiHIV activity (Fig. 5.89).

Fig. 5.89 Structure of Nitidine.

Fig. 5.89 Structure of Nitidine.

Huperzine-A from Lycopodium (Huperzia) serrata and galantamine obtained from Galanthus nivalis, respectively, have anticholinesterase activity and are used in Alzheimer's dementia (Figs. 5.90, 5.91).

Huperzine Structure
Fig. 5.90 Structure of Huperzine-A.
Piperidine Alkaloids Crinum

The bulb of Haemanthus albiflos contains alkaloids including lycorenine and tazettine. Hamelia patens contain oxindole alkaloids including palmirine and rumberine. Heimia salicifolia contains alkaloids including lythrine, sinicuichine, heimine, nesodine, sinine (lythrindine), vertine and cryogenine. Cryogenine decreases spontaneous motor activity, hypothermia, blepharoptosis and ataxia. Lythrine and vertine are diuretic. Adina cordifolia contains alkaloids including adifoline, cordifoline, 10-deoxy cordifoline and 10-deoxy adifoline. Adifoline is a central nervous system depressant and hypotensive in experimental animals.

Solanaceous alkaloids

Solanaceae is one of the medicinally important families, many plants of these possess narcotic properties and constitute the drugs used in indigenous systems with great ethnobotanical diversity. The alkaloids isolated from the plants of Solanaceae have been successfully utilized in modern medicine particularly ophthalmic practice.

Atropa belladonna contains 0.3-0.6% of alkaloids, mainly (-)-hyoscyamine. Belladonna root has only slightly higher alkaloid content at 0.4% mainly (-)-hyoscyamine. Minor alkaloids including (-)-hyoscine and cuscohygrine are also found in the root. The Datura stramonium leaf usually contains 0.2-0.45% of alkaloids, principally (-)-hyosycamine and (-)-hyoscine in a ratio of about 2:1. Datura sanguinea, yields leaf material with a high (0.8%) alkaloid content in which the principal component is (-)-hyoscine. Datura meteloides contain meteloidine (Fig. 5.92). The alkaloid content of hyoscyamus is relatively low at 0.045-0.14%, but this can be composed of similar proportions of (-)-hyoscine and (-)-hyosycamine. Egyptian henbane, Hyosycamus muticus, has much higher alkaloid content than H. niger.

Fig. 5.92 Structure of Meteloidine.

Fig. 5.92 Structure of Meteloidine.

The alkaloids distributed in Solanaceae are of tropine or pyridine type. Tropine alkaloids are formed by combination of Tropic acid and Tropine. Tropine alkaloids are tropane derivatives. Some alkaloids are pyridine (cuscohygrine) or piperdine (isopelliterine) derivatives. Depending upon the basic nucleus, the alkaloids found in Solaneacea are classified into the following types:

1. Soladulcidine type

2. Solasodine type

3. Tomatidenol type.

The majority of alkaloids have anticholinergic activity. They act by inhibiting acetylcholine. Atropine (Fig. 5.5) is used as a mydriatic (to dilate the pupil) in ophthalmic practice and as an antidote to morphine poisoning. Hyoscine (Fig. 5.5) is used as an antispasmodic and the salt available is hyoscine butyl bromide. Hyoscine also has a significant anti-emetic effect, and that is why it is used for the treatment of motion sickness.

Withania alkaloids deserve special mention. Isopelletrine has antihelmenthic activity whereas somniferine is a sedative. The total alkaloids of roots have a variety of pharmacological actions. In animal models, the alkaloids have shown hypotensive and analeptic activity. Solasodine has glucocorticoid-like effects, hypocholesterolaemic and antiatherosclerotic activity. Nicotine exists in liquid form that is resorbed through the skin.

The majority of alkaloids are toxic. 100 mg of atropine is sufficient for killing a person as it causes respiratory distress. Daturine alkaloid present in Datura alba and other species, accounts for the toxicology of Datura. Daturine is converted into atropine in the human body and it causes death from asphyxiation. Solasodine possesses embryotoxic activity and cumulative effects. The toxicity (LD50) in mice orally is 27.5 mg/kg. Solanine is a protoplasmic poison, which acts on amoeboid cells of the body and causes heamolysis. It has been used as an agricultural poison.

Scopolamine and hyoscyamine (Fig. 5.5) also possess toxic activity and poisoning causes delirium, which is due to central nervous system excitation. Nicotine is a well-known toxic substance. Common symptoms of poisoning with Solanaceous alkaloids include restlessness, delirium, mania, hallucinations, asphyxiation, sleep, urinary problems, constipation and death. Cestrum diurnum contains alkaloids including nicotine and nornicotine (Fig. 5.72) Cestrum nocturnum contains alkaloids including nornicotine, cotinine and myosmine.

Table 5.2 indicates the lethal dose (LD50) of therapeutically important alkaloids of Solanaceae.

Table 5.2 LD50 values of therapeutically active alkaloids found in Solanaceae.

SNo.

Name of alkaloid

LD50

1.

Atropine

400mg/kg

2.

Hyoscyamine

375mg/kg mice (i.p)

3.

Hyoscine

700-1,300mg/kg mice (s.c).

4.

Homatropine

6783mg/kg

5.

Nicotine

0.3 mg/kg

6.

Solasonine (Solanine)

2.8mg/kg

7.

Solasodine

27.5mg/kg mice (orally)

8.

Tomantine (Lycopersicin)

80mg/kg mice (orally)

i.p =intraperotoneal s.c = subcutaneous.

i.p =intraperotoneal s.c = subcutaneous.

Solanine

Tomantine

CH3

Tomatidine

Fig. 5.93 Alkaloids of Solanaceae (see Fig. 1.4 also).

Solanum dulcamara contains steroid alkaloid glycosides (0.07 to 0.4%). The alkaloid spectrum differs widely with the variety. Tomatidenol variety—a-solamarine, p-solamarine. Soladulcidine variety— soladulcidinetetraoside. Solasodine variety—solasonine and solamargine. The chief alkaloids of Solanum nigrum include solasonine, solamargine, and P-solamargine.

Lobelia alkaloids

Lobelia inflata contains about 0.2-0.4% of alkaloids, of which the piperidine derivative lobeline (Fig. 5.73) is the chief constituent. Minor alkaloids identified include lobelanine (Fig. 5.94).

Convolvulaceae alkaloids

Convolamine and convolvine are obtained from Convolvulus sp. They have anesthetic activity. Elymoclavine is obtained from Ipomoea nil

Lobeline

Lobelanine

Fig. 5.94 Structure of Lobelia alkaloids.

Lobeline

Lobelanine

Fig. 5.94 Structure of Lobelia alkaloids.

O CH3

Convolamine

OH H3C CH

Convolamine

OH H3C CH

Convolvine

Convolvine

oh

n ch3

Elymoclavine Fig. 5.95 Alkaloids of Convolvulaceae.

Pyrrolizidine alkaloids (Fig. 5.96)

Alkaloids are present in many plants ranging from non-poisonous forms to highly fatal toxic forms. Pyrrolizidine alkaloids are one such type, which are highly toxic principles present in Boraginaceae, Compositae, and Leguminosae families. The intoxication is caused by the oral intake of the plants containing the alkaloids either in food or medicinal form. Plants containing pyrrolizidine alkaloids are sometimes contaminated with agricultural crops also.

At least 100 types of pyrrolizidine alkaloids are present in plants. The majority of them are hepatotoxic. The varied manifestations of liver injury caused by pyrrolizidine alkaloids containing herbs are acute and chronic hepatitis, steatosis, hepatic fibrosis, zonal or diffuse hepatic necrosis, bile duct injury, veno-occlusive disease, acute liver failure, and carcinogenesis.

Teucrium chamaedrys (germander) causes severe, acute hepatocellular injury. Traditionally it has been used for reducing weight. An elevated level of aminotransferase enzyme has been observed after the intake of the drug.The toxic principle of the herb has not been detected but the presence of pyrrolizidimne alkaloids has been postulated.

Symphytum officinale (comfrey) contains a number of pyrolizidine alkaliods including echinatin, lycopsamine, 7-acetylly cops amine, echimidine, lasiocarpine, symphytine and intremedine. Due to the presence of pyrolizidine alkaloids, the use of the drug has been banned in number of countries.The comfrey alkaloids have hepatotoxic and carcinogenic potential. Some companies are introducing pyrrolizidine alkaloid free comfrey extracts.

Cynoglossum officinale (Hound's tongue) is also known to contain pyrrolizidine alkaloids including heliosupine, 7-angeloylheliotridine and acetylheloisupine. The herb in experiments has shown that it induces paralysis in peripheral nerve endings in frogs. The exact cause of this is not known, but because of the presence of the pyrrolizidine alkaloids in the herb, the use should be abolished.

The following genera also contain pyrrolizidine alkaloids Senecio longilobus, Lycopodium serratum, Heliotropium eichwaldii, Helitropium indicum, Larrea maxima (chaparral), Crotolaria assamica, Crotolaria juncea,Crotolaria retusa, Eupatorium sp., Alkanna tinctoria (alkanna) Mentha pulegium and Tussilaga farfara (Colt's foot).

All human beings are believed to be susceptible to hepatotoxic pyrrolizidine alkaloids. Home remedies and consumption of herbal teas in large quantities can be a risk factor and are the most likely cause of alkaloid poisonings. Evidence of toxicity may not become apparent until sometime after the alkaloid is ingested. The acute illness has been compared to the Budd-Chiari syndrome (thrombosis of hepatic veins, leading to liver enlargement, portal hypertension, and ascites).

Early clinical signs include nausea and acute upper gastric pain, acute abdominal distension with prominent dilated veins on the abdominal wall, fever, and biochemical evidence of liver dysfunction. Fever and jaundice may be present. In some cases the lungs are affected; pulmonary edema and pleural effusions have been observed. Lung damage may be prominent and has been fatal. Chronic illness from ingestion of small amounts of the alkaloids over a long period proceeds through fibrosis of the liver to cirrhosis, which is indistinguishable from cirrhosis of other etiology.

OH OH

OH OH

Indicine

H3C| OH

CO OH CO CH2 O

Monocrotaline

Monocrotaline

CH3 ch3

Senecionine

CH3 ch3

Seneciphylline

Senecionine

Was this article helpful?

0 0
Dealing With Asthma Naturally

Dealing With Asthma Naturally

Do You Suffer From ASTHMA Chronic asthma is a paralyzing, suffocating and socially isolating condition that can cause anxiety that can trigger even more attacks. Before you know it you are caught in a vicious cycle Put an end to the dependence on inhalers, buying expensive prescription drugs and avoidance of allergenic situations and animals. Get control of your life again and Deal With Asthma Naturally

Get My Free Ebook


Responses

  • SAGRAMOR
    What is DL in isopelleterine?
    4 years ago

Post a comment